This manual applies to Federal agency drug testing
programs that come under Executive Order 12564 and the Department of Health and
Human Services (HHS) Mandatory Guidelines.
Chapter
1. The Medical Review
Officer (MRO)
2. Federal Custody and
Control Form
3. The MRO Review Process
4. Specific Drug Class
Issues
5. Documentation and
Recordkeeping
6. Additional MRO
Responsibilities
Chapter 1. The Medical Review Officer (MRO)
An essential part of the drug testing program is the final review of results as
required by the Mandatory Guidelines for Federal Workplace Drug Testing
Programs initially published in the Federal Register on April 11, 1988
(53 FR 11970-11989) and revised in the Federal Register on June 9, 1994
(59 FR 29908-29931). A positive laboratory test result does not automatically
identify an employee or job applicant as an illegal drug user. An individual
with a detailed knowledge of possible alternative medical explanations is
essential in performing this final review of results. The Medical Review
Officer (MRO) fulfills this important function.
An MRO is defined as a licensed physician who receives laboratory results, has
knowledge of substance abuse disorders, and has appropriate medical training to
interpret and evaluate an individual’s positive test result together with his
or her medical history and any other relevant biomedical information. Only
individuals holding either a Doctor of Medicine (M.D.) or Doctor of Osteopathy
(D.O.) degree may serve as MROs for federally regulated programs.
The MRO may be an employee or a contractor for the Federal agency; however, 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. Additionally,
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 this
requirement 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:
(1) Determine that the information on the Federal drug testing custody and
control form (CCF) is forensically and scientifically supportable;
(2) Interview the donor when required;
(3) Make a determination regarding the test result;
(4) Report the verified result to the Federal agency (employer); and
(5) Maintain records and confidentiality of the information.
It is recommended that MROs maintain a Standard Operating Procedure manual to
ensure consistency and improve overall quality of the review process and
participate in continuing education activities.
From initial requirements that an MRO be a licensed physician with knowledge of
substance abuse disorders, practical requirements have evolved regarding the
availability of various training programs. These programs ensure that MROs are
familiar with current regulations and receive the latest information on
interpreting drug testing results. Although there is no regulatory requirement
for formal certification at the present time, the training courses offered by
the various professional organizations have served a very important role in
providing continuing education programs.
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
(847) 818-1800
American Society of Addiction Medicine (ASAM)
4601 North Park Avenue, Suite 101
Chevy Chase, MD 20815
(301) 656-3920
American Association of Medical Review Officers (AAMRO)
17 Running Brook Court
Durham, NC 27713
(919) 489-5407
The listing of these organizations is not an endorsement by the Federal
government nor is attendance at one of their courses a regulatory requirement.
Chapter 2. Federal Drug Testing Custody and Control Form
For specimens collected under the Guidelines, an Office of Management and
Budget (OMB) approved Federal Drug Testing Custody and Control Form (CCF) must
be used to document the collection of a specimen at the collection site. The
CCF is available from a number of different sources (e.g., laboratories,
collectors, MROs).
A sample of the CCF (OMB No. 0930-0158, Exp. Date: 6/30/2003) is on the SAMHSA
web site (www.health.org/workpl.aspx). All discussions throughout this
revised manual refer to this version of the CCF form.
The CCF has five copies that are distributed as indicated:
Copy 1. Laboratory Copy
Copy 2. Medical Review Officer Copy
Copy 3. Collector Copy
Copy 4. Employer Copy
Copy 5. Donor Copy
Chapter 3. The MRO Review Process
A. Administrative Review of the CCF
The MRO reviews the MRO Copy of the CCF, or if not available, a legible copy of
any copy signed by the donor, which was received directly from the collection
site. The MRO ensures that:
(1) An OMB-approved CCF was used for the specimen collection.
(2) There is a specimen ID number on the top of the form along with the name
and address of the laboratory testing the specimen.
(3) Step 1 has all the required information (i.e., employer name and address,
MRO name, address and phone number, donor SSN or other ID number, reason for
the test, tests to be performed, collection site information).
(4) The collector marked one of the temperature boxes, one of the specimen
collection boxes, and the observed collection (if it was an observed
collection) in Step 2 on the CCF.
(5) The collector provided his or her printed name, a signature, date and time
for the collection, and a comment (if appropriate) on the "Remarks" line in
Step 2 on the CCF. The collector also provided the specific name of the
delivery service that was used to transfer the specimen to the laboratory.
Note: The collector must use the "Remarks" line in Step 2 to identify any
problem that may have occurred during the collection (e.g., donor refused to
sign the donor statement on Copy 2 of the CCF, temperature of the specimen was
outside the acceptable range and a second direct observed collection was
conducted, why a specimen was not collected, why an observed collection was
conducted, specimen appears to be adulterated). The identification of these
types of problems are for informational use by the laboratory and the MRO and,
generally by themselves, are insufficient to cancel the test.
(6) Step 5 on the CCF gives the donor identifying information (i.e., printed
name, signature, date signed, daytime phone number, business phone number, and
date of birth).
The MRO reviews Copy 1 of the CCF that is received from the testing laboratory.
Note: A laboratory may transmit a result (negative or non-negative) to an MRO
by either faxing the completed Copy 1 or transmitting a scanned image of the
completed Copy 1 by computer. A fax or scanned image of a completed Copy 1 is
sufficient, by itself, for reviewing a negative result. For a non-negative
result, the laboratory must send a hard copy of a completed Copy 1 to the MRO
before the MRO can report the result to the employer.
Copy 1 is similar to Copy 2, but has the following additional information:
(1) An accession number, if assigned by the laboratory, appears on the top of
Copy 1 along with the specimen ID number.
(2) The accessioner at the laboratory completed Step 4 (i.e., the accessioner
provided a printed name and signature, indicated whether the primary specimen
bottle seal was or was not intact, and indicated to whom or where the specimen
bottle was released).
(3) Step 5a indicates the test result (i.e., the test result for a single
specimen or the test result for the primary specimen (Bottle A) from a split
specimen collection) and has the printed name and signature of the certifying
scientist and date signed. There may also be a comment on the "Remarks" line if
the laboratory identified a problem with the specimen. The "Test Lab" line must
also be completed if the test laboratory is different than the name appearing
on the top of Copy 2.
Note: A comment on the "Remarks" line may identify either an administrative or
a technical problem when the specimen was received or during the testing
process (e.g., the seal on the primary specimen bottle was broken upon receipt,
why the laboratory reported the specimen as adulterated or substituted, why the
specimen was rejected for testing, why the laboratory reported an "Invalid
Result"). The MRO must consider these comments when making a determination.
Note: Many laboratories also provide a separate computer generated report that
gives much of the same information contained on Copy 1 of the CCF.
Note: If Copy 1 and Copy 2 are complete, it would appear that the collector
followed the required collection procedure and the laboratory correctly tested
and reported the test result.
If the MRO finds that the laboratory made an administrative error on Copy 1 or
failed to identify an administrative error made by the collector, the MRO must
contact either the collector or the laboratory (whichever made the
administrative error) to determine if the collector or the laboratory can
provide a Memorandum For Record (MFR) to recover/correct the administrative
error.
(a) If the laboratory or the collector provides an MFR to recover/correct the
administrative error, the MRO reports the verified result (i.e., whether the
analytical test result was determined to be negative, positive, adulterated,
substituted, or invalid result) to the employer and retains the MFR as part of
the records associated with the testing of the specimen.
