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Medical Review Officer Manual
for Federal Agency Workplace Drug Testing Programs

November 1, 2004 (Effective Date)

This manual provides additional guidance to supplement the medical review officer requirements contained in the Mandatory Guidelines for Federal Workplace Drug Testing Programs that were published in the Federal Register on April 13, 2004 (69 FR 19644), with a November 1, 2004, implementation date.

Note: This manual does not apply to specimens collected under the Department of Transportation Procedures for Transportation Workplace Drug and Alcohol Testing Programs (49 CFR Part 40).

Previous Versions of this Manual are Obsolete

Table of Contents

Chapter

Chapter 1.  The Medical Review Officer (MRO)

The final review of results is an essential component of any drug testing program. A positive laboratory test result does not automatically identify an employee or job applicant as an illegal drug user, nor does a laboratory result of invalid, substituted, or adulterated automatically identify specimen tampering. An individual with a detailed knowledge of possible alternative medical explanations must interpret non-negative results in the context of information obtained from the donor interview. HHS requires the Medical Review Officer (MRO) to fulfill this important function.

The HHS Mandatory Guidelines define an MRO as a licensed physician holding either a Doctor of Medicine (M.D.) or Doctor of Osteopathy (D.O.) degree who has:

  • Knowledge about and clinical experience in controlled substance abuse disorders,
  • Detailed knowledge of alternative medical explanations for laboratory positive drug test results,
  • Knowledge about issues relating to adulterated and substituted specimens, and
  • Knowledge about possible medical causes for specimens reported as having an invalid result.

MRO training programs are available from various professional organizations to ensure that MROs are familiar with current regulations and receive the latest information on interpreting test results. Although HHS does not require formal certification for MROs at the present time, training courses have served a very important role in providing continuing education for MROs.

The MRO serves as the common point of contact between all parties involved in a drug test (i.e., the donor, the collector, the laboratory, and the Federal agency's designated representative). The MRO may be an employee or a contractor for a Federal agency; however, the following restrictions apply:

  • The MRO must not be an employee or agent of or have any financial interest in the laboratory for which the MRO is reviewing drug testing results, and
  • The MRO must not derive any financial benefit by having an agency use a specific drug testing laboratory or have any agreement with the laboratory that may be construed as a potential conflict of interest.

The purpose of these prohibitions is to prevent any arrangement between a laboratory and an MRO that would prevent the MRO from reporting a problem identified with a laboratory's test results or testing procedures.

The MRO has the following responsibilities:

  • Determine that the information on the Federal Drug Testing Custody and Control Form (Federal CCF) is correct and complete,
  • Interview the donor when required,
  • Make a determination regarding the drug test results,
  • Report the result to the Federal agency, and
  • Maintain records and confidentiality of the information.

HHS recommends that each MRO use the guidance contained in this manual to ensure consistency and to improve the overall quality of the review process.

The following professional organizations offer courses and information for licensed physicians who are interested in the MRO specialty:

      American College of Occupational and Environmental Medicine (ACOEM)
      1114 North Arlington Heights Road
      Arlington Heights, IL 60004-4770
      Telephone: 847- 818-1800
      Fax: 847-818-9266
      www.acoem.org

      American Society of Addiction Medicine (ASAM)
      4601 North Park Avenue, Upper Arcade #101
      Chevy Chase, MD 20815
      Telephone: 301- 656-3920
      Fax: 301-656-3815
      www.asam.org

      American Association of Medical Review Officers (AAMRO)
      P.O.Box 12873
      Research Triangle Park, NC 27709
      Telephone: 1-800-489-1839
      Fax: 919-490-1010
      www.aamro.com

Note: The listing of these organizations is not an endorsement by the Federal government.

Chapter 2.  The Federal Drug Testing Custody and Control Form

Federal agencies are required to use the Office of Management and Budget (OMB) approved Federal CCF for their agency workplace drug testing programs.

The following employers are prohibited from using the Federal CCF:

  • Private-sector companies
  • States
  • Department of Justice programs
  • Non-DOT testing conducted by DOT-regulated employers

The Federal CCF is usually provided by the laboratory that will test the specimen and is also available from other sources (e.g., forms suppliers, collectors, MROs).

A sample of the Federal CCF is on the SAMHSA website at http://workplace.samhsa.gov/. All discussions in this manual refer to this version of the Federal CCF (OMB Number 0930-0158).

The Federal CCF consists of 5 copies that are distributed by the collector as follows:

    Copy 1 - Laboratory Copy - sent to the laboratory with the specimen bottle(s)

    Copy 2 - MRO Copy - sent to the MRO

    Copy 3 - Collector Copy - retained by the collector

    Copy 4 - Employer Copy - sent to the Federal agency

    Copy 5 - Donor Copy - given to the donor when the collection process is complete

Each Federal CCF is printed with a unique specimen identification number. The Federal CCF includes labels with the same ID number that the collector places on the specimen bottle(s) to link the specimen to information on the CCF. Information that is pre-printed or written on the Federal CCF includes:

  • Name, address, and contact information for the collection site, collector, Federal agency/employer, MRO, and testing laboratory,
  • Donor identifying information,
  • Reason for test, and
  • Test(s) to be performed.

The collector initiates the chain of custody documentation for the specimen using the Federal CCF. The term "chain of custody" refers to documentation of all handling of a specimen. Chain of custody documents provide evidence that the specimen was secure and its integrity was maintained from the time of collection to its final disposition.

The Federal CCF is sealed and shipped with the specimen bottle(s) to the laboratory. The laboratory staff member who receives and processes the specimen for testing (i.e., the accessioner) verifies the information that is on the bottle(s) and on the Federal CCF and signs the Federal CCF. Thereafter, laboratory staff members document the chain of custody of the specimen and all aliquots taken for testing using internal laboratory forms.

The laboratory must be in a secure facility, with access limited to authorized personnel. Individual areas within the laboratory (e.g., receiving/accessioning area, testing areas, sample preparation area, specimen storage areas) are usually separately secured, to limit access to staff with job duties in the area. All visitors to secured areas must be escorted and their access must be documented.

Certified laboratories must ensure the security and integrity of regulated specimens, and follow strict chain of custody procedures to provide a forensically acceptable record of the specimen's handling. This requires that all specimens be kept in secured storage or in the line of sight custody of an authorized individual, with appropriate chain of custody entries (i.e., signature, date, and action/purpose of each custody transfer) made at the time of actions. In addition, laboratories are required to maintain the confidentiality of donor information by restricting access to records of regulated specimens.

When a specimen's testing is complete, the certifying scientist at the laboratory reviews all data and associated documentation for the specimen including the Federal CCF. The certifying scientist annotates the specimen's results by marking the appropriate boxes on the Federal CCF, and including any additional comments concerning the specimen's testing or processing on the "Remarks" line. By signing the certification statement on the Federal CCF, this individual attests that the specimen was handled and tested in accordance with Federal requirements.

For non-negative results, the laboratory must send the laboratory copy of the Federal CCF (Copy 1) or a legible image of Copy 1 to the MRO. The laboratory is allowed to send a computer-generated report in addition to the Federal CCF.

  • The copy of the Federal CCF (Copy 1) will be marked with one or more of the following non-negative results:
    • Positive for one or more drugs,
    • Adulterated (with the adulterant or pH value recorded on the "Remarks" line),
    • Substituted (with the creatinine and specific gravity values recorded on the "Remarks" line), or
    • "Invalid result" (with the reason for the invalid result recorded on the "Remarks" line).
  • These are separate results. For example, "invalid result" does not refer to the drug(s)/drug metabolite(s) marked positive. The MRO should contact the laboratory if there is any confusion about the reported results.

For negative results, the laboratory is allowed to report the results using a computer-generated report (i.e., the completed Federal CCF is retained by the laboratory).

