DRUG TESTING ADVISORY BOARD
OPEN SESSION
June 8, 1999

Mr. Stephenson (HHS): Good morning. This is the open session of the Drug Testing Advisory Board meeting and we would like to ask everyone to sign in if they haven't already done so we have a record of who is here. Thank you very much.

Dr. Vogl (HHS): A brief update from HHS, especially for the public attendees. The last time we mentioned that we are working on revising the Federal custody and control form. I placed several copies of the draft version over on the table with the other materials to be handed out today.

We have been working on this for the past several months. We have industry representatives assisting us in putting this form together and we are close to a version we will use in preparing a Federal Register notice and then publishing it in the Federal Register for public comment for either 60 or 90 days.

We hope to do that before the end of July. After we receive the public comments, we will get the working group back together, and anyone else who is interested can participate, and we will develop the final revised form by the early part of next year. This will then be submitted to OMB for approval.

The implementation would be early 2001. We have to allow several months for the laboratories and anyone else to continue using their existing supply of forms. There would be some date established beyond which the current form could no longer be used.

If you have any comments, mail or fax them to us, and we will consider them in working through this process.

Mr. Stephenson: We are all involved and interested in substance abuse and the workplace, that nexus, and the issues that we've always brought to the table in those kinds of discussions have been focused on accuracy, reliability, and interpretation of results for drug testing as it might be part of a comprehensive drug-free workplace program. On March 23rd to 25th, many of us were able to participate in a workplace focused track of a National Prevention Congress. It was one of nine different agenda areas. Out of that group there were 30 different sets of proposals that were put forth to a group of between 350 and 500 people, depending on which day of the meeting you were at. At the end of that meeting, there was a summary report and the part of the group that was still at the meeting, about 40 percent of the total number that had attended, voted on what they thought were the most important agenda items. The number one item identified that came out of the Prevention Congress was the establishment and promotion of comprehensive drug-free workplace programs. That doesn't mean that there were any things that were less important, but what it meant was it was almost a common sense approach that workplaces are at a nexus for a lot of our social agendas that are going on right now, and I think over the last decade we have demonstrated that a high quality program of drug testing can contribute significantly to many of these issues. It protects the public, it protects the individual being tested, and it protects private sector businesses who don't have government regulations to fall on, but must in fact rely on the quality of whatever program they institute themselves.

I thought I would share that with you because it's an important piece for us. It's also consistent with one of the four demand reduction goals for the national prevention strategy out of the Office of National Drug Control Policy. We see this as an important area for us to continue to work towards.

It's kind of ironic, but on the flip side of that same point, I have to tell you that we do not have a confirmation for the September meeting of the Drug Testing Advisory Board because we do not have the necessary funds to travel the members of the Board for that meeting. We are still working on that and we have not canceled it at this time, but we may have to reschedule or move it to the next fiscal year. The primary reason for this is the government plans 18 months ahead for any budget year and, in this particular year, we have spent a lot of time and converted many of what had been planned to be one-day drug testing meetings into two-day sessions to accommodate our agenda to address alternative drug testing matrices and technologies. Because of that, we have consumed all of the dollars that were available and we're still looking for more. Realize that this is going to be a little bit tougher for us than it has been before to get through to the end of this year for any more public meetings. We will certainly try to do that, and we will let the public know as soon as we have an answer.

Mr. Edgell (DOT): I have one thing that I would like to mention at this time, Part 40 has left our office and is in the Department for internal review. After that, we will assimilate the comments and continue the cycle to release it as an NPRM. My crystal ball is cloudy on when that might be, but it is a significant first step and we are on our way to first base with this.

ORAL FLUID TESTING

Dr. Bush (HHS): First on the agenda is oral fluid testing. I'll ask Dr. Sam Niedbala to make a brief presentation and then we'll take it from there.

Dr. Niedbala (STC): The way I'd like to do this is to start every meeting with the bottom line first. If we start with the bottom line first, our working group had its meeting in Pennsylvania in early May. At that meeting, we approached the topic of oral fluid or saliva testing for drugs of abuse by looking at principles first. This is an interesting fluid because there are a variety of ways that it's being used right now and in the future for potential workplace testing. There were some basic principles that had to be discussed and established before we could go further with, perhaps, the more technical details.

Let me review the bottom line conclusions, recommendations, observations that we had at that meeting.

Number one, and this was probably a point that could have been debated, but actually the group -- and I have to compliment everybody that attended - they were very cooperative, very positive in how they looked at the project. The number one issue was that products should reflect drug levels as nanogram per mL of drug in saliva. Therefore, in the future, the recommendation will be that every device normalizes reporting units to this standard. That was a key principle because in a few minutes as we look at one of our other table summaries you will see that there are different devices that collect it along different principles, but if every device calculates back to saliva in nanograms per mL then it becomes a way for us to normalize future products. That was probably the number one thing. If we could accomplish anything at this meeting, we wanted to get to that bullet point.

Number two was, at least at first cut, the list of analytes will mimic those tested in current urine programs and that there is additional data needed specifically for 6-acetylmorphine.

The third one is that the working group for on-site testing should include saliva-based on-site products in their discussions. This group is going to focus on the laboratory testing because it was too much to try and do both at the same time. The recommendation was that that group take on normalizing whether it's urine-based or saliva-based on-site testing in their working group and that this group would look solely at those devices that will be collected in the field and tested back in the laboratory.

The next bullet point was that all products should be FDA-cleared -- they should go through that scrutiny.

Lastly, we talked a great deal about tests to validate the sample and that human IgG was discussed as a possible marker for determining the sample adequacy.

These were the major points that we got through in terms of discussion items. We have another two-day meeting scheduled for mid-July in Pennsylvania, and we'll be at that time intending to go through each of the individual steps, and prior to the meeting we have committed to one another to circulate the information so we come prepared to summarize some of the other individual sessions.

Let me go through a little bit of the data behind things, focusing on the meeting. We listed at the meeting those devices that we knew to be commercially available or somewhere on the near-term horizon and we looked at the companies that offer them and the technology.

In simplistic terms, the way you should look at this is that for these three companies collect in the field and send the specimens back to the laboratory for analysis, and the confirmation also takes place in the laboratory. Whereas these two companies for on-site, perform the test and then it goes on for confirmation.

This is one of the reasons why we decided and recommended that we separate on-site from laboratory-based testing for oral fluids. There is just too much difference in the two in what they need to accomplish and the scope of what the group may be able to review. That was part of one of those conclusions.

Next was the analytes. Again, what we tried to do is go through the list of the most commonly performed tests and take a look at what it is we see as the cutoff for the screen and the confirmation based on the information to date. All of this is precluded on people bringing to future meetings scientific data to support things. In general terms, this is the way we concluded cutoffs to be for the moment, the analytes and metabolites that we would target, and then for confirmation testing also what we would be targeting.

As you can tell, for amphetamines the levels are fairly high in saliva 100 ng/mL screening and 75 ng/mL; THC (parent) with a screening cutoff of about 2 ng/mL and a confirmation level of 1 ng/mL; cocaine 10 ng/mL, confirmation 5 ng/mL; opiates 10 ng/mL, confirmation also 10 ng/mL. You will see free morphine, codeine, as the targets with 6-AM to be determined. That's some of the scientific data we have to come back to the table with. For PCP, we looked at a screening cutoff of 5 ng/mL, confirmation also at 5 ng/mL.

We did go through all of the sections in terms of the factors for reliable testing. Again, I'm trying to boil this down to the things that we had committed to one another or were at least able to take a look at.

When we got to MRO issues we started to look at topics for future meetings.

One of the issues was, was saliva different from urine in target analytes, and again the overall was that it appears to be about the same, 6-AM is questionable, and the clinical study data needs review, and this is something that was committed to.

Is there data to establish differences between abuse and exposure? Also, the list of possible explanations to be discussed/defined as interferences. We listed some of these: for cocaine, cocaine passive exposure; for THC, THC passive exposure, THC hemp oil, marinol; for opiates, passive smoke exposure, poppy seeds; amphetamines, to consider OTC the Vicks inhaler, D versus L, etc. -- just the common list that needs to be detailed for the Board, and we intend to do that at our future meeting as best as possible.

From the meeting itself, we concluded that there were no issues identified, as we looked through the factors, that would prevent future use of saliva as part of the comprehensive drug testing program for the workplace. We stopped at the end and specifically said, are there any killer issues that this group identifies when we look through the list, and there were none that we could see that could not be answered given some time and attention to gathering up the information. In addition, there were data that were promised by members of the working group to help facilitate this next meeting in July. This will include a review of GC/MS methods and performance characteristics to date, a review of potential interferences using saliva, discussions around data, also data and methods to assure specimen integrity -- this is a key one -- and then finally, further discussion of cutoffs for screening and confirmation based on what the companies will bring forward.

If you go through the factors, as we went through each one, we left it as P, I, or the blank, and a lot of the issues that were P's now became Blanks. It became that because as we discussed the factors we didn't think there was anything we could not overcome. You won't see information underneath each one of those bullet points as of yet because this working group has to fill in those blanks.

Dr. Bush: Let's take a look at the purple book which was updated from the one that you may recall from the last meeting, if you were here. Flip to the oral fluids section.

Mr. Stephenson: For the public attendees who haven't attended one of these before, each of you should have a copy of this. You will absolutely be lost without it. But this is an update that Dr. Vogl has done, taking it literally from the transcript of our last meeting, taking input from the various reports of working groups and putting it into this document.

Dr. Bush: In the oral fluids section, you see the issues that were inherent and the integral parts of the draft, the matrix defined in a brief manner, but nevertheless forming the cornerstone for the factors for accurate and reliable drug testing. We have formed a train of events from the very beginning of the development of this table, and have had submission of information and discussion amongst the Board and the technical working group input, and that's annotated then. Look at factor number B, the collector. You can see that under the first issue, training, there's information that was posted, how the matrix looked as of 8-20-1998. Then following our last Drug Testing Advisory Board we had additional information that led us to a change in the evaluation of those factors and where we were in the progress of their evaluation and how they fit into the table now. I'd like to turn it over to Dr. Caplan and Sam. How would you like to work this, since you were the gentlemen who were at the meeting?

Dr. Caplan (DTAB Member): This book doesn't have the May meeting in it?

Mr. Stephenson: Yes, it does.

Dr. Vogl: I put in whatever comments were submitted.

Dr. Caplan: I don't think it will take long because we're in between two meetings. As Sam indicated, we had a very good one-day meeting, but it was the first meeting of this group, and we did identify a lot of things and they're going to come back in the second meeting in July, and I really believe we can wrap it up then, so that whenever we meet next, whether September or October, we'll have most of the answers. I guess it's instructive to flip through the pages. Do you have notes from your meeting with you?

Dr. Niedbala: Yes. The overheads are actually here, so if we get to something that's a discussion item we can view it.

Dr. Caplan: I think we can go quickly page by page and see if you want to make a comment, if I remember a comment, if anybody in the audience or the Board wants to throw something new or additional in. I suspect for this group, I believe all the known manufacturers were at the meeting.

Dr. Niedbala: Yes.

Dr. Caplan: The number is small and all the parties were there. I'm not looking like there's something big missing that we haven't gotten yet. If that's the case, that's where we need people to speak up.

We are starting with A.1, and these are items about the collection site. Some of these things were already prior to this meeting blank, so they weren't in the old book. They weren't discussed in the meeting, but we can quickly go through them.

Dr. Vogl: I wanted to make it a complete section so I added all the factors that were always "Yes" or "blanks" from the beginning.

Dr. Caplan: That's exactly the point. Therefore, we didn't discuss some of those pages again. However, if there is anything new or new thoughts about them as we go through, because the next step and the next meeting is to add supporting information for the areas that we already said are okay. The fact we said they were generally okay by discussion will now by the group have to be followed up to say why that's the case. We can't just end up with a book like this that has all blanks and say it's okay. It's going to have to be filled in. To find out and identify the issues which were problematic or need attention, we want to identify them first.

We have to go back and fill in the whole book, because we need to say why it is okay. Are there any comments along those lines with regard to the collection site? It was never considered that there were any issues. This is A.1, 2, 3, and 4. There were never really any issues there. In fact, one of the stronger points about oral fluids testing and collection is that invariably it's going to be a witnessed collection since the individual has to be there and the collector has to be there physically with the donor, unlike urine. The site would be a lot easier to manage and the individuals that are being given the device to use will essentially have to be under direct observation. This whole issue about specimen substitution, adulteration, all those things, should be much more manageable to control. Do you have any other comment on A?

Dr. Niedbala: No.

Dr. Caplan: Anybody else have anything they'd like to add about that? (No response.)

The collector, B.1. This was, prior to the spring meeting, considered to be without any other issue, and certainly we'd have to fill in what the training should be and the fact that there are a number of different models. Therefore, the collection process, again by comparison, like urine, there won't be only one way to do it.

Regardless of what lab it would be, there will be device-specific collection issues perhaps. That would kind of follow how the alcohol program is today, so there is a model for that. And there didn't seem to be any concern there.

Dr. Niedbala: I think one key point that Yale made is that as we discuss things, whether it's proficiency testing or collection protocols and training issues, I think the DOT model for alcohol saliva offers us a starting point, and we intend on taking a lot of the strategy in our approach to each one of these.

Dr. Caplan: The next one was B.2, collector certification. Again, we already changed that one to yes. There are going to be some issues which are brought, when this is all done, are going to be across the board issues, meaning that if we don't certify certain people in one field we'll probably look at whether certification is needed in a variety of areas.

We agree that certification is possible. Whether certification is required or what level, that's going to be a policy type determination at a later date. From the technical working group, that's certainly possible.

Dr. Caplan: Again, if any of you are representatives of groups that are involved in collection, I know there are a number of movements going on with regard to urine collection and improved programs and certification of urine collectors and all that. This should follow a similar thing. Again, like the DOT alcohol model, there is obviously going to have to be some sort of collection training protocol. Whether it's a model program or whether it's a certification process or whether it's manufacturer-driven will be a policy thing. All of them are readily possible, and I suspect that we will as a group make a recommendation along those lines, but that's as far as you can go. Any other comments on the collector and the certification of collectors? (No response.)

Dr. Caplan: Collection devices, C.1 and 2, again, there was no problem. There may be something, but on the principle of the devices and things that may come there are at least three and maybe four different ways that the saliva can be collected. That is why Sam indicated when he started one of the big issues was are we going to revert this to a specific uniform entity, which we decided would be appropriate and recommended that, or do we have to look at different cutoffs, because a lot of these devices collect the saliva and dilute it automatically. Why don't you just summarize those again.

Dr. Vogl: I know the working group changed it to a yes. I didn't change it here because there were no comments provided in your summary that supported changing that to a blank.

Dr. Niedbala: The only comment I'd make is at that next meeting to make a consensus statement about each one of these, either a very specific one or a general overview kind of statement, to give a recommendation and even some guidance, if possible.

Mr. Stephenson: What you're really saying is we'll discuss it here, but we're not at this point putting forth the evidence or the information to have us consider it and then officially change it in the document, that you've already got the next working group meeting set up and that after that that's when you'll have it all packaged?

Dr. Niedbala: That's right.

Mr. Stephenson: Okay, that's fine.

Dr. Caplan: You were going to comment on how they collect the specimens.

Dr. Niedbala: This is a complex picture because there are different manufacturers who offer different modes of collection. Some claim whole saliva, others claim to collect something that also has some of the blood components in it. Because of the different technologies that are available, the important point here is that there are some basic pieces here that go along with each and every collector.

Obviously, you all have to put something in your mouth that's going to absorb something, and that each manufacturer will have to substantiate against the guidelines or the criteria that are being addressed by the group or recommended by the group to normalize their device against everybody else's. I think this will create the ability for different technologies to come to market, but yet have good stringent scientific criteria in order to present their products.

Dr. Caplan: Does anyone want to make any further comments on this?

Mr. Good (Avatar): I think Sam said earlier that the cutoffs were calculated back to whole saliva rather than looking at the cutoff based upon the sample collected and I think that was what you said here. It doesn't change that consideration on the cutoffs. We're still working back to saliva.

Dr. Caplan: Any other comments about the collection device?

Mr. Stephenson: We are discussing factors where you've got a few issues and we'll make these changes with the written materials at the next meeting; is that correct?

Dr. Caplan: Generally. I don't think there were any specific issues we want to change, to try to change the categories for now.

Mr. Stephenson: Right. These are just an opportunity to go through dialogue.

Dr. Caplan: The next was C.2, and I don't believe there was anything there.

Then C.3 was the FDA clearance. We could comment further on that one. You focused on it before. You might want to reiterate it now.

Dr. Niedbala: Yes. For all parts what I'm noticing, because I hadn't seen this before today, is that you had taken a lot of transcript language and put it in here. Whoever reads this, whether it's this part or any other part, you have to understand this was part of that dialogue of ten or so of us in the room. As you read these things, more questions may come up and I guess they can be directed back, which we're happy to clarify. But in this particular section the whole concept was that FDA should review these products, and that was one of the overall bullet points.

Dr. Caplan: If you want to consider that one, that is one that will probably get us from a B to a blank.

Dr. Vogl: You mean that oral fluids endorses or would want to have FDA clearance?

Dr. Caplan: Yes

Mr. Stephenson: The issue is we need to take that into consideration, as you already referenced here, that's going to become a policy call that we would look at a later time. Your recommendation is that it would be a blank because you think that this is something that is positive.

Dr. Caplan: Right, and that could be noted here on your next edition, that that is the recommendation.

Dr. Niedbala: Yes.

Mr. Crouch (Board member): I have a couple questions, Sam. We talked about this the other day. As I understand this, the test is tied to the collection device.

Dr. Niedbala: Yes.

Mr. Crouch: If someone took a collection device and used another, say, a non-STC/ RIA kit that did not have FDA approval –

Dr. Niedbala: Correct. As another way of looking at it, there are collection devices, some of those named, that have FDA clearances as a collection device, but not for any intended purpose. The analogous type of application would be something like HIV. The FDA has cleared devices along with test kits for HIV. Similarly now, they've done collection devices plus kits for saliva.

Mr. Crouch: Does it preclude someone from buying another device and using STC's immunoassay?

Dr. Niedbala: Yes, because the kits, as an example, all are calibrated for use with this one collection device. If someone were to take a kit and use it on a different collector with a different fluid, different technology principle, it could have entirely different performance characteristics with that other device. So a laboratory would have to be very careful about doing that, whether it's an STC kit or somebody else's kit, because there will be differences.

Mr. Crouch: Do you see a potential for someone -- and I guess it's already out there -- to make a generic collection kit and then it would be up to the laboratory to validate whether or not that kit works for them? Is that still acceptable under FDA?

Dr. Niedbala: Then you get into the whole home brew question for the laboratories, and that has its own set of criteria and issues. But the medical device manufacturer cannot knowingly have an FDA clearance for something and then sell the product for something else.

Dr. Caplan: Is your question whether or not it can go to multiple laboratories if the laboratory was linked, if the laboratory process was linked to it

Mr. Crouch: No. My question is are they two independent phenomena or two independent clearances, one device, one kit, or are they more likely tied together?

Dr. Niedbala: They're tied together.

Dr. Sample (Board member): Is that always or in some cases, because I thought I heard you say there are some devices that are cleared just as collection devices independent of the test methodology.

Dr. Niedbala: If there are cleared devices by FDA and somebody would use -- and again this is just my experience FDA. I don't know if there is anybody here in the room that can speak to this. But if there is a cleared device for no intended use for collection of saliva and then somebody uses it for a cleared purpose, then they would be in violation because the kit they're using has not been matched to it and it doesn't have the claim substantiated by FDA for safety and effectiveness.

Mr. Crouch: What about a 510k, where somebody comes along and shows equivalency with their device, equivalent results to the ones you're getting with your device in your kit? Are they then cleared only as a collection device or are they cleared as a collection device and a test?

Dr. Niedbala: It depends on what they would claim. It really comes down to that. If they had a different collection device and they used someone's kits that were also used with someone else's, then, sure, that could become another cleared application and intended purpose for that kit.

Mr. Stephenson: I'd like to go back to what Sam had originally said, that he is not purporting to be an official spokesperson for FDA. Our questions to him are only a reflection of his experience and his interpretation of what he thinks FDA would want to have. It's probably fairly accurate historically, but that doesn't predict where FDA may wish to go in the future.

Dr. Niedbala: And I'll quote FDA: At this time we will choose to regulate according to what we see to be appropriate. Having done about 40 or 45 of these submissions, that's where I come from in the experience.

Mr. Sample: In relating the drug concentrations back to nanograms per milliliter of saliva or oral fluid, that's really being tied as well to the testing methodology, is that correct? It's not really device driven. It's device plus the coupling with that test methodology.

Dr. Niedbala: That's correct. And I would envision for the first set of kits that are cleared right now by FDA that those manufacturers, myself included, have to go back and restate the package inserts to reflect that so that all users can look at the same sort of apples to apples comparisons.

Dr. Sample: I guess where I'm going with that question is that in the case of oral fluid you really are almost -- you almost have to be paired with test device and testing methodology because of this need to get back to nanogram per milliliter of original saliva regardless or irrespective of the collection device used.

Dr. Niedbala: Yes, I would think so.

Dr. Caplan: Maybe we're confusing on-site with the laboratory. The laboratory scenario, which we've decided to focus on here, we need to collect it, we need to send it to multiple laboratories. So it would be necessary that a device to collect the specimen and that device be FDA cleared to collect. Then it would have to be tested by multiple laboratories. What's not clear to me from what you've just said is whether or not each laboratory would have to clear a method for this to be cleared.

Dr. Niedbala: No, not each laboratory. The manufacturers would have to have a clearance for a particular use with a particular device.

Dr. Caplan: It's a use meaning a laboratory-based test, but a laboratory-based test doesn't have to be cleared to have a collection device?

Dr. Walsh (Walsh Group): We went through the same issue. There are two different types of clearance here that are kind of getting mixed. Sam alluded to it. When Sudormed came up with the sweat patch it had been cleared by FDA as a medical supply and they tried to market it as a drug test, and the FDA, with encouragement of this office, formerly at NIDA, shut them down on that issue and forced them to go back around and to have it cleared under the Medical License Act. This leads me to my question, that I think Denny was getting at. Sam, do you see that the diagnostic manufacturers who are developing assays would have to specify the collection device in their application to FDA for clearance?

