Effective Date: February 1, 2024

Medical Review Officer Guidance Manual 

for Federal Workplace Drug Testing Programs

Department of Health and Human Services

Substance Abuse and Mental Health Services Administration

Center for Substance Abuse Prevention

Division of Workplace Programs
Medical Review Officer Guidance Manual

for Federal Workplace Drug Testing Programs

Note: This manual applies to Federal agency drug testing programs that come under Executive Order 

12564 dated September 15, 1986, section 503 of Public Law 100-71, 5 U.S.C. section 7301 note dated July 

11, 1987, the Department of Health and Human Services Mandatory Guidelines for Federal Workplace 

Drug Testing Programs using Urine (88 FR 70768) dated October 12, 2023 (effective February 1, 2024), 

and the Department of Health and Human Services Mandatory Guidelines for Federal Workplace Drug 

Testing Programs using Oral Fluid (88 FR 70814) dated October 12, 2023 (effective October 10, 2023). 

This manual does not apply to specimens submitted for testing under U.S. Department of 

Transportation (DOT) Procedures for Transportation Workplace Drug and Alcohol Testing Programs 

(49 CFR Part 40). 

This revision of the manual includes a reorganization of material in the manual and updates for oral 

fluid. The current version of this manual and other information including MRO Case Studies are 

available on the Drug Testing page under Medical Review Officer (MRO) Resources on the SAMHSA 

website: 

https://www.samhsa.gov/workplace

Previous versions of this manual are obsolete.
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Table of Contents

1. Introduction ................................................................................................................... 1-1 

1.1 The Federal Drug Testing Program ..................................................................... 1-1 

1.2 The Medical Review Officer (MRO)................................................................... 1-3 

1.2.1 MRO Requirements, Restrictions, Responsibilities................................. 1-3 

1.2.2 Federal Agency Responsibilities for Designating an MRO ..................... 1-6 

2. The Federal Drug Testing Custody and Control Form ................................................. 2-1 

2.1 General Information............................................................................................. 2-1 

2.2 Use of an Electronic Federal CCF ....................................................................... 2-3 

2.3 Federal CCF Content Requirements .................................................................... 2-4 

2.3.1 Test Facility Identification....................................................................... 2-5 

2.3.2 Specimen Labels/Seals............................................................................. 2-5 

2.3.3 Required Statements ................................................................................ 2-5 

2.4 Federal CCF Distribution..................................................................................... 2-6 

2.4.1 Paper Federal CCF................................................................................... 2-6 

2.4.2 Digital Federal ECCF .............................................................................. 2-6 

2.5 Test Facility Report to MRO ............................................................................... 2-7 

3. Drug Testing ................................................................................................................. 3-1 

3.1 Federal Workplace Drug Testing Overview ........................................................ 3-1 

3.1.1 Drugs ........................................................................................................ 3-1 

3.1.2 Specimen Collection ................................................................................ 3-2 

3.1.2.1 Urine ............................................................................................ 3-2 

3.1.2.2 Oral Fluid..................................................................................... 3-5 

3.1.3 Security and Chain of Custody ................................................................ 3-7 

3.1.4 Specimen Validity.................................................................................... 3-8 

3.1.4.1 Urine ............................................................................................ 3-9 

3.1.4.2 Oral Fluid..................................................................................... 3-9 

3.1.5 Testing.................................................................................................... 3-10 

3.1.5.1 Urine .......................................................................................... 3-10 

3.1.5.2 Oral Fluid................................................................................... 3-12 
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3.2 Test Methods ...................................................................................................... 3-13 

3.2.1 Initial Drug Tests ................................................................................... 3-13 

3.2.2 Confirmatory Drug Tests ....................................................................... 3-15 

3.2.3 Specimen Validity Tests........................................................................ 3-15 

3.2.3.1 Urine .......................................................................................... 3-15 

3.2.3.2 Oral Fluid................................................................................... 3-15 

3.2.4 Split (B) Specimen Testing.................................................................... 3-16 

3.2.4.1 Urine .......................................................................................... 3-16 

3.2.4.2 Oral Fluid................................................................................... 3-17 

3.3 IITF or Laboratory Reports................................................................................ 3-18 

3.4 Specimen and Records Storage.......................................................................... 3-19 

4. MRO Review and Reporting Procedures ...................................................................... 4-1 

4.1 Administrative Review of Documents................................................................. 4-1 

4.1.1 MRO Copy of the Federal CCF (Copy 2) ................................................ 4-2 

4.1.2 Test Facility Report—Federal CCF (Copy 1) and/or ComputerGenerated Electronic Report.................................................................... 4-4 

4.1.3 Federal CCF or Specimen Errors............................................................. 4-8 

4.1.4 Federal CCF Remarks............................................................................ 4-13 

4.1.5 Actions Based on Administrative Review ............................................. 4-13 

4.1.5.1 Procedure to change the Donor ID Number. ............................. 4-18 

4.1.6 Use of an Expired Federal CCF ............................................................. 4-18 

4.2 Donor Interview................................................................................................. 4-18 

4.3 Handling of Multiple Results or Multiple Collections During the Same 

Testing Event ..................................................................................................... 4-22 

4.4 Split Specimen Tests.......................................................................................... 4-22 

4.5 Interpretation and Result Verification ............................................................... 4-24 

4.5.1 IITF and Laboratory Results .................................................................. 4-25 

4.5.2 Donor Explanation ................................................................................. 4-27 

4.5.3 Prescriptions ........................................................................................... 4-27 

4.5.4 State Initiatives and Laws...................................................................... 4-29 

4.5.5 Changing a Verified Test Result ............................................................ 4-30 

4.6 Documentation and Recordkeeping ................................................................... 4-30 
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4.7 Reporting............................................................................................................ 4-31 

4.7.1 Federal Agency Reports......................................................................... 4-31 

4.7.2 Biannual Reports (Secretary or Designated HHS Representative)........ 4-33 

4.8 Confidentiality ................................................................................................... 4-33 

4.9 Discrepancies That May Require the MRO to Cancel a Test............................ 4-34 

5. Interpretation of Results and Drug Information............................................................ 5-1 

5.1 Amphetamines (AMP)......................................................................................... 5-2 

5.1.1 Amphetamine (AMP) and Methamphetamine (MAMP)......................... 5-2 

5.1.1.1 Drug Testing ................................................................................ 5-3 

5.1.1.2 Enantiomer Drug Testing10 .......................................................... 5-5 

5.1.1.3 Background .................................................................................. 5-6 

5.1.1.4 Routes of Administration............................................................. 5-6 

5.1.1.5 Metabolism and Excretion ........................................................... 5-7 

5.1.1.6 Pharmaceuticals and Use ............................................................. 5-7 

5.1.2 Designer Sympathomimetic Substances 

(Methylenedioxymethamphetamine (MDMA) and 

Methylenedioxyamphetamine (MDA)) ................................................... 5-9 

5.1.2.1 Drug Testing .............................................................................. 5-10 

5.1.2.2 Background ................................................................................ 5-11 

5.1.2.3 Routes of Administration........................................................... 5-12 

5.1.2.4 Metabolism and Excretion ......................................................... 5-12 

5.1.2.5 Pharmaceuticals and Use ........................................................... 5-12 

5.2 Cannabinoids (THC) .......................................................................................... 5-13 

5.2.1 THC and THCA..................................................................................... 5-13 

5.2.1.1 Drug Testing .............................................................................. 5-13 

5.2.1.2 Background ................................................................................ 5-15 

5.2.1.3 Routes of Administration........................................................... 5-15 

5.2.1.4 Metabolism and Excretion ......................................................... 5-16 

5.2.1.5 Pharmaceuticals and Use ........................................................... 5-16 

5.3 Cocaine (COC)33 ................................................................................................ 5-21 

5.3.1 Benzoylecgonine and Cocaine ............................................................... 5-21 

5.3.1.1 Drug Testing .............................................................................. 5-21 

5.3.1.2 Background ................................................................................ 5-23 

5.3.1.3 Routes of Administration........................................................... 5-23 
v 

5.3.1.4 Metabolism and Excretions........................................................ 5-24 

5.3.1.5 Pharmaceuticals and Use ........................................................... 5-24 

5.4 Opioids37 (OPI).................................................................................................. 5-25 

5.4.1 Morphine and Codeine ........................................................................... 5-27 

5.4.1.1 Drug Testing .............................................................................. 5-28 

5.4.1.2 Background ................................................................................ 5-29 

5.4.1.3 Routes of Administration........................................................... 5-30 

5.4.1.4 Metabolism and Excretion ......................................................... 5-30 

5.4.1.5 Pharmaceuticals and Use ........................................................... 5-31 

5.4.2 Oxycodone, Hydrocodone, Oxymorphone, Hydromorphone ................ 5-32 

5.4.2.1 Drug Testing .............................................................................. 5-32 

5.4.2.2 Background ................................................................................ 5-34 

5.4.2.3 Routes of Administration........................................................... 5-34 

5.4.2.4 Metabolism and Excretion ......................................................... 5-35 

5.4.2.5 Pharmaceuticals and Use ........................................................... 5-37 

5.4.3 Poppy Seeds ........................................................................................... 5-37 

5.4.4 6-Acetylmorphine (6-AM)..................................................................... 5-38 

5.4.4.1 Drug Testing .............................................................................. 5-38 

5.4.4.2 Background ................................................................................ 5-40 

5.4.4.3 Routes of Administration........................................................... 5-40 

5.4.4.4 Metabolism and Excretion ......................................................... 5-40 

5.4.4.5 Pharmaceuticals and Use ........................................................... 5-41 

5.5 Phencyclidine (PCP)53 ....................................................................................... 5-41 

5.5.1 Phencyclidine ......................................................................................... 5-41 

5.5.1.1 Drug Testing .............................................................................. 5-41 

5.5.1.2 Background ................................................................................ 5-43 

5.5.1.3 Routes of Administration........................................................... 5-43 

5.5.1.4 Metabolism and Excretion ......................................................... 5-43 

5.5.1.5 Pharmaceuticals and Use ........................................................... 5-44 

5.6 Other Non-Negative Reports ............................................................................. 5-44 

5.6.1 Dilute Specimens................................................................................... 5-44 

5.6.1.1 Urine .......................................................................................... 5-44 

5.6.2 Substituted Urine Specimens ................................................................. 5-45 

5.6.2.1 Background ................................................................................ 5-45 

5.6.2.2 MRO Actions............................................................................. 5-46 

5.6.3 Adulterated Urine Specimens................................................................ 5-47 
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5.6.3.1 Background ................................................................................ 5-47 

5.6.3.2 MRO Actions............................................................................. 5-51 

5.6.4 Invalid Specimens.................................................................................. 5-52 

5.6.4.1 Background ................................................................................ 5-52 

5.6.4.2 MRO Actions............................................................................. 5-55 

6. Additional Medical Review Officer Responsibilities................................................... 6-1 

6.1 Federal Agency Blind Samples............................................................................ 6-1 

6.2 Insufficient Specimen .......................................................................................... 6-3 

6.2.1 Urine ........................................................................................................ 6-3 

6.2.1.1 Permanent or Long-Term Medical Condition and Required 

Negative Test ............................................................................... 6-6 

6.2.2 Oral Fluid................................................................................................. 6-7 

6.2.2.1 Permanent or Long-Term Medical Condition and Required 

Negative Test ............................................................................. 6-10 

6.3 Occupational and Public Safety......................................................................... 6-11 

6.4 Donor Rights to Information .............................................................................. 6-12 

6.5 Protection of Personally Identifiable Information (PII) ..................................... 6-12 

6.6 External Service Providers ................................................................................. 6-14 

Appendixes

Appendix A: Glossary........................................................................................................... A-1 

Appendix B: Sample of CCF—Test Facility Copy (1) and MRO Copy (2) .........................B-1 

Appendix C: Example IITF Supplemental CCF....................................................................C-1 

Appendix D: Urine Specimen Drug Testing Panel and Reporting Criteria .......................... D-1 

Appendix E: Drug Schedule Information .............................................................................. E-1 

Appendix F: MRO Verification Statement for External Service Provider ............................ F-1 

Bibliography ....................................................................................................... Bibilography-1 

Drug Information References ................................................................................................R-1

List of Tables

Table 1. Immunoassay Tests .................................................................................. T-1 

Table 2. Examples of Specimen Validity Test Methods ........................................ T-2 
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Table 3a. Required Comments for IITF and Laboratory Specimen Reports -

Urine.......................................................................................................... T-4 

Table 3b. Required Comments for Laboratory Specimen Reports - Oral Fluid ....... T-7 

Table 4. Medical Review Officer Actions for Primary (A) Specimen Reports ...... T-8 

Table 5. Medical Review Officer Actions for Split (B) Specimen Reports .......... T-14 

Table 6. Some Substances That Metabolize to Amphetamine and 

Methamphetamine ................................................................................... T-18
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1. Introduction

This guidance is intended to assist Medical Review Officers (MROs) in carrying out 

their regulated responsibilities under the Mandatory Guidelines for Federal Workplace Drug 

Testing Programs using Urine (88 FR 70768) and the Mandatory Guidelines for Federal 

Workplace Drug Testing Programs using Oral Fluid (88 FR 70814). For the purposes of this 

document, abbreviations “UrMG” and “OFMG” are used to refer to the guidelines using 

urine and oral fluid, respectively, and “Mandatory Guidelines” is used as the general term. 

This guidance does not establish legally enforceable responsibilities but may reference 

actions or responsibilities that are required under statutory or regulatory authorities. The use 

of the words “should” or “may” in this guidance means that something is suggested or 

recommended, but not necessarily required by law. 

1.1 The Federal Drug Testing Program

Following the identification of heroin use by military personnel in Southeast Asia 

during the Vietnam era, then President Nixon and Secretary of Defense Melvin Laird (at the 

urging of Dr. Jerome Jaffee, the President’s Drug Advisor) in 1971 initiated drug tests on 

returning servicemen. Anyone who tested positive in Vietnam was required to undergo a 

brief rehabilitation treatment and have negative tests before returning to the United States.

This approach of testing for heroin and rehabilitation was followed until 1982 when 

“worldwide” surveys indicated a high rate of drug abuse among service members. The 

Department of Defense extended testing to include marijuana. Tests for marijuana and batch 

procedures for chain of custody and testing were developed. Many of the “common industry 

standards” such as cutoff levels, isomer testing, and the need for two different analytical 

procedures for positive specimens were developed as well as the introduction of gas 

chromatography/mass spectrometry as the “Gold Standard” for confirmation testing.

Following the success of this program, recommendations from the President’s 

Commission on Organized Crime and the Anti-Drug Abuse Act of 1986, President Reagan 

established testing for Federal Civil Service employees in safety and sensitive positions by 

Executive Order 12564 (1986)—an order that was soon followed by Public Law 100-71 

(1987). The U.S. Department of Health and Human Services (HHS) was given administrative 

responsibility and funding to implement the program. Since that time the collection 

procedures, testing methods, and medical review processes as well as comprehensive 

certification and inspections of certified laboratories have evolved and are well documented. 
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The program currently resides in the Division of Workplace Programs (DWP) of the 

Substance Abuse and Mental Health Services Administration (SAMHSA).

DWP is responsible for providing oversight for the Federal Drug-Free Workplace 

Program aimed at deterring and detecting illicit use of drugs by workers in the Federal

workforce. DWP also administers the National Laboratory Certification Program (NLCP), 

the HHS accreditation program for laboratories to conduct forensic drug testing for Federal

agencies. Two types of test facilities may become HHS-certified: laboratories that perform 

both initial and confirmatory testing (urine and oral fluid); and instrumented initial test 

facilities (IITFs) that perform initial testing (urine only). 

Subpart L, section 12.1, of the OFMG prohibits an IITF from testing oral fluid 

specimens for a Federal agency’s workplace drug testing program. This decision was 

primarily due to the limited specimen volume of oral fluid collected from the donor. 

In addition to administering the Federal Workplace Drug Testing Program DWP 

provides: 

■ Assistance to organizations and businesses establishing drug-free workplace 

programs (including drug testing); 

■ A Drug Free Workplace Helpline (800-967-5752) and a website at 

www.samhsa.gov/workplace; 

■ Primary substance abuse prevention information for workplace health and wellness 

programs; 

■ Information on intervention, treatment, and recovery for employee assistance 

programs; 

■ Management of the contract that administers the NLCP program (currently with RTI 

International) to certify all laboratories that are permitted to test Federal Civil Service 

employees and federally mandated employees; 

■ Requirements for MROs for training and for the review and verification of federally 

mandated drug testing results; and 

■ Coordination with the Office of National Drug Control Policy on the President’s 

National Drug Control Strategy. 

The numbers of specimens tested at HHS-certified laboratories expanded when the 

U.S. Department of Transportation (DOT) required that workers in regulated industries be 

tested at HHS-certified laboratories. The DOT program is administered separately from the 
1-3 

Federal Civil Service Program but coordinates program requirements with the DWP. This 

Medical Review Officer Guidance Manual (hereinafter, “the manual”) does not apply to 

specimens collected and tested under the DOT program. 

1.2 The Medical Review Officer (MRO)

An essential component of any drug testing program is a comprehensive final review 

of laboratory results, which includes review of appropriate documentation, as well as an 

interview with the donor of the specimen to discover whether or not an acceptable medical 

explanation exists for the laboratory result. A confirmed positive test result reported from a 

laboratory does not automatically identify an employee or job applicant as having misused 

drugs, nor does a laboratory result of invalid, adulterated, or substituted automatically 

identify a person as having tampered with a specimen. A physician with a detailed 

knowledge of possible legitimate medical explanations must determine drug test results in the 

context of all information including the test result and the donor interview. HHS requires the 

MRO to fulfill this important function. In the remainder of this manual the term “illicit drug 

use” will be used to represent not only illegal drug use, but also unauthorized pharmaceutical

drug use. 

1.2.1 MRO Requirements, Restrictions, Responsibilities

The Mandatory Guidelines define that an MRO must be a currently licensed 

physician holding either a Doctor of Medicine (M.D.) or Doctor of Osteopathy (D.O.) degree 

who has— 

■ Knowledge regarding the pharmacology and toxicology of illicit drugs; 

■ The training necessary to serve as an MRO, specifically the following: 

– The collection procedures used to collect Federal agency specimens;

– The interpretation of test results reported by HHS-certified IITFs and laboratories 

(e.g., negative, positive, adulterated, rejected for testing, invalid, substituted, and 

[for urine] negative/dilute);

– The chain of custody, reporting, and recordkeeping requirements for Federal 

agency specimens; 

– The HHS Mandatory Guidelines for each authorized specimen type (urine and 

oral fluid); and

– The procedures for interpretation, review (e.g., donor interview for legitimate 

medical explanations, review of documentation provided by the donor to support 

a legitimate medical explanation), and reporting of results specified by any 

Federal agency for which the individual may serve as an MRO. 
1-4 

■ Satisfactorily passed an initial examination administered by a nationally recognized 

entity or a subspecialty board that has been approved by the Secretary to certify 

MROs; 

■ At least every 5 years, completed requalification training on the above topics and 

satisfactorily passed a requalification examination administered by a nationally 

recognized entity or a subspecialty board that has been approved by the Secretary to 

certify MROs; and 

■ Certified MROs must complete training on any Mandatory Guidelines revisions 

including any changes to the drug and biomarker panels prior to their effective date, 

to continue serving as an MRO for Federal agency specimens.

The MRO serves as the common point of contact between all participants in a drug 

test (i.e., the donor, the collector, the test facility, 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, an 

HHS-certified laboratory or IITF for which the MRO is reviewing drug test results; 

and 

■ The MRO must not derive any financial benefit by having an agency use a specific 

test facility or have any agreement with an HHS-certified laboratory or IITF that may 

be construed as a potential conflict of interest.

The purpose of these prohibitions is to prevent any arrangement between an IITF or a 

laboratory and an MRO that could possibly influence the MRO and prevent the reporting of a 

problem identified with the test results or testing procedures. 

The MRO has the following responsibilities:

■ Review all positive, adulterated, rejected for testing, invalid, and substituted test 

results. (See also Table 4 - Medical Review Officer Actions for Primary (A) 

Specimen Reports; and Table 5 - Medical Review Officer Actions for Split (B) 

Specimen Reports) 

■ Ensure that specimens reported as negative and (for urine) negative/dilute are 

properly reviewed and reported to the agency’s designated representative. Staff under 

the direct, personal supervision of the MRO may review and report negative and (for 

urine) negative/dilute test results to the agency’s designated representative. The MRO 

must review at least 5% of the negative results reported by staff to ensure the MRO 

staff are properly performing the review process. This review should include all 

specimens that required corrective action; 
1-5 

■ Discuss potential invalid results (for reason other than pH, creatinine, specific gravity, 

or nitrite reported as ≥200 mcg/mL and <500 mcg/mL using a nitrite confirmatory 

test) with the HHS-certified laboratory to determine whether further testing at another 

HHS-certified laboratory is warranted;

■ Complete action on a report from an HHS-certified laboratory or IITF by— 

– Reviewing the information on the MRO copy of the Federal Custody and Control 

Form (CCF) that was received from the collector and the report received from the 

laboratory or IITF; 

– Interviewing the donor when required (e.g., to verify the existence of prescribed 

medication that could explain the result and/or to collect evidence of the 

prescription and subsequent dispensing of that prescription); 

– Making a determination regarding the result; and 

– Reporting the verified result to the Federal agency. 

■ Maintain all records for a minimum of two years while maintaining the 

confidentiality of the information. The MRO may discard hardcopy records six

months after conversion to electronic records (with appropriate security); 

■ Conduct a medical examination of the donor or a review of the examining physician’s 

findings and determine “refusal to test” or “cancelled test” when a collector reports 

that the donor was unable to provide a specimen and an alternate specimen (i.e., 

another authorized specimen type, urine, or oral fluid) was not collected; 

■ Monitor the frequency of errors and notify responsible parties to take corrective 

action to prevent recurrence; 

■ Review the results of Federal agency blind samples and perform the initial 

investigation into discrepant results; and

■ Request additional testing (as allowed) to help in the determination of a final result 

for a donor specimen. 

HHS recommends that each MRO use the information contained in this manual to 

ensure consistency and to improve the overall quality of the MRO review process. A glossary 

of terms used in this manual is found in Appendix A. 

The UrMG (88 FR 70768, effective February 1, 2024) and OFMG (88 FR 70814, 

effective October 10, 2023) are on the SAMHSA website: 

www.samhsa.gov/workplace/resources. 
1-6 

1.2.2 Federal Agency Responsibilities for Designating an MRO

Before allowing an individual to serve as an MRO for the agency, a Federal agency 

must verify and document the following: 

■ that the individual satisfies all requirements in Section 1.2.1, including certification 

by an MRO certification organization that has been approved by the Secretary; and 

■ that the individual is not an employee, agent of, or have any financial interest in an 

HHS-certified laboratory that tests the agency’s specimens. 

The Federal agency must verify and document that each MRO reviewing and 

reporting results for the agency: 

■ completes training on any revisions to these Guidelines, including any changes to the 

drug and biomarker testing panels, prior to their effective date;

■ at least every five years, maintains their certification by completing requalification 

training and passing a requalification examination; and

■ provides biannual reports to the Secretary or designated HHS representative as 

required in Section 4.7.2. 

The Federal agency must ensure that each MRO reports drug test results to the agency 

in accordance with Sections 4.7.1. 

■ Before allowing an MRO to report results electronically, the agency must obtain 

documentation from the MRO to confirm that the MRO and any external service 

providers ensure the confidentiality, integrity, and availability of the data and limit 

access to any data transmission, storage, and retrieval system.
2-1 

2. The Federal Drug Testing Custody and Control Form

2.1 General Information

Federal agencies are required to use the Federal Custody and Control Form (CCF) 

approved by the Office of Management and Budget (OMB) for their agency workplace drug 

testing programs. The Federal CCF is available from a number of different sources (e.g., 

IITFs, laboratories, collectors, consortia/third-party administrators, and Medical Review 

Officers [MROs]).

The Federal CCF may be a paper (hardcopy) form or an electronic form (ECCF) 

which may be a digital form or a combination electronic and paper format, used as follows:

■ Paper CCF. A hardcopy form formatted in accordance with the OMB-approved form 

and signed using handwritten (i.e., “wet”) signatures; 

– Option 1: a preprinted, five-part carbonless form; or 

– Option 2: a multiple-part CCF that is printed at the collection site prior to the 

collection. 

At a minimum, the collector prints Copy 1 and Copy 2 on carbonless paper for 

signatures.

■ Digital CCF (ECCF). An electronic document used to record all CCF events from 

collection through reporting and signed by the collector and donor using electronic 

signatures or “digitized” signatures (made using a signature pad); or 

■ Combination Electronic/Paper CCF. There are two types of combination electronic 

and paper ECCF systems:

o Option 1. An electronic form is used to document the collection process, 

printed, and signed using handwritten (i.e., “wet”) signatures. The donor signs 

in Step 5 of Copies 2-5 using a wet-signature and the collector signs in Step 4 

of Copies 1-5 using a wet-signature. 

At a minimum, the collector prints Copy 1 and Copy 2 on carbonless paper for 

wet-signatures. 

o Option 2. An electronic form is used to document the collection process, 

signed using electronic signatures (e.g., collector and donor “digitized” 

signatures made using a signature pad), and the collector prints Copy 1 with 

his or her electronic signature. The printout of ECCF Copy 1 must be 

designated as the single authoritative copy of the ECCF. 

A proof of the 2023 Federal CCF and guidance for its use are on the SAMHSA 

website: https://www.samhsa.gov/workplace/drug-testing. OMB approved the use of the 
2-2 

2023 Federal CCF as of May 1, 2023, for urine and oral fluid specimens. Examples of the 

Test Facility Copy (1) and the MRO Copy (2) of the Federal CCF are shown in Appendix B. 

(See Notes for Expired CCFs below.) 

Employers are prohibited from using the Federal CCF for

■ Private-sector employee drug testing, with the exception of transportation industry 

testing conducted under the DOT regulations; 

■ State workplace drug testing programs; or 

■ Department of Justice drug testing programs. 

The use of a non-Federal CCF, an expired Federal CCF, or incorrect form for a 

Federal agency specimen does not, in and of itself, constitute a reason for the test facility to 

reject the specimen for testing or for the MRO to cancel the test. All parties (collector, 

laboratory or IITF, MRO, employer) must take all practical action to correct a recoverable 

error so that the test is not cancelled. For example, in rare cases, a collector may use a nonfederal form or incorrect Federal CCF for a Federal agency collection by mistake or as the 

only means to conduct a collection under unusual circumstances (e.g., post-accident test with 

insufficient time to obtain a Federal CCF). In these cases, the collector must submit a 

memorandum for the record (MFR) with the specimen, and the test facility must test and 

report the specimen. The form used and the collector’s MFR should provide all information 

required on the Federal CCF. 

Notes for Expired CCFs: 

– The 2023 Federal CCF is the same as the expired 2020 Federal CCF. Therefore, 

use of the 2020 Federal CCF is approved and no MFR is required.

– Use of an expired Federal CCF (2017 or earlier) with a urine specimen may be 

recoverable with a collector MFR. Expired (urine only) CCFs are not allowed for 

oral fluid specimens unless the collector includes the required oral fluid collection 

information at the time of collection.

If a laboratory or an IITF discovers the use of a non-federal or incorrect federal form, 

the test facility processes and tests the specimen but holds the report. The collector is notified 

to provide an MFR stating the reason the correct Federal CCF was not used for the Federal 

agency collection. If the collector does not provide an MFR after at least 5 business days, the 

IITF or laboratory will report a “rejected for testing” result to the MRO who will cancel the 

test. 
2-3 

If an MRO discovers the use of a non-federal or an incorrect Federal form, the 

collector is notified to provide an MFR with the reason for using the incorrect form. If the 

collector does not provide an MFR after at least 5 business days, the MRO will cancel the 

test. 

If the collector provides an MFR within at least 5 business days, the laboratory should 

send a copy of the MFR received from the collector to the MRO or include a comment on the 

Federal CCF and electronic report noting that an MFR was received. The lab can reanalyze 

the specimen using regulated procedures at the request of the MRO if the specimen is 

negative for all drugs or positive only for a regulated analyte (not if specimen is positive for 

non-regulated analyte). For reanalyzed specimens, the laboratory or IITF must send a 

corrected report with the test results obtained for the specimen.

The MRO must implement procedures and administrative, technical, and physical 

controls to ensure donor privacy by restricting access to donor information and drug test 

results recorded on hardcopy and electronic Federal CCFs, or entered into a computer system 

or database. Access to donor information and drug test results must be limited to those 

individuals requiring access to fulfill job duties. Such individuals must receive training to

make them aware of their responsibilities for protecting the information. All drug testing 

service providers, including MROs, must maintain the confidentiality of Federal CCF 

information from the time the donor information is obtained through transmission/transport 

of the Federal CCF, specimen testing, reporting, and records handling (i.e., storage, retrieval, 

and final destruction). (See additional information in Chapter 6, Section 6.6, of this manual, 

including requirements for external service providers.) 

2.2 Use of an Electronic Federal CCF

A Federal agency may use the urine and oral fluid Federal CCFs as an electronic 

document in its Federal workplace drug testing program. An electronic Federal CCF (ECCF) 

must be the functional equivalent of a paper Federal CCF with respect to specimen type, 

content, integrity, accuracy, and accessibility. 

Before implementing a Federal ECCF, HHS-certified laboratories and IITFs must 

provide documentation on the ECCF system for HHS review and authorization for its use. 

The documentation will be submitted through the National Laboratory Certification Program 

(NLCP), and the ongoing review of records, procedures, and practices associated with the 

ECCF will be part of the NLCP inspection process. SAMHSA maintains the list of HHScertified test facilities (laboratories and IITFs) approved to use an ECCF, with the ECCF 
2-4 

system(s) that each is authorized to use, on the SAMHSA website: 

www.samhsa.gov/workplace/resources. 

The ECCF system provider and the Federal agencies and drug testing service 

providers (e.g., collectors, test facilities, MROs) who use digital or combination electronic 

and paper Federal CCFs must implement procedures and administrative, technical, and 

physical controls to ensure the confidentiality, integrity, and availability of electronic 

records, and to ensure that electronic signatures are the legally binding equivalent of 

traditional handwritten (“wet”) signatures. These procedures and controls include, but are not 

limited to, the following: 

■ System validation on a lab-by-lab basis; 

■ The ability to generate accurate and complete copies of records in both human 

readable and electronic forms suitable for inspection, review, and copying upon 

request of authorized parties (e.g., the MRO, Federal agency, or SAMHSA); 

■ Protecting records to enable accurate and ready retrieval throughout the records’ 

retention period; 

■ Limiting system access to authorized individuals. Procedures must be in place for 

managing the user authentication system (e.g., assignment, review, revocation); 

■ Maintaining secure, computer-generated, time-stamped audit trails to independently 

record the date and time of operator entries and actions that create, modify, or delete 

records from the time of initiation of the Federal CCF (changes should be evident 

when reviewing the original record, and any electronic or paper copy of the original 

record); and 

■ Using authority checks to ensure that only authorized individuals use the system, sign 

a record electronically, access the operation or computer system input or output 

device, alter a record, or perform the operation at hand. 

2.3 Federal CCF Content Requirements

The Federal CCF contains information for the test facility (i.e., on Copy 1), 

information for the MRO (i.e., on Copy 2), and information for the collection site (i.e., on 

Copy 3). The remaining copies, which are identical to the collection site copy, are for the 

employer and donor. 

A paper Federal CCF includes a legend (i.e., copy number and recipient name) at the 

bottom of each copy. A Federal ECCF is not required to have the legend at the bottom of 

Copy 2-5. 
2-5 

2.3.1 Test Facility Identification

■ At the top of the Federal CCF, the test facility must be identified by one of the 

following:

– A specific IITF or laboratory name and address; 

– A list of addresses with checkboxes to allow the collector to check the box for the 

IITF or laboratory to which the specimen will be shipped; or

– A corporate name and telephone number (the collector will annotate the address 

of the IITF or laboratory to which the specimen will be shipped, or the test facility 

that receives the specimen for testing will annotate its address). 

2.3.2 Specimen Labels/Seals

The tamper-evident specimen bottle/tube labels/seals may be at the bottom or the side 

of Copy 1 or may be separate from the form. There must be two labels/seals: one marked 

with the letter “A” to designate the primary (A) specimen and the other marked with the 

letter “B” to designate the split (B) specimen. Each label/seal must have the following: 

■ The same specimen identification (ID) number that is at the top of the Federal CCF; 

■ A place for the collector to annotate the date of the collection; 

■ A place for the donor to initial the label/seal after it is placed on the specimen 

bottle/tube; 

■ The label/seal must allow for placement without covering the specimen container 

expiry date for oral fluid; and

■ The label/seal size must allow for observation of the specimen. 

2.3.3 Required Statements

The wording of required statements must be identical to that on the OMB-approved 

Federal CCF. The statements must be provided as follows:

■ Display of the Public Burden Statement: 

– Paper Federal CCF: printed on the back of Copies 1 - 5; or 

– Federal ECCF: provided to CCF recipients as a separate page (i.e., with the 

electronically transmitted Federal CCF copies). The Public Burden Statement may 

be displayed on screen or posted at the collection site for the donor and collector, 

and/or provided to the donor as a hardcopy. 

■ Privacy Act Statement (For Federal Employees Only):

– Paper Federal CCF: printed on the back of the donor copy (Copy 5); or 
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– Federal ECCF: provided to the donor as a separate page (e.g., hardcopy, onscreen, 

posted at the collection site).

■ Note: Instructions for Completing the Federal Drug Testing Custody and Control 

Form have been removed from the back of the Federal CCF form. SAMHSA 

instructions for completing the Federal CCF for urine and oral fluid are on the 

SAMHSA website: https://www.samhsa.gov/workplace/drug-testing.

2.4 Federal CCF Distribution

Employers, collectors, test facilities, and MROs are responsible for ensuring the 

security of data transmissions and limiting access to any data transmission, storage, and 

retrieval systems for Federal CCFs. (See Chapter 6, Section 6.6, of this manual for 

requirements for the use of third-party service providers.) 

At the end of the collection, the collector distributes the CCFs as described below.

2.4.1 Paper Federal CCF

■ Copy 1 (Test Facility Copy) is signed by the collector and is shipped with the 

specimen package to the laboratory or the IITF. This paper form is the specimen 

chain of custody.

■ Copy 2 (MRO Copy) signed by the donor is sent to the MRO by one of the following 

methods: 

– The original is sent by courier or mail; or

– A copy is sent via fax or provided electronically. The collector maintains the 

original Copy 2 in the collection site records.

■ Copy 3 (Collector Copy) is maintained in the collection site records. 

■ Copy 4 (Employer copy) is sent via fax, courier, or mail, or is provided electronically. 

■ Copy 5 (Donor copy) is given to the donor or, if acceptable to the donor, may be

provided electronically. 

Note: CCF definitions are in Section 2.1 (General Information) of this chapter. The 

steps above apply to both a paper Federal CCF and a combination electronic and paper 

Federal ECCF. The collector will have at least two CCF pages (Copy 1 and Copy 2) for 

distribution (see Appendix B: Sample of CCF). When fewer than five parts are printed, the 

collector distributes copies of Copy 2 in lieu of separate CCF Copies 3-5. 

2.4.2 Digital Federal ECCF

■ Copy 1 (test facility copy) is signed by the collector and is provided electronically to 

the laboratory or the IITF. This electronic form is the specimen chain of custody. To 
2-7 

facilitate linkage of the specimen package to the Federal ECCF sent to the test 

facility, the collector must either:

– Include a printed copy of the Test Facility copy (i.e., Copy 1) of the Federal CCF 

with the specimen; or 

– Apply a label to the outside of the specimen package with the specimen ID 

number, test facility name, and contact information, and collection site name and 

contact information.

■ Copy 2-5 is electronically signed by the donor, maintained as an electronic file, and: 

– A copy is provided electronically to the MRO; 

– A copy is maintained in the collection site records;

– A copy is provided electronically to the employer; and 

– A copy is provided to the donor. The donor may request a printed copy or a copy 

that is electronically provided. 

Note: The Instructions for Completing the Federal Drug Testing Custody and Control 

Form for Specimen Collection have been removed from the back of the Federal CCF form. 

SAMHSA instructions for completing the Federal CCF for urine and oral fluid are on their 

website. See MRO Manual section 2.3.3. 

2.5 Test Facility Report to MRO

When testing has been completed, the laboratory or IITF records the results for a 

primary specimen (Bottle/Tube A) on the Federal CCF Copy 1 by marking the appropriate 

result boxes and includes any additional comments concerning the specimen’s testing or 

processing on the “Positive”, “Remarks”, and “Test Facility” lines. The original Federal CCF 

Copy 1 is retained in the specimen records at the test facility that reported the result. The 

laboratory or IITF reports results to the MRO as described below.

The test facility must fax, courier, mail, or electronically provide the completed 

Federal CCF (copy of Copy 1) to the MRO, with one exception. The test facility may report 

specimens as negative or (for urine) negative-dilute using only a computer-generated 

electronic report, provided that the report contains all required elements, to ensure that the 

test result is properly associated with the MRO copy (Copy 2) of the Federal CCF. (See 

Chapter 4, Sections 4.1.1 and 4.1.2 of this manual for the required elements.)

For all urine specimens forwarded by an IITF to a laboratory, the reporting laboratory 

must also send a copy of the completed IITF Supplemental CCF to the MRO. This chain of 

custody form documents the transfer of the urine specimen to the laboratory. The laboratory 
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may fax, courier, mail, or electronically provide this form. An example form is provided as 

Appendix C of this manual.

For non-negative specimens, laboratories are required to report all results for the 

specimen as supported by their data. Therefore, the MRO may receive a Federal CCF marked 

with more than one of the following results: 

■ Positive for one or more drugs (with the analyte and ng/mL concentration recorded on 

the Positive line); 

■ Adulterated (with the adulterant or pH value recorded on the Remarks line); and

■ Substituted (with the urine creatinine and urine specific gravity values recorded on 

the Remarks line).

■ Invalid Result (with the reason for the invalid result and value, as appropriate, 

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. 
3-1 

3. Drug Testing

3.1 Federal Workplace Drug Testing Overview

3.1.1 Drugs 

Federal agencies must test each specimen for marijuana and cocaine and their 

metabolites, and are authorized to test each specimen for other Schedule I or II drugs as 

provided in the drug testing panel. SAMHSA will publish the drug test analytes and cutoffs 

(i.e., the “drug testing panel”) for initial and confirmatory drug tests in the Federal Register 

each year. The authorized drug testing panels will also be available on the SAMHSA website

at https://www.samhsa.gov/workplace. Appendix D lists the drug testing panel analytes (i.e., 

drugs and drug metabolites) and test cutoffs specified by the UrMG and OFMG. SAMHSA 

publishes a list of all HHS-certified laboratories, the specimen type(s) each laboratory is

certified to test, and the ECCF approved laboratory list. The list is updated as needed. These 

drug testing resources are included on the SAMHSA website: 

www.samhsa.gov/workplace/resources/drug-testing 

Testing for an drugs other than those in the drug testing panel is allowed for the 

following reasons:

■ A Federal agency may test a specimen for another drug, on a case-by-case basis, 

when the agency is conducting a specimen collection for reasonable suspicion or 

post-accident testing. The specimen may be tested for any drugs listed in Schedule I 

or II of the Controlled Substances Act (other than drugs listed in Appendix D or when 

used pursuant to a valid prescription or when used as otherwise authorized by law). 

Information on drug schedules is available on the Drug Enforcement Administration 

(DEA) website, https://www.dea.gov. 

■ A Federal agency may routinely test its federal employees’ workplace specimens for 

a drug or drug class not listed in the drug testing panel described in Appendix D when 

the agency has been granted a waiver by the Secretary of the Department of Health 

and Human Services (HHS) to do so. 

For any circumstance where testing for drugs other than those in the drug testing 

panel is justified or authorized as described above, the Federal agency or the MRO will 

arrange the additional testing at an HHS-certified laboratory. The MRO will contact the 

laboratory Responsible Person (RP) who in turn will notify HHS and the NLCP of the MRO 

request for additional testing. Alternatively, the Federal agency representative may notify 

HHS of the request directly. HHS will review the request for the additional test and provide a 

written acknowledgment to the RP to proceed with the test. 
3-2 

The NLCP maintains a list of HHS-certified laboratories that will test regulated 

specimens for one or more Schedule I or II drugs upon request from a Federal agency. HHS 

provides the updated list to Federal agencies upon request. The information includes the 

laboratory name, address, contact information, and the Schedule I or II drug(s). If an initial 

test is not available for an additional Schedule I or II drug, the Federal agency may request 

the laboratory analyze the drug by testing two separate aliquots of a specimen using the 

confirmatory analytical method. The Federal Government classifies controlled substances 

under five schedules in the Controlled Substances Act (CSA). The CSA is available on the 

Drug Enforcement Administration (DEA) website at: https://www.dea.gov/druginformation/csa and a description is included in Appendix E. 