Chapter 3.  Urine Drug Testing

A Federal agency may collect urine specimens using either a single specimen collection procedure or a split specimen collection procedure. The collector prepares a split specimen by pouring the urine from the collection container into two bottles, which are then labeled as the A Bottle and the B Bottle. All specimens (including all aliquots taken from the original specimens) are handled using strict chain of custody procedures to provide a clear record of each specimen's handling from the time it was collected until final disposition by the laboratory.

HHS-certified laboratories may routinely only test Federal agency specimens for amphetamines, marijuana, cocaine, opiates, and phencyclidine. However, testing for an additional drug may occur for one of the following reasons:

  • There is reasonable suspicion/cause or a post-accident incident for which testing for another drug listed in Schedule I or II of the Controlled Substances Act is justified (see Section B, Drug Information, below); or
  • A Federal agency was granted a waiver by the Secretary of HHS to routinely test its employees for another drug or drug class.

For any circumstance where testing for an additional drug is justified or authorized, the Federal agency must prepare a memorandum explaining why the specimen is being tested for the additional drug. The memorandum is given to the collector and the collector then marks the "Other" box in Step 1 on the Federal CCF and specifies the name of the drug(s) to be tested. The memorandum from the Federal agency is attached to the Federal CCF when the urine specimen is transferred to the laboratory. If the memorandum is not provided to the laboratory, the laboratory must not test for the additional drug noted on the Federal CCF.

For forensic as well as scientific acceptability, laboratories are required to perform initial and confirmatory tests on a specimen to support a non-negative result. Initial drug and specimen validity tests are performed on all specimens. Those specimens that have negative initial drug test results and acceptable initial specimen validity test results are reported as negative. Specimens that are presumptive drug positive, substituted, or adulterated are subjected to confirmatory testing using a different test method that is usually more specific than the initial test.

The donor is given the opportunity to request a retest when his or her specimen is reported as positive, substituted, or adulterated. The retest (i.e., an aliquot of the single specimen collection or Bottle B of a split specimen collection) is performed at a second certified laboratory.

If the donor chooses not to request specimen retesting, a Federal agency may have a single or split specimen retested as part of a legal or administrative proceeding to defend an original positive, adulterated, or substituted result.

Laboratories are required to maintain the following specimens in a secure frozen storage area for at least one year after reporting the result:

  • Drug positive specimens
  • Substituted specimens
  • Adulterated specimens
  • Invalid specimens
  • Split specimens (B Bottles) of the primary specimens listed above
  • Any specimens or specimen aliquots received from another laboratory for retesting

A Federal agency may request the laboratory to retain a specimen for a longer period (e.g., specimens under legal challenge).

Laboratories may discard rejected specimens after reporting them as rejected to the MRO.

A. Test Methods

An MRO is not required to be as technically knowledgeable of the analytical procedures and data as a laboratory certifying scientist. However, the MRO must know what tests were used to generate the specimen results that he or she reviews and should understand the general scientific principles of the technologies.

Certified laboratories are required to use immunoassay for initial drug tests and to use gas chromatography/mass spectrometry (GC/MS) for confirmatory drug tests.

Immunoassay
Immunoassays are immunochemical testing methods that use antigen activity to identify drug analytes. Antibodies to the drug analyte (i.e., the antigen) are produced. A known amount of the antibody is added to a specimen along with drug that has been labeled with an enzyme or radioactive label. The drug in the specimen competes with the labeled drug for the antibody, to form an antigen-antibody complex. Various methods are used to measure the amount of drug present in the specimen. Immunoassays are used as initial drug tests, the preliminary test to identify presumptive positive specimens. The method is not specific enough to use as a confirmatory test. For example, many structurally similar drugs may cross-react with an immunoassay reagent, giving a positive result. Specimens that are positive by immunoassay are tested using GC/MS as a confirmatory test, to specifically identify and quantitate the drug or drug metabolite.

Table 1 provides brief descriptions of common immunoassays used for drugs of abuse.

Gas Chromatography/Mass Spectrometry (GC/MS)
Gas chromatography is a chromatographic technique for separating and analyzing mixtures of chemical substances in a gas or vapor mobile phase by adsorption on a stationary phase. GC/MS is a combined technique coupling a mass spectrometer (MS) with a GC instrument. Urine specimens must undergo a specimen preparation process (i.e., extraction) prior to GC/MS analysis. After the GC has separated the analytes in a specimen, the specimen enters the MS, which identifies and quantitates the separated analytes. The MS creates charged particles (ions) and separates them according to their mass-to-charge (m/z) ratios. The ions form unique mass spectra, which are used to identify analytes.

While the Guidelines do not specify the methods to be used for initial and confirmatory specimen validity tests,laboratories are required to use a pH meter for the initial and confirmatory pH tests and a refractometer measuring to at least four decimal places for the initial and confirmatory specific gravity tests. Laboratories must use appropriate, validated methods for all specimen validity tests.

Table 2 provides brief descriptions of some methods that may be used for specimen validity tests.

B. Drug Information

The Federal Government classifies controlled substances under 5 schedules established under the Controlled Substances Act (CSA):

Schedule I:

  • The drug or other substance has a high potential for abuse.
  • The drug or other substance has no currently accepted medical use in treatment in the United States.
  • There is a lack of accepted safety for use of the drug or other substance under medical supervision.

Schedule II:

  • The drug or other substance has a high potential for abuse.
  • The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions.
  • Abuse of the drug or other substances may lead to severe psychological or physical dependence.

Schedule III:

  • The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II.
  • The drug or other substance has a currently accepted medical use in treatment in the United States.
  • Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence.

Schedule IV:

  • The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III.
  • The drug or other substance has a currently accepted medical use in treatment in the United States.
  • Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III.

Schedule V:

  • The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule IV.
  • The drug or other substance has a currently accepted medical use in treatment in the United States.
  • Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule IV.

The President's Executive Order 12564 defines "illegal drugs" as those under Schedule I or Schedule II. The U.S. Drug Enforcement Administration (DEA) enforces the provisions of the CSA.

Cannabinoids (Marijuana)

1. Background

Cannabinoid-containing compounds come from the hemp plant, Cannabis sativa. The principal psychoactive agent in cannabinoids is delta 9 tetrahydrocannabinol (THC). Certified laboratories are required to use confirmatory testing for cannabinoids that specifically identifies delta-9-THC.

Cannabinoid-containing compounds are found in two forms, marijuana and hashish. Marijuana is a mixture of crushed leaves, flowers, and sometimes the stems of the cannabis plant. Hashish contains the dried resinous secretions of the cannabis plant and, in general, has a higher concentration of THC than marijuana.

Marijuana is a Schedule I drug. Medical marijuana is a controversial issue, and there has been some scientific evidence that smoked marijuana is beneficial for patients with debilitating symptoms such as unmanageable pain and vomiting. However, use of marijuana is not an acceptable alternative medical explanation for a positive confirmed drug test result in federally-regulated drug testing programs.

Dronabinol is chemically synthesized delta-9-tetrahydrocannabinol (THC). It is the sole pharmaceutical source of THC and is available as Marinol® (Roxane Laboratories). The drug has psychoactive effects that may present safety issues.

Nabilone (Cesamet®) is a synthetic cannabinoid available in Europe. This drug does not metabolize to delta-9-THC. Therefore, the use of Nabilone is not an acceptable medical explanation for a positive confirmed drug test.

Cannabinoids produce a pleasant euphoria or "high" and a sense of relaxation and well-being that is commonly followed by drowsiness. The initial psychoactive effects of smoking THC occur within minutes, reach a peak within 10-30 minutes and may persist for 2-4 hours. Intoxication temporarily impairs concentration, learning, and perceptual motor skills. Reduced functional ability lasts for at least 4-8 hours after a dose of marijuana. Psychomotor performance may be impaired long after the acute subjective effects have ended. In one study, experienced pilots demonstrated impaired performance in a flight simulator for 24 hours after a dose, long after the subjective "high" had disappeared9. Functional impairment is not well understood in cases of prolonged, heavy marijuana use, because behavioral and physiological tolerance develops.