Dr. Niedbala: Yes.

Dr. Walsh: Then any on-site test would essentially be a package deal that would include specifying the collection devices that could be used with the kit and demonstrate data as part of their application process with FDA?

Dr. Niedbala: Yes, to separate out laboratory based testing at least from what's discussed so far is that they would have a certain screening kit that's used in the laboratory and that the collection devices matched to that. The precedent was set with the sweat patch and also has been set recently with those devices or those products that have been cleared already for saliva. I would anticipate that stays the same. On-site, to me making a saliva alcohol test, it's a single use collector with a single use device, and I think that's the way it comes prepackaged.

Mr. Crouch: How many cleared collection devices and/or processes are there right now?

Dr. Niedbala: As collectors alone?

Mr. Crouch: For drug testing.

Dr. Niedbala: For drug testing, I would imagine we would consider two. Avatar has a saliva collector, but that's for on-site. There's one right now.

Dr. Sample: If there was more than one and those oral fluid specimens could be going to a variety of laboratories, those laboratories then would need to have a different screening procedure for each device that they receive?

Dr. Niedbala: That's a potential issue. The laboratory I would imagine would normalize against that problem in their collection kits only using a certain device.

Dr. Caplan: It doesn't prevent the device from coming on the market, which just links to a variety of things in the laboratory. The ones now are linked to specific products because, I guess, there hasn't been a market just to collect and send to a laboratory. That's clarifying. I wasn't sure about that before we started this, but definitely the laboratory is doing the immunoassay test, if that's the one they're doing, that has been cleared by the FDA with the collecting device in the laboratory before they do the confirmation.

Dr. Niedbala: That's correct.

Dr. Caplan: I guess in that case they can't just take the fluid in the buffer and use another immunoassay.

Dr. Niedbala: Right.

Mr. Stephenson: I remind everyone this is a discussion and clarification that's internal to the Board and not necessarily encumbering the FDA for any potential use. I will tell you that I think the dialogue here and perhaps in the other segments where we deal with the other technologies and specimens should have the same kind of focus, with a sense of the experience of the participants that can be taken back through our transcript process and shared with FDA, because it may be a reflection of some things that will help position them to help clarify. Again, no one in the public should take this as a definitive statement of direction by anybody in the Federal government. But it is a very enlightening dialogue.

Mr. Crouch: Is the process proprietary or can the laboratory use a collection device and their own methodology? It just would not be an FDA-cleared process then.

Dr. Niedbala: On that particular issue, I don't know what the regulations state for the laboratories. I think that comes back to the home brew questions and all the quality control requirements that go along with doing that by a laboratory.

Dr. Isenschmid (Board member): Sam, you said you could not knowingly sell your collection product if a laboratory was not using the FDA-cleared protocol.

Dr. Niedbala: That's correct. FDA holds the manufacturers accountable for that and there are precedents where they've gone and, as was said earlier, asked companies to stop selling products because they did not have the proper clearances to do so. And I'm glad they're going to comment on everything I've said, good or bad.

Mr. Stephenson: Do you want to know what they've said?

Dr. Niedbala: Sure.

Dr. Caplan: Well, the key here, as Bob has said, as we go across this we have to decide what we want to recommend and what we want to ask FDA to do as well with us. The example, good or bad, is the urine, dilutions of urine, agents and other reagents in the laboratory, which this agency has had an agreement with FDA that said this was an appropriate practice and it's checked through the inspection process. So there are things that will have to come out of this that will be the recommendations, that we might want the product with initial FDA collection, but this program might be able to modify that by some arrangement either within the program or with the FDA. But the discussion is important to find out what's out there, how they work, and what each element is up against as they put their product or their process into the marketplace.

Anything else on the collection devices, which is C.3?

Dr. Caplan: C.4, which is impact of device on specimen, probably that's covered with the previous discussion.

Dr. Niedbala: Right.

Dr. Caplan: D.1, which is the specimen and the body site, that was already done.

Dr. Niedbala: We know what site it is.

Dr. Caplan: Do we know what it is?

Dr. Niedbala: No, that's the problem.

Dr. Caplan: No, that's the other. Anybody want to make any comments on the uniformity of the oral fluids specimen? We know it comes from multiple sources and it could be diluted with other things.

I'm still on D.1, which is the body site. We are collecting it from the mouth. I'm just asking if there are any comments and whether there's any problem. As the group, when the group met there did not seem to be any concern about whether or not the specimen was so substantially variable in the mouth that it couldn't be used.

Dr. Niedbala: I agree. We didn't spend a whole lot of time on this. In other sections, we talked about influences in the oral cavity, but not any issues directly of saliva or oral fluids alone, yes.

Dr. Mitchell (RTI): I do think the question came up here in our discussions whether or not two specimens or two samples taken from either side of the mouth would be the same, and I don't think there was a resolution to that at that point in time.

Dr. Niedbala: No. On that issue we had committed to bringing back to the next meeting before the working group to look at that question. Bilateral collection will be addressed at that time.

Dr. Caplan: D.2, multiple testing.

Mr. Liddy (Walsh Group): I wanted to, in terms of body or site, to discuss whether we're going to consider stimulated versus unstimulated saliva and condition, because at the working group meeting we were discussing about how some devices to collect you might want to give the donor a lozenge or a sour condition so there was stimulated saliva, and is that going to affect the concentration of the drug in the saliva. If there should be a policy about that, that's basically what I'm asking.

Dr. Niedbala: I know we touched on it. Ed Cone had some comments on it because a lot of his studies were done with stimulated saliva. But I don't remember what we concluded other than it should be on the agenda and we should make some sort of statement about it, or at least the manufacturers should supply data on whether stimulated versus unstimulated.

What we will do is walk a line on some of these where the manufacturer may say, I've collected unstimulated saliva and then I've gone on to test that and that's all I can claim. If you do something different than that, you're outside of what's been claimed and validated for those conditions. That would be probably the starting point, but we should also collect any data and put that on the agenda.

Mr. Stephenson: If you look at two areas, one area would be delta-9-THC, its presence in any subsequent test or collection of oral fluids; and something you put on your issues that you still needed to address, passive smoke from opiates. These are two issues that I would think are a little different. They're not external contaminations per se, but they're markers for difference between the presence in saliva from perhaps smoking or ingestion versus coming back out as a reflection of plasma levels or something like that. I think that's one of the areas that's unique for saliva that you might want to address, because there's always a temptation to draw correlations, i.e., potential for impairment measurement. I think those are two that you'd want to look at.

Dr. Caplan: Along those lines, there is going to be one major issue and that will probably come later in the pharmacologic end, is that in saliva we are measuring essentially parent THC which is adhering to the mouth, not having been metabolically absorbed and excreted. The question there, which parallels your question, is whether or not this process -- whether it can be used for direct impairment or not is a longer question, but whether or not that parallels in time a detection window equivalence. That is one fairly fundamental question that still needs some further elucidation. It has been shown that we're able to see that, but in this case we're not seeing THC which is absorbed and excreted. We're seeing a phenomenon of adhesion and then release over a similar period of time. One may ultimately want to argue that on its merits and we'll probably get to that. But the technique for detection is not metabolic. It's a little bit different.

D.2, I guess we're finished with D.2, multiple testing.

D.3, potential to split the specimen. That's what you mentioned earlier.

Dr. Niedbala: Bilateral collection.

Dr. Caplan: We're looking at bilateral collection and what those differences are.

Dr. Sample: I'm not sure it should be a blank at this point until we resolve some of those questions.

Dr. Caplan: Which ones?

Dr. Sample: On the split specimens.

Dr. Caplan: It was already a blank.

Dr. Sample: No, it was a P.

Dr. Caplan: It was created with a blank. It was changed to yes. I think the conclusion was that the specimens could be split. Now, whether the split of the specimen is of a uniform specimen once it's collected, the integrity of the composition of which is variable, or whether there are two separate collections might be the issue you're talking about now. But whether it could be split or not was the reason it went to the yes. I mean, you could collect what you're collecting, whether it is a specimen into the buffer, and then you could split that specimen into two component parts so you have an equal split of whatever you got. That's different than the bilateral collection, which is collecting it twice for two different sides of the mouth. This is why -- this process that we're going through of changing these things the best we can doesn't preclude the fact that when this is over we have to go back and look at all the blanks and say why and do this again across the board. So I don't think we need to be real concerned. We still have to justify the blank. The idea was is it possible.

Dr. Sample: I guess my concern is I don't want us to think that this issue was closed because it seems to me there's a lot of open issues still with respect to how one would deal with split specimens with oral fluids.

Mr. Stephenson: This is an example where I think internal consistency across the specimens is important to look at, too, because we're going to have to measure these at about the same point in time in terms of information to make a policy decision on them in terms of how we want to go about this. I think there are some science issues here that are unique to the collection device and maybe to all the related things with it, and I'm a little concerned if we have gone to a blank for saliva and yet for hair and on-site we've left it at a P, which is apparently, Barry, what you're kind of saying. It's possible that you're concerned that we've gone directly to a blank. Sam, would you have any problems?

Dr. Sample: Which implies that we've laid all the issues to rest and I don't think we have.

Mr. Stephenson: Could I suggest that we consider this one going back to a P in your area and that you will add this to your list of things to provide additional materials for after your July meeting.

Dr. Caplan: Okay, absolutely.

Mr. Stephenson: All right.

Dr. Caplan: All right. For the record, we'll make D.3 "P" again. D.4, specimen stability and storage. We still have data coming on that, right?

Dr. Niedbala: Yes, and that's going to be based on data that I took the responsibility to work on. I still believe each device is going to have to substantiate. If you tie that back to an FDA review process, stability, storage stability, is one of the things you have to answer.

Dr. Caplan: Section E, the collection procedure. E.1, donor ID, I don't think there's anything there. There was a lot on E.2, preparation of donor. Any other comment on that? There wasn't anything new that came out of the meeting on that?

Dr. Niedbala: No, not at all. Prepare donor for specimen, this one ties into a couple of other assumptions, which is what's the protocol with the waiting period or anything that's required before you actually collect the specimen, and to substantiate that there's no influence of food or soda or anything else that you might have done for a period of time before collecting a specimen. We said we would come back and discuss this one at length to be sure that the 10 minutes or 15 minutes, whatever the final recommendation is, has the scientific information behind it to substantiate that that waiting period is correct.

Mr. Crouch: Is this to ensure that there isn't something else in the mouth, or is this to ensure that the sample would be representative of possibly plasma or blood concentration?

Dr. Niedbala: No. The screening kits will claim certain interferents that have been tested and those interferents need to be substantiated against specimens collected from people who have taken or been dosed with all of those potential things, soda, orange juice, etcetera. This is -- at least the discussion is viewed more from the standpoint of the procedural aspects of collecting a specimen from a donor and how are you sure that the specimen -- or that the donor is now ready and that the specimen will be valid.

Dr. Caplan: The next two, E.3 and 4, there was nothing. E.5, specimen integrity and evaluation, there was a lot of discussion about that. You mentioned a few things, and the discussion focused more on, A, the fact that it's almost an essentially observed collection, so you're going to get what you're going to get. The question was whether or not there was a marker, IgG or amylase or other things, which could be used like creatinine for urine, to look at whether an adequate specimen has been collected.

Dr. Niedbala: There were some literature references handed out to the group and we're going to come back and look at additional data, because this IgG test has been performed on all the clinical specimens collected to date that we've done and we'll use that as an example of a starting point to evaluate if it's an adequate marker. I think the principle was everybody agreed that some marker to show sample adequacy is important in sample integrity.

Dr. Caplan: E.6, anything further on that with respect to deter tampering and adulteration? (No response.)

Dr. Caplan: There was discussion about the types of devices, how it gets the saliva out, whether the person cooperates or how much they have to cooperate. I believe that was it. There weren't any other issues associated with that. That's still not concluded.

Transportation, no problem there.

Section G, laboratory testing, G.1, criteria for accessioning. I don't think there's any issues there.

G.2, short and long-term storage. Any further comment there? (No response.)

There was something from the meeting on the stability of 6-AM. Any other? (No response.)

G.3, specimen identity. Does anyone have any further comment on that?

Dr. Niedbala: No. I think the one thing we did talk about was this, at least for a few minutes, since this was a very easy specimen to collect and observe, that any potential adulteration -- one part is that direct observation is very easy and should be identified without too much problem.

Dr. Caplan: G.4.a, initial testing. That's the issue of FDA cleared. Sam covered that earlier. G.4.b, initial test to detect HHS target analytes. There was a lot of discussion about that, and the THC issue that I mentioned earlier was the biggest question or concern. I guess, surprisingly, that the information is that there are more metabolites and less parent drugs than at least I thought we were going to hear about detected. Do you want to comment any further about the correlations on these?

Dr. Niedbala: You mean in terms of windows of detection or metabolites?

Dr. Caplan: I was thinking of windows, but it might be another question since I can't predict the next question that's coming.

Dr. Niedbala: We had committed to one another to summarize the windows of detection concerning urine and other fluids between now and July, and then we'll be able to present that as a data summary to the Board to follow up on that.

Dr. Caplan: G.4.c, use established testing levels. There was a lot of discussion about the cutoffs. The key thing was normalizing all products to a saliva concentration instead of the dilutions which many used today, and the suggested cutoffs at this time, as Sam showed you earlier, they're also on this sheet. I think a couple people had some more data. Is this the revised data?

Dr. Niedbala: Yes, it is.

Dr. Caplan: I know there was some data which actually was revised after the meeting based on experience which couldn't be directly recollected at that time, but that's up to date here. This is the best thought of all the people that are doing this, the laboratories that are doing this, at this time. They may need a little revision, but it's close.

Dr. Niedbala: Mike Peat had committed to coming back with that info.

Dr. Vogl: Isn't that for each collection device -- do you know or can you determine how much saliva is actually absorbed, plus or minus a certain amount?

Dr. Niedbala: That's where we had discussions early on, because some of the devices may collect -- for example - If somebody spit on a piece of filter paper and shipped it back to the laboratory, there's a finite amount of liquid that was absorbed into an area. It's the same thing with these other collectors. The caveat is, though, that several of them have a fluid in the tube that acts as a preservative when it's shipped back to the laboratory. So there's a dilution. But you can back-calculate that and therefore normalize. That created the opportunity then for us to normalize all of the devices.

Dr. Caplan: While that might not be known today, that was doable and would be required in any process to make it uniform. Today the saliva goes on a device. The exact amount collected is not measured. It may have been studied at one time, but it's not that precisely known, and then it's diluted and the results are done on the basis of diluted concentrations. We decided that that would have to be -- the amount of saliva collected by a particular absorbing device would have to be known and then the dilution back-calculated to saliva units, so that anybody that came home with other devices would have to meet that criteria in the future.

Dr. Vogl: I think we talked about this briefly the last time. Are these levels or concentrations near the limit of detection, or have you arbitrarily selected concentrations that are three or five times higher than your LOD or LOQ?

Dr. Niedbala: No. The data that we have talked about with people committing to coming back with confirmation was based on ROC analysis comparing urine and oral fluid specimens which all were confirmed with GC/MS. The cutoffs selected were done analytically, the same way that it was done for the sweat patch several years ago. FDA has suggested that be the way, and I think some of the more recent NCCLS documents on how to look at new methods for immunoassay, also tie into using ROC analysis. It's not simply based on looking at two or three standard deviations from the zero and saying that's the lowest we can detect, therefore, that is the cutoff. It really is based on the clinical specimens that have been examined, both negative and positive populations, and then predict a value against those.

Dr. Caplan: G.4.d, initial test acceptable performance around the cutoff. This was an area that needed further information. The laboratories that do it have some information, but it was not available at that time and would have to be obtained. So there was no change there. G.4.e, initial test, ability to repeat initial test. I don't have anything on that.

Dr. Caplan: Dr. Mitchell, I don't recall anything specifically discussed about that, so that's still pending.

Confirmatory test on G.5.A. Any comments on that? The comments were made by Mike Peat, who has most of the data on that. Again, the data is forthcoming to support that. It is routinely being done.

Dr. Sample: There is evidence that traditional GC/MS will detect parent THC at 1 ng/mL in 150 microliters of oral fluid?

Dr. Caplan: Traditional?

Dr. Sample: Yes.

Dr. Mitchell (RTI): Repeat your question?

Dr. Sample: I'm wondering if there's adequate sensitivity with the usual GC/MS instrumentation that's employed by many laboratories to detect one ng/mL in a 150 microliter specimen of oral fluid.

Dr. Mitchell: 150 microliters, where is that? Is that from the earlier table?

Dr. Sample: Yes, it said 150 to 500 microliters is the specimen size. I'm talking about bench top type.

Mr. Crouch: Bench top CI. I think it's going to be a challenge, but certainly some chemical ionization methods would work.

Dr. Caplan: I don't know what methods are being used. Mike was going to go into that. That was additional information. He does not use HP equipment, right?

Mr. Crouch: Right.

Dr. Mitchell: I think that was one of the issues we said we had to wait and see the data in order to evaluate it.

Dr. Caplan: It was possible. Whether it was possible with the 5700 HP's or not and which ones was really not discussed. It was definitely possible with other GC/MS instrumentation, not necessarily MS/MS. That's data that should be coming back at the next meeting.

Mr. Good: I wondered, Sam, if these include the dilution or if they're also worked back to saliva? Is the real sensitivity one-third of that stated, or would it in fact be 3 nanograms for a 3 to 1 dilution?

Dr. Niedbala: For the GC/MS, Carl, or for the screening assays?

Mr. Good: For the confirmatory assays.

Dr. Caplan: The confirmatory assay will have to be run on the diluted, whatever specimen is submitted. It's going to have to have sensitivity sufficient to do that.

Mr. Good: These levels are really three times higher than what you'd actually have to obtain in the laboratory? Or is the actual confirmatory level 3 nanograms of THC, or is it three-tenths of a nanogram?

Dr. Niedbala: The table, that first table I put up which had the confirmatory methods, that matched it as ng/mL saliva. That did have the levels in there. Yes, this first one. Both are stated as ng/mL in saliva.

Mr. Good: A GC/MS on the eluted sample would have to be three-tenths of a nanogram if you went back to one nanogram?

Dr. Caplan: Right. But if it's diluted, you could use a larger volume. If you were to use the same 150 microliters, you'd have to be more sensitive.

Dr. Niedbala: Yes.

Dr. Caplan: I lost track of where I was. We went back to G.5.a, confirmatory test. We talked about G.5.a, which is more data. We needed a lot more data about the methods. They are being performed by several laboratories, but we did not have data at the last meeting to review and that's a problem for the next meeting.

Cutoffs reflecting drug use, G.6. That's the window, and we do need -- we are in search of more data for that.

Dr. Niedbala: The other comment we had on that is that we are comparing it to urine testing with GC/MS as the gold standard in every case.

Dr. Jacobs (Board member): I think we need to look at all of the different testings here and look more at the cutoffs. I'm not sure how some of those cutoffs are relating to each other or to some of the relationships. The recent raise in opiate cutoff -- and now I see here that what we see, the opiate looks very low. Are we going to get into the same type of situation with the very low opiate cutoff we just changed in urine?

I'm not sure what the relationship here between the different saliva, sweat, hair, urine, the different cutoffs are, and what they mean and what they relate to. I think all of the different working groups are going to have to look at these questions.

Mr. Stephenson: I think that's a good preface to remind us as we go through each of these sections, to look at this, because ultimately we're going to run out of science to help inform us and we're going to have to sit down and make some decisions about where this program needs to go, and that kind of information has got to be present.

Dr. Sample: I have a general question. I see that on several of these things we're saying more data is needed or more data will be provided at the next meeting, but yet they've been changed to a "B" or a blank, and I'm wondering if more data is still needed wouldn't that mean that it's possible and not that it's been resolved?

Dr. Caplan: Yes. The problem with doing these assessments is when you have one group of this size, you have another group of that size, and everybody says this can be done -- which is why we're doing it multiple times.

Mr. Stephenson: This again is what we have said before, that you're going to come back with more information. I think for purposes of the clarification and standardization we will wait until the next time before using any of this for any judgment purposes. This is an interim document that's simply being looked at.

Dr. Caplan: Correct. I want to reiterate, the process of making something move along just means we have more information. In the end, we have to go back to every blank and re-approve why it's blank and fill that in with information. In order not to focus on doing that first and to focus on trying to do the things we seem to be missing, we are forcing more things in that direction for later evaluation to get to the -- "to spend the time on the bigger issues."

G.7, internal QC program. Any comments on that? John?

Dr. Mitchell: No.

Dr. Caplan: You were there. We've got to use you. There weren't any issues discussed.

H.1, certified laboratory program. Nothing to prevent doing this in the future, but a number of things would have to be done to achieve that sort of thing. Do you want to make further comments on that?

Dr. Mitchell: Currently there's not a certification program available for saliva, and neither is there an external PT program. Those issues -- we talked about them and what would have to be done. It certainly appears to be possible.

Dr. Caplan: The same thing on H.2, external PT specimens.

Dr. Niedbala: We had talked about the external PT and using the sort of analogy for the future, in other words, the idea being that there may be a specimen group created and that different collectors and test methods may all become a bank of data each comparing their methods against those specimens, and then that would have to be monitored to have this external PT program. Is that fair? Do you want to add to that? As one potential way of going about doing this.

Dr. Mitchell: Right, that was one of the questions. The question was whether or not it would be advisable to send the PT samples to the laboratory on the device or whether it should be submitted as a solution, a saliva solution which contained analytes. That's a decision that would have to be made after more information is gained, I think, for some time. I think it's possible.

Mr. Stephenson: One of the things that comes up at this point, I'd like to draw the attention for the public and again for the Board that as we look at the external PT program as a part of an initial certification review and ongoing proficiency challenge as part of our continuing certification, we've requested that RTI begin the process of looking at how to create those specimens and at what levels they should perform.

One of the things that we'll be talking about will be how they can participate during these group meetings, and we'll be coming back to help inform the Board. As we learn more about what happens in the individual small working groups, it will also help inform us about the things we need to be doing in parallel to develop the PT programs that will help for the initial certification and ongoing maintenance process. And that goes across all the specimens.