(b) If the laboratory or the collector cannot provide an MFR to
recover/correct the administrative error and the MRO believes that the
administrative error has a significant impact on the validity of the entire
collection and testing process, the MRO may make and report a "Test Canceled"
determination. If the MRO believes the administrative error does not have a
significant impact on the validity of the collection or testing process, the
MRO may report the verified result (i.e., whether the analytical test was
determined to be negative, positive, adulterated, substituted, or invalid
result) and must describe the administrative error that could not be
recovered/corrected.
Note: When an MRO reports a "Test Canceled" result because the MRO believes
that the administrative error has had a significant impact on the validity of
the collection and testing process, it is the employer’s decision whether or
not to immediately collect another urine specimen from the donor. Certain
tests, such as, pre-employment, return to duty, require having a valid negative
drug test result.
B. Technical Review of Single Specimen or Primary (Bottle A) Specimen Test
Result
Note: It is assumed that the copies of the CCF were complete and all the
information was accurate, except in some cases when the laboratory reports a
"Rejected for Testing" result.
A specimen is defined to be:
(a) Dilute if the creatinine is < 20 mg/dL and the specific gravity
is < 1.003, unless the criteria for a substituted specimen are met.
(b) Substituted (i.e., the specimen does not exhibit the clinical signs or
characteristics associated with normal human urine) if the creatinine
concentration is < 5 mg/dL and the specific gravity is <
1.001 or > 1.020.
(c) Adulterated if the nitrite concentration is > 500 g/mL.
(d) Adulterated if the pH is < 3 or > 11.
(e) Adulterated if an exogenous substance (i.e., a substance which is not a
normal constituent of urine) or an endogenous substance at a higher
concentration than normal physiological concentration is present in the
specimen.
When the laboratory reports a:
Negative Result
The MRO makes a "Negative" determination, completes Step 6 on Copy 2 of the
CCF, and reports the "Negative" result to the employer.
If a laboratory also marked the dilute box, the MRO verifies the test result as
"Negative," marks the dilute box, and informs the employer that the next time
the donor is selected for a drug test the employer may require the specimen to
be collected under direct observation because the specimen was dilute.
Note: A comment indicating that the specimen was dilute does not affect the
validity of a "Negative" test result.
Positive Result
The MRO interviews the donor. If the donor is unable to provide a valid
alternative medical explanation, a positive laboratory test result is
determined as a "Positive" by the MRO. If the donor provides a valid
alternative medical explanation, the MRO reports the test result as "Negative."
The MRO completes Step 6 on Copy 2 of the CCF and reports the appropriate
result to the employer.
If a laboratory also marks the dilute box, the MRO reports the verified test
result (i.e., either "Positive" or "Negative"), marks the dilute box, and
informs the employer that the next time the donor is selected for a drug test
the employer may require the specimen to be collected under direct observation
because the specimen was dilute.
Rejected for Testing Result
A laboratory will report a "Rejected For Testing" result and give the reason
for rejecting the specimen when either of the following circumstances occur:
(1) The specimen is not tested because a fatal flaw was identified when the
specimen was accessioned (e.g., the specimen bottle seal was not intact upon
receipt by the laboratory, the specimen ID number on the specimen bottle does
not match the specimen ID number on the CCF, the specimen bottle contained
insufficient volume, the specimen in Bottle A had a different appearance than
the Bottle B specimen).
(2) The specimen test result is not reported because the collection site was
unable to provide a Memorandum for Record to correct/recover a flaw identified
on the CCF or on the specimen bottle label/seal (e.g., the collector could not
recall actually measuring the specimen temperature and had not checked the
temperature box).
Note: If the collection site provides an MFR to correct/recover a flaw, the
laboratory does not report a "Rejected for Testing" result but reports a
"Negative" or "Positive" result as appropriate and a copy of the MFR is
provided to the MRO when the test results are reported.
A "Rejected for Testing" result is determined by the MRO as a "Test Canceled"
result. The MRO completes Step 6 on Copy 2 of the CCF and reports a "Test
Canceled" result along with the reason for the cancellation to the employer.
The MRO must also inform the employer that an immediate collection of another
specimen is permitted, if the employer needs a "Negative" drug test result
(e.g., pre-employment, return to duty, and follow-up tests require a "Negative"
result).
Adulterated or Substituted Result
Adulteration refers to a donor’s attempt to externally add something to his or
her urine specimen in an attempt to affect the drug test. There are several
products sold through the internet and advertised in drug culture magazines for
this intended purpose.
Substitution refers to a donor’s attempt to replace his or her urine specimen
with "clean" urine, synthetic urine, water, or other fluid during the
collection procedure.
An "Adulterated" or "Substituted" result is determined by the MRO as a "Refusal
to Test." The MRO completes Step 6 on Copy 2 of the CCF and reports a "Refusal
to Test" result along with the reason to the employer.
Note: When a specimen is reported adulterated or substituted, the laboratory
does not report a "Positive" drug test result even though the laboratory may
have conducted and completed the confirmatory test.
Note: When a specimen appears to have an interferant that prevents the
detection of the drug/metabolite in the confirmatory test and there is
significant reduction or no recovery of the internal standard even after
multiple extraction attempts, the laboratory may consult with the MRO and send
the specimen to another HHS certified laboratory that has the capability of
conducting scientifically suitable validity tests to identify the interfering
substance/adulterant. If this process does not identify the interferant, the
second laboratory will report an "Invalid Result."
Invalid Result
A laboratory will report an "Invalid Result" when either of the following
circumstances occur:
(1) The specimen is unsuitable for testing (e.g., physical appearance of the
specimen is unacceptable and may affect the ability to analyze the specimen);
(2) Valid initial drug test results cannot be obtained (e.g., a laboratory is
unable to obtain a valid initial test result for each initial test and cannot
specifically identify the cause); or
(3) An unknown substance interferes with the confirmatory test.
The MRO must interview the donor to determine if the donor can provide any
possible reason why the specimen could not be properly tested by the laboratory
(e.g., medical illness, prescription medications, health food supplements).
Note: Tolectin® (Tolmetin - a non-steroidal anti-inflammatory medication),
Flagyl® (metronidazole - an antifungal and antibacterial agent), and Cipro®
(ciprofloxacin - an antibacterial agent) are the only known prescription
medications that may interfere with some immunoassay tests.
If the donor is unable to give an explanation, provides a valid prescription
for one of the above medications, or denies having tampered with the specimen,
the MRO completes Step 6 on Copy 2 of the CCF, reports a "Test Canceled"
result, and informs the employer that another specimen must be collected using
a direct observed collection. The collection of a second specimen may possibly
provide information needed to determine the reason why the first specimen was
reported as "Invalid Result." If the second specimen collected using direct
observation exhibits the same behavior as the first specimen, the MRO again
reports the result for the second specimen as "Test Canceled" and recommends to
the employer that no further action is required because the donor is either
taking a valid prescription medication that interferes with the drug test or
there is some unknown endogenous substance present in the donor’s urine that
prevents getting a valid drug test result.
C. Interview Donor
For the situations described above that require the MRO to interview the donor,
the MRO contact and interview with the donor must include the following steps:
(1) The MRO or an assistant makes the initial contact with the donor as soon as
possible after receiving the result from the laboratory. There are no specific
regulatory time lines, but the first attempt to contact the donor is usually
within 24 hours after receiving either the electronic transmission (if there is
one) or the hard copy of the CCF (Copy 2) from the laboratory.
(2) The MRO or an assistant makes a positive identification of the donor when
the donor is actually contacted (e.g., asks the donor to provide his or her
SSN).