3.1.2 Specimen Collection

Only specimen types authorized by Mandatory Guidelines for Federal Workplace 

Drug Testing Programs may be collected. The MRO must be familiar with the specimen 

collection procedures required by the Mandatory Guidelines. A Federal agency may collect 

urine and/or oral fluid for its workplace drug testing program. 

For non-MRO determined refusals to test, the collector stops the collection, notifies 

the Federal agency by means (e.g., telephone, e-mail, or secure fax) that ensures that the 

notification is immediately received, documents the refusal to test including the reason on the 

Federal CCF, and (c) sends all copies of the Federal CCF to the Federal agency’s designated

representative. 

3.1.2.1 Urine

The HHS Urine Specimen Collection Handbook (available at 

https://www.samhsa.gov/workplace/drug-testing) contains guidance for collectors to 

supplement the urine collection procedures required by the UrMG. 

The collector shall instruct the donor to wash and dry the donor’s hands prior to 

urination. After washing the donor’s hands, the donor must remain in the presence of the 

collector and must not have access to any water fountain, faucet, soap dispenser, cleaning 

agent, or any other materials which could be used to adulterate or substitute the specimen. If 

the donor refuses to wash the donor’s their hands when instructed by the collector, this is 

considered a non-MRO determined refusal to test. 

The collector asks the donor to empty the donor’s pockets and display the contents to 

ensure no items are present that could be used to adulterate or substitute the specimen. If an 
3-3 

item is present that appears to have been brought to the collection site with the intent to 

adulterate, substitute, or dilute the specimen (e.g., a commercial drug culture product or other 

item for which the donor has no reasonable explanation), this is a non-MRO determined 

refusal to test. If an item that could be used to adulterate, substitute, or dilute the specimen 

(e.g., common personal care products such as eyedrops, mouthwash, or hand sanitizer) 

appears to have been inadvertently brought to the collection site, the collector must secure 

the item and continue with the normal collection procedure. If the donor refuses to show the 

collector the items in their pockets, this is a non-MRO determined refusal to test. 

The collector must inform the donor that, once the collection procedure has begun, 

the donor must remain at the collection site (i.e., in an area designated by the collector) until 

the collection is complete. This includes the wait period (i.e., up to 3 hours or until the donor 

has provided a sufficient urine specimen) if needed to provide a sufficient specimen. Failure 

to follow these instructions is a non-MRO determined refusal to test. 

Each Federal agency urine specimen is collected as a split specimen. The collector 

prepares a split urine specimen by pouring the specimen from the collection container into 

two bottles, which are then designated as Bottle A (the primary (A) specimen) and Bottle B 

(the split (B) specimen). 

The collection procedure begins when the collector will provide or the donor may 

select a specimen collection container that is clean, unused, wrapped/sealed in original 

packaging and compliant with Subpart G - Urine Specimen Collection Containers and 

Bottles. The specimen collection container package will be opened in view of the donor. 

The collector, in the presence of the donor, pours the urine from the collection 

container into two specimen bottles to be labeled “A” and “B.” The collector pours at least 

30 mL of urine into Bottle A and at least 15 mL into Bottle B, and caps each bottle. 

The collector notes any unusual behavior or appearance of the donor on the Federal 

CCF. If the collector detects any conduct that clearly indicates an attempt to tamper with a 

specimen (e.g., substitute urine in plain view or an attempt to bring into the collection site an

adulterant or urine substitute), this is a non-MRO determined refusal to test

The collector measures the temperature of the specimen within 4 minutes of receiving 

the specimen from the donor. The collector records on the Federal CCF whether or not the 

temperature is in the acceptable range of 32°-38°C/90°-100°F. If the temperature of the 

specimen is outside the range of 32°-38°C/90°-100°F, that is a reason to believe that the 
3-4 

donor may have adulterated or substituted the specimen. Another specimen must be collected 

under direct observation. The collector forwards both specimens (i.e., from the first and 

second collections) to an HHS certified laboratory for testing and records a comment on the 

Federal CCF for each specimen. If the donor fails to remain present through the completion 

of the collection or declines to have a direct observed collection to provide a second 

specimen as required, the collector stops the collection and reports the non-MRO determined 

refusal to test. 

The collector inspects the specimen to determine if there is any sign indicating that 

the specimen may not be a valid urine specimen (e.g., unusual color, presence of foreign 

objects or material, unusual odor). The collector notes any unusual finding on the Federal 

CCF. A specimen suspected of not being a valid urine specimen must be forwarded to an 

HHS-certified laboratory for testing. When there is any reason to believe that a donor may 

have adulterated or substituted the specimen, another specimen must be obtained as soon as 

possible under direct observation. The collector must forward both specimens (i.e., from the 

first and second collections) to an HHS-certified laboratory for testing and record a comment 

on the Federal CCF for each specimen. The collector must determine the volume of urine in 

the specimen container. If the donor fails to remain present through the completion of the 

collection or declines to have a direct observed collection to provide a second specimen as 

required, this is a non-MRO determined refusal to test. 

The collector must never combine urine collected from separate voids to create a 

specimen. If the volume is less than 45 mL, the collector discards the specimen and 

immediately collects a second specimen using the same procedures as for the first specimen. 

The collector may give the donor a reasonable amount of liquid to drink for this purpose 

(e.g., an 8 ounce glass of water every 30 minutes, but not to exceed a maximum of 40 ounces 

over a period of 3 hours or until the donor has provided a sufficient urine specimen). 

However, the donor is not required to drink any fluids during this waiting time. If the donor 

has not provided a sufficient specimen (i.e., at least 45 mL) within three hours of the first 

unsuccessful attempt to provide the specimen, the collector records the reason for not 

collecting a urine specimen on the Federal CCF, notifies the Federal agency’s designated 

representative for authorization to collect an alternate specimen, and sends the appropriate 

copies of the Federal CCF to the MRO and to the Federal agency’s designated representative. 

The Federal agency may choose to provide the collection site with a standard protocol to 

follow in lieu of requiring the collector to notify the agency’s designated representative for 

authorization in each case. If an alternate specimen is authorized, the collector may begin the 
3-5 

collection procedure for the alternate specimen. If the donor fails to remain present through 

the completion of the collection, refuses to provide a second specimen as required or refuses 

to provide an alternate specimen as authorized, this is a non-MRO determined refusal to test. 

3.1.2.2 Oral Fluid

The HHS Oral Fluid Specimen Collection Handbook (available at 

https://www.samhsa.gov/workplace/drug-testing) contains guidance for collectors to 

supplement the collection procedures required by the OFMG. 

The collector shall instruct the donor to wash and dry the donor’s hands under the 

collector’s observation, and to keep their hands within view and avoid touching items or 

surfaces after handwashing. If the donor refuses to wash their hands when instructed by the 

collector, this is a non-MRO determined refusal to test. 

If the collector will not keep the donor under direct observation from this point until 

the end of the collection, the collector asks the donor to empty the donor’s pockets and 

display the contents to ensure no items are present that could be used to adulterate or

substitute the specimen. If an item is present that appears to have been brought to the 

collection site with the intent to adulterate, substitute, or dilute the specimen (e.g., a 

commercial drug culture product or other item for which the donor has no reasonable 

explanation), this is a non-MRO determined refusal to test. If an item that could be used to 

adulterate, substitute, or dilute the specimen (e.g., common personal care products such as 

eyedrops, mouthwash, or hand sanitizer) appears to have been inadvertently brought to the 

collection site, the collector must secure the item and continue with the normal collection 

procedure. If the donor refuses to show the collector the items in their pockets, this is a nonMRO determined refusal to test. 

The collector must inform the donor that, once the collection procedure has begun, 

the donor must remain at the collection site (i.e., in an area designated by the collector) until 

the collection is complete. This includes the wait period (i.e., up to 1 hour must be provided 

or until the donor has provided a sufficient oral fluid specimen) if need to provide a sufficient 

specimen. Failure to follow these instructions is a non-MRO determined refusal to test. 

If the collector’s inspection of the donor’s oral cavity reveals any items that could 

impede or interfere with the collection of an oral fluid specimen (including abnormally 

colored saliva, candy, gum, food, tobacco), or the donor claims to have “dry mouth”, the 

collector gives the donor water (e.g., up to 4 oz) to rinse their mouth. The donor may drink 
3-6 

the water. The collector must then wait 10 minutes before beginning the specimen collection. 

If the donor refuses to remove an item or refuses to rinse, this is a non-MRO determined 

refusal to test. 

Each Federal agency oral fluid specimen is collected as a split specimen. Two 

specimens (Tube A [the primary (A) specimen], Tube B [the split (B) specimen]) are 

collected (1) concurrently or serially, and independently sealed in the presence of the donor; 

or (2) as a single specimen using a single collection device, subdivided into a primary Tube 

A specimen and a split Tube B specimen, and independently sealed in the presence of the 

donor. The second serial specimen collection must begin within two minutes after the 

completion of the first collection. 

The collection procedure begins when the collector will provide or the donor may 

select the specimen collection device(s) that are clean, unused, wrapped/sealed in original 

packaging and compliant the Subpart G. The device(s) must be within the manufacturer’s 

expiration date printed on the specimen tube(s). The specimen collection container package 

will be opened in view of the donor. 

A volume of at least 1 mL of undiluted (neat) oral fluid is collected for the specimen 

designated as primary Tube A and a volume of at least 1 mL of undiluted (neat) oral fluid is 

collected for the specimen designated as split Tube B.

The collector notes any unusual behavior or appearance of the donor on the Federal 

CCF. If the collector detects any conduct that clearly indicates an attempt to tamper with a 

specimen (e.g., an attempt to prevent the device from collecting sufficient oral fluid; an 

attempt to bring into the collection site an adulterant or oral fluid substitute), this is a nonMRO determined refusal to test collector must report a non-MRO determined refusal to test.

The collector inspects the specimen to determine if there is any sign indicating that 

the specimen may not be a valid oral fluid specimen (e.g., unusual color, presence of foreign 

objects or material). The collector notes any unusual finding on the Federal CCF and takes 

action (e.g., recollection) to obtain an acceptable specimen. If the donor fails to remain 

present through the completion of the collection, fails to follow the instructions for the 

collection device, refuses to begin the collection process after a failure to collect the 

specimen, refuses to provide a split specimen as instructed by the collector, or refuses to 

provide an alternate specimen when directed to do so, this is a non-MRO determined refusal

to test. 
3-7 

If the donor states that they could provide a specimen after drinking some fluids after

they demonstrate their inability to provide a specimen after 15 minutes of using the collection 

device, there is insufficient volume or no oral fluid collected using the device, the collector 

gives the donor a drink (up to 8 ounces) and waits an additional 10 minutes before beginning 

the specimen collection. If the donor simply needs more time before attempting to provide an 

oral fluid specimen, the donor may choose not to drink any fluids during the 1 hour wait 

time. If the donor states that they are unable to provide an oral fluid specimen, the collector 

records the reason for not collecting an oral fluid specimen on the Federal CCF, notifies the 

Federal agency’s designated representative for authorization to collect an alternate specimen, 

and sends the appropriate copies of the Federal CCF to the MRO and to the Federal agency’s 

designated representative. The Federal agency may choose to provide the collection site with 

a standard protocol to follow in lieu of requiring the collector to notify the agency’s 

designated representative for authorization in each case. If an alternate specimen is 

authorized, the collector may begin the collection procedure for the alternate. If the donor 

fails to remain present through the completion of the collection, refuses to provide a second 

specimen as required or refuses to provide an alternate specimen as authorized, this is a nonMRO determined refusal to test. 

3.1.3 Security and Chain of Custody 

The Mandatory Guidelines specify requirements for collection sites, laboratories, and 

IITFs to ensure the security and integrity of specimens and to maintain confidentiality of 

donor and drug test information. Collection sites, laboratories, and IITFs must be secured, 

with access limited to authorized personnel, to prevent unauthorized access to specimens, 

aliquots, and records. 

Permanent sites used solely for specimen collection must be secured at all times. At 

facilities that are not dedicated specimen collection sites, access to the areas used for 

specimen collections must be restricted to authorized personnel only during the collection. 

Individual areas within an IITF or laboratory (e.g., receiving/accessioning area, testing areas, 

sample preparation area, and specimen and records storage areas) must be separately secured 

to limit access to staff with job duties in the area. All visitors to secured areas within a test 

facility must be escorted and their access must be documented.

All Federal agency 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. The collector initiates the chain of custody documentation for the specimen using 
3-8 

the Federal CCF, and must maintain line-of-sight custody or provide for the secure storage of 

specimens from the time the specimen is collected until the urine bottles or oral fluid tubes 

are sealed in a shipping container prior to transfer. Because specimens are sealed in packages 

that would indicate any tampering during transit to the test facility, there is no requirement 

for delivery service personnel (e.g., couriers, express carriers, postal service personnel) to 

document chain of custody. 

Laboratories and IITFs annotate the appropriate chain of custody section of the 

Federal CCF upon receipt of the specimen and continue chain of custody documentation 

using internal forms. At the test facility, all specimens and all aliquots taken from each 

specimen are kept in secured storage or in the line of sight 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 the action. When an IITF forwards a urine specimen to a 

laboratory for testing, the IITF initiates a separate chain of custody form (i.e., IITF 

Supplemental Custody and Control Form) to document the transfer to the laboratory. This 

form is sent with the Federal CCF to the laboratory and is used by the laboratory to continue 

the chain of custody documentation. An example form is provided in Appendix C of this 

manual. 

3.1.4 Specimen Validity

HHS-certified laboratories are authorized to test each specimen for one or more 

biomarkers as provided in the biomarker testing panel. All specimen validity tests must be 

validated by the HHS-certified laboratory and approved by the NLCP and SAMHSA. MROs 

can contact the NLCP or SAMHSA to identify tests and individual labs approved to conduct 

additional testing.

HHS-certified laboratories are authorized to perform tests for drugs other than those 

in the drug testing panel and/or specimen validity tests on a case-by-case basis as necessary 

to provide information that the MRO would use to report a verified drug test result (e.g., 

specimen validity tests [for oral fluid]; specimen validity tests or tetrahydrocannabivarin [for 

urine], ). HHS-certified laboratories are not authorized to routinely test for drugs or 

biomarkers other than those included in the drug testing panel or the biomarker testing panel 

and/or specimen validity tests at the request of an MRO without prior authorization from the 

Secretary or designated HHS representative, with the exception of the determination of d, l 

stereoisomers of amphetamine and methamphetamine. Laboratories are allowed to perform
3-9 

additional testing for d, l stereoisomers on a case-by-case basis based on MRO request or 

routinely based on positive initial or positive confirmatory test results. 

SAMHSA will publish the drug and biomarker test analytes and cutoffs (i.e., the 

“drug testing panel” and “biomarker testing panel”) for initial and confirmatory drug and 

biomarker tests in the Federal Register each year. The drug and biomarker testing panels will 

also be available on the Internet at https://www.samhsa.gov/workplace. 

This drug testing panel will remain in effect until the effective date of a new drug 

testing panel published in the Federal Register.

3.1.4.1 Urine

Specimen validity testing must be performed for each Federal agency urine specimen. 

For urine specimens, at a minimum, creatinine and pH must be determined for each 

specimen, specific gravity must be determined for each specimen with creatinine less than 

20.0 mg/dL, and one or more tests for oxidizing adulterants must be performed. 

HHS-certified laboratories are authorized to test each specimen for one or more 

biomarkers as provided in the biomarker testing panel. 

Additional testing may be performed if a specimen exhibits abnormal characteristics 

(e.g., unusual odor or color, semi-solid characteristics), causes reactions or responses 

characteristic of an adulterant during initial or confirmatory drug tests (e.g., non-recovery of 

internal standard, unusual response), or contains an unidentified substance that interferes 

with the confirmatory analysis. 

Specimen validity tests must be performed for the split specimen (Bottle B) when a 

laboratory fails to reconfirm a drug analyte reported positive in the primary specimen (Bottle 

A). 

3.1.4.2 Oral Fluid

HHS-certified laboratories are authorized to test each specimen for one or more 

biomarkers as provided in the biomarker testing panel. 

Federal agencies are authorized to test each specimen for one or more biomarkers as 

provided in the biomarker testing panel and, upon an MRO’s request, to test an oral fluid 

specimen to determine specimen validity using, for example, a test for a specific adulterant.
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Additional testing may be performed if a specimen exhibits abnormal characteristics 

(e.g., unusual odor, color, or semi-solid characteristics), causes reactions or responses 

characteristic of an adulterant during initial or confirmatory drug tests (e.g., non-recovery of 

internal standard, unusual response), or contains an unidentified substance that interferes 

with the confirmatory analysis. 

3.1.5 Testing

3.1.5.1 Urine

Test facilities must be certified by HHS in order to test Federal agency workplace 

specimens. HHS publishes a monthly list of certified test facilities in the Federal Register and 

on the SAMHSA website: https://www.samhsa.gov/workplace. The two types of test 

facilities allowed under the UrMG are IITFs and laboratories. 

IITFs perform only the initial screening test for a urine specimen, and are allowed to 

report urine specimens as negative, negative, and dilute, and rejected for testing. Dilute is 

defined as creatinine greater than 5.0 mg/dL but less than 20.0 mg/dL and the specific gravity 

is equal to or greater than 1.002 but less than 1.003. Federally regulated specimens with all 

other presumptive results (positive, adulterated, and substituted) reported by an IITF must be 

forwarded to an HHS-certified laboratory for further testing.

Laboratories perform all tests for a urine specimen (initial and confirmatory) and are 

the only facilities that may report specimens as positive, adulterated, substituted, invalid, and 

dilute. Certified laboratories report urine specimen as dilute when the creatinine is greater 

than 5.0 mg/dL and less than 20.0 mg/dL and the specific gravity is equal to or greater than 

1.002 but less than 1.003; or the creatinine concentration is equal to or greater than 2.0 

mg/dL, but less than 20.0 mg/dL and the specific gravity is greater than 1.0010 but less than 

1.0030. 

For forensic and scientific acceptability, laboratories are required to perform initial 

and confirmatory tests using separate aliquots of a specimen to support a positive, 

adulterated, or substituted result. The confirmatory test uses a different test method that is 

usually more specific than the initial test. Laboratories must also test two separate aliquots of 

a urine specimen prior to reporting the specimen as invalid. Urine specimen reporting criteria 

are in Appendix D. 

In most cases, the MRO is not allowed to request retesting of a primary specimen 

(Bottle A). Primary (A) specimens may be reanalyzed only— 
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■ When a Federal agency has requested reanalysis as part of a legal or an administrative 

proceeding to defend an original positive, adulterated, or substituted result; 

■ When the MRO has requested analysis of the primary (A) specimen for adulteration

because a second HHS-certified laboratory failed to reconfirm the drug(s) reported in 

the primary (A) specimen, and reported that the split (B) specimen was adulterated. In 

this case, the MRO reports the failed to reconfirm result and the refusal to test, and 

gives the donor 72 hours to request that the first laboratory (i.e., that reported primary 

[A]) retest the primary specimen (A) for the adulterant. If the second laboratory 

reported the split (B) specimen as substituted, the MRO reports the failed to 

reconfirm result and the refusal to test, and gives the donor 72 hours to request that 

the first laboratory: 

– For urine substitution based upon creatinine and specific gravity, review the 

specific gravity and creatinine results of the primary (A) specimen; or 

– For substitution based upon biomarker testing, test the primary (A) specimen 

using its confirmatory test for the biomarker.

■ When HHS has directed the laboratory to reanalyze the specimen. 

The MRO may request additional/different testing of a primary specimen (Bottle A)

or split (Bottle B) urine specimens under the following circumstances: 

■ The laboratory has notified the MRO that the initial or confirmatory test result is 

invalid due to a possible presence of an adulterant and the MRO would like to have 

additional/different testing completed. 

■ The specimen is confirmed positive for methamphetamine and the MRO elects to 

have d, l enantiomer testing performed. This testing may be performed on a case-bycase basis or, for primary (A) specimens, with a blanket request from the MRO.

■ When additional test information on a positive result may be useful to the MRO in 

determining the final test result. For example, the MRO may request testing for

metabolites such as norhydrocodone and noroxycodone which may be helpful to the 

MRO in determining a final test result when a prescription does not support the 

laboratory’s reported results. Another example would be the use of a test for the 

presence of Δ9-tetrahydrocannabivarin (THCV) to confirm the use of cannabis as 

opposed to pharmaceutical THC. 

When the primary specimen (Bottle A) is reported as positive, adulterated, or 

substituted, the donor is given an opportunity to request testing of the split specimen (Bottle 

B) at a second HHS-certified laboratory. If a donor does not ask to have the split specimen 

(Bottle B) tested, a Federal agency may have the split urine specimen tested as part of a legal 

or an administrative proceeding to defend an original positive, adulterated, or substituted 

result.
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3.1.5.2 Oral Fluid

Test facilities must be certified by HHS in order to test Federal agency workplace 

specimens. HHS publishes a monthly list of certified test facilities in the Federal Register and 

on www.samhsa.gov/workplace. The only test facilities allowed under the OFMG are 

laboratories. Only HHS-certified laboratories are authorized to test oral fluid specimens for 

Federal agency workplace drug testing programs. 

Oral fluid specimens are usually collected using a device, which may or may not 

contain a diluent. HHS-certified laboratories must process oral fluid specimens using 

validated procedures that are specifically for the collection device used to collect the 

specimen. The NLCP maintains a list of HHS-certified oral fluid laboratories and the 

device(s) that each laboratory tests. 

Laboratories may report oral fluid specimens as negative, positive, adulterated, 

substituted and invalid. 

For forensic and scientific acceptability, laboratories are required to perform initial 

and confirmatory tests using separate aliquots of a specimen to support a positive, 

adulterated or substituted result. The confirmatory test uses a different test method that is 

usually more specific than the initial test. Laboratories must also test two separate aliquots of 

an oral fluid specimen prior to reporting the specimen as invalid. Oral fluid specimen 

reporting criteria are in Appendix D. 

In most cases, the MRO is not allowed to request retesting of a reported primary (A) 

specimen. Primary (A) specimens may be reanalyzed only— 

■ When a Federal agency has requested reanalysis as part of a legal or an administrative 

proceeding to defend an original positive, adulterated or substituted result;

■ When HHS has directed the laboratory to reanalyze the specimen; or

■ When the MRO has requested analysis of the primary (A) specimen for adulteration

or substitution because a second HHS-certified laboratory failed to reconfirm the 

drug(s) reported in the primary (A) specimen, and reported that the split (B) specimen 

was adulterated or substituted. In this case, the MRO reports the failed to reconfirm 

result and the refusal to test, and gives the donor 72 hours to request that the first 

laboratory (i.e., that reported primary (A) specimen) retest the primary specimen (A) 

for the adulterant or substituted result. 
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The MRO may request additional/different testing of a primary (A) or split (B) oral 

fluid specimens under the following circumstances: 

■ The laboratory has notified the MRO that the initial or confirmatory test is invalid due 

to possible presence of an adulterant and the MRO would like to have 

additional/different testing completed. 

■ The specimen is confirmed positive for methamphetamine and the MRO elects to 

have d,l enantiomer testing performed. This testing may be performed on a case-bycase basis or, for primary specimens, with a blanket request from the MRO. 

■ When additional test information on a positive result may be useful to the MRO in 

determining the final test result. For example, the MRO may request additional 

specimen validity testing (e.g., tests for a biomarker and/or an adulterant) on a caseby-case basis. 

When the primary (A) oral fluid specimen is reported as positive, adulterated, or 

substituted, the donor is given an opportunity to request testing of the split (B) specimen at a 

second HHS-certified laboratory. If a donor does not ask to have the split (B) oral fluid

specimen tested, a Federal agency may have the split (B) oral fluid specimen tested as part of 

a legal or an administrative proceeding to defend an original positive, adulterated or 

substituted result.

3.2 Test Methods

An MRO is not required to be as technically knowledgeable of analytical procedures 

and data as a certifying scientist; however, the MRO must know what tests were used to 

generate the specimen results that he/she reviews and should understand the general scientific 

principles of the testing procedures. HHS-certified laboratories are required to validate all

methods prior to implementation to ensure that they are accurate and reliable for testing of 

Federal workplace drug testing specimens.1

3.2.1 Initial Drug Tests

Laboratories and IITFs are required to use either immunoassay or an alternate 

technology (e.g., spectrometry, spectroscopy) for initial drug tests. 

Immunoassays are testing methods that use antigen (drug) and antibody binding to 

identify drug analytes. The antibodies are produced to be drug-specific. A known amount of 

antibody is added to a specimen, along with a drug that has been labeled to distinguish it 

from the drug in a donor’s specimen. The labeled drug and the unlabeled drug (if any) 

compete for the antibody to form an antigen-antibody complex. The ratio of the labeled and 
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unlabeled drug bound to the antibody allows the measurement of the amount of drug in the 

donor’s specimen. Immunoassays are used as initial drug tests to identify specimens that 

require further testing. 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 must be further tested 

using a different analytical method as a confirmatory test. For drug classes with multiple 

initial test analytes (such as opioids and amphetamines), the UrMG and OFMG allow a 

single immunoassay test for the drug class or separate immunoassay tests. When one test is 

used, the test is calibrated with one analyte from the group identified as the target analyte. 

The cross-reactivity of the immunoassay to each of the other analytes in the group must be 

80% or greater. Alternatively, the laboratory may use separate immunoassay tests for the 

analytes within the group. 

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

abuse.

A laboratory or IITF may use a technology other than immunoassay to differentiate 

negative specimens from those requiring further testing. Technological advances have led to 

increased throughput and lower costs that enable the use of such methods in initial testing. 

For marijuana metabolite, cocaine metabolite, and heroin metabolite initial tests using an 

alternate technology that is specific for the target analyte, the confirmatory test cutoff must 

be used (i.e., 15 ng/mL for urine Δ9- tetrahydrocannabinol-9- carboxylic acid [THCA], 100 

ng/mL for urine benzoylecgonine, 2 ng/mL for oral fluid Δ9- tetrahydrocannabinol [THC], 2 

ng/mL for oral fluid 6-acetylmorphine [6-AM]). For drug classes with multiple initial test 

analytes (such as codeine/morphine, hydrocodone/hydromorphone, oxycodone/

oxymorphone, methylenedioxymethamphetamine (MDMA)/methylenedioxyamphetamine 

(MDA), amphetamine/methamphetamine, and, for oral fluid only, cocaine/

benzoylecgonine), one or all analytes from the group must be used to calibrate the test, 

depending on the technology. For a specimen to be positive by the initial test, at least one 

analyte within the group must have a concentration equal to or greater than the initial test 

cutoff or, alternatively, the sum of the individual analyte concentrations must be equal to or 

greater than the initial test cutoff. Any specimen that is positive by the initial test must be 

subjected to a confirmatory test using the confirmatory test cutoff, which is applied to each 

individual analyte. In addition, for forensic defensibility, the confirmatory test is performed 

on a separate aliquot of the specimen.
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3.2.2 Confirmatory Drug Tests 

Laboratories are required to use a confirmatory drug test method that specifically 

identifies and quantifies the drug or drug metabolite. The analytical method used for the 

confirmatory drug test must combine chromatographic separation and mass spectrometric 

identification. For confirmatory drug testing, the UrMG and OFMG require laboratories to 

use a combined analytical method coupling a chromatographic instrument with a mass 

spectrometer (MS). Chromatographic techniques such as gas chromatography (GC) and 

liquid chromatography (LC) are used to separate and analyze mixtures of chemical 

substances. After the chromatographic instrument has separated the analytes in a specimen, 

the specimen enters the MS, which identifies and quantifies 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. Specimens 

must undergo a specimen preparation process (i.e., extraction) prior to GC-MS analysis and 

may require preparation prior to LC-MS/MS analysis. Tandem MS methods using multiple 

reaction monitoring (MRM) analysis are also allowed and provide additional analytical 

benefits.

3.2.3 Specimen Validity Tests

3.2.3.1 Urine

The UrMG specify test method requirements for some urine specimen validity tests 

(e.g., refractometry for specific gravity testing, pH meter tests for the initial and confirmatory 

pH tests; however, it is not possible to provide guidance on test methods for all substances 

that may be used to adulterate or validate a urine specimen. As new adulterants are identified, 

IITFs and laboratories are permitted to implement appropriate tests for their analysis. There 

may be more than one acceptable test method for a particular analyte. All specimen validity 

tests must be scientifically and forensically supportable.

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

validity tests.

3.2.3.2 Oral Fluid

The OFMG specify that laboratories are authorized to test each specimen for one or 

more biomarkers as provided in the biomarker testing panel and, upon a Medical Review 

Officer’s request, to test an oral fluid specimen to determine specimen validity using, for 

example, a test for a specific adulterant. Each invalid, adulterated or substituted specimen 

validity test result must be based on an initial specimen validity test on one aliquot and a 
3-16 

confirmatory specimen validity test on a second aliquot. The OFMG do not specify tests or 

test method requirements for oral fluid initial and confirmatory specimen validity testing if 

performed upon request by the Medical Review Officer. It is not possible to provide 

guidance on test methods for all substances that may be used to adulterate or validate an oral 

fluid specimen. As new adulterants are identified, laboratories are permitted to implement 

analysis for HHS-approved adulterants. There may be more than one acceptable test method 

for a particular analyte. All specimen validity tests must be scientifically and forensically 

supportable. 

3.2.4 Split (B) Specimen Testing

The second HHS-certified laboratory must report the result to the MRO using the 

HHS-specified nomenclature published with the drug and biomarker testing panels. 

3.2.4.1 Urine

A donor may request testing of the split (B) urine specimen at a second HHS-certified 

laboratory to reconfirm or refute a positive, adulterated, or substituted result reported for the 

primary (A) specimen. The second laboratory tests the split (B) specimen using only the 

confirmatory test(s) needed to reconfirm the primary (A) specimen result(s). The laboratory 

performs drug tests at the laboratory’s limit of detection (LOD) or limit of quantification 

(LOQ)—not the HHS cutoffs. For substitution based on biomarker testing: The laboratory 

must test for the biomarker using its confirmatory test (i.e., using the confirmatory test 

analytes and cutoffs in the biomarker testing panel). Otherwise, split (B) specimen 

reconfirmations for adulterated and substituted specimens are performed at the HHS cutoffs 

for primary (A) specimens. For adulterants without a specified cutoff (e.g., glutaraldehyde, 

chromium [VI], pyridine, halogens [such as, chlorine from bleach, iodine], peroxidase, 

peroxide, other oxidizing agents), the laboratory must use its confirmatory specimen validity 

test at the laboratory’s LOQ to reconfirm the presence of the adulterant. The laboratory is 

required to inform the MRO of the laboratory’s LOD/LOQ, but the reconfirmation report is 

issued as a qualitative “reconfirmed” or “failed to reconfirm” result only. If the laboratory 

fails to reconfirm one or more drug analytes reported as positive in the primary (A) 

specimen, the laboratory performs specimen validity tests for the split (B) specimen.

If the split (B) specimen testing laboratory (laboratory B) believes that the analyte 

(i.e., drug, drug metabolite, adulterant) is present in the split (B) specimen but cannot 

reconfirm its presence, the laboratory must consult with the MRO and the NLCP to decide 

whether to send the split (B) specimen to a third HHS-certified laboratory for additional 
3-17 

confirmatory testing. For Federal specimens, the MRO must submit a signed request to the 

split (B) specimen testing laboratory to have the additional testing done at a third laboratory. 

This is not required for DOT-regulated urine specimens. The third laboratory should use a 

confirmatory test method more similar to that used by the first laboratory (i.e., the laboratory 

that reported the primary (A) specimen result).

3.2.4.2 Oral Fluid

A donor may request testing of the split (B) oral fluid specimen at a second HHScertified laboratory to reconfirm or refute a positive or adulterated result reported for the 

primary (A) specimen. Prior to sending an oral fluid specimen or aliquot to another HHScertified laboratory, the sending laboratory must ensure that the receiving laboratory has 

validated procedures for testing specimens using the specific collection device. If a 

laboratory receives a primary or split (B) specimen for additional testing and the laboratory 

does not have validated procedures for the additional test(s) using the same collection device, 

that laboratory must notify the sending laboratory and obtain MRO authorization to send the 

specimen to another HHS-certified laboratory that has validated procedures. 

The second laboratory tests the split (B) specimen using only the confirmatory test(s) 

needed to reconfirm the primary (A) specimen result(s). The laboratory performs drug tests at 

the laboratory’s limit of detection (LOD) or limit of quantification (LOQ)—not the HHS 

cutoffs. Split (B) specimen reconfirmations for adulterated specimens are performed at the 

laboratory’s LOQ. When testing the split (B) specimen for substitution based on biomarker 

testing, the laboratory must test for the biomarker using its confirmatory test (i.e., using the 

confirmatory test analytes and cutoffs in the biomarker testing panel). The second HHScertified laboratory may only conduct the confirmatory biomarker test(s) needed to reconfirm 

the substituted result reported by the first HHS-certified laboratory. The laboratory is 

required to inform the MRO of the level that is that laboratory’s LOD/LOQ, but the 

reconfirmation report is issued as a qualitative “reconfirmed” or “failed to reconfirm” result 

only. MRO Manual chapter 4, section 4.5, Interpretation and Result Verification, has 

additional information concerning testing of split (B) specimens. If the laboratory fails to 

reconfirm one or more drug analytes reported as positive in the primary (A) specimen, the 

laboratory may perform specimen validity test(s) for the split (B) specimen.

If the split (B) testing laboratory (laboratory B) believes that the analyte (i.e., drug, 

drug metabolite, adulterant) is present in the split (B) but cannot reconfirm its presence, the 

laboratory must consult with the MRO and the NLCP to decide whether to send the oral fluid 
3-18 

specimen to a third HHS-certified laboratory for additional confirmatory testing. The third 

laboratory must have validated confirmation methods that are specific to the specimen 

collection device. For Federal specimens, the MRO must submit a signed request to the split 

testing laboratory to have the additional testing done at a third laboratory. This is not required 

for DOT-regulated oral fluid specimens. The third laboratory should use a confirmatory test 

method more similar to that used by the first laboratory (i.e., the laboratory that reported the 

primary (A) specimen result).

3.3 IITF or Laboratory Reports

An MRO may not request SVT values for a specimen that is reported only as 

negative or positive. For example, an MRO may not request creatinine results for a specimen 

that was reported as positive for codeine. 

A dilute finding is reported as a CCF Step 5A checkbox and a Remarks comment 

only in conjunction with a negative or positive result. Laboratories must report the creatinine 

and specific gravity values supporting a dilute finding (i.e., negative-dilute, and positivedilute).

Laboratories must report ALL “non-negative” test results for a specimen. For 

example, a laboratory MUST report a specimen substituted AND ALSO positive for a given 

drug metabolite if the criteria for both results have been met. Laboratories must report the 

numerical values of specimen validity test results that support an adulterated result (i.e., 

confirmatory adulterant test result, confirmatory pH test result), substituted result (i.e., 

confirmatory creatinine and specific gravity values), or invalid result (as appropriate). 

■ For negative and (for urine) negative/dilute results, the laboratory and IITF is allowed 

to report results using only a computer-generated report.

■ For rejected for testing specimens, the laboratory or IITF must send a copy or a 

legible image of the test facility Federal CCF Copy 1 to the MRO. The laboratory or 

IITF is allowed to send a computer-generated report in addition to the Federal CCF. 

■ For positive, adulterated, invalid, and substituted results, the laboratory must send a 

copy or a legible image of the test facility Federal CCF Copy 1 to the MRO. The 

laboratory is allowed to send a computer-generated report in addition to the Federal 

CCF.

■ For specimens other than negative, laboratories are required to report all results for a 

specimen as supported by their data. Therefore, the MRO may receive a Federal CCF 

marked with more than one of the following results:
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– Positive for one or more drugs (with the analyte name and concentration recorded 

on the Positive line);

– Adulterated (with the adulterant or pH value recorded on the Remarks line);

– Substituted (with the biomarker value recorded on the Remarks line or [for urine 

only] with the creatinine and specific gravity values recorded on the Remarks 

line); or 

– Invalid result (with the reason for the invalid result and value, as appropriate, 

recorded on the Remarks line). 

Note: These are separate results. For example, “invalid result” does not refer to the 

drug(s)/drug metabolite(s) reported positive. The MRO should contact the laboratory 

if there is any confusion about the reported results.

■ If the report is provided by electronic means, the electronic transmission must be 

secure (e.g., a Web portal in which the MRO can log into a password-protected site to 

download the scanned copy of the Federal CCF Copy 1 or by encryption). 

■ An HHS-certified laboratory or IITF must report results using the HHS-specified 

nomenclature published with the drug and biomarker testing panels. 

3.4 Specimen and Records Storage

Laboratories are required to maintain the following specimens in a secure frozen 

storage area for at least 1 year after reporting:

■ Drug positive specimens; 

■ Substituted specimens;

■ Adulterated specimens;

■ Invalid specimens; 

■ Split (B) specimens of the primary (A) specimens listed above; and

■ Any split (B) specimens or primary (A) specimen aliquots received from another 

laboratory for testing.

A Federal agency may request the laboratory to retain a specimen for a longer period 

(e.g., specimens under legal challenge). The agency’s request must be in writing and must 

specify the period of time for specimen retention. 

Laboratories and IITFs may discard negative, rejected, and (for urine) negative-dilute 

specimens after reporting them to the MRO. If a specimen is rejected due to a missing 
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collector signature and no MFR to provide the signature is received, the specimen will be 

held for at least 5 business days prior to reporting and then discarded. 

Collection site records (e.g., collector copies of the Federal CCF) must be maintained 

for at least two years by the collector or collector employer. IITFs and laboratories must 

maintain records generated to support test results for a minimum of two years. A Federal 

agency may request the test facility to maintain a copy of the documentation package for a 

urine specimen that is under legal challenge (see Chapter 6, Section 6.4, Donor Rights to 

Information). The agency’s request must be in writing and must specify the period of time for 

record retention. MROs must also maintain all drug test records for a minimum of two years. 

See Chapter 4, Section 4.6 for additional information.

The MRO and external service providers must ensure the confidentiality, integrity, 

and availability of the data and limit access to any data transmission, storage, and retrieval 

system. Hardcopy records may be discarded six months after conversion to electronic 

records.
4-1 

4. MRO Review and Reporting Procedures

The MRO must review all positive, adulterated, rejected for testing, invalid test, and 

substituted results before reporting the results, in a timely manner, to the Federal agency’s 

designated representative. This applies even if the first test was cancelled and another 

specimen was collected from the donor due to the administrative problem (e.g., collector 

failed to provide an MFR when directed). Staff under the direct, personal supervision of the 

MRO may review and report negative and (for urine) negative-dilute specimen results. The 

MRO must review at least 5% of the specimen results reported by MRO staff to ensure that 

staff is properly performing the review process. If a staff member reports a negative/dilute, 

the staff member or MRO reports a negative/dilute result to the agency and directs the 

agency to immediately collect another specimen from the donor. Refer to Section 4.5.5 for 

changing a verified test result.

The MRO process consists of— 

■ Administrative review of documents; 

■ Interview with the donor (as required);

■ Handling split (B) specimen test requests (as required);

■ Result interpretation and verification;

■ Documentation and recordkeeping; 

■ Reporting the drug test to the Federal agency’s designated representative;

■ Confidentiality; and

■ Discrepancies to cancel test.

No regulatory requirements exist for MROs to use specific procedures to review drug

tests; however, using a standard procedure better ensures that the MRO review for each

specimen is consistent and complete. A simple checklist can be helpful in assuring consistency

and completeness of the process.

4.1 Administrative Review of Documents

Note: The following descriptions and instructions are for the MRO Copy (Copy 2) of 

the Federal CCF.
4-2 

Note: The MRO should check to ensure that neither the donor nor collector has listed 

medications as part of their completion of Copy 2. This information would also appear on the 

client/employer Copy 4, which is not to be used to disclose medications or medical 

conditions. Since entries made on Copy 2 will not appear on the laboratory Copy 1, it is the 

MROs responsibility to notify the collection site to prevent future problems.

Note: All copies of the CCF are sent to the Federal agency’s designated 

representative for non-MRO determined refusals to test. The MRO does not review these 

records.

4.1.1 MRO Copy of the Federal CCF (Copy 2) 

The collector is required to send the MRO copy of the Federal CCF (paper Copy 2 or 

electronic Copy 2) to the MRO within 24 hours, or 1 business day after the collection. If the 

MRO receives a test report for a specimen without having received the MRO copy of the 

Federal CCF, the MRO must contact the collector. If a paper Federal CCF was used and the 

MRO Copy 2 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). If an electronic copy was used, the MRO must contact the 

collector to resend the MRO copy (Copy 2). 

The MRO checks for the following items on Copy 2 of the Federal CCF (not all are 

essential to report a specimen). 