In addition to tolerance, a mild abstinence syndrome may follow abrupt termination of very high dose, chronic marijuana use. Withdrawal signs include irritability, sleep disturbance, diminished appetite, gastrointestinal distress, salivation, sweating, and tremors. Marijuana abstinence syndromes are uncommon when used at the doses usually taken in this country.

Routes of administration:

  • Marijuana - smoking (preferred), and oral (i.e., eating)
  • Hashish - smoking (preferred), and oral (i.e., eating)

2. Metabolism and Excretion

Cannabinoids are usually smoked. Trans-pulmonary absorption occurs quickly and causes a direct psychoactive response in the brain. Cannabinoids are sometimes eaten because the drug also is absorbed through the gastrointestinal tract; however, gastro-intestinal absorption occurs much more slowly. THC is distributed into different parts of the body where it is metabolized, excreted, or stored. The THC that is stored in fatty tissue gradually reenters the blood stream at very low levels, permitting metabolism and eventual excretion. THC is metabolized extensively in the liver and the major metabolite is 11-nor-Delta9- tetrahydrocannabinol 9 carboxylic acid (delta-9 THCA).

The immunoassay procedures detect multiple metabolites of marijuana, while the GC/MS procedures specifically identify and quantitate delta-9 THCA. To be reported positive under the HHS Guidelines, a specimen must test positive at or above the 50 ng/mL cutoff for the initial test and have a concentration of delta-9 THCA that is equal to or greater than the 15 ng/mL confirmatory cutoff level. Infrequent marijuana use may cause positive initial test results for 1-5 days2. With repeated smoking, THC accumulates in fatty tissue. Chronic smokers slowly release THC over a longer time and may continue to produce detectable levels of drug for longer periods of time.

Cocaine

1. Background

Cocaine is an alkaloid from the coca plant that is usually sold as cocaine hydrochloride, a fine, white crystalline powder. "Freebasing" is a method used to chemically alter cocaine hydrochloride to remove the hydrochloride salt. "Crack" is one form of free base cocaine that has become popular in recent years. It is sold as small lumps or shavings and is the product of a manufacturing process that uses sodium bicarbonate or ammonia rather than a flammable solvent. Because it survives high temperatures, crack is smoked, resulting in absorption into the bloodstream that is as rapid as injection. Cocaine is metabolized within hours of administration and; therefore, the Federal drug testing program requires analysis for cocaine as its major metabolite benzoylecgonine.

Cocaine has only a limited legal use in the United States as a topical anesthetic in ear, nose, and throat surgery. It is a widely used drug of abuse and is classified as a Schedule II drug.

Cocaine produces psychomotor and autonomic stimulation with a euphoric subjective "high." Larger doses may induce mental confusion or paranoid delusions. Serious overdoses cause seizures, respiratory depression, cardiac arrhythmias, and death.

Short-term tolerance (tachyphylaxis) develops when several doses of cocaine are administered over a brief period. Among chronic users, the stimulant effect may seem progressively weaker, and exhaustion, lethargy, and mental depression appear. Cocaine abusers often report vocational impairment due to exhaustion even though they do not use the drug at work.

Patients withdrawing from cocaine experience moderate lethargy and drowsiness, severe headaches, hyperphagia, vivid dreams, and some mental depression. These symptoms usually subside within a few days to a few weeks.

Routes of administration:

  • Intranasal (i.e., snorting) is the most common
  • Smoking the "freebase" or "crack" form of the drug
  • Intravenous injection

2. Metabolism and Excretion

Cocaine is rapidly and extensively metabolized by liver and plasma enzymes to its major metabolite benzoylecgonine. Benzoylecgonine is more persistent and can usually be detected for up to 2 days after a single dose. Cocaine and benzoylecgonine are not significantly stored in the body. Therefore, even after heavy, chronic use, urine specimens will be negative when collected a few days after last use.

Opiates

1. Background

The term "opiate" specifically refers to natural alkaloids extracted from the opium poppy. The term "opioid" refers to synthetic opiates and opiate-like drugs in addition to the naturally occurring opiates. Opioids are classified as narcotics. The Federal agency drug testing program's focus is on illicit use of morphine, codeine, and heroin:

  • Morphine - is the most abundant naturally occurring opiate and is considered the prototype of the opioid class of drugs. Morphine is available as a prescription drug (Schedule II) and is used primarily for its potent analgesic properties.
  • Codeine - can be naturally occurring; however, it can also be synthesized chemically by 3-O-methylation of morphine. Codeine medications are available by prescription and over-the-counter (Schedule III, Schedule IV, and Schedule V), depending on concentration and preparation. Codeine is commonly used in analgesic, antitussive, and anti-diarrheal agents.
  • Heroin (diacetylmorphine) - is a semisynthetic opiate obtained by reacting natural morphine with acetic acid. Heroin has no legitimate medical use in the United States and is only available illegally (Schedule I). Heroin is not easily detected in urine and therefore usage is determined by detection of its intermediate metabolite 6-acetylmorphine (6-AM).

Cognitive and psychomotor performance can be impaired by opiates, although the duration and extent of impairment depend on the type of opiate, the dose, and the experience and drug history of the user. Ingestion of low to moderate amounts produces a short lived feeling of euphoria followed by a state of physical and mental relaxation that persists for several hours. Opioid intoxication may cause meiosis, a dull facies, confusion or mental dullness, slurring of speech, drowsiness, or partial ptosis (i.e., nodding, the head drooping toward the chest and then bobbing up).

It is common for opioid abusers to develop tolerance and therefore continually increase the dose taken in an attempt to maintain the euphoric effect. All opiates are physically and psychologically addictive, and produce withdrawal symptoms that differ in type and severity. Flu-like symptoms are common during opiate withdrawal (e.g., watery eyes, nausea and vomiting, muscle cramps, and loss of appetite).

Routes of administration:

  • Morphine - injection, intranasal (i.e., snorting), oral (i.e., tablets), and smoking
  • Codeine - injection and oral (i.e., tablets, elixir)
  • Heroin- intravenous injection, intranasal (i.e., snorting), and smoking

Additional issues regarding opioids:

  • Poppy seeds are a significant dietary source of codeine and/or morphine.
  • In December 1998, HHS revised the Mandatory Guidelines for Federal Workplace Drug Testing Programs to increase the initial testing and confirmatory cutoffs for opiates (i.e., from 300 ng/ml to 2000 ng/ml) and require laboratories to test all morphine positive specimens for heroin metabolite (6-AM). These measures were taken to eliminate most specimens that test positive due to poppy seed ingestion or due to the use of legitimate morphine or codeine medication.
  • Synthetic or semi-synthetic narcotics do not metabolize to codeine, morphine, or 6-acetylmorphine. These include, but are not limited to:
    • alphaprodine (Nisentil®)
    • hydromorphone (Dilaudid®)
    • oxymorphone (Numorphan®)
    • hydrocodone (Hycodan®, Lorcet-HD®, Vicodin®)
    • dihydrocodeine (Synalgos®)
    • oxycodone (Percodan®, Percocet®, Tylox®)
    • propoxyphene (Darvon®)
    • methadone (Dolophine®)
    • meperidine (Demerol®)
    • fentanyl (Duragesic®, Sublimaze®)
    • pentazocine (Talwin®)
    • buprenorphine (Buprenex®, Subutex®)

Table 3 provides a representative sample of the prescription and non-prescription products that contain codeine or morphine.

Note: Further information regarding the interpretation and reporting of opiates is found in the Interpretation and Result Verification Section (i.e., Chapter 5, Section C.)


2. Metabolism and Excretion

Morphine is rapidly absorbed and excreted as:

  • unchanged morphine
  • glucuronide conjugates
    • morphine-3-glucuronide (primary metabolite)
    • morphine-6-glucuronide

Morphine and its metabolites can be detected in urine up to about four days after its use. Morphine is not metabolized to codeine.