Note: An assistant to the MRO may make the initial contact with the donor. This
initial contact is useful since it is often time consuming to locate a donor,
especially if the donor travels frequently or the donor’s phone number is
incorrect. The assistant’s role must be limited to locating and making the
initial contact with the donor. Once the donor is contacted and his or her
identification is verified, the MRO must continue the interview.
(3) The MRO tells the donor, before obtaining any information, that any
confidential medical information provided by the donor during the review
process may be disclosed to the employer.
(4) The MRO informs the donor that the laboratory has reported either a
"Positive" drug test result or an "Invalid Result."
(5) The MRO asks the donor if there is any possible explanation for either
result.
Note: If the donor voluntarily admits to illegal drug use consistent with the
test results, the MRO must advise the donor that a verified "Positive" result
will be reported to the employer.
Note: If the donor claims to have used a legally prescribed medication or the
drug use was associated with a legitimate medical procedure, the MRO must
require the donor to provide the appropriate documentation (e.g., medical
record, doctor's report, copy of a prescription). The MRO must give the donor a
deadline for submitting the medical information.
(6) If a split specimen was collected and the Bottle A specimen was reported
"Positive," the MRO informs the donor of the opportunity to request that the
split specimen be tested. If the donor requests the split specimen to be
tested, the MRO directs the laboratory to send Bottle B to another certified
laboratory for confirmatory testing.
(7) If the information submitted by the donor is or is not sufficient to
support the legitimate medical use of a prescription medication that would
cause the "Positive" test result for the drug reported by the laboratory, the
MRO reports the result to the employer as a verified "Negative"or "Positive,"
respectively, and completes Step 6 on Copy 2 of the CCF.
Note: Ideally, the MRO is always able to contact the donor, obtain the
appropriate information, and make a determination during or immediately after
the interview. However, this is not always the case. Occasionally, the MRO is
unable to contact the donor for various reasons (e.g., the donor has moved, no
longer works for the employer, or was a job applicant and has moved).
The MRO may verify a positive test as "Positive" without having communicated
directly with the donor (i.e., a non-contact determination) for the following
reasons:
(1) The donor expressly declines the opportunity to discuss the test result;
(2) The MRO, after making all reasonable efforts, has not been able to contact
the donor within 14 days of the date on which the MRO receives the "Positive"
test result from the laboratory; or
(3) The employer 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 employer.
The MRO must establish guidelines as to what constitutes a reasonable effort to
contact the donor and must document all attempts that were made to contact the
donor. When contacting the employer regarding the effort made to contact the
donor, the MRO may not reveal the test result or any information about the drug
test. The employer must confidentially direct the donor to contact the MRO
within 5 days and must inform the MRO once the donor has been so instructed or
if unable to contact the donor.
D. Retest Request
Single Specimen or Primary (Bottle A) Specimen
Before making a determination on a "Positive" test result, only the MRO is
permitted to request a retest of a single specimen or the primary (Bottle A)
specimen from a split specimen collection if there is any question regarding
the accuracy or validity of the test result. The MRO’s request must be based on
a review of technical information (provided by the laboratory or donor) that
makes the MRO believe that the result may be scientifically insufficient and,
therefore, believes that a retest would be useful before making the
determination.
Note: The MRO can request that the retesting of the original specimen be
performed by the same laboratory or that an aliquot of the single specimen be
sent for a retest to another certified laboratory. The Mandatory Guidelines are
silent with respect to who chooses the second laboratory. The only requirement
is that the second laboratory is certified by HHS whether it is chosen by the
agency/employer, donor, MRO, or the first laboratory.
Note: It is unacceptable for an MRO to automatically request a retest on every
specimen. There must be a sound justifiable scientific basis for each retest
request.
Note: To ensure that a specimen is available if a retest is requested either by
an MRO or by an official administrative or judicial proceeding, HHS requires
laboratories to place all specimens confirmed positive in properly secured
frozen storage for a minimum of one year. This is generally a sufficient amount
of time to allow for a retest to occur; however, the time may be extended
beyond one year by either the employer or an administrative/judicial official
to allow completion of any litigation/arbitration that may be ongoing with the
donor. If split specimens were collected, the laboratory keeps both specimen
bottles frozen for one year. If Bottle B was sent to another laboratory for
confirmatory testing, that laboratory retains Bottle B in frozen storage for
one year.
The MRO must request the retest of a single specimen or the primary (Bottle A)
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
specimen was tested and must contain the following information:
(1) MRO name and address (use MRO letterhead);
(2) Laboratory name and address (i.e., Laboratory A) where original analysis
was performed;
(3) Specimen I.D. Number (i.e., number on the Custody and Control Form);
(4) Laboratory Accession Number (i.e., the number assigned by Laboratory A to
the specimen when it was accessioned); and
(5) Request confirmatory retest for the drug/metabolite reported by Laboratory
A.
Note: If the retest is to be performed at a different certified laboratory
(Laboratory B), the MRO also includes the name and address of this certified
laboratory. Laboratory B may be selected by the MRO, the employer in its
contract with the laboratory that tested the single specimen (Laboratory A), or
by the donor.
Note: The result of a retest of a single specimen is reported by the laboratory
using an appropriate laboratory report form to the MRO.
Split (Bottle B) Specimen
After making the determination that the primary Bottle A specimen is
"Positive," the MRO must inform the donor of his or her right to request an
analysis of the split (Bottle B) specimen. The donor’s request to have the
split specimen tested must be made through the MRO. Although the time allowed
for a retest request may vary, the donor is given a maximum of 72 hours to
initiate the request. This will ensure that the analysis of the split specimen
is performed in a timely manner.
The MRO must request the testing 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 specimen was tested
and must contain the following information:
(1) MRO name and address (use MRO letterhead);
(2) Laboratory name and address (i.e., Laboratory A) where analysis of the
primary (Bottle A) specimen was performed;
(3) Specimen I.D. Number (i.e., number on the Custody and Control Form);
(4) Laboratory Accession Number (i.e., the number assigned by Laboratory A to
the specimen when it was accessioned);
(5) Request confirmatory test for drug/metabolite reported by Laboratory A; and
(6) Name and address of the laboratory (i.e., Laboratory B) selected to test
the Bottle B specimen.
Note: Laboratory B may be selected by the MRO, the employer in its contract
with Laboratory A, or by the donor.
Note: Laboratory B will report the result for the split (Bottle B) specimen on
Copy 1 of the CCF to the MRO. The MRO reports the result to the employer and
the donor.
E. Retest Result
Single Specimen or Primary (Bottle A) Specimen
If the retesting of the original specimen fails to reconfirm the original
laboratory result, the MRO will report the result as "Negative" to the
employer.
Note: Since this retest was performed because the MRO had concerns regarding
the validity of the positive test result reported by the laboratory, the MRO
cannot make a determination before the retest result is reported to the
MRO by the laboratory.
Note: When a retest does not reconfirm the presence of a drug, the MRO must
contact the appropriate regulatory office. The regulatory office will conduct
an investigation to determine the reason for not reconfirming the presence of
the drug and to ensure that appropriate corrective action is implemented.
Split (Bottle B) Specimen
If the testing of the split (Bottle B) specimen reconfirms the presence of the
drug/drug metabolite, the MRO verifies the result for the split (Bottle B)
specimen as "Reconfirmed" on Copy 2 of the CCF.
If the testing of the split (Bottle B) specimen fails to reconfirm the result
reported by the laboratory that tested the primary (Bottle A) specimen, the MRO
verifies the result as "Failed to Reconfirm"along with the reason on Copy 2 of
the CCF
Note: Since the "Positive" result for the primary (Bottle A) specimen had been
reported to the employer by the MRO, the employer will be required to reverse
any personnel action that may have been taken against the donor. Additionally,
the donor reenters the group of individuals subject to random testing as if the
test had not been conducted.