■ The correct Federal CCF approved by the Office of Management and Budget (OMB) 

was used to document the specimen collection.

■ The Federal CCF contains the specimen identification (ID) number.

■ Specimen collected is identified as either urine or oral fluid.

■ Each test facility is identified by one of the following:

– A specific laboratory or IITF name and address at the top of the Federal CCF;

– A list of addresses with checkboxes at the top of the Federal CCF (the collector 

checks the box for the test facility to which the specimen will be delivered); or

– A corporate name and telephone number at the top of the Federal CCF (Note: the 

test facility that reports the specimen results to the MRO will annotate Copy 1 to 

include the specific name and address in the “Test Facility” line in Step 5a).

■ The Federal CCF was properly completed (see also sections 6.5 and 6.6). 
4-3 

– Step 1 contains— 

o Federal agency name and address and employer ID number (as appropriate); 

o MRO name or MRO company name, address (i.e., street address; not a Post 

Office Box number), telephone number, and fax number; 

o Donor’s ID (e.g., social security number [SSN], employee ID number) or 

collector’s remark in Step 2 if the donor refuses to provide the SSN or ID 

number); 

o Testing authority (i.e., Department of Health and Human Services [HHS], 

Nuclear Regulatory Commission [NRC], Department of Transportation 

[DOT] and the specific mode administration, or United States Coast Guard 

[USCG]);

o Reason for the test; 

o Drug tests to be performed; and

o Collection site information (i.e., address, telephone number, and fax number). 

– Step 2 documents that— 

o Specimen collected is either Urine or Oral fluid;

o The collection was:

• A split specimen; 

• A single-specimen collection; or

• No specimen was collected and why (if applicable). 

Note: Split specimen collections are required for Federal agency specimens.

o For urine: 

• The temperature of the urine specimen was, or was not, within the 

required temperature range;

• 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. 

o For oral fluid:

• The specimen collection split type:

► Serial; 

► Concurrent; or

► Subdivided. 

• Each collection device is within expiration date; 

• The specimen collection device volume indicator(s) observed; and
4-4 

• Comments on the “Remarks” line (as appropriate) recording the 

collector’s observations or explanatory comments concerning the donor, 

the specimen, or collection events. 

Note: Split specimen collections are required for Federal agency specimens.

– Step 3 contains— 

o Collector’s printed name;

o Collector’s signature;

o Date and time of the collection; and

o Specific name of the delivery service that specimen bottle(s)/tube(s) were 

released to for transfer the specimen to the test facility.

– Step 4 contains— 

o Donor’s printed name; 

o Donor’s signature; 

o Date signed;

o Donor’s email address;

o Donor’s daytime telephone number; 

o Donor’s evening telephone number; and 

o Donor’s date of birth. 

4.1.2 Test Facility Report—Federal CCF (Copy 1) and/or Computer-Generated Electronic 

Report 

Certified laboratories and IITFs report drug test results to the MRO using a legible 

image or copy of the Federal CCF Copy 1 and/or a computer-generated electronic report. The 

Federal CCF Copy 1 is used to report all positive, adulterated, invalid, rejected, and 

substituted specimens. The test facility may send a computer-generated electronic report in 

addition to the Federal CCF Copy 1 for these specimens. The test facility may send only a 

computer-generated electronic report for negative and (for urine) negative-dilute specimens. 

The MRO must have procedures in place to ensure the confidentiality of the reports (i.e., 

hardcopy and electronic). 

The test facility may send reports by courier or mail or use various electronic means 

(e.g., fax, computer, secure electronic transmission). Transmissions of the reports must 

ensure confidentiality and the results may not be reported verbally by telephone. IITFs, 

laboratories, and other service providers must ensure the confidentiality, integrity, and 

availability of the data and limit access to any data transmission, storage, and retrieval 
4-5 

system. (See Chapter 6, Section 6.6, of this manual for requirements for the use of external 

service providers.)

The MRO checks for the following items on the Federal CCF Copy 1 (not all are 

essential to report a specimen): 

■ The specimen ID number on the test facility copy of the Federal CCF (Copy 1) and/or 

any other report matches that on the MRO copy (Copy 2) for the identified donor. 

■ Copy 1 (the test facility copy) of the Federal CCF was properly completed. 

– Step 4 contains— 

o Laboratory or IITF accessioner’s printed name;

o Accessioner’s signature;

o Date of receipt; 

o Documentation of the primary (A) specimen (Bottle/Tube A) seal condition 

upon receipt at the test facility; 

o Documentation for Specimen Bottle(s)/Tube(s) Released to, and

(for oral fluid) the expiration dates for each primary/single specimen 

collection device and the split specimen collection device. 

If the manufacturer puts the same expiration date on the outer package as that 

on the specimen tube(s) in the package, it is acceptable for the collector to 

record the outer package dates in Step 4 of the Federal CCF. The accessioner 

records the oral fluid collection device expiration date on the A specimen tube 

as the Primary/Single Specimen Device Expiration Date, and the expiration 

date on the B specimen tube as the Split Specimen Device Expiration Date. If 

the collector recorded the expiration dates in Step 4 of the Federal CCF, the 

accessioner verifies the recorded expiration dates versus those on the A and B 

specimen tubes. If an expiration date differs from that on the tube, the 

accessioner makes a single line through the incorrect date, records the date

that is on the tube, and initials and dates the annotation. The accessioner must 

proactively document their verification of the expiration dates:

o For a paper or combination electronic/paper Federal CCF Copy 1, the 

accessioner documents their verification in Step 4. On the Copy 1 form, the 

accession must initial each expiration date.

o For an electronic (digital) Federal CCF Copy 1, the accessioner documents 

their verification electronically (i.e., on the ECCF or in the specimen record in 

the laboratory information system).

– Step 5a contains— 

o Primary (A) specimen test results including confirmatory concentration 

(ng/mL) of each drug or drug metabolite reported for a Positive result; 
4-6 

o Certifying technician’s or certifying scientist’s printed name; 

o Certifying technician’s or certifying scientist’s signature;

o Date of result certification;

o Comments on the Remarks line (as appropriate) as follows:

• Comments as required by HHS for specimens reported as adulterated, 

rejected for testing, invalid result, substituted or (for urine) dilute (see 

Table 3); and

• Observations or explanatory comments recorded by laboratory or IITF 

staff concerning the specimen.

o Name and address of the test facility reporting the specimen results (if not at 

the top of the Federal CCF).

– If the split (B) specimen (Bottle/Tube B) was tested, Step 5b contains— 

o Name and address of the split testing laboratory;

o Results for the split (B) specimen, with the certifying scientist’s signature and 

printed name and the date of certification; and 

o If a separate Split Specimen Report was sent, a reference to the separate 

laboratory report is recorded in the Reason line in Step 5b of the Federal CCF

Copy 1. 

■ For a split (B) specimen, the laboratory’s Split Specimen Report was properly 

completed and contains, at a minimum, the following information and laboratory 

result:

– Laboratory name and address;

– MRO’s name and fax number;

– Specimen ID number; 

– Laboratory accession number;

– Donor’s ID (SSN or employee ID number), if provided; 

– RECONFIRMED result requires the following:

o For RECONFIRMED drug results: the specific drug analyte(s) reconfirmed;

o For RECONFIRMED ADULTERATED results: adulterated with the 

measurand(s) reconfirmed; and

o For RECONFIRMED SUBSTITUTED: substituted with the biomarker or (for 

urine) the creatinine and specific gravity values. 

– FAILED TO RECONFIRM result(s) require the following:

o For FAILED TO RECONFIRM drug results: the specific drug analyte(s) not 

reconfirmed;
4-7 

o For FAILED TO RECONFIRM adulterated results: NOT ADULTERATED 

with the measurand(s) not reconfirmed; and

o (for urine) for FAILED TO RECONFIRM substituted results: NOT 

SUBSTITUTED.

– FAILED TO RECONFIRM drug results requires the following:

o The specimen validity tests performed; and 

o The results of all specimen validity tests (screening/differential, initial, 

confirmatory), and the determination based on specimen validity testing (i.e., 

adulterated with adulterant/reason, invalid [with required comment], or 

substituted with confirmatory biomarker or creatinine and specific gravity 

values).

– Certification statement;

– Certifying scientist’s signature, printed name, and certification date;

– Required comments/explanatory remarks for reconfirmed results; and

– Required comments/explanatory remarks for failed to reconfirm results.

■ Memoranda for the record from the collector, laboratory, or IITF to address any 

correctable discrepancies identified (see Section 4.1.3, Federal CCF or Specimen 

Errors);

■ The computer-generated electronic report (if any) contains the HHS-required 

information as follows:

– Test facility name and address;

– Federal agency name;

– MRO’s name;

– Specimen ID number;

– Donor’s ID from the Federal CCF (e.g., SSN, employee ID number); 

– Collector’s name and telephone number;

– Reason for test (if provided); 

– Date of collection;

– Date received at IITF and/or laboratory; 

– Certifying technician’s or certifying scientist’s name;

– Date certifying technician or certifying scientist released the results;

– Federal CCF result(s) annotated; and

– Additional comments concerning the specimen’s testing and processing, as listed 

in the Remarks line of the Federal CCF.
4-8 

■ The information on the computer-generated electronic report (if any) is consistent 

with that on the test facility copy of the Federal CCF (Copy 1). 

4.1.3 Federal CCF or Specimen Errors

A laboratory, MRO, or IITF may identify errors made on a Federal CCF. A 

laboratory or IITF may identify a problem with a specimen during processing. (See Section 

4.1.5 for MRO actions in response to identified problems.) The various types of errors are 

outlined below: 

1. Fatal flaws that result in specimen rejection by the IITF or laboratory and test 

cancellation by the MRO include the following: 

■ Specimen ID numbers on the Federal CCF and the label/seal of either the primary 

(Bottle/Tube A) or split specimen (Bottle/Tube B) do not match, or the number is 

missing on either the Federal CCF or the primary or split specimen bottle label/seal.

■ The specimen bottle label/seal is missing, misapplied, broken, or shows evidence of 

tampering on the primary specimen (Bottle/Tube A) and the split specimen 

(Bottle/Tube B) cannot be redesignated as the primary specimen.

■ For oral fluid, the primary (A) specimen was collected using an expired device (i.e., 

the device expiration date precedes the collection date) and the split (B specimen 

cannot be re-designated as the primary (A) specimen. 

■ The collector’s signature and printed name are omitted from the Federal CCF.

■ For oral fluid, the collector failed to document observation of the volume indicator(s) 

at the time of collection for a collection device containing a diluent. 

■ There is insufficient specimen volume for testing in the primary specimen 

(Bottle/Tube A), and the split specimen (Bottle/Tube B) cannot be redesignated as the 

primary specimen.

■ The accessioner at the laboratory or IITF failed to document the primary (Bottle/Tube 

A) specimen seal condition on the Federal CCF and the split specimen (Bottle/Tube 

B) cannot be redesignated as the primary specimen.

■ In addition to documenting seal condition on the Federal CCF, the laboratory may 

require a proactive entry by the accessioner to document the seal condition by 

choosing either intact or not intact in the laboratory information management system 

(LIMS). It is not sufficient for the accessioner to make an entry only when the seal is 

not intact. To recover the accessioner’s omission of the required seal condition 

information on the Federal CCF, the certifying technician/scientist may recover the 

omission with an MFR and must verify that the seal condition was proactively 

documented in the LIMS at the time of accessioning.
4-9 

■ The specimen was received at the HHS-certified laboratory or IITF without a Federal 

CCF. 

■ The specimen was collected using an unapproved ECCF system. 

■ The Federal CCF was received at the HHS-certified laboratory or IITF without a 

specimen.

■ The collector performed two separate collections using one Federal CCF. 

■ The HHS-certified laboratory or IITF identified a flaw other than those above that 

prevents testing or affects the forensic defensibility of drug test and cannot be 

corrected. 

■ The specimen ID number on either the primary or split specimen bottle/tube label/seal

is not unique. 

■ The collector used an expired collection device for the primary oral fluid specimen 

and Tube B cannot be redesignated as the primary (A) specimen.

■ For oral fluid specimen collection devices with diluent, the collector did not 

document observation of the device volume indicator(s) at the time of collection. This 

is not a fatal flaw for undiluted (neat) oral fluid specimens.

2. Correctable discrepancies that result in specimen rejection and/or cancellation unless 

corrected by a memorandum for the record (MFR) from the collector or IITF (as applicable) 

include the following:

■ The collector failed to sign the Federal CCF (but the printed name is present). The 

laboratory must hold the specimen and attempt to obtain a memorandum for the 

record to recover the collector’s signature. If the error is corrected, the test result is 

reported. If the signature is not recovered after at least 5 business days, the laboratory 

must report rejected for testing and indicate the reason on the Federal CCF.

■ The collector used a non-federal form or an incorrect/expired Federal CCF (and the 

specimen was tested in accordance with Mandatory Guidelines requirements). The 

laboratory must contact the collector for an MFR to explain the use of the nonFederal or incorrect/expired Federal CCF and ensure that all required information is 

present. If the explanatory MFR is not obtained after at least 5 business days, the 

laboratory must report a rejected for testing result and indicate the reason on the 

Federal CCF. 

■ For an oral fluid specimen collected using a non-Federal or expired Federal CCF, the 

collector must document observation of the device volume indicator(s) on the Federal 

CCF or an MFR at the time of the collection and send the documentation to the 

laboratory with the specimen. 
4-10 

■ The IITF redesignated the primary specimen (Bottle A) and split specimen (Bottle B), 

but failed to include a comment on the Federal CCF. The laboratory must contact the 

IITF for an MFR to explain the redesignation. If the explanatory MFR is not obtained 

after at least 5 business days, the laboratory must report a rejected for testing result 

and indicate the reason on the Federal CCF. 

■ The specimen was received with Federal CCF Copy 2-5, the accessioner documents 

receipt on an internal chain of custody form and the specimen is placed on hold and is 

not tested. The laboratory must contact the collector to send the Federal CCF Copy 1 

with collector wet signature along with an explanatory MFR. If the Federal CCF 

Copy 1 and the explanatory MFR are not obtained after at least 5 business days, the 

laboratory must report a rejected for testing result and indicate the reason on the 

Federal CCF.

■ The specimen was received with reprint ECCF without the collector’s wet signature, 

the accessioner documents receipt on the ECCF received and the specimen is placed 

on hold and is not tested. The laboratory must contact the collector to send the ECCF 

with the collector’s wet signature and printed name along with an explanatory MFR. 

If the ECCF and the explanatory MFR are not obtained after at least 5 business days, 

the laboratory must report a rejected for testing result and indicate the reason on the 

Federal CCF.

■ If the collector cannot provide the required documentation (e.g., no longer works at 

the collection site) for the errors described in the above paragraphs, the collection site 

supervisor may provide the documentation. For example, for an ECCF, the collection 

site supervisor may sign the authoritative copy (if available) OR a reprint of Copy 1 

using their wet signature verifying that the collector who signed the Federal CCF 

performed the collection. The collection site supervisor must send the signed Copy 1 

to the laboratory via courier/mail. Both the collector’s electronic signature and printed 

name must be on Copy 1. The collection site supervisor may also send the required 

MFR to the laboratory. 

■ The laboratory must send a copy of the MFR received from the collector to correct 

the error of using the wrong CCF to the MRO or, alternatively, include a comment on 

the CCF and electronic report identifying the error and noting that an MFR was 

received. The specimen is rejected if an MFR is not obtained.

3. Federal CCF omissions and discrepancies that are considered insignificant when they 

are infrequent (e.g., when a collector or a laboratory or an IITF staff member does not make 

the error more than once a month). Examples include, but are not limited to: 

■ Incorrect laboratory or IITF name and address;

■ Incomplete/incorrect/unreadable employer name or address;

■ When the Federal CCF does not include an MRO company name, the MRO name is 

missing or incorrect; 
4-11 

■ Incomplete/incorrect MRO address;

■ Transposition of numbers in the donor’s social security number or ID number; 

■ Missing/incorrect telephone or fax number;

■ A “Reason for Test” box is not marked;

■ A “Drug Tests to be Performed” box is not marked; 

■ For oral fluid, the Oral Fluid” box is not marked (i.e., by the collector or laboratory) 

■ A box is not marked under Step 2, “Collection”; 

■ For oral fluid, the box titled “Each Device Within Expiration Date?” is not marked

■ The “Observed” box is not marked for an observed urine collection;

■ No collection site address; (When no collection information is on the Federal CCF, 

the laboratory must process the specimen. If no MFR obtained after at least 5 days, 

the laboratory will report results with comment e.g., “unable to recover missing 

information.”) 

■ The collector’s printed name is missing, but the collector’s signature is properly 

recorded;

■ The time of collection is not indicated;

■ The date of collection is not indicated; 

■ Incorrect/missing name of delivery service; 

■ Donor’s name included on the test facility copy of the Federal CCF or on seal labels; 

■ Signature present without printed name (i.e., of collector, accessioner, certifying 

technician, or certifying scientist);

■ The collector has changed or corrected information by crossing out the original 

information but did not date and initial the change. 

■ No urine specimen temperature block mark and no explanatory comment in the 

Remarks line (see Section 4.1.4, Federal CCF Remarks). The laboratory must contact 

the collector for an MFR to explain the omission. If, after at least 5 business days, the 

collector cannot provide a MFR to attest to the fact that the collector did measure the 

specimen temperature, the HHS certified laboratory or IITF may report the test result 

for the specimen but indicates that the collector could not provide a memorandum to 

recover the omission.
4-12 

■ Omitted/incorrect specimen type on Federal CCF – accessioner marks correct 

checkbox, and (if marked) lines through incorrect checkbox, initials and dates the 

edit.

■ Incorrect Federal CCF or ECCF expiration date for oral fluid collection device – the 

accessioner makes a forensic edit to record the date that is on the tube (See Chapter 4, 

Section 4.1.2, Copy 1, step 4). 

4. Administrative errors that are judged by the MRO to have a significant impact on the 

forensic defensibility of the results and may require the MRO to cancel a test unless 

corrected by an MFR. Examples include, but are not limited to: 

■ The donor’s signature is missing on the MRO Copy 2 of the Federal CCF and the 

collector failed to provide a statement that the donor refused to sign the form. The 

MRO must contact the collector for an explanatory MFR. If the MRO does not 

receive the MFR after waiting at least 5 business days, the test is cancelled.

■ There is no certifying scientist signature on the Federal CCF for a positive, 

adulterated, invalid, or substituted specimen. The MRO must contact the certifying 

scientist for an explanatory MFR that the review was properly conducted. If the MRO 

does not receive the MFR after waiting at least 5 business days, the test is cancelled.

■ The electronic report from the laboratory did not contain all required data elements 

for a drug positive, adulterated, invalid, or substituted specimen. The MRO must 

contact the laboratory for a corrected report. If the MRO does not receive the 

corrected report after waiting at least 5 business days, the test is cancelled.

5. Report discrepancies may be identified by a laboratory or an IITF after a report has been 

sent to the MRO or may be identified by an MRO during administrative review. The IITF or 

laboratory must reissue the report and/or send an MFR to document the correct information 

in the specimen records. Examples include:

■ Incorrect or outdated Federal CCF information (e.g., account number); 

■ Data entry errors due to illegible or misread Federal CCF information;

■ Data review or transcription errors by the certifying technician or certifying scientist;

■ A discrepancy between the Federal CCF and electronic report; 

■ The accessioner failed to identify an oral fluid collection incorrect expiration date and 

the device was not expired; or 

■ Test cancelled – the accessioner failed to identify an incorrect expiration date and the 

device was expired.
4-13 

4.1.4 Federal CCF Remarks

Collectors are required to include comments on the Remarks line in Step 2 (the 

collector’s section) of the Federal CCF to document any unusual donor behavior or incidents 

occurring during the collection. Laboratory and IITF 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), as well as explanatory reporting comments 

required by the program (e.g., the basis for reporting a specimen as adulterated, the basis for 

reporting a specimen as invalid, the reason for rejection, or [for urine] creatinine and specific 

gravity values supporting a substituted result, —see Table 4 at the end of this manual).

The MRO evaluates whether the information provided on the Federal CCF Remarks 

line has a significant impact on the forensic defensibility of the drug test results. If the MRO 

believes the forensic defensibility of the results is affected, the MRO either attempts to obtain 

an MFR or cancels the test.

4.1.5 Actions Based on Administrative Review 

1. When a fatal flaw is identified (as defined in Section 4.1.3-1), the following may occur: 

■ If a laboratory or IITF identifies the error, the IITF or laboratory rejects the specimen 

and reports the specimen as rejected for testing to the MRO. The reason for rejection 

is included on the Federal CCF Copy 1 and any other report to the MRO. 

■ If the MRO receives a rejected for testing specimen report or identifies a fatal flaw 

during review, the MRO cancels the test.

■ The MRO reports the cancellation and the reason to the Federal agency, which then 

determines whether or not to immediately collect another specimen for the same type 

(i.e., urine or oral fluid) from the donor.

2. When a correctable discrepancy (as defined in Sections 4.1.3-2 and 4.1.3-4) by the 

collector or IITF is identified by the IITF, the laboratory, or the MRO, the responsible party 

is notified to provide an MFR to address the error.

■ For a missing collector signature, the following may occur:

– If the collector provides an MFR, the IITF or laboratory includes a copy of the 

MFR with the report to the MRO. The MRO reports the verified result to the 

Federal agency and maintains the MFR in the files for the specimen.

– If the collector does not provide an MFR, the IITF or laboratory holds the 

specimen for a minimum of 5 business days after requesting the MFR, then 

reports the specimen as rejected for testing and discards the specimen. The reason 

for rejection is included on the report(s) to the MRO. The MRO cancels the test 
4-14 

and notifies the Federal agency of the cancelled test and the reason for 

cancellation.

■ For a regulated specimen submitted with a non-Federal CCF or expired Federal CCF, 

the following may occur: 

– For an oral fluid specimen collected using a non-federal or expired Federal CCF, 

the collector must document observation of the device volume indicator(s) on the 

Federal CCF or an MFR at the time of the collection and send the information to 

the laboratory with the specimen. The laboratory will reject the specimen if the 

collector did not document observation of volume indicator(s) at the time of 

collection. This requirement applies to oral fluid specimens collected using a 

device with a diluent, not to neat oral fluid specimens. 

– The collector must provide the laboratory with an MFR explaining why the 

incorrect form was used and providing all information required on the Federal 

CCF.

■ For a regulated specimen submitted with an incorrect Federal CCF, the following 

may occur:

– If the laboratory received Copy 2-5 of the Federal CCF, the laboratory may not 

begin testing the specimen until it receives Copy 1 with the collector’s wet 

signature and an MFR explaining the receipt of the incorrect copy. 

– The laboratory must either send a copy of the MFR to the MRO or include a 

comment on the CCF and electronic report identifying the error and noting that an 

MFR was received. The specimen is rejected if the signed Copy 1 and an MFR 

are not obtained. 

■ For a regulated specimen submitted with a non-Federal form, the following may 

occur: 

– If the collector provides an MFR and the specimen was tested in accordance with 

the UrMG or OFMG, the IITF or laboratory will report the specimen based on test

results. The MRO reports the verified result to the Federal agency and maintains 

the MFR in the files for the specimen.

– If the collector provides an MFR but the specimen was tested as nonregulated 

using procedures different from those used for regulated specimens, the 

laboratory or IITF must follow guidance provided in the NLCP Manual for Urine 

Laboratories and the NLCP Manual for Oral Fluid Laboratories (Use of NonRegulated CCF) for use of a non-regulated CCF for a regulated specimen and 

requests to upgrade a non-regulated specimen to a regulated test. 

If the specimen is negative for all drugs or positive only for a regulated analyte, 

the laboratory must reanalyze the specimen using regulated procedures after 

receiving a signed request from the MRO. For reanalyzed specimens, the 

laboratory or (for urine) IITF may send an MFR with the certification statement 

from the Federal CCF and the certifying scientist’s signatures, name, and date.
4-15 

The MRO reports the verified result to the Federal agency and maintains the MFR 

in the files for the specimen. 

If the specimen is positive for a non-regulated analyte, the MRO is not allowed to 

request an upgrade to a regulated test. The laboratory must reject the request and 

not re-analyze the specimen. If a laboratory is unable to change a specimen from 

non-regulated to regulated, the laboratory must reject the specimen. If the 

specimen is reported as rejected for testing, the IITF or laboratory discards the 

specimen and includes the reason for rejection on the report(s) to the MRO. The 

MRO cancels rejected tests and notifies the Federal agency of the cancelled test 

and the reason for cancellation. 

Use of Non-Regulated ECCF:

For requests to change a non-regulated test collected with an ECCF to a regulated 

test using a combination electronic/paper CCF Option 1: 

– If the ECCF system is the same as HHS-approved system, the specimen can be 

reported as regulated if the following required documents are obtained: 

o Laboratory MFR signed by the RP attesting that the ECCF system is same as 

the HHS-approved system; and 

o MFR from collector that explains the use of the incorrect form. 

– If the ECCF system is not the same as HHS-approved system and specimen 

collection is not post-accident or reasonable suspicion/cause, it cannot be changed 

to regulated.

– If the ECCF system is not the same as HHS-approved system and specimen 

collection is post-accident or reasonable suspicion/cause, the laboratory must 

notify the NLCP and the Federal agency for guidance. 

– For requests to change a non-regulated test collected with an ECCF to a regulated

test using a combination electronic/paper CCF Option 2: 

– If the ECCF system is the same as HHS-approved system and the authoritative 

copy was received with specimen, the specimen can be reported as regulated if the 

following required documents are obtained: 

o Laboratory MFR signed by the RP attesting that the ECCF system is same as 

the HHS-approved system; and 

o MFR from collector that explains the use of the incorrect form. 

– If the ECCF system is the same as the HHS-approved system and the authoritative 

copy was not received with specimen, the specimen can be reported as regulated 

if the following required documents are obtained: 

o Laboratory MFR signed by the RP attesting that the ECCF system is same as 

the HHS-approved system; 

o MFR from collector that explains the use of the incorrect form and explains 

why the authoritative copy was not sent 
4-16 

Note: The laboratory must obtain Copy 1 of the CCF with the collector’s wet 

signature prior to testing the specimen. 

­ If the ECCF system is not the same as HHS-approved system and specimen 

collection is not post-accident or reasonable suspicion/cause, the laboratory will 

not change it to regulated and will reject the specimen. 

­ If the ECCF system is not the same as HHS-approved system and specimen 

collection is post-accident or reasonable suspicion/cause, the laboratory will 

notify NLCP and the Federal agency for guidance. 

To change a regulated specimen (submitted using a Federal CCF) to a nonregulated test the laboratory must take actions as follows:

­ If the laboratory has not performed any testing on the specimen, the laboratory 

must request an MFR from the collector (or collection site supervisor if the 

collector is not available) explaining the use of the incorrect form. Once the MFR 

is received, the laboratory will process the specimen using the laboratory’s 

procedures for non-regulated specimens and report the specimen as a nonregulated drug test. 

­ If the laboratory has performed any testing on a specimen collected using the 

Federal CCF, the laboratory must report the specimen as a regulated specimen to 

the MRO. The laboratory must take action as follows: 

o The laboratory may “downgrade” specimens reported as Negative, Invalid 

Result, or Rejected for Testing to a non-regulated test upon receiving a signed 

request from the MRO.

o For specimens reported to the MRO as Positive and/or Adulterated, the 

laboratory must take additional action as follows:

• The laboratory must consult with the Federal agency, 

• The laboratory must provide the confirmed test result and the specimen 

identification number to the Federal agency, and 

• If the Federal agency determines that the test is non-regulated rather than a 

regulated test, the laboratory must include a statement regarding that 

determination in the specimen records. 

■ If the collector does not provide an MFR for the situations described above, the IITF 

or laboratory holds the specimen for a minimum of 5 business days after requesting 

the MFR, then reports the specimen as rejected for testing and discards the specimen. 

The reason for rejection is included on the report(s) to the MRO. The MRO cancels 

the test and notifies the Federal agency of the cancelled test and the reason for 

cancellation.

■ For a regulated urine specimen received at an HHS-certified laboratory with 

redesignated primary (A) specimen (Bottle A) and split (B) specimen (Bottle B) 
4-17 

bottles and no IITF explanatory comment on the Federal CCF, the laboratory must 

proceed as follows: 

­ If the IITF provides an MFR, the laboratory includes a copy of the MFR with the 

report to the MRO. The MRO reports the verified result to the Federal agency and 

maintains the MFR in the specimen records.

­ If the IITF 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 for testing and discards the specimen. The reason for rejection is 

included on the report(s) to the MRO. 

3. When a significant administrative error is identified by the MRO (as defined in Section 

4.1.3-4), the MRO notifies the responsible party to provide an MFR to address the error. If 

the MFR is not provided within at least 5 business days after this notification, the MRO must 

cancel the test.

4. When a report discrepancy is identified (as defined in Section 4.1.3-5), the IITF or 

laboratory must reissue a report and/or provide an explanatory MFR, depending on the 

significance of the discrepant information. A reissued report will be either— 

■ A corrected report when the IITF or laboratory has changed specimen ID or result 

(e.g., corrected donor’s ID or test facility accession number; a positive result changed 

to negative; a positive result for a different drug; a substituted result changed to 

invalid). The reissued report must be identified as a “corrected report” and have the 

retransmission date on the report; or 

■ An amended report when the IITF or laboratory has changed information other than 

the specimen ID or result (e.g., employer name, account number) or has provided 

additional information for a reported specimen (e.g., additional quantitative results, 

methamphetamine enantiomer results for a specimen reported as positive for 

methamphetamine). The report will be reissued with the revised/new information.

5. The MRO should document and monitor the frequency of errors made by collectors, IITF 

staff, and laboratory staff. 

HHS-certified IITFs and laboratories have been instructed to note and report test 

results to the MRO when an identified error was caused by the collector. HHS-certified 

laboratories have also been instructed to note and report to the MRO when they have 

identified procedural or documentation errors made by IITF staff. The MRO also may 

identify errors during an administrative review. The MRO should maintain a record of such 

errors. When the MRO identifies frequent errors (i.e., more than once a month) by an 

individual collector or staff member at an IITF or a laboratory— 

■ The MRO notifies the responsible party of the errors;
4-18 

■ The collector/collection site, IITF, or laboratory takes appropriate corrective actions 

(e.g., revises procedures, retrains the individual and other staff) and submits a copy of 

documentation of the action(s) to the MRO; and 

■ The MRO maintains the documentation of error notification and corrective action 

response in its records. 

■ If errors continue after MRO notification, the MRO reports the collector/collection 

site, IITF, or laboratory to the Federal agency and the NLCP. 

4.1.5.1 Procedure to change the Donor ID Number. 

The Donor ID Number (e.g., social security number or employee ID number) is 

recorded in Step 1 of the Federal CCF. If the MRO identifies a difference between the Donor 

ID Number on the Federal CCF and the number in the employer or MRO records (e.g., a 

transposition of numbers), the ID may be corrected. In such cases, the MRO may include a 

memorandum for the record (MFR) in their records for that drug test to explain the 

discrepancy. The MRO may also request that the laboratory change the Donor ID Number in 

the laboratory records to the different ID number by submitting an MFR to the laboratory.

That MFR must include an explanation of the reason for the change. The Federal CCF is not 

to be modified. The laboratory will provide a report or corrected report with the updated ID 

number and the reason for the change. 

4.1.6 Use of an Expired Federal CCF

The 2023 Federal CCF was approved for use on May 1, 2023. Additional information 

is available at https://www.reginfo.gov/ (enter the OMB number 0930-0158 in the search 

area). A proof of the 2023 Federal CCF and Guidance for its use are available for viewing on 

the SAMHSA website: https://www.samhsa.gov/workplace. Because the 2023 Federal CCF 

is the same as the expired 2020 Federal CCF, use of the 2020 Federal CCF is approved. 

IITFs and laboratories must treat the use of the 2017 Federal CCF for urine specimens as a 

correctable discrepancy. The 2017 Federal CCF is not authorized for use with oral fluid 

specimens.

4.2 Donor Interview

The MRO must attempt to contact and interview the donor when the donor’s 

specimen is reported by the laboratory as positive, adulterated, substituted, and/or invalid. 

The MRO should attempt to contact a donor promptly after receiving the report (usually 

within 24 hours). The MRO, or MRO staff, should make at least three attempts to contact a 

donor within a 72-hour period. MRO staff members are limited to conducting the initial 

contact with the donor in order to schedule the discussion between the MRO and the donor. 
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Federal CCFs may include the following donor contact information: donor’s daytime and 

evening telephone numbers (e.g., cell phone number, direct work telephone number, home 

telephone number); work e-mail address; and personal e-mail address. MROs should utilize 

all of the contact information made available on the Federal CCF. When contacting donors, 

MROs should also 1) communicate that the MRO is authorized to discuss the donor’s drug 

test result under Section 13.5 of the Mandatory Guidelines, 2) provide notice to the donor to 

contact the MRO within specified timeframe, and 3) provide the donor with the MRO’s 

contact information. For all attempts to contact a donor by phone, MROs should document 

the time, date, telephone number used, and whether a message was left for the donor. MROs 

should also document when a donor declines an opportunity to discuss drug testing results 

with the MRO. 

If a donor does not contact the MRO within five business days of the first attempt, or 

otherwise expressly declines an opportunity to discuss a drug test result with the MRO, the 

MRO should follow the procedures for when a donor fails to provide a legitimate medical (or 

other) explanation for a drug test result. (For example, see sections 13.5(d) through (f) in the 

UrMG and sections 13.5(c) through (e) in the OFMG.) 

1. The interview process occurs as follows:

■ The donor must be positively identified by the MRO or staff requesting that the donor 

provide identifying information (e.g., employee ID number, SSN) 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.) 

■ The MRO informs the donor, prior to obtaining any information, that medical 

information provided during the interview that affects medical qualification or safety 

may be disclosed to the Federal agency. 

■ The MRO informs the donor of the laboratory test result(s).

■ The MRO takes action based on the donor’s response, as follows:

– If the donor admits illicit use of a drug consistent with the test results or admits 

that he/she tampered with the specimen, advise the donor that the test result will 

be reported to the Federal agency. 

– If the donor does not admit to illicit use of a drug or specimen tampering, ask the 

donor if there is any possible explanation for the test result(s):

o If the donor provides a legitimate explanation (e.g., claims that a positive 

result was due to a prescribed medication, that the positive result was due to a 
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drug administered by a health care professional, or that a medication may 

have interfered with the drug test), the donor must provide appropriate 

supporting documentation as determined by the MRO. 

o If the donor has no legitimate medical explanation for the result, advise the 

donor that the test result will be reported to the Federal agency. 

■ For positive, adulterated, or substituted results: Inform the donor that they may have 

the split (B) specimen tested at a second certified laboratory. The split specimen test 

request must be made within 72 hours of the interview with the MRO. NOTE: donors 

are not allowed to request split (B) specimen testing when the primary (A) specimen 

was reported as invalid as described in Chapter 4, Section 4.4. 

■ If the donor requests split (B) specimen testing, use the procedures described in 

Chapter 4, Section 4.4 (Split Specimen Tests) to direct the laboratory to send the split 

specimen to another certified laboratory for confirmatory testing.

■ If the donor does not request testing of the split (B) specimen, document that the 

donor was informed of the opportunity to test the split specimen. 

■ The reporting of the primary (A) specimen result occurs immediately after the MRO 

has reviewed the information contained on Copy 2 and Copy 1 of the Federal CCF (as 

described above) and has completed the interview with the donor and received all 

documentation necessary for the result determination. The Federal agency is notified 

of the result and whether the donor has chosen to have the split (B) bottle tested at a 

second laboratory. 

2. Refusal to Test

The UrMG and OFMG specify the circumstances under which a collector or an MRO 

reports a “refusal to test” to the Federal agency. The Federal agency will review for 

disciplinary action against the donor, up to and including removal from Federal employment. 

An applicant’s refusal to take a pre-employment test may result in non-selection for Federal 

employment. The MRO reports a “refusal to test” to the Federal agency in the following 

instances where: 

■ The donor refuses to participate at any point in the drug testing process, including: 

■ Fails to appear for any test within a reasonable time, as determined by the Federal 

agency, consistent with applicable agency regulations, after being directed to do so by 

the Federal agency; 

■ Fails to remain at the collection site until the collection process is complete;

■ Fails to provide a specimen (e.g., urine, oral fluid, or another authorized specimen 

type) for any drug test required by the Mandatory Guidelines or Federal agency

regulations; 
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■ Fails to provide a sufficient amount of urine or oral fluid when directed, and it has 

been determined, through a required medical evaluation, that there was no legitimate 

medical explanation for the failure; 

■ Fails or declines to participate in an alternate specimen collection as directed by the 

Federal agency or collector; 

■ Fails to undergo a medical examination or evaluation, as directed by the MRO as part 

of the verification process. In the case of a Federal agency applicant/pre-employment 

drug test, the donor is deemed to have refused to test on this basis only if the Federal 

agency applicant/pre-employment test is conducted following a contingent offer of 

employment. If there was no contingent offer of employment, the MRO will cancel 

the test; 

■ Fails to cooperate with any part of the testing process (e.g., disrupt the collection 

process; fail to wash hands or rinse their mouth after being directed to do so by the 

collector; refuse to provide a split specimen); 

■ Brings materials to the collection site for the purpose of adulterating, substituting, or 

diluting the specimen;

■ Attempts to adulterate, substitute, or (for urine) dilute the specimen;

■ Admits to the collector or MRO that they have adulterated or substituted the

specimen; 

■ Fails to permit the observation or monitoring of provision of a urine specimen in a 

direct observed or monitored urine collection; or 

■ Possesses or wears a prosthetic or other device that could be used to interfere with the 

urine collection process. 

■ The drug test result is verified by the MRO as adulterated or substituted.

Exception: For a Federal agency applicant/pre-employment test, if the donor does not 

undergo a medical evaluation and there has been no offer of employment contingent upon the 

drug test, the MRO cancels the test. For a pre-employment drug test, the collection is 

initiated at the time the donor receives or selects a specimen collection container. If the donor 

departs the collection site after this point, the collector reports a refusal to test.

When the MRO reports a “refusal to test” based on the donor’s refusal to participate 

during the drug testing process, the MRO must immediately notify the Federal agency’s 

designated representative using a secure method (e.g., telephone, fax, email). 
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4.3 Handling of Multiple Results or Multiple Collections During the Same Testing 

Event

1. The HHS-certified laboratory may report multiple results for a primary (A) specimen.

See also Appendix Tables 4 and 5 

■ The MRO must report all verified positive, adulterated, “refusal to test” or 

substituted results to the agency.

■ If an invalid result was reported in conjunction with a positive, adulterated, or 

substituted result, do not report the verified invalid result to the Federal agency at this 

time. The MRO reports the verified invalid result(s) for the primary (A) urine 

specimen only if the split specimen is tested and reported as a failure to reconfirm.

2. In the event the MRO is aware that two (or more) specimens were collected from one 

donor during a single collection event and were submitted to the laboratory for testing, the 

MRO must reconcile the testing results as follows:

■ If both specimens were verified negative, report the result as negative (single report). 

■ If one specimen was verified negative and the other was not (i.e., the specimen was 

verified as positive, adulterated, invalid, and/or substituted or (for urine) 

negative/dilute), report only the verified result(s) other than negative. 

■ If both specimens were verified as positive, adulterated, and/or substituted, report all 

results. For example, if verified, report a positive and the refusal results to the Federal 

agency. 

■ If one specimen has been verified and the HHS-certified laboratory has not reported 

the result(s) of the other specimen— 

– Report verified result(s) of positive, adulterated, or substituted immediately and 

do not wait to receive the result(s) of the other specimen; and

– Do not report a verified result of negative, negative/dilute, or invalid for the first 

specimen to the Federal agency. Hold the report until the results of all specimens 

have been received and verified.

■ When the HHS-certified laboratory reports an invalid result for one or more 

specimens, follow the procedures in Section 4.3.1 above. 

4.4 Split Specimen Tests

Note: Donors are not authorized to request split (B) specimen testing of primary (A) 

specimens reported as invalid. For a positive, adulterated, or substituted result reported on a 

primary (A) specimen, a donor may request through the MRO that the split (B) specimen be 

tested by a different (i.e., second) HHS-certified laboratory to verify the result reported by 

the first HHS-certified laboratory. 
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If a donor chooses not to have the split (B) specimen tested by a second HHScertified laboratory, a Federal agency may have a split (B) specimen retested as part of a 

legal or administrative proceeding to defend an original positive, adulterated, or substituted 

result (see also Sections 3.1.5.1 and 3.1.5.2). 

The following are rules for handling split specimen requests for positive, adulterated, 

or substituted specimens: 

■ The MRO must inform the donor that the donor has the opportunity to request testing 

of the split (B) specimen when the MRO informs the donor that the primary (A) 

specimen is being reported as positive, adulterated, or substituted to the Federal 

agency. The donor has 72 hours from the time of his/her notification of the nonnegative result to request the split (B) specimen test. The MRO must document the 

donor’s verbal request in the MRO records.