Codeine (methylmorphine) is also rapidly absorbed and is excreted as:

  • unchanged codeine
  • morphine
  • glucuronide conjugates
    • codeine-6-glucuronide
    • morphine-3-glucuronide
    • morphine-6-glucuronide

The presence of both codeine and morphine in urine indicate the recent use of codeine; however, morphine alone may be detected as a remnant of codeine that has been completely metabolized.

Heroin (diacetylmorphine) is deacetylated to its primary metabolite 6-AM (also known as 6-monoacetylmorphine, 6-MAM) within minutes of administration. Therefore, heroin itself is rarely detected in urine. 6-AM is mostly likely to be detected within the first 24 hours post-administration because of its rapid metabolism to morphine. Codeine may be found in the urine of heroin users as a result of codeine present as a contaminant in the morphine used to synthesize the heroin.

Amphetamines

1. Background

Amphetamine and methamphetamine are substances regulated under the Controlled Substances Act as Schedule II stimulants. Both drugs have been used for treating attention deficit disorder in children, obesity, and narcolepsy.

Amphetamine and methamphetamine are central nervous system stimulants that initially produce euphoria, a feeling of well-being, increased self-esteem and appetite suppression followed by restlessness and irritability. A single therapeutic dose often enhances attention and performance, but exhaustion eventually occurs and performance deteriorates as the effects wear off. Frequently, repeated high dose use produces lethargy, exhaustion, mental confusion, and paranoid thoughts.

Tolerance can develop to the effects of amphetamine and methamphetamine. A typical therapeutic dose is 5 milligrams. Individuals who abuse these drugs are reported to inject up to one gram in a single intravenous dose. Physical dependence is modest. Lethargy, drowsiness, hyperphagia, vivid dreams, and some mental depression may persist for a few days to several weeks after abrupt termination of repeated high doses.

Amphetamine and methamphetamine exist in two isomeric structural forms known as enantiomers. Enantiomers are non -superimposable mirror images. The two isomers of each substance are designated as d- (dextro) and l- (levo), indicating the direction in which they rotate a beam of polarized light. As do many pharmacological enantiomers, the d- and l- isomers have distinct pharmacological properties. In this case, the d- isomer of each substance has a strong central nervous system stimulant effect while the l- isomer of each substance has primarily a peripheral action. Illegally manufactured amphetamine and methamphetamine are principally found as the d-isomer. However, significant amounts of the l- isomer of each substance may be present depending on the starting materials used by the clandestine laboratories.

Routes of administration:

  • Amphetamine - oral (i.e., tablets or capsules), intravenous injection, smoking, and intranasal (i.e., snorting)
  • Methamphetamine - oral (i.e., tablets or capsules), intravenous injection, smoking, and intranasal (i.e., snorting)


Table 4 provides a representative sample of products containing amphetamines.


2. Metabolism and Excretion

Nearly half of a methamphetamine dose is recovered from urine unchanged. A small percentage is demethylated to amphetamine and its metabolites. The excretion rate of methamphetamine is also increased when urine is acidic.

Amphetamine is excreted as both unchanged amphetamine and as hydroxylated metabolites. Typically, about one quarter of an administered dose is excreted as unchanged amphetamine, but this varies widely with urinary pH; the drug stays in the body longer when urine is alkaline, allowing re-absorption and thus allowing more of it to be metabolized. In 24 hours, about 80 percent of a dose will be excreted if urine is acidic, while less than half is excreted if urine is alkaline.

A single therapeutic dose of amphetamine or methamphetamine can produce a positive urine for about 24 hours depending upon urine pH and individual metabolic differences. High dose abusers may continue to generate positive urine specimens for 2 to 4 days after last use.

Generally, the amphetamine/methamphetamine result reported by the laboratory does not indicate the specific enantiomer because the laboratory procedure is set up to only identify and quantitate the presence of amphetamine and/or methamphetamine. In order to determine which enantiomer is present, an additional analysis must be performed.

The enantiomer identification may be useful in determining if a donor has been using a Vicks Inhaler®, a prescription medication, or abusing an illegal drug; however, the presence of the l- isomer of either amphetamine or methamphetamine does not by itself rule out illegal use.

Phencyclidine

1. Background

Phencyclidine (PCP), an arylcyclohexylamine, was first synthesized in the 1950's as a general anesthetic. Street names include Angel Dust, Crystal, Killer Weed, Supergrass, and Rocket Fuel. PCP's synthesis is relatively simple for clandestine laboratories. Phencyclidine's use as a human anesthetic was discontinued because it produced psychotic reactions (i.e.,"emergence delirium"), but the drug remains in use as a veterinary tranquilizing agent. PCP is currently a Schedule II controlled substance.

PCP has a variety of effects on the central nervous system. Intoxication begins several minutes after ingestion and usually lasts eight hours or more. PCP is well known for producing unpredictable side effects, such as psychosis or fits of agitation and excitability. The severe debilitating physical and psychological effects of PCP abuse and the extremely unpredictable behavior caused by the drug clearly have drastic effects on performance.

Intoxication may result in persistent horizontal nystagmus, blurred vision, diminished sensation, ataxia, hyperreflexia, clonus, tremor, muscular rigidity, muteness, confusion, anxious amnesia, distortion of body image, depersonalization, thought disorder, auditory hallucinations, and variable motor depression or stimulation, which may include aggressive or bizarre behavior.

Ketamine is the only analog of PCP that has any legitimate use. It is currently used in veterinary treatment. Ketamine does not cross-react with PCP initial or confirmatory testing.

Routes of administration:

  • Smoking (preferred)
  • Oral
  • Intranasal (i.e., snorting)
  • Intravenous injection

2. Metabolism and Excretion

PCP is well absorbed by any route and is excreted as unchanged PCP and as conjugates of hydroxylated PCP. About 10 to 15 percent of the PCP dose is excreted in the urine as unchanged drug. PCP is a weak base which concentrates in acidic solutions in the body. Because of gastric acidity, PCP repeatedly re-enters the stomach from plasma, and is re-absorbed into plasma from the basic medium of the intestine.

Generally, PCP is considered detectable in urine for several days to several weeks depending on the frequency of use.

C. Adulterant Information

"Adulterated" is the term used for a specimen that has been altered by the donor in an attempt to defeat the drug test. The goal is to affect the ability of the laboratory to properly test the specimen for drugs and/or to destroy any drug or drug metabolite that may be present in the specimen. Many substances can be used to adulterate a urine specimen in vitro, including common household products, commercial chemicals, and commercial products developed specifically for drug test specimen adulteration. Adulterants are therefore readily available, may be easily concealed by the donor during the collection procedure, and can be added to a urine specimen without affecting the temperature or physical appearance of the specimen. To identify adulterated specimens, HHS requires certified laboratories to perform a pH test and a test for one or more oxidizing compounds on all regulated specimens. Laboratories are also allowed to test regulated specimens for any other adulterant, providing they use initial and confirmatory tests that meet the validation and quality control requirements specified by the HHS Guidelines.

An adulterant may interfere with a particular test method or analyte, but not affect others. For example, an adulterant may cause false negative marijuana (cannabinoids) results using a particular immunoassay reagent, but not affect the test results for other drugs. The same adulterant may not affect the test results obtained using a different immunoassay reagent or different immunoassay method. It is also possible for an adulterant to cause false positive drug test results, rather than the intended false negative. The initial drug test required for Federal workplace programs (immunoassay) is more sensitive to adulterants than the required confirmatory drug test (GC/MS). Currently, the GC/MS assays for marijuana metabolite (THCA) and opiates appear to be affected by adulterants more than GC/MS assays for other drugs.