Note: The Federal agency must notify the appropriate regulatory office whenever
a "Failed to Reconfirm" result has occurred on a split (Bottle B) specimen. The
regulatory office will investigate the "Failed to Reconfirm" result and attempt
to determine the reason for the inconsistent results. HHS will report its
findings to the Federal agency including recommendations and/or actions taken
to prevent the recurrence of the "Failed to Reconfirm" result.
There is a technical problem that occasionally occurs when Laboratory B retests
an aliquot of a single specimen or tests a split (Bottle B) specimen that had
been reported "Positive" by Laboratory A. Laboratory B is unable to reconfirm
the presence of the drug or metabolite reported by Laboratory A because it uses
a different analytical procedure and/or instrumentation. These differences
occasionally prevent a Laboratory B from reconfirming the presence of a drug or
metabolite because the analytical results do not satisfy all the criteria
required to make a positive identification.
Note: If Laboratory B believes that the drug or metabolite is present in the
aliquot of the single specimen or the split (Bottle B) specimen that was
received from Laboratory A, but cannot reconfirm the presence of the drug or
metabolite, Laboratory B, after consultation with the MRO, may send the aliquot
of the single specimen or the split (Bottle B) specimen to Laboratory C for
confirmatory testing. The MRO may also request Laboratory A to send another
aliquot of the single specimen to Laboratory C if there is an insufficient
quantity of urine remaining in the aliquot of the single specimen tested at
Laboratory B. Laboratory C should be selected such that it uses a confirmation
method more similar to that used by Laboratory A.
F. Report Verified Result to Employer
The MRO may report all verified (negative and non-negative) results to the
agency/employer by either faxing a completed Copy 2, transmitting a scanned
image of a completed Copy 2, or faxing a separate report using a
letter/memorandum format. A verified result may not be reported to the employer
until the MRO has completed the review process. The MRO must send to the
agency/employer a hard copy of either the completed Copy 2 or the separate
letter/memorandum report for all non-negative results.
Note: If the MRO uses a letter or memorandum format, it must include, at a
minimum, the following: donor name and/or SSN, specimen I.D. number from the
CCF, the verified test result (if positive, list specific drug(s)), the MRO’s
printed name and signature, and the date the determination was made. The MRO
may list results for several specimens on one memorandum or letter. The MRO
report may include relevant comments provided by the collector and/or
laboratory on the CCF as well as other information, such as, documentation of
attempts to contact the donor or a statement of the donor's refusal to
cooperate with the medical review process. The MRO may add any information
provided by the donor (especially at the donor's request) to the verified
result report. Such additional information must not, however, reveal specific
confidential medical information.
F. Full Documentation Package
A donor or employer will occasionally request the testing laboratory to provide
a complete package of analytical data, chain of custody records, and other
administrative documents associated with the testing of a particular specimen.
This package is generally referred to a "full documentation package"
The request must always be submitted to the laboratory through the MRO. A full
documentation package must include copies of the batch test results that
contain the test result for the donor’s specimen, internal and external chain
of custody documents for the batch of specimens that contain the donor’s
specimen, and any other relevant information pertaining to the testing of the
donor’s specimen.
Although each documentation package is different, it must contain all the
information needed to determine if the test result reported by the laboratory
is, in fact, scientifically and forensically supportable. The MRO is encouraged
to contact the laboratory to discuss the information contained in the
documentation package prior to sending it to the donor or employer. The MRO may
find that additional information (e.g., a description of the laboratory’s chain
of custody procedures, a description of the laboratory’s quality assurance
program) would be helpful in reviewing the full documentation package.
G. Occupational and Public Safety
Executive Order 12564 used the term "illegal drugs" to refer to any controlled
substance that was included in Schedule I or II of the Controlled Substances
Act. The Executive Order also stated that the term illegal drugs "does not mean
the use of a controlled substance pursuant to a valid prescription or other
uses authorized by law."
Note: The purpose of this policy is to ensure that a Workplace drug testing
program does not intentionally identify an individual who is receiving
legitimate medical care and, thereby, provides confidential medical information
to an employer or anyone else.
There is, however, a public safety issue associated with information that a
donor may provide to an MRO during the review of a drug test result. That is,
the donor may be taking a legal prescription medication as treatment for a
medical condition and the medication may have possible side effects that may
impair the mental and/or physical abilities required for the performance of
potentially hazardous tasks (e.g., driving a car or truck, operating
machinery).
If the side effects of a legitimately prescribed medication have a possible
impact on the safety aspects of the work performed by a donor, the MRO must
decide what must be done with the information. Although the Guidelines require
an MRO to verify a drug test result as a negative result if the donor has
legally taken a prescription medication, it is recommended that the MRO contact
the prescribing physician to discuss the possible impact that the medication
may have on the safety aspects of the work performed by the donor.
Additionally, some occupations have restrictions that prohibit an individual
from taking specific medications which may, otherwise, be allowable for other
occupations. In these instances, the MRO may inform the individual responsible
for certifying that the donor is qualified to perform that job that the donor
is taking a medication that is restricted for an individual in that occupation
or that the medication may affect the individual’s ability to perform a safety
sensitive occupation.
H. State Initiatives and Laws
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 uses are inconsistent with the performance of safety-sensitive,
health-sensitive, and security-sensitive positions, and with other testing
circumstances.
Note: Medical Review Officers shall not accept a prescription or the
verbal or written recommendation of a physician for a Schedule I substance as a
legitimate medical explanation for the presence of a Schedule I drug or
metabolite in a Federal employee/applicant specimen.
Chapter 4. Specific Drug Class Issues
A. Amphetamines
1. Background
Amphetamine and methamphetamine are substances regulated under the Controlled
Substances Act (CSA, 21 U.S.C. § 801 et seq.), and implementing regulations as
Schedule II stimulants (see 21 CFR § 1308.12(d)). Schedule II substances have
legitimate medical uses, but also have a high potential for abuse. Both drugs
have been used for treating attention deficit disorder in children, obesity,
and narcolepsy.
Amphetamine and methamphetamine are central nervous system stimulants. 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 five 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 are usually taken orally as tablets or
capsules. Abusers inject the drugs intravenously, sometimes take them by
intranasal "snorting," and by smoking. Absorption from the gastrointestinal
tract is good and they are distributed throughout the body.
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 reabsorption 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.
Methamphetamine and amphetamine 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.
Generally, the methamphetamine/amphetamine result reported by the laboratory
does not indicate which enantiomer is present because the laboratory procedure
is set up to only identify and quantify the methamphetamine/amphetamine that is
present. 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.
The presence of the l- isomer of either amphetamine or methamphetamine
does not by itself rule out illegal use.
Illegally manufactured amphetamine and methamphetamine often contain
significant amounts of the l- isomer of each substance. This depends on the
starting materials used by the clandestine laboratories.
The following prescription medications contain d-amphetamine or racemic d,l-amphetamine
(i.e., equal amounts of d- and l-amphetamine):
Adderall®
Benzedrine®
Biphetamine®
Dexedrine®
Durophet®
Obetrol®
The following prescription medication contains d-methamphetamine:
Desoxyn® (Gradumet®)
The following substances are known to metabolize to methamphetamine (and
amphetamine):
Benzphetamine (Didrex®)
Dimethylamphetamine
Famprofazone
Fencamine
Furfenorex
Selegiline (Deprenyl, Eldepryl®)
The following substances are known to metabolize to amphetamine:
Amphetaminil
Clobenzorex (Dinintel®, Finedal®)
Ethylamphetamine
Fenethylline (Captagon®)
Fenproporex (Tegisec®)
Mefenorex (Pondinil®)
Mesocarb
Prenylamine
Note: These lists are not all inclusive.