■ The MRO must request testing of the split (B) specimen in writing (i.e., a 

memorandum or letter format). For oral fluid split (B) specimen testing, the

laboratory selection must be compatible with the split (B) specimen collection device 

type. The written request may be mailed, faxed, or electronically sent to the 

laboratory where the primary (A) specimen was tested and must contain the following 

information: 

– MRO’s name and address (on MRO letterhead);

– Laboratory name and address (i.e., Laboratory A) where the primary specimen 

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 testing 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 

test the split (B) specimen.

■ Laboratory B may be selected by the MRO, the Federal agency, or the donor. In most 

instances when split (B) specimen testing is requested, the first laboratory will have 

blanket purchase agreements with two or three other certified laboratories to facilitate 

the billing and payment process.

■ If the split specimen cannot be tested by another HHS-certified laboratory (e.g., 

insufficient volume, lost in transit, split (B) specimen not available, or another 

certified laboratory to perform the test): 

– The MRO reports to the Federal agency that the test is cancelled and the reason 

for cancellation;
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– The MRO directs the Federal agency to immediately collect another specimen 

using direct observation, with no notice given to the donor until immediately 

before the collection; or

– If the test is cancelled because no other certified laboratory tests for the specific 

adulterant, the MRO notifies the appropriate regulatory office.

■ If Laboratory B cannot complete testing (e.g., due to interference with the test 

method), but believes a measurand is present, the laboratory will consult the NLCP to 

identify another HHS-certified laboratory that may be able to perform the test(s) 

needed to reconfirm or refute the primary (A) specimen results. Laboratory B will 

contact the MRO and provide information to assist the MRO in deciding whether to 

send the split specimen to a third laboratory (Laboratory C) and, if so, to select the 

HHS-certified laboratory to serve as Laboratory C. The MRO must submit a signed 

request to send the split specimen to a third laboratory. (If the split specimen cannot 

be tested by another HHS-certified laboratory, the MRO follows the procedures 

outlined above.) 

■ The split testing laboratory reports split (B) specimen test results to the MRO using a 

copy of Copy 1 of the Federal CCF. The laboratory may also provide a computergenerated electronic report and the laboratory’s urine or oral fluid Split Specimen 

Report form. The laboratory’s Split Specimen Report is required for specimens 

reported as failed to reconfirm to provide additional information (e.g., specimen 

validity test results). The laboratory may send reports by courier or mail, or use 

various electronic means (e.g., fax, computer, secure electronic transmission). 

Transmissions of the reports must ensure confidentiality and the results must not be 

reported verbally by telephone. (See Chapter 6, Section 6.6, of this manual for 

requirements for the use of external service providers.) 

■ The MRO must take actions in response to the split testing laboratory’s reported 

results as outlined in Table 5 (Reference: Section 14.6 of the UrMG or Section 14.5 

of the OFMG).

■ The MRO reports the result to the Federal agency, but must not disclose the 

numerical values of drug test results to the agency. The MRO notifies the appropriate 

regulatory office of any failed to reconfirm test.

■ The MRO must report drug test results using the HHS-specified nomenclature 

published with the drug and biomarker testing panels. 

4.5 Interpretation and Result Verification

Chapter 5, Drug Information and Interpretation of Results, provides information on 

the drugs authorized for testing in Federal agency workplace programs, including the current 

Controlled Substances Act (CSA) schedules, signs/symptoms of abuse, and metabolism 

information. 
4-25 

SAMHSA has developed urine and oral fluid MRO Case Studies to illustrate MRO 

interpretation and result verification in various real-life scenarios. SAMHSA will review and 

update the case studies periodically based on reported incidents and issues raised in forensic 

workplace drug testing. The urine and oral fluid MRO Case Studies are available on the 

SAMHSA website: https://www.samhsa.gov/workplace/drug-testing. 

The MRO determines the drug test results based upon— 

■ Specimen type (e.g., urine or oral fluid) 

■ The results reported by the test facility; 

■ The donor’s explanation and supporting documentation; and 

■ The MRO’s medical assessment of the donor’s responses during the interview and 

physical signs during any face-to-face interview.

The MRO must report only verified results to the Federal agency. The MRO must not 

inform the Federal agency of a positive, adulterated, or substituted laboratory result if it has

been verified as negative. The MRO must not disclose drug concentration results to the 

agency. 

Table 4 describes MRO actions to be taken and required reports for primary (A) 

specimen results.

Table 5 describes MRO actions to be taken and required reports for split specimen 

(Bottle B) results.

4.5.1 IITF and Laboratory Results 

Laboratory and IITF staff are available to answer MRO questions concerning 

reported drug test results; however, IITFs and 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 

and IITFs to report Federal agency specimen results. Only HHS-certified laboratories are 

authorized to test oral fluid specimens for Federal agency workplace drug testing program. 

These criteria are described in Appendix D. 
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After receiving a drug test report, the MRO should contact the laboratory and/or IITF 

whenever additional information is needed. For example, the MRO may wish to clarify the 

IITF’s or laboratory’s administrative and analytical procedures or obtain 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 for a split specimen) must be made by the MRO in writing. The written 

request may be mailed, faxed, or electronically sent to the test facility.

The term “invalid result” is used for a specimen when a scientifically supportable test 

result cannot be established for the specimen due to an unidentified adulterant, an interfering 

substance, an abnormal physical characteristic, or an endogenous substance at an abnormal 

concentration (see Appendix D). A specimen is not reported as invalid result and negative. If 

an invalid result was reported in conjunction with a positive, adulterated, or substituted result 

(see Section 4.3 above), this is a separate result that does not refer to the validity of the 

testing. The laboratory will only report specimens as positive, adulterated, or substituted 

based on scientifically supportable test results. The MRO should contact the laboratory if 

there is any confusion about the reported results. The MRO reports the verified positive, 

adulterated, and/or substituted results to the agency, but reports the verified invalid result(s) 

for the primary (A) specimen only if the split specimen is tested and reported as a failure to 

reconfirm. 

When the MRO receives a sole 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). Exceptions to this 

rule are urine specimens reported as invalid based on creatinine and specific gravity results, 

on pH, or on a confirmatory nitrite test concentration > 200 and < 500 mcg/mL. It is unlikely 

that testing by another certified laboratory would provide a different result when a specimen 

is reported as invalid for these reasons.

When reviewing a specimen that meets invalid criteria based on oxidant testing, the 

MRO should be aware of the oxidant testing performed on the specimen. (See Appendix D, 

Specimen Reporting Criteria, for the oxidant tests used by HHS-certified laboratories.) When 

an MRO chooses to send an invalid-oxidant specimen to another laboratory for additional 

testing, the specimen should be tested at an HHS-certified laboratory with initial and 

confirmatory oxidant tests that will identify specific oxidants of interest (e.g., nitrite, 

chromium VI, and iodate). NLCP will provide assistance in identifying a laboratory that

meets these criteria.
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4.5.2 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 positive, adulterated, invalid, or 

substituted result. For the explanation to be accepted, the donor should provide acceptable 

supporting documentation to the MRO. If the alternative explanation for a positive, 

adulterated, invalid, or substituted result is acceptable and supported by documentation as 

outlined below, the MRO must verify the result as negative. 

4.5.3 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 should provide 

the medicine container with the appropriately labeled prescription (or the label from the 

container), a copy of the medical record documenting the valid medical use of the drug 

during the time of the drug test, or other information acceptable to the MRO. There is an 

additional concern in the case of invalid results. Certain antibiotics and nonsteroidal antiinflammatory drugs (NSAIDs) are known to cause immunoassay interferences. In those cases 

of potential interference, the verification of prescriptions or medical records should be 

completed in the same manner as a positive test result.

When reviewing the positive test result, the MRO will take all reasonable and 

necessary steps to verify the authenticity of all prescriptions, medical records, and other 

medical information provided by the donor that may be relevant to determining whether a 

legitimate medical explanation for the positive drug test exists. Contact with the prescribing 

physician may be helpful for the MRO in coming to this decision if the donor has provided 

any consent that may be required. A prescription may be verified by means such as: 

■ Photos sent by text, e-mail, or fax showing enough angled shots of the bottle label 

that the MRO can verify the name of the donor on the label, prescription number, 

name of the drug, prescribing physician, date filled, number of pills in the 

prescription, number of refills, and the pharmacy name, address, and contact 

information. 

■ A verification call to the pharmacy (after the MRO has verbally obtained the 

information in the item above from the donor and documented it on the MRO record). 

■ A copy of a pharmacy printout showing the medication dispensing history. 

■ A signed statement from, or phone discussion with, the prescribing physician. In all 

cases, the MRO should verify that the contact was with the prescribing physician. For 

example, the MRO may request the DEA number or state license number. For 
4-28 

additional security, the MRO may obtain the physician’s telephone number from 

another source (e.g., online search) and call the individual to verify identity. 

Under no circumstances can prescriptions be legally transferred from a different 

individual to a donor in the event the donor exhausts his or her own prescription medication, 

even if the other individual’s medication is identical and prescribed for the same medical 

condition (Controlled Substances Act Revised 2010, Pharmacist’s Manual, Section VIII—

Dispensing Requirements—Required Information for Prescription Labels. 

https://www.deadiversion.usdoj.gov/GDP/(DEA-DC-046R1)(EODEA154R1)_Pharmacist's_Manual_DEA.pdf). “Federal Food and Drug Administration 

regulations require that the label of any drug listed as a "controlled substance" in Schedules 

II, III, or IV of the CSA must, when dispensed to or for a patient, contain the following 

warning: “CAUTION: Federal law prohibits the transfer of this drug to any person other 

than the patient for whom it was prescribed.” 

A donor’s Schedule III, IV, or V prescription medication may be transferred between 

pharmacies for refill dispensing on a one-time basis only. However, Schedule II prescription 

medications are issued only once, do not have refills, and cannot be transferred between 

pharmacies (Title 21 Code of Federal Regulations, Part 1306.25—Transfer between 

pharmacies of prescription information for Schedules III, IV, and V controlled substances for 

refill purposes. https://www.dea.gov/drug-information/csa).

Executive Order (E.O.) 12564, section 3(a) requires the “head of each Executive 

agency” to “establish a program to test for the use of illegal drugs by employees in sensitive 

positions.” In addition, E.O. 12564, Sec. 7(c) defines, “illegal drugs” as “a controlled 

substance included in Schedule I or II, . . . the possession of which is unlawful under Chapter 

13 of that title. The term “illegal drugs” does not mean the use of a controlled substance 

pursuant to a valid prescription or other uses authorized by law.” Accordingly, for purposes 

of the Federal Drug-free Workplace Program, “illegal drug” use is defined as the use of an 

unlawfully possessed drug under Federal law, and does not include situations that involve 

legal drug use. Accordingly, neither the Mandatory Guidelines (nor this Manual) sanction the 

reporting of a donor’s legal drug use even when such use may raise safety concerns. 

When determining whether a legitimate medical explanation exists for a positive test, 

the MRO should consider whether a medication was used during the time period for which it 

was legitimately prescribed, if such a time period is specified. If a donor possesses a valid 

prescription with no time limitations on the drug’s use (even if the dispensed prescription is 
4-29 

past its expiration date), the donor’s specimen should be reported as negative. If a donor does 

not possess a valid prescription that would supply a legitimate medical explanation for the 

positive drug test result, the specimen should be reported as positive. 

Please note that an MRO’s decision to contact a donor’s employer for the purpose of 

addressing safety concerns associated with a donor’s legal drug use is not required, 

sanctioned, or authorized by the Mandatory Guidelines. Rather, an MRO’s decision to 

contact an employer regarding safety issues related to a donor’s valid prescription is subject 

to the MRO’s independent and voluntary choice, and subject to any obligations the MRO 

may have with the donor’s employing agency. Additional information related to this issue is 

provided in Chapter 6, Section 6.3, Occupational and Public Safety. 

4.5.4 State Initiatives and Laws

State initiatives and laws, which make marijuana or marijuana preparations available 

to an individual, with or without a physician’s 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. For purposes of the Federal Drug Free 

Workplace Program, Federal law pertaining to marijuana control supersedes State marijuana 

laws, and therefore, a physician’s recommendation for marijuana use is not a legitimate 

medical explanation for a positive marijuana test. 

The use of any substance included in Schedule I of the CSA, whether for nonmedical 

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 safetysensitive, health-sensitive, and security-sensitive positions, and with drug-free workplace 

programs. 

The 2018 Agricultural Improvement Act (Farm Bill) removed hemp from the 

definition of marijuana within the Controlled Substances Act (CSA). In addition, the act

defined that Δ9-tetrahydrocannabinol (THC) level in hemp-derived products must be no 

greater than 0.3 percent on a dry weight basis. Studies have shown that some cannabidiol 

(CBD) products’ labeling does not accurately reflect their content and may contain trace 

amounts of THC despite claims of being “THC Free.” Regardless of whether a CBD product 

was derived from hemp meeting the regulations in the Farm Bill, employees are not free from 

the risk of testing positive for THC metabolite if they use these products. As such, an 
4-30 

employee’s drug test may be positive for the THC metabolite, Δ9-tetrahydrocannabinol-9-

carobxylic acid (THCA), due to THC in the CBD product.32

The MRO must not accept a 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.

4.5.5 Changing a Verified Test Result 

■ Note: Designated Agency Representatives (DER) (or Designated Program 

Coordinators [DPC]) are responsible for processing non-MRO determined situations

(i.e., collection-based issues that may qualify as refusal to test). DERs and DPCs

cannot change a MRO-verified report. DERs and DPCs follow agency-specific 

administrative guidance that may result in non-MRO determined test cancellations 

and refusals to test. See Section 3.1.2 for non-MRO determined action. 

Only the MRO may change a previously a MRO-verified negative (or non-negative) 

test result, refusal to test or test cancellation in the following situations:

■ If an interview with the donor was not initially done and the donor presents 

information within 60 days of the verification to document that unavoidable 

circumstances (e.g., serious illness, injury) prevented contact with the MRO or 

Federal agency. Under these circumstances, the MRO may change a test result if the 

donor presents a legitimate medical explanation for the confirmed test result;

■ If information is received that was not available at the time of the original verification 

indicating an error was made by the laboratory; or 

■ If the MRO made an administrative error and reported the incorrect result. 

4.6 Documentation and Recordkeeping

Accurate recordkeeping is essential in documenting all aspects of the MRO review 

process. All MRO activities should be properly documented to show that procedures were 

consistent with the Mandatory Guidelines. The MRO should maintain documentation of all 

communications (written and oral) with— 

■ Donors; 

■ Collectors;

■ Federal agency representatives;

■ IITF personnel; and 

■ Laboratory personnel.
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The Mandatory Guidelines require MROs to retain drug test records for a minimum 

of two years from the date of collection. Hardcopy records may be discarded six months after 

conversion to electronic records. The MRO must ensure the confidentiality, integrity, and 

availability of the data and limit access to any data transmission, storage, and retrieval 

system. The MRO should have records management procedures to ensure proper disposition 

of records in accordance with the required retention schedule, and have a business 

discontinuance plan that ensures proper storage of records that have not reached the end of 

the retention period (e.g., maintain records or transfer to a secure archival location). (See 

additional information in Chapter 6, Section 6.6, of this manual, including requirements for 

external service providers.)

Documentation for each specimen must be retained in the MRO files and normally 

includes such items as: 

■ Documentation to support a legitimate explanation for the drug test result (e.g., copies 

of prescriptions, labels from prescription bottles, notes that a prescription was verified 

at a pharmacy or by the treating physician); 

■ Letters or notes received from an employee, relative, or physician providing 

treatment; or

■ Documentation of MRO actions regarding the test (e.g., attempts to contact the donor, 

documentation of the donor interview, any checklists used by the MRO and MRO 

staff for the record).

Some MROs may serve as primary care providers and retain medical records related 

to that function. MRO records must be separated from other medical and personnel records 

for an individual. 

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 private legal opinion. 

4.7 Reporting

4.7.1 Federal Agency Reports 

After the review and verification processes have been completed, the MRO reports 

the final, verified result(s) for a specimen to a Federal agency using Copy 2 of the Federal 

CCF or a report using a letter/memorandum format. The MRO may send reports by courier 
4-32 

or mail or use various electronic means (e.g., fax, computer, secure electronic transmission). 

Reporting instructions are detailed in Tables 4 and 5. The reporting of the primary (A) 

specimen result occurs immediately after the MRO has reviewed the information contained 

in Copy 1 and Copy 2 of the Federal CCF (as described above) and has completed the 

interview with the donor. The MRO notes in the report to the Federal agency if the donor has 

chosen to have the split (B) specimen tested at a second laboratory.

The report must include the following: 

■ Donor’s name and SSN or employee ID number; 

■ Specimen’s ID number from the Federal CCF;

■ Result for the test as indicated on the Federal CCF;

■ Relevant comments provided by the collector, laboratory, and/or IITF on the Federal 

CCF;

■ Specimen type (e.g., urine or oral fluid) 

■ Relevant information from the MRO (e.g., documentation of attempts to contact the 

donor, a statement of the donor’s refusal to cooperate with the medical review 

process);

■ Information provided by the donor (especially at the donor’s request) to the report 

(Note: This must not include specific confidential medical information);

■ MRO’s printed name and signature; and

■ Date reported.

The MRO must not disclose any numerical values of drug test results to the Federal 

agency unless law or regulation requires that disclosure. Drug testing is a prevention and 

deterrent method that is often part of a comprehensive drug-free workplace program to detect 

the presence of illicit drugs, or certain prescription drugs. The important factor is if the drug 

and/or drug metabolite is present - quantitative drug values are rarely useful because the level 

may be increasing or decreasing and the numerical level will vary with the urine specimen 

concentration (dilution) or oral fluid concentration (partitioning). 

The MRO must report drug test results using the HHS-specified nomenclature 

published with the drug and biomarker testing panels. 
4-33 

Note: Test results for specific federal agencies may require additional administrative 

reporting tasks. For example, the DOT Federal Motor Carriers Safety Administration 

(FMCSA) requires MROs to report DOT FMCSA Part 382 Violation drug test results to the 

FMCSA Drug & Alcohol Clearinghouse. Refer to agency specific requirements.

4.7.2 Biannual Reports (Secretary or Designated HHS Representative)

An MRO must send to the Secretary or designated HHS representative a biannual 

report of Federal agency specimens that were reported as positive for a drug or drug 

metabolite by a laboratory and verified as negative by the MRO. The report must not include 

any personally identifiable information for the donor and must be submitted by mail, fax, or 

other secure electronic transmission method within 14 working days after the end of the 

biannual period (i.e., in January and July). The biannual report must contain the following 

information: 

■ Reporting period (inclusive dates); 

■ MRO name, company name, and address; 

■ Federal agency name; and 

■ For each laboratory-reported positive drug test result that was verified as negative by 

the MRO:

– Specimen identification number;

– Laboratory name and address;

– Positive drug(s) or drug metabolite(s) verified as negative;

– MRO reason for verifying the positive drug(s) or drug metabolite(s) as negative 

(e.g., a donor prescription [the MRO must specify the prescribed drug]); 

– All results reported to the Federal agency by the MRO for the specimen; and

– Date of the MRO report to the Federal agency.

An MRO must provide copies of the drug test reports that the MRO has sent to a 

Federal agency when requested to do so by the Secretary. 

If an MRO did not verify any positive laboratory results as negative during the 

reporting period, the MRO should file a report that states that the MRO has no reportable 

results during the applicable reporting period. 

4.8 Confidentiality

The Mandatory Guidelines require the MRO to: 
4-34 

■ Report the verified result(s) of the drug test to a Federal agency in a manner designed 

to ensure the confidentiality of the information; and

■ Maintain the confidentiality of the information received during the review process, 

including the following (see exceptions below): 

– Information related to the donor’s medical condition; 

– Medications; 

– Medical diagnosis; and 

– Medical history. 

Despite this general requirement to maintain the confidentiality of medical 

information, there may be certain circumstances in which an MRO is required to provide 

such information to other parties. In these instances, prior to the donor interview, the MRO 

should inform the donor of the circumstances in which disclosure of information may occur. 

4.9 Discrepancies That May Require the MRO to Cancel a Test

The MRO must attempt to correct the following errors:

■ A missing donor’s signature on the MRO Copy 2 of the Federal CCF and the 

collector did not note that the donor refused to sign. The MRO must contact the 

collector to obtain a statement that the donor refused to sign the MRO copy. If the 

collector cannot provide that statement after at least 5 business days following 

collection, the MRO must cancel the test.

■ The certifying scientist failed to sign the laboratory Copy 1 of the Federal CCF for a 

specimen being reported drug positive, adulterated, invalid, or substituted. The MRO 

must contact the certifying scientist to obtain a statement that he/she inadvertently 

forgot the signature on the laboratory report, but that the certification review was 

properly conducted. If the MRO does not obtain the statement from the certifying 

scientist after waiting at least 5 business days, the MRO must cancel the test.

■ The electronic report provided by the HHS-certified laboratory or HHS-certified IITF 

as the sole report for a negative or (for urine) negative-dilute specimen does not 

contain the required data elements to ensure that the test result is properly associated 

with the MRO Copy 2 of the Federal CCF. (See Chapter 4, Section 4.1.2, for the list 

of required elements.) The MRO must contact the laboratory or the IITF to obtain a 

corrected electronic report. If the laboratory or IITF does not transmit a corrected 

copy after waiting at least 5 business days, the MRO must cancel the test.
5-1 

5. Interpretation of Results and Drug Information

As described in the Federal Workplace Drug Testing Overview, MRO Manual section 

3.1.1, Drugs, Federal agencies must test each urine specimen for marijuana metabolite, and 

cocaine metabolite (benzoylecgonine), while each oral fluid specimen must be tested for 

marijuana, cocaine, and cocaine metabolite (benzoylecgonine). Federal agencies are 

authorized to test each specimen for other Schedule I or II drugs as provided in the drug 

testing panel. SAMHSA will publish the drug test analytes and cutoffs (i.e., the “drug testing 

panel”) for initial and confirmatory drug tests in the Federal Register each year. The drug 

testing panels will also be available on the SAMHSA website 

https://www.samhsa.gov/workplace. Appendix D lists the drug testing panel analytes (i.e., 

drugs and drug metabolites) and test cutoffs specified by the UrMG and OFMG. 

Drug and/ or drug metabolite detection times are influenced by many 

pharmacological and chemical factors associated with the drug, dose, route of administration, 

frequency of drug use, biology of the individual, specimen type, and the sensitivity of the 

detection system. In general, detection times in oral fluid are somewhat shorter than observed 

for urine. In oral fluid, drugs of abuse are detected for 5 to 48 hours after use, whereas in 

urine, the detection time is 1.5 to 4 days or longer with chronic drug use.2,3 Positivity rates 

for oral fluid reported for non-regulated workplace testing are the same as or higher than 

urine positivity rates. These rates demonstrate the equivalency of these specimen types in 

identifying drug use, despite differences in drug detection times. 

Compared to urine, the composition of oral fluid is dynamic and varies with the rate 

of saliva production (flow rate). The pH of saliva is generally acidic, but may range from 6.0 

to 7.8, depending upon the rate of saliva flow. As saliva flow increases, levels of bicarbonate 

increase, thus increasing pH.4 Drugs enter oral fluid primarily by diffusion from blood and by 

deposition in the oral cavity from active drug use by oral, transmucosal, smoked, inhaled, and 

insufflated routes. The movement of drugs from blood (plasma) to oral fluid depends upon 

certain physicochemical properties of the drug including lipophilicity, degree of ionization, 

and the degree of drug binding with plasma proteins.5 Lipid-soluble molecules pass through 

cell membranes more efficiently than those that are more water soluble (e.g., drug 

metabolites). Consequently, parent (unmetabolized) drug is frequently the predominant 

analyte identified in oral fluid. Biological membranes are not permeable to the drug fraction 

that is bound to plasma proteins or to drug that is in the ionized state; hence only free, non-
5-2 

protein bound and non-ionized drug in plasma can diffuse into saliva. Consequently, oral 

fluid drug concentrations are closely related to the free, unbound drug in blood (plasma). 

For drugs that are weak bases (e.g., cocaine, opioids, amphetamines, and 

phencyclidine), drug concentrations in oral fluid are frequently higher than plasma 

concentrations as a result of “ion trapping” due to oral fluid’s higher acidity relative to 

plasma. Despite these restrictions, drug transfer from blood to oral fluid is a rapid process as 

demonstrated by consistent positive tests for drug in oral fluid two to five minutes following 

an intravenous injection of heroin or cocaine.6,7

 Deposition of drugs in oral fluid can also 

occur from external sources. For example, drugs in food sources (e.g., morphine in poppy 

seeds) are a potential source of contamination.8 Drug residues can initially be deposited in 

high concentration in oral fluid during active drug administration by oral, transmucosal, 

smoked, inhaled, and insufflated routes.6,7,9

 Generally, deposited drug residues disappear 

rapidly because of inherent self-cleansing mechanisms of the oral cavity (e.g., saliva 

production and subsequent swallowing). 

5.1 Amphetamines (AMP)

5.1.1 Amphetamine (AMP) and Methamphetamine (MAMP)

A positive test would be comprised of any or all analytes (amphetamine, 

methamphetamine) with a confirmed urine concentration equal to or greater than 250 ng/mL 

or a confirmed oral fluid concentration equal to or greater than 25 ng/mL. 

Amphetamine and methamphetamine are available as prescription medications and a 

donor who tests positive for one or more amphetamines may have legally used the drug(s). 

However, there are no non-prescription or OTC medications that contain these 

sympathomimetics and these substances are differentiated from the amphetamines during 

testing and will not be misidentified as MDMA, MDA or other amphetamines using a 

confirmatory test as required by the Mandatory Guidelines. 

The MRO must assess the laboratory result and the information from the donor to 

verify the drug test positive. 

The MRO may request the quantitative results of amphetamine analytes below the 

cutoff for a specimen reported positive for one or more amphetamine analytes. This 

information may be helpful to the MRO in assessing the medical explanation provided by the 

donor. 
5-3 

■ Note: Effective February 1, 2024, laboratories are no longer required to quantitate at 

least 100 ng/mL amphetamine in a Federal agency or DOT-regulated urine specimen

in order to report a positive methamphetamine result or to identify amphetamine 

above the LOD to report a split specimen as reconfirmed for methamphetamine. NRC

will issue a Federal Register Notice with changes to their regulations if they remove

this requirement.

Certified laboratories are required to validate all confirmatory assays (urine and oral 

fluid) prior to use with Federal agency specimens. For amphetamine 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. In February 2013, the 

National Laboratory Certification Program (NLCP) added substituted phenethylamines to the 

performance testing (PT) program to ensure all certified laboratories were distinguishing 

those from the amphetamines. 

5.1.1.1 Drug Testing

See Appendix D tables and below for urine and oral fluid reporting criteria. 

For grouped analytes (i.e., two or more analytes that are in the same drug class and 

have the same initial test cutoff):

■ Initial Test

– Immunoassay: The test must be calibrated with one analyte from the group 

identified as the target analyte. The cross-reactivity of the immunoassay to the 

other analyte(s) within the group must be 80 percent or greater; if not, separate 

immunoassays must be used for the analytes within the group. 

– Alternate technology: Either one analyte or all analytes from the group must be 

used for calibration, depending on the technology. At least one analyte within the 

group must have a concentration equal to or greater than the initial test cutoff or,

alternatively, the sum of the analytes present (i.e., equal to or greater than the 

laboratory’s validated limit of quantification) must be equal to or greater than the 

initial test cutoff.

■ Confirmatory Test 

– Mass spectrometry: The test method must use an analytical method combining 

chromatographic separation and mass spectrometric identification (i.e., gas 

chromatography/mass spectrometry (GC-MS), liquid chromatography/mass 
5-4 

spectrometry (LC-MS), GC-MS/MS, LC-MS/MS] or equivalent. The test must be 

calibrated with each analyte from the group identified as the target analytes. Test 

method calibration must include at least one calibrator at the confirmatory cutoff.

(a) Urine

(b) Oral Fluid

When the MRO requests that a split specimen (Bottle/Tube B) be tested for 

amphetamine and/or methamphetamine, the second laboratory performs confirmatory testing 

for both amphetamine and methamphetamine but reports only the analyte(s) reported positive 

by the first laboratory (as specified in the MRO retest request). The second laboratory reports 

analytes as reconfirmed or failed to reconfirm. The following rules apply: 

■ The second laboratory does NOT apply the HHS cutoff (e.g., urine 250 ng/mL, oral 

fluid 25 ng/mL) to split specimens. The laboratory must use its established limit of 

detection (LOD) or limit of quantification (LOQ) as the decision point for 

determining whether a drug has been reconfirmed in the retest specimen.

■ For urine, the laboratory must identify the presence of amphetamine (at or above the 

laboratory’s established LOD for the assay) in order to report methamphetamine as 

reconfirmed,

■ An MRO may request the quantitative result of amphetamine or methamphetamine 

below the cutoff for a specimen reported positive for the other analyte. This 

information may be helpful to the MRO in assessing the medical explanation 

provided by the donor. 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

(ng/mL)

Amphetamine/ Methamphetamine 500 Amphetamine

Methamphetamine

250 

250 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory Test 

Analyte 

Confirmatory Test 

Cutoff 

(ng/mL)

Amphetamine/

Methamphetamine 

50 Amphetamine

Methamphetamine

25

25
5-5 

5.1.1.2 Enantiomer Drug Testing10

An enantiomer in chemical terms is a drug that exists in two forms that are mirror 

images but are not superimposable. This is exemplified by the right and left hands of a 

person which are mirror images but not superimposable. Amphetamines are of particular 

interest as enantiomers because the d-methamphetamine has much greater activity than the lmethamphetamine and the most common confirmation methods do not distinguish the d- and 

l- forms. 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. Amphetamine 

confirmatory tests specifically identify amphetamine and methamphetamine if present, but do 

not distinguish between enantiomers (unless a chiral assay is employed as discussed below). 

Therefore, there is a possibility that a laboratory positive result could be reported for lmethamphetamine and/or l-amphetamine.

(Comment: Enantiomer test results aid in result interpretation.10 Some laboratories 

perform enantiomer testing as part of their test protocol and include the results in the 

original report. If this is not the case, the MRO may request the completion of the chiral 

assay on individual specimens following the interview with the donor or may have a blanket 

request for all amphetamine/methamphetamine results. The latter may be a desirable action 

for the MRO to allow the MRO to initiate the interview with the donor with a definitive result 

in hand. In addition, there can be a significant time savings in the case of the blanket 

request—the testing laboratory can proceed directly to completing the test or sending the 

primary (A) specimen for the additional testing for enantiomers. The number of 

amphetamines reported and requiring the chiral assay is relatively small and the MRO may 

obtain concurrence from the Federal agency on the blanket request. Although few 

laboratories perform the d,l-amphetamine assay, HHS [NLCP] can provide a laboratory 

name for testing of the amphetamine enantiomers, as needed.) 

Some laboratories may employ a chiral GC-MS or LC-MS/MS assay that 

distinguishes between the d- and l-enantiomers (isomers) and determines the relative 

percentages of each enantiomer for both amphetamine and methamphetamine. 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 an aliquot of urine or oral fluid specimen 

container A to another certified laboratory for d- and l-enantiomer testing. The MRO may 

order enantiomer testing for all specimens with positive amphetamines initial test results, all 

specimens with a positive methamphetamine confirmatory test result, or request such testing 
5-6 

on a case-by-case basis (e.g., when the MRO receives a methamphetamine positive result 

from a laboratory and the donor reports use of a nasal inhaler product within days prior to the 

test).

5.1.1.3 Background 

Amphetamine and methamphetamine are substances regulated under the CSA as 

Schedule II sympathomimetic stimulants. Both drugs have been used for treating attention 

deficit disorder in children, obesity, and narcolepsy and 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 mg. Individuals who abuse these drugs are reported to inject up 

to 1 g in a single 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 lisomers 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.

5.1.1.4 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). 
5-7 

Abusers may use in a variety of methods, including intravenous injection and 

smoking. 

5.1.1.5 Metabolism and Excretion

(a) Urine

Nearly half of a methamphetamine dose is recovered from urine unchanged. A small 

percentage of methamphetamine is demethylated to amphetamine by the polymorphic 

cytochrome P450 enzyme CYP 2D6. 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 the 

genomic expression of the CYP2D6 gene and 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 74% of a dose will be excreted unchanged if urine is acidic, while 1 to 2 % 

is excreted if urine is alkaline. Phenotype expression of the CYP2D6 depends upon the 

genome and may range from poor to ultra-rapid metabolizers. Generally, amphetamine and 

methamphetamine are considered detectable in urine for 2 to 3 days. 

Note that detection of amphetamines in urine is affected by pH as acidic conditions 

enhance drug elimination.

(b) Oral Fluid

Amphetamine appears rapidly in oral fluid as unchanged amphetamine.11

Methamphetamine and its metabolite, amphetamine, also appear rapidly in oral fluid with 

methamphetamine as the major constituent.

12,13 Both amphetamine and methamphetamine 

appearance in oral fluid are affected by pH. Amphetamine and methamphetamine detection 

in oral fluid is generally one day.12

5.1.1.6 Pharmaceuticals and Use 

(a) Prescription Drug Products

A single therapeutic dose of amphetamine or methamphetamine can produce a 

positive urine test 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 
5-8 

identify and quantitate the presence of amphetamine and/or methamphetamine. 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 an over-the-counter 

(OTC) product that contains l-methamphetamine (also called l-desoxyephedrine or 

levmetamfetamine), 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.

Products containing amphetamine and/or methamphetamine and substances that are 

metabolized to amphetamine and/or methamphetamine are available by prescription or OTC. 

MROs should have access to references with up-to-date information on such products.14

Table 6 lists some substances known to metabolize to amphetamine and 

methamphetamine.

A number of drugs contain, or are metabolized to, amphetamine or 

methamphetamine. One example is selegiline (Eldepryl®), a brain monoamine oxidase 

inhibitor used in the adjunctive treatment of Parkinson’s disease and depression. Selegiline is 

metabolized to l-methamphetamine and l-amphetamine. Another example is benzphetamine 

(Didrex®). Benzphetamine is metabolized to d-methamphetamine and d-amphetamine. A disomer and l-isomer differentiation will reveal the presence of only l-methamphetamine and 

l-amphetamine after the ingestion of selegiline. 

Examples of trade names of drugs that may produce a positive result for only 

amphetamine include Adderall® and Vyvanse®. 

Examples of trade names of drugs that may produce a positive result for 

methamphetamine and/or amphetamine (metabolite of methamphetamine) include Desoxyn®, 

Eldepryl®* and Didrex®*. Additional information is presented in Table 6. The use of 

enantiomeric analysis is useful in distinguishing methamphetamine abuse from prescription 

medications. 

*Note: Eldepryl® (selegiline) metabolizes to the l-enantiomer and Didrex®

(benzphetamine) metabolizes to d-methamphetamine.

(b) Non-prescription Drug Products

Some non-prescription products contain sympathomimetic amines that can cause a 

positive result on an initial immunoassay test. The confirmatory test is specific for 
5-9 

methamphetamine and amphetamine. Specimens containing sympathomimetic amines will 

not be reported positive by the laboratory after conducting the confirmatory test. Some overthe-counter (OTC) products (e.g., inhalers) contain l-methamphetamine (also called ldesoxyephedrine or levmetamfetamine). Enantiomer analysis may be used to verify that a 

positive methamphetamine result was due to the use of such products. There may be a trace 

amount of the d-isomer present because a very slight amount of d-methamphetamine may be 

present as a contaminant in the OTC drug and a contaminant of the analytical procedure. If 

there is greater than 80% l-methamphetamine, the results are considered to be consistent with 

OTC use. If there is more than 20% d-methamphetamine present, the results indicate the use 

of some source other than the OTC product, and the result is verified as positive. This is a 

very conservative interpretation. 

Note: donors reporting the use of nasal inhaler products is commonly referred to as 

the “Vicks defense” even though Vicks products no longer contain l-metamfetamine (lmethamphetamine).

5.1.2 Designer Sympathomimetic Substances (Methylenedioxymethamphetamine (MDMA) 

and Methylenedioxyamphetamine (MDA)) 

A positive test would be comprised of any or all analytes (MDMA, MDA) with a 

confirmed urine concentration equal to or greater than 250 ng/mL or a confirmed oral fluid 

concentration equal to or greater than 25 ng/mL. 

A positive MDMA or MDA result is evidence of illegal drug use. There are no 

prescription, non-prescription or OTC medications that contain these designer 

sympathomimetics and there are no legal medical uses of the substances. These substances 

are differentiated from the amphetamines during testing and will not be misidentified as 

amphetamine, methamphetamine, or other amphetamines using a confirmatory test as 

required by the Mandatory Guidelines. 

Certified laboratories are required to validate all confirmatory assays (urine and oral 

fluid) prior to use with Federal agency specimens. For MDMA and MDA confirmatory 

assays, each laboratory must document the assay’s ability to identify and accurately 

quantitate MDMA and MDA in the presence of high levels of sympathomimetic amines and 

also demonstrate that these compounds are not misidentified as MDMA or MDA (i.e., by 

analyzing samples containing sympathomimetic amines without MDMA or MDA). These 

experiments must be performed on at least an annual basis to verify the assay’s continued 

performance. In February 2013, the National Laboratory Certification Program (NLCP) 
5-10 

added substituted phenethylamines to the performance testing (PT) program to ensure all 

certified laboratories were distinguishing those from the MDMA and MDA. 

5.1.2.1 Drug Testing

See Appendix D tables and below for urine and oral fluid reporting criteria. 

For grouped analytes (i.e., two or more analytes that are in the same drug class and 

have the same initial test cutoff):

■ Initial Test

– Immunoassay: The test must be calibrated with one analyte from the group 

identified as the target analyte. The cross-reactivity of the immunoassay to the 

other analyte(s) within the group must be 80 percent or greater; if not, separate 

immunoassays must be used for the analytes within the group. 

– Alternate technology: Either one analyte or all analytes from the group must be 

used for calibration, depending on the technology. At least one analyte within the 

group must have a concentration equal to or greater than the initial test cutoff or, 

alternatively, the sum of the analytes present (i.e., equal to or greater than the 

laboratory’s validated limit of quantification) must be equal to or greater than the 

initial test cutoff.

■ Confirmatory Test 

– Mass spectrometry: The test method must use an analytical method combining 

chromatographic separation and mass spectrometric identification (i.e., gas 

chromatography/mass spectrometry (GC-MS), liquid chromatography/mass 

spectrometry (LC-MS), GC-MS/MS, LC-MS/MS] or equivalent. The test must be 

calibrated with each analyte from the group identified as the target analytes. Test 

method calibration must include at least one calibrator at the confirmatory cutoff.

(a) Urine

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

(ng/mL)

MDMA/MDA 500 

MDMA

MDA

250 

250 
5-11 

(b) Oral Fluid

When the MRO requests that a split specimen (Bottle/Tube B) be tested for MDA 

and/or MDMA, the second laboratory performs confirmatory testing for both MDA and 

MDMA but reports only the analyte(s) reported positive by the first laboratory (as specified 

in the MRO retest request). The second laboratory reports analytes as reconfirmed or failed 

to reconfirm. The following rules apply: 

■ The second laboratory does NOT apply the HHS cutoff (e.g., urine 250 ng/mL, oral 

fluid 25 ng/mL) to split specimens. The laboratory must use its established limit of 

detection (LOD) or limit of quantification (LOQ) as the decision point for 

determining whether a drug has been reconfirmed in the retest specimen.

■ The laboratory must identify the presence of MDMA or MDA (at or above the 

laboratory’s established LOD for the assay) in order to report MDMA or MDA as 

reconfirmed,

■ An MRO may request the quantitative result of MDA or MDMA below the cutoff for 

a specimen reported positive for the other analyte. This information may be helpful to 

the MRO in assessing the medical explanation provided by the donor. 

5.1.2.2 Background 

3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy,” “Molly,” “E,” “XTC”) 

and its major, active metabolite, 3,4-methylenedioxyamphetamine (MDA, EA-1299, “Love”) 

are psychoactive amphetamines regulated under the CSA as Schedule I hallucinogens. Both 

MDMA and MDA are available as illicit parent drugs and are used at “rave” parties; these 

drugs may be used with other drugs or the same tablets may actually contain other drugs such 

as ephedrine, dextromethorphan, ketamine, caffeine, cocaine, methamphetamine, or even 

synthetic cathinones (bath salts). 

MDMA and MDA are central nervous system stimulants and are used recreationally 

as hallucinogens with effects similar to those of mescaline and amphetamines. MDMA also 

acts as an entactogen—a drug that can increase self-awareness and empathy.