When a laboratory is unable to obtain a valid drug test result or when drug or specimen validity tests indicate a possible unidentified adulterant, the laboratory reports the specimen to the MRO as "invalid result" (see Interpretation and Result Verification section below). When an MRO receives an "invalid" specimen report, it is incumbent upon him/her to discuss with the laboratory whether additional tests should be performed by the laboratory or by another certified laboratory. It may be possible to obtain definitive drug test results for the specimen using a different drug test method or to confirm adulteration using additional specimen validity tests. The choice of the second laboratory and/or additional tests will be dependent on the suspect adulterant and the validated characteristics of the different drug tests. Laboratory staff should be knowledgeable of their tests' validated characteristics including effects of known interfering substances, and be able to recommend whether additional testing is worthwhile.

HHS allows certified laboratories to test for any adulterant. It is not possible to provide specific program guidance for all substances that may be used as adulterants; however, HHS has included specific requirements in the Guidelines for pH analysis and for the analysis of known adulterants listed below:

pH of human urine is usually near neutral (pH 7), although some biomedical conditions affect urine pH. HHS set the program cutoffs for pH based on a physiological range of approximately 4.5 to 9. Specimens with pH results outside this range are reported as invalid. An extremely low pH (i.e., less than 3) or an extremely high pH (i.e., at or above 11) is evidence of an adulterated specimen.

Nitrite is an oxidizing agent that has been identified in various commercial adulterant products. Nitrite (NO2) is produced by reduction of nitrate (NO3). Nitrite in high concentrations is toxic to humans especially infants, causing methemoglobinemia by oxidizing the iron in hemoglobin. Nitrate and, to a lesser extent, nitrite are present in the environment. Nitrite may be present in human urine from the following sources:

  • Food: Sodium nitrite is used as part of the curing process for meat (e.g., ham, wieners). Nitrates are present in vegetables (e.g., celery, spinach, beets, radishes, cabbage).
  • Drinking water: Water sources may become contaminated with nitrate and nitrite due to run-off from farms using nitrogen fertilizers, from septic systems, and from livestock feedlots. The levels of nitrate and nitrite in public drinking water supplies are monitored because of the potential health threat to infants under six months of age.
  • Occupational exposure: Workers in explosives and pharmaceuticals manufacturing may be exposed to nitrates.
  • Medications: Organic nitrate and nitro compound drugs (e.g., used for angina, congestive heart failure, ulcers) metabolize to inorganic nitrite ion. Inorganic nitrite/nitrate salts have limited medical uses (e.g., used for cyanide poisoning).
  • Endogenous production: The enzyme nitric oxide synthase (NOS) catalyzes the endogenous formation of nitric oxide radical, which oxidizes to nitrite and nitrate. This may result in normal human urine containing a small amount of nitrate with an extremely small ratio of nitrite.
  • Pathological conditions: Some infectious and inflammatory conditions (e.g., sepsis, asthma, rheumatoid arthritis, tuberculosis, inflammatory bowel disease, Alzheimer's disease, multiple sclerosis) induce another enzyme (i.e., inducible NOS) that catalyzes the formation of nitric oxide radical.
  • Medical treatments: Some medical treatments (e.g., Interleukin-2 in cancer treatment) can induce NOS and result in nitrite in the urine.
  • Urinary tract infections: Some urinary tract infections are caused by bacteria that, if present in large numbers, may reduce nitrate to nitrite by microbial action.

Because low levels of nitrite may be present in human urine due to the reasons listed above, HHS set a cutoff level of 500 mcg/mL for adulteration and 200 mcg/mL for invalid results. These concentrations are well above levels seen in human urine. Therefore, these reasons do not explain a nitrite adulterated result.

Chromium (VI) is a strong oxidizing agent that has been identified in various commercial adulterant products. The most common forms of the element chromium are chromium (0), chromium (III), and chromium (VI). All have industrial uses. Both chromium (III) and chromium (VI) are used for chrome plating, dyes and pigments, leather tanning, and wood preserving. Chromium (III) is an essential nutrient and is always present in humans. Chromium (VI) is toxic and has been shown to be a human carcinogen. The presence of chromium (VI) in a urine specimen is indicative of adulteration. HHS set an initial test cutoff level of 50 mcg/mL for chromium (VI).

Surfactants, including ordinary detergents, have been used to adulterate urine specimens. Surfactants have a particular molecular structure made up of a hydrophilic and a hydrophobic component. They greatly reduce the surface tension of water when used in very low concentrations. Foaming agents, emulsifiers, and dispersants are surfactants that suspend an immiscible liquid or a solid, respectively, in water or some other liquid. Surfactants tend to clump together when in solution, forming a laminar surface between the fluid and air with their hydrophobic components along the surface and their hydrophilic components in the fluid. Often surfactants will form "bubbles" (micelles) within the fluid: a small sphere of hydrophilic "heads" surrounding a pocket containing the hydrophobic "tails." They can also form bubbles in air (i.e., two nested spheres of surfactant with a thin layer of water between them, surrounding a pocket of air) and can form "antibubbles" in fluid (i.e., a layer of air surrounding a pocket of water).

Halogens are the four elements fluorine, chlorine, bromine, and iodine. Halogen compounds have been used as adulterants. The term "halogen" (from the Greek hals, "salt," and gennan, "to form or generate") was given to these elements because they are salt formers. None of the halogens can be found in nature in their elemental form. They are found as salts of the halide ions (F-, Cl-, Br-, and I-). Fluoride ions are found in minerals. Chloride ions are found in rock salt (NaCl), the oceans, and in lakes that have a high salt content. Both bromide and iodide ions are found at low concentrations in the oceans, as well as in brine wells. The assays used by certified laboratories identify halogen compounds that act as oxidants. These do not include the halogen salts that may be present in a urine specimen. The presence of an oxidative halogen in a urine specimen is evidence of adulteration.

Glutaraldehyde is a clear, colorless liquid with a distinctive pungent odor sometimes compared to rotten apples. One of the first effective commercial adulterants was found to contain glutaraldehyde. Glutaraldehyde is used as a sterilizing agent and disinfectant, leather tanning agent, tissue fixative, embalming fluid, resin or dye intermediate, and cross-linking agent. It is also used in X-ray film processing, in the preparation of dental materials, and surgical grafts. Glutaraldehyde reacts quickly with body tissues and is rapidly excreted. The most common effect of overexposure to glutaraldehyde is irritation of the eyes, nose, throat, and skin. It can also cause asthma and allergic reactions of the skin. Glutaraldehyde at any detectable level in a urine specimen is evidence of adulteration.

Pyridinium chlorochromate is a strong oxidizing agent that has been identified in some commercial adulterants. This compound is confirmed by urine drug testing laboratories using a confirmatory test for pyridine. Pyridine is a colorless liquid that can be prepared from crude coal tar or from other chemicals. Pyridine formed from the breakdown of natural materials results in very low levels in air, water, and food. It is used as a solvent, and also used in the preparation of medicines, vitamins, food flavorings, paints, dyes, rubber products, adhesives, insecticides, and herbicides. There is little information on the health effects of pyridine, although some animal studies and human case reports have noted liver damage from exposure to pyridine. Human exposure may occur by various means (e.g., inhalation or dermal exposure of workers in industries that make or use pyridine, inhalation of pyridine released into air from burning cigarettes or hot coffee, exposure to air or water contaminated from hazardous waste sites or landfills). The U.S. Food and Drug Administration (FDA) allows its use as a flavoring agent in food preparation. Pyridine at any detectable level in a urine specimen is evidence of adulteration.

D. Dilution/Substitution

A donor may attempt to decrease the concentration of drugs or drug metabolites that may be present in his or her urine by dilution. Deliberate dilution may occur in vivo by consuming large volumes of liquid, often in conjunction with a diuretic, or in vitro by adding water or another liquid to the specimen. Donors also have been known to substitute urine specimens with drug-free urine or other liquid during specimen collection. Due to donor privacy considerations, collections for federally regulated drug testing programs are routinely unobserved. Therefore, dilution and substitution may be undetected by collectors and be viable methods for defeating drug tests. There are products on the market today purporting to "cleanse" the urine prior to a drug test; many of which are diuretics. There are also products designed specifically for urine specimen substitution, including drug-free urine, additives, and containers/devices to aid concealment. Many such devices have heating mechanisms to bring the substituted specimen's temperature within the range set by HHS to determine specimen validity at the time of collection (i.e., 32º to 38ºC/90º to 100ºF). Some include prosthetic devices to deceive the observer during a direct observed collection.