3. Interpreting Laboratory Result
The donor provides the following response:
(a) Claims to have been taking a prescription medication.
(1) The MRO requests the donor to provide a copy of the prescription or the
sample bottle with the appropriately labeled prescription.
Note: The prescription must be for a drug that contains either amphetamine,
methamphetamine, or a substance that can metabolize to amphetamine or
methamphetamine. If the prescription does not satisfy this requirement, the
drug in the prescription provided by the donor is not a valid medical
explanation for the positive amphetamine result and the "Positive" laboratory
result is verified as a "POSITIVE."
Note: If the donor had completed taking the prescribed medication by the time
he or she is contacted, the donor may no longer have the prescription bottle.
When this occurs, the donor must provide a copy of the medical record that
documents the valid medical use of the drug during the time of the drug test.
There may be a need to contact the prescribing physician or the pharmacist who
filled the prescription to verify the information provided by the donor.
Note: If a donor has been taking a prescription medication that contains
methamphetamine or amphetamine for a long time, there must be appropriate
justification for their long term use because of the high potential for abuse.
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.
Note: Selegiline is a brain monoamine oxidase inhibitor used in the adjunctive
treatment of Parkinson’s disease and for depression. Selegiline is metabolized
to l-methamphetamine and l-amphetamine. A d- and l- isomer differentiation will
reveal the presence of only l-methamphetamine and l-amphetamine after the
ingestion of Selegiline.
(2) If this alternative medical explanation is substantiated for a specimen
containing only l-methamphetamine/l-amphetamine, the MRO must
verify and report the result as a "Negative."
(b) Claims to have used a Vicks Inhaler®.
(1) Since the Vicks Inhaler® contains l-methamphetamine, there is a
possibility that a laboratory positive result could be reported for l-methamphetamine
and/or l-amphetamine.
(2) The MRO may request the laboratory to perform a d-, l- isomer
differentiation.
Note: Although one would expect to see 100% l-methamphetamine following Vicks
Inhaler® use, there may be a trace amount of d- isomer present because a
very slight amount of d-methamphetamine may be present as a contaminant
in the Vicks Inhaler® and a contaminant of the analytical procedure.
(3) After the laboratory conducts the isomer differentiation, if there is
greater than 80% l-methamphetamine, the results are considered to be
consistent with Vicks Inhaler® use and the result is verified as a "Negative."
Note: This is a very conservative interpretation.
(4) If there is more than 20% d-methamphetamine present, the results
indicate the use of some source other than the inhaler and the result is
verified as a "Positive."
(c) Claims to have used other over-the-counter medications.
(1) The MRO would verify the laboratory result as a "Positive."
Note: There are no over-the-counter medications, other than the Vicks Inhaler®,
that contain either d- or l- methamphetamine or amphetamine. Although we know
that some sympathomimetic amines can test positive on an immunoassay test, they
will not be reported positive by the laboratory after conducting the
confirmatory test; the confirmatory GC/MS test is specific for methamphetamine
and amphetamine.
The NLCP requires that a specimen reported as a "Positive" for methamphetamine
only (i.e., above the confirmatory test level of 500 ng/mL), it must also
contain amphetamine (which is a metabolite of methamphetamine) at a
concentration equal to or greater than 200 ng/mL. The amphetamine will not be
reported as "Positive" by the laboratory unless its concentration exceeds the
500 ng/mL confirmatory test level. In the case of a report stating only a
methamphetamine positive, the MRO may contact the laboratory to verbally
confirm that amphetamine was present between 200 and 500 ng/mL.
(d) Admits or denies using any substance illegally. The MRO verifies the result
as a "Positive" for amphetamine and/or methamphetamine.
B. Cocaine
1. Background
Cocaine is an alkaloid from the coca plant, Erythroxylon coca. It usually is
obtained as cocaine HCl, but those who smoke the drug prepare the "freebase" or
"crack" form, chemically removing the HCl. This form better survives the high
temperatures involved in smoking.
Cocaine is widely used in the United States, and unlike most other drugs, its
prevalence of abuse continues to expand.
Cocaine produces psychomotor and autonomic stimulation with a euphoric
subjective "high." Larger doses may induce mental confusion or paranoid
delusions, and serious overdoses cause seizures, respiratory depression,
cardiac arrhythmias, and death.
Cocaine abusers, even if they do not use the drug at work, often report
vocational impairment due to exhaustion; they use the drug until late at night.
Among chronic users, exhaustion, lethargy, and mental depression appear, and
the stimulant effect may seem progressively weaker. But the drug is highly
reinforcing; repeated experiences with it tend to drive further episodes of
self-administration. After repeated exposures, many patients say that although
the drug no longer produces much of a "high," they are unable to abstain.
Short-term tolerance (tachyphylaxis) develops when several doses of cocaine are
administered over a brief period. Reports of weaker "highs" with repeated use
also suggest tolerance. However, animal studies show "reverse tolerance," with
certain behavioral effects becoming stronger upon repeated administration. So
the question of tolerance to cocaine remains an area for further research.
Patients withdrawing from cocaine experience moderate lethargy and drowsiness,
severe headaches, hyperphagia, vivid dreams, and some mental depression. These
symptoms usually abate within a few days to a few weeks.
Cocaine usually is taken by one of three routes: intranasal "snorting" is the
most common; its "freebase" or "crack" form of the drug is smoked, utilizing
the pulmonary route; and intravenous injections.
2. Metabolism and Excretion
Cocaine is rapidly and extensively metabolized by liver and plasma enzymes. The
major metabolite, benzoylecgonine, is more persistent; it usually is detected
for 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.
3. Interpreting Laboratory Result
The donor provides the following response:
(a) Claims to have used a prescription medication or was given cocaine during a
medical or dental procedure.
Note: There are no prescription medications that contain cocaine. However, the
medical community uses TAC (tetracaine, adrenalin, cocaine) as a topical
preparation prior to various surgical procedures and may use cocaine by itself
as a topical vasoconstrictive anesthetic for various ear, nose, throat, and
bronchoscopy procedures. If cocaine is used, the licensed physician performing
the procedure would document its use in the donor’s medical record. Cocaine is
structurally unique and does not resemble any of the other topical anesthetics,
such as Novocain®, Xylocaine® (lidocaine), benzocaine, etc. Although these
compounds have analgesic properties, there is no structural similarity to
cocaine or its metabolite (benzoylecgonine).
(1) Request the donor to provide a copy of the medical record that documents
the recent use of cocaine as a topical anesthetic.
(2) If this alternative medical explanation is substantiated, the MRO must
verify and report the result as a "Negative."
Note: Keep in mind that the medical use must have occurred within 2 to 3 days
prior to when the urine specimen was collected. Use at an earlier time will not
cause a positive urine test.
(b) Claims passive inhalation of crack cocaine.
(1) Allow the donor to describe the circumstances pertaining to how and when
the passive exposure occurred.
(2) Passive inhalation is not an alternative medical explanation for the
presence of benzoylecgonine in the donor’s urine.
Note: A comprehensive study conducted at NIDA’s Addiction Research Center (E.J.
Cone, D. Yousefnejad, M.J. Hillsgrove, B. Holicky, and W.D. Darwin. Passive
Inhalation of Cocaine. J.Anal.Toxicol. 19:399-411(1995)) has demonstrated that
individuals passively exposed to "crack" smoke did not produce a urine positive
for cocaine using the established testing levels.