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

(ng/mL)

MDMA/MDA 50

MDMA

MDA

25

25
5-12 

MDMA and MDA 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. Illegal manufacture of MDMA and MDA is without regard to amounts of disomer or l-isomer. Certified laboratory urine and oral fluid drug testing do not distinguish 

between d-isomers and l-isomers of either MDMA or MDA. 

5.1.2.3 Routes of Administration

■ MDMA—oral (i.e., tablets or capsules). 

■ MDA—oral (i.e., tablets or capsules).

Abusers may use in a variety of methods, including intravenous injection and 

smoking. 

5.1.2.4 Metabolism and Excretion

(a) Urine

MDMA is metabolized primarily by demethylation to form the active metabolite, 

MDA, and breaking the methylenedioxy bridge to form hydroxymethoxy- and dihydroxyderivatives. Generally, MDMA or MDA is detectable in urine for 1 to 2 days. 

(b) Oral Fluid 

MDA appears rapidly in oral fluid as the unchanged drug MDA. MDMA and its 

active metabolite, MDA, also appear within hours in oral fluid with MDMA as the major 

constituent.15 Limited studies have shown MDMA and MDA detectable in oral fluid for 71 

and 47 hours, respectively, in oral fluid.15

5.1.2.5 Pharmaceuticals and Use 

(a) Prescription Drug Products

MDMA and MDA, in both enantiomeric forms, are regulated as Schedule I drugs and 

are not available as pharmaceuticals.

(b) Non-prescription Drug Products

The popular term “Molly” (slang for “molecular”) refers to the pure crystalline 

powder form of MDMA, usually sold in capsules. A tablet contains approximately 100 mg, 

although street samples vary in dose and potency, and a typical oral dose is one to two 

tablets. The drug’s effects last approximately 3 to 6 hours, although it is not uncommon for 
5-13 

users to take a second dose of the drug as the effects of the first dose begin to fade. These 

effects include feelings of energy, altered sense of time, and pleasant sensory experiences 

with enhanced perception. Negative symptoms include tachycardia, dry mouth, jaw 

clenching, and muscle aches. It is commonly taken in combination with other drugs. 

5.2 Cannabinoids (THC)

5.2.1 THC and THCA

A positive test would be comprised of a confirmed marijuana metabolite Δ9-

tetrahydrocannabinol-9-carboxylic acid (THCA) urine concentration equal to or greater than 

15 ng/mL or a confirmed oral fluid Δ9-tetrahydrocannabinol (THC) concentration equal to or 

greater than 2 ng/mL 

As of the publishing date of this manual, marijuana remains a Schedule I drug, and 

marijuana use is not an acceptable medical explanation for a positive drug test result in any 

Federal agency drug testing program. An oral or written recommendation from a licensed 

physician or medical professional does not exempt the donor from this rule. If the donor 

admits the use of medical marijuana, the MRO verifies the result as positive. 

Certified laboratories are required to validate all confirmatory assays (urine and oral 

fluid) prior to use with Federal agency specimens. For confirmatory assays, each laboratory 

must document the assay’s ability to identify and accurately quantitate urine THCA and oral 

fluid THC. These experiments must be performed on at least an annual basis to verify the 

assay’s continued performance.

5.2.1.1 Drug Testing

See Appendix D tables for urine and oral fluid reporting criteria. 

For single analytes (i.e., one analyte that is in the drug class and a single initial test 

cutoff):

■ Initial Test

– Immunoassay: The test must be calibrated with one analyte from the group 

identified as the target analyte. The cross reactivity of the immunoassay to the 

other analyte(s) within the group must be 80 percent or greater; if not, separate 

immunoassays must be used for the analytes within the group. 

An initial test must be calibrated with the target analyte (i.e., ∆-9-
5-14 

tetrahydrocannabinol-9-carboxylic acid [THCA] for urine and ∆-9-

tetrahydrocannabinol [(THC] for oral fluid).

– Alternate technology: Either one analyte or all analytes from the group must be 

used for calibration, depending on the technology. At least one analyte within the 

group must have a concentration equal to or greater than the initial test cutoff or, 

alternatively, the sum of the analytes present (i.e., equal to or greater than the 

laboratory’s validated limit of quantification) must be equal to or greater than the 

initial test cutoff.

– The confirmatory test cutoff must be used for an alternate technology initial test 

that is specific for the target analyte (i.e., 15 ng/mL for urine THCA and 2 ng/mL 

for oral fluid THC).

■ Confirmatory Test 

– Mass spectrometry: The test method must use an analytical method combining 

chromatographic separation and mass spectrometric identification (i.e., gas 

chromatography/mass spectrometry (GC-MS), liquid chromatography/mass 

spectrometry (LC-MS), GC-MS/MS, LC-MS/MS] or equivalent. The test must be 

calibrated with the analyte from the group identified as the target analyte. Test 

method calibration must include at least one calibrator at the confirmatory cutoff. 

(a) Urine

(b) Oral Fluid

When the MRO requests that a split urine specimen (Bottle/Tube B) be tested for 

THCA or a split oral fluid specimen (Container B) for THC, the second laboratory performs 

(for urine) confirmatory testing for THCA or (for oral fluid) THC analyte reported positive 

by the first laboratory (as specified in the MRO retest request). The second laboratory reports 

analytes as reconfirmed or failed to reconfirm. The following rules apply: 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

(ng/mL)

Marijuana (THCA) 50 THCA 15 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

(ng/mL)

Marijuana (THC) 4 THC 2 
5-15 

■ The second laboratory does NOT apply the HHS cutoff (e.g., urine THCA 15 ng/mL, 

oral fluid THC 2 ng/mL) to split specimens. The laboratory must use its established 

limit of detection (LOD) or limit of quantification (LOQ) as the decision point for 

determining whether a drug has been reconfirmed in the retest specimen.

■ The laboratory must identify the presence of urine THCA or (for oral fluid) THC (at 

or above the laboratory’s established LOD for the assay) in order to report either 

urine THCA or oral fluid THC as reconfirmed.

5.2.1.2 Background 

Marijuana, Cannabis sativa, is controlled under Schedule I of the CSA and contains 

many cannabinoid substances. The principal psychoactive agent in cannabinoids is 

Δ9-tetrahydrocannabinol (delta-9-tetrahydrocannabinol, commonly referred to as THC). 

Certified laboratories are required to use confirmatory testing that specifically identifies the 

major marijuana metabolite, Δ9-tetrahydrocannabinol-9-carboxylic acid (commonly referred 

to as THCA, Δ9-THCA or THC-COOH).16

Some cannabinoids produce euphoria or a “high” and a sense of relaxation that is 

commonly followed by drowsiness. The initial psychoactive effects of smoking marijuana 

occur within minutes, reach a peak within 10 to 30 minutes, and may persist for 2 to 4 hours. 

Intoxication temporarily impairs concentration, learning, and perceptual motor skills. 

Reduced functional ability lasts for at least 4 to 8 hours after a dose of marijuana, beyond the 

user’s perception of the high. 

5.2.1.3 Routes of Administration

■ Dronabinol-oral (i.e., capsules and liquid solution).

■ Marijuana—smoking, oral (i.e., eating), vaping, and inhalation through a hash pipe. 

■ Hashish—smoking (preferred) and oral (i.e., eating). 

■ Wax, shatter, dabs, extracts—inhaled, smoked, or vaping (especially by e-cigarettes).

Abusers may use in a variety of methods. In previous years, marijuana was generally 

consumed by smoking cannabis of rather limited drug concentration. Over the past few 

decades, cannabis potencies have increased substantially and methods have been developed 

to provide highly concentrated products. A variety of cannabis preparations have become 

available for consumption by smoking, inhalation, oral ingestion, and other routes of 

administration.
5-16 

5.2.1.4 Metabolism and Excretion

Cannabinoids are usually smoked, vaped, or vaporized through a water pipe. 

Transpulmonary absorption occurs quickly, putting THC into the bloodstream and causing a 

direct psychoactive response in the brain. Cannabinoids are sometimes eaten because the 

drug is also absorbed through the gastrointestinal tract; however, gastrointestinal 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 

bloodstream at very low levels, permitting metabolism and eventual excretion. THC is 

metabolized extensively in the liver and the major metabolite is THCA.

(a) Urine

Current urine immunoassay procedures have significant cross reactivity to many 

marijuana compounds and metabolites that are excreted in urine, while the confirmatory test 

specifically identifies and quantifies the single metabolite THCA. The THCA metabolite that 

is confirmed has been found to account for approximately 30% of the urine immunoassay 

response—the explanation for the difference in the initial test cutoff of 50 ng/mL and the 

confirmatory cutoff of 15 ng/mL. To be reported positive, a specimen must test positive at or 

above the 50 ng/mL cutoff for the initial test and have a concentration of THCA that is equal 

to or greater than the 15 ng/mL confirmatory cutoff. Infrequent marijuana use may cause 

positive initial test results for 1 to 5 days. Chronic smokers slowly release THCA over a 

longer time and may continue to produce detectable levels of THCA for longer than 5 days. 

(b) Oral Fluid

THC is reliably present in oral fluid immediately after smoked cannabis 

administration and remains detectable for 24–30 hours or longer. The major source of THC 

in oral fluid occurs from deposition in the mouth during smoking, vaping or oral use.17 THC 

appears at its highest concentration in oral fluid immediately after smoking marijuana.18-21

Initial high concentrations of THC in oral fluid decline rapidly within the first 30 minutes 

after use and thereafter decline over time in a manner similar to that observed for THC in 

plasma and serum. 

5.2.1.5 Pharmaceuticals and Use 

(a) Prescription Drug Products

(i) Pharmaceuticals

Dronabinol is available as Marinol® (Roxane Laboratories) in 2.5 mg, 5 mg, or 10 mg 

soft gelatin capsules for oral administration. When a donor claims to have a prescription for 
5-17 

dronabinol, the MRO should allow the donor the opportunity to provide the supporting 

documentation. A valid prescription for dronabinol is a legitimate medical explanation for a 

positive THCA urine drug test result but not a positive THC oral fluid drug test result. Use of 

Marinol® does not produce a positive oral fluid THC result.22,23

 Marinol® is approved for 

treatment of anorexia associated with weight loss in patients with a confirmed diagnosis of 

acquired immune deficiency syndrome (AIDS) and for treating nausea and vomiting 

associated with cancer chemotherapy in patients who have failed to respond adequately to 

conventional antiemetic treatments. The drug has psychoactive effects that may present 

safety issues and patients prescribed Marinol® should be warned not to drive, operate 

complex machinery, or engage in hazardous activity. 

THC preparations from Cannabis sativa contain Δ9-THC and a number of closely 

related cannabinoids including Δ9-tetrahydrocannabivarin (THCV). Marinol® is produced by 

a synthetic process that leads primarily to THC but with no THCV. As a result, THCV 

testing may distinguish between dronabinol use and cannabis use, or may identify an 

individual who uses cannabis in addition to prescribed dronabinol; however, studies indicate 

that THCV is not present in all strains of cannabis and there is variability in the 

concentrations among strains of cannabis.24-26 As a result, the MRO must carefully consider 

the case if a THCA positive result is presented along with the results of a THCV assay. If the 

analytical results show the presence of THCV, the result may be useful to confirm the use of 

cannabis; however, if the THCV assay does not show the presence, the information has little 

use in interpretation of the drug testing result. 

Nabilone (Cesamet®) is a synthetic cannabinoid. This drug does not metabolize to 

THC or THCA, so would not produce a positive drug test. Therefore, the use of Nabilone is 

not an acceptable medical explanation for a positive confirmed drug test.

Epidiolex® (GW Pharma Ltd, United Kingdom) is an FDA-approved cannabidiol 

(CBD)-enriched product for the control of intractable epilepsy in children. Epidiolex is CBD 

and contains trace THC. Therefore, high daily doses of this compound have the potential to 

cause a positive drug test.

Compounds or substances that have not been approved by FDA cannot be used as a 

legitimate medical explanation. For example, Sativex® (GW Pharma Ltd, UK) is not

currently FDA-approved. Sativex® contains THC and CBD and is proposed as treatment for 

symptom improvement in adult patients with moderate to severe spasticity. Use of Sativex®

may result in a positive drug test for THCA. Another example is a product named Charlotte’s 
5-18 

Web Oil that is being advertised in Colorado to treat similar symptoms. The product appears 

to be a marijuana extract enriched with higher ratios of CBD to THC. Use of this product 

might result in a positive THCA test. The DEA has reiterated their position on the extracts of 

marijuana such as CBD or Charlotte’s Web Oil. CBD is currently being illegally produced 

and marketed in the United States in violation of the CSA and the Federal Food, Drug, and 

Cosmetic Act. Because this extract is a derivative of marijuana, it falls within the definition 

of marijuana under Federal law and is listed as Schedule I. 27

(ii) Medical Marijuana

At this time, marijuana remains a Schedule I drug, and marijuana use is not an 

acceptable medical explanation for a positive drug test result in any Federal agency drug 

testing program. A prescription or written recommendation from a licensed physician or 

medical professional does not exempt the donor from this rule. If the donor admits the use of 

medical marijuana, the MRO verifies the result as positive.

(b) Non-prescription Drug Products

(i) Marijuana

Current marijuana is much stronger than the plant of the 1960s. Plants that produce 

high concentrations of THC are not grown from seeds, but from cuttings of high producers to 

retain the genetic characteristics of the parent plant. As a result, concentrations of THC in 

current crops frequently exceed 10% and are often much higher. The growing plants are 

trimmed to remove excess undergrowth and stems and prevent loss of nutrients to enhance 

flowering. When the plants flower, the buds are manicured to remove large leaves and the 

trimmed buds are dried. The trimmings are saved and used to prepare various products. The 

buds are generally smoked and the dried resin beads can be used as “kief” or pressed into 

hash for storage and smoked or used in other ways. A relatively recent and dangerous 

procedure for getting high is using “Dabs.” The THC is extracted from trimmings using a 

highly flammable solvent such as butane and then concentrated to make an amber-like 

material called “wax” that is very high in THC (60%–80%). The “wax” is volatilized by a 

propane flame and the person dabbing inhales as the THC is volatilized in a “piece,” pulling 

the smoke into the person’s lungs. THC is also prepared and consumed in candy, baked 

goods, beverages, and other foods. The significance of the changes in growth and use of 

marijuana is that the THC concentration is increasing in the plants and users are now 

extracting and purifying the THC to enhance their hits. 
5-19 

(ii) Passive Inhalation of Marijuana

Passive inhalation (i.e., an inadvertent exposure to marijuana) are frequent excuses 

for positive urine tests for THCA and positive oral fluid tests for THC; however, it remains 

SAMHSA’s position that passive exposure to a drug (e.g., second-hand marijuana smoke) is 

not a legitimate medical explanation for a positive marijuana test result under the Mandatory 

Guidelines. The basis for this position is that scientific studies have shown that there is very 

little possibility that a donor can test positive for the confirmatory analyte THCA in the urine 

as the result of passive exposure.28 Prolonged exposure to high levels of second-hand 

marijuana smoke may result in detectable levels of THCA in the urine if the individual 

willingly exposes themselves to extreme levels of second-hand marijuana smoke on a 

sustained basis and in an enclosed space. In a similar study of passive inhalation and oral 

fluid THC, prolonged exposure to high levels of second-hand marijuana smoke may result in 

detectable levels of oral fluid THC but for only up to 3 hours after the individual willingly 

exposes themselves to extreme levels of second-hand marijuana smoke on a sustained basis 

and in an enclosed space.29 

Federal agencies may consider willful and sustained exposure to extreme levels of 

second-hand marijuana smoke as a form of active marijuana use even though the route of 

administration is through second-hand smoke. When a donor claims that his/her positive 

THCA urine test or positive THC oral fluid test was due to passive inhalation, the MRO may 

not accept this as a legitimate explanation for a positive THCA (urine) or for a positive THC 

(oral fluid). 

(iii) Hemp Products 

The 2014 Agricultural Act legalized growing and cultivation of “industrial hemp” 

(marijuana with a THC content of 0.3 percent or less) for agricultural research purposes 

where permitted under state law; however, the Act does not permit the production of nonFDA-approved drug products made from cannabis.30 “Non-consumable” hemp items (e.g., 

clothing, industrial solvents, and animal feed mixtures) are considered noncontrolled 

substances and are not subject to any of the CSA requirements regardless of their THC 

content. 

The 2018 Agricultural Improvement Act (Farm Bill), signed into law on 20 

December 2018, removed hemp from the definition of marijuana within the Controlled 

Substances Act (CSA).31 The Farm Bill states that the Δ9-tetrahydrocannabinol (THC) level 

in hemp-derived products must be no greater than 0.3 percent on a dry weight basis in order 
5-20 

to satisfy the revised definition of “hemp” provided in the Farm Bill. Studies have shown that 

some cannabidiol (CBD) products’ labeling does not accurately reflect their content. 

Cannabis based products containing a THC level greater than 0.3 percent on a dry 

weight basis do not fall under the Farm Bill’s definition of hemp even if they are labeled as 

such. In one study, the amount of CBD in 69 percent of the 84 tested CBD products was 

inconsistent with that on the label, and some products contained unlabeled cannabinoids, 

including THC in amounts up to 6.4 mg/mL. As such, an employee’s drug test may be 

positive for the THC metabolite, Δ9-tetrahydrocannabinol-9-carobxylic acid (THCA), due to 

THC in the CBD product.32 

When a donor claims that his/her positive THCA test was due to ingestion or use of a 

legal hemp product, the MRO may not accept such explanations as a legitimate explanation 

for a positive THCA test result. 

(iv) Cannabinoid Isomers 

The cannabinoid isomer Δ8-tetrahydrocannabinol (delta-8-tetrahydrocannabinol, 

commonly referred to as Δ8-THC) is a psychoactive cannabinoid agent that metabolizes to 

Δ8-tetrahydrocannabinol-9-carboxylic acid (commonly referred to as Δ8-THCA or Δ8-THCCOOH). The Δ8-THC and Δ8-THCA cannabinoid isomers cross-react with oral fluid and 

urine initial test immunoassays, respectively. Oral fluid specimens containing Δ8-THC and 

urine specimens containing Δ8-THCA could produce positive initial test results, even in the 

absence of Δ9-THC and Δ9-THCA. HHS-certified laboratories are required to successfully 

confirm and quantify oral fluid Δ9-THC and urine Δ9-THCA in the presence of Δ8-THC and

Δ8-THCA, respectively.

Conversion of water-soluble CBD to Δ9-THC, using THC-free CBD products (an oil, 

a water-soluble CBD powder, and a water-soluble nano-emulsion formulation) incubated in 

synthetic gastric fluid, did not convert CBD to Δ8-THC. The nano-emulsion CBD 

formulation demonstrated <0.065% conversion and was the highest conversion to Δ9-THC

observed. Resulting Δ9-THC concentrations would be less than “THC-free” or “<0.3% 

THC” levels in CBD products. Based upon a daily dose of 30 mg CBD, it is unlikely that 

gastric CBD conversion to Δ9-THC will produce a positive urinary drug test for Δ9-THCCOOH (50 ng/mL cutoff), but more extensive conversion in vivo and/or use of other 

products, cannot be ruled out. 
5-21 

The subject of cannabinoid isomers is rapidly evolving and may outpace the 

publication schedules for the MRO Manual. MROs should look for program updates as they 

become available from SAMHSA, the DOT, and MRO professional associations. 

5.3 Cocaine (COC)33

5.3.1 Benzoylecgonine and Cocaine 

A positive test would be comprised of a confirmed cocaine metabolite 

(benzoylecgonine) urine concentration equal to or greater than 100 ng/mL or a confirmed 

oral fluid concentration of any or all analytes (cocaine, benzoylecgonine) equal to or greater 

than 8 ng/mL. 

There are no prescription, non-prescription or OTC medications that contain cocaine. 

However, the medical community uses a solution containing 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. Other 

anesthetics are differentiated from cocaine and or benzoylecgonine during testing and will 

not be misidentified as either cocaine or benzoylecgonine using a confirmatory test as 

required by the Mandatory Guidelines. 

Certified laboratories are required to validate all confirmatory assays (urine and oral 

fluid) prior to use with Federal agency specimens. For confirmatory assays, each laboratory 

must document the assay’s ability to identify and accurately quantitate urine 

benzoylecgonine and oral fluid benzoylecgonine and cocaine. These experiments must be 

performed on at least an annual basis to verify the assay’s continued performance. 

5.3.1.1 Drug Testing

See Appendix D tables for urine and oral fluid reporting criteria.

For single and grouped analytes (i.e., one analyte in the drug class; or two or more 

analytes that are in the same drug class and have the same initial test cutoff):

■ Initial Test

– Immunoassay: The test must be calibrated with one analyte from the group 

identified as the target analyte. The cross-reactivity of the immunoassay to the 

other analyte(s) within the group must be 80 percent or greater; if not, separate 

immunoassays must be used for the analytes within the group. 

– Alternate technology: Either one analyte or all analytes from the group must be 

used for calibration, depending on the technology. At least one analyte within the 
5-22 

group must have a concentration equal to or greater than the initial test cutoff or, 

alternatively, the sum of the analytes present (i.e., equal to or greater than the 

laboratory’s validated limit of quantification) must be equal to or greater than the 

initial test cutoff. 

– The confirmatory test cutoff must be used for an alternate technology initial test 

that is specific for the target analyte (i.e., 100 ng/mL for urine benzoylecgonine). 

■ Confirmatory Test 

– Mass spectrometry: The test method must use an analytical method combining 

chromatographic separation and mass spectrometric identification (i.e., gas 

chromatography/mass spectrometry (GC-MS), liquid chromatography/mass 

spectrometry (LC-MS), GC-MS/MS, LC-MS/MS] or equivalent. The test must be 

calibrated with each analyte from the group identified as the target analyte. Test 

method calibration must include at least one calibrator at the confirmatory cutoff.

(a) Urine

(b) Oral Fluid

When the MRO requests that a split urine specimen (Bottle/Tube B) be tested for the 

cocaine metabolite, benzoylecgonine, or a split oral fluid specimen (Container B) for cocaine 

and/or benzoylecgonine, the second laboratory performs confirmatory testing for (for urine) 

benzoylecgonine or (for oral fluid) cocaine and/or benzoylecgonine analyte(s) reported 

positive by the first laboratory (as specified in the MRO retest request). The second 

laboratory reports analytes as reconfirmed or failed to reconfirm. The following rules apply: 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

(ng/mL)

Cocaine metabolite 

(Benzoylecgonine)

150 Benzoylecgonine 100 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

(ng/mL)

Cocaine/Benzoylecgonine 15

Cocaine

Benzoylecgonine

8

8
5-23 

■ The second laboratory does NOT apply the HHS cutoff(s) (e.g., urine 

benzoylecgonine 100 ng/mL, oral fluid cocaine 8 ng/mL and/or benzoylecgonine 8 

ng/mL single or combination) to split specimens. The laboratory must use its 

established limit of detection (LOD) or limit of quantification (LOQ) as the decision 

point for determining whether a drug has been reconfirmed in the retest specimen. 

■ The laboratory must identify the presence of urine benzoylecgonine or (for oral fluid) 

cocaine and/or benzoylecgonine (at or above the laboratory’s established LOD for the 

assay) in order to report either urine benzoylecgonine or oral fluid cocaine and/or 

benzoylecgonine as reconfirmed.

5.3.1.2 Background 

Cocaine, an alkaloid from the coca plant, is regulated under the CSA as Schedule II 

stimulant. Cocaine is usually sold as cocaine hydrochloride—a fine, white crystalline 

powder. Cocaine is rapidly metabolized to its major metabolite, benzoylecgonine. It is a 

widely used drug of abuse. The Federal Workplace Drug Testing Program requires analysis 

for the cocaine metabolite benzoylecgonine in urine specimens. Cocaine has only a limited 

legal use in the United States as a topical anesthetic in ear, nose, and throat surgery. 

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.34

5.3.1.3 Routes of Administration

■ Cocaine— oral, intravenous injection, smoking, and intranasal (i.e., snorting, 

inhalation). 

■ Abusers may use in a variety of methods, including intravenous injection and 

smoking. Smoking the “free base” or “crack” form of the drug has become the 

predominate route. 
5-24 

5.3.1.4 Metabolism and Excretions 

(a) Urine

Cocaine is rapidly and extensively metabolized by liver and plasma enzymes to its 

major metabolite, benzoylecgonine.35 The detection window may be longer using the 150 

ng/mL initial test cutoff and 100 ng/mL confirmatory test cutoff specified by the Mandatory 

Guidelines. Cocaine and benzoylecgonine are not significantly stored in the body. Therefore, 

even after heavy, chronic use, urine specimens may be negative when collected several days 

after last use. Benzoylecgonine can usually be detected in urine for 2 to 3 days after a single 

dose. 

(b) Oral Fluid

Cocaine appears in oral fluid within minutes after use following intravenous, nasal 

and smoked administration.6

 Cocaine is rapidly metabolized to benzoylecgonine that also is 

excreted in oral fluid. At different times after use, cocaine and benzoylecgonine may be 

present singly or in combination in oral fluid. Generally, cocaine and or benzoylecgonine are 

detectable in oral fluid for 1 to 2 days.9

5.3.1.5 Pharmaceuticals and Use 

(a) Prescription Drug Products

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. 

The medical use must have occurred no more than 2 or 3 days prior to when the urine 

specimen was collected. Use at an earlier time may not cause a positive urine test. 

(b) Non-prescription Drug Products

“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. Crack is 

smoked because unlike cocaine hydrochloride, free-base cocaine survives high temperatures 

and is absorbed into the bloodstream as rapidly as if it were injected. 

Other potential explanations for a cocaine result include the following: 
5-25 

■ Topical Anesthetics. Cocaine is structurally unique and does not resemble any of the 

other topical anesthetics, such as lidocaine, benzocaine, etc. Although these 

compounds have analgesic properties, there is no structural similarity to cocaine or its 

metabolite (benzoylecgonine), nor are any of these compounds metabolized to 

cocaine or its metabolites. Specimens containing these substances will not be reported 

positive by the laboratory for benzoylecgonine. 

■ Passive Inhalation of Crack Cocaine. Comprehensive scientific studies have 

demonstrated that individuals passively exposed to “crack” smoke do not produce a 

urine positive test for cocaine using the HHS cutoffs for initial and confirmatory 

testing.36 When a donor claims that the positive benzoylecgonine test was due to 

passive inhalation, the MRO should allow the donor to describe the circumstances 

pertaining to how and when the passive exposure occurred. Passive inhalation is not 

an acceptable alternative medical explanation for the presence of benzoylecgonine in 

the donor’s urine.

■ Coca Leaf Tea. In the early 1980s, health food stores sold a tea under the trade name 

“Health Inca Tea.” It was discovered that this tea contained decocainized coca leaves 

with detectable amounts of cocaine present and the U.S. Food and Drug 

Administration (FDA) banned the importation of this tea into the United States. 

Therefore, any tea sold using the name “Health Inca Tea” should not contain any 

cocaine. When a donor claims that the positive benzoylecgonine test was due to 

drinking a beverage with coca leaves as an ingredient, the MRO should allow the 

donor to explain where and when the tea was purchased. Drinking “Health Inca Tea” 

or other beverage purporting to contain coca leaves is not an acceptable alternative 

explanation for the presence of benzoylecgonine in the donor’s urine. 

5.4 Opioids37 (OPI)

Opioids are classified as narcotics—drugs that in moderate doses dull the senses, 

relieve pain, and induce deep sleep. Excessive doses of such drugs cause stupor, coma, or 

convulsions. The terms “opiates” and “opioids” are defined in the glossary in Appendix A. 

For this manual, the term “opioids” is used to represent morphine, codeine, heroin, 

hydrocodone, hydromorphone, oxycodone, and oxymorphone. 

Cognitive and psychomotor performance can be impaired by opioids, although the 

duration and extent of impairment depend on the type of opioid, 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 miosis, confusion or mental dullness, slurring 

of speech, drowsiness, or nodding—the head drooping toward the chest and then bobbing up 

(“on the nod”). 
5-26 

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 opioids are 

physically and psychologically addictive and produce withdrawal symptoms that differ in 

type and severity. Flu like symptoms are common during opioid withdrawal (e.g., watery 

eyes, nausea and vomiting, muscle cramps, and loss of appetite). 

The opioids have agonist or partial agonist activity at the opioid receptor and may or 

may not have structural similarity to the principal opium alkaloids. The use of opioids is a 

major illicit drug problem around the world, considering the impact on public health and 

public order.38 In the United States, the problem of diverted pharmaceutical opioids is 

reaching crisis proportions. About one-sixth of the people aged 12 and older who started drug 

use in 2010 began with abuse of prescription painkillers from various sources.39 

Effective October 1, 2017, HHS revised the Mandatory Guidelines to include the 

semisynthetic 6-keto opioids oxycodone, oxymorphone, hydrocodone, and hydromorphone 

as analytes, in addition to codeine and morphine. Examples of pharmaceuticals that do not 

metabolize to the opioids above include, but are not limited, to the following:

■ Propoxyphene; 

■ Methadone; 

■ Meperidine;

■ Fentanyl; 

■ Pentazocine;

■ Buprenorphine; and 

■ Tramadol.

The Federal Workplace Drug Testing Program’s goal regarding opioids is to detect 

the illicit use of morphine, codeine, heroin, oxycodone, oxymorphone, hydrocodone, and 

hydromorphone. For specimens that have been reported positive for one or more of these 

opioid analytes, an MRO may request quantitative results below the cutoff for any of the 

other opioid analytes tested. This information may be helpful to the MRO in assessing the 

medical explanation provided by the donor. The requests may be for an individual specimen 

or a blanket request for all quantitative results when one or more opioid analytes is reported 

as positive.
5-27 

5.4.1 Morphine and Codeine 

A positive urine test for codeine and or morphine would be comprised of a confirmed 

concentration equal to or greater than 2000 ng/mL codeine or 4000 ng/mL morphine. A 

positive oral fluid test for codeine and or morphine would be comprised of a confirmed 

concentration equal to or greater than 15 ng/mL codeine or 15 ng/mL morphine All of these 

drugs are available as prescription medications and a donor who tests positive for one or 

more opioids may have legally used the drug(s). These opioids are differentiated during 

testing and will not be misidentified using a confirmatory test as required by the Mandatory 

Guidelines. 

The MRO must assess the laboratory result and the information from the donor to 

verify the drug test positive. The opioid drug class poses some unique challenges with regard 

to interpretation because a positive result may be from a legitimate source, including the 

following:

■ Codeine or morphine may be present due to consumption of poppy seeds. 

■ A positive result for any of the opioid analytes (with the exception of 6-AM) may be 

from legitimate use of a drug product. 

For urine specimens, the confirmatory cutoffs for codeine and morphine (i.e., 2000 

and 4000 ng/mL, respectively) are above concentrations seen in urine after consumption of 

poppy seed food products. 

For oral fluid specimens positive for codeine and/or morphine, HHS included 

additional criteria in the OFMG as follows:

■ When a laboratory reports codeine and/or morphine positive with a quantitative result 

less than 150 ng/mL (i.e., 10 times the confirmatory test cutoff): 

– The MRO reports the result as negative when the donor does not admit to 

unauthorized use of the drugs that caused the positive result(s). 

– The MRO shall report the result as positive when the donor admits unauthorized 

use of the drug(s) that caused the positive result. 

■ When a laboratory reports codeine and/or morphine positive with a quantitative result 

equal to or greater than 150 ng/mL: 

– The MRO must report the result as negative when the donor provides a legitimate 

medical explanation (e.g., valid prescription) for the positive result(s). 

– The MRO shall report the result as positive when the donor is unable to provide a 

legitimate medical explanation. 
5-28 

Note: Consumption of food products is not a legitimate medical explanation for 

the donor having morphine or codeine at or above this concentration. 

Certified laboratories are required to validate all confirmatory assays (urine and oral 

fluid) prior to use with Federal agency specimens. For opioid confirmatory assays, each 

laboratory must document the assay’s ability to identify and accurately quantitate 6-

acetylmorphine, codeine, hydrocodone, hydromorphone, morphine, oxycodone, and 

oxymorphone in the presence of opioid metabolites (e.g., norcodeine, norhydrocodone, 

norhydromorphone, noroxycodone, noroxymorphone) and also demonstrate that these 

compounds are not misidentified as 6-acetylmorphine, codeine, hydrocodone, 

hydromorphone, morphine, oxycodone, and oxymorphone. These experiments must be 

performed on at least an annual basis to verify the assay’s continued performance. 

5.4.1.1 Drug Testing

See Appendix D tables and below for urine and oral fluid reporting criteria. 

For grouped analytes (i.e., two or more analytes that are in the same drug class and 

have the same initial test cutoff):

■ Initial Test

– Immunoassay: The test must be calibrated with one analyte from the group 

identified as the target analyte. The cross-reactivity of the immunoassay to the 

other analyte(s) within the group must be 80 percent or greater; if not, separate 

immunoassays must be used for the analytes within the group. 

– Alternate technology: Either one analyte or all analytes from the group must be 

used for calibration, depending on the technology. At least one analyte within the 

group must have a concentration equal to or greater than the initial test cutoff or, 

alternatively, the sum of the analytes present (i.e., equal to or greater than the 

laboratory’s validated limit of quantification) must be equal to or greater than the 

initial test cutoff.

■ Confirmatory Test 

– Mass spectrometry: The test method must use an analytical method combining 

chromatographic separation and mass spectrometric identification (i.e., gas 

chromatography/mass spectrometry (GC-MS), liquid chromatography/mass 

spectrometry (LC-MS), GC-MS/MS, LC-MS/MS] or equivalent. The test must be 

calibrated with each analyte from the group identified as the target analyte. Test 

method calibration must include at least one calibrator at the confirmatory cutoff.
5-29 

(a) Urine

(b) Oral Fluid

When the MRO requests that a split specimen (Bottle B) be tested for codeine and/or 

morphine, the second laboratory performs confirmatory testing for both codeine and 

morphine but reports only the analyte(s) reported positive by the first laboratory (as specified 

in the MRO retest request). The second laboratory reports analytes as reconfirmed or failed 

to reconfirm. The following rules apply: 

■ The second laboratory does NOT apply the HHS cutoff (e.g., urine 2000 ng/mL 

codeine and 4000 ng/mL morphine, oral fluid 15 ng/mL) to split specimens. The 

laboratory must use its established limit of detection (LOD) or limit of quantification 

(LOQ) as the decision point for determining whether a drug has been reconfirmed in 

the retest specimen.

■ The laboratory must identify the presence of morphine or codeine (at or above the 

laboratory’s established LOD for the assay) in order to report morphine and/or 

codeine as reconfirmed,

■ An MRO may request the quantitative result of morphine or codeine below the cutoff 

for a specimen reported positive for the other analyte. This information may be 

helpful to the MRO in assessing the medical explanation provided by the donor. 

Initial Test 

Analyte 

Initial Test 

Cutoff 

(ng/mL)

Confirmatory Test 

Analyte 

Confirmatory Test 

Cutoff 

(ng/mL)

Codeine/Morphine 2000 

Codeine

Morphine

2000 

4000 

Initial Test 

Analyte 

Initial Test 

Cutoff 

(ng/mL)

Confirmatory Test 

Analyte 

Confirmatory Test 

Cutoff 

(ng/mL)

Codeine/Morphine 30

Codeine

Morphine

15

15
5-30 

5.4.1.2 Background 

Morphine is the most abundant naturally occurring opiate and is representative of the 

opioid class of drugs. Morphine is regulated under the CSA as Schedule II opiate. Morphine 

is commonly used for its potent analgesic properties. 

Codeine is regulated under the CSA as Schedule II opiate. Codeine is commonly used 

as an analgesic, antitussive, and antidiarrheal agent. Codeine was first isolated in 1832 and is 

an opioid analgesic with weak affinity for the mu opioid receptor. In its pure form, codeine is 

considered a Schedule II compound but is classified as a Schedule III compound when 

combined with other weak analgesics (such as acetaminophen) and as Schedule V when in 

liquid cough suppressant preparations. Its analgesic potency is approximately 10% that of 

morphine. Codeine is produced commercially by 3-0-methylation of morphine. 

Codeine is most often dispensed based on a physician’s valid prescription: however, 

codeine may be available in certain preparations (e.g., liquid antitussive) without a 

prescription at the pharmacy counter in certain local jurisdictions throughout the United 

States, depending on state laws. If codeine is obtained legitimately through a pharmacy under 

those circumstances, the pharmacy will create and retain a record that can be verified by the 

MRO. In the absence of verification for the record of sale of the codeine preparation from the 

pharmacy, the MRO must report the result as positive.

5.4.1.3 Routes of Administration

■ Morphine— oral (i.e., tablets), rectal, intravenous injection, smoking, and intranasal 

(i.e., snorting). 

■ Codeine— oral (i.e., tablets and liquid solution) and intravenous injection.

■ Heroin—intravenous injection, intranasal (i.e., snorting), and smoking. 

■ Poppy seeds-oral (i.e., food, tea).

Abusers may use in a variety of methods, including intravenous injection and 

smoking. 

5.4.1.4 Metabolism and Excretion

(a) Urine

Morphine is rapidly absorbed and excreted as unchanged morphine, morphine-3-

glucuronide (primary metabolite) and morphine-6-glucuronide conjugates, and minor 

metabolites (e.g., hydromorphone, normorphine, morphine-3-ethereal sulfate, morphine-3,6-
5-31 

diglucuronide). Generally, morphine and its metabolites can be detected in urine up to about 

4 days after morphine 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), and minor metabolites (e.g., hydrocodone, norcodeine, 

normorphine, morphine-3-ethereal sulfate, morphine-3,6-diglucuronide.) 

(b) Oral Fluid

Morphine is rapidly absorbed, appears in oral fluid following use of morphine, heroin 

and poppy seeds.7,40 Morphine detected in oral fluid following ingestion of poppy seeds 

indicated that morphine was positive for a shorter interval of 1-2 hours.8 Single dose studies 

of codeine demonstrated codeine is detected in oral fluid within an hour but morphine was 

not detected.41

5.4.1.5 Pharmaceuticals and Use 

(a) Pharmaceutical Drug Products 

Many pharmaceuticals containing opioids are available by prescription, although 

codeine may be obtained over the counter in some cases. MROs should have access to 

references with up-to-date information on such products. 

Examples of morphine trade names include Roxanol®, MS Contin®, Roxanol-T®, 

Kadian®, Duramorph®, Embeda®, MorphaBond®, Avinza®, Arymo ER®, Astramorph PF®, 

Oramorph SR®, Infumorph®, and RMS®. Embeda® is a combination of morphine and 

naltrexone. 

Examples of codeine combination product trade names include Fioricet®, Colrex®, 

Tylenol with Codeine #3®, Tylenol with Codeine #4®, Phenflu CDX®, Maxiflu CD®, 

Rolatuss®, Fiorinal with Codeine III®, Fiortal with Codeine®, SOMA Compound with 

Codeine®, Empirin with Codeine®, Ambenyl®, Dimetane DC®, Notuss-NX®, and 

Promethazine VC with Codeine®. 

(b) Non-Pharmaceutical Drug Products

Poppy seeds may be a significant dietary source of morphine and/or codeine. To 

alleviate this problem and to distinguish between heroin and legitimate morphine/codeine 

use, HHS has set the initial testing cutoff for urine morphine and codeine at 2000 ng/mL and 

confirmatory cutoffs at 4,000 ng/mL and 2,000 ng/mL, respectively. 
5-32 

Note: Heroin contaminated with acetylcodeine may produce positive test results for 

morphine, and codeine in addition to 6-acetylmorphine. 

5.4.2 Oxycodone, Hydrocodone, Oxymorphone, Hydromorphone 

A positive test for hydrocodone, hydromorphone, oxycodone, or oxymorphone would 

be comprised of any or all analytes with a confirmed urine concentration equal to or greater 

than 100 ng/mL or a confirmed oral fluid concentration equal to or greater than 15 ng/mL. 

All of these drugs are available as prescription medications and a donor who tests 

positive for one or more opioids may have legally used the drug(s). There are no nonprescription or OTC medication that contain these opioids. These opioids are differentiated 

during testing and will not be misidentified using a confirmatory test as required by the 

Mandatory Guidelines. 

Certified laboratories are required to validate all confirmatory assays (urine and oral 

fluid) prior to use with Federal agency specimens. For opioid confirmatory assays, each 

laboratory must document the assay’s ability to identify and accurately quantitate 6-

acetylmorphine, codeine, hydrocodone, hydromorphone, morphine, oxycodone, and 

oxymorphone in the presence of opioid metabolites (e.g., norcodeine, norhydrocodone, 

norhydromorphone, noroxycodone, noroxymorphone) and also demonstrate that these 

compounds are not misidentified as 6-acetylmorphine, codeine, hydrocodone, 

hydromorphone, morphine, oxycodone, and oxymorphone. These experiments must be 

performed on at least an annual basis to verify the assay’s continued performance. 

5.4.2.1 Drug Testing

See Appendix D tables and below for urine and oral fluid reporting criteria. 

For grouped analytes (i.e., two or more analytes that are in the same drug class and 

have the same initial test cutoff):

■ Initial Test

– Immunoassay: The test must be calibrated with one analyte from the group 

identified as the target analyte. The cross-reactivity of the immunoassay to the 

other analyte(s) within the group must be 80 percent or greater; if not, separate 

immunoassays must be used for the analytes within the group. 

– Alternate technology: Either one analyte or all analytes from the group must be 

used for calibration, depending on the technology. At least one analyte within the 

group must have a concentration equal to or greater than the initial test cutoff or, 
5-33 

alternatively, the sum of the analytes present (i.e., equal to or greater than the 

laboratory’s validated limit of quantification) must be equal to or greater than the 

initial test cutoff.

■ Confirmatory Test 

– Mass spectrometry: The test method must use an analytical method combining 

chromatographic separation and mass spectrometric identification (i.e., gas 

chromatography/mass spectrometry (GC-MS), liquid chromatography/mass 

spectrometry (LC-MS), GC-MS/MS, LC-MS/MS] or equivalent. The test must be 

calibrated with each analyte from the group identified as the target analyte. Test 

method calibration must include at least one calibrator at the confirmatory cutoff. 

(a) Urine

(b) Oral Fluid

When the MRO requests that a split specimen (Bottle B) be tested for hydrocodone, 

hydromorphone, oxycodone, or oxymorphone, the second laboratory performs confirmatory 

testing for hydrocodone, hydromorphone, oxycodone, or oxymorphone and reports only the 

analyte(s) reported positive by the first laboratory (as specified in the MRO retest request). 

The second laboratory reports analytes as reconfirmed or failed to reconfirm. The following 

rules apply: 

■ The second laboratory does NOT apply the HHS cutoff (e.g., urine 100 ng/mL, oral 

fluid 15 ng/mL) to split specimens. The laboratory must use its established limit of 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory Test 

Analyte

Confirmatory Test 

Cutoff 

(ng/mL)

Hydrocodone/Hydromorphone 300 Hydrocodone

Hydromorphone

100 

100 

Oxycodone/Oxymorphone 100 Oxycodone

Oxymorphone

100 

100 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory Test 

Analyte

Confirmatory Test 

Cutoff 

(ng/mL)

Hydrocodone/Hydromorphone 30 Hydrocodone

Hydromorphone

15

15

Oxycodone/Oxymorphone 30 Oxycodone

Oxymorphone

15

15
5-34 

detection (LOD) or limit of quantification (LOQ) as the decision point for 

determining whether a drug has been reconfirmed in the retest specimen.

■ The laboratory must identify the presence of hydrocodone, hydromorphone, 

oxycodone, or oxymorphone (at or above the laboratory’s established LOD for the 

assay) in order to report for hydrocodone, hydromorphone, oxycodone, or 

oxymorphone as reconfirmed. 

5.4.2.2 Background 

Hydrocodone and oxycodone are widely used and abused in the United States. 

Hydrocodone, hydromorphone, oxycodone, and oxymorphone are regulated under CSA as 

Schedule II opiates. 

Hydrocodone is a semisynthetic opioid derived from codeine and is indicated for 

moderate to moderately severe pain as well as symptomatic relief of a nonproductive cough. 

It is a very commonly prescribed opioid. Hydrocodone, like codeine, has weak binding to the 

mu opioid receptor and acts as a pro-drug metabolizing to hydromorphone, which has 

significantly stronger mu opioid receptor binding activity. 

Hydromorphone is a semisynthetic opioid that acts as an agonist on the mu opioid 

receptor with 7 to 10 times the potency of morphine. Hydromorphone is also a metabolite of 

hydrocodone via O-demethylation. 

Oxycodone is available in pure form or in combination with acetaminophen or 

aspirin. Oxycodone has high oral bioavailability with a structure similar to hydrocodone with 

an added hydroxyl group on the number 14 carbon atom. 

Oxymorphone has approximately 10 times the potency of morphine for analgesia. 

5.4.2.3 Routes of Administration

■ Hydrocodone—oral (i.e., tablet, capsule, liquid, or extended-release tablet or liquid). 

■ Hydromorphone—oral (i.e., tablet or extended-release tablet), rectal, and intravenous 

injection.

■ Oxycodone—oral (i.e., liquid, tablet, capsule, and extended-release tablet). 

■ Oxymorphone—oral (i.e., tablet or extended-release tablet). 

Abusers may use in a variety of methods, including intravenous injection and 

smoking. 
5-35 

5.4.2.4 Metabolism and Excretion

(a) Urine

Note: Hydrocodone has been reported to be a minor metabolite of codeine and 

hydromorphone has been reported to be a minor metabolite of morphine.41-43 

Hydrocodone is metabolized to norhydrocodone, hydromorphone, and minor 

metabolites such as hydrocodol and hydromorphol. There is little conjugation of 

hydrocodone; however, a significant percentage of the hydromorphone is conjugated and 

excreted as the glucuronide conjugate. The predominant excretion product of hydromorphone 

is the glucuronide conjugate. Hydromorphol is a very minor metabolite. Interpretation of 

urine tests for hydrocodone is complicated by its metabolism to hydromorphone, which is 

also available commercially and misused. An investigation of a single, oral, immediate 

release, 20 mg dose of hydrocodone was completed using 12 healthy, drug-free adults. The 

hydrocodone was administered in a controlled clinical setting and urine specimens were 

collected at timed intervals for up to 52 hours. Hydrocodone appeared within 2 hours 

followed by the appearance of hydromorphone. Hydrocodone exhibited peak concentrations 

higher than the metabolite, hydromorphone, which was excreted extensively as a conjugate. 

At the cutoff concentration of 50 ng/ml, detection times were around 28 hours for 

hydrocodone and 26 hours for hydromorphone. Using 100 ng/mL as the cutoff, the study 

shows that hydrocodone and hydromorphone may be detectable in urine for one day.44 

Oxymorphone is extensively metabolized and is excreted as a glucuronide conjugate 

and as a 6-oxymorphol glucuronide conjugate. Oxycodone is metabolized by N- and Odemethylation, 6 keto reduction and conjugation. A metabolite of oxycodone, oxymorphone, 

is a potent narcotic analgesic while another metabolite, noroxycodone, is not active. 

Additional metabolites are noroxymorphone and the minor metabolites as noroxycodols and 

oxycodols. Interpretation of urine tests for oxycodone is complicated by its metabolism to 

oxymorphone, which is also available commercially and misused. A single administration of 

a low dose of oxycodone (20 mg) characterized the metabolism and disposition of oxycodone 

in human urine. Oxycodone appeared in the urine in about 2 hours and was generally found 

along with oxymorphone. Peak concentrations of oxycodone and metabolites occurred 

between 3 and 19 hours. The mean peak concentration of oxycodone was higher than that of 

the oxymorphone, but the oxycodone concentration declined more quickly than the 

concentration of oxymorphone. At a cutoff concentration of 50 ng/mL, detection times were 

approximately 30 hours for oxycodone and oxymorphone. Some final specimens at relatively 
5-36 

low concentrations contained only oxymorphone. Using 100 ng/mL as the cutoff, the study 

shows that oxycodone and oxymorphone are generally detectable in urine for one day.45 

(b) Oral Fluid

Both oxycodone and oxymorphone have been reported to be readily detectable in oral 

fluid specimens collected from pain patients.46,47 Oxycodone is metabolized in relatively 

minor amounts to oxymorphone.48 Oxymorphone is a potent analgesic used for pain relief 

orally and parenterally, and is primarily metabolized by conjugation.49 Hydromorphone 

appears rapidly in oral fluid following intravenous administration.50 

A single administration of a 2 low doses of immediate-release 

hydrocodone/acetaminophen (10/325 mg) characterized the metabolism and disposition of 

hydrocodone in human oral fluid. Hydrocodone appeared in the oral fluid within 15 minutes. 

The metabolite norhydrocodone appeared 0.25-1 hours post dosing. Hydromorphone was not 

detected. Peak concentrations of hydrocodone occurred between 0.3 and 4 hours; the 

norhydrocodone between 1 and 8 hours. The mean peak concentration of hydrocodone was 

higher than that of the norhydrocodone, but the hydrocodone concentration declined more 

quickly than the concentration of noroxycodone. At a cutoff concentration of 1 ng/mL, 

detection times were approximately 30 hours for hydrocodone and 18 hours for 

norhydrocodone. Using 15 ng/mL as a cutoff, the study shows that hydrocodone is generally 

detectable in oral fluid for less than one day.51 

A single administration of a low dose of controlled-release oxycodone (20 mg) 

characterized the metabolism and disposition of oxycodone in human oral fluid. Oxycodone 

appeared in the oral fluid in 15-30 minutes. The metabolite noroxycodone appeared 1.5-5 

hours post dosing. Oxymorphone was frequently not detected. Peak concentrations of 

oxycodone and metabolites occurred between 2.5 and 8 hours. The mean peak concentration 

of oxycodone was higher than that of the noroxycodone, but the oxycodone concentration 

declined more quickly than the concentration of noroxycodone. At a cutoff concentration of 1 

ng/mL, detection times were approximately 34 hours for oxycodone and noroxycodone. 

Using 15 ng/mL as a cutoff, the study shows that oxycodone is generally detectable in oral 

fluid for one day.52
5-37 

5.4.2.5 Pharmaceuticals and Use 

(a) Prescription Drug Products

Many pharmaceuticals containing opioids are available by prescription. MROs should 

have access to references with up-to-date information on such products. 

 Examples of hydrocodone trade names include Vicodin®, Lortab®, Anexsia®, 

Dolorex Forte®, Donatussin®, Drocon-CS®, Endacof XP®, Histussin D®, Hycet®, 

Hydrocet®, Liquicet®, Lorcet®, Lorcet Plus®, Lortab Elixir®, Maxidone®, Norco®, 

Polygesic®, Stagesic®, Vicodin®, Vicoprofen®, Xodol®, Zydone®, and Zohydro® 

Examples hydromorphone trade names include Dilaudid®, Exalgo®, and Hydromorph 

Contin®. 

Examples of oxycodone trade names include Percocet®, Percodan®, Oxycontin®, 

Combunox®, Dazidox®, Endocet®, Endocodone®, Endodan®, ETH-Oxydose®, Lynox®, 

Magnacet®, Narvox®, Oxycontin®, Oxyfast®, OxyIR®, Percocet®, Percodan®, 

Percolone®, Primlev®, Perloxx®, Roxicet®, Roxicodone®, Roxiprin®, Taxadone®, 

Tylox®, and Xolox®. 

Examples of oxymorphone trade names include Opana® and Numorphan®.

(b) Non-prescription Drug Products

There are no non-prescription drug products with hydrocodone, hydromorphone, 

oxycodone, or oxymorphone. 

5.4.3 Poppy Seeds 

Poppy seeds may be a significant dietary source of morphine and/or codeine. To 

alleviate this problem and to distinguish between heroin and legitimate morphine/codeine 

use, HHS has set the opiates initial testing at 2000 ng/mL and confirmatory cutoffs for 

morphine and codeine at 4000 ng/mL and 2000 ng/mL, respectively. In October 2010, HHS 

revised the Mandatory Guidelines to require laboratories to test all Federal agency specimens 

for heroin metabolite (6-AM) regardless of morphine concentration by performing a 6-AM 

initial test and confirmatory test. The requirement was implemented because data from

laboratories indicated that 6-AM could be present in specimens with morphine less than 2000 

ng/mL. 
5-38 

Eating a normal dietary amount of poppy seeds can cause a urine specimen to test 

positive for morphine and codeine. The concentration of morphine can be substantial, with 

usually very low concentrations or no detectable codeine. In many instances, a donor will not 

know that poppy seeds can cause a positive test or realize that he/she had eaten poppy seeds 

around the time the urine was collected. HHS included additional criteria in the Mandatory 

Guidelines to distinguish between specimens testing positive due to opioids abuse and 

specimens testing positive due to poppy seeds. See 5.5.1 above. 

5.4.4 6-Acetylmorphine (6-AM) 

A positive test would be comprised of a confirmed urine 6-AM concentration equal to 

or greater than 10 ng/mL or a confirmed oral fluid 6-AM concentration equal to or greater 

than 2 ng/mL. 

A positive 6-AM result is evidence of illegal drug use. There are no prescription, nonprescription or OTC medications that contain heroin and there are no legal medical uses of 

heroin. 6-AM is differentiated from the opioids drugs during testing and will not be 

misidentified using a confirmatory test as required by the Mandatory Guidelines. 

Certified laboratories are required to validate all confirmatory assays (urine and oral 

fluid) prior to use with Federal agency specimens. For opioid confirmatory assays, each 

laboratory must document the assay’s ability to identify and accurately quantitate 6-AM in 

the presence of high levels of opioids and opioid metabolites and also demonstrate that these 

compounds are not misidentified as 6-AM (i.e., by analyzing samples containing opioids and 

opioid metabolites without 6-AM). These experiments must be performed on at least an 

annual basis to verify the assay’s continued performance. The National Laboratory 

Certification Program (NLCP) includes opioids and opioid metabolites in the performance 

testing (PT) program to ensure all certified laboratories are distinguishing those from the 6-

AM. 

5.4.4.1 Drug Testing

See Appendix D tables and below for urine and oral fluid reporting criteria. 

For single analytes (i.e., one analyte that is in the drug class and a single initial test 

cutoff):

■ Initial Test
5-39 

– Immunoassay: The test must be calibrated with one analyte from the group 

identified as the target analyte. The cross reactivity of the immunoassay to the 

other analyte(s) within the group must be 80 percent or greater; if not, separate 

immunoassays must be used for the analytes within the group. 

– Alternate technology: Either one analyte or all analytes from the group must be 

used for calibration, depending on the technology. At least one analyte within the 

group must have a concentration equal to or greater than the initial test cutoff or, 

alternatively, the sum of the analytes present (i.e., equal to or greater than the 

laboratory’s validated limit of quantification) must be equal to or greater than the 

initial test cutoff.

– The confirmatory test cutoff must be used for an alternate technology initial test 

that is specific for the target analyte (i.e., 2 ng/mL for oral fluid 6-AM).

■ Confirmatory Test 

– Mass spectrometry: The test method must use an analytical method combining 

chromatographic separation and mass spectrometric identification (i.e., gas 

chromatography/mass spectrometry (GC-MS), liquid chromatography/mass 

spectrometry (LC-MS), GC-MS/MS, LC-MS/MS] or equivalent. The test must be 

calibrated with the analyte from the group identified as the target analyte. Test 

method calibration must include at least one calibrator at the confirmatory cutoff.

(a) Urine

(b) Oral Fluid

When the MRO requests that a split specimen (Bottle/Tube B) be tested for 6-AM, 

the second laboratory performs confirmatory testing for 6-AM and reports only the analyte(s) 

reported positive by the first laboratory (as specified in the MRO retest request). The second 

laboratory reports analytes as reconfirmed or failed to reconfirm. The following rules apply: 

■ The second laboratory does NOT apply the HHS cutoff (e.g., urine 10 ng/mL, oral 

fluid 2 ng/mL) to split specimens. The laboratory must use its established limit of 

detection (LOD) or limit of quantification (LOQ) as the decision point for 

determining whether a drug has been reconfirmed in the retest specimen.

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory Test 

Analyte

Confirmatory Test 

Cutoff 

(ng/mL)

6-Acetylmorphine 10 6-Acetylmorphine 10 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory Test 

Analyte

Confirmatory Test 

Cutoff 

(ng/mL)

6-Acetylmorphine 4 6-Acetylmorphine 2
5-40 

■ The laboratory must identify the presence of 6-AM (at or above the laboratory’s 

established LOD for the assay) in order to report 6-AM as reconfirmed.

5.4.4.2 Background 

Heroin (diacetylmorphine), a semisynthetic opioid, is regulated under the CSA as 

Schedule II opium derivative. Heroin is obtained by reacting natural morphine with acetic 

anhydride. Heroin has no legitimate medical use in the United States and is only available 

illegally (Schedule I). 

5.4.4.3 Routes of Administration

■ Heroin—intravenous injection, smoking, and intranasal (i.e., snorting).

■ Abusers may use in a variety of methods, including intravenous injection and 

smoking. 

5.4.4.4 Metabolism and Excretion

(a) Urine

Heroin is not easily detected in urine and, therefore, usage is determined by detection 

of its metabolite 6-acetylmorphine (6-AM). There is no legitimate medical explanation for a 

6-AM positive result. Heroin itself is rarely detected in urine. Heroin (diacetylmorphine) is 

deacetylated to its primary metabolite, 6-acetylmorphine (6-AM), within minutes of 

administration. 6-AM is metabolized to morphine, so morphine is generally present (i.e., at or 

above the program cutoff of 2000 ng/mL) in positive 6-AM specimens. Generally, 6-AM is 

most likely to be detected within the first 24 hours post-administration because of heroin’s 

rapid metabolism to morphine. 

Note: There are reasons that morphine may not be present or is present below 2000 

ng/mL in a positive 6-AM specimen (e.g., if the donor used heroin close to the time of 

collection, if the donor has a metabolic defect in the metabolism of 6-AM resulting in 

prolonged excretion, if a donor’s morphine metabolic pathways have been altered, or if 

another substance interacted with 6-AM or morphine). There have been reports of these 

“atypical” specimens containing 6-AM without detectable morphine. Therefore, heroin itself 

is not detected in urine and 6-AM is rarely detected. 

Note: Heroin contaminated with acetylcodeine may produce positive test results for 

morphine, and codeine in addition to 6-acetylmorphine. 
5-41 

(b) Oral Fluid

Heroin (diacetylmorphine) is deacetylated to its primary metabolite, 6-AM, within 

minutes of administration. 6-AM appears in oral fluid within minutes following smoked or 

injected heroin administration.7 Generally, 6-AM detection in oral fluid is one day or less. 

5.4.4.5 Pharmaceuticals and Use 

(a) Prescription Drug Products

Heroin is regulated by the CSA as a Schedule I drug and is not available as a 

pharmaceutical product. 

(b) Non-Prescription Drug Products

There are no non-prescription products that contain heroin. 

Note: Heroin contaminated with acetylcodeine may produce positive test results for 

morphine, and codeine in addition to 6-acetylmorphine. 

5.5 Phencyclidine (PCP)53

5.5.1 Phencyclidine 

A positive test would be comprised of a confirmed urine phencyclidine concentration 

equal to or greater than 25 ng/mL or a confirmed oral fluid phencyclidine concentration equal 

to or greater than 10 ng/mL. 

A positive phencyclidine result is evidence of illegal drug use. There are no 

prescription, non-prescription or OTC medications that contain phencyclidine and there is no 

legal medical use of phencyclidine. There are no other substances that can be misidentified as 

phencyclidine using a confirmatory test as required by the Mandatory Guidelines. 

Certified laboratories are required to validate all confirmatory assays (urine and oral 

fluid) prior to use with Federal agency specimens. For phencyclidine confirmatory assays, 

each laboratory must document the assay’s ability to identify and accurately quantitate 

phencyclidine. These experiments must be performed on at least an annual basis to verify the 

assay’s continued performance.

5.5.1.1 Drug Testing

See Appendix D tables and below for urine and oral fluid reporting criteria. 
5-42 

For single analytes (i.e., one analyte that is in the drug class and a single initial test 

cutoff):

■ Initial Test

– Immunoassay: The test must be calibrated with one analyte from the group 

identified as the target analyte. The cross reactivity of the immunoassay to the 

other analyte(s) within the group must be 80 percent or greater; if not, separate 

immunoassays must be used for the analytes within the group. 

– Alternate technology: The test must be calibrated with one analyte from the group 

identified as the target analyte. The cross reactivity of the immunoassay to the 

other analyte(s) within the group must be 80 percent or greater; if not, separate 

immunoassays must be used for the analytes within the group. 

■ Confirmatory Test 

– Mass spectrometry: The test method must use an analytical method combining 

chromatographic separation and mass spectrometric identification (i.e., gas 

chromatography/mass spectrometry (GC-MS), liquid chromatography/mass 

spectrometry (LC-MS), GC-MS/MS, LC-MS/MS] or equivalent. The test must be 

calibrated with phencyclidine. Test method calibration must include at least one 

calibrator at the confirmatory cutoff.

(a) Urine

(b) Oral Fluid

When the MRO requests that a split specimen (Bottle B) be tested for phencyclidine, 

the second laboratory performs confirmatory testing for phencyclidine analyte reported 

positive by the first laboratory (as specified in the MRO retest request). The second 

laboratory reports analytes as reconfirmed or failed to reconfirm. The following rules apply: 

■ The second laboratory does NOT apply the HHS cutoff (e.g., urine 25 ng/mL, oral 

fluid 10 ng/mL) to split specimens. The laboratory must use its established limit of 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory Test 

Analyte

Confirmatory Test 

Cutoff 

(ng/mL)

Phencyclidine 25 Phencyclidine 25 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory Test 

Analyte

Confirmatory Test 

Cutoff 

(ng/mL)

Phencyclidine 10 Phencyclidine 10
5-43 

detection (LOD) or limit of quantification (LOQ) as the decision point for 

determining whether a drug has been reconfirmed in the retest specimen.

■ The laboratory must identify the presence of phencyclidine (at or above the 

laboratory’s established LOD for the assay) in order to report phencyclidine as 

reconfirmed,

5.5.1.2 Background 

Phencyclidine, an arylcyclohexylamine, is regulated under the CSA as a Schedule II 

depressant.

54 Phencyclidine was first synthesized in the 1950s as a general anesthetic

(Sernyl®). Street names include Angel Dust, Crystal, Killer Weed, Supergrass, and Rocket 

Fuel. Phencyclidine 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. 

Phencyclidine has a variety of effects on the central nervous system. Intoxication 

begins several minutes after ingestion and usually lasts 8 hours or more. Phencyclidine 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 phencyclidine 

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.55

5.5.1.3 Routes of Administration

■ Phencyclidine— oral (i.e., tablets, capsules), intravenous injection, smoking 

(preferred), and intranasal (i.e., snorting). 

■ Abusers may use in a variety of methods, including intravenous injection and 

smoking. 

5.5.1.4 Metabolism and Excretion

(a) Urine

Phencyclidine is well absorbed by any route and is excreted unchanged and as 

conjugates of hydroxylated phencyclidine. About 4% to 19% of the phencyclidine dose is 

excreted in the urine as unchanged drug. Phencyclidine is a weak base that concentrates in 
5-44 

acidic solutions in the body. Because of gastric acidity, phencyclidine repeatedly re-enters 

the stomach from plasma and is reabsorbed into plasma from the basic medium of the 

intestine. Generally, phencyclidine is considered detectable in urine for several days to 

several weeks depending on the frequency of use. 

(b) Oral Fluid

Phencyclidine has been measured in oral fluid following different routes of 

administration.56,57 Phencyclidine detection in oral fluid is at least one day. 

5.5.1.5 Pharmaceuticals and Use 

(a) Prescription Drug Products

Phencyclidine is regulated as a Schedule II drug and is not available as a 

pharmaceutical.

(b) Non-prescription Drug Products

There are no non-prescription medications that contains this drug. 

5.6 Other Non-Negative Reports 

The MRO must report a verified test result to an agency by faxing a completed MRO 

copy of the Federal CCF, transmitting a scanned image of the completed MRO copy of the 

Federal CCF, or faxing a separate report using a letter or memorandum format. If a report is 

sent electronically, the MRO must ensure the security of the transmission. In most cases, the 

Federal agency will be expected to provide the medical examination to ensure the report is 

unbiased. 

5.6.1 Dilute Specimens

MRO actions are shown in Table 4, Medical Review Officer Actions for Primary (A) 

Specimen Reports.

5.6.1.1 Urine

This section on dilution/substitution deals only with urine specimens. A dilute 

finding may be reported in conjunction with a positive or negative urine drug test. A donor 

may produce urine that meets the program criteria for dilution under some conditions, 

including the following: 

■ Working in hot weather conditions and drinking large amounts of fluid;

■ Taking a diuretic; or
5-45 

■ Drinking large volumes of fluids immediately before providing the specimen.

■ Medical conditions such as pituitary disorders (syndrome of inappropriate antidiuretic 

hormone secretion [SIADH]), diabetes, pregnancy, etc. 

A certifying technician at an IITF may report a urine specimen as dilute in 

conjunction with a negative drug test only when the creatinine test result is greater than 5.0 

mg/dL but less than or equal to 20.0 mg/dL and the specific gravity is equal to or greater than 

1.002 but less than 1.003. 

When creatinine is less than or equal to 5.0 mg/dL, the IITF must send the specimen 

to an HHS-certified laboratory for testing. Certified laboratories certified laboratory report 

urine specimen as dilute when the creatinine is greater than 5.0 mg/dL and less than 20.0 

mg/dL and the specific gravity is equal to or greater than 1.002 but less than 1.003; or the 

creatinine concentration is equal to or greater than 2.0 mg/dL but less than 20.0 mg/dL and 

the specific gravity is greater than 1.0010 but less than 1.0030. 

A certifying technician at a laboratory may report a urine specimen as dilute in 

conjunction with a negative drug test. A certifying scientist at a laboratory may report a urine 

specimen as dilute in conjunction with a positive or negative drug test 

The MRO’s response to a dilute urine specimen report depends on whether the drug 

test result is verified as positive or negative (see section 5.6.4.2 of this manual). MRO actions 

are shown in Table 4, Medical Review Officer Actions for Primary (A) Specimen Reports.

5.6.2 Substituted Urine Specimens

MRO actions are shown in Table 4, Medical Review Officer Actions for Primary (A) 

Specimen Reports.

5.6.2.1 Background 

The HHS criteria for identifying substituted urine specimens are based on the 

physiological ranges for creatinine concentration and specific gravity value of normal human 

urine. Laboratories and IITFs are required to measure the creatinine concentration in all 

regulated urine specimens, and to test specific gravity for specimens with creatinine 

concentration less than 20.0 mg/dL. There are established program cutoffs for identifying 

invalid and dilute, or substituted specimens based on the paired creatinine and specific 

gravity test results. Appendix D describes Specimen Reporting Criteria from the Mandatory 

Guidelines. 
5-46 

A donor may attempt to decrease the concentration of drugs or drug metabolites that 

may be present in his/her urine by dilution. Dilution may occur in vivo, by consumption of 

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 these 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 an observed collection. 

To identify diluted and substituted specimens, HHS developed criteria for evaluating 

specimens for the following human urine characteristics:

■ Creatinine is endogenously produced and cleared from the body by the kidneys. It is a 

normal constituent in urine. Normal human urine creatinine concentrations are at or 

above 20.0 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 dissolved 

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.

■ Biomarker analysis may be used to determine if commercially prepared material is 

being used to substitute for the authentic urine specimen; however, the reporting of 

the specimen will be as an invalid specimen.

5.6.2.2 MRO Actions

If the donor denies substituting the specimen, the donor is given the opportunity to 

prove the ability to produce urine that meets substitution criteria as described below.
5-47 

■ If the donor claims to have personal characteristics such that his/her urine normally 

satisfies the substitution criteria— 

– The MRO requests that the donor demonstrate this by providing a urine specimen 

that is collected following routine procedures for direct observation.

– The second specimen must meet the criteria for “substituted” and provide a 

reasonable basis to conclude that the donor’s personal characteristics are a 

legitimate medical explanation.

■ 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 donor must provide a copy of the medical record showing 

the creatinine and specific gravity values to support that claim. 

5.6.3 Adulterated Urine Specimens

MRO actions are shown in Table 4, Medical Review Officer Actions for Primary (A) 

Specimen Reports.

5.6.3.1 Background 

“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 test facility 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. Therefore, adulterants are 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, provided 

they use initial and confirmatory tests that meet the validation and quality control 

requirements specified by the Mandatory 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 initial drug test results, rather than the intended false negative. The immunoassay 

initial drug test is more sensitive to adulterants than the required confirmatory drug test 
5-48 

method. Currently, gas chromatography /mass spectrometry (GC-MS) assays for marijuana 

metabolite (THCA) and opioids appear to be affected by adulterants more than GC-MS

assays for other drugs.

When an IITF is unable to obtain a valid initial urine drug test result or when the IITF 

urine drug or specimen validity tests indicate a possible unidentified adulterant, the IITF 

sends the urine specimen to an HHS-certified laboratory for testing. 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 must contact the MRO prior to reporting a 

specimen as invalid to discuss 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 suspected 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. 

Note: Laboratories are not required to contact the MRO when a urine specimen meets 

criteria for reporting as invalid based on creatinine and specific gravity results, on pH, or on a 

confirmatory nitrite test concentration below 500 mcg/mL. It is unlikely that testing by 

another certified laboratory would provide different results. 

Because it is not possible to provide specific program guidance for all substances that 

may be used as adulterants, HHS allows certified IITFs and laboratories to test for any 

adulterant; however, HHS has included specific requirements in the Mandatory Guidelines 

for pH analysis and for the analysis of the known adulterants listed below. Appendix D 

describes Specimen Reporting Criteria from the Mandatory Guidelines.

The 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 4.0) or an extremely high pH (i.e., at or above 

11) is evidence of an adulterated specimen.

Research has shown that a specimen’s pH may increase up to 9.5 in vitro when the 

specimen is subjected to high temperatures for an extended time. Therefore, conditions 
5-49 

during specimen transport and storage may cause the pH to be within the invalid range (i.e., 

greater than or equal to 9 and less than 11.0). Note: See Table 4, Medical Review Officer 

Actions for Primary (A) Specimen Reports, concerning specimens reported as invalid based 

on pH in the greater than or equal to 9.0 to 9.5 range. 

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 runoff 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.
5-50 

Because low levels of nitrite may be present in human urine due to the reasons listed 

above, HHS set a cutoff level greater than or equal to 500 mcg/mL for adulteration and 200 

mcg/mL as an invalid result. 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. HHS set an initial 

test cutoff level of 50 mcg/mL for chromium (VI). Because the presence of chromium (VI) in 

a urine specimen is indicative of adulteration, laboratories report a specimen as adulterated 

when chromium (VI) is present at any concentration at or above the confirmatory test limit of 

quantification (LOQ).

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 

respectively, a gas, an immiscible liquid, or a solid in water or some other liquid. Surfactants 

tend to clump together when in solution, forming a surface between the fluid and air, with 

their hydrophobic components in the air and their hydrophilic components in the fluid. Often, 

surfactants will form “bubbles” within the fluid: a small sphere of hydrophobic “heads” 

surrounding a pocket of air containing the hydrophilic “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 “anti-bubbles” in fluid (i.e., a layer of air 

surrounding a pocket of water). HHS set an initial test cutoff level of 100 mcg/mL 

dodecylbenzene sulfonate equivalents. Laboratories report a specimen as adulterated when a 

surfactant is verified as present at or above a concentration equivalent to 100 mcg/mL 

dodecylbenzene sulfonate using a confirmatory test. 

Halogens are the four elements fluorine, chlorine, bromine, and iodine. Halogen 

compounds have been used as oxidizing adulterants. None of the halogens can be found in 

nature in their elemental forms. The assays used by certified laboratories identify halogen 

compounds that act as oxidants. These do not include the halogen salts (e.g., NaCl, KCl, NaI) 
5-51 

that may be present in a urine specimen. An oxidative halogen present at any concentration at 

or above the confirmatory test LOQ 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 present 

at any concentration at or above the confirmatory test LOQ 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 is 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 FDA allows its use as a flavoring agent in food 

preparation. Pyridine present at any concentration at or above the confirmatory test LOQ is 

evidence of adulteration.

5.6.3.2 MRO Actions

The MRO is required to attempt to contact the donor to 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 or oral fluid

specimen to meet the criteria for an adulterated result under the HHS Mandatory Guidelines.
5-52 

5.6.4 Invalid Specimens 

MRO actions are shown in Table 4, Medical Review Officer Actions for Primary (A) 

Specimen Reports.

5.6.4.1 Background 

(a) Urine

“Invalid” refers to a result reported by a laboratory for a urine specimen that contains 

an unidentified adulterant or interfering substance, has an abnormal physical characteristic,

has an endogenous substance at an abnormal concentration that prevents the laboratory from 

completing testing or obtaining a valid urine drug test result, or the concentration of a 

biomarker is not consistent with that established for human urine. HHS-certified laboratories 

are required to contact the MRO to discuss an invalid urine report for reason other than pH, 

creatinine, specific gravity, or nitrite reported as ≥200 mcg/mL and <500 mcg/mL by a nitrite 

confirmatory test. A primary (A) specimen reported as invalid for a test may be sent out for 

additional testing if the HHS-certified laboratory and the MRO conclude that additional 

testing may provide a definitive result for that specimen. A urine specimen reported as 

invalid for pH, creatinine, specific gravity, or nitrite reported as ≥200 mcg/mL and <500 

mcg/mL by a nitrite confirmatory test may not be sent out for additional testing. The HHS 

Guidelines specify the analytical methods to be used by HHS-certified laboratories for these

tests and there are no definitive test methods to apply to these specimens to provide a 

definitive result. (Note that additional testing should only be considered in the absence of a 

confirmed positive, adulterated, or substituted result and only if additional or different testing 

may lead to a definitive positive, negative, or adulterated drug test result.) If a specimen 

exhibits abnormal characteristics (e.g., unusual odor or color), causes reactions or responses 

characteristic of an adulterant during initial or confirmatory drug tests (e.g., non-recovery of 

internal standard, unusual response), or contains an unidentified substance that interferes 

with the confirmatory analysis, then additional testing may be performed.

An HHS-certified laboratory reports a primary (A) urine specimen as an invalid result 

when: 

■ Interference 

– Interference occurs on the initial drug tests on two separate aliquots (i.e., valid 

initial drug test results cannot be obtained); 

– Interference with the drug confirmatory assay occurs on two separate aliquots of 

the specimen and the laboratory is unable to identify the interfering substance; 
5-53 

■ The physical appearance of the specimen (e.g., viscosity) is such that testing the 

specimen may damage the laboratory’s instruments; 

■ The specimen has been tested and the appearances of the primary (A) and the split 

(B) specimens (e.g., color) are clearly different; 

■ A urine specimen reported as invalid for creatinine < 2.0 mg/dL and specific gravity 

acceptable (e.g., > 1.0010 and < 1.0200); 

■ A urine specimen reported as invalid for creatinine > 2.0 mg/dL and specific gravity 

< 1.0010; 

■ A urine specimen reported as invalid for pH greater than or equal to 4.0 and < 4.5 or 

pH greater than or equal to 9.0 and < 11.0; 

■ A urine specimen reported as invalid for nitrite greater than or equal to 200 mcg/mL 

and < 500 mcg/mL; 

■ A urine specimen reported as invalid for oxidant activity (e.g., greater than or equal to 

200 mcg/mL nitrite equivalents, greater than or equal to 50 mcg/mL Chromium VI 

equivalents, or > halogen or other oxidant LOQ); or 

■ A urine specimen reported as possible aldehyde or surfactant activity.

Biomarker analysis may be used to determine if a commercially prepared material is 

being used to substitute for the authentic urine specimen. Recent products entering the 

market and intended as substitute specimens have included creatinine and other biological 

materials (such as uric acid) to defeat the laboratory biomarker assays. A certified laboratory 

may complete analyses for biomarkers to attempt to detect the use of substitution to defeat 

the drug testing process. An HHS-certified laboratory reports a primary (A) specimen as an 

invalid result when the specimen is not consistent with human urine based on laboratory 

specimen validity testing (e.g., for a biomarker). Invalid urine results are reported by the 

laboratory to the MRO as described in Appendix D and Table 3. The MRO then reports as 

described in Chapter 5, Section 5.6. 

(b) Oral Fluid

“Invalid” refers to a result reported by a laboratory for an oral fluid specimen that

contains an unidentified adulterant or interfering substance, has an abnormal physical 

characteristic, has an endogenous substance at an abnormal concentration that prevents the 

laboratory from completing testing or obtaining a valid oral fluid drug test result. HHScertified laboratories are required to contact the MRO to discuss an invalid oral fluid report. 

A Medical Review Officer may request to test an oral fluid specimen for a specific 
5-54 

adulterant. A primary (A) oral fluid specimen reported as invalid for a test may be sent out 

for additional testing if the HHS-certified laboratory and the MRO conclude that additional 

testing may provide a definitive result for that specimen. The Mandatory Guidelines do not 

specify the analytical methods to be used by HHS-certified laboratories for these additional 

tests and there are no definitive test methods to apply to these specimens to provide a 

definitive result. (Note that additional testing should only be considered in the absence of a 

confirmed positive, adulterated, or substituted result and only if additional or different testing 

may lead to a definitive positive, negative, or adulterated drug test result.) If a specimen 

exhibits abnormal characteristics (e.g., unusual odor, color, or semi-solid characteristics), 

causes reactions or responses characteristic of an adulterant during initial or confirmatory 

drug tests (e.g., non-recovery of internal standard, unusual response), or contains an 

unidentified substance that interferes with the confirmatory analysis, then additional testing 

may be performed. 

An HHS-certified laboratory reports a primary (A) oral fluid specimen as an invalid 

result when: 

■ Interference with testing

– Interference occurs on the initial drug tests on two separate aliquots (i.e., valid 

initial drug test results cannot be obtained); 

– Interference with the confirmatory drug test occurs on two separate aliquots of the 

specimen and the laboratory is unable to identify the interfering substance;

■ The physical appearance of the specimen (e.g., viscosity) is such that testing the 

specimen may damage the laboratory’s instruments; 

■ The specimen has been tested and the appearances of the primary (A) and the split 

(B) specimens (e.g., color) are clearly different; or

■ A specimen validity test on two separate aliquots of the specimen is not valid for

testing. 

The OFMG do not require routine specimen validity testing for oral fluid testing. The 

MRO must request biomarker testing for oral fluid.

Invalid oral fluid results are reported by the laboratory to the MRO as described in 

Appendix D and Table 3. The MRO then reports as described in Chapter 5, Section 5.6.4.2, 

and Tables 4 and 5. 
5-55 

5.6.4.2 MRO Actions

The MRO is required to attempt to contact the donor to give the donor an opportunity 

to explain any reason for the invalid result (e.g., provide information on medications or a 

medical condition) for urine or oral fluid invalid specimens due to a possible adulterant or for 

specimens with an abnormal physical characteristic. 

Prior to reporting a urine or oral fluid invalid result to the MRO, the laboratory must 

contact the MRO to decide whether additional/different testing would be of use to obtain a 

definitive result EXCEPT when (for urine) the invalid result is based on creatinine and 

specific gravity, pH, or a confirmatory nitrite test result greater than or equal to 200 mcg/mL 

and less than 500 mcg/mL. 

If a urine or oral fluid invalid result was reported in conjunction with a positive, 

adulterated, or substituted result, the MRO does not report the verified invalid result to the 

Federal agency at this time. The MRO takes action for the verified invalid result(s) for the 

primary (A) specimen only when: 

• The MRO verifies the positive, adulterated, or substituted result as negative based on 

a legitimate medical explanation or (for oral fluid) codeine and/or morphine 

concentrations less than 150 ng/mL; or 

• The split (B) specimen is tested and reported as a failure to reconfirm the positive,

adulterated, or substituted result reported for the primary (A) specimen. 

When the laboratory reports an invalid result for the primary (A) specimen, the MRO 

must contact the donor to determine if there is a legitimate explanation for the invalid result. 

Note: The MRO is NOT required to contact the donor for urine specimens invalid due to 

discrepant creatinine/specific gravity values, for urine specimens invalid due to abnormal 

pH, or for urine specimens that contain nitrite ≥200 mcg/mL and <500 mcg/mL by a 

nitrite confirmatory test.

In the case of a urine invalid result based upon of 9.0 to 9.5, when the donor has no 

other medical explanation for the pH in this range, the MRO must consider there is evidence 

of elapsed time and high temperature that could account for the pH value.58 The MRO may

contact the collection site, IITF, and/or laboratory to discuss time and temperature issues 

(e.g., time lapsed from collection to receipt at the testing facility, likely temperature 

conditions between the time of collection and transportation to the testing facility, specimen 

storage conditions). See Table 4. 
5-56 

Urine and Oral Fluid review and reporting – see also Table 4

• If the donor provides a legitimate explanation (e.g., a prescription medicine) or (for urine) 

if the MRO determines that time and temperature account for the pH in the 9.0 to 9.5 pH 

range, the MRO reports a test cancelled result with the reason for the invalid result and 

informs the Federal agency that a recollection is not required because there is a legitimate 

explanation for the invalid result. 

Exception: If a negative result is required (e.g., for a Federal agency applicant/preemployment, return to duty, or follow-up test), follow procedures as described below. 

• If the donor is unable to provide a legitimate explanation or (for urine) if the MRO 

determines that time and temperature fail to account for the pH in the 9.0 to 9.5 range, the 

MRO reports a test cancelled result with the reason for the invalid result and directs the

Federal agency to immediately collect another specimen from the donor using (for urine) 

a direct observed collection. 

• If the specimen collected (direct observation for urine) provides a valid result, the MRO 

reports the result in accord with Chapter 5 and Table 4 of this manual. 

• If the specimen collected (direct observation for urine) provides an invalid result, the 

MRO reports this as a test cancelled and recommends that the agency collect another 

authorized specimen type (e.g., urine or oral fluid). 

If the Federal agency does not authorize collection of another specimen type, the MRO 

consults with the agency to arrange for a clinical evaluation to determine whether there is 

a legitimate medical reason for the invalid result. The Federal agency immediately directs 

the donor to obtain, within five days, an evaluation from a licensed physician, acceptable 

to the MRO, who has expertise in the medical issues raised by the donor’s failure to 

provide a specimen. The MRO may perform this evaluation if the MRO has appropriate 

expertise. See Insufficient Specimen section 6.2 of this manual for medical evaluation. 

.
6-1 

6. Additional Medical Review Officer Responsibilities

6.1 Federal Agency Blind Samples

Federal agencies are required to have blind samples submitted with donor specimens 

to each IITF and laboratory to which the collector sends employee specimens for the Federal 

agency. Each Federal agency must send at least 3% blind samples along with its donor 

specimens based on the projected total number of donor specimens collected per year (to a 

maximum of 400 blind samples). Approximately 75% of the blind urine samples submitted 

each year by an agency must be negative, 15% must be positive for one or more drugs, and 

10% must be either adulterated or substituted. Approximately 75% of the blind oral fluid 

samples submitted each year by an agency must be negative and 25% must be positive for 

one or more drugs. Efforts should be made to submit some of the blind samples each quarter. 

Blind samples are helpful in determining the acceptability of the entire testing process (i.e., 

from the collector’s submission of a specimen to a test facility until a result is reported to the 

Medical Review Officer [MRO]).

The UrMG and OFMG include requirements for blind samples as follows:

■ Urine:

– A blind sample that is positive must be prepared at a concentration 1.5–2 times 

the initial drug test cutoff for one or more of the SAMHSA drug test panel drugs 

or metabolites(see Appendix D, Specimen Reporting Criteria).

– A blind sample that is positive must be validated by the supplier as to its content 

using appropriate initial and confirmatory tests.

– A blind sample that is negative (i.e., certified to contain no drug) must be 

validated by the supplier as negative using appropriate initial and confirmatory 

tests.

– A blind sample that is adulterated must be validated by the supplier using 

appropriate initial and confirmatory tests and have the characteristics to clearly 

show that it is an adulterated sample at the time it is validated by the supplier.

– A blind sample that is substituted must be validated by the supplier using 

appropriate initial and confirmatory tests and must have the characteristics to 

clearly show that it is a substituted sample at the time it is validated by the 

supplier. 

– The supplier must provide information on the blind sample’s content, validation, 

expected results, and stability to the collection site/collector sending the blind 

samples to the laboratory or IITF, and must provide the information upon request 

to the MRO, the Federal agency for which the blind sample was submitted, and 

the Department of Health and Human Services (HHS).
6-2 

■ Oral Fluid:

– The blind quality must be in the same specimen collection device as used by the 

agency and laboratory. 

– A blind sample that is positive must be prepared at a concentration 1.5–2 times 

the initial drug test cutoff for one or more of the SAMHSA drug test panel drugs 

or metabolites (see Appendix D, Specimen Reporting Criteria).

– A blind sample that is positive must be validated by the supplier as to its content 

using appropriate initial and confirmatory tests.

– A blind sample that is negative (i.e., certified to contain no drug) must be 

validated by the supplier as negative using appropriate initial and confirmatory 

tests.

– The supplier must provide information on the blind sample’s date of manufacture, 

content, validation, expected results, expiration date, and validated stability to the 

collection site/collector sending the blind samples to the laboratory, and must 

provide the information upon request to the MRO, the Federal agency for which 

the blind sample was submitted, and the Department of Health and Human 

Services (HHS).

The blind samples may be purchased by the Federal agency and supplied to the 

collector, or purchased by the collector and submitted to an IITF or a laboratory with an 

agency’s specimens. Each blind sample should be sent to the collection site in the collection 

device utilized by the laboratory and in addition, oral fluid should be accompanied by the 

expiration date for the sample as well as instructions for storage of the oral fluid blind sample 

before shipment. Each blind sample is submitted as if it were a donor specimen. This requires 

the collector to complete a Federal Custody and Control Form (CCF) and to properly label 

the specimen bottle(s)/tube(s) containing the sample. Because there is no donor associated 

with a blind sample, the collector generates a fictitious social security number (SSN) or 

employee identification (ID) number and fictitious initials to write on the specimen 

bottle/tube label/seal. The collection site should ensure that the oral fluid blind sample will 

be received by the laboratory at least 5 days before the expiration of the sample.

The collector or the Federal agency that purchased the blind samples must forward 

information to the MRO, so he/she will have the information necessary to determine if the 

correct result was reported. On the MRO copy of the Federal CCF, the collector indicates 

that the sample is a “blind sample” where the donor would normally provide a signature 

(Step 5 on Copy 2 of the Federal CCF). 
6-3 

An incorrect result does not automatically indicate that the IITF or laboratory made 

an analytical error. For example, there could have been a problem with the sample itself (e.g., 

stability, concentration) or the collector may not have properly submitted the sample.

When an IITF or a laboratory reports a result different from the one expected based 

on information provided by the supplier of the blind sample, the MRO must conduct an 

initial investigation to determine the cause of the error. The Mandatory Guidelines require 

the MRO to: 

■ Contact the laboratory or IITF and attempt to determine if the laboratory or IITF 

made an error during the testing or reporting of the sample; 

■ Contact the supplier of the blind sample and attempt to determine if the supplier made

a mistake when preparing the blind sample and (for oral fluid) whether the sample 

was tested within the stability period for the sample; 

■ Contact the collector and attempt to determine if the collector made a mistake when 

preparing the blind sample for transfer to the IITF or laboratory; and

■ Notify both HHS and the Federal agency for which the blind sample was submitted 

(if there is no obvious reason for the inconsistent result). 

When contacted by an MRO, HHS will investigate the blind sample error to 

determine the exact cause of the incorrect result. HHS will provide a report of investigative 

findings and corrective actions taken by the HHS-certified IITF or laboratory to the Federal 

agency. HHS will also ensure notification of all other Federal agencies for which the IITF or 

laboratory performs testing and will coordinate any action necessary to prevent recurrence of 

the error.

6.2 Insufficient Specimen

When another specimen type (e.g., urine or oral fluid) was collected as authorized by 

the Federal agency, the MRO reviews and reports the test result in accordance with the 

Mandatory Guidelines for Federal Workplace Drug Testing Programs using the alternate

specimen.

6.2.1 Urine 

If the laboratory reports insufficient urine volume, the MRO consults with the 

laboratory and the collection site to determine the reason for the insufficient urine volume. If 

the insufficient urine volume is due to leakage in transit or laboratory error (e.g., spill), the 

MRO may consider the basis for the test and contact the agency concerning the test. The 
6-4 

MRO must inform the Federal agency that the cancelled test does not serve the purpose of a 

negative test result (i.e., the donor may not begin or resume performing safety-sensitive 

functions because a negative drug test result is needed). The MRO is NOT required to 

contact the donor for urine specimens insufficient due to spillage or error. If the insufficient 

urine volume is due to a limited collection that was not noted, the MRO will implement the 

medical evaluation procedure. 

When a donor has difficulty providing sufficient urine during a collection, the donor 

is given the opportunity to attempt to provide a specimen during a period of time up to 3 

hours. The collector will give the donor a reasonable amount of liquid to drink over this 

period (e.g., an 8-ounce glass of water every 30 minutes, not to exceed a maximum of 40 

ounces over 3 hours). When a collector reports that a donor did not provide a sufficient 

amount of urine for a drug test or donor claims that they have a medical condition, the MRO 

must reconcile the testing results. When another specimen type (e.g., oral fluid) was collected 

as authorized by the Federal agency, the MRO reviews and reports the test result in 

accordance with the Mandatory Guidelines for Federal Workplace Drug Testing Programs 

using the alternate specimen. When the Federal agency did not authorize the collection of an 

alternate specimen, the MRO consults with the Federal agency. The Federal agency

immediately directs the donor to obtain, within 5 days, a medical evaluation from a licensed 

physician, acceptable to the MRO, who has expertise in the medical issues raised by the 

donor’s failure to provide a specimen. The MRO may perform this evaluation if the MRO

has appropriate expertise. 

The purpose of the evaluation is to determine whether the donor has an ascertainable 

physiological condition that, with a high degree of probability, could have prevented him or 

her from providing a sufficient amount of urine during the collection. This does not include 

unsupported assertions of “situational anxiety” or dehydration. Permanent or long-term 

medical conditions are those physiological (e.g., urinary system dysfunction), anatomic, or 

psychological abnormalities documented as being present prior to the attempted collection, 

and considered not amenable to correction or cure for an extended period of time. If so, the 

physician must further determine whether the medical condition is a permanent or long-term 

disability that would prevent the donor from providing sufficient urine for an extended or 

indefinite time. For urine drug testing, examples include the following:

■ Destruction of the glomerular filtration system leading to renal failure;

■ Unrepaired traumatic disruption of the urinary tract; 
6-5 

■ Diagnosis of “social anxiety disorder” that has been medically documented and meets 

the DSM criteria. 

Acute or temporary medical conditions such as cystitis, urethritis, or prostatitis may 

interfere temporarily but do not receive the same considerations as the conditions listed as 

examples. Unsupported assertions of “situational anxiety” or dehydration are not considered 

valid reasons and shall be regarded as a refusal to test. 

As the MRO, if another physician will perform the evaluation, you must provide the 

other physician with the following information and instructions: 

■ The circumstances necessitating the medical evaluation (i.e., that the donor was 

required to provide urine for a federally regulated drug test but was unable to provide 

a sufficient urine or oral fluid as required for the test and an alternate specimen was 

not collected) ; and 

■ The consequences of a refusal to take a drug test for the Federal agency (see 

Chapter4, Section 4.2, Refusal to Test); and

■ That the examining physician must agree to submit a written statement and 

instructions for submitting the written statement to the MRO with a recommendation 

for the MRO’s determination and the basis for the recommendation. (The statement 

must not include any detailed information on the donor’s medical condition beyond 

that necessary to explain the recommendations.) 

As the MRO, if another physician performed the evaluation, you must consider and 

assess the referral physician’s recommendations in making your determination. You must 

make one of the following determinations and report it to the Federal agency in writing: 

■ That the donor’s medical condition has or, with a high degree of probability, could 

have precluded the donor from providing a sufficient amount of urine, but is not a 

permanent or long-term disability. The MRO reports a test cancelled to the Federal 

agency; or 

■ That a permanent or long-term medical condition has, or with a high degree of 

probability could have, precluded the employee from providing a sufficient amount of 

urine and is highly likely to prevent the employee from providing a sufficient amount 

of urine for a very long or indefinite period of time. As the MRO, you must follow 

the requirements of UrMG Section 13.7 as appropriate. If Section 13.7 is not 

applicable, you report a test cancelled result to the Federal agency and recommend 

that the agency authorize collection of an alternate specimen type (e.g., oral fluid) for 

any subsequent drug tests for the donor; or 

■ That there is not an adequate basis for determining that the donor’s medical condition 

has or, with a high degree of probability, could have precluded the donor from 
6-6 

providing a sufficient amount of urine. The MRO reports a refusal to test to the

Federal agency. 

When a Federal agency receives a report from the MRO indicating that a test is 

cancelled, the agency takes no further action with respect to the donor. When a test is 

canceled and the MRO recommends collection of an alternate specimen type (e.g., oral 

fluid), the agency takes no further action with respect to the donor other than designating 

collection of an alternate specimen type (i.e., using Mandatory Guidelines for that specimen

type) for any subsequent collections, in accordance with the Federal agency plan. The donor 

remains in the random testing pool. 

In making a determination based on the medical evaluation, the MRO must consider 

and assess the recommendations made by the referral physician. The MRO reports in writing 

to the Federal agency as follows:

■ Refusal to test when the MRO determines that there is no adequate basis for 

determining a medical condition interfered with the collection; or

■ Test cancelled when the MRO determines that the donor’s medical condition 

interfered with the collection. The Federal agency takes no further action and the 

donor remains in the random testing pool, unless a negative result is required (e.g., for 

a Federal agency applicant/pre-employment, follow-up, or return-to-duty test). In 

such cases, the Federal agency takes action as required in the Federal agency plan or 

as described below.

6.2.1.1 Permanent or Long-Term Medical Condition and Required Negative Test 

Additional actions are required when the Federal agency does not authorize collection 

of an alternate specimen (e.g., urine or oral fluid), the MRO determines that a donor has a 

permanent or long-term medical condition that would likely prevent provision of a sufficient 

urine specimen for an extended or indefinite time, and the reason for the drug test was: 

■ Federal agency applicant/pre-employment; or 

■ Follow-up; or

■ Return-to-duty. 

In these cases, the MRO must conduct a medical evaluation or, alternatively, ensure 

that a medical evaluation is conducted by another licensed physician acceptable to the MRO 

to determine if there is clinical evidence of drug use. The MRO may also consult with the 
6-7 

donor’s physician and/or the referral physician (i.e., who evaluated the donor after the failure 

to provide a sufficient specimen).

The MRO reports in writing to the Federal agency as follows:

■ “Negative” when the medical evaluation reveals no clinical evidence of drug use. 

– The MRO report must include the following information concerning the medical 

evaluation(s) of the donor: 

■ The basis for the determination that a permanent or long-term medical condition 

exists, making provision of a sufficient urine specimen impossible; 

■ The basis for determining that no signs and symptoms of drug use exist; and 

■ Recommend that the agency authorize collection of an alternate specimen type (e.g., 

oral fluid) for any subsequent collections.

■ “Test cancelled” when the medical evaluation reveals clinical evidence of drug use. 

– The MRO report must include the following information concerning the medical 

evaluation(s) and any further medical examinations of the donor: 

■ The reason for the determination that a permanent or long-term medical condition 

exists, making provision of a sufficient urine specimen impossible; 

■ The reason for determining that signs and symptoms of drug use exist; and 

■ The Federal agency is not authorized to allow the donor to begin or resume official 

functions because a negative test is required.

6.2.2 Oral Fluid

The laboratory may test oral fluid specimens that are collected on or before the 

collection device expiration date (see also section 4.1.1). If the laboratory reports insufficient 

oral fluid volume, the MRO consults with the laboratory and the collection site to determine 

the reason for the insufficient oral fluid volume. If the insufficient oral fluid volume is due to 

leakage in transit or laboratory error (e.g., spill), the MRO may consider the basis for the test 

and contact the agency concerning the test. The MRO must inform the Federal agency that 

the cancelled test does not serve the purpose of a negative test result (i.e., the donor may not 

begin or resume performing safety-sensitive functions because a negative drug test result is 

needed). The MRO is NOT required to contact the donor for oral fluid specimens insufficient 

due to spillage or error. If the insufficient oral fluid volume is due to a limited collection that 

was not noted, the MRO will implement the medical evaluation procedure. 
6-8 

When a donor is unable to provide an oral fluid specimen or the donor claims that 

they have a medical condition that prevents opening their mouth for inspection, the Federal 

agency may authorize the collection of an alternate specimen (e.g., urine). When the collector 

reports that the donor did not provide a sufficient amount of oral fluid for a drug test, the 

MRO must reconcile the testing results. When another specimen type (e.g., urine) was 

collected as authorized by the Federal agency, the MRO reviews and reports the test result in 

accordance with the Mandatory Guidelines for Federal Workplace Drug Testing Programs 

using the alternate specimen. When the Federal agency did not authorize the collection of an 

alternate specimen, the MRO consults with the Federal agency. The Federal agency

immediately directs the donor to obtain, within five days, a medical evaluation from a 

licensed physician, acceptable to the MRO, who has expertise in the medical issues raised by 

the donor’s failure to provide a specimen. The MRO may perform this evaluation if the MRO 

has appropriate expertise. 

The purpose of the evaluation is to determine whether the donor has an ascertainable 

physiological condition or medical documentation, existing prior to the collection attempt, of 

a psychological disorder that, with a high degree of probability, could have prevented him or 

her from providing a sufficient amount of oral fluid during the collection. A medical 

condition includes an ascertainable physiological condition. Permanent or long-term medical 

conditions are those physiological, anatomic, or psychological abnormalities documented as 

being present prior to the attempted collection, and considered not amenable to correction or 

cure for an extended period of time. 

As the MRO, if another physician will perform the evaluation, you must provide the 

other physician with the following information and instructions: 

■ The circumstances necessitating the medical evaluation (i.e., that the donor was 

required to provide oral fluid for a federally regulated drug test but was unable to 

provide at least 1 mL of neat oral fluid as required for the test and an alternate 

specimen was not collected); 

■ The consequences of a refusal to take a drug test for the Federal agency (see 

Chapter4, Section 4.2, Refusal to Test); and 

■ That the examining physician must agree to submit a written statement and 

instructions for submitting the written statement to the MRO with a recommendation 

for the MRO’s determination and the basis for the recommendation. (The statement 

must not include any detailed information on the donor’s medical condition beyond 

that necessary to explain the recommendations.) 
6-9 

As the MRO, if another physician performed the evaluation, you must consider and 

assess the referral physician’s recommendations in making your determination. You must 

make one of the following determinations and report it to the Federal agency in writing: 

■ That the donor’s medical condition has or, with a high degree of probability, could 

have precluded the donor from providing a sufficient amount of oral fluid, but is not a 

permanent or long-term disability. The MRO reports a test cancelled to the Federal 

agency; or 

■ That a permanent or long-term medical condition has, or with a high degree of 

probability could have, precluded the employee from providing a sufficient amount of 

oral fluid and is highly likely to prevent the employee from providing a sufficient 

amount of urine for a very long or indefinite period of time. As the MRO, you must 

follow the requirements of UrMG Section 13.7 as appropriate. If Section 13.7 is not 

applicable, you report a test cancelled result to the Federal agency and recommend 

that the agency authorize collection of an alternate specimen type (e.g., urine) for any 

subsequent drug tests for the donor; or 

■ That there is not an adequate basis for determining that the donor’s medical condition 

has or, with a high degree of probability, could have precluded the donor from 

providing a sufficient amount of oral fluid. The MRO reports a refusal to test to the 

Federal agency. 

When a Federal agency receives a report from the MRO indicating that a test is 

cancelled, the agency takes no further action with respect to the donor. When a test is 

canceled and the MRO recommends collection of an alternate specimen type (e.g., urine), the 

agency takes no further action with respect to the donor other than designating collection of 

an alternate specimen type (i.e., using the Mandatory Guidelines for that specimen type) for 

any subsequent collections, in accordance with the Federal agency plan. The donor remains 

in the random testing pool. 

In making a determination based on the medical evaluation, the MRO must consider 

and assess the recommendations made by the referral physician. The MRO reports in writing 

to the Federal agency as follows:

■ Refusal to test when the MRO determines that there is no adequate basis for 

determining a medical condition interfered with the collection; or

■ Test cancelled when the MRO determines that the donor’s medical condition 

interfered with the collection. The Federal agency takes no further action and the 

donor remains in the random testing pool, unless a negative result is required (e.g., for 

a Federal agency applicant/pre-employment, follow-up, or return-to-duty test). In 
6-10 

such cases, the Federal agency takes action as required in the Federal agency plan or 

as described below.

6.2.2.1 Permanent or Long-Term Medical Condition and Required Negative Test 

Additional actions are required when the Federal agency does not authorize collection 

of an alternate specimen (e.g., urine), the MRO determines that a donor has a permanent or 

long-term medical condition that would likely prevent provision of a sufficient oral fluid 

specimen for an extended or indefinite time, and the reason for the drug test was: 

■ Federal agency applicant/pre-employment; or

■ Follow-up; or

■ Return-to-duty. 

In these cases, the MRO must conduct a medical evaluation or, alternatively, ensure 

that a medical evaluation is conducted by another licensed physician acceptable to the MRO 

to determine if there is clinical evidence of drug use. The MRO may also consult with the 

donor’s physician and/or the referral physician (i.e., who evaluated the donor after the failure 

to provide a sufficient specimen).

The MRO reports in writing to the Federal agency as follows:

■ “Negative” when the medical evaluation reveals no clinical evidence of drug use. 

– The MRO report must include the following information concerning the medical 

evaluation(s) of the donor: 

o The basis for the determination that a permanent or long-term medical 

condition exists, making provision of a sufficient oral fluid specimen 

impossible; 

o The basis for determining that no signs and symptoms of drug use exist; and 

o The recommendation that the agency authorize collection of an alternate

specimen type (e.g., urine) for any subsequent collections.

■ “Test cancelled” when the medical evaluation reveals clinical evidence of drug use. 

– The MRO report must include the following information concerning the medical 

evaluation(s) and any further medical examinations of the donor: 

o The reason for the determination that a permanent or long-term medical 

condition exists, making provision of a sufficient oral fluid specimen 

impossible; and 

o The reason for determining that signs and symptoms of drug use exist. 
6-11 

– The Federal agency is not authorized to allow the donor to begin or resume 

official functions because a negative test is required. 

6.3 Occupational and Public Safety

Executive Order 12564 uses the term “illegal drugs” to refer to any controlled 

substance included in Schedule I or II of the Controlled Substances Act (CSA) and not to 

refer to the use of a controlled substance pursuant to a valid prescription or other uses 

authorized by law. 

The purpose of this policy is to ensure that a workplace drug testing program does not 

incorrectly identify an individual who is receiving medical care as misusing drugs and, 

thereby, provide confidential medical information to an agency. 

There is a public safety issue associated with information that a donor may provide to 

an MRO during the review of a 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 an MRO is given information that indicates that a donor’s use of a legitimately 

prescribed medication creates a safety risk (given the donor’s job functions), the MRO may 

be faced with a decision about what to do with this information. The Mandatory Guidelines 

do not address this situation, and they do not require MROs to determine whether a valid 

prescription medication can be used safely while performing a donor’s work functions. 

Therefore, before an MRO decides to discuss safety information related to a donor’s valid 

prescription (i.e., legal drug use) with the donor’s agency, the MRO should consult (1) the 

terms of the service agreement with the agency, (2) any agency policies or rules that govern 

such circumstances, and/or (3) private legal counsel. In addition, if an MRO’s service 

agreement with an agency does not address how to handle safety information related to a 

donor’s valid prescription, the MRO should discuss this issue with the agency. Please be 

advised, however, that nothing in this section or manual is intended to reflect a SAMSHA or 

an HHS position regarding whether an MRO’s disclosure of safety information in the context 

of a donor’s legal drug use is legal or appropriate in any given circumstance because this 

issue is outside the scope of the Mandatory Guidelines. 
6-12 

6.4 Donor Rights to Information 

An individual who is the subject of a drug test may, upon written request through the 

MRO and the Federal agency, have access to records relating to his/her drug test; any records 

relating to the results of any relevant certification, review, or revocation of certification 

proceedings; and a documentation package (at the donor’s expense). A donor or Federal 

agency will occasionally request laboratory and/or an IITF to provide a complete package of 

analytical data, chain of custody records, and other administrative documents associated with 

the testing of a particular specimen. The documentation package may also be referred to as a 

“data package” or “litigation package.” The request must always be submitted to the test 

facility through the MRO. 

A standard documentation package provided by an HHS-certified IITF or laboratory 

consists of the following items:

■ A cover sheet that provides a brief description of the drug testing procedures and 

specimen validity tests performed on the donor’s specimen; 

■ A table of contents that lists, by page number, all documents, and materials in the 

package;

■ A copy of the Federal CCF with any attachments, internal chain of custody 

documents for the specimen, memoranda (if any), and a copy of the electronic report 

(if any) generated by the laboratory or IITF;

■ A brief description of the initial drug tests and specimen validity test procedures, 

instrumentation, batch quality control requirements, and copies of the test data for the 

donor’s specimen with all calibrators and controls identified and copies of all internal 

chain of custody documents related to these tests; 

■ For a laboratory: a brief description of confirmatory drug tests and confirmatory 

validity tests procedures, instrumentation, batch quality control requirements, and 

copies of the test data for the donor’s specimen with all calibrators and controls 

identified and copies of all internal chain of custody documents related to these tests;

■ A copy of the résumé or curriculum vitae for the certifying technician or certifying 

scientist that certified the test result; and

■ A copy of the résumé or curriculum vitae for each of the laboratory’s Responsible 

Persons or each of the IITF’s Responsible Persons/Technicians.

6.5 Protection of Personally Identifiable Information (PII)

PII is information that can be used to distinguish or trace an individual’s identity 

alone or when combined with other personally identifiable information that is linked or 
6-13 

linkable to a specific individual. PII that may be on the Federal CCF includes the donor’s 

SSN or employee ID number, name, date of birth, telephone numbers, and employment 

status. All Federal agencies and service providers involved in the Federal Workplace Drug 

Testing Program (e.g., clients, laboratories, collectors, employers, external service providers, 

and MROs) are responsible for maintaining the confidentiality of drug testing information 

and safeguarding the donor’s PII on the Federal CCF. As the use of electronic means of 

communications in the MRO business increases, it is incumbent on the MRO and all persons 

with access to this information to ensure that all donor PII is protected.

All Federal agencies and drug testing service providers must implement procedures 

and administrative, technical, and physical controls to ensure donor privacy by restricting 

access to PII and to drug test results on hardcopy and electronic Federal CCFs or drug test 

results entered into a computer system or database. It is not acceptable for service providers 

to use Federal CCF forms with incorrect or outdated MRO information (e.g., MRO 

name/organization, address, fax number). It is incumbent upon the laboratory or IITF to be 

proactive and take steps to prevent the use of outdated information which may lead to a 

violation of donor PII. Clients and collectors should edit incorrect information and provide 

correct information printed on CCF forms.

SAMHSA has determined that the name of the MRO is not an essential element on 

the Federal CCF. The MRO may be a sole practitioner or an MRO company with more than 

one practitioner (i.e., group/organization). Effective November 17, 2022, when the Federal 

CCF includes the name of an MRO company, laboratories will no longer be required to take 

action when the Federal CCF does not include the name of an MRO or when the MRO name 

is different on the CCF and electronic report. 

Laboratories must continue to take action for a missing or incorrect MRO name when 

an MRO company name is not present and for other discrepant information (e.g., MRO 

company name, address, contact information). Laboratories must address the discrepant 

information by verifying the information in the laboratory computer system, ensuring the 

collector has the correct information, and providing new CCFs with correct information to 

the client.

Access to donor PII and drug test results must be limited to those individuals 

requiring access to fulfill job duties. Such individuals must receive training to make them 

aware of their responsibilities for protecting the information. Confidentiality must be 

maintained from the time the donor’s PII is obtained through transmission/transport of the 
6-14 

urine or oral fluid Federal CCF, specimen testing, and records handling (i.e., storage, 

retrieval, and final destruction).

MROs are required to provide a written verification to each HHS-certified laboratory 

and HHS-certified IITF for which they review results that the devices used to receive reports 

are in a secure area. This verification must be provided annually. If the MRO obtains 

laboratory drug test reports electronically via either a laboratory-owned system or a 

laboratory-contracted external service provider (as described in Section 6.6), the MRO or 

MRO company must provide a letter to the laboratory annually attesting to the security and 

confidentiality of the information (e.g., username, password) that allows access to the 

system. For example, many laboratories provide Web-based online access to results to allow 

the MRO (or designated employees) to log in to the portal and download results. To control 

and protect information, the MRO must ensure that the access information is carefully 

protected and is only known by key personnel and changed immediately upon the departure 

of any employee possessing the password. 

6.6 External Service Providers 

An external service provider (e.g., third party administrator, ECCF provider, software 

service provider, cloud service provider) may perform services on behalf of the MRO or 

MRO company related to regulated drug testing. For example, an MRO, MRO employer, or 

MRO group, may have a contractual agreement with an external service provider to provide 

administrative services and/or receive MRO copies of the Federal CCF from collectors and 

reports from HHS-certified laboratories and IITFs, provide these documents to the MRO, and 

store these and other MRO records.

MROs who use external service providers are strongly encouraged to enter into a 

binding written agreement/contract (i.e., between the MRO, the MRO’s employer, or the 

MRO’s group, and an authorized representative of the external service provider) that 

specifies responsibilities of the external service provider as they relate to regulated drug 

testing. Appendix F of this manual provides an MRO Verification Statement that specifies 

the priority elements that should be addressed in an MRO agreement/contract with an 

external service provider. In addition, the MRO or MRO company whose name appears on 

the Federal CCF as the MRO of record is responsible for ensuring that the external service 

provider complies with applicable requirements of the Mandatory Guidelines (e.g., Subparts 

M and N), unless the MRO’s employer or group provides documentation that designates 
6-15 

another MRO within its organization as responsible for the external service provider’s 

compliance with the Guidelines. 

To ensure that MROs or MRO companies are properly identified (on Federal CCFs), 

MROs, MRO employers, or MRO groups should provide Federal agencies with 

documentation that designates the name of a specific MRO or the MRO company name to be 

listed in the agency’s Federal CCFs. It is also recommended that this documentation be 

provided to a Federal agency within seven business days following the execution of a binding 

agreement between the Federal agency and the MRO (or the MRO’s employer/group) for the 

provision of MRO services that are subject to the UrMG and OFMG. MROs, MRO 

employers, and MRO groups that have an existing agreement with a Federal agency to 

provide MRO services as of the effective date of this manual should provide the 

documentation described in this paragraph to the Federal agency within 30 calendar days 

following the effective date of this manual if such documentation has not been provided 

previously. 

MROs are also strongly encouraged to ensure their external service providers adhere 

to any specific Federal agency requirements. 

Section 4.6 of this manual addresses MRO documentation and recordkeeping, 

including the requirement for the MRO to retain drug test records for a minimum of two 

years from the date of collection. MROs using an external service provider to maintain their 

records must ensure that such records are discarded in accordance with the required retention 

schedule. MROs should also ensure that their external service providers have a business 

discontinuance plan that addresses records disposition. Records must be returned to the MRO 

or to another location/entity that has been agreed to by the MRO. 

HHS-certified laboratories and IITFs are not allowed to report drug test results to 

entities other than the MRO of record (i.e., MRO or MRO company whose name is listed on 

the Federal CCF) prior to obtaining an MRO Verification Statement (see Appendix F), or 

similar statement—from the MRO, MRO’s employer, or MRO’s group—that documents that 

an external service provider is authorized to receive and/or disseminate federally regulated 

drug testing information and records on the MRO’s behalf. 
A-1 

APPENDIX A: GLOSSARY

The following definitions are primarily excerpted from the HHS Mandatory 

Guidelines for Federal Workplace Drug Testing Programs using Urine (UrMG, Effective 

February 1, 2024) and the HHS Mandatory Guidelines for Federal Workplace Drug Testing 

Programs using Oral Fluid (OFMG, Effective October 10, 2023), but may include additional 

definitions.

Accessioner. The individual who signs the Federal Custody and Control Form at the 

time of specimen receipt at the HHS-certified laboratory or the HHS-certified IITF. 

Adulterated Specimen. A specimen that has been altered, as evidenced by test results 

showing either a substance that is not a normal constituent for that type of specimen or 

showing an abnormal concentration of a normal constituent (e.g., nitrite in urine). 

Aliquot. A portion of a specimen used for testing. 

Alternate Responsible Person. The person who assumes professional, organizational, 

educational, and administrative responsibility for the day-to-day management of the HHScertified laboratory when the Responsible Person is unable to fulfill these obligations.

Alternate Responsible Technician. The person who assumes professional, 

organizational, educational, and administrative responsibility for the day-to-day management 

of the HHS-certified IITF when the responsible technician is unable to fulfill these

obligations. 

Alternate Technology Initial Drug Test. An initial drug test using technology other 

than immunoassay to differentiate negative specimens from those requiring further testing.

Batch. A number of specimens or aliquots handled concurrently as a group. 

Biomarker. An endogenous substance used to validate a biological specimen.

Biomarker Testing Panel. The panel published in the Federal Register that includes 

the biomarkers authorized for testing, with analytes and cutoffs for initial and confirmatory 

biomarker tests, as described under OFMG/UrMG Section 3.4. 
A-2 

Blind Sample. A sample submitted to an HHS-certified test facility for quality 

assurance purposes, with a fictitious identifier, so that the test facility cannot distinguish it 

from a donor specimen.

Calibrator. A sample of known content and analyte concentration prepared in the 

appropriate matrix used to define expected outcomes of a testing procedure. The test result of 

the calibrator is verified to be within established limits prior to use. 

Cancelled Test. The result reported by the MRO to the Federal agency when a 

specimen has been reported to the MRO as an invalid result (and the donor has no legitimate 

explanation) or the specimen has been rejected for testing, when a split specimen fails to 

reconfirm, or when the MRO determines that a fatal flaw or unrecovered correctable flaw 

exists in the forensic records (as described in Sections 15.1 and 15.2 of the UrMG and 

OFMG).

Carryover. The effect that occurs when a sample result (e.g., drug concentration) is 

affected by a preceding sample during the preparation or analysis of a sample. 

Certifying Scientist (CS). The individual responsible for verifying the chain of 

custody and scientific reliability of a test result reported by an HHS-certified laboratory. 

Certifying Technician (CT). The individual responsible for verifying the chain of 

custody and scientific reliability of negative, rejected for testing, and (for urine) 

negative/dilute results reported by an HHS-certified laboratory or an HHS-certified IITF.

Chain of Custody (COC) Procedures. Procedures that document the integrity of each 

specimen or aliquot from the point of collection to final disposition.

Chain of Custody Documents. Forms used to document the control and security of the 

specimen and all aliquots. The documents may account for an individual specimen, aliquot, 

or batch of specimens/aliquots and must include the name and signature of each individual 

who handled the specimen(s) or aliquot(s) and the date and purpose of the handling. 

Collection Device. A product that is used to collect an oral fluid specimen and may 

include a buffer or diluent.

Collection Container. A receptacle used to collect a donor’s drug test specimen.

Collection Site. The location where specimens are collected.
A-3 

Collector. A person trained to instruct and assist a donor in providing a specimen. 

Confirmatory Drug Test. A second analytical procedure performed on a separate 

aliquot of a specimen to identify and quantify a specific drug or drug metabolite. 

Confirmatory Specimen Validity Test. A second test performed on a separate aliquot 

of a specimen to further support an initial specimen validity test result.

Control. A sample used to evaluate whether an analytical procedure or test is 

operating within predefined tolerance limits. 

Cutoff. The analytical value (e.g., drug, drug metabolite, or biomarker concentration) 

used as the decision point to determine a result (e.g., negative; positive; adulterated; invalid; 

or substituted) or the need for further testing.

Dilute Specimen. A urine specimen with creatinine and specific gravity values that 

are lower than expected but are still within the physiologically producible ranges of human 

urine. 

Donor. The individual from whom a specimen is collected.

Drug Testing Panel. The panel published in the Federal Register that includes the 

drugs authorized for testing, with analytes and cutoffs for initial and confirmatory drug tests, 

as described under Section 3.4 of the UrMG and OFMG. 

External Service Provider. An independent entity that performs services related to 

Federal Workplace Drug Testing on behalf of a Federal agency; a collector/collection site; an 

HHS-certified laboratory; a Medical Review Officer (MRO); or (for urine) an HHS-certified 

Instrumented Initial Test Facility (IITF).

Failed to Reconfirm. The result reported for a split (B) specimen when a second 

HHS-certified laboratory is unable to corroborate the result reported for the primary (A) 

specimen.

Federal Drug Testing Custody and Control Form (Federal CCF). The Office of 

Management and Budget (OMB)–approved form that is used to document the collection and 

chain of custody of a specimen from the time the specimen is collected until it is received by 

the test facility (i.e., HHS-certified laboratory or HHS-certified IITF). It may be a paper 
A-4 

(hardcopy), electronic (digital), or combination electronic and paper format (hybrid). The 

form may also be used to report the test result to the Medical Review Officer.

Gender Identity. Gender identity means an individual’s internal sense of being male 

or female, which may be different from an individual’s sex assigned at birth. 

HHS. The Department of Health and Human Services.

Initial Drug Test. An analysis used to differentiate negative specimens from those 

requiring further testing.

Initial Specimen Validity Test. The first analysis used to determine if a specimen is 

adulterated, invalid, substituted, or (for urine) dilute.

Instrumented Initial Test Facility (IITF). A permanent location where (for urine) 

initial testing, reporting of results, and recordkeeping are performed under the supervision of 

a Responsible Technician. 

Invalid Result. The result reported by an HHS-certified laboratory in accordance with 

the established criteria (i.e., in Section 3.9 of the UrMG and Section 3.8 of the OFMG) when 

a positive, negative, adulterated, or substituted result cannot be established for a specific drug 

or specimen validity test.

Laboratory. A permanent location where initial and confirmatory drug testing, 

reporting of results, and recordkeeping are performed under the supervision of a Responsible 

Person. 

Limit of Detection (LOD). The lowest concentration at which the analyte (e.g., drug 

or drug metabolite) can be identified. 

Limit of Quantification (LOQ). For quantitative assays, the lowest concentration at 

which the identity and concentration of the analyte (e.g., drug or drug metabolite) can be 

accurately established.

Lot. A number of units of an item (e.g., reagents, quality control material, oral fluid 

collection device) manufactured from the same starting materials within a specified period of 

time for which the manufacturer ensures that the items have essentially the same 

performance characteristics and expiration date.
A-5 

Measurand. A physical quantity, property, or condition that is measured. In MRO use, 

this refers to a laboratory test result that is more general than analyte and that includes other 

characteristics, such as specific gravity and pH. 

Medical Review Officer (MRO). A licensed physician who reviews, verifies, and 

reports a specimen test result to the Federal agency. 

Monitor. The person assigned to monitor collection of the specimen for a ‘monitored’ 

collection according to UrMG section 8.12. The monitor’s gender must be the same as the 

donor’s (which is based on the donor’s gender identity) unless the monitor is a medical 

professional. The monitor is not required to be a trained collector. 

Monitored Collection. Collection procedure used when a monitored collection is 

required by UrMG Section 8.11. Same as a routine collection except the monitor provides 

visual privacy while being alert for signs of tampering. The monitor listens at the door of a 

restroom with no stall or enters a stall restroom with the donor, but must stay outside the 

individual stall. The monitor must not touch or handle the collection container, unless the 

monitor is also serving as the collector, and must not watch the donor urinate into the 

collection container.

Negative Result. The result reported by an HHS-certified laboratory or an HHScertified IITF to an MRO when a specimen contains no drug and/or drug metabolite, or the 

concentration of the drug or drug metabolite is less than the cutoff for that drug or drug class. 

Non-Medical Use of a Drug. The use of a prescription drug, whether obtained by 

prescription or otherwise, other than in the manner or for the time period prescribed, or by a 

person for whom the drug was not prescribed.

Observed Collection. Collection procedure used when a direct observed collection is 

required by UrMG Section 8.9. Same as a routine collection except the observer is in the 

restroom or stall and watches the urine pass from the body of the donor to the collection 

container. The observer maintains visual contact with the specimen until the donor hands the 

container to the collector. The collection container cannot be handled by the observer unless 

the observer is also serving as the collector.

Observer. The person assigned to observe the collection of the specimen for a ”direct 

observed” collection according to UrMG section 8.10. The observer’s gender must be the 
A-6 

same as the donor’s (which is based on the donor’s gender identity). The observer is not 

required to be a trained collector, but must be trained as an observer. 

Note: HHS has revised Sections 4.4(b), 8.1(b), and 8.10 of the UrMG to allow the donor 

to be observed by a person whose gender matches the donor’s gender, which is 

determined by the donor’s gender identity (defined above and in UrMG Section 1.5). The 

donor’s gender identity may be the same as or different from the donor’s sex assigned at 

birth. 

Before an observer is selected, the collector informs the donor that the gender of the 

observer will match the donor’s gender, which is determined by the donor’s gender 

identity. The collector then selects the observer to conduct the observation: 

■ The collector asks the donor to identify the donor’s gender on the Federal CCF and 

initial it. 

■ The donor will then be provided an observer whose gender matches the donor’s 

gender. 

■ The collector documents the observer’s name and gender on the Federal CCF. 

Opiates. The term used to describe naturally occurring substances known as alkaloids 

derived from the opium poppy plant (e.g., codeine; morphine; and heroin, which is produced 

by the acetylation of morphine) that bind to specific receptors in the central nervous system 

and have analgesic as well as narcotic effects.

Opioids. A term that has expanded in scope over time and is used broadly to describe 

various compounds that bind to specific receptors in the central nervous system and have 

analgesic as well as narcotic effects. The broadly used term “opioids” includes naturally 

occurring alkaloid compounds known as opiates (e.g., codeine, morphine, and heroin); semisynthetic compounds (e.g., hydrocodone, hydromorphone, methadone, oxycodone, and 

oxymorphone); and synthetic compounds (e.g., fentanyl). Opioids may or may not have 

structural similarity to the opium alkaloids. 

Oral Fluid Specimen. An oral fluid specimen is collected from the donor’s oral cavity 

and is a combination of physiological fluids produced primarily by the salivary glands. 

Oxidizing Adulterant. A substance that acts alone or in combination with other 

substances to oxidize drug or drug metabolites to prevent the detection of the drugs or drug 

metabolites, or affects the reagents in either the initial or confirmatory drug test.
A-7 

Performance Testing (PT) Sample. A program-generated sample sent to a laboratory 

or to an IITF to evaluate performance.

Positive Result. The result reported by an HHS-certified laboratory when a specimen 

contains a drug or drug metabolite equal to or greater than the confirmatory test cutoff.

Reconfirmed. The result reported for a split (B) specimen when the second HHScertified laboratory corroborates the original result reported for the primary (A) specimen.

Rejected for Testing. The result reported by an HHS-certified laboratory or HHScertified IITF when no tests are performed on a specimen because of a fatal flaw or an 

unrecovered correctable error (see Sections 4.1.3-1 and 4.1.3-2 of this MRO Guidance 

Manual).

Responsible Person (RP). The person who assumes professional, organizational, 

educational, and administrative responsibility for the day-to-day management of an HHScertified laboratory.

Responsible Technician (RT). The person who assumes professional, organizational, 

educational, and administrative responsibility for the day-to-day management of an HHScertified IITF. 

Sample. A performance testing sample, calibrator, or control used during testing; or a 

representative portion of a donor’s specimen.

Secretary. The Secretary of the U.S. Department of Health and Human Services.

Specimen. Fluid or material collected from a donor at the collection site for the 

purpose of a drug test. 

Split Specimen Collection (for Urine). A collection in which the specimen collected 

is divided into a primary (A) specimen and a split (B) specimen, which are independently 

sealed in the presence of the donor. 

Split Specimen Collection (for Oral Fluid). A collection in which two specimens 

[primary (A) and split (B)] are collected, concurrently or serially, and independently sealed 

in the presence of the donor; or a collection in which a single specimen is collected using a 

single collection device and is subdivided into a primary (A) specimen and a split (B) 

specimen, which are independently sealed in the presence of the donor. 
A-8 

Standard. Reference material of known purity or a solution containing a reference 

material at a known concentration.

Substituted Specimen. A specimen that has been submitted in place of the donor’s 

specimen, as evidenced by the absence of a biomarker or a biomarker concentration 

inconsistent with that established for a human specimen, as indicated in the biomarker testing 

panel, or (for urine) creatinine and specific gravity values that are outside the physiologically 

producible ranges of human urine, in accordance with the criteria to report a urine specimen 

as substituted in UrMG Section 3.7. 

Undiluted (neat) oral fluid. An oral fluid specimen to which no other solid or liquid 

has been added. For example, see OFMG Section 2.4: a collection device that uses a diluent 

(or other component, process, or method that modifies the volume of the testable specimen) 

must collect at least 1 mL of undiluted (neat) oral fluid.
B-1 

APPENDIX B: 

SAMPLE OF CCF—TEST FACILITY COPY (1) AND MRO COPY (2)
FEDERAL DRUG TESTING CUSTODY AND CONTROL FORM

SPECIMEN ID NO. ACCESSION NO.

STEP 1: COMPLETED BY COLLECTOR OR EMPLOYER REPRESENTATIVE

A. Employer Name, Address, I.D. No.

C. Donor SSN, Employee I.D., or CDL State and No.

D. Specify Testing Authority: HHS NRC Specify DOT Agency: FMCSA FAA FRA FTA PHMSA USCG

F. Drug Tests to be Performed: THC, COC, PCP, OPI, AMP THC & COC Only

B. MRO Name, Address, Phone No. and Fax No.

0000001

OMB No. 0930-0158

STEP 3: Collector affixes seal(s) to bottle(s)/tube(s). Collector dates seal(s). Donor initials seal(s). Donor completes STEP 5 on Copy 2 (MRO Copy)

STEP 4: CHAIN OF CUSTODY - INITIATED BY COLLECTOR AND COMPLETED BY TEST FACILITY

I certify that the specimen given to me by the donor identified in the certification section on Copy 2 of this form 

was collected, labeled, sealed and released to the Delivery Service noted in accordance with applicable federal requirements.

Name of Delivery Service

Signature of Collector

(PRINT) Collector’s Name (First, MI, Last) Date (Mo/Day/Yr) Time of Collection

AM

PM / 

X

COPY 1 - TEST FACILITY COPY

80308

PRESS HARD - YOU ARE MAKING MULTIPLE COPIES

STEP 5A: PRIMARY SPECIMEN REPORT - COMPLETED BY TEST FACILITY

/ / 

Signature of Certifying Technician/Scientist (PRINT) Certifying Technician/Scientist’s Name (First, MI, Last) Date (Mo/Day/Yr)

RECEIVED AT LAB OR IITF: SPECIMEN BOTTLE(S)/TUBE(S)

RELEASED TO:

Signature of Accessioner

(PRINT) Accessioner’s Name (First, MI, Last)

Primary Specimen

Seal Intact

 NO

If NO, Enter remark

in Step 5A. Date (Mo/Day/Yr)

X

X

Version C 6May2020

STEP 5b: COMPLETED BY SPLIT TESTING LABORATORY

Laboratory Name

Laboratory Address Signature of Certifying Scientist (PRINT) Certifying Scientist’s Name (First, MI, Last)

X

 NEGATIVE REJECTED FOR TESTING ADULTERATED SUBSTITUTED INVALID RESULT

 DILUTE

 POSITIVE for:

Analyte(s) in ng/mL

REMARKS:

Test Facility (if different from above) : 

I certify that the specimen identified on this form was examined upon receipt, handled using chain of custody procedures, analyzed, and reported in accordance with applicablefederal requirements.

 YES

SPECIMEN BOTTLE(S)/TUBE(S) RELEASED TO:

(Mo/Day/Yr)

/ / 

STEP 2: COMPLETED BY COLLECTOR (make remarks when appropriate).

COLLECTION: Split Single None Provided, Enter Remark.

URINE: Collector reads urine temperature within 4 minutes. Temperature between 90o and 100o F? Yes No, Enter Remark Observed, Enter Remark

ORAL FLUID: Split Type: Serial Concurrent Subdivided Each Device Within Expiration Date? Yes No Volume Indicator(s) Observed

REMARKS: 

Primary/Single Specimen Device Expiration Date: Split Specimen Device Expiration Date: 

E. Reason for Test: Pre-employment Random Reasonable Suspicion/Cause Post Accident Return to Duty Follow-up Other (specify)

 Other (specify) 

 Phone 

Fax

Other

/ 

 URINE ORAL FLUID

 RECONFIRMED FAILED TO RECONFIRM - REASON 

I certify that the split specimen identified on this form was examined upon receipt, handled using chain of custody procedures,

analyzed, and reported in accordance with applicable federal requirements.

/ /

G. Collection Site Address: Collector Contact Info: 

(Mo/Day/Yr)

/ / 

/ / 

Date (Mo/Day/Yr)

SPECIMEN A

0000001

Date (Mo/Day/Yr)

SPECIMEN B

0000001

Date (Mo/Day/Yr)

/ /

/ /
FEDERAL DRUG TESTING CUSTODY AND CONTROL FORM

SPECIMEN ID NO. 0000001

OMB No. 0930-0158

COPY 2 - MEDICAL REVIEW OFFICER COPY

STEP 5: COMPLETED BY DONOR

STEP 6: COMPLETED BY MEDICAL REVIEW OFFICER - PRIMARY SPECIMEN

I certify that I provided my specimen to the collector; that I have not adulterated it in any manner; each specimen bottle/tube used was sealed with a tamper-evident seal 

in my presence; and that the information provided on this form and on the label affixed to each specimen bottle/tube is correct.

After the Medical Review Officer receives the test results for the specimen identified by this form, he/she may contact you to ask about prescriptions and 

over-the-counter medications you may have taken. Therefore, you may want to make a list of those medications for your own records. THIS LIST IS NOT 

NECESSARY. If you choose to make a list, do so either on a separate piece of paper or on the back of your copy (Copy 5). – DO NOT PROVIDE THIS 

INFORMATION ON THE BACK OF ANY OTHER COPY OF THE FORM. TAKE COPY 5 WITH YOU.

Signature of Donor (PRINT) Donor’s Name (First, MI, Last) Date (Mo/Day/Yr)

/ /

Daytime Phone No. ) Evening Phone No. Date of Birth / /

In accordance with applicable federal requirements, my verification is:

 NEGATIVE POSITIVE for: 

 DILUTE

 REFUSAL TO TEST because – check reason(s) below: TEST CANCELLED

 ADULTERATED (adulterant/reason):

 SUBSTITUTED

 OTHER: 

REMARKS: 

Signature of Medical Review Officer (PRINT) Medical Review Officer’s Name (First, MI, Last)

(Mo/Day/Yr)

X

X

STEP 7: COMPLETED BY MEDICAL REVIEW OFFICER - SPLIT SPECIMEN

 TEST CANCELLED

In accordance with applicable federal requirements, my verification for the split specimen (if tested) is:

 RECONFIRMED for: 

 FAILED TO RECONFIRM for:

REMARKS: 

Signature of Medical Review Officer (PRINT) Medical Review Officer’s Name (First, MI, Last)

X

 URINE ORAL FLUID

Date (Mo/Day/Yr)

/ / 

Date (Mo/Day/Yr)

/ / 

STEP 1: COMPLETED BY COLLECTOR OR EMPLOYER REPRESENTATIVE

A. Employer Name, Address, I.D. No. B. MRO Name, Address, Phone No. and Fax No.

STEP 3: Collector affixes seal(s) to bottle(s)/tube(s). Collector dates seal(s). Donor initials seal(s). Donor completes STEP 5 on Copy 2 (MRO Copy)

STEP 4: CHAIN OF CUSTODY - INITIATED BY COLLECTOR AND COMPLETED BY TEST FACILITY

I certify that the specimen given to me by the donor identified in the certification section on Copy 2 of this form 

was collected, labeled, sealed and released to the Delivery Service noted in accordance with applicable federal requirements.

Name of Delivery Service

Signature of Collector

(PRINT) Collector’s Name (First, MI, Last) Date (Mo/Day/Yr) Time of Collection

AM

PM / 

X

SPECIMEN BOTTLE(S)/TUBE(S) RELEASED TO:

STEP 2: COMPLETED BY COLLECTOR (make remarks when appropriate).

COLLECTION: Split Single None Provided, Enter Remark.

URINE: Collector reads urine temperature within 4 minutes. Temperature between 90o and 100o F? Yes No, Enter Remark Observed, Enter Remark

ORAL FLUID: Split Type: Serial Concurrent Subdivided Volume Indicator(s) Observed

REMARKS: 

E. Reason for Test: Pre-employment Random Reasonable Suspicion/Cause Post Accident Return to Duty Follow-up Other (specify)

 Other (specify) 

 Phone 

Fax

Other

/ 

 URINE ORAL FLUID

Collector Contact Info:

F. Drug Tests to be Performed: THC, COC, PCP, OPI, AMP THC & COC Only

G. Collection Site Address:

ACCESSION NO.

Each Device Within Expiration Date? Yes No 

Email address: ( ( ) 

C. Donor SSN, Employee I.D., or CDL State and No.

D. Specify Testing Authority: HHS NRC Specify DOT Agency: FMCSA FAA FRA FTA PHMSA USCG
C-1 

APPENDIX C: 

EXAMPLE IITF SUPPLEMENTAL CCF

Specimen I.D. #:______________________________________

IITF Accession #:___________________________________

IITF Name: ___________________________________ NLCP IITF No._______ 

IITF address: _____________________________ Bottle A and Bottle B included 

______________________________ CCF Copy 1 included 

___________________________________________________________ 

I certify that the specimen identified on the Federal CCF was examined upon receipt, handled using chain of 

custody procedures, analyzed, and resealed in accordance with applicable Federal requirements.

SPECIMEN BOTTLE(S) 

RELEASED TO:

_________________________ 

Name of Delivery Service

Signature of Certifying Technician

 / /

(Print) Certifying Technician Name (First, M I, Last) Date (Mo/Day/Yr)

RECEIVED AT LABORATORY

BOTTLE A

SEAL INTACT

YES 

NO 

If NO, enter Remark below

Signature of Accessioner

 

 / /

(Print) Accessioner Name (First, M I, Last) Date (Mo/Day/Yr)

Laboratory Remarks: ___________________________________________________________ 

______________________________________________________________________________ 

______________________________________________________________________________ 

Date Specimen Released by Specimen Received by Purpose
D-1 

APPENDIX D: 

URINE SPECIMEN DRUG TESTING PANEL AND REPORTING CRITERIA

This drug testing panel will remain in effect until the effective date of a new drug testing 

panel published in the Federal Register: 

Initial Test Analyte

Initial Test 

Cutoff 1

(ng/mL)

Confirmatory Test 

Analyte

Confirmatory Test 

Cutoff 

(ng/mL)

Marijuana metabolite 

(THCA)2 50 3 THCA 15 

Cocaine metabolite (Benzoylecgonine)

(BZE) 

150 3 Benzoylecgonine 100 

Codeine/Morphine

(COD/MOR)

2000 

Codeine

Morphine

2000 

4000 

Hydrocodone/Hydromorphone

(HYC/HYM)

300 Hydrocodone

Hydromorphone

100 

100 

Oxycodone/Oxymorphone

(OXYC/OXYM)

100 Oxycodone

Oxymorphone

100 

100 

6-Acetylmorphine 

(6-AM)

10 6-Acetylmorphine 10 

Phencyclidine

(PCP)

25 Phencyclidine 25 

Amphetamine/Methamphetamine

(AMP/MAMP)

500 Amphetamine

Methamphetamine

250 

250 

MDMA4/MDA5 500 

MDMA

MDA

250 

250 

1

For grouped analytes (i.e., two or more analytes that are in the same drug class and have the same initial test 

cutoff):

Immunoassay: The test must be calibrated with one analyte from the group identified as the target analyte. The 

cross-reactivity of the immunoassay to the other analyte(s) within the group must be 80 percent or greater; if not, 

separate immunoassays must be used for the analytes within the group.

Alternate technology: Either one analyte or all analytes from the group must be used for calibration, depending on 

the technology. At least one analyte within the group must have a concentration equal to or greater than the initial 

test cutoff or, alternatively, the sum of the analytes present (i.e., equal to or greater than the laboratory’s validated 

limit of quantification) must be equal to or greater than the initial test cutoff.

2

An immunoassay must be calibrated with the target analyte, ∆-9-tetrahydrocannabinol-9-carboxylic acid (THCA).

3

Alternate technology (THCA and benzoylecgonine): The confirmatory test cutoff must be used for an alternate 

technology initial test that is specific for the target analyte (i.e., 15 ng/mL for THCA, 100 ng/mL for 

benzoylecgonine).

4

Methylenedioxymethamphetamine (MDMA)

5

Methylenedioxyamphetamine (MDA)
D-2 

Drug Analyte Terminology and Abbreviations for Electronic Reports (Urine)

THCA Marijuana metabolites1

BZE Cocaine metabolite2

COD/MOR Codeine/Morphine

HYC/HYM Hydrocodone/Hydromorphone

OXYC/OXYM Oxycodone/Oxymorphone

6-AM 6-Acetylmorphine

PCP Phencyclidine

AMP/MAMP Amphetamine/Methamphetamine

MDMA/

MDA

Methylenedioxymethamphetamine/ 

Methylenedioxyamphetamine

1 “THCA” or “delta-9-tetrahydrocannabinol-9-carboxylic acid” for the confirmatory analyte

2 “BZE” or “Benzoylecgonine” for the confirmatory analyte

NOTES: 

The electronic report should clearly indicate whether the laboratory uses a single or multiple immunoassays for 

grouped analytes (e.g., one test for amphetamine, methamphetamine, MDMA, and MDA, or one test for 

amphetamine/methamphetamine and a separate test for MDMA/MDA). For grouped initial test analytes (e.g., 

hydrocodone and hydromorphone), it is not acceptable to only list the target analyte for the assay (i.e., 

hydrocodone). 

The drug testing panel will include drugs authorized for testing in Federal Workplace Drug Testing Programs, with 

the required test analytes and cutoffs; 

The biomarker testing panel will include biomarkers authorized for testing in Federal Workplace Drug Testing 

Programs, with the required test analytes and cutoffs; and

HHS-certified IITFs, HHS-certified laboratories, and Medical Review Officers must use the nomenclature (i.e., 

analyte names and abbreviations) published in the Federal Register with the drug and biomarker testing panels to 

report Federal workplace drug test results.

Negative

An IITF or a laboratory will report a urine specimen as negative when the specimen has valid 

negative results at any point in the testing process and when— 

■ All initial test results are below the initial test cutoffs; or

■ Confirmatory test results are below the confirmatory test cutoffs; 

And

■ Specimen validity test results are in the acceptable range. Validity test results are not 

reportable for valid specimens. 

Positive

A laboratory will report a urine specimen as positive for a drug/drug metabolite when— 

■ The specimen’s initial test result is at or above the initial test cutoff for the drug class; 
D-3 

And

■ The specimen’s confirmatory drug test result (i.e., on a separate aliquot) is at or above 

the confirmatory test cutoff for the specific drug/drug metabolite. 

■ Note: Specimen validity test results may or may not be in the acceptable range. 

Validity test results are not reportable for valid specimens.

Dilute

An IITF or laboratory will report a urine specimen as dilute in conjunction with a negative drug test 

when— 

■ The creatinine concentration is greater than 5.0 mg/dL but less than 20.0 mg/dL; 

And

■ The specific gravity is greater than or equal to 1.002 but less than 1.003.

A laboratory will report a urine specimen as dilute in conjunction with a positive or negative drug test 

when— 

■ The creatinine concentration is greater than or equal to 2.0 mg/dL but less than 20.0 

mg/dL; 

And

■ The specific gravity is greater than 1.0010 but less than 1.0030. 

Substituted

A laboratory will report a urine specimen as substituted when both the initial and confirmatory tests (i.e., 

tests on separate aliquots) document that— 

■ The creatinine concentration is less than 2.0 mg/dL; 

And

■ The specific gravity is less than or equal to 1.0010 or greater than or equal to 1.0200. 

■ or 

■ A biomarker is not detected or is present at a concentration inconsistent with that 

established for human urine for both the initial (first) test and the confirmatory 

(second) test on two separate aliquots (i.e., using the test analytes and cutoffs listed in 

the biomarker testing panel).

Adulterated

A laboratory will report a urine specimen as adulterated when both the initial and confirmatory test results 

(i.e., tests on separate aliquots) meet one of the following criteria:

■ The pH is less than 4.0 or equal to or greater than 11.0. 
D-4 

■ Nitrite is present equal to or greater than 500 mcg/mL for both initial test (nitrite 

colorimetric or general oxidant colorimetric) and a different confirmatory test (e.g., 

multiwavelength spectrophotometry, ion chromatography, capillary electrophoresis). 

■ Chromium (VI) is present equal to greater than 50 mcg/mL for initial test (either 

general oxidant colorimetric or chromium (VI) colorimetric) and equal to or greater 

than the LOQ for a different confirmatory test (e.g., multi-wavelength 

spectrophotometry, ion chromatography, atomic absorption spectrophotometry, 

capillary electrophoresis, inductively coupled plasma-mass spectrometry). 

■ A halogen (e.g., chlorine from bleach, iodine, fluorine) is present for initial test 

(either general oxidant colorimetric [equal to or greater than 200 mcg/mL nitriteequivalent cutoff or equal to or greater than 50 mcg/mL chromium (VI)-equivalent 

cutoff] or equal to or greater than the LOQ for a halogen colorimetric) and equal to or 

greater than the LOQ for a different confirmatory test (e.g., multi-wavelength 

spectrophotometry, ion chromatography, inductively coupled plasma-mass 

spectrometry).

■ Glutaraldehyde is present for initial test (either aldehyde or characteristic 

immunoassay response on one or more drug immunoassay initial tests) and is equal to 

or greater than the LOQ for a different confirmatory test (e.g., GC-MS). 

■ Pyridine (pyridinium chlorochromate) is present for initial test (either general oxidant 

colorimetric [equal to or greater than 200 mcg/mL nitrite-equivalent cutoff or equal to 

or greater than 50 mcg/mL chromium (VI)-equivalent cutoff] or equal to or greater 

than 50 mcg/mL chromium (VI)-colorimetric) and equal to or greater than the LOQ 

for a different confirmatory test (e.g., GC-MS).

■ Surfactant is present equal to or greater than 100 mcg/mL for both initial test 

(surfactant colorimetric using dodecylbenzene sulfonate-equivalent cutoff) and for a 

different confirmatory test (e.g., multi-wavelength spectrophotometry using 

dodecylbenzene sulfonate-equivalent cutoff). 

■ The presence of any other adulterant not specified above is verified using an initial 

test on the first aliquot and a different confirmatory test on the second aliquot.

■ The specimen contains a substance that is not a normal constituent of human urine (at 

or above the LOQ of a confirmatory test for the specific substance). 

■ The specimen contains an endogenous substance at a concentration that is not a 

normal physiological concentration (at or above the LOQ of a confirmatory test for 

the specific substance).
D-5 

Invalid Result

A laboratory will report an invalid result for a urine specimen when results for two separate aliquots meet 

one of the following criteria:

1. Creatinine concentration and specific gravity results are discrepant. 

a. The creatinine concentration is less than 2.0 mg/dL on both the initial and confirmatory 

creatinine tests and the specific gravity is greater than 1.0010 but less than 1.0200 on either or 

both of the initial and confirmatory specific gravity tests.

b. The specific gravity is less than or equal to 1.0010 on both the initial and confirmatory 

specific gravity tests and the creatinine concentration is greater than or equal to 2.0 mg/dL on 

either or both of the initial and confirmatory creatinine tests.

2. The pH is outside the acceptable range. 

a. The pH result is greater than or equal to 4.0 and less than 4.5 using either a colorimetric pH 

test or pH meter for the initial test and a pH meter for the confirmatory test.

b. The pH result is greater than or equal to 9 and less than 11 using either a colorimetric pH test 

or pH meter for the initial test and a pH meter for the confirmatory test.

Note: See Table 4, Medical Review Officer Actions for Primary (A) Specimen Reports, concerning 

specimens reported as invalid based on pH of 9.0 to 9.5.

3. Nitrite is present, but below the program cutoff for adulteration. 

a. Nitrite is greater than or equal to 200 mcg/mL using a nitrite colorimetric test for both the 

initial and confirmatory tests.

b. Nitrite is greater than or equal to the equivalent of 200 mcg/mL nitrite using a general oxidant 

colorimetric test for both the initial and confirmatory tests.

c. Nitrite is greater than or equal to 200 mcg/mL using a nitrite colorimetric test or a general 

oxidant colorimetric test and is greater than or equal to 200 mcg/mL but less than 500 

mcg/mL for a confirmatory test using a different method (e.g., multi-wavelength 

spectrophotometry, ion chromatography, capillary electrophoresis). 

4. The possible presence of chromium (VI) is determined by testing two separate aliquots using the 

same chromium (VI) colorimetric test with a cutoff greater than or equal to 50 mcg/mL chromium 

(VI). 
D-6 

5. The possible presence of a halogen (e.g., chlorine from bleach, iodine, fluorine) is determined by 

testing two separate aliquots using the same halogen colorimetric test with a cutoff greater than or 

equal to the LOQ, or relying on the odor of the specimen as the initial (first) test and testing one 

aliquot using the halogen colorimetric test.

6. The possible presence of glutaraldehyde is determined by testing two separate aliquots using the same 

aldehyde test (aldehyde present) or testing two separate aliquots using the initial test drug tests to 

verify characteristic immunoassay responses on one or more of the tests.

7. The possible presence of an oxidizing adulterant is determined by testing two separate aliquots using 

the same general oxidant colorimetric test (with a greater than or equal to 200 mcg/mL nitriteequivalent cutoff, a greater than or equal to 50 mcg/mL chromium (VI)-equivalent cutoff, or a 

halogen concentration greater than or equal to the LOQ).

8. The possible presence of a surfactant is determined by testing two separate aliquots using the same 

surfactant colorimetric test with a greater than or equal to 100 mcg/mL dodecylbenzene sulfonateequivalent cutoff, or using a foam/shake test for the initial (first) test and testing one aliquot using the 

surfactant colorimetric test.

9. Interference with the initial test drug test occurs on two separate aliquots (i.e., valid initial test drug 

test results cannot be obtained). 

Note: Some substances may interfere with some initial test tests. Cross-reactivity information is 

included in package inserts provided by the immunoassay reagent manufacturer. Laboratories are 

required to contact the MRO prior to reporting a specimen as invalid based on initial test interference, 

and laboratory personnel should be knowledgeable of possible interferents.

10. Interference with the confirmatory drug test occurs on two separate aliquots and the laboratory is 

unable to identify the interfering substance.

11. A specimen validity test (i.e., other than the tests listed above) on two separate aliquots of the 

specimen indicates that the specimen is not valid for testing. 

A laboratory will report an invalid result for a urine specimen when the laboratory identifies an abnormal 

physical characteristic and— 

■ The physical appearance of the specimen is such that testing the specimen may 

damage the laboratory’s instruments; 

■ The physical appearances of Bottles A and B are clearly different (note the laboratory 

tests the A Bottle); 

■ The laboratory suspects tampering but has no evidence of a specific substance; 
D-7 

■ The laboratory suspects a specific substance (e.g., bleach or glutaraldehyde based on 

odor), but does not test for that substance and is unable to locate a Department of 

Health and Human Services [HHS]–certified laboratory to perform the testing; or

■ The MRO does not authorize the laboratory to send the specimen for 

additional/different specimen validity testing. 
D-8 

Oral Fluid SPECIMEN Drug Testing Panel AND REPORTING CRITERIA

This drug testing panel will remain in effect until the effective date of a new drug testing 

panel published in the Federal Register: 

Initial Test Analyte

Initial Test 

Cutoff 1

(ng/mL)

Confirmatory Test 

Analyte

Confirmatory Test 

Cutoff 

(ng/mL)

Marijuana 

(THC)2 4 3 THC 2 

Cocaine/Benzoylecgonine

(COC/BZE)

15

Cocaine

Benzoylecgonine

8 

8 

Codeine/Morphine

(COD/MOR)

30 Codeine

Morphine

15

15

Hydrocodone/Hydromorphone

(HYC/HYM)

30 Hydrocodone

Hydromorphone

15

15

Oxycodone/Oxymorphone

(OXYC/OXYM)

30 Oxycodone

Oxymorphone

15

15

6-Acetylmorphine 

(6-AM)

4 3 6-Acetylmorphine 2 

Phencyclidine

(PCP)

10 Phencyclidine 10

Amphetamine/Methamphetamine

(AMP/MAMP)

50 Amphetamine

Methamphetamine

25

25

MDMA4/MDA5 50

MDMA

MDA

25

25

1

For grouped analytes (i.e., two or more analytes that are in the same drug class and have the same initial test 

cutoff):

Immunoassay: The test must be calibrated with one analyte from the group identified as the target analyte. The cross 

reactivity of the immunoassay to the other analyte(s) within the group must be 80 percent or greater; if not, 

separate immunoassays must be used for the analytes within the group.

Alternate technology: Either one analyte or all analytes from the group must be used for calibration, depending on 

the technology. At least one analyte within the group must have a concentration equal to or greater than the initial 

test cutoff or, alternatively, the sum of the analytes present (i.e., equal to or greater than the laboratory’s validated 

limit of quantification) must be equal to or greater than the initial test cutoff.

2

An immunoassay must be calibrated with the target analyte, ∆-9-tetrahydrocannabinol (THC). 

3

Alternate technology (THC and 6-AM): The confirmatory test cutoff must be used for an alternate technology 

initial test that is specific for the target analyte (i.e., 2 ng/mL for THC, 2 ng/mL for 6-AM).

4

Methylenedioxymethamphetamine (MDMA)

5

Methylenedioxyamphetamine (MDA)
D-9 

Drug Analyte Terminology and Abbreviations for Electronic Reports (Oral Fluid)

THC Marijuana1

COC/BZE Cocaine/Cocaine metabolite

COD/MOR Codeine/Morphine

HYC/HYM Hydrocodone/Hydromorphone

OXYC/OXYM Oxycodone/Oxymorphone

6-AM 6-Acetylmorphine

PCP Phencyclidine

AMP/MAMP Amphetamine/Methamphetamine

MDMA/MDA Methylenedioxymethamphetamine/ 

1 “THC” or “delta-9-tetrahydrocannabinol” for the confirmatory analyte

NOTES: The electronic report should clearly indicate whether the laboratory uses a single or multiple 

immunoassays for grouped analytes (e.g., one test for amphetamine, methamphetamine, MDMA, and MDA, or 

one test for amphetamine/methamphetamine and a separate test for MDMA/MDA). For grouped initial test 

analytes (e.g., hydrocodone and hydromorphone), it is not acceptable to only list the target analyte for the assay 

(i.e., hydrocodone). 

The drug testing panel will include drugs authorized for testing in Federal Workplace Drug Testing Programs, with 

the required test analytes and cutoffs; 

The biomarker testing panel will include biomarkers authorized for testing in Federal Workplace Drug Testing 

Programs, with the required test analytes and cutoffs; and

HHS-certified IITFs, HHS-certified laboratories, and Medical Review Officers must use the nomenclature (i.e., 

analyte names and abbreviations) published in the Federal Register with the drug and biomarker testing panels to 

report Federal workplace drug test results.
D-10 

Negative

A laboratory will report an oral fluid specimen as negative when the specimen has valid negative results 

at any point in the testing process and when— 

■ All initial test results are below the initial test cutoffs; or

■ Confirmatory test results are below the confirmatory test cutoffs;

And

■ If performed, specimen validity test results are in the acceptable range. Validity test 

results are not reportable for valid specimens.

Positive

A laboratory will report an oral fluid specimen as positive for a drug/drug metabolite when— 

■ The specimen’s initial test result is at or above the initial test cutoff for the drug class;

And

■ The specimen’s confirmatory drug test result (i.e., on a separate aliquot) is at or above 

the confirmatory test cutoff for the specific drug.

Substituted Result

A laboratory will report an oral fluid specimen as substituted when a biomarker is not detected or is 

present at a concentration inconsistent with that established for human oral fluid for both the initial (first) 

test and the confirmatory (second) test on two separate aliquots (i.e., using the test analytes and cutoffs 

listed in the biomarker testing panel).

Adulterated Result

A laboratory will report an oral fluid specimen as adulterated result when the presence of an adulterant is 

verified using an initial test on a first aliquot and a different confirmatory test on a second aliquot.

Invalid Result

A laboratory will report an invalid result for an oral fluid specimen when results meet one of the 

following criteria: 

■ Interference with the initial drug test occurs on two separate aliquots (i.e., valid initial 

drug test results cannot be obtained); 

■ Interference with the confirmatory drug test occurs on two separate aliquots and the 

laboratory is unable to identify the interfering substance; or 

■ A specimen validity test on two separate aliquots of the specimen indicates that the 

specimen is not valid for testing. 

A laboratory will report an invalid result for an oral fluid specimen when the laboratory identifies an 

abnormal physical characteristic and- 
D-11 

■ The physical appearance of the specimen (e.g., viscosity) is such that testing the 

specimen may damage the laboratory’s instruments; or 

■ The specimen has been tested and the appearances of the Tubes A and B are clearly 

different (note the laboratory tests the A Tube). 
E-1 

APPENDIX E: 

DRUG SCHEDULE INFORMATION

The Federal government classifies controlled substances under five schedules established under 

the Controlled Substances Act (CSA). Information on drug schedules is available on the Drug 

Enforcement Administration (DEA) website (https://www.dea.gov). 

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.
E-2 

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 DEA enforces the provisions of the CSA.
F-1 

APPENDIX F:

MRO VERIFICATION STATEMENT FOR EXTERNAL SERVICE PROVIDER

I, the undersigned, have or My employer/MRO company/group, [NAME], has a binding agreement with an 

external service provider, [NAME], to perform the following (check all that apply):

 Receive MRO copies of the Federal CCF from collectors

 Receive laboratory/IITF reports of drug test results (i.e., Federal CCFs, electronic reports)

 Manage MRO data (e.g., donor contact information, donor interview documentation, statistical 

reports, billing, and invoicing)

 Store MRO records related to Federal/federally regulated drug tests

 Provide MRO reports of Federal/federally regulated drug tests to the Federal agency/employer for: 

 urine specimens oral fluid specimens

 Provide and manage a Federal ECCF system (i.e., as a third party ECCF system provider)

 Other (describe): _____________________________________________________

The agreement specifies [NAME of external service provider]’s responsibilities as an external service 

provider for federally regulated drug testing and requires compliance with all applicable Subparts of the United 

States Department of Health and Human Services (HHS) Mandatory Guidelines for Federal Workplace Drug 

Testing Programs including, but not limited to, restrictions and conditions with respect to regulated specimen 

and drug test information and records.

I have verified that the agreement/contract requires compliance with the following priority elements:

1. Limiting access to regulated specimen information

2. Implementing appropriate safeguards to prevent unauthorized use or disclosure of the 

information

3. Reporting any use or disclosure of regulated specimen information not addressed in the 

agreement, including incidents that constitute data breaches

4. Disclosing information to HHS that is related to regulated specimens and drug tests

5. Arranging for disposition of regulated specimen data (i.e., disposal in accordance with 

specified record retention periods; transfer to the MRO or to another location/entity, if 

agreed to by the MRO, upon termination of the agreement/contract)

6. Notifying me prior to allowing any of the external service provider’s subcontractors to 

have access to regulated specimen and drug test information

7. Ensuring that the external service provider’s subcontractors agree to the same restrictions 

and conditions that apply to the external service provider with respect to regulated 

specimen and drug test information 

I hereby authorize [NAME of external service provider] to receive and/or disseminate federally regulated 

drug testing information and records on my behalf and in accordance with our binding agreement.

I certify that the statements and information presented above are true and correct as of this date.

Medical Review Officer (MRO) DATE

(signature and printed name)
T-1 

TABLES

Table 1. Immunoassay Tests 

Method Abbreviation Description

Enzyme Immunoassay EIA 

An immunoassay based on competition for antibody binding 

sites between drug in the specimen and drug labeled with an 

enzyme. Enzyme activity decreases when drug binds to the 

antibody. Drug concentration in the specimen is measured by 

the change in enzyme activity. 

Kinetic Interaction of 

Microparticles in Solution KIMS

An immunoassay based on the principle of the kinetic 

interaction of microparticles in a solution. Drug content of the 

specimen is directly proportional to inhibition of microparticle 

aggregation. 

Cloned Enzyme Donor 

Immunoassay CEDIA

An immunoassay utilizing enzyme fragments engineered by 

recombinant DNA techniques. Two fragments, the enzyme 

donor (ED) and enzyme acceptor (EA), are inactive when 

separated. Enzyme activity decreases when the ED drug 

fragment is bound, so the drug concentration in the specimen 

can be measured in terms of enzyme activity (i.e., drug 

concentration and enzyme activity are directly related). 

Fluorescence Polarization 

Immunoassay FPIA

An immunoassay based on competition between drug in the 

specimen and drug labeled with a fluorophore. Light emitted by 

the fluorescently labeled drug/antibody complex retains its 

polarized characteristics. The specimen’s fluorescence 

polarization value is inversely related to the drug concentration.

Microplate Enzyme-Linked 

Immunosorbent Assay ELISA 

A competitive binding enzyme immunoassay using drugspecific antibodies that are immobilized in the wells of a 

microplate. 

Note: Other types of immunoassays to detect drugs and/or metabolites exist and may be used to test Federal agency

specimens. The Medical Review Officer (MRO) may contact the Instrumented Initial Test Facility (IITF) or 

laboratory as needed for information on the immunoassay method used for the initial drug test, if not listed above.
T-2 

Table 2. Examples of Specimen Validity Test Methods 

Method Measurand Description

Atomic Absorption 

Spectrophotometry 

(AAS)

Adulterant 

concentration (e.g., 

chromium VI)

An analytical method in which a sample is vaporized in a flame 

or graphite furnace. Elemental atoms absorb ultraviolet or 

visible light at a specific wavelength and make transitions to 

higher electronic energy levels. The adulterant concentration is 

determined from the amount of absorption at the specific 

wavelength.

Capillary 

Electrophoresis (CE) 

Adulterant 

concentration (e.g., 

nitrite, chromium 

VI)

An electrophoretic separation technique using a small-bore, 

fused silica capillary tube. This separation technique is based on 

the mobility of ions in an electric field. Positively charged ions 

migrate towards a negative electrode and negatively charged 

ions migrate toward a positive electrode. Ions have different 

migration rates depending on their total charge, size, and shape, 

which allows them to be separated. 

Characteristic 

Immunoassay (IA) 

Drug Test Responses

Adulterant

concentration (e.g., 

glutaraldehyde)

Characteristic responses are exhibited by some IA tests in the 

presence of adulterants. This enables laboratories to develop 

criteria for initial drug test data that help identify a specific 

adulterant. If the IA response is validated by a laboratory for a 

specific adulterant, the laboratory may accept the abnormal 

results as the initial test for that adulterant. For the confirmatory 

test, laboratories must use a definitive method for identifying 

the adulterant (e.g., GC-MS for glutaraldehyde).

Colorimetry

pH, creatinine 

concentration, 

adulterant 

concentration 

(general or specific 

tests)

An analytical procedure based on comparison of the color 

developed in a solution of the tested material with that of a 

standard solution. In a colorimetric test, reagents are added to a 

sample and a reaction occurs, producing color. Because the 

intensity of the color is related to the concentration of the 

measurand, the measurand is determined by visually measuring 

the color or electronically measuring the intensity of light at 

selected wavelengths (i.e., spectrophotometry). This process is 

also used in some IA detection processes (e.g., ELISA).

Enzyme Immunoassay 

(EIA)

Albumin,

Immunoglobulin G 

(IgG) concentration

An immunoassay based on competition for antibody binding 

sites between measurand in the specimen and measured labeled 

with an enzyme. Enzyme activity decreases when drug binds to 

the antibody. Measurand concentration in the specimen is 

measured by the change in enzyme activity.

Gas Chromatography/ 

Mass Spectrometry 

(GC-MS) 

Adulterant 

concentration (e.g., 

glutaraldehyde, 

pyridine) 

GC is a technique for separating and analyzing mixtures of 

chemical substances in their gas or vapor phase. GC-MS is a 

combined technique coupling an MS instrument 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 measurands in a specimen, the 

specimen enters the MS, which may be used to identify and 

quantify the separated measurands. The MS creates charged 

particles (ions) and separates the ions according to their massto-charge (m/z) ratios. The ions form unique mass spectra, 

which are used to identify measurands.

High-Performance 

Liquid Chromatography 

(HPLC)

Adulterant 

concentration (e.g., 

nitrite, chromium 

VI)

A chromatographic technique for separating and analyzing 

chemical substances in solution. Separation is based on 

absorption, partition, ion exchange, or size exclusion while the 

measurand remains in solution.

(continued)
T-3 

Table 2. Examples of Specimen Validity Tests (continued)

Method Measurand Description

Inductively-Coupled 

Plasma-Mass 

Spectrometry (ICP-MS)

Adulterant

concentration (e.g., 

chromium, 

halogens, 

surfactants)

An analytical method in which the sample is introduced into a 

RF-induced plasma in the form of a solution, vapor, or solid. The 

temperature of the plasma may exceed 6000°C. The high thermal 

energy and electron-rich environment of the ICP results in the 

conversion of most atoms into ions. An MS is used to detect ions 

at different masses, allowing signals of individual isotopes of an 

element to be identified.

Ion Chromatography 

(IC)

Adulterant

concentration (e.g., 

nitrite, chromium 

VI, halogens)

A form of liquid chromatography that uses ion-exchange resins to 

separate atomic or molecular ions based on their interactions with 

the resin. Its greatest utility in the Federal program is for analysis

of anions for which there are no other rapid analytical methods. It 

is also commonly used for the analysis of cations and the 

separation of larger molecules such as amino acids and proteins.

Microplate EnzymeLinked Immunosorbent 

Assay 

Albumin

A competitive binding enzyme immunoassay using measurandspecific antibodies that are immobilized in the wells of a 

microplate. 

Multi-Wavelength 

Spectrometry (MWS)

Adulterant 

concentration (e.g., 

nitrite, chromium 

VI, halogens, 

surfactants)

A method that uses multiple wavelengths of light (or other 

electronic transmissions) to identify a measurand. The method 

generates corrected absorbance values that are related to the 

measurand concentration. 

Potentiometry

pH, oxidizing 

adulterant 

concentration

The measurement of the electrical potential difference between 

two electrodes in an electrochemical cell. A pH meter is one type 

of potentiometer