To identify diluted and substituted specimens, HHS developed criteria for evaluating specimens for the following human urine characteristics:

Creatinine is a protein produced by muscle and cleared from the body by the kidneys. It is a normal constituent in urine. Normal human urine creatinine concentrations are greater than 20 mg/dL. Abnormal levels of urine creatinine may result from excessive fluid intake, glomerulonephritis, pyelonephritis, reduced renal blood flow, renal failure, myasthenia gravis, or a high meat diet.

Specific gravity is a measure of the density of a substance compared to the density of water. For urine, the specific gravity is a measure of the concentration of particles in the urine. Normal values for the specific gravity of human urine range from approximately 1.0020 to approximately 1.0200. Decreased urine specific gravity values may indicate excessive fluid intake, renal failure, glomerulonephritis, pyelonephritis, or diabetes insipidus. Increased urine specific gravity values may result from dehydration, diarrhea, excessive sweating, glucosuria, heart failure, proteinuria, renal arterial stenosis, vomiting, and water restriction.

Laboratories are required to test the creatinine in all regulated specimens, and to test specific gravity for specimens with creatinine less than 20 mg/dL. There are established program cutoffs for identifying invalid, dilute, or substituted specimens based on the paired creatinine and specific gravity test results. Appendix A describes Laboratory Reporting Criteria from the HHS Guidelines.

Chapter 4.  The MRO Review and Reporting Process

The MRO must review all non-negative test results (i.e., positive, adulterated, substituted, invalid) and all negative and dilute specimens before reporting the results to the Federal agency's designated representative. Negative specimen results may be reviewed and reported by staff under the direct, personal supervision of the MRO.

The MRO process consists of:

  • Administrative review of documents,
  • Interview with the donor (as required),
  • Handling retest requests (as required),
  • Result interpretation and verification, and
  • Reporting of results to the Federal agency's designated representative.

No regulatory requirements exist requiring MROs to use specific procedures to review drug tests; however, using a standard procedure better ensures that the MRO review for each specimen is complete and thorough. A simple checklist can be helpful in assuring consistency and completeness of the process.

A. Administrative Review of Documents

1. MRO Copy of the Federal CCF (Copy 2)

The collector is required to send the MRO Copy of the Federal CCF (Copy 2) to the MRO within 24 hours or one business day after the collection. If the MRO receives a laboratory test report for a specimen without having received the MRO copy of the Federal CCF, the MRO must contact the collector. If the MRO copy is not available, the MRO must obtain another legible copy of the Federal CCF (e.g., collector or employer copy) that has been signed by the donor and has the donor's name and telephone number(s).

The following items are verified for Copy 2 of the Federal CCF:

a. The correct OMB-approved Federal CCF was used to document the specimen collection.

b. The Federal CCF contains the specimen identification number.

c. The testing laboratory is identified by one of the following:

  • A specific laboratory name and address at the top of the CCF,
  • A list of addresses with check boxes at the top of the Federal CCF (the collector checks the box for the laboratory to which the specimen will be delivered), or
  • A corporate name and telephone number at the top of the Federal CCF and the specific laboratory address in the "Test Lab" line in Step 5a.

d. The Federal CCF was properly completed:

  • Step 1 contains:
    • Federal agency name and address,
    • MRO name, address, and telephone number,
    • Donor identification (e.g., SSN, employee identification number),
    • Reason for the test,
    • Tests to be performed, and
    • Collection site information (i.e., address, telephone number, and fax number)
  • Step 2 documents that:
    • The temperature of the specimen was or was not within the required temperature range,
    • The collection was a split specimen or single specimen collection,
    • No specimen was collected and why (if applicable),
    • A direct observed collection was performed and why (if applicable), and
    • Comments on the "Remarks" line (as appropriate) recording the collector's observations or explanatory comments concerning the donor, the specimen, or collection events.
  • Step 4 contains:
    • Collector's printed name,
    • Collector's signature,
    • Date and time of the collection, and
    • Specific name of the delivery service that was used to transfer the specimen to the laboratory.
  • Step 5 contains:
    • Donor's printed name,
    • Donor's signature,
    • Date signed,
    • Donor's daytime telephone number,
    • Donor's evening telephone number, and
    • Donor's date of birth.

2. Laboratory Report - Federal CCF (Copy 1) and/or Computer-Generated Electronic Report

Certified laboratories report drug test results only to the MRO. The laboratory and the MRO must have procedures in place to ensure the confidentiality of the reports (i.e., hardcopy and electronic). The laboratory may send drug test reports by:

  • Courier,
  • Mail,
  • Secure fax, and
  • Secure electronic transmission.

The following items are verified for the laboratory report for a specimen:

a. The specimen identification number on the laboratory copy of the Federal CCF (Copy 1) and/or on any other laboratory report matches that on the MRO copy (Copy 2) for the identified donor.

b. The Federal CCF was properly completed:

  • Step 4 contains:
    • Accessioner's printed name,
    • Accessioner's signature, and
    • Documentation of the bottle seal condition upon receipt at the laboratory.
  • For a single or primary (Bottle A) specimen, Step 5a contains:
    • Test results,
    • Certifying scientist's printed name,
    • Certifying scientist's signature,
    • Date of result certification,
    • Comments on the "Remarks" line (as appropriate):
      • Quantitative test results
      • Comments as required by HHS for specimens reported as "adulterated," "rejected for testing," or "invalid result"
      • Observations or explanatory comments recorded by laboratory staff concerning the specimen, and
    • Name and address of the testing laboratory (if not on the top of Copy 1).
  • For a retest specimen, Step 5b contains:
    • Test results,
    • Certifying scientist's printed name,
    • Certifying scientist's signature,
    • Date of result certification,
    • Comments on the "Remarks" line (as appropriate):
      • Quantitative test results
      • Comments as required by HHS for specimens that failed to reconfirm
      • Observations or explanatory comments recorded by laboratory staff concerning the specimen, and
    • Name and address of the testing laboratory.

c. The laboratory has included a memorandum from the collector to address any correctable flaws identified. See Section 3 below.

d. The computer-generated electronic report (if any) contains the HHS-required information as follows:

  • Laboratory name and address,
  • Federal agency name,
  • MRO name,
  • Specimen identification number,
  • Donor identification from the Federal CCF (e.g., SSN, employee ID number),
  • Collector name and telephone number,
  • Reason for test (if provided),
  • Date of collection,
  • Date received at laboratory,
  • Certifying scientist's name,
  • Date certifying scientist released the results,
  • Test results, and
  • Additional comments concerning the specimen's testing and processing, as listed in the "Remarks" line of the Federal CCF.

e. The information on the computer-generated electronic report (if any) is consistent with that on the laboratory copy of the Federal CCF (Copy 1).

3. Federal CCF or Specimen Errors

A laboratory or an MRO may identify errors made on a Federal CCF, or a laboratory may identify a problem with a specimen during processing. The various types of errors are outlined below:

a. Uncorrectable errors that result in specimen rejection by the laboratory and test cancellation by the MRO:

  • Specimen ID number on the Federal CCF and bottle label/seal do not match or the number is missing on either the Federal CCF or the specimen bottle label/seal,
  • Specimen bottle label/seal is missing or broken on the specimen from a single specimen collection or on a primary specimen (Bottle A) of a split specimen collection and the split specimen (Bottle B) cannot be redesignated as the primary specimen,
  • The collector's signature and printed name are omitted from the CCF, or
  • There is insufficient specimen volume for testing.

b. Correctable errors that result in specimen rejection and/or cancellation unless corrected by a memorandum for the record (MFR) from the collector:

  • The collector failed to sign the CCF (but the printed name is present), or
  • The collector used a non-Federal form or an expired version of the Federal CCF.

c. Federal CCF omissions and discrepancies that are considered insignificant when they are infrequent (i.e., when a collector does not make the error more than once a month). Examples include, but are not limited to:

  • No collection date/time,
  • No courier entry,
  • No specific delivery service name, or
  • Donor name included on the laboratory copy of the CCF.

d. Administrative errors made by laboratory staff that are judged by the MRO to have a significant impact on the forensic defensibility of the results unless corrected by an MFR. Examples include, but are not limited to:

  • No accessioner signature on the CCF,
  • No documentation of bottle seal condition on the CCF, or
  • No certifying scientist signature on the CCF.