(3) MRO verifies and reports the result as a "Positive."
(c) Claims to be ingesting "Health Inca Tea."
Note: In the early 1980s, health food stores were selling a tea under the
tradename "Health Inca Tea." When it was discovered that this tea contained
decocanized coca leaves with detectable amounts of cocaine present, the U. S.
Food and Drug Administration banned the importation of this tea into the United
States. Therefore, any tea being sold using the name "Health Inca Tea" should
not contain any cocaine.
(1) Allow the donor to explain where and when the tea was purchased.
(2) Drinking "Health Inca Tea" is not an alternative medical explanation for
the presence of benzoylecgonine in the donor’s urine.
(3) MRO verifies and reports the result as a "Positive."
(d) Admits or denies using cocaine. The MRO verifies the result as a "Positive"
for cocaine.
C. Marijuana
1. Background
Marijuana comes from the hemp plant, Cannabis sativa. The principal
psychoactive agent in marijuana is delta-9-tetrahydrocannabinol (THC).
Marijuana produces a pleasant euphoria or "high," commonly followed by
drowsiness. Intoxication temporarily impairs concentration, learning, and
perceptual-motor skills. Thus, for at least 4-6 hours after a dose of
marijuana, employees probably function with reduced abilities. Preliminary
studies suggest that performance is impaired long after the acute subjective
effects have ended. Experienced pilots in a flight simulator were impaired for
at least 24 hours after a dose, long after the subjective "high" had
disappeared. Functional impairments are less well understood in cases of
prolonged, heavy marijuana use, because although THC accumulates in the body,
behavioral and physiological tolerance also 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 at the doses at which the drug is usually taken in this country.
2. Metabolism and Excretion
Marijuana is usually smoked; transpulmonary absorption rapidly gets
psychoactive drugs to the brain. Since the drug also is absorbed from the
gastrointestinal tract, although much more slowly, marijuana sometimes is
eaten. THC leaves the bloodstream and 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-tetrahydrocannabinol -9-carboxylic
acid (delta-9 THCA).
The immunoassay procedures detect multiple metabolites of marijuana, while the
GC/MS procedure specifically identifies and quantitates the delta-9 THCA
metabolite. To be reported positive, a specimen must screen positive at or
above the 50 ng/mL cutoff and have a concentration of the delta-9 THCA that is
equal to or greater than the 15 ng/mL confirmatory cutoff level. Considering
these cutoffs, a person with no marijuana experience who smokes a single
marijuana cigarette may be positive for 1-3 days. But with repeated smoking,
THC accumulates in fatty tissue; so frequent, chronic smokers slowly release
THC over a longer time and may continue to produce detectable levels below the
cutoff values for longer periods of time (depending upon the assay cutoff).
3. Interpreting Laboratory Result
The donor provides the following response:
(a) Claims to have used a prescription or over-the-counter medication.
Note: Dronabinol is chemically synthesized delta-9- tetrahydrocannabinol (THC).
It is available under the trade name Marinol® in 2.5, 5, or 10 mg soft gelatin
capsules for oral administration. Marinol® may be used for stimulating appetite
and preventing weight loss in patients with a confirmed diagnosis of AIDS and
treating nausea and vomiting associated with cancer chemotherapy. Additionally,
a few individuals have been permitted by a court order to use THC for the
management of glaucoma. Patients that are prescribed Marinol® should be warned
not to drive, operate complex machinery, or engage in hazardous activity.
Note: There are no other prescription or over-the-counter medications that
contain cannabinoids or any other substances that might be identified as or
metabolized to THC or its acid metabolite.
(1) Request the donor to provide a copy of the medical record or court order
that would document the legal use of Marinol® or marijuana.
(2) If this alternative medical explanation is substantiated, the MRO must
verify and report the result as a "Negative."
(b) Claims passive inhalation or unknowing ingestion.
Note: Passive inhalation, unknowing ingestion (i.e., an inadvertent exposure to
marijuana), or eating hemp seeds is frequently claimed as the basis for a
positive urine test. Passive inhalation of marijuana smoke does occur and can
result in detectable levels of THC and its metabolites in urine. Clinical
studies have shown, however, that it is highly unlikely that a nonsmoking
individual could unknowingly inhale sufficient smoke by passive inhalation to
result in a high enough drug concentration in urine for detection at the cutoff
levels used in the Federal program. Similarly, it is extremely difficult to
achieve detectable levels through unknowing ingestion of hemp plant material
(such as, leaves, stems) or eating food products containing hemp seeds. The
studies also show that any measurable peak concentration in urine occurs within
several hours after the exposure.
(1) Allow the donor to describe the circumstances pertaining to how and when
the passive exposure, unknowing ingestion, or eating hemp seeds occurred.
(2) Generally, the circumstances will not approximate what would be needed to
explain the presence of THC in the donor’s urine.
(3) MRO verifies and reports the result as a "Positive."
Note: Additionally, none of the reasons mentioned in b1 above constitute an
alternative medical explanation.
(c) Admits or denies using marijuana. The MRO verifies the result as a
"Positive" for cannabinoids.
D. Opiates
1. Background
Opioids are a large class of analgesic drugs, the effects of which are
stereospecifically antagonized by naloxone. Opiates refer to natural products
derived from the juice of the opium poppy (loosely applied to morphine
derivatives). The opium poppy flower is the source of the natural opiate
prototype alkaloid, morphine. The opium poppy is also the source of the
naturally occurring alkaloid codeine; codeine is also synthesized chemically
for inclusion in medications available through prescription and
over-the-counter. Heroin (or diacetylmorphine) is a semisynthetic opiate
obtained by reacting natural morphine with acetic acid. Heroin has no
legitimate medical uses in the United States and is only available illegally
(DEA Schedule I).
Opioid intoxication may cause miosis, a dull facies, confusion or mental
dullness, slurring of speech, drowsiness, partial ptosis, or "nodding" (the
head drooping toward the chest and then bobbing up).
Tolerance develops to opioid effects, and abusers escalate doses when possible.
Physical dependence results in a moderate, nonlethal, "flu"-like abstinence
syndrome with nausea, diarrhea, coryza, occasional vomiting, weakness, malaise,
"gooseflesh," and mydriasis. 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.
Heroin and morphine are usually injected, but may be smoked as opium once was,
or "snorted" (insufflated) onto the nasal mucosa.
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.
The following prescription medications contain morphine:
Astramorph PF®
Duramorph®
MSIR®
MS Contin Tablets®
Roxanol®
The following prescription medications contain codeine:
Actifed with Codeine Cough Syrup®
Codimal PH® Syrup
Dimetane-DC Cough Syrup®
Emprin with Codeine®
Fiorinal with Codeine®
Phenaphen with Codeine®
Robitussin A-C®
Triaminic Expectorant with Codeine®
Tylenol with Codeine(#1, 2, 3, or 4)®
Tussar-2®
Note: The above lists are only a representative sample of the prescription
medications that contain codeine or morphine.
The following nonprescription products contain opium (i.e., morphine):
Amogel PG®
Diabismul®
Donnagel-PG®
Infantol Pink®
Kaodene with Paregoric®
Quiagel PG®
Paregoric
The following nonprescription product contains codeine:
Kaodene with Codeine®
Note: Each listed nonprescription product is used as an antidiarrheal. They are
generally availably over-the-counter; however, nonprescription sale is
prohibited in some states. Paregoric alone is a Schedule III prescription drug,
but in combination with other substances is a Schedule V over-the-counter
product.