Dr. Caplan: The CAP analogy that's noted on there is the difference in procedure. In most of the PT that we've been involved in with urine, there is basically one specimen and everybody gets the same thing and does it the same way. But clinical laboratories that test for a particular analyte may test it by a number of different methods. Usually the point of care type methods have a number of nuances, often the data is grouped by method or process-specific. That would be new or something that we would have to consider, if that was the case. That's because of the need of the large groups that CAP serves to do 100,000 clinical tests, and do a PT for it. You run into a lot of method-specific things and a lot of other arguments. That's why we say the analogy here, it's the method-specific classification of processing. We certainly want to avoid that if we can, but that was discussed.

Laboratory inspection. Any other comment on that? That's certainly possible to do.

H.4, blind samples, any comment on that? There was discussion.

Dr. Mitchell: Certainly, if an external PT program appears to be possible, then this would also be possible.

Dr. Caplan: Right. It's just a matter of whether they use simulated specimens or collect real specimens. This is another thing that CAP has dealt with, and in a lot of the CAP surveys they are simulated specimens. The urine, many of the urine specimens that are made for CAP purposes are synthetic urine. We may have to look at that if there are other situations here where we can't use the direct fluid.

Reporting, there really wasn't anything there, nothing at all with reporting. The whole reporting, the I section, 1, 2, 3, 4, I guess there wasn't a lot of discussion around this. There didn't seem to be any need.

MRO, the J section. Again, we didn't spend any time at that meeting on this. Does anybody here have any comments on any of the MRO-related things? We have to know more about the window in the clinical studies.

Mr. Stephenson: I don't want to underplay this, but it's an important area. When we say we need more information, I think it becomes one of the critical elements that safeguards the entire process, is how we inform and educate those that we have charged as doing the final audit for our entire program, the medical review officer. So maybe at a time when we get a little further along we can actually set up a part of our Board meeting when we have this information, we think we have it, and actually offer it for discussion with a group of medical review officers as a part of this process and see where the comfort level is there.

Dr. Caplan: The miscellaneous issues. We already discussed the dose response, the dose-time-response situation. Is there anything further on that? That was one of Sam's first slides. And the same thing with specimen contamination. I think that's it. Anybody else want to make any comments on anything along the update of the saliva review process? Anybody that was at the meeting? John and Sam and myself and Charlie.

Mr. Meeker (PharmChem Laboratories): I have a question on the adulterant issue. Have you looked at the possibility of someone having something like adulterated candy where they could put something under their tongue and it would dissolve? I don't know if it's possible, but it would seem like if you put something in your mouth you get a very high concentration of some adulterant in the saliva. Have you looked at that possibility?

Dr. Niedbala: Again, this working group is going to look at all of this. We have tested a number of things that go from toothpaste through soda or orange juice. I don't know of an adulterant tablet. I'm sure we're creating a new industry as we speak. But we have not found something that -- as long as, if someone does that and then we properly collect the specimen, call it the 10 or 15-minute waiting period, then we've taken those specimens and tested negatives and spikes, we don't see differences from normal activities like that.

Dr. Caplan: And there would be consideration, as Sam mentioned earlier, in this process of some sort of monitoring period or perhaps mouth-rinsing period, and maybe we should all promote sodium hydroxide chew tabs on the Internet and take care of these people right up front.

SWEAT TESTING

Mr. Stephenson: At this time we're going to begin with our next segment, which is on sweat testing, and to predict that this will not take the remainder of the morning. We'll have some choices to think about a little bit later on. I would like to retain the integrity of each of the segments, so that we're not breaking up any presentation to go to lunch. But if we do break a little bit early, then we may go to lunch a little bit early and then come back, and then we'll begin hair testing and then come back. Neil Fortner is going to give the presentation on sweat testing.

Mr. Fortner (PharmChem Labs): I think we're just going to go through the list.

Mr. Stephenson: Is your intention to try to provide information for purposes of making changes in the grid, or are you just doing an update?

Mr. Fortner: No, we had the first working group of the sweat testing the middle of May, the same week that the oral fluids had theirs. From that meeting there were a number of discussions, issues, and a consensus from the group, and those are some of the issues we'd like to go through. Those were the outstanding issues which I had sent to Walt, and I see that Walt has incorporated the comments into the format so we could go through and review that, and hopefully we'll be able to get through that this morning without too much difficulty.

I think just for general review, we'll just go through the checklist.

B.1 at the March meeting was moved to a blank on collector training.

B.2, certification, was also moved to a blank at the March meeting.

C.1 was already a blank from previous meetings, as was C.2.

C.3, FDA clearance if required. At the last meeting we had discussions that the patches, sweat patch, is cleared both as a collection device and then we'll see in subsequent issues also cleared under a 510k format. So that had been moved at the last meeting.

Mr. Stephenson: Approved under a 510k?

Mr. Fortner: Maybe "approved" is the wrong word. "Cleared" is the appropriate term under the FDA. It is, both as a collection device and then subsequent applications for detection.

C.4 was already a blank.

D.1, specimen body site, was a blank.

The first issue of discussion then comes to D.2, multiple testing. In the May working group meeting we spent a fair amount of time discussing clarification and definition of what constitutes a specimen, because this was an issue that was raised in the March DTAB meeting. The conclusion that the group reached was that the patch itself functions as a collection device. If you think about how this operates, the biological sample is sweat which is deposited, evaporated in essence, and concentrated on the device. Then that device is placed into a suspension solution, which we've gone through before, which is a 75/25 methanol/methyl acetate buffer, and in essence resuspending the drugs and producing an eluate that can then be subjected to standard testing. It was the consensus of the group that, while sweat is the biological specimen, what is really being tested by the laboratory is the subsequent eluant from the patch, and the patch serves as a collection device.

Now, one of the issues that had come up before was multiple testing and availability or how much sample is there to test, and we spent some time discussing that. Without making any current changes to the existing protocol, we had the opportunity to tour the testing laboratory in our facility. One of the things that was noticed is the current technology that we use to subsequently separate the patch from the eluant is analogous to a urine separator device, and that doesn't completely remove all of the eluant from the patch. There's about a half mL that's left in the bottom underneath this tube.

We've used an early predicate device which was developed I believe for saliva by Starsted, called a Salivette, and it's a centrifuge tube that has a small hole in it. You could in essence place the patch and the eluate in that and centrifuge it, which would force all the fluid out of the patch, so we gain another half mL in testing.

Now, one of the things that was discussed, is there any reason why you could not increase the total elution sample volume to either 3.5 or 4 mL's, because the consensus of the group was still that the drugs be expressed ng/mL of eluant, and this would give you almost double what the current testing volume is to allow for subsequent retests going back and forth. That was one of the recommendations from the group, to move it to a 3 to 4 mL extraction.

Dr. Bush: That's going to concomitantly require a change in all your GC/MSs, your confirm methods, because you're going to have a more dilute specimen?

Mr. Fortner: Not necessarily. I'm not sure that we would reach that conclusion. We have more than enough sensitivity currently using the existing methods.

Dr. Bush: That's where I was going. That's fine. But that was considered? Because if you change one thing that early on in the nature of what you're testing and the concentration of the analytes therein, it trickles down through the process.

Mr. Fortner: You're looking at a cutoff for most of the drugs of 10 ng/mL, which you have an LOD of about 2 for most of those. I don't believe adding additional eluate is going to impinge on that.

Dr. Bush: No compromise, all right.

Mr. Meeker: We also discussed that the only other change that we could slightly modify would be to increase the volume injected in the GC/MS. Typically they inject 1 to 2 microliters. They could do it with 2-3 microliters.

Dr. Bush: Good point.

Mr. Fortner: To expand on that, with the exception of the THC, which is done by negative CI, these other ones are currently done on HP 5970 MSD's. The sensitivity on those is not a real big issue, or at least with the patch we have plenty of sensitivity.

Based on that, it was the recommendation of the group that this be moved to a blank. It was a P in the March meeting.

Dr. Jacobs: I think that's probably a good idea. I think the questions have been answered here and we probably should move it to a blank.

Dr. Bush: Wait a minute. We have to come to some closure on this. There's a move, then, to change the P on this issue to a blank. I heard Dr. Jacobs state that clearly. Do we have agreement by all members of the Board that this is an appropriate thing to do?

Dr. Sample: Are we saying then that the eluate is the specimen?

Dr. Jacobs: Yes.

Dr. Saker (Board member): How do we standardize, then, to compare data from different laboratories? We have to have a standard because if not one laboratory is going to get a certain amount for the volume and another laboratory a different volume.

Mr. Fortner: I think you need to restandardize the reconstitution. Currently it's at a certain amount. It's at 2.5. Moving it to 3 or 4 would then become the standardization. It's a standardization across the board, because if you reconstitute with more or less you will certainly change the concentration per milliliter.

Dr. Jacobs: I think that there may still be some questions that we need answered, but this particular question - is the volume size of the specimen sufficient to conduct several tests - I think that has been answered.

Dr. Sample: I would agree with that. The reason I was asking is the eluate, the specimen, really relates to the next question.

Dr. Jacobs: It's called a setup, huh?

Dr. Sample: Yes.

Dr. Bush: Do you want to, then, review and change, possibly change P to a blank before you talk about the next? Is that okay? Are they independent in your mind?

Dr. Sample: I think they're independent. We've defined now that the eluate is the specimen. There is sufficient volume to do multiple testing from that eluate. I would not have any problem with changing D.2 from a P to a blank.

Dr. Bush: I've heard that from a couple Board members. Any Board members not in favor of that change? Okay, we'll change the P to a blank.

Mr. Fortner: D.3, potential to split specimen. At the March meeting, we had moved this from a P to a blank. We had discussed that in the strictest sense of the word a split is two patches, not a split of the 4 mL's. I think the approach that we had gone through under a formal split would be a separate patch not tested by laboratory A, and that would just mean the application currently of two patches. Based on that, we had moved it from a P to a B.

Dr. Bush: Right.

Mr. Fortner: D.4, stability in storage. This was in the last meeting moved to a blank.

I don't believe that there were any outstanding issues in section E, collection procedure, E.1 through 5. Unless there are other issues on that, we can just move to E.6, which is deter tampering, adulteration. In the March meeting this was moved to a blank. In the working group meeting we had some other discussions on this. We have already spoken with 3M Corporation with respect to incorporating another technology into the Tegaderm adhesive that uses two different degrees of adhesive, so that when the patch is physically removed it's detectable and it will either show a void or a letter or something along those lines. 3M indicated to us that the next time they produce a lot, which is probably later this year, they would be able to incorporate that technology. It's analogous if you've seen envelopes that have "Confidential" or "Void" when you open them. That uses two adhesive properties to produce that "Void." Analogous to that is the other technology incorporated to deter tampering, adulteration.

Dr. Vogl: Is there a change?

Mr. Fortner: I think it was already a blank. We had changed it. I was just providing additional information.

E.7, transportation, was already a blank from the last meeting.

G.1, laboratory testing criteria for accessioning, was a blank.

G.2, short term and long term storage. In the March meeting this was a P. There was a question raised at the last meeting, can we demonstrate stability of the drug? At the end of this handout section, we went and retrieved samples that were more than a year old, so eligible for discard, and we went back and did re-analysis of those. Those summaries, the data are contained in those tables. We had already gone through and shown stability of the patch or the drugs on the patch under dry conditions, so this is one to look at under methanolic acetate buffer. The study did show that the specimens originally confirmed positive reconfirmed after one year of storage. There are some differences in the actual levels in one or two, and I think in one we didn't get a qualifying ion issue off of that, but the drug was certainly there. One of the things that we noticed in there is there is some conversion or it looks to be conversion of cocaine to benzoylecgonine in which the levels, even though these are in a methanol acetate buffer, decrease from the cocaine and saw a corresponding increase in benzoylecgonine, but not in all cases.

Dr. Sample: The methamphetamine from March 5th that doubled or nearly doubled, that's a pretty good stability.

Mr. Fortner: The other thing that is important in looking at this, remember this is a primary methanol acetate buffer solution. They're not in Teflon caps. They're in plastic caps. What we suspect is we got some evaporation even though they're frozen or in a freezer. We're suspecting -- we didn't have any way to normalize against anything else. What we suspect is some evaporation of the eluate. It's not across the board. It's only in that particular case.

Dr. Sample: You're suggesting that all the others showed degradation of methamphetamine, but this specimen perhaps was not as tightly capped?

Mr. Fortner: It was a single point calibration. It's not a multi-point calibration in a curve. What we're really focusing on right now is it a positive negative at 10 nanograms. So there could be certainly linearity issues in some of these as well. But the focus was do we have a positive now, do we have a positive a year plus later.

Dr. Mitchell: The big concern should be with the opiates and the 6-AM. Considering that you have -- your solution is methanol acetate - I'd be worried about the conversion of morphine to 6-AM.

Mr. Fortner: Acetylation.

Dr. Mitchell: Yes, that would be my one concern. I do see that the 6-AM's do appear to go up.

Mr. Stephenson: You've explained how that may have been, and that looks rather consistent across most of your retesting, most of it. But have you figured out how you will correct that.

Mr. Fortner: In terms of normalization?

Mr. Stephenson: Or secured storage.

Mr. Fortner: I think what you'd have to look at is a better storage system that would cap these bottles tighter, possibly Teflon-lined. Right now it's a plastic cap on it. It's fine on the urine side. We use plastics because they freeze. But we've got predominant methanol in here. It's not going to freeze at any temperature. I think a better capping system would eliminate or reduce that evaporation potential.

Mr. Stephenson: What an interesting phenomenon, though. Would you have ever predicted this was one of the things you would have seen? This is what this kind of real experimentation produces, real world results rather than something that you prophecy.

Mr. Fortner: I don't think we would have ever predicted some of these phenomena.

Dr. Bush: It appears from a review of the data that you have reconfirmation of the results from the initial test.

Mr. Fortner: Yes, looking at stability. If you were to apply it at a limit of detection or re-test, I think you would have agreement in terms of positive and at some time later positive.

Dr. Welch (Board member): This is re-testing the extract, right, not re-testing of the second patch?

Mr. Fortner: It's re-testing of the extract. Currently there are not dual patches worn.

The group reviewed this data at the working group meeting and based off of this reconfirmation, it was the consensus of the group to move this from a P to a B.

Dr. Bush: Right. Would the Board like any further discussion or would like to entertain discussion, further discussion of changing this from a P to a blank?

Dr. Welch: If we're going to call a split specimen two patches, I think we need some information about what happens to that second patch if it's stored for a year or a certain amount of time.

Mr. Fortner: The original 510k filings had 30-day stability at room temperature under a variety of conditions. Certainly under the DOT guidelines with respect to split you could redo that and extend it to 60 days.

Dr. Bush: I'm just looking to see where that might fit in a little better, because what we're talking about here is short and long term storage.

Dr. Sample: What we're saying is for the purposes of the A, the specimen is the eluate, but for purposes of the B the specimen is the patch.

Dr. Vogl: Yes, a split specimen.

Dr. Bush: That's what it would appear to be, because nothing would happen in laboratory A to the B patch. That would stay in situ, stored in whatever mechanism, under whatever conditions, and then upon request for re-test would be taken out and subject to any extraction and analytical procedures at that time.

So we'd have to look at patch storage over time. But that would be under -- that would fall back under D.3 actually, even a subset of that, potential to split specimens. Certainly the fact is you can split the specimen by wearing two patches, but then it's what happens to that second patch.

Dr. Vogl: You could just qualify it. It involves both the B patch or the eluate from A, both under this category. We just have to state what we are talking about, i.e., the long term storage of the eluate.

Mr. Fortner: It would be more appropriate, since we already talked about it in E.3, it's possible to split, now you're talking about short and long term storage.

Dr. Vogl: And that applies to both.

Dr. Bush: That would be at this point, then, documented for.

Mr. Fortner: What we're looking at is some additional data for patch B.

Dr. Vogl: For patch B.

Mr. Fortner: For 60 days.

Mr. Stephenson: For stabilizing or normalizing the eluate itself for long term storage, and that probably is a container issue.

Mr. Fortner: I think that that's a container issue. While it's possible to look at some of the other components in sweat for normalization, that would be very difficult. It evaporates. It's just going to concentrate it into more.

Mr. Stephenson: Volume is volume.

Mr. Fortner: I think a different storage container to minimize evaporation loss, and then some data on 60 day storage of patch B.

Mr. Stephenson: Do you have your next meeting scheduled?

Mr. Fortner: Right now we're looking at the middle of August.

Mr. Stephenson: Well, if you started something now you would have the data by then.

Mr. Fortner: We would have the data by then.

Mr. Stephenson: Why don't you think about that and leave it where it is for now, and then come back with it at that time. The march will not go on without you.

Dr. Vogl: Let me ask, your 510k submission and everything, the summaries you gave us, it talks about the dry patch and the storage of it, the stability of it for 20 days, 30 days.

Mr. Fortner: Right, right.

Dr. Vogl: Do we feel we need a longer time period for stability of the dry patch?

Mr. Crouch: Where did the 60 days come from?

Dr. Vogl: I don't know. That's why I'm asking. Here all the previous discussions were 28 days. If it's the split, it has to be tested within a couple of weeks.

Dr. Sample: No. They have that 60-day window.

Dr. Baylor (RTI): It's 30 days to request, 60 days or destroy it.

Dr. Sample: Right, 60 days to destroy it. Then in theory they need stability up to 60 days.

Dr. Vogl: That's fine.

Mr. Stephenson: Then you've still got the ability to do that study and to come up with the data by the time you have the working group meeting.

Dr. Sample: It has to be tested in 30.

Dr. Vogl: The donor has to request the re-test within 72 hours.

Dr. Sample: Right, of being notified by the medical review officer.

Dr. Vogl: Right. Let's assume that all happens within two weeks. If it's not requested, they have to keep the bottle at least for 60 days.

Dr. Sample: Yes, there is an inconsistency there in terms of the timing. But nevertheless, the current policy is that we have to keep the specimen for 60 days. And I guess if we were notified between 30 and 60 days we'd still have to honor that request.

Mr. Stephenson: Yes, it's a protection issue for the donor.

Mr. Fortner: Requests come in much longer than 60 days.

Dr. Vogl: HHS policy on splits would be to keep the split for a year. That's our policy, for positives. Theoretically -- it depends on regulations or implementation of our program, to include sweat -- it could be, if we all agree, to keep the dry patch for a year.

Dr. Sample: Then stability would have to be up to a year.

Dr. Vogl: You can't get that by the September date.

Mr. Fortner: No, that's a little tough.

Mr. Stephenson: But that's a good question. You ought to come up with a proposal on how to do the prospective study and try to do a fix on your container issues so that you've got both of those addressed the next time you come back to the large group.

Mr. Fortner: All right, we'll leave that as a P for now.

Dr. Bush: For now, based on the discussions.

Mr. Fortner: G.3, can identify adulterated/substituted specimens. That was moved to a B at the March meeting.

G.4,a, initial test, FDA cleared test. The working group -- in part, one of the things that we did was reviewed the 510k's and actually provided copies for those members that asked for them. I think we had sent some of those.

Dr. Bush: Yes, you did.

Mr. Fortner: Based on that, whether this becomes an issue addressed on an overall basis, it was the consensus of the group, because these are FDA 510k's, that we should move it to a blank.

Dr. Vogl: I'm not sure. It would be for the sweat patch, but not necessarily for some other device to collect sweat. If we write general regulations -- your device is cleared, but –

Mr. Fortner: Well, it's cleared as a device and the applications, the test, the screening analyzer or the screening test, which is what this talks about, the initial testing, are FDA cleared. Now, whether the group ultimately decides this has to be adapted or applied across the board is a different issue. But the consensus of the working group is they are FDA cleared and move it to a blank.

Dr. Bush: And they're cleared in tandem, in a similar manner to what Sam Niedbala was talking about this morning, the collection device with the testing methodology that follows that?

Mr. Fortner: No. That's not an absolute requirement. They're not linked. The device is not linked to a specific application. You could use another device. You could use RIA or something else with the same type of sensitivity. Now, we happened to use an STC ELISA-based product, but that particular product is FDA cleared.

Dr. Vogl: The clearance is for the sweat patch and the data just happen to be based on using the ELISA equipment?

Mr. Fortner: No. It says FDA, initial test, FDA cleared test. I mean, this says, has the immunoassay been submitted, the 510k, for this particular application, and the answer is yes.

Dr. Jacobs: I suggest if there isn't any more comment that we move it to a blank.

Dr. Bush: I'm trying to frame my thoughts, because FDA is currently in a decision making process concerning test devices and collection devices and subsequent tests that are performed on specimens contained in those devices. At this time, I think it would be a prudent measure to just leave this for the time being.

Your points are well taken. They're included in here as part of the record. But I think we'll just wait until the next Board meeting, and at that time maybe FDA -- some decisions may be made in writing from the FDA concerning their policies. I just want to be consistent in our conveying of knowledge and information back and forth between this Board and other federal agencies who are addressing similar testing issues.

Dr. Baylor: If consistency is the desire, then wouldn't urine have to be moved back to an I also?

Dr. Bush: We'll get there, won't we, Mike?

Mr. Stephenson: We're going through these one at a time and this is one of the issues that we talked about at the beginning of the day, was this an element we'll want to have dialogue on and provide information on to help inform that potential FDA linkage.

Dr. Baylor: I just didn't see urine on the agenda.

Dr. Bush: It's on the agenda. Okay. For now we'll just leave it as it is, discussion well noted, and we'll turn the page.

Mr. Fortner: G.4.B, detect HHS analytes. At the March meeting that was moved to a B.

G.4.C, use HHS established testing levels. This was an I at the last meeting. In the working group meeting that we had we reviewed how the cutoff levels which are listed on this page up above were established and they were done through ROC approach, using controlled dose with the exception of PCP. And this was part of what was submitted to and reviewed, cleared through the FDA process.

Although they represent different levels than they are in the urine, I think you'll have that with all the different alternate matrix, and the consensus on this is we've moved it to a B.

Dr. Jacobs: I think we may be a little preliminary here in accepting these cutoffs, and that ties into all the other cutoffs of all the other specimens we're collecting. By making a blank I think we are saying HHS is accepting these cutoff levels. I think they can do these. I think they're good numbers. I'm just unsure how they relate to what we want them to relate to or what they actually mean at this point.