4. Federal CCF Remarks

Collectors are required to include comments on the "Remarks" line in Step 4 (the collector's section) of the Federal CCF to document any unusual donor behavior or incidents occurring during the collection. Laboratory staff are required to include comments on the "Remarks" line in Step 5a of the Federal CCF to document any issues concerning the specimen (e.g., redesignation of the A and B Bottles), as well as explanatory reporting comments required by the program (e.g., the basis for reporting a specimen as adulterated, the basis for reporting an "invalid result," reason for rejection).

The MRO evaluates whether information provided on the Federal CCF "Remarks" lines have a significant impact on the forensic defensibility of the drug test results. If the MRO believes the forensic defensibility of the results is affected, he or she either attempts to obtain an MFR or cancels the test.

5. Actions Based on Administrative Review

When an uncorrectable error is identified (see Item 3.a above):

    a. If the laboratory identifies the error, the laboratory rejects the specimen for testing and reports the specimen as rejected to the MRO. The reason for rejection is included on the laboratory report(s) to the MRO.

    b. If the MRO receives a rejected for testing report or identifies an uncorrectable error during review, the MRO cancels the test.

    c. The MRO reports the cancellation and the reason to the Federal agency, which then determines whether or not to immediately collect another urine specimen from the donor.

When a correctable documentation/specimen error (see Item 3.b above) by the collector is identified by either the laboratory or the MRO, the collector is notified to provide an MFR to address the error:

    a. If the collector provides an MFR:

    • The laboratory includes a copy of the MFR with the report to the MRO.
    • The MRO reports the verified result (see Section D below) to the Federal agency and maintains the MFR in the files for the specimen.
    b. If the collector does not provide an MFR:
    • The laboratory holds the specimen for a minimum of 5 business days after requesting the MFR, then reports the specimen as rejected and discards the specimen. The reason for rejection is included on the laboratory report(s) to the MRO.
    • The MRO cancels the test and notifies the Federal agency of the cancelled test and the reason for cancellation.

When the laboratory and/or MRO document frequent insignificant errors by an individual collector (see Item 3.c):

    a. The MRO notifies the collector/collection site of the errors.

    b. The collector/collection site takes appropriate corrective actions (e.g., revises procedures, retrains the individual and other collectors at the collection site) and submits a copy of documentation of the action(s) to the MRO.

    c. The MRO maintains the documentation of error notification and corrective action response in his or her records.

B. Donor Interview

The MRO must contact the donor and interview the donor when the donor's specimen is reported by the laboratory as non-negative (i.e., positive, adulterated, substituted, invalid).

The MRO must attempt contact as soon as possible after receiving the report (usually within 24 hours). The MRO copy of the Federal CCF will contain daytime and evening telephone numbers for the donor.

The MRO should establish guidelines as to what constitutes a reasonable effort to contact a donor. All attempts made to contact the donor must be documented.

If the MRO, after making all reasonable efforts, has been unable to contact the donor within 14 days after the date on which the MRO received the test result from the laboratory:

1. The MRO must inform the Federal agency of his or her inability to contact the donor.

    a. The MRO must not reveal the test result or any information about the drug test.

    b. The Federal agency must:

    • Confidentially direct the donor to contact the MRO within 5 days, and
    • Inform the MRO once the donor has been directed to contact the MRO or if the Federal agency was unable to contact the donor.

2. The MRO may verify a test result without having communicated directly with the donor (i.e., a non-contact determination) for the following reasons:

    a. The donor expressly declines the opportunity to discuss the test result, or

    b. The Federal agency has contacted the donor and instructed the donor to contact the MRO, but the donor has not contacted the MRO within 5 days after being contacted by the Federal agency.

The Interview Process

1. Request the donor to provide information that will verify the donor's identity (e.g., employee identification number, SSN) to ensure that it agrees with the information documented on the Federal CCF. (This step may be done by staff under the MRO's supervision; however, the MRO must personally perform all other steps of the interview process as listed below).

2. Inform the donor, prior to obtaining any information, that confidential medical information provided during the review process may be disclosed to the Federal agency.

3. Inform the donor of the laboratory reported test result(s).

4. Take action based on the donor's response:

    a. If the donor admits use of an illegal drug consistent with the test results or admits that he or she tampered with the specimen, advise the donor that the test result will be reported to the Federal agency.

    b. If the donor does not admit use of an illegal drug or specimen tampering, ask the donor if there is any possible medical explanation for the test result:

    • If the donor provides a possible medical explanation (e.g., claims that a positive result was due to a legally prescribed medication or that the drug use was associated with a valid medical procedure), require the donor to provide appropriate supporting documentation within a specified time.
    • If the donor has no valid medical explanation for the result, advise the donor that the test result will be reported to the Federal agency.

5. For positive, substituted, or adulterated results: Inform the donor that he or she may have the specimen retested at a second certified laboratory. The retest request must be made within 72 hours of the interview with the MRO. (Note that donors are not allowed to request retesting of specimens reported as invalid.)

    a. If the donor requests a retest, use the procedures described in Section C (Handling Retest Requests) to direct the laboratory to send the retest specimen to another certified laboratory for confirmatory testing.

    b. If the donor does not request a retest, document that the donor was informed of and declined the opportunity for a retest.

C. Handling Retest Requests

Note: Donors are not allowed to request retesting of specimens reported as invalid.

The following are rules for handling retest requests for positive, adulterated, or substituted specimens:

1. The donor has 72 hours from the time the MRO notified the donor that his or her specimen was reported positive, adulterated, or substituted to request the retest.

2. The MRO must request the retest of a single specimen or the test of the split (Bottle B) specimen in writing (i.e., a memorandum or letter format). The written request may be mailed, faxed, or electronically sent to the laboratory where the primary specimen was tested and must contain the following information:

  • MRO name and address (use MRO letterhead),
  • Laboratory name and address (i.e., Laboratory A) where original analysis was performed,
  • Specimen ID Number on the Federal CCF,
  • Laboratory Accession Number (i.e., the number assigned by Laboratory A to the specimen when it was accessioned),
  • Request for confirmatory retest for the drug/metabolite, adulterant, or substitution reported by Laboratory A, and
  • Name and address of the HHS-certified laboratory (i.e., Laboratory B) selected to retest the specimen (i.e., aliquot of a single specimen or the split (Bottle B) specimen).

3. Laboratory B may be selected by the MRO, the Federal agency, or the donor. In most instances where retesting is requested, the first laboratory will have blanket purchase agreements with 2 or 3 other certified laboratories to make the billing and payment process easier.

4. If the specimen cannot be tested by a second laboratory (e.g., insufficient volume, lost in transit, Bottle B not available, no other certified laboratory tests for the specific adulterant), the MRO shall direct the Federal agency to immediately collect another specimen using a direct observed collection procedure.

  • If the test is cancelled because no other certified laboratory tests for the specific adulterant, the MRO notifies the appropriate regulatory office.

5. The second HHS-certified laboratory reports retest results directly to the MRO using Copy 1 of the Federal CCF.

6. The MRO reports the result to the Federal agency and the donor.

D. Interpretation and Result Verification

The Drug Information section above provides information on the drugs specified in the HHS Mandatory Guidelines for testing in Federal agency workplace programs, including the current CSA schedules, signs/symptoms of abuse, and metabolism information.