The following substance metabolizes to morphine:
Heroin
2. Metabolism and Excretion
Heroin (diacetylmorphine) is rapidly deacetylated to 6-acetylmorphine (6-AM;
also called 6-monoacetylmorphine, 6-MAM), and, therefore, heroin itself is
rarely ever detected in the urine. Heroin's characteristic metabolite, 6-AM, is
rapidly deacetylated to morphine, and will likely not be detected in most urine
specimens of heroin users. Since codeine is a naturally occurring alkaloid in
the same opium poppy juice that is the source of morphine used as the starting
material for heroin synthesis, codeine may be found in the urine of heroin
users.
Morphine is rapidly absorbed and excreted as unchanged morphine and as
conjugated glucuronides (i.e., morphine-3-glucuronide, morphine-6-glucuronide).
The primary metabolite is morphine-3-glucuronide. Morphine and its metabolites
can be detected in urine up to about 4 days after its use.
Codeine (methylmorphine) is also rapidly absorbed and is excreted as unchanged
codeine, morphine, and glucuronide conjugates.
Since the body metabolizes codeine to morphine, both substances (i.e., codeine
and morphine) may occur in the urine following the use of codeine. Recently
ingested codeine explains the presence of both drugs in the urine specimen
(i.e., parent drug codeine and morphine metabolite). After the ingestion of a
legitimate medical preparation containing codeine, there comes a time when
parent codeine has been completely excreted or metabolized to morphine, so that
morphine only is detected in the urine.
Ingestion of morphine in any form will never account for the presence of
codeine in the urine (codeine is not a metabolite of morphine).
Note: There are a number of synthetic or semisynthetic analgesics available
including, but not limited to, alphaprodine (Nisentil®), hydromorphone
(Dilaudid®), oxymorphone (Numorphan®), hydrocodone (Hycodan®), dihydrocodeine
(Paracodin®), oxycodone (Percodan®), propoxyphene (Darvon®), methadone
(Dolophine®), meperidine (Demerol®), fentanyl (Sublimaze®), pentazocine
(Talwin®), and buprenorphine (Buprenex®). These drugs do not metabolize
to either codeine, morphine, or 6-acetylmorphine. When a donor presents a
prescription for a narcotic analgesic, the MRO must verify that it does not
contain codeine or morphine and, therefore, cannot metabolize to codeine,
morphine, or 6-acetylmorphine.
3. Interpreting Laboratory Result
The opiate drug class poses some unique challenges with regard to interpreting
a positive test result. A positive for codeine or morphine may be a result of a
donor having taken a prescription medication that contains codeine or morphine
or a donor consuming normal dietary amounts of poppy seeds. In addition, for
the opiate drug class, there is a requirement to document clinical evidence of
illegal use.
Note: Before an MRO verifies a confirmed positive result for opiates, he or she
shall determine that there is clinical evidence - in addition to the urine test
- of illegal use of any opium, opiate, or opium derivative. The main issue is
the MRO must substantiate that there is "clinical evidence of illegal use" of
an opiate substance before a positive result reported by a laboratory can be
verified as a "Positive." Clinical evidence of illegal use may include, but is
not limited to: a donor admits taking a prescription medication containing
codeine or morphine that was prescribed to another individual; recent needle
marks; or behavioral and psychological signs of acute opiate intoxication or
withdrawal. If "clinical evidence of illegal use" is not present, the MRO must
verify the "Positive" result reported by the laboratory as a "Negative" result
to the employer.
Note: The 6-acetylmorphine metabolite comes only from heroin; therefore, its
presence confirms the illegal use of heroin. When the presence of 6-AM is
confirmed, there is no requirement for clinical evidence.
Note: For a positive morphine or codeine test result, an MRO may have a blanket
written request on file at the laboratory to routinely receive the quantitative
values associated with a positive codeine and morphine result. The MRO also may
request quantitative information on the presence of codeine below the cutoff
for specimens which have been reported positive for morphine only. This
information may be helpful to the MRO in assessing the medical explanation
provided by the donor.
Note: Quantitative test results may not be requested by the MRO from the
testing laboratory on a routine basis for the other drug categories, but may be
requested on a case-by-case basis.
The donor provides the following response:
(a) Admits taking morphine or codeine illegally or using heroin. The MRO
verifies the result as a "Positive" for the drug reported by the laboratory.
(b) Claims to have taken a prescription medication.
The MRO requests the donor to provide a copy of the prescription or the
medication with the appropriately labeled prescription.
Even if no valid medical explanation is provided by the donor, the MRO must
verify and report the result as "Negative" unless there is clinical evidence of
the abuse or illegal use of opiate drugs.
Note: The presence of 6-acetylmorphine (6-AM) confirms the illegal use of
heroin and, therefore, it is not necessary to verify clinical evidence of
illegal use.
Note: The MRO must verify as "Negative" any codeine or morphine test result for
which the donor has taken a legally prescribed codeine or morphine medication.
Note: Occasionally, a donor will reveal information regarding the use of a
narcotic analgesic (that does not contain codeine or morphine) believing that
this medication was the reason for the positive codeine or morphine. Assuming
that it was a legally prescribed medication, this confidential medical
information cannot be provided to the employer and is not an explanation for
the positive codeine or morphine. Since the use of a narcotic analgesic may
have a possible effect on the ability of the donor to perform a specific task
(such as, driving a vehicle), it may be appropriate to discuss the use of the
medication with the prescribing physician. See Section G in Chapter 4 regarding
the reporting of this information.
(c) Claims to have eaten foods that contain poppy seeds.
One reason for the requirement for clinical evidence of abuse or illegal use in
opiate testing is that eating a normal dietary amount of poppy seeds can cause
a urine specimen to test positive for morphine and codeine (i.e., they contain
trace amounts of morphine with or without codeine). In many instances, a donor
will not know that poppy seeds can cause a positive test or that he or she had
eaten poppy seeds at the time the urine was collected. The concentration of
morphine can be substantial, with usually very low concentrations or no
detectable codeine. Unless clinical evidence of abuse or illegal use of opiates
is verified, the MRO must verify and report the result as a "Negative."
E. 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 ("emergence delirium"),
and its more prolonged use as a veterinary tranquilizing agent also has
stopped. PCP is currently a DEA Schedule II controlled substance, has no
current therapeutic role, and all uses are illegal. The preferred route of
ingestion is smoking, but it may be eaten, snorted, or injected intravenously.
PCP is best classified as a hallucinogen and 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. PCP clearly has drastic effects on performance. Clinical cases
have documented the severe debilitating physical and psychological effects of
PCP abuse and the extremely unpredictable behavior caused by the drug.
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.
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 percent of the PCP dose is excreted in
the urine as the parent compound. PCP is a weak base which concentrates in
acidic solutions in the body. Because of gastric acidity, PCP repeatedly
reenters the stomach from plasma, later returning 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.
3. Interpreting Laboratory Result
The donor provides the following response:
(a) Admits or denies using PCP. The MRO verifies the result as "Positive" for
PCP.
(b) Claims to have taken a prescription or over-the-counter medication. The MRO
verifies the result as "Positive" for PCP. There are no prescription or
over-the-counter medications that contain PCP, legal medical uses of PCP, or
any other substances that can be misidentified as PCP using gas
chromatography/mass spectrometry.
Chapter 5. Documentation and Recordkeeping
A. Recordkeeping
Accurate recordkeeping is essential in documenting all aspects of the MRO
review process. All communications, written or oral (including, but not limited
to, those with donors, employer representatives, laboratory personnel, and
collectors) must be appropriately documented.
Although the Guidelines do not specify the length of time that MROs must retain
these records, it is recommended that they be maintained for a minimum of two
years from the date of collection, or as otherwise provided by law or contract
with the employer.
Note: This two-year recommendation agrees with the requirement that each
laboratory must retain records associated with the testing of a specimen for a
minimum of 2 years.
No regulatory requirements exist requiring MROs to use a specific procedure to
review drug tests; however, using a standard procedure is likely to ensure that
each MRO review is complete and thorough. The use of a simple checklist will
ensure that certain activities are always documented.
Documentation must normally include such things as copies of prescriptions or
labels on prescription bottles, or notes that a prescription was verified at a
pharmacy or by the treating physician. Any letters or notes received from an
employee, relative, or physician providing treatment must be retained in the
file.
Finally, MRO records must be separated from other medical and personnel records
kept on an individual. For example, some physicians may also serve as a primary
care provider and retain medical records related to that function.
B. Confidentiality
The Guidelines require the MRO to report the final result of the drug test to
an employer in a manner designed to ensure the confidentiality of the
information. The MRO also has a responsibility to maintain the confidentiality
of the information received during the review process, including information
related to the donor's medical condition, medications, medical diagnosis, and
medical history. This role is particularly important with respect to confirmed
"Positive" drug test results, and especially for those that may be verified by
the MRO as "Negative" due to an alternative legitimate medical explanation.
Despite this general requirement to maintain the confidentiality of medical
information, there are certain circumstances in which the MRO may provide such
information to other parties. In these instances, the MRO must inform the
donor, prior to the medical interview, that disclosure of information learned
as part of the medical review process may occur if, in the judgment of the MRO,
the information suggests there is a significant safety hazard associated with
the information or there is a medical disqualification of the donor under an
applicable regulation.
Note: Such information may also be released under other circumstances specified
by Federal agency regulations.
Even when the MRO releases otherwise confidential information due to such
concerns, the MRO must attempt to release as little specific information as
possible and release such information only to parties with a clear
need-to-know. Such parties include physicians responsible for medical
certification of the donor, Federal agency officials as required by regulation,
or designated employer representatives.
Diagnoses or other specific details of medical information do not need to be
provided to non-medical personnel. For example, employer representatives may
only need to be informed that a safety hazard may exist and that the MRO needs
to provide specific information to the physician responsible for making medical
qualification decisions regarding the donor. In general, unless required by
regulation or law, the MRO must only discuss specific medical information with
other physicians or qualified health professionals.
A donor has the right, upon written request, to records relating to his or her
drug test. In addition, information can be requested by a subpoena or court
order. If an MRO has any concern regarding the release of information
associated with drug testing results, the MRO may want to obtain a legal
opinion.
Chapter 6. Additional MRO Responsibilities
A. Blind Quality Control Samples
Federal agencies and most employers regulated by DOT are required to have blind
quality control samples submitted with the donor specimens. Blind quality
control samples are helpful in determining if the entire testing process (i.e.,
from the collection of the specimen until a result is reported by the MRO)
satisfies all requirements.
The blind quality control samples must be certified by immunoassay and GC/MS
and have stability data which verifies their performance over time. The
requirement to have certification data ensures that the blind quality control
samples purchased from different sources are acceptable.
Generally, the employer will request the collector to purchase the blind
samples or may provide them to the collector. In either case, the collector
must submit each quality control sample as if it were a donor specimen. This
requires completing a CCF and properly labeling a specimen bottle. Since there
is no donor associated with a quality control sample, the collector must
generate a fictitious social security number or employee identification number
and fictitious initials to be written on the specimen bottle label/seal. On
Copy 2 of the CCF (MRO copy), the collector must indicate that the specimen is
a "Quality Control Sample" where a donor would normally print his or her name.
In addition, the collector or the employer, whichever purchased the blind
samples, must forward that information to the MRO. This will allow the MRO to
determine if the laboratory reported the correct result.
Note: An incorrect result reported by the laboratory does not automatically
indicate that the laboratory made an analytical error. For example, there could
have been a problem with the stability and/or concentration of the quality
control sample or the collector did not properly submit the sample.
If the laboratory reports a result different from the one expected based on
information provided by the manufacturer of the blind sample, the MRO must
contact the laboratory to determine if there is an obvious reason why the
laboratory did not report the expected result. If there is no obvious reason,
the MRO may request the laboratory to retest the specimen or have an aliquot
sent to another certified laboratory for confirmatory testing. If the retest
result confirms the original result reported by the laboratory, it is most
likely that an error occurred at the collection site or there was a problem
with the quality control sample as purchased. If the retest result does not
confirm the original result, the laboratory likely made an error.
Note: A false negative result (i.e., the laboratory reports a negative on a
blind sample when a positive result was expected) is a concern, but must not be
considered serious unless it occurs frequently and the MRO would not be
expected to request the laboratory to retest the blind sample. However, a false
positive (i.e., the laboratory reports a positive on a blind sample when a
negative result is expected) is serious and must be investigated.
If the retest result has confirmed that a false positive was reported by the
laboratory on a blind quality control sample, the MRO must contact the
employer. The MRO must then contact the appropriate regulatory office who will
conduct an investigation in an attempt to determine the exact cause of the
false positive. When the specific cause is identified, appropriate corrective
will be taken. The regulatory office will share the findings with the MRO.
B. Shy Bladder
Occasionally, a donor is unable to provide a specimen upon arrival at the
collection site because he or she either urinated recently or has a "shy
bladder." Generally, the term "shy bladder" refers to an individual who is
unable to provide a sufficient specimen either upon demand or when someone is
nearby during the attempted urination.
If it is believed that an individual has a "shy bladder," the employer must
arrange to have the donor evaluated, as soon as practical after the attempted
collection, by a licensed physician (e.g., the MRO, a physician acceptable to
the employer, the employer’s occupational health physician) to determine
whether the donor’s inability to provide a specimen is genuine or constitutes a
refusal to provide a specimen.
The examining physician shall determine, in his or her reasonable medical
judgment, that a medical condition has or, with a high degree of probability,
could have precluded the employee from providing an adequate amount of urine
(e.g., a urinary system dysfunction or a documented preexisting psychological
disorder). An evaluation must include a review of any pertinent medical records
and may include evaluative testing such as blood chemistries for kidney
function or other physiologic factors likely to affect urine output.
Unsupported assertions of "situational anxiety" or dehydration are not
considered valid reasons for a donor’s failure to provide an adequate amount of
urine when sufficient time has elapsed and fluid volume has been ingested and
shall be regarded as a refusal to take a test.
The examining physician shall provide to the MRO a brief written statement
describing his or her conclusion and the basis for it. The written statement
shall not include detailed information on the medical condition of the donor.
Upon receipt of the written statement from the examining physician, the MRO
shall report his or her conclusions to the employer in writing.
C. Testing for an Additional Drug
HHS certified laboratories may only test regulated specimens for amphetamines,
marijuana, cocaine, opiates, and phencyclidine. However, testing for an
additional drug may occur for the following reasons:
(1) 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; or
(2) 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 collector marks the "Other" box in Step 1 on the CCF and
specifies the name of the drug(s) to be tested. There must also be a memorandum
from the Federal agency attached to the CCF explaining why the specimen is
being tested for the additional drug. Otherwise, the laboratory must not test
for that additional drug.
Since the MRO will be reviewing a test result that is not a normal part of the
Federal Workplace Drug Testing Program, the MRO may want to obtain a full
documentation package from the laboratory to assess the forensic and scientific
acceptability of the test result.