Dr. Bush: Part of our responsibility in the total picture of the program is to take a look at interpretation of results that come from each and every one of these tasks, and I think that's part of the hesitancy here to accept these numbers without a sufficient amount of information on interpretation. We may be able to get a lot of that, Neil, from information that was provided in your submissions that you shared with us, the submissions to the FDA. But I'm not in the position -- I have not had time to go through it with that kind of detail to look at interpretation issues in these cutoffs, because it's very important for us to know what these results mean. We're the ones that get the calls from the medical review officers. We need to train the medical review officers to make sure that employees are given the benefit of the interpretation of the results based on the cutoffs we choose. Is that fair?

Dr. Jacobs: Yes. Do you have more data -- I think I know the answer. Do you have more data comparing these levels of your sweat patch to urine collected at any time during this, or blood samples, hair samples? Any relationship to anything else other than these standards?

Mr. Fortner: No hair in these studies. The one large clinical study, which was in the Michigan Department of Corrections, had, I don't remember the exact number, 10,000 urines and a thousand or so patches. That is information and data that's in the FDA file that you have. You only have volume 1.

Mr. Stephenson: Are you participating in any of the marijuana studies that's going on at the Addiction Research Center?

Mr. Fortner: Yes.

Mr. Stephenson: There will be at least one specimen group?

Mr. Fortner: There's marijuana and actually I think some of the work that's also being done, there's some methamphetamine and similar cocaine work being done. And they're using patches as well as every other conceivable.

Mr. Stephenson: But the point is that there will be some comparison issues between blood and I think saliva and sweat.

Mr. Fortner: From my understanding, Dr. Heustis is collecting just about everything it's possible to humanly collect.

Dr. Jacobs: Neil, could you also accept -- I see amphetamines, cocaines, and opiates all have the same cutoffs. That's something we're not used to seeing in urine. Is there some reason you have to same cutoff for all those, or just address it any way you can.

Mr. Fortner: Only in the sense that when we went through and did the analysis, or actually some of the other agencies did the analysis under ROC, those were the high confidence levels. If you look at the one paper by John Fade and Vina Spieler on methamphetamine, it actually suggests we should be doing screening at 5 nanograms. But you get a higher confidence level at 10.

Dr. Sample: Neil, would these cutoffs have been changed on the basis that you've changed the volume of the eluate from 3.5 to 4 mills?

Mr. Fortner: No. The calibrators are made up in a comparable volume.

Dr. Jacobs: You're still high enough above the level of detection that these are no problem?

Mr. Fortner: Yes.

Dr. Sample: But in the notes it's expressed as ng/mL using 2.5 mL eluate. If you change the volume of eluate --

Mr. Fortner: Do you drop them down?

Dr. Sample: Yes, for comparability, so that the decision point is the same.

Mr. Fortner: You could go to that approach.

Dr. Sample: Well, that changes the set point.

Mr. Fortner: Yes, it does.

Dr. Sample: If you're using the larger volume to do the elution and you don't change the cutoff, you've now changed your set point relative to those ROC curves.

Mr. Fortner: Depending on what you diluted it to, if you diluted it to 4 mL's you could do a proportional change on the cutoff.

Mr. Stephenson: That's where the devil is in the details, right, and that's exactly what this is about.

Mr. Fortner: The sensitivity of these assays, the levels are significantly above the background, and I don't think there's any problem with running plus or minus 25 percent controls even at these levels.

Dr. Caplan: If you're going to continue to change those -- and I think you said the committee agreed or your group agreed with reporting it this way.

Mr. Fortner: Yes.

Dr. Caplan: Wouldn't it be better to report them as nanograms per patch?

Mr. Fortner: Or per total volume. It's a calculation. You could do that. It's a conversion back to total drug per patch.

Dr. Caplan: As we go forward, to keep changing these things it won't be clear. If we're able to standardize or normalize and say it's some minimum nanograms per patch regardless of the volume of the eluate, that's what you adjust. But the rule or the guideline would follow a set number which would be not changeable.

Mr. Fortner: I think currently you'd be looking at 25 nanograms per patch at that level.

Dr. Caplan: That's okay.

Mr. Fortner: That would almost say you could vary the reconstitution as long as it was per patch. But I think the discussion was you want to keep that the same.

Dr. Vogl: Didn't you say the last time they're only extracting or removing 60 to 70 percent that's on the patch the first time?

Dr. Jacobs: I think just previously we tried to move with the saliva group to a nanogram per milliliter, and now we're moving in the other direction back to the device. Whichever way it is, I think we should be consistent.

Mr. Meeker: I think this was a big discussion that we had in the group, whether it should be nanograms per patch or nanograms per mL. We kind of went back and forth as well. The reason we decided on nanograms per mL at the end is because we are talking about someone with a retest of the elution solvent. To be consistent between the laboratories, we'd want to have it reported ng/mL.

Mr. Crouch: All the retest laboratory has to know is what the dilution volume was and they can report it as nanograms per patch, too.

Mr. Meeker: No argument there.

Mr. Stephenson: I think that's a good point and I think it's one thing we're going to need to talk about across different specimens and matrices, to look at which way we want to standardize that. Where science can inform us, that's fine. But I think Yale has already said this before, that we need, at the end of the day we're going to need to make a judgment call on this. The more information we have on this, the better internal construction we'll make across these different specimens. Why don't we go ahead and move on.

Mr. Fortner: Where were we? Where did we leave off on 4.G.c, use HHS assessment level?

Dr. Bush: My thought was that we are not sure of the interpretation of these levels at this time and where they fit into the scheme of things with what we're used to seeing. We're clear that you can accurately and reliably achieve these levels, these cutoffs are reasonable and well thought out and well shown in your FDA submissions.

Right now what you are hearing is a little bit of thought on the part of the Drug Testing Advisory Board on how do we proceed with establishing the cutoffs. You're going to have to give us -- this puts the onus back on us for further discussion and evaluation of what we feel about these cutoffs relative to others. Do we have enough information to say, these are HHS-embraced and endorsed cutoffs? We may need some more information on that.

Mr. Stephenson: I'd link those two together, what's on page 22 and what's on page 24, and you need to be internally consistent across the two of them and look to see what the alternatives would be.

Mr. Fortner: On to page 21, G.4.c is an I.

Dr. Bush: Yes, for now.

Mr. Fortner: G.4.d was a blank at the last meeting.

G.4.e, ability to repeat initial test. I'm not sure, Bob, on your comment on linking this to page 22.

Mr. Stephenson: 22 and 24 both. We want to go forward and look at the issues across all of those.

Mr. Fortner: Well, I read it as the procedure allows initial test to be repeated, whether it's 2 mL's or 4 mL's or 5 mL's. We're talking 20 microliters or so for an initial test. So I think that G.4.e, it's the consensus of the group could be moved to a B. There's certainly more than enough specimen to do initial testing several times.

Dr. Bush: Do we have discussion on this? Any members of the Board, do we have discussion on this?

Dr. Sample: Let's vote.

Dr. Bush: Ready to vote. Ready to vote on this, G.4.e for a change from an I to a blank? All in favor? (A show of hands.)

Mr. Fortner: G.5.a, confirmatory test uses MS for identification and quantitation. In the March meeting this was moved to a B.

G.5.b is already a blank, as is G.5.c.

Dr. Sample: I think it's the same question for the confirmatory cutoff as it is for the screening cutoffs.

Dr. Bush: I know.

Mr. Fortner: You're back to G.5.b, Barry?

Dr. Sample: Yes.

Dr. Jacobs: I think probably we've moved these to a blank because we said they were capable of calibrating the procedure around a cutoff, but I think that the bigger question here may be what is HHS' testing cutoff concentration for these.

Dr. Sample: Right.

Dr. Jacobs: Until those cutoffs are established, perhaps this shouldn't be a blank.

Mr. Fortner: Does this move everybody back to an I or an P?

Dr. Bush: Yes, it looks that way.

Dr. Jacobs: It looks that way.

Mr. Crouch: I think we got lost here, because the last presentation and this presentation is suggesting that here's some cutoffs and this can be done, and what we're arguing is that, well, we're not sure those are right, but that's incumbent upon us to figure that out and not upon these guys to present more data unless we ask them for it. I'm not sure we should change these back, because it's really HHS' or the Board or whomever's privy to set what this cutoff is going to be. There are some suggested. We don't have to accept them, but I think they're doing their job in presenting some that they think will work based on the literature and based on their experience.

Dr. Jacobs: Would we leave it a blank if we just add after "HHS testing," "cutoff concentration when established by HHS"?

Mr. Fortner: That would apply to G.4.c as well.

Mr. Crouch: I agree.

Dr. Sample: We just need to be consistent here.

Dr. Bush: So where are we, G.4.c?

Mr. Davis (RTI): Neil, you indicate that the analyte for confirmatory testing is delta-9-THC.

Mr. Fortner: Yes.

Mr. Davis: And G.4.b, you indicate 11 or delta-9-THC, being the acid?

Mr. Fortner: No, that's not correct. I mean, what we see is the parent.

Mr. Davis: Okay.

Mr. Fortner: Clearly the immunoassays will have some cross-reactivity with the parent metabolite, but everything we've looked for is the parent drug. So that would be a correction typo on 19. We'll change that. On 19 that will be delta-9, consistent then with 24.

Now, G.4.c. Clearing my mind again, we're going to say when HHS establishes, or the same wording, G.4.c and G.5.b?

Mr. Crouch: That's my suggestion, with a note that HHS and/or the Board needs to verify that these are reasonable cutoffs.

Mr. Stephenson: Yes, this is part of your issues that you're looking across these different areas. Is that wording you'd like to see in this area?

Dr. Caplan: We're going to be looking at them all again.

Mr. Stephenson: Yes, exactly. Across each of these we would say the same kind of thing at this point, and that would be some wording which would be consistent with HHS cutoffs when determined by the Board, when established.

Dr. Bush: When established.

Dr. Caplan: That's one issue. The other issue is how they're established. I mean, whether they're established as per dilution or per unit. It has to be uniform, but that's a separate question, using the cutoffs.

Mr. Stephenson: We will craft some words on that.

Dr. Sample: Okay. Is G.4.c back to a blank or are we leaving it as an I or a P?

Mr. Fortner: Or is G.5.b now?

Dr. Vogl: No, it stayed blank. It's just we need to agree. HHS needs to know what they are.

Dr. Sample: G.4.c is now a blank.

Dr. Jacobs: A star.

Dr. Sample: A star, a new category, a star.

Mr. Stephenson: The idea is this is a learning process for everyone and we become more informed with each of these individual sets of reports. We're finding a new area for consistency across them. That begins to shift us into this area of policy discussions later on. We're going to have to go there anyway. We're just talking about it, but it's a very serious issue and it's one that has a lot of impact.

Mr. Fortner: I think Yale said, even when you get them all to B's, there's still another process, going back, reviewing, and establishing policy.

Mr. Stephenson: Yes, and there may be more of a need for information then and dialogue, depending on that issue of what it is that you are standardizing against, how you standardize.

Dr. Caplan: That's another part of the process. It's not for the working groups to worry about right now.

Mr. Fortner: We've satisfied both of those questions.

Moving on to G.5.c, page 25. This asks for performance around the cutoff, and in the March meeting this had been moved to a blank.

G.6., in the March meeting this had been moved to a blank.

G.7 has been a blank for the last few meetings.

Section H, the QC and QA certified laboratory program. I think we've been working on a program. We have one agency outside the U.S. in development, but at this point I think the certified laboratory program has not been established. We'll leave it as a P.

H.2, external PT samples. This is part of a certified laboratory program. I think that we have discussed a number of ways to do it. It is possible. The recommendation was to leave it as a P at this point.

Dr. Mitchell: There's a couple of things. The cutoff question that we had earlier as to whether it should be on per mL of fluid or per patch will make a difference as to whether the program is going to be a qualitative or a quantitative program. If it's on the patch, it can be quantitative. If it's on a per mL, it would end up being a quantitative program approach. The reason for that is the recovery is not 100 percent from the patch. Therefore, if you put it on a per mL basis and the laboratories will not have to spike the calibrator's controls onto the patch, they can just spike it directly into the fluid and utilize that as their calibrator's controls. I think PharmChem is spiking the patches, so it doesn't matter to them.

Mr. Fortner: You would treat the standard control the same way you would treat a big sample.

Mr. Crouch: We don't adjust any matrix for recovery. That's incumbent upon the laboratory.

Mr. Fortner: I think what John is saying is if you're recovering from a patch and your standard or your controls are not spiked onto a patch and it's subsequently recovered, you can have a bias in that certain degree.

Mr. Crouch: To me, that's the laboratory's problem. You just set up methods that work based on the analysis of the specimen, and the specimen is the patch.

Mr. Fortner: I think there's a consensus on that.

Mr. Stephenson: I think this is an issue that John was wise to wait in the sense that we're going to have to also address it later on and which direction we're going to go in terms of PT.

Dr. Bush: When you prepare your PT material now, blinds or opens, do you spike the patch?

Mr. Fortner: Yes. The interesting thing, it needs to be a patch that's either worn or has been exposed to a synthetic sweat, if you will. It's like spiking a dry sponge. It won't absorb material.

Dr. Bush: John, just for the record, help me understand that a little bit. If we're looking at the result reporting as a per mL in terms of the units or per patch, per mL will be the quantitative program?

Dr. Mitchell: Qualitative per mL.

Dr. Bush: Per mL would be the qualitative.

Dr. Mitchell: It has the potential of being qualitative because of the differences in the elution from the patches, and the variation between laboratories is going to be much greater.

Dr. Vogl: Couldn't you spike the patch with the internal standard before you elute?

Mr. Fortner: You'd have a lot of positives with your screen.

Mr. Stephenson: This is exactly the kind of thing where this is part of the dialogue between RTI and their presence and participation in these working groups, and it might be one of the things you'd want to schedule as part of the discussion for your next small working group. If RTI can structure questions, that might be something at some point to put together.

 

Dr. Bush: Based on everything that was just said, I'm reflecting back to oral fluids discussions from this morning and I'm not sure. I can't make the leap between qualitative versus quantitative.

Mr. Crouch: Well, this morning what they said was based on saliva or oral fluids collected, and to be consistent I think it needs to be the patch, because once the patch is eluted or once the drug is eluted from the patch then the concentration becomes sort of arbitrary. If the patch is the specimen, then the concentration or the amount needs to relate back to the patch and then people can use whatever elution volume they want to use. It doesn't matter.

Dr. Caplan: You're using an elution volume because it's convenient and you get a certain recovery, which you study, I assume.

Mr. Fortner: Yes.

Dr. Caplan: You could either calibrate, so to speak.

Mr. Fortner: I don't think you'd want to use less.

Dr. Caplan: But you could use more. I'm saying you could get -- what's your recovery? I don't know, 70?

Mr. Fortner: About 60 to 70 percent.

Dr. Caplan: But you could get that out if you did a double elution, for example.

Mr. Fortner: Yes.

Dr. Caplan: You could also with a fixed volume probably get within 5 percent, recoverable percent elution.

Mr. Fortner: Yes, I would think so.

Dr. Caplan: Those are the kind of things, that go back to the saliva. Unfortunately, the specimen here doesn't have integrity and it only has integrity if you take it all off or you know the relative amount that comes off on a regular basis. But it would have to be equated back to that amount on the patch for consistency somehow.

Mr. Fortner: You express it per device.

Dr. Caplan: Exactly, per device.

Dr. Sample: When we were talking about oral fluids, we changed H.1, certified laboratory program, to a blank because there's nothing to prevent future construction of programs to quote what's on here. On that basis, I would say the same would apply to sweat.

Why would we leave sweat as a P?

Mr. Fortner: Because I had always interpreted this as a P is possible. If you want to do that you can move everything to a B and say we'll just bring the data.

Dr. Sample: I'm looking for consistency again in terms of how we're evaluating each of these alternative specimens.

Mr. Stephenson: You keep that in the front of your mind for every one of these as we go along to challenge.

Dr. Sample: A big flashing board up there, so we can remember what we decided on the previous ones?

Mr. Stephenson: That's why we've got a transcript.

Dr. Bush: That's exactly why we have the transcripts, and that's exactly why I have to go back over this where we're looking at per mL of saliva as the specimen and per patch here. I just wanted -- I wasn't real clear on that.

Dr. Sample: John, what's your opinion again in terms of having a certified laboratory program for sweat? Do you recommend a blank for that or a P?

Mr. Stephenson: It doesn't matter at this point.

Mr. Davis: As long as it's consistent.

Dr. Sample: Right.

Mr. Davis: It's up to the Board whether it would be called blank or a P. It is possible, but it isn't in existence now.

Dr. Sample: But blank means can satisfy requirement, is the definition of a blank.

Mr. Davis: I guess my recommendation would be P.

Dr. Sample: Then oral fluid is also a P.

Dr. Bush: Where are we here?

Dr. Caplan: A blank means it's there and it's sort of been established. A P means it can be done, but it has not necessarily been established. Those kinds of things are P's. It may be hovering in between. We know we can do it, there's no inhibition, but it hasn't been done, so there's not a model out there.

Mr. Fortner: That's how I had always interpreted the difference between a P and a blank. It's ultimately for the Board to decide how they apply these.

Dr. Caplan: As far as the subgroups are concerned, P's or blanks are all you need to get to.

Mr. Stephenson: The purpose of this dialogue is to help inform you for the issues that you need to focus on for your next working group meeting, and I think for purposes here you've gotten that kind of feedback.

Mr. Fortner: Yes.

Mr. Stephenson: Laboratory inspection programs, the next one.

Dr. Bush: H.3.

Mr. Fortner: I'm going to have to play the devil's advocate and now say, if H.1 was a P, following that line of thought, should H.3 be P's?

Mr. Stephenson: Yes, because it's the same issue in terms of consistency.

Mr. Davis: It's possible, but it doesn't yet exist.

Mr. Stephenson: And you'd want to have further dialogue, too, before there was an inspection program established for your program, and you don't necessarily have that from us.

Mr. Fortner: I believe that would be appropriate.

Dr. Bush: So do we.

Mr. Stephenson: I agree and a P is fine. Again, the purpose of discussion for this group, at this time, is to help in an interchange between members of the Board and the small working group such that you can focus on issues that you need to get to a point. I think without us trying to do a horse race with every individual column having an I or a P or a blank in it, the purpose of this discussion for two of these presentations today has primarily been to get us to a point where there's a good understanding between the Board and the small industry-based working group that you can continue your work to get information that will help us ultimately make the kind of decisions that we've got to make about the program, how to write a proposed rule, how to get it out for discussion, and what are some of the underlying principles that we need to deal with. We're getting there.

Dr. Jacobs: We've been having a conversation here about what the meaning of P and B is, and P says possible and B says can satisfy requirement. Maybe B has become requirement satisfied and so maybe we've kind of changed the definition here of what a B is. Somebody say something here. Is that what the feeling is? That if it's a B it has met the requirement, it's done, rather than can satisfy the requirement?

Dr. Sample: I agree, it sounds like it's changed. Originally I thought B meant that not only is it possible, but we have sufficient information to say that it can satisfy the requirement, not that it necessarily exists yet.

Dr. Jacobs: Do we want to change that definition or do we want to leave it the way it is here?

Dr. Bush: When this grid was first developed back in 1997, I remember very clearly Dr. Skip Jones, who was key in helping us develop this grid, telling me clearly we would come to this point, and we made it today, where we're confused a little bit with the definitions that seemed so clear to us back then. Now we've come so far that we're having trouble seeing exactly in the context of that very sketchy, yet clear, grid. We're there. We're now getting into much more detail than that first grid set us up to get.

Mr. Stephenson: I think the bottom line for us here today is that we're looking across specimens. We're looking at -- strike this as a philosophical discussion about where we go. You start out with a concept, we're looking across the specimens to try to create one rewrite of a proposed rule that will incorporate all of the alternative specimens and technologies. To do that, we need certain information, certain constructs that will help us at each stage that have been defined as elements within this grid. For purposes of clarification, whether it's a P or a blank, for purposes of the internal working groups or the small working groups, it's probably not going to make a lot of difference as to where we ultimately get, because ultimately you're going to have to go back and measure across these different specimens, maybe in September or October when we have a lot of this work done. The areas that are important are looking at those areas where we had I's, or if we ever created an N and say you can't do it and that becomes a true barrier to going beyond where we are. I don't think that's where we are right now.

Dr. Sample: I thought that even P's meant that we needed more information back from the working groups, and I thought that a blank meant that we were satisfied and we don't need any further information from the working group. I feel like we've taken a step backward and muddied that by saying, well, P could mean that we don't need more information, but a P could also mean that we do need more information.

Mr. Stephenson: If we all had our philosophical and scientific hats on and we had it all in front of us right now across all these specimens and could answer each one of these elements and maintain it in our minds across all of them and then start the framing discussions for a rule, yes. But we're learning and we've got to re-inform ourselves. I think for purposes to get Neil off the hot seat here and let him continue doing something productive in his life, I think we're doing what he needs to hear from us, and we're getting a sense from him what it is we might want to ask questions on. If you have more specific questions you want to ask, ask him. Do it now. If there's something that you want from him that's beyond, instruct him. Can we go ahead and continue?

Dr. Bush: We're still on H.3.

Mr. Fortner: It's a blank. It's a yes. The last the information is that five laboratories are doing sweat testing and they're being inspected and there is a program.

Dr. Bush: We're going to move ahead.

Mr. Fortner: Moving along, H.4 is a blank.

I.1, reporting. I think all of the reporting sections were blank from the last meeting.

That would take us to section J, MRO. J.1, interpreting results. Now, pursuant to the working group meeting, it was the group consensus that this section on interpretation or results should remain as an I pursuant to development of some other formal training or frequently asked questions expounding on that.

Dr. Bush: Yes.

Dr. Vogl: What do you have now as far as what information is given to the Department of Corrections where you're doing all the testing? Just when it's positive? Is there information given on interpreting it?

Mr. Fortner: We have a series just based on inquiries we've received or issues have been raised in proceedings of what we call frequently asked questions. They go from why do I have a positive patch but a negative urine, to what could this mean in interpretation? That's part of what's being already put together.

Mr. Stephenson: And you have case law, too. You have actual case law decisions.

Mr. Fortner: Case law, yes. I think somewhere in the back there's some case law.

Mr. Stephenson: It's continuing even as we speak.

Mr. Fortner: Yes. J.2, alternative medical explanations. Again, we believe that this should remain as an I pursuant to some other development and some work. One of the questions that was raised I believe back in March was some data on efficiency of the alcohol pad removal if drugs are intentionally or somehow deposited on the skin. We have several studies that are under way. I thought we would have data summarized by today's meeting. We have just not been able to get that done. We will certainly have a significant amount of data for the next working group on that. But for alternative -- for two different reasons, we would recommend that that stay as an I.

MRO training, which is J.3. I believe that that ties in to some of the other issues in J.1 and J.2. I would leave it as a P.

K.1, we actually had some discussions on during the working group. With the exception of PCP, we have data that was in the FDA 510k filings and have looked at some different controlled studies and some different conditions. To be honest with you, the working group didn't understand what it was being asked to provide, what additional information was needed. So I am posing the question. It's a result related to dose/time response.

Dr. Bush: I think your question, what does it take to get from a P to a B, I think just a couple of questions ago you heard some of that. Do you want to do it again?

Mr. Fortner: Well, this was written some time ago.

Dr. Bush: The same things that you were asking.

Mr. Stephenson: But we've asked it in the group now. It's not going to be a barrier in the proceeding. The issue of having it as a blank or a P at this stage in the development and in your dialogue with us as the Board is not a barrier to anything.

Mr. Fortner: I understand that.

Mr. Stephenson: It's not going to be a barrier later on.

Mr. Fortner: Based on the data that we did in the working group, it was the consensus that we could move this to a B.

Dr. Vogl: Somewhere you had negative patches, volunteers, and then they were given the drug and you took patches off and you showed what minimum dose you needed to get a positive patch result. You have the studies.

Dr. Bush: That was in your FDA submissions.

Mr. Fortner: I do believe that that data satisfies this question of concentration of drug or metabolite related to the time and dose response --

Dr. Jacobs: Let's move it to a B.

Dr. Bush: Do we have a vote?

Mr. Crouch: You've got to state the question before you can vote.

Dr. Bush: Shall the Board change question K.1, miscellaneous issues, result related to dose-time response, from a P to a B, based on the information that has been presented to us?

Mr. Stephenson: All those in favor?

Dr. Bush: All those in favor, aye, or raise your hand. (A show of hands.)

Mr. Stephenson: Okay.

Mr. Fortner: I believe the last question was K.2, which was a blank from the last meeting. Then you have one of the issues that came up, suggested by one of the participants in the working group was whether or not DTAB would consider an additional section in the grid entitled judicial review.

Mr. Stephenson: That's a good idea and it's one where I think we can be instructive because there are applications in other environments than the workplace which may affect case law decisions anyway. We might as well begin to do that. I think there's probably cases where that's true with almost all the specimens.

Dr. Bush: With almost all the specimens, that will help us make informed decisions about how we proceed with each of these alternative matrices.

Mr. Stephenson: Case law does have a way of defining issues. It's beyond our scientific analysis and they tend to come up. I think in your case law area the one that we're looking at is methamphetamine, and that's one that will become -- continue to be an ongoing issue for some time. Every different specimen technology might have a similar thing pop up. It's a good idea. Do the members of the Board agree that we should add an element that would be case law review? Calling the question, all those in favor of adding an element to the grid that would add case law review? All those in favor hold up your hand.

Dr. Bush: I think Shirley had some discussion first.

Dr. Welch: I just had a question. Do we need to add a piece to the grid or do we just want information?

Mr. Fortner: It might just go under additional information.

Dr. Welch: Would it be a requirement?

Mr. Stephenson: It would be in the grid. Is there additional case law information, yes or no and then see attached.

Dr. Caplan: Who's going to get it? Is that something you can get through your attorney?

Mr. Stephenson: It's something we can certainly pursue. But I would imagine each of the industries has an adequate starter, so it would give us an edge of the universe to look at anyway.

Dr. Bush: We'd ask each of the groups to provide case law, to track that on their own or are made aware of it because of their own direct participation, to please provide us that information so that it will be easier for us to get the complete cases, etcetera.

Dr. Mitchell: And that includes cases not upheld?

Dr. Bush: Absolutely, cases upheld, cases not upheld. Judicial review.

Mr. Stephenson: Yes, cases. Neil, have you had any in court that have not been upheld?

Mr. Fortner: Not to the best of my knowledge.

Mr. Crouch: That was a witness's response.

Mr. Fortner: Unfortunately, there are cases where we are not present. The other issue out of the working group was there were some recommendations for modifying the chain of custody just to make it more clear in terms of application and removal, delineating the two halves of the chain, because they looked somewhat similar and they thought that making it either different color or different print or something.

Dr. Vogl: You mean the form that you currently use?

Mr. Fortner: The form that we currently use. The left side is for application, the right side is for removal.

Mr. Stephenson: Would you like to have some input into the collection and chain of custody form that we are developing? Would you like to see it?

Mr. Fortner: We actually have members that have been attending the meetings. I appreciate that. I believe that brings us to the end of this section.

HAIR TESTING

Dr. Selavka: We're going to give you a rundown on the outcome of the first, second, and third meeting of the hair testing working group that met on three different occasions in San Antonio. I am a laboratory director in Massachusetts. I'm also the scribe and the whipping boy to come before you and give you the input.

These are all the disclaimers that apply. I'm just talking for me. I am trying to talk for the hair testing working group, but everybody else that's mentioned, I'm not talking for them and it's not official policy. Of course, you've heard all the disclaimers before.

In any case, what I'm going to give you is a series of presumptions that hopefully will be useful for discussion topics, give you historical perspective on where this group's been and what we've given you, and a little bit about the iterative process of knowledge that we see at work within this protocol development, the areas of consensus that we have, and then we'll go over each of the elements separately on which there is more discussion to do today.

One of the presumptions you could make, I suppose, is everything is perfect. The reality is everything isn't perfect. Regardless of the matrix we're talking about, we all believe and I think understand together the complementariness of life is important to remember and it's part of the reason why we've been working on what we've been working on.

The current protocol works for all situations. I think we can agree that that is probably not the case either. Depending on what you get, that's how you should determine what to apply. We have technologies available. I think the goal of this group and DTAB, in general, is to build the very best workplace drug testing program that can be built, using the best technologies available.

We would like to believe that the courts uphold our forensic tests without question. We know that that's no longer the case and really has never been. It is the nature of the courts to be an adversarial process and, therefore, there will always be people, no matter what we do regulatorily speaking or even as scientists, someone will be able to poke a fork into us and find a soft spot, no matter what we do. I think we have to remember that.

We may fool ourselves by thinking we know everything we're supposed to know or can know, and that's not true, never will be. It is the nature of science, the nature of life, to be iterative and to allow us new understanding.

I want to step back just for a second and remind all of us that there are a number of unusual samples for which we're not trying to create regulatory guidelines and to promulgate rulemaking. A number of these would be very difficult to collect. We may want to collect them on some people, but we won't be allowed to.

What we have done is selected a number of complementary matrices for recognition of different drugs and metabolite packages related to different kinds of use and exposure situations. I wanted to put this up here just as a reminder, sort of a road map of where we are and what you have given us to do.

The detection windows that are available from oral fluids, from blood and its products, from urine, sweat, and hair are very different: Sweat looking prospectively, hair looking long in the past, and oral fluids, blood, and its products sort of give you a one-day window or so, with urine giving you a three to five-day window.

All these technologies, though, had a starting point, whether it was urine drug testing -- it started as a clinical testing paradigm, turned into a forensic one in the seventies. It had its own issues of immunoassays being used twice as a certification, if you will, or GC/FID of marijuana being used as confirmatory where there's a little bump on the chromatogram.

We started somewhere. The nice part is I think we have enough history in drug testing environments, in general, to know what good and bad forensic science looks like. But there were some -- there are some modern accreditation issues, even within urinalysis, including artifactual issues, issues of adulteration and hydration and interferences with tests, some lack of interpretive rigor for opiates, for example. We've had this constant struggle of what to do with the opiate cutoff to get around some interpretive issues. And the latest case, Campbell and some other cases that are now citing Campbell as some suggestion that the way we do GC/MS or MS/MS experiments isn't being accepted by the courts perfectly. We still have some work to do and we always will.

The point of this slide is we are never done, no matter what the technology is. Sweat testing is in its relative infancy, as is oral fluid testing, as is hair testing. But we can build upon the good program that your analysis provides for us.

We have been going, though, and I think you can always tell when you've made it by what happens in the Sunday paper. If you didn't see this before, I put it up for your use: Catbert, evil director of human resources, looks on his screen and sees Wally and thinks: "You're next." He says: "You've been selected for an employee drug test." "Why am I the only one that ever gets chosen randomly?" "Oh, you must be very unlucky at work. I'm sure you compensate by being lucky at love." Anyway. "Our next drug test uses hair samples. To be safe, give me six hairs and one whole eyebrow. I'll come back in an hour and say I lost the box." You know you've made it when you're in the comics.

Hair drug testing has been going on long enough for us to have reached a good point. We've had a good series of working group meetings to provide you with some good data. I just want to remind you of the iterative process of knowledge. Things don't happen in a vacuum. We build upon the past, and we will build upon what we do today in the future. It's the nature of what we do.

I've shown you this many times before. You've asked us to think outside the box and to come together, form consensus, not be a group of -- not be a bunch of individual laboratories, but be a group of stakeholders in hair drug testing, and I think that's what we've tried to do.

This started with a survey in '97 of the seven major laboratories doing this kind of work. Those people at that time gave us a number of pieces of data that we brought to DTAB and helped form the matrix at the beginning. We do realize that the alternative matrices are the little fish, and as we examine things we find that there are significant areas of consensus.

I should remind us also that this working group is composed predominantly of active hair laboratory staff people. However, it does have a number of outside scientists, medical review officers, a number of observers and guests, people who don't want to say they're there, but they're there.

There are a number of issue-specific invitees that we did. We brought in people that we would consider contrarians to the popular feeling within hair drug testing laboratories of what is right and what is wrong.

I think Lieutenant Colonel Jacobs can verify the fact that we are fueled by donuts at these meetings, usually with high fat content. It was a voluntary process. We did invite people to the meetings. The first one had 9 people, the second 16, and the third 15 people. We've also had international liaison with the international hair club for men, if you will.

We have reached consensus on a large number of points. You heard from us at the last meeting, but I'll go over the ones that we have consensus on within our group: how much to collect; what type of hair to collect; what length of hair to collect; the good stability of drugs in hair based on data that we have from laboratories; the integrity of the collection process is good.

We have now chosen screening analytes and cutoffs for all analytes and analyte classes that are a consensus within all of the operating laboratories in the field. We've defined screen precision around the cutoff, the confirmation analytes, and their precision requirements around the cutoff. We've defined confirmation cutoffs to limit claims of external contamination, but for no matrices is there an elimination of that. It just limits it.

For specific metabolites, within the opiates, amphetamine, cocaine, and THC class we asked for metabolites and not parents only, and we have a number of rules around how to report them.

We've defined sources of open quality control positive material, how to get them, and how to design a blind PT protocol. We'll go over that today.

We've defined interpretive guidelines that we can all agree upon within the field; alternative medical explanations that are very similar to those used in other toxicological paradigms.

We've looked at the dose-response relationships and the comprehensiveness of the PT program that's currently being used, and we defined it as another iterative process. We'll start somewhere and we'll let it grow from there, as we have with other matrices.

We've also defined MS/MS and traditional single separation MS guidelines.

One other place where we found consensus is we've decided together that bias is a normal component of all bio-marker tests. If you look at "bias" as a word definition form and look at how it applies in toxicological settings, there is bias in everything. We believe that animal models do not perfectly correlate with the human experience that is seen in laboratories that do any kind of testing in hair in normal populations, and we don't think that low dose studies can be perfectly extrapolated for interpretive purposes and be thought to be dispositive upon the matter.

There are some areas where we have reached new consensus or reached areas where there is just no consensus available or it's not needed, but needs discussion. On the biophysiological and cultural specifications, a brand new review and a meta-analysis has now been performed and the review has been published by Tom Mieczkowski and the meta-analysis is going to be presented at the international meeting this summer.

Decontamination challenges, we've found some consensus on that, how you might go about defining them for the laboratories that choose to participate in the Federal workplace program with hair.

We've defined for you, as you asked us to do last time, what research programs we would like to see funded and have them taken up for hair drug testing and other matrices.

We have looked at the external review of the MS/MS criteria. We have a group of people we'd like to send it to, with your permission. And we'd like to create a frequently asked questions document to replace that that's now at this point about ten years old, based on 12 year old literature. We'd like to update it with all the newest information.

The bottom line on all of this is the information you want looks something like this, and for all of the matrices, including ours, the information available looks something like that. That's the reality of our situation. That's what we've been faced with and that's what we've tried to address.

We haven't been caught up by this too much and twisted into knots, and we don't expect stasis. We don't think we're going to be standing still. After today, new knowledge will come out tomorrow that's going to be built on what we did today.

We also challenge the idea through falsifiability. Any time that someone says this is or is not the truth as we understand it, we have to remember that it's an iterative process. We can challenge it and change what is known each day, and it's really a question of balance. I use my hair balance slide here.

One other thing I wanted to remind you of is, in laboratories that are currently doing hair drug testing in populations, be their workplace or other forensic applications, there's already a program of quality control. In those laboratories there are already programs of quality assurance. The only thing missing at this point are national standards upon which the quality assurance programs can be normalized. That's it. The laboratories are already doing quality assurance.

So those that are using these laboratories are not under any predisposition that they need national standards in order to get a good quality product out of their laboratory. They will know it by how the service delivery is and whether the results are supportable, which they have been.

I want to acknowledge the fact that you have been able to bring us together as a group of workers and stakeholders on three occasions. We really appreciate that. We know that that's unusual in the history of drug testing, to have it done this way, and we really appreciate that we were able to do it. I want to acknowledge those members of the hair drug testing working group, there was a large number of them, actually almost 25 separate people, and then all of the laboratories that have participated over the last few years in putting this information together.

That brings us to the book and the specific elements. I've listed each of them in the following slides, and if you don't mind I'll just sit down and we'll go through them and take your questions one by one.

Page 5 regarding FDA clearance. This is under hair, page 5. We believe that basically DTAB will have to collaboratively solve the problem of FDA collection with the FDA. It's not up to the hair testing working group. But it does remain -- it has an I on it. Perhaps it should be a P. We don't know. But that's an element that we'll never be able to change by giving you scientific data.

Dr. Jacobs: Could I ask those out there that do hair testing, do you have any thoughts at all on FDA input?

Mr. Stephenson: This is the issue that we brought up with two working groups this morning and I think this is the issue where we are now in the third one.

Mr. Thistle (Pychemedics): Since we're dealing with page 5, this is the collection device FDA clearance, as far as I think we're concerned, we don't have a collection device. This issue came about a number of years ago, if you remember, with the FDA thinking that the envelope was a collection device and the FDA has gone away from that position.

Just in terms of specifically C.3, collection device, we don't think we have a device for that purpose. The other FDA issue I think still remains, and that's your call. I just wanted to point out the difference.

Dr. Selavka: Matrix elements D.2, 3, and 4 are inclusive of pages 8 through 10 in your document. Essentially, these question the ability of hair drug testing laboratories to collect sufficiently sized samples to provide for multiple tests, split samples, and questions about stability and storage, stability of drugs in hair, and during storage.

What we have done today is basically specified a 70 milligram amount is sufficient for testing, the stability in our eyes is good for retest, the demonstration in literature is sufficient, and not only can you do a split sample collection at the time of the initial collection, one of the things that's useful about hair is that after a collection has been done the first time and a test has been found to be positive, if someone questions the test we can actually go back to the head or body of the person from whom it was collected and gather another sample that represents roughly the same time period as the initial sample. It's something that's difficult to do with any other kind of matrix. That's actually a benefit of this matrix.

I've asked John Irving to bring along some 75 milligram samples for you. The last time we had this discussion, where I was from taking a whole hunk of hair was no big deal, take a whole head if you wanted to, so I wasn't familiar with 75 milligram samples. John brought along a bunch of those, and he's going to pass them around.

Mr. Irving (Psychemedics): We have measured out 75 milligrams of hair at the 3.9 length of hair that we measured.

Dr. Selavka: These are all the same?

Mr. Irving: They're all the same, yes. We collect all the way down to the scalp and we would take the hair, we would have it in an envelope to show what is the root end. We measure 3.9 from the root end out, cut that, and that would be the 75 milligrams as required. If the hair is shorter, if it's only half that length, we need 75 milligrams, so we're going to need twice the amount of strands of hair if the hair's not that long. These have already been cut to the 3.9 cm length. This individual had hair about this long (indicating).

Dr. Jacobs: All these samples are the same?

Mr. Irving: The same individual, taken at different parts.

Dr. Jacobs: What we have are 75 milligram samples?

Mr. Irving: Yes, 75 milligram samples at the 3.9 cm length otherwise agreed to. And that's sufficient for numerous tests, screening tests, and confirmation tests.

Dr. Selavka: Again, in the absence of available head hair or if there is a cosmetic issue with having 3.9 cm removed from the head, we did make provisions for alternative collections from the underarm, chest, back, leg, or arm. We did not specify pubic hair collection for workplace testing purposes, although they're routinely used in other forensic circles. We decided to take them out of the Federal workplace proposal that we gave to you. Any discussion on that before I go on?

Dr. Caplan: Are you doing them all at one time? You said multiple testing.

Dr. Selavka: Well, 2, 3, and 4, the way that you had specified in the outcome document last time was 3 relied on 2 and 4 relied on 3 and 2. I just took all three of them together.

Dr. Caplan: Do you have a recommendation? You just mentioned two things. One is the hair specimen itself, which I guess could be split, and the other was going back to the individual. For the purpose of this program, are you recommending one or the other?

Dr. Selavka: We decided that split samples are actually being collected by the New York City Police Department, for example, and a couple of other users of hair drug testing for current application. We would leave it up to the program to decide whether you want to do split sample collection at the time of collection or whether you could take advantage of the fact that you could always go back a week later and get ostensibly the same sample.

Dr. Caplan: How about a technique for collecting a split specimen? Would you take the hair that you circulated and longitudinally separate it, taking in two places?

Dr. Selavka: I don't think it would be the recommendation. I'll speak for them, although we didn't talk specifically about this issue. It would probably be better to collect two separate samples in two different folders on the head at the time of collection, rather than trying to split it, because once you've collected a hair sample in essence pulling it apart can become somewhat problematic. I think it's better to collect it, basically hold it, cut it, seal it, hold it, cut it, seal it.

Dr. Jacobs: Carl, would you like to lead the discussion here on how many tests this 75 milligrams of hair would do? How many drugs can we look at on this or how much would be left for a retest?

Dr. Selavka: The 75 was determined based on 10 milligram aliquots being used for the testing. Those 10 milligram aliquots are generally used, a single aliquot for a screen. Some laboratories do another aliquot for a second screen. Some laboratories then follow up with confirmatory testing on 10 milligram aliquots. Generally, two drugs being positive in a hair sample is about as high as you get, but they've had other polydrug positive findings. This should provide sufficient amounts plus an additional amount left over for a retest that may be requested by a client, either by the test laboratory or by an outside laboratory to whom that remaining sample could be delivered.

Dr. Sample: Colonel Jacobs, is that a departure from the discussion the last time? I thought I recalled the usual practice was to do a single digestion and then take multiple aliquots from that single preparation, as opposed to going back and taking 10 milligram portions of fresh hair and doing a digestion each time.

Dr. Selavka: I believe the formal process in the laboratories that do this to any extent is to have a separate weighing exercise after the initial findings are in hand. So you would do your immunoassay and then if you have a positive you have to go back to your original hair sample and take another 10 milligram aliquot and then go from there.

Dr. Sample: Is that true for all the laboratories who are doing hair testing?

Dr. Selavka: I'd have to ask. We have another couple of laboratories here. John, is that how you do it?

Mr. Irving: Yes.

Dr. Selavka: And then Christine?

Dr. Moore (U.S. Drug Testing Laboratories): Yes.

Dr. Selavka: U.S. Drug Testing Labs says yes. I know APL does it that way and NMS does it that way. I cannot speak for Poison Laboratory or ATI.

Dr. Sample: Thank you.

Dr. Vogl: Theoretically you could get seven separate 10 milligram samples, digest them, and do an analysis, if you had 75 milligrams, right?

Dr. Selavka: Theoretically. Like urine, it's hard to get the last drop out of a hair package. After you get so much out of it, the rest is more difficult by static electricity and other means it's sticking to the package.

Dr. Vogl: If it's positive from the first 10 milligram sample, if there's one or two drugs, you would go back. If it were two drugs, you would go back and do two separate 10 milligram samples. Half of the original sample would be intact and would be available for testing down the road.

Dr. Selavka: On the question of how to do the confirmatory testing when there's a dual positive screen finding, some laboratories do confirmations that would be inclusive of opiates and amphetamines in the same extract. In that case, you may have a single aliquot relating to dual confirmed positives for those two drug classes. On the other hand, other laboratories take a single aliquot for each drug class for which positive confirmation is desired. It kind of depends. I should also say that not every laboratory wants to do 10 milligram aliquots. Some want to do bigger aliquots. This gave them some flexibility to be able to do an adequate amount of testing even with what they would consider a very small sample.

Mr. Stephenson: What you have here reflects a consensus across the working group members, who are actually practitioners in laboratories, that this would be a minimal collection standard that would allow for these tests, and this then sets a standard by which you can say if you go above that you're addressing issues of cosmetics versus comfort for what you can do with the test. But you have some consensus here. That's a pretty big area of change, isn't it.

Dr. Selavka: I would say that the nature of the collection process is that you will routinely get more than 75 milligrams. That's the goal of the collection devices. 75 milligrams we would consider the minimum that you want to collect –

Mr. Stephenson: Exactly.

Dr. Selavka: -- in order to provide a sufficient sample.

Mr. Stephenson: And there's a consensus across the different members of the working group in that area, as part of what your report is?

Dr. Selavka: Yes.

Dr. Jacobs: At present we do not have a blank and I want to know is there anything else that people can see here that we need to look at to change letters?

Dr. Bush: We have D.2 and D.3 that kind of go together here.

Dr. Jacobs: Yes, D.2 and D.4 kind of relate.

Dr. Bush: Well, not the stability.

Dr. Jacobs: If we have enough here, I think the stability and storage will answer that.

Dr. Sample: If we haven't done the studies looking at long term storage.

Mr. Stephenson: They might have. I don't know if they have or not.

Dr. Sample: That really was a question.

Dr. Selavka: The laboratories have studied the stabilities and the five drug classes that are of interest to the Federal workplace program are all stable at room or refrigerated temperatures in hair over a one-year period. The only one that had any degradation that was mentioned in hair specifically from the first meeting on is cocaine. We saw about a 10 percent degradation from cocaine to benzoylecgonine in room temperature conditions in one laboratory. All the others did not recognize that, did not experience it, plus they're all refrigerating, or many of them are refrigerating samples anyway. And under conditions of refrigeration the one laboratory did not have intrusive degradation.

Our feeling also was if we use it at least as a starting point, with some of the features of the current workplace program, that kind of degradation will be acceptable.

Mr. Stephenson: I think Aaron had raised a point that he would like to see if there are other issues the Board wants to raise in order to address an issue of change. Now, in a couple of the other working groups it was just information, but here they're offering some basic things. If you want to couch some questions as you go along in an area where there's concurrence, go ahead and make the changes at this time.

Dr. Sample: I think certainly that D.2 and D.3 could go to a blank based on the information that we have here. I guess the only question that I would have is have we seen enough data or do we need to see any data, or more data with respect to stability? But if there's evidence out there that they're stable for a year or more -- and a 10 percent of degradation of cocaine in my mind is not significant.

Mr. Stephenson: Is that information going to be made available in a formal set of material for later on?

Dr. Selavka: It's probably a good launching point for that question to be applied to all matrices and all groups for the Board's purpose.

Mr. Stephenson: Absolutely.

Dr. Selavka: If you need to see everything that we relied on to make our recommendations, you're going to be inundated with a mountain of books and papers and articles. We thought what you told us to do was get the people together who know about this stuff and decide together whether it exists or not. Now, if someone were to challenge you during Federal rulemaking you would have to, I presume, look to the Advisory Group to pony that stuff up for you. You'd say: You told us it was okay; where is it?

Mr. Stephenson: Is there a condensed version of, here are three tables showing numbers we got from various studies?

Dr. Sample: Or published references.

Dr. Selavka: Yes, and that standard will be held for all the working groups.

Mr. Stephenson: I would think it would have to.

Dr. Caplan: We were talking about this earlier that eventually, and I think you may be a little further along since you started earlier on this, is that these pages, regardless of what letter or thing is on the top, have to be filled out with summary information about why each of those is okay, a table if it's appropriate to summarize your information, and any references, not the papers but the references. And that's for everybody in all things.

We're not going to be able to put this together in the end unless we have notes of this summary nature coming out of each group for each question in the same fashion. In the end, all the other groups -- I know some are further behind. This page is fairly full. Maybe we can condense it, but we will need that. We're not going to remember all that.

We obviously don't want reams of paper to go through. But you do want the citations and bullet notes as to what you agreed on, like you just made a statement that one year, except. Okay, we need that statement in here, and we'll come back to you if we need to prove it. But if you have agreed upon that and that's a statement, then those statements need to be listed for us.

Dr. Selavka: Okay.

Mr. Stephenson: Is there any disagreement that we could move these two areas, D.2 and 3, from P to blank?

Dr. Bush: I think we need a vote.

Mr. Stephenson: Everybody in favor of changing D.2 and D.3, hold your hand up. (A show of hands.) All right, you have D.2 and D.3 changed to blanks.

Dr. Selavka: D.4 we owe you a table and references.

Dr. Sample: One or the other. We don't need both.

Dr. Bush: I like my tables referenced.

Dr. Caplan: You won't know what to ask for if you don't have the references listed.

Dr. Selavka: E.6, deterring tampering, adulteration. When looking at the definitions of tampering and adulteration, we have to find not only those two, but also unsuitable samples. And after the last meeting we did go back and we've redefined unsuitable sample as something, more simply stated, as a sample which exhibits characteristics which preclude proper laboratory testing. This becomes a much more useful definition on a practical basis in the laboratory. There are so many ways that a sample can become unsuitable for the laboratory's procedures, and I think if we use our historical knowledge of urine and blood and other biological materials testing we would all recognize that. I would call your attention to that definition on page 13. We do think that we have exceeded the urine drug testing standard of care on this point, in that as far as tampering goes these are observed collections. They have that availability as far as tampering goes to get around the issue of integrity at the collection point from an evidentiary standpoint. That's useful.

All hair collections are going to be observed, so you're going to know whether someone is tampering, in other words changing samples or otherwise manipulating the sample at the time of collection. That doesn't cover all situations, but it covers at least that one.

Mr. Stephenson: In this regard, every specimen is going to have its optimal potential for being gamed. We know that. One of the things we've heard of, and I'd like your comment on this, whether this is urban folklore or whether it's a reality, there is the story that one of the ways that a hair specimen becomes unsuitable for testing is to purchase over-the-counter head lice and have them shipped in the process. This is one of those things we've "heard about," and I'm not sure it's real, but it's kind of funny. It would be one of those examples of a unique marketing effort focused at a particular matrix.

Dr. Sample: Give yourself lice.

Dr. Bush: We've envisioned a couple of different ways for that, because you're putting nits on the hair. We're not the only ones who have talked about this.

Dr. Selavka: Actually, Ray Kelly did talk about it, and I'll let John Irving from Psychemedics also discuss it. At our last meeting this particular issue came up. We were talking about jumpers.

Dr. Jacobs: John, please don't pass those samples around.

Mr. Irving: You have to give yourself head lice, because the individual who is doing the collection is behind you. They have the hair in their hand and the donor never gets to touch the hair. So he has to give himself head lice. It's not a case of contaminating the sample. He's got to contaminate himself.

Mr. Stephenson: Has it ever happened?

Mr. Irving: Every once in a while we get head lice.

Mr. Stephenson: Is it becoming an issue where you're seeing it as an attempt by somebody to do this?

Mr. Irving: No, we don't see it as an attempt. We see it in some of what we call the PDD-90's, where the parent collects hair from a child. You see it more, probably more there than anything else. But it's not an issue as far as we're concerned.

Dr. Selavka: From a testing standpoint, I suppose if you were to test the lice along with the hair it might complicate the interpretation a bit. What we've decided on at this point and what I've written in this last bullet is we see this very much as an iterative process, just like we do with urine. When someone challenges the system with a new way to beat the system, you issue program documents, you tell us what you would like the program response to be across the board, and we would follow those. Hopefully, there would be adequate ability of the program to respond in real time, as it does now for urine problems.

Dr. Jacobs: Does the Board feel that these questions on tampering have been answered for the hair discussion? (No response.)

Mr. Stephenson: Would the Board be satisfied with a P, if not a blank? Is it possible to move this off of the insufficient knowledge area with what has been provided? How many are in favor of moving this from an I to a P on this issue? Can I see a show of hands? (A show of hands.)

Mr. Stephenson: Okay, we've got it.

Dr. Caplan: There are two parts to this. One is the sample substitution, but there's still the question of treatments of hair that the individual might do prior to getting it collected. Everybody's convinced, once it's collected, that's going to be a pretty good process, but what happens before that? That may be, as you said, an iterative process. We may not be able to predict them all right now and it probably would be stupid to predict it because it probably would change by the time you get through this.

Dr. Sample: An observed collection precludes substitution. It does not preclude tampering or adulteration.

Dr. Selavka: Correct. That's why we defined them differently. Tampering and adulteration and unsuitable samples have been defined, and I would guess program documents would follow some sort of hierarchy of this as to this is how the person could try to beat the test one way and another way, here's how we could respond or, at least, recognize that potential.

Mr. Stephenson: Okay.

Dr. Selavka: G.3 starts on page 17 of your document. This is related to identifying adulterated and substituted samples. We would go back again to the unsuitable sample definition and, again, using urine drug testing as the standard, we think unsuitability is pretty clear and observed collections take care of the problem of substituted samples.

Dr. Jacobs: Any discussion on this from anyone?

Dr. Caplan: Can we have a little comment from someone on the experience of the industry on the types of things that might have been done to hair and how that affected any process or if it affects any process?

Dr. Jacobs: Could someone talk about bleached hair perhaps?

Dr. Caplan: Bleached or stripped, or the other things, colors.

Dr. Selavka: I'm going to defer to John Irving, and I'm sure if Ray Kelly were here, and he does regret that he was unable to join us, he'd be up here.

Mr. Irving: Most of the things that have been done to the hair will strip the outside of the hair and where we're testing is really the inside of the hair. In the worst case situation they're doing some of the work for us. They're taking out any possible environmental contamination. They've done the first wash steps for us when we digest the hair. The only way they're going to be able to really beat the system is if they actually kill their hair, if they treat it to the point where it becomes brittle. That's really about the only thing they can do. Otherwise they can't strip out the drug because it's so ingrained in the internal matrix of the hair.

Dr. Jacobs: If they treat it so that it becomes brittle, it's very obvious to the collector and to the laboratory?

Mr. Irving: It's obvious and we report it out as unsuitable. Whatever definition we want to use, term we want to use as an unsuitable sample, just like we do with urine, it would apply to that type of sample.

Dr. Jacobs: Do you know what they do to the hair to make it that brittle?

Mr. Irving: We have only had a couple cases where it occurs. We can't tell. They just overtreat it, change color every day, bleach it. In these cases, I don't necessarily think it's an attempt to beat the drug test as much as more a statement of their lifestyle, which may go along with the drugs, too.

Dr. Caplan: Do you have any criteria for things that are currently considered unsuitable?

Mr. Irving: If we feel that there's no structural integrity to the hair, then we report it out as an unsuitable sample. We still test it, but if it comes out positive we let them know. If it comes out negative, we report it out as unsuitable sample.

Dr. Sample: How do you define structural integrity?

Mr. Irving: It becomes powdery. The hair is so brittle that it breaks when you try to align it. It's breaking off in your hands. And the people that do this, do it on a continual basis. You find that the people who do the accessioning in hair testing laboratories are a lot more sophisticated than in the urine laboratories. They do this on a daily basis. They see hundreds of hairs a day, so they know when a hair has been treated extensively. We can go back and look at it under a microscope. We can test it with stain to see the structural integrity of the hair also. We'll do that before we report it out.

Dr. Sample: Do any of the other laboratories represented here have other criteria for specimen suitability for their hair samples?

Dr. Jacobs: Have you done any studies or looked at any hair to see if percent positives are different between hair that might be treated and that which isn't treated?

Mr. Irving: No. We're gathering some of that type of data now, but I don't have anything I can give you.

Dr. Jacobs: Okay.

Dr. Moore: What we have found is that if you bleach the hair after someone's taken drugs, you do tend to degrade the amount of drug that's there. If, however, you bleach or dye the hair and actually make it more porous before you take drugs, you actually increase the amount of drug that's in the hair. It could work either way. You could get someone who would have more than you would expect. You're not helping yourself by bleaching your hair, depending again on your lifestyle. We actually write down if it's been obviously bleached or colored on the report, but it doesn't really affect the positive nature of the test.

Dr. Mitchell: If the drug is incorporated at the root, how can treating external hair cause an increase of incorporation into the hair?

Dr. Moore: I think it's the porosity of the hair, in general. There has been a lot of work done on different types of hair -- thin hair, wider hair, thick hair, African American hair, Caucasian hair. They're all different and with the porosity of it, it would tend to uptake more drug.

Dr. Caplan: Over a period of time?

Dr. Moore: Yes.

Dr. Caplan: I think you're asking it acutely. If you did it today, it probably isn't going to do you any good if you get tested tomorrow. But if you had done it a week ago and regularly.

Dr. Mitchell: Scientifically, I don't see it. It would have to be as a result of some type of either sweat or something coming up and incorporating in. It would be something other than incorporation at the root in order to incorporate more. That's the way I see it. I may be wrong, but that's just my logic.

Mr. Stephenson: Well, the issue here is that we may be asked for some information on what are some of the experiences and that might be one of the things that could be done in the summary, like a checklist of things to be done, in the sense that there was a comment made about the role of the collection site's sophistication. You might want to say that this is a shared responsibility for detection and how that would happen. That could also be the case with several of our other specimens, that we'd want to look at some summary information as to the role that each participant in the sequence plays in identifying an adulterated or substituted specimen. We'll get that in some of our summary data later on. Carl, is that okay?

Dr. Selavka: Yes.

Mr. Stephenson: Do we want to move this from an I to a P? Is this an area where it's consistent with the thoughts of the Board? Are we beyond that? Is there any discussion? (No response.)

Mr. Stephenson: A show of hands in favor of moving it from an I to a P? (A show of hands.)

Dr. Selavka: G.4.a, on page 18. This essentially is the same question as we've talked about before, and that is FDA clearance. It's one that we can't resolve for you.

Mr. Stephenson: This is an interest issue. You have addressed it from the point of view that we have asked the other two reporting groups this morning, and in that context where it stands as an I or a P or a blank is not an issue, but your input will help guide us as to where we go in our discussion.

Dr. Selavka: The initial test target analytes and the levels at which those analytes will be standardized in the immunoassays have now been determined for all classes. There is one change from the information that you have. What I want to do is draw your attention to the screen rather than your pieces of paper. Since I forwarded this to the program for the summary that you have in front of you, we have finally made our final consensus on THC. The target analyte will be THC acid at one picogram per milligram equivalent. That turned out the laboratories had to go back to some raw data to figure out whether that was or was not where they'd like to be. Everybody is pretty happy with that now. All the other ones are unchanged from the meeting that we had last time.

Dr. Bush: Taking a look in the far right cutoff column on THC, you have your target analyte THCA and the cutoff, one picogram equivalent per milligram. Can you talk to me about what those equivalents are?

Dr. Selavka: As we've written in here --

Dr. Bush: Okay. I haven't had a chance to read it.

Dr. Selavka: Okay. This is the same language we had in it the last time.

Mr. Stephenson: But we've had the discussion on the other, in the other two working groups as to what we're going to deal with. We're dealing with a patch, we're dealing with an eluate, we're dealing with, you know --

Dr. Selavka: Yes. I'll draw your attention on page 19 to the second smaller font size paragraph, starting with "The calibration of initial test methods." Essentially, you're standardizing on a single analyte in an immunoassay, but you recognize that cross-reactivity to other substances within that class of substances are going to lead to a total package of findings of positive or negative. It's the nature of an immunoassay method that cross-reactive substances will combine with your target analyte in the matrix or extract of the matrix and provide you with that answer, positive or negative. It just gets at immunoassays being responsive to an equivalent of such.

Dr. Bush: Thank you.

Dr. Selavka: I confused you by giving you something you already knew, which I apologize for.

Dr. Sample: But we don't look at any other analytes in any other specimen matrix in equivalents.

Dr. Selavka: We do.

Dr. Sample: We don't say it. I'm talking about in words, not the reality of immunoassays.

Dr. Selavka: We were being too exact. This was previously an I G.4.b and G.4.c.

Dr. Welch: It goes into the pool for all the rest of us to talk about it jointly.

Dr. Jacobs: I think up to the Board to make a table with all the numbers with the different matrices and look at them and determine what they mean and how they compare.

Dr. Bush: We may need more information to get there.

Dr. Jacobs: We might.

Mr. Stephenson: Are you participating in any of the marijuana hair analysis issues going on at the Addiction Research Center?

Dr. Selavka: The only hair testing being done in my laboratory right now are comparisons of hairs among rapists and their victims.

Mr. Stephenson: The issue is are you aware of the studies at the Addiction Research Center regarding an ongoing marijuana study, in which we believe hair may become one of the samples studied? I don't know whether any of the individuals in the working group would have that.

Dr. Selavka: I'm not aware of it.

Mr. Stephenson: The expression of interest is adequate, all right.

Dr. Selavka: I cannot speak to whom the researchers are going to use for their laboratory.

Dr. Vogl: When you say the target analyte, does that indicate you will be using that drug or metabolite for your calibrators in determining the cutoff?

Dr. Selavka: Yes. That's the only way we wish to use that. That's what you would spike into an extract to digest or whatever to calibrate your immunoassay.

Page 23, G.4.e, relates to the ability to repeat an initial test. Again, I would bring us back to the initial discussion. 75 milligrams should be enough. You can do split sample collections. You can also get a new sample, and you've seen a demonstration of how much that looks like.

Mr. Crouch: What is the average digest buffer volume? Do you take 10 milligrams of hair for the immunoassay? What volume is that taken up in?

Dr. Selavka: I believe there is some variability from laboratory to laboratory. I can speak for NMS. We took it into a 500 picoliter sample solution. I don't know what Psychemedics is using.

Mr. Irving: We used 2.4 milliliters.

Dr. Selavka: 2.4 milliliters for a 10 milligram sample.

Mr. Irving: 2.4 milliliters for a 10 milligram sample.

Dr. Selavka: You're doing radioimmunoassay for single analytes, right?

Mr. Irving: Yes.

Dr. Selavka: If you're doing the method that has a single, if you're doing ELISA's, which have a certain volume needed, your testing would be based on that or make dilutions appropriately.

Dr. Jacobs: Based on the prior discussion and the size of the sample, I would suggest we move G.4.e to a blank.

Mr. Stephenson: Any discussion by members of the Board? (No response.)

Dr. Sample: We were just doing a little bit of marveling at the sensitivity of these assays, where such a small amount of material produces a positive response for immunoassay. It's extremely sensitive.

Mr. Stephenson: The question that Aaron had asked is to move G.4.e from an I to a blank. Okay, it's now a blank.

Dr. Selavka: Pages 24 and 25 are for element G.5.a. This relates to the use of mass spectrometry. We previously told you that we were proposing certain standards for figures of merit and acceptability of figures around those figures of merit for MS experiments, and at the last meeting you said, what about traditional single quad mass spectrometry, give us some standards for that. We did that on page 25. They are very similar to what you're used to, and we would still say we need a blue ribbon panel for our MS/MS review. We've given you a few names on page 25. Obviously, these are just recommendations from us. You can choose whomever you'd like or scrap the whole thing and just believe us. We really propose that we put this out to the community. There is an active community within mass spectrometry looking at forensic standards for different kinds of samples right now. I'm aware of them working, but I haven't seen an outcome from them in a good four months.

Mr. Stephenson: Do we have a member of the Board who would be interested in working in this arena, perhaps to construct an opportunity for such a review panel?

Mr. Crouch: Yes.

Dr. Jacobs: I'd be glad to do that also.

Mr. Stephenson: Why don't we see if we can structure this and certainly meet with you. I think it's an issue that we ought to look across the board, and I know Denny has another pet that he wants to look at, too, at the same time.

Dr. Selavka: This is already a P before, so we were really providing you with more input than you asked for.

Mr. Stephenson: This is to follow up what you suggested on the panel. I think it's consistent with a lot of the areas. It's consistent with the review that we need to do anyway.

Dr. Selavka: G.5.b, starts on page 26, but I will draw your attention to page 27. Page 27 has the final table from all of our deliberations and it's critical that you have seen this table and understand what we have done here so that you can understand interpretive guidelines, MRO things, and so forth. What we've added here is, what we think is interpretative here, is we've got some rigor to these tables where metabolites, except for PCP, metabolites require the reporting of any analyte classes for confirmation. For amphetamines, we've specified that a laboratory should be able to process d and l isomer differentiation requests either internally or have a laboratory that can do it for them. Codeine would be the only stand alone opiate value that could be reported. Morphine and 6-AM couldn't be reported unless there was another analyte in the opiate class. Cocaine, we had told you before about the use of the parent molecule plus ratios to benzoylecgonine or the presence of cocaethylene or norcocaine as supportive of an overall cocaine positive class finding. THC acid would be single molecule reported, but it is a metabolite.

There was a good deal of discussion within the group about the use of the ratio at 10 percent for benzoylecgonine to cocaine. Some thought that that was a little pessimistic and might exclude a few people, but we think that that's appropriate at this point. We made the program as we would propose it to you to bend over backwards for someone. If there's discussion to be had on whether that could have come from some source other than an ingestion source, we want to nip that in the bud as much as possible, recognizing that there will always be a story for every positive regardless of matrix.

Dr. Bush: Based on the myriad of specimens that have been tested, most of them fit the pattern of having a parent and a metabolite present?

Dr. Selavka: At the cutoffs that we're defining here. Laboratories have not traditionally chosen a cocaine at one nanogram per milligram, for example. Most of them had had lower amounts, 0.5 or even lower. In those situations where you start to reach the threshold of sensitivity of the instrumentation, it's harder to find the metabolites. But as you raise the cutoff for cocaine to 1, you're routinely going to be hitting these metabolite packages without a problem.

Mr. Stephenson: Is this a consensus issue that you have across practitioners in your different laboratories that they'd be willing to address?

Dr. Selavka: This was, much like the sample volume, one of those areas where we started all over the place and we were able to reach a consensus of all the laboratories that participated.

Mr. Stephenson: Congratulations, really.

Dr. Selavka: This was one of the points where I thought we had better reach out to the community of international stakeholders, as well as the laboratories who didn't normally participate, and try to at least tell them what was being proposed and elicit input when I could get it. As with any committee, once the meeting was over I would send these documents out, and if I got a handful of responses that was a lot. As proposed standards, you have public comment periods. Any laboratory that's participating in the future workplace program that's being designed will give you input as to whether they could or couldn't meet this standard and why they think it's a lousy idea. We've tried to get all the lousy idea statements now and incorporate them into these final proposed standards.

Dr. Caplan: Is there no concentration of morphine alone that would be reported?

Dr. Selavka: Under these conditions, that's correct.

Dr. Sample: We're ignoring the numbers on page 26 and only using page 27, is that correct?

Dr. Selavka: Yes.

Dr. Sample: Page 27 is the most recent set of consensus values?

Dr. Selavka: Yes.

Dr. Bush: Back to Yale's most recent question about a morphine alone will not be reported. That's what I'm hearing.

Dr. Selavka: Right.

Dr. Bush: Was there discussion as to maybe why? Based on interpretive issues? What came into that decision?

Dr. Selavka: A lot of things. I think one of those is the poppy seed issue. We want to make sure that we recognize that for hair. If someone's using heroin, you're usually going to find 6-acetylmorphine. The whole issue of reporting a morphine alone becomes less important to the program trapping those who are using heroin. You're going to find 6-acetylmorphine along with morphine in those kinds of cases. A person who has a prescribed morphine is not going to be triggering a positive under the circumstances. We thought that that assisted the medical review officer's interpretive reality. In addition, if someone's using poppy seeds our understanding from the literature is you'd have to eat so many you'd be sick from it. We shouldn't see poppy seed positives in hair, so that interpretive issue is gone. If someone has a prescription for morphine, you're not going to -- unlike urine, you're not going to get to that point where the MRO is having to evaluate it. Morphine alone we're not going to be reporting.

Dr. Bush: It's a silent alternative medical explanation for the presence.

Dr. Selavka: Nice way to put it, yes.

Mr. Stephenson: Again, I go back to a comment made this morning, I think at a point in time, maybe later on this summer, it would be beneficial to begin to introduce our MRO's on these alternative specimens and technologies. To begin the process of allowing them to ask the questions that they would need to ask, and to make sure that we have the potential for sharing with them what it is that we're doing with these new technologies and begin to build that process to introduce this to the various training mechanisms that would be out there for MRO's because this is going to be a whole new ball game for an lot of folks. I don't think it's just hair. I think it's all of these. We're going to need to address this issue in a consistent way. I'd like to ask if there's anybody in the group that would like to participate in a focused effort to add some MRO attention and focus in this whole area over the summer and as we go into the fall. Let us know.

Dr. Selavka: I've been doing it already. I think voluntarily the MRO organizations are bringing people in to talk about this.

Mr. Stephenson: Identify some other people. Each of the working groups, identify some folks that you've worked with that have an MRO niche or focus on this so we can begin to address this, and let's begin to share the experiences. We'll put something together in this regard.

Dr. Vogl: What's the reason behind not reporting the 6-AM by itself?

Dr. Selavka: In the laboratories' experiences that would be a very unusual finding. In fact, they couldn't think of a situation where they had had a 6-AM alone in the absence of morphine. Therefore, in the interest of recognizing that someone could try to doctor up a sample, why not build in some sort of -- they'd have to doctor it up with both analytes. I hate to put it -- that's a pejorative way of saying there's trickery and things that can go on with people trying to show that one matrix may not be good or whatever. This would be one way to try to trap that. It's got to have a realistic package of metabolites in order for it to pass muster.

Mr. Stephenson: It's also a reasonableness issue, and I think it's one that's good to advance now rather than later. That's fine.

Dr. Sample: I have a question about the GC/MS issues, on the sensitivities of those mass spectrometry issues. Can anyone comment on what the sensitivity is on those, the LC/MS assays or GC/MS assays, whatever is being used as a confirmatory mass spectral analysis?

Dr. Selavka: If you mean if I know how many picograms per unit going into the mass spectrometer?

Dr. Sample: You inject X number of nanograms, picograms or whatever you're injecting. What's the minimum amount that you can inject and detect?

Dr. Selavka: The strategies chromatographically are very similar to those that are used in any other traditional toxicology laboratory, which is one or two microliter injections in GC and probably between 10 and 200 microliter injections in LC, depending on the column.

Dr. Sample: What's the total amount of material, of drug material, in that 100 to 200 microliter injection on the LC segment?

Dr. Selavka: Well, since I went to a public school in America, I don't do math in my head. I'll let you do the math backwards. From the amount that we're looking for in reporting limits, knowing that we can actually detect less than that, we can probably detect as little as 40 percent of these cutoff values or better in what's being injected.

Mr. Crouch: Is anybody using LC/MS for marijuana?

Dr. Selavka: Someone was.

Mr. Crouch: Because you can inject half the volume by LC/MS, but you cannot do that by GC/MS.

Dr. Selavka: Right. I want to say NMS has been experimenting with LC/MS already, LC/MS/MS. But we drew in the guidelines because we knew it would be coming down the road. We could have CE/MS down the road, even though that's hideously small injection volumes. But yes, we are pushing the envelope on sensitivity. As you know well, the instruments available today are very good, much better than they used to be, and are allowing us to do this. It's not for the faint of heart.

Dr. Bush: How do they hold up to a production schedule where you need everybody, all the instruments up, tuned, running on a shift kind of basis to meet the mission, meet the product load, production load?

Dr. Selavka: I'm only familiar with a relatively low volume laboratory. I would guess probably 20 percent down is normal.

Mr. Irving: We're using LC/MS/MS for the cocaines and that is just up, no down time with it whatsoever in the space of the last six months. The GC/MS/MS, because of the levels we're looking at the extraction processes are really, really, really intensive to clean it up. We're dealing with extremely clean instruments all the time. We have to keep them that way. But 20 percent down time on the GC/MS/MS is actually about the worst we have. From a production standpoint, we're doing better than 2,000 samples per day for screening purposes. We haven't had any trouble maintaining production.

Dr. Sample: What's the extraction efficiency?

Mr. Irving: Because of cleanup, probably no better than 50 percent. The idea is not to get any contamination into these instruments at all. We're having to also do lower levels when we start looking at the wash kinetics also.

Dr. Sample: I think it would be helpful to know what your on-column sensitivities are.

Mr. Irving: Why don't we give that to Carl. There's no problem getting that.

Mr. Stephenson: I think those would be one of the issues to look at with a smaller working group in the GC/MS issues.

Mr. Irving: Yes, we can do it that way.

Mr. Stephenson: Build that in as one of the things you want to look at.

Dr. Moore: From my point of view, I agree with John that the extraction really is a big issue. You need the cleanest sample you can possibly get to get these sensitivities. On the list that we have, they're all no problem for us except the THC. We don't have MS/MS, at least we don't have the triple quad MS/MS. We use the bench top negative CI 5973, which is nice, and we routinely get to 0.5 picograms per milligram for confirms. We can do that. But looking at these levels, I know we'll have to go back and get ten times better. We have some things to work on. The down time is not really an issue, not the same as it would be with a bigger instrument.

Mr. Crouch: Is that based on a 10 milligram sample?

Dr. Moore: No, that's based on a 50 milligram sample.

Dr. Sample: 5-0?

Dr. Moore: 5-0, yes.

Dr. Sample: And it's 0.5?

Dr. Moore: Yes.

Dr. Sample: And this is 0.05, so that's one one-hundredth and five times more samples.

Dr. Moore: I said we had work to do.

Dr. Sample: It's a challenge, yes.

Mr. Meeker: A couple things on these cutoffs. The THC, for example, I was sitting in the background at your last meeting and the impression I got was the THC cutoff was going to be decided by two laboratories and that they were to provide the information to the testing group for a decision base on the cutoff. Since you haven't met since then, how was that decision, just based on those two laboratories and nobody's reviewed the data?

Dr. Selavka: That was for the screening assay, not for confirmation. Confirmation was determined two meetings ago.

Mr. Meeker: Okay. Secondly, on these confirmations, for example on the cocaine and BE, has there been any statistical analysis of those cutoffs as far as the false positives or false negatives by adding the BE relative to the cocaine itself that the group reviewed?

Dr. Selavka: Yes, Psychemedics and APL both provided data about what would happen if you set the cutoff here, here, or here. Dr. Kidwell, from the Navy, also provided some data in looking at his experience and those of the other laboratories as to what happens or how many samples fall out of the positive category, and that was used for setting the initial ratio of 10 percent. You're going to lose some, that's the bottom line.

Dr. Jacobs: Could I suggest that when you supply data for D.4 that you include some of this that we were just talking about so people can see it.

Dr. Selavka: Yes. And on the data, what exactly would you like us to address?

Mr. Stephenson: D.4.

Dr. Selavka: D.4 was about stability and storage. What else would you like in there related to cutoffs or whatever?

Dr. Jacobs: We had some data that was stability around the cutoff. Could you maybe have a table or a couple pages of that showing that it was done and what numbers they got?

Mr. Stephenson: You've got an original test, a retest, and the storage issue. You can get all three of them packed into one table in one place.

Dr. Jacobs: Right.

Dr. Selavka: Okay. G.6 is on Pages 29 through 31. I thought I'd summarize this as -- and this is a lot of writing, I recognize that. There are specific metabolite requirements now and what we think are overly cautious elevated cutoffs. We do recommend -- and I know there was discussion at the last DTAB meeting that a review policy will never be put in place for some participants in workplace testing. We would just recommend to you again that you institute a program that systematizes a review for any individual who feels that their testing results are wrong for whatever reason they'd like to bring forward, specific circumstances, regardless of matrix. But obviously this is your decision. We also have proposed things in our research and development that you asked us to put together on pages 53 to 54, items number 4 and 7, to provide you our suggestions for research that could be done in order to provide even more information on element G.6 of the matrix. That is, in other words, we could perform a literature survey and finally do some real world dosing experiments, which we recognize is a fantasy that will never happen in the United States. We appreciated your consideration of that fantasy and we could at least write it down for you. The best way to get at this issue is to do some prospective studies with real amounts of drugs, which won't happen here, but we thought we'd write it down for you.

Mr. Stephenson: There are two things that I picked up on here that we might be able to address. One is, in a review process for policy we're not just starting with one time in here, but this is a living program. We're going to demonstrate multiple learning curves we're going to go through, and we're certainly going to see not only new drugs and new problems we haven't even considered, but we're going to see new technologies and new sensitivities of detection over time. So the routinization of what we've got in fact is part of this process. What would be the trick point to this? Would it be, for instance, a literature search across all of the different matrices, that we say there are certain threshold areas that become triggers when you start to see these things, and you make sure that we put them out. We could create such a shell for such a literature review that could then be made available, maybe on a web site or whatever, for people to look at, and that this would be one of those sentinel devices that would be out there. If you can create that for your area and give us an example of what you'd like to see included in that, we can do it as a test. We could actually do that. I would suggest to all the other working groups that we do the same thing in their area.

The second thing you talk about was do we want to go beyond where we are with doing tests with real drugs and real people? What about the short hand of that, looking at comparability of data through some proficiency challenges that we would do across the laboratories? Again, that's an area where we would invite participation and an integration to what RTI has been charged to begin to explore. Maybe we can accelerate that. In your case, if you're making this as a proposal we could at least do that part if we could get a matrix for how to get the data compared across the different participating laboratories and then have you determine what you'd like to see come out of that review. What is it you expect to see from the cross-comparability? We could do that. Those are things we could commit to do within the next few months.

Dr. Selavka: I would say wholeheartedly we agree. In fact, one of the first research points or suggestions for federally sponsored support of continuing the process of developing hair drug testing is to initiate the proficiency and performance testing program, to start to get that historical knowledge upon which, the baseline from where we're going the build from. I'd love to see that happen.

Mr. Stephenson: Let's work with the RTI group to make sure that that is where we go. That doesn't mean we put anybody else on the back burner from the alternative matrices. I think you are at a point of consensus where this is something that needs to be done. Let's work with it and let's get it going.

Dr. Bush: As to the literature searches, I can help with some support on that. You just need to see me and let's see how we can proceed on that, okay.

Dr. Selavka: Yes.

Mr. Stephenson: Again, this is a challenge to each of the other working groups to provide an outline, maybe some expert sets of researchers or articles, publications that you want to find in any search that was done, and then we'll create that search such that we'll find those, and we'll see what we also catch in that same net.

Dr. Selavka: Okay. Since G.6 was a P last time, we just brought it to your attention that we have added additional information.

H.1 begins on page 33. As far as having a certified laboratory program, that is why you brought us together and we propose to go for it, and that will turn this from a P into a blank.

H.2, as far as external PT goes, if you read the definition at the top of the page, that is PT samples can be prepared that challenge the ability of the laboratories to identify, analyze, and determine their concentration. That is a very traditional performance test program, but a performance test program. We have gone further and we have defined both and we've made some suggestions. We had some great input last meeting from one of your guests, who just led us through the process by which this iterative development could happen. I think because of that we came out with some very good specifications of how the program could be designed and implemented and build upon itself pretty well and maybe with not too great of an expense. Hopefully you'll appreciate that there was significant input from your local quarter.

Mr. Stephenson: Are we in a position to move this one from an I into a P? Is there any disagreement? Let's see a show of hands, those in favor of moving changing this to a P? All right.

Dr. Selavka: H.4 begins on page 37. The discussion from last time gives you our initial feeling on this issue that it is possible to submit negative or positive samples as if they were donor samples. We believe that not only is it possible, it's already been done. Laboratories already have blind PT programs in place and have historical data to support that the programs can work, in that undetected blind PT's are making their way through laboratories and providing their user agencies, be they corporate manufacturers or others that use these laboratories, with data that they can use to evaluate the service level of their laboratories. We think the ones that are in place now are sufficiently objective, it is difficult to find some drug positive hairs for use in the blind program, and that's the only hurdle that really remains and that's one that could be addressed in the previous discussion on pages 34 to 35.

Mr. Stephenson: Do we want to link those two positions together? Do you want to link those two together in this?

Dr. Selavka: We philosophically have at our level.

Dr. Jacobs: It's been suggested that if we can get any data back saying how laboratories did on this, that that would be very helpful.

Dr. Bush: Specifically, what was the specimen, what was it, what could it have, what did it look like, how was it submitted to the submitter's knowledge, and what did the laboratory do with it? How did it come back, was there any quantification associated with it? Things like that.

Mr. Stephenson: It's strictly from a perspective of not trying to score the existing process, but to inform us as to how to craft this for the future program.

Dr. Selavka: I think you can be comfortable with the blinded. If you were blind to the laboratory involved, I think they'd probably be comfortable doing that.

Dr. Bush: Absolutely. Never a problem on that, just to let you know. We don't need to attribute information to any specific laboratory. That's not the point. We're just looking for the data.

Dr. Selavka: I can say that, as it is with most laboratories that are part of a good process, they look at this part of the process with pride and they hold it out to people that they'd like to sell their drug testing to as a positive part of their process.

Mr. Stephenson: We should look forward to this as something that, if blinded properly, this could become part of the data set that could be shared for purposes of construction of a new program or a framework. Again, I'm looking primarily at RTI to take this on as part of the framework challenge. Is that okay?

Dr. Selavka: I'm speaking for the laboratories and I presume they're going to be happy to do it. They must because it's an important aspect of a Federal workplace program.

Mr. Stephenson: Are there any laboratories that are here that would like to speak to that specific issue?

VOICE: There's no problem with that.

 

Mr. Stephenson: Anybody else participating? (No response.)

Dr. Selavka: Would that become a P?

Dr. Bush: I'll reserve that until we see some data. That's my thought. I'm a data hound, so I need some data.

Dr. Selavka: Okay. J.1 is 42 to 44 in your handout. I think the definition is useful to reread, and that is: "Scientific information is available to allow an MRO to properly interpret a positive test result." The fact that we have all I's for all matrices is just the reality in which we move. It's a never-ending quest for more information, more data. It's kind of a moving target. Again, taking you back to how we defined a positive, it does involve metabolites, elevated cutoffs, a recommended review policy, and some research that we think would give some more data for this. I guess we find ourselves in that same situation as most other endeavors. We'd like to have more information in order to perfectly interpret every finding. We'll never be there, but we'll never stop trying.

Mr. Stephenson: I think this is an area where we're going to begin to address this through an MRO focus group, and I think we'll start doing this from two sides. I think we need to have the participation of that target audience in this kind of thing actively involved. Again, this becomes in fact one of your charges, Carl, that you talked about and that we talked about from your perspective, and anyone else who wants to participate.

Dr. Selavka: Just to remind us. J.2, page 45, we think by definition this is really similar for all matrices. On a situation by situation basis or a case by case basis, hair does provide some unique features that allow for interpretations to be done differently than they would be with sweat or with oral fluid or with urines. But we think it's going to be another iterative process. You can have program documents that come out to assist people in taking realistic medical explanations and making the right decision for the employee involved in that case. We're not sure what data specifically you would like from us. We talked about poppy seeds, but for medical explanations if you're being dosed with a drug, if it's a nitrogenous base it's likely to end up in your hair, and if it's one of those that falls into the five categories it's likely to come up positive. If you're not being dosed with it, that isn't likely to be the case under a medical condition.

Mr. Stephenson: Again, this is one that goes under your charge, and I would suggest that we go back to urine and we add laboratory-based urine and on-site urine in the same areas of broadening our understanding of the baseline and we capture this across the board for all the matrices.

Dr. Bush: A suggestion here from one who has trained a lot of MRO's and one who gets a lot of medical review officer calls and many different questions concerning drug tests. The MRO's are the source of an awful lot of great information. I'm going to suggest, even though we're going to set up that MRO working group and all of this, you may be more familiar and closer to the MRO's who -- MRO hair testing as part of their job responsibilities. I bet you they have talked with persons at the laboratories, the technical types, to try to evaluate the merits of what the donor says. That can provide a great data base from which to start developing: Just evaluate what's been heard. Frequently asked questions.

Mr. Stephenson: Or frequently stated excuses.

Dr. Selavka: That's one of the reasons why we did involve two MRO's as part of the working group. And they gave us illustrations that some of us who were in other circumstances had never heard of. So it did work that way. We'll do the same thing and reach out to MRO's for training, ask for that feedback.

Dr. Bush: Thank you.

Dr. Selavka: Page 46, J.3. This is MRO training. We think the I should be a P. Laboratories are already training MRO's, so it is possible. That it hasn't been done on a wide basis is merely a matter of where we are in the history of hair testing.

Mr. Stephenson: Here we go, another one.

Dr. Selavka: I know the laboratories that are already doing it have programs for MRO's and are happy to extend those or modify those as needed.

K.1 starts on page 47.

Mr. Stephenson: Do you want to address the issue of fees? Is it an issue that anybody cares about at this point? It's going back onto your charge anyway as a group. I just don't want to have somebody think that there's a score card of change. Is there a concern right now on your part that this be changed from an I to a P?

Dr. Selavka: Absolutely, yes. We thought it should be a P all along since they were already doing it, since that means if possible. But that's not our call. We'd love it to be a P. Anything that's an I means we have to keep coming together, and we're sick of getting together, so we want to not get together any more. If you turn it into a P, we can do stuff by e-mail and nothing formal really has to happen from us.

Dr. Bush: Do you have documentation, a course syllabus and stuff that is used in the training of MRO's? I've never seen any of it.

Mr. Stephenson: We do the same thing for saliva and sweat. Whatever gets presented, we do the same thing.

Dr. Bush: Quite frankly, you know, for the urine drug testing MRO training sessions I receive copies of everything. I participate in the development of those materials and then also receive the final copy of what's used annually. It's kind of on an annual update, annual training cycle.

Dr. Jacobs: I'm seeing some heads nodding. We'll get some to you.

Dr. Bush: Okay, we'll get some.

Mr. Stephenson: Is there any issue on changing this from an I to a P in this area? Any discussion?

Mr. Crouch: I think we ought to see some examples, some manuals or syllabuses.

Mr. Stephenson: Have we seen examples for the saliva and the sweat testing? Did they bring those in?

Mr. Crouch: Yes.

Mr. Stephenson: Okay. So maybe upon submission of examples we could then move this from an I to a P. Is that the sense of the Board?

Dr. Bush: Yes.

Mr. Stephenson: Is it? Okay, I see enough heads nodding.

Dr. Selavka: As far as K.1 goes, we did have one question that has continued to be of interest to us, the difference between dose response and dose time response. They aren't the same. We're wondering if that was an inadvertent word droppage. Dose response is typically an interpretation that's made related to blood results and so forth. You wouldn't do that with urine, you wouldn't do that with oral fluid or hair in any of these common alternative matrices. You might be able to do it with oral fluid as it tracks blood concentrations. Was it meant to be time response or dose response, because it's been talked about as dose response and we're not sure that's correct. In any case, if it is dose response we refer you back to pages 29 to 31 on point G.6, and our discussions would be the same.

Mr. Stephenson: We've had this discussion before. Yale, would you care to weigh in on this? I think you were the guy who explained this last time.

Dr. Caplan: Then you probably ought to read it back out of the transcript.

Mr. Stephenson: There he goes again. This is the third time in the day he's got that crisp, fine answer.

Dr. Caplan: I think it's dose related to time of effect. That's what we meant by that.

Dr. Selavka: That's good. That's how we took it, because we figured you can't do that for the other matrices and it didn't make sense, so we questioned it.

Dr. Caplan: It has to do with the window. The question is what is the window and what are we finding in that window.

Dr. Sample: What type of use.

Dr. Selavka: We haven't changed our consensus opinion. That is, a single use or exposure is not, is not likely to lead to a positive result. We don't see those circumstances happening, and the single dose studies, the values that comes out of it, the ones that do it the way laboratories do it for real samples, we're not going to find those samples as positives. So this should be for multiple uses.

Dr. Sample: And what frequency?

Dr. Selavka: You don't know for every person, for every drug. It depends on how much they take, how they use it, etcetera.

Mr. Stephenson: That's still part of the interpretation of results, too, isn't it?

Dr. Selavka: Yes.

Dr. Caplan: To the degree that you know it, in a sample of one-half inch, a person using it once an average amount would be detected? Yes, no? Twice, three times, four times? If that's known that would be useful.

Mr. Meeker: I have two questions. The first one is here you say the time period represents approximately 90 days. Is there a comparison between the head hair and the alternative body sites? Like armpit hair, does that grow slower, so we have a longer detection? Secondly, if it is a slower rate of growth does that mean there's going to be less incorporated? Maybe you can detect it in head hair with a smaller dose or a certain dose; will you be able to detect that in the alternative sites?

Dr. Selavka: I'm not sure. Should I answer that or is that just for the record?

Mr. Stephenson: It's up to you.

Dr. Selavka: Head hair grows more quickly than other body hair, so the time period represented is different for the same length of hair. That's taken into account in the interpretive guidelines that laboratories use in their findings. We didn't explicitly state that here. This would be a good place to put it. As far as how many uses it takes to be positive in any particular type of hair, I don't think data exists to be able to say it's twice as many uses of a given drug at a certain level in order to be positive on pubic hair versus head hair or underarm hair versus head hair. I don't think that research exists.

We do have beard hair studies. There are studies of arm hair versus head hair where there is some data out there. But I don't think it's complete enough to say for every drug class exactly how that relationship would work.

My own supposition, and it's only that, based on literature and our own findings, is pubic hair samples tended to have higher concentrations per unit mass than head hair samples did. That suggests that the incorporation rate is similar in both types, but one is growing faster, you're using the same mass, therefore you're going to have higher concentrations in the slower growing hair. A person who ostensibly uses the same amounts as the rest of the population of users, pubic hair would then go up, head hair would go down, relative to one another. But that's a supposition. Did that make any sense at all? To those of you who haven't worked hair for a while, it's kind of weird. You have to think about hair very differently than you do urine. Do you think we need language in here to address that?

Me. Meeker: I think if you're talking about the window of detection, yes, you ought to address that and say this grows at a slower rate and, therefore, the window might vary. Or else it should be incorporated in some MRO training.

Dr. Selavka: Or both.

Mr. Meeker: Or both.

Dr. Sample: Do you take different lengths from different sites, so that might counterbalance some of the incorporation rates?

Dr. Selavka: No. You're really using the collection device to get a sufficient mass of hair to provide amounts for testing. The length is what it is and you try to get enough hair to do the test. Any discussion on changing this one? (No response.)

Mr. Stephenson: To the members of the Board, do you have adequate information at this time to recommend a change from an I to a P? Those in favor, let's see a show of hands. (No response.) Those opposed to changing from an I to a P at this time? (A show of hands.) Okay, you need more information.

Dr. Selavka: What would you like?

Dr. Jacobs: Could you address what kind of information is needed, so that we have some guidance.

Dr. Selavka: There are literally 400 papers out there that we could probably bring in that show, and at least a dozen controlled dose experiment papers, that show the more you dose somebody with, the more ends up in hair. It's the same relationship we have with most other matrices. The growth rate papers are out there.

Mr. Stephenson: Could we put this with the MRO development issue as part of what's being developed, because that's the heart of what all this is about.

Dr. Selavka: Certainly.

Mr. Stephenson: Then look at this as kind of a batch process, because that's where it's going to be used.

Dr. Sample: I think the controlled dosing study information would be helpful in trying to get a handle on what this time relationship is -- obviously coupled with the dose, but what the time relationship is with your detection windows are. There's a statement that the time period represents approximately 90 days. Well, what does that mean? From what we've said, it's obviously not a single dose any time, a single dose any time within the last 90 days. Does it mean two doses or five doses or ten doses? Or does that mean for a heavy user up to 90 days after they've stopped using? I guess trying to understand what these statements mean and then having the backup documentation would be helpful.

Dr. Bush: I can tell you that, just as a follow-on to what Barry Sample just said, whenever I present MRO training sessions I use peer reviewed articles like that, data like that, to construct scenarios for MRO's, because they will hear things. They'll have to use this as part of their evaluative process. So this will fit in.

Mr. Stephenson: How about that being a part of what you construct for your literature review guide as part of the dummy set and we'll use that to help structure this whole thing.

Dr. Bush: That's good.

Dr. Selavka: All right.

Mr. Crouch: In addition, on page 8, D.2, it does allow for alternate body site collection of hair. If we're going to collect that and test it then we need to somehow be able to interpret it. All the data may not be out there, but we should know as much about it as we can.

Dr. Selavka: There's actually lots of data on the hair growth rate.

Mr. Crouch: I think it's more than growth rate.

Dr. Selavka: You know the length of hair you have. What you need is the growth rate to know what time period it represents. It's as easy as it is. There's nothing complicated about it.

Mr. Crouch: If it's not complicated, it won't take long.

Dr. Selavka: I'm just saying it's possible.

Dr. Caplan: It will be useful to say that if the rates are 60 percent of the other rate, then how would that equate to the 75 milligram specimen, 10 milligram?

Dr. Selavka: I understand.

Dr. Caplan: And how that's likely to detect, better or worse.

Mr. Stephenson: Carl, Walt Vogl in his infinite common sense wisdom has said that we have a document on our web site that has about 800 citations on hair testing technology. You might want to look at that and frame some of that as kind of a starting point. Let's make sure we've got something that's positive and constructive, rather than just an aggregate collection, and that might give you a starting point to look at. Again, the purpose is for us to create a new search engine to be able to consistently collect this and to do it over time again and again and again, so that we're always trying to harvest new information.

Dr. Bush: Page 43, there's a statement that "Quant values for positive results may be useful in evaluating scenarios." I think we need some information about what those values are, especially for the alternative medical explanation of what levels do you see in this passive exposure scenario.

Mr. Stephenson: Carl, you've got that?

Dr. Selavka: Yes. Okay, K.2 on pages 48 to 49, specimen contamination. Here what we've suggested is that it's possible to create a group of samples that could be used to challenge laboratories' abilities to decontaminate hair. What we've agreed is, what the consensus is in the group, is that there is more than one way to skin this cat and different laboratories will end up doing it differently. We should be performance-based as opposed to methodological-based on this particular category. That's our feeling. You should challenge us with something, and if the laboratory can't meet that challenge they don't get to play. If you challenge them with it and they get it right, that should be the criteria that's used for authenticating that laboratory's ability to comply with the standard.

Mr. Stephenson: Okay. You've got that figured out, RTI? That's a piece that goes into the proficiency challenge, then?

Dr. Bush: We have discussed this, Carl, and the best way to go ahead with gathering data concerning proficiency at a laboratory, there's going to be quite a variety of different specimens that will challenge different aspects of how the drug got there.

Mr. Stephenson: Again, this is not an issue of indifference because it remained an I, but it's an issue of focused effort over the next two, three, four months at the most. You'll have some very defining information on it.

Dr. Selavka: We look forward to that. I know the laboratories are looking forward to this. It's been done in an ad hoc way over the last few years. With the NIST work, we could really do a good job of defining these kinds of samples.

Mr. Stephenson: Absolutely.

Dr. Selavka: Okay. Color bias you asked us to address. I would bring to your attention, there's a brand new review out. Tom Mieczkowski has just published a book called "Drug Testing Technology." I don't get a cut of the proceeds. I would suggest, if you haven't seen it yet, grab it. It's got a lot of interesting chapters in it, one of which is chapter 15, which is essentially a review of the racial bias controversy in the use of hair analysis. It looks at every published study and a number of unpublished things that were available to him, to try to make some sense of the data themselves. It suggests in conclusion that there is no bias. He's also done a meta-analysis of all available data and that will be published this summer at the International Society of Hair Drug Testing. So those are two places. If you haven't read this chapter, it's worth reading. It's new, but it looks at all the old data, too. It's a CRC publication, 1999, "Drug Testing Technology: Assessment of Field Applications." There are a number of hair-related chapters in there.

Dr. Sample: Has anyone done a prospective study in drug-free individuals that has examined the issue of color bias?

Dr. Selavka: In drug-free individuals looking for background levels of drugs, I presume?

Dr. Sample: You validate that they were drug-free to begin with, and then administer drugs to the volunteers, and determine if there's any difference in rates of incorporation or any bias.

Dr. Selavka: That has been the goal of a number of studies, to try to get at that, where you've demonstrated drug-free individuals, dose them with drugs, and try to see if there's differences among sub-populations by race, ethnicity, socioeconomic categories, hair color, and other things. All of that is reviewed very nicely in this chapter.

Mr. Stephenson: Are we at a point where you have about concluded?

Dr. Selavka: Just about. You had asked us for a wish list of things, our wish list. So I'm going to go ahead and make your day. We want to initiate the PT program just as soon as funding becomes available. That would be a contribution DTAB could make to the whole world on this. I mean, we could do a great job for everybody if you fund it.

There are a number of things on our wish list. The wish list is pages 53 and 54, but basically items 2, 4, 5, and 7 all get at differences between environmental exposures and ingestion scenarios of various types. We would like to see some prospective and retrospective studies from the laboratories themselves, to look at samples that have been collected over time and try to score them as far as hair color or whatever, porosity or whatever, and do that kind of work. That takes a little bit of money, but it could be done. Cutoff selection, we think all the matrices need to have some well-defined parameters around how cutoffs are selected. It would be useful to have controlled dosing experiments that would provide for this, or literature searches or something.

We don't want to meet again, but we think we'd like to take all the things that have been done overall these meetings that we've had in the interim, e-mails and so forth, to try to turn out a document. The SOFT consensus document is 10 years old and it's based on 12 year old information. It was good at the time, but we'd like to revisit it. We think this is an appropriate forum with it. However, we recognize that DTAB within HHS may not be the appropriate forum. If you don't want to charter us to do this, if we could at least have your permission to do it under the auspices of some organization or at least just as a stand-alone group of guys and girls that came together to talk about this stuff. We'd like to put it out there for people to see. We spent a lot of time doing this. We don't want it to just disappear into the mists of a few meetings.

Mr. Stephenson: What you bring to the table as a voluntary effort is in the public domain. We will help you make visible those things that you choose to do with that product and analysis of that product. What I will say is the ultimate group process will be the creation of a proposed public rule and having it become a final rule and beginning the program, and that's what we're about. To the extent that we don't confuse a document coming out at this point with conclusionary results that would come out of this group, I have no problem with your doing what you wish to do. I think generally we have tried very hard in this group to make the transcripts of these public sessions a part of the public domain by putting them on the Internet, to make them available in text with attributions. And anything that can be constructed to help do that better is fine, and maybe a summary of what you've done and a good history could be something that could happen. But my bet is that there will be a similar kind of opportunity in other matrices and specimens, too.

Dr. Selavka: Thank you.

Mr. Crouch: I'd just like to add two things. I think you guys have done a great job with this. Two things. You said that DTAB should initiate a PT program and DTAB should start some of these things, like maybe a change in the SOFT consensus document. DTAB can't do any of those things. DTAB has no money, really has no authority to do anything, but advise HHS.

Dr. Selavka: Yes, I recognize we're advisory to you, who are advisory to them. So on the food chain we're still the little fish.

Mr. Crouch: Well, we're not much bigger.

Dr. Selavka: Thanks very much on behalf of the whole hair testing work group.

Mr. Stephenson: Carl, I want to thank you again for your presentation. It was great. Can we get a copy of your slides, just for the wisdom part, the part that you spun through at the beginning? It was very enlightening. I've been remiss a little bit earlier. We will try to provide time for some public comments. Any individuals who wish to make public comments, could they let our representative from our support contractor, CDM, know and we'll try to make available some time. You will speak in the order in which you have identified yourself to our CDM folks.

At this time we have some information updates on on-site testing.

ON-SITE TESTING

Dr. Caplan: Donna has asked me to co-chair with Bob Willette to re-initiate or begin a new process with regard to on-site testing. There has been a working group that goes way back to the earlier conferences that we had, the big conferences, which was kind of an individual-wide working group representing a lot of manufacturers and had a lot of products. Very little has happened with that in this time, and not necessarily because, I don't think because it's any more or less important, but because it was more limited in the things, the outcomes that were likely compared to the other specimen types. So we have spent a fair amount of time in the last two years on the other specimens.

Conceptually, you reach a point where there begins to be enough information and there has to be more from the Board and HHS to decide and using the information. So we're passed the preliminary acquisition stage. For on-site testing, it was decided to change the approach a little bit and we are planning -- the dates aren't real clear yet. We are planning to have an initial meeting here in this hotel in August, and it's the 2nd, 3rd, 4th, in that range, two days, approximately two days.

What we're going to do at that meeting, we're going to try to notify all the interested parties that we know about and deal with the issues of what is out there, summarize what is out there, probably by asking each of the manufacturers of particular devices to make a presentation, but not a sales presentation, answering 10 or 12 questions like what's the fundamental technology, what's the detection system, things like that, so we can summarize the products.

We're going to have two working meetings with Bob Willette, myself, and HHS between now and August to prepare for this. All the details will be coming out later.

Then we're going to have this two-day meeting to go through the technology and the issues. The fact that it's urine limits some of the things. It is still urine, and we're going to focus on the on-site part of it.

The other two things that are likely to be associated with that, again to facilitate this whole process, is, as was indicated by Sam Niedbala earlier, is that we will look at other on-site devices, particularly saliva, at the same time since there are certain commonalities there, rather than put them in the saliva matrix.

Also, the process will begin at that meeting for looking at urine laboratory-based possible changes. Dan Isenschmid (Board Member) and Mick Smith (Armed Forces Institute of Pathology) are sharing the group to do that, which is also forming or will be formulating in the next couple weeks but prior to that meeting the things that are needed to do that, what are the questions that have come up on this program that would be worth some review in conjunction with the on-site parameter, which is close akin to that, and then the rest of the possible specimens or matrices.

So that is the plan to deal with urine and on-site testing conceptually, and it'll round out in the next month. The meeting dates are still unknown. I think the plan will be that we will notify laboratories, because laboratories in general should have some interest in this. We don't want to tell you until we know what the format is, whether it's worth your coming. Hopefully there will be enough time in this two-day period to deal with some of the on-site issues and some of the laboratory issues.

We may decide after we go over this that it's going to be totally the on-site and the laboratory will be done elsewhere. We will be going back to the previous group, which is the NOTA group and the people that are in there, to notify them of the meeting.

The concept will not be exactly like the current working groups, a little bit more along the lines of how we had the preliminary meeting, but actually something in between, at least for this first meeting. After this first meeting, we will decide how detailed these issues are and whether there needs to be smaller working groups to round it out or whether the group will just meet again.

That's kind of the overview and the plan to deal with the other two aspects of this, reminding everyone that in the end we're going to have to put them all together and go across the grid, which we hope will come back by the end of the year, that kind of information, to the Board where we can take a look at this in a more succinct manner. That's the plan.

Dan's going to handle the review of laboratory-based testing, and I think one of the plans there will be to contact the laboratories for some information. So Dan can talk to you a little about that.

Dr. Isenschmid: We certainly will want to get information from the laboratories, based on the years of testing experience with the urine matrix, what the pros as well as the cons are in the various laboratories' experience with that particular matrix and what kinds of things may be revisited. Certainly, there are things on the grid that need to be reconsidered, and there may also be things outside that grid that need to be considered for urine. We certainly don't want to limit ourselves to what's on the grid, but I think there's going to be things that need to be looked at that go beyond that, and maybe include other analytes and things like that.

I think we will be looking heavily to the laboratories, based on their experience and from their work at looking at the various issues that should be revisited for the urine drug testing matrix, while going across and looking at all the other matrices and all the other things that were asked from those matrices, and to re-evaluate that in the context of the urine specimen.

I think that's where we're going to be headed at that point in time. I think it's going to -- out of the very nature of the fact that we're dealing with the same matrix, on-site and laboratory-based urine drug testing should not be considered in a vacuum and should be considered in a similar vein, particularly as related to confirmatory testing.

Also, initial testing is going to have ramifications in what is decided in on-site testing versus the current requirements for laboratory-based urine testing for initial tests.

Dr. Caplan: At this point, unless you have more definitive information, what we need from the audience, are any suggestions about things that should be included or you'd like to see included in any of these discussions. Now is the time to throw the ideas forward because we're going to be formulating it in the next month or so and then trying to develop the agenda for that meeting. And the only notification probably we'll be able to do is through the NOTA type group and the people that are on that list and the laboratory group. If there are other people here who want to get further information, make sure you let the HHS office know to put you on the mailing list. I don't think there'll be time to put this in any other notification, like the Federal Register.

Dr. Bush: The dates we have here at the hotel are August 2nd, 3rd, and 4th. We have the meeting room across the way. We have a room that will seat 40 classroom-style already scheduled. I'm not sure what kind of interest we'll get. Maybe we'll get a larger room, double it up. I'm just not sure. We'll have to decide whether we want to meet Monday and Tuesday August 2nd and 3rd or if we want to instead maybe travel on Monday and meet Tuesday and Wednesday. I'm not sure how it's really going to fall out. We'll have to let people know after a couple of decisions are made following the wrap-up of this meeting and discussion over the next few days.

Mr. Stephenson: We'll make a commitment to make this information available on our web site. Is there anybody who does not know how to get a hold of us on the Internet or where our site is?

Dr. Bush: It's easy: www.health.org/workpl.aspx.

Mr. Stephenson: That takes you into a sub-menu that's available under what's called Drugline. It's a national clearinghouse on drug information. There is a workplace issues area. We'll put it up on the Internet, and so it will be a place that you can find it.

We'll try to let everybody else know. If you hear about it and you know somebody else, use the telephone, word of mouth, e-mail, and let folks know, too. We'll make a concerted effort to make sure that this is an open meeting that you guys can attend if you want to.

Dr. Bush: At least you know the week that it's going to be.

Mr. Stephenson: We are at a point of doing a summary and public comments. I'd like to ask if there are any members of the public who'd like to make any public comments to the group.

Mr. Shults (AAMRO): There were a couple times during the proceeding this morning where I wanted to talk up, but I said, I'll just wait until the end, because the comments are sort of global in one sense. It has really been remarkable to me watching the Board over the last year or two, how much has been accomplished in terms of filling out these complex matrices. It reminds me a little bit of the history of astronomy, and I'll tell you why. It's really the first science. As some of you know, the difficulty with early astronomers was how do you describe the movement of heavenly bodies when the basic concept was that the Earth was the center of the universe. So it was a very difficult problem, and a lot of the discussions over what a specimen is or how does it compare, what are the detection levels, remind me of those early mathematical calculations. I think we've come to a transition, recognizing -- and of course, what's the center of the universe? The center of the universe is urine-based drug laboratory testing. So how does everything compare to that? How do the rest of these technologies spin?

I think now, listening to the discussion today, what Bob had mentioned is that you were going to take a look at that as well as a moving body as well. And I think that that represents a transitional stage, and to see how all these things relate to each other in that context.

The other transitional stage is that it's very important, I think, to get much more involved with the MRO practice. To some degree, the wagon that we build doesn't have wheels until you put the MRO on, or the MRO are the wheels of the wagon, so to speak, because that's really where the wheels meet the road. That's the interface between the technology, the policy, the donor, the employer, and the science to some degree or another.

I was going to talk to Bob this morning and say: You know, I really would like to volunteer myself and to work with the subgroups. And before I had a chance to say that, Bob asked me if I could be more active in working with the subgroups in sort of providing what we know and consolidating this into a syllabus and training programs for the medical review officers. I think that that represents a transitional period, because we do talk about these things in these training programs, but we've done it in a context of being an advanced program. But the last year, I think all of you have seen in looking in this field, we've seen a tremendous, a tremendous transition in terms of what's available in the non-regulated field. We're seeing a lot of on-site testing. I've gotten papered with press releases about saliva testing and alternative technologies.

In the real world it's happening out there, and to what degree do the MRO's need to get this information I think has become critical. We're looking at including this into our basic training program. With that, that's the end of the astronomy lesson.

Mr. Stephenson: Are there any other public comments that any members of the public wish to make? (No response.)

Mr. Stephenson: In summary, I'd like to close with what I opened with this morning. I don't have any more definitive information about availability of funds to hold the next Drug Testing Advisory Board meeting in the month of September. We will advise you at a point in time as soon as we can. I think the earliest I'm going to have an answer for that is probably this Thursday.

It gives you an idea of how cash-constrained one can become when you make a decision about the process of the work we're going on with here to be held up in the amount of about $5,000, and that is all we're talking about. But when it becomes funds that you can't expend because they aren't there, it becomes another issue.

So we'll have to let you know whether the next meeting is on or off. We'll do it within the next week and let you know at that time.

I'd like to suggest that we've seen a lot of movement in the grid, in the development of the information, and I think it's been consistent and evenhanded across the board. I think we are all learning more about the issues that are kind of end game. We're no longer just middle game, but we're looking toward the issues of how to go beyond just the science and the documentation of the science elements and the data, and how to use that to form the knowledge and wisdom to make the right kind of public policy decisions, and that's another transition point that we're at in the program right now.

The process has been open, it's been public, and it's been incredibly instructive for us who've been on the inside of the program. We've seen the creation of an issue for PT's and in that regard have issued a challenge to Research Triangle Institute to begin that process. I'll tell you, just to share a little bit, that we have had some of those discussions and we will be going forward with this in as aggressive manner as possible.

We have talked about the issue of MRO and a focus on the MRO issues, and I think Ted Shults has addressed that. I think Carl and any others of you who wish to participate in this group process, we welcome that participation. I think it's critical that we do a deliberate outreach to the thousands upon thousands of MRO's through their professional organizations to see what kind of input, what kind of case studies, what kind of wisdom they have because I think it's going to be critical as we look at this area.

I think the last thing is that we need to address the issues of how to go about some of these prospective studies or the controlled dosing studies, and realize that these take a lot of lead time, take a lot of money, and take an awful lot of focus of political will to get these onto the busy agenda of the few research facilities that could possibly do them.

We need to identify the best protocols and the best opportunities where the information is most critically needed and then make that as a proposal. We're also going to have to identify sources of funding for this kind of activity and to get the support from those within the Department as well as those within the administration to see that we can actually achieve these things.

We also need to find out how much can be contributed from the industries and what can be done from your side, because clearly we cannot do it all. You have demonstrated a willingness and an ability to come together with us over the last couple years, and with these small working groups I think we've got a great deal of movement and I am encouraged by the whole process. I think it's much better than we've ever had before, and I hope that we can continue to keep it as a model.

We are becoming a learning community in the way that we've dealt with these issues. I don't think we'll ever go back to the way we were before. And I'm amazed that we were able to start a program and retain it over time with as little as we did know back then. But we're here now, we're much better informed, and I think we're in a much better position to go forward on all of these areas.

I thank each and every one that has participated in this process, for helping to make that possible, and continuing to provide assistance.

Dr. Caplan: You said you wanted to set some dates for next year, or do you want to defer that?

Mr. Stephenson: We're going to have to look at an issue of when we can have the next DTAB meeting, and that will shift us perhaps from September into October, and if that happens we would probably then shift from December to January. If we can simply offset this one a little bit, we'll try to set those dates and make those available.

We'll communicate with each member of the Board, and look at your calendars and propose some alternative dates, and we'll do that. It's much more cumbersome than doing it in a group, but we need to do that. We recognize your calendars fill up quickly, months in advance. Once we've done that, then we'll let the rest of the public know and we'll put it on the web site along with the other things.

Are there any other issues that any of the members of the Board wish to bring to the attention? Any members of the public? (No response.)

Mr. Stephenson: At this time I'd like to close the open session of the Drug Testing Advisory Board. Thank you very much for being here.