The MRO interprets drug test results based on:

  • The laboratory results,
  • The donor's explanation and supporting documentation, and
  • The MRO's medical assessment of the donor's behavior and physical symptoms during the donor interview.

The MRO must report only verified results to the Federal agency. The MRO must not inform the Federal agency when a positive, adulterated, or substituted result was verified as negative.

Table 5 describes MRO actions to be taken for primary specimen results.

Table 6 describes MRO actions to be taken for retest specimen results.

Laboratory Results

Laboratory staff are available to answer MRO questions concerning reported drug test results. However, laboratories are strictly prohibited from providing any information about a specimen's result prior to completion of testing and are prohibited from providing any drug test results over the telephone.

The Mandatory Guidelines provide specific reporting criteria for certified laboratories to report Federal agency specimen results. These criteria are described in Appendix A. The laboratory must report all non-negative results for a specimen, as supported by data.

After receiving a drug test report, the MRO should contact the laboratory whenever additional information is needed. For example, the MRO may wish to clarify the laboratory's administrative and analytical procedures, or obtain quantitative results or other information that could be useful in evaluating the validity of a donor's explanation. General information may be given over the telephone. Requests for information about a specific specimen (e.g., quantitative results) must be made by the MRO in writing. The written request may be mailed, faxed, or electronically sent to the laboratory.

The term "invalid result" is used when a scientifically supportable negative test result cannot be established for a specimen due to an unidentified adulterant, an interfering substance, an abnormal physical characteristic, or an endogenous substance at an abnormal concentration (see criteria in Appendix A).

When the MRO receives a report of "invalid result," the MRO must discuss the result with the laboratory to determine if additional testing by another certified laboratory could provide a definitive result (i.e., negative, positive, or adulterated). Specimens reported as invalid based on creatinine and specific gravity results or on pH are exceptions to this rule. The MRO is not required to contact the laboratory when a specimen is reported as invalid for these reasons. It is unlikely that testing by another certified laboratory would provide different results.

Donor Explanation

As noted previously, one of the purposes for a donor interview is to allow a donor the opportunity to provide an alternative explanation for a non-negative drug test result. For the explanation to be accepted, the donor must provide acceptable supporting documentation to the MRO. If the alternative explanation for a positive, adulterated, or substituted result is acceptable and supported by documentation as outlined below, the MRO must verify the result as negative.

Prescriptions

If the donor claims to have taken a prescribed medicine that contains either the drug reported positive or a substance that can metabolize to that drug, the donor must provide one of the following:

  • A copy of the prescription,
  • The medicine container with the appropriately labeled prescription (or the label from the container), or
  • A copy of the medical record documenting the valid medical use of the drug during the time of the drug test.

The MRO may contact the prescribing physician or the pharmacist who filled the prescription to verify the information provided by the donor.

If the donor has been taking a prescription medication that contains a drug with a high potential for abuse for a long time, there must be appropriate justification for the long term use. The MRO must contact the prescribing physician to express concern that the continued use of the medication may present a significant safety problem for the donor while on the medication.

State initiatives and laws which make available to an individual a variety of illicit drugs by a physician's prescription or recommendation do not make the use of these illicit drugs permissible under the Federal Drug-Free Workplace Program. These State initiatives and laws are inconsistent with Federal law and put the safety, health, and security of Federal workers and the American public at risk.

The use of any substance included in Schedule I of the Controlled Substance Act, whether for non-medical or ostensible medical purposes, is considered a violation of Federal law and the Federal Drug-Free Workplace Program. These drugs have no currently accepted medical use in treatment in the United States and their use is inconsistent with the performance of safety-sensitive, health-sensitive, and security-sensitive positions, and with drug-free workplace programs.

The MRO must not accept a prescription or the verbal or written recommendation of a physician for a Schedule I substance as a valid medical explanation for the presence of a Schedule I drug or metabolite in a Federal employee/applicant specimen.


Interpretation of Results

Dilute Specimens

A laboratory may report a specimen as dilute in conjunction with a positive or negative drug test. A donor may produce urine that meets the program criteria for dilution under some conditions including:

  • Working in hot weather conditions drinking large amounts of fluid,
  • Taking a diuretic, or
  • Drinking fluids immediately before providing the specimen.

The MRO actions to be taken in response to a dilute specimen report depend on whether the drug test result is positive or negative. These MRO actions are shown in Table 5.

Substituted Specimens

The HHS criteria for identifying substituted specimens are based on the physiological ranges for creatinine concentration and specific gravity value of normal human urine. If the donor denies substituting the specimen, he or she is given the opportunity to prove the ability to produce urine that meets substitution criteria as described below.

1. If the donor claims to have consumed a large quantity of fluids prior to providing the urine specimen:

    a. The MRO requests the Federal agency to have the donor provide another specimen collected using a direct observed collection procedure and have the collector document that the donor drank a similar quantity of fluids prior to providing the specimen.

    b. If the creatinine and specific gravity results for the second specimen are similar to the results for the first specimen, this is considered a legitimate explanation for the substituted result.

2. If the donor claims to have a pre-existing, documented medical condition that causes the donor's urine to meet both the creatinine and specific gravity criteria for a substituted specimen, the MRO requests the donor to provide a copy of the medical record to support that claim.

3. If the donor claims to have personal characteristics (e.g., race, gender, weight, diet, working conditions) such that his or her urine normally satisfies the substitution criteria:

    a. The MRO requests the donor to demonstrate that he or she can normally produce a substituted specimen.

    b. The demonstration must provide a reasonable basis to conclude that the donor's personal characteristics are a legitimate medical explanation.

Adulterated Specimens

The MRO is required to contact the donor and give the donor an opportunity to explain the adulterated result and to demonstrate that the presence of the adulterant occurred through normal physiological means. However, the program criteria for adulteration definitively prove adulteration. There is no valid medical explanation for a urine specimen to meet the criteria for an adulterated result under the HHS Mandatory Guidelines.

Amphetamines

Depending on the amphetamines confirmation method (e.g., derivatization procedure, instrument parameters) used by a laboratory, it is possible for some structurally similar compounds (i.e., sympathomimetic amines) to be converted to methamphetamine during GC/MS analysis. HHS instituted the following assay validation and reporting requirements that prevent the possibility of false positive methamphetamine results due to this conversion:

1. Laboratories are required to quantitate at least 200 ng/mL amphetamine in a specimen in order to report a positive methamphetamine result. As described previously, methamphetamine metabolizes to amphetamine. This occurs quickly, via a simple demethylation reaction. Because the sympathomimetic amines are not converted to amphetamine, the presence of amphetamine is supporting evidence for methamphetamine use.

2. Certified laboratories are required to validate all assays prior to use with Federal agency specimens. For amphetamines confirmatory assays, each laboratory must document the assay's ability to identify and accurately quantitate methamphetamine and amphetamine in the presence of high levels of sympathomimetic amines and also demonstrate that these compounds are not misidentified as methamphetamine or amphetamine (i.e., by analyzing samples containing sympathomimetic amines without methamphetamine or amphetamine). These experiments must be performed on at least an annual basis, to verify the assay's continued performance.

Enantiomers
Most immunoassays used as the initial test in Federal workplace drug testing programs are focused on d-methamphetamine. However, the l-methamphetamine enantiomer and amphetamine enantiomers cross-react with the immunoassay reagents. Amphetamines GC/MS assays identify both amphetamine and methamphetamine and do not distinguish between enantiomers. Therefore, there is a possibility that a laboratory positive result could be reported for l-methamphetamine and/or l-amphetamine.

Laboratories may employ a chiral GC/MS assay that distinguishes between the d- and l- enantiomers and determines the relative percentages of each. HHS does not require each certified laboratory to have this capability. Upon written request of the MRO, the laboratory may perform the test or send a specimen to another certified laboratory for d- and l- enantiomer testing.

When the MRO receives a methamphetamine positive result from a laboratory, he or she may order enantiomer testing to aid in result interpretation, as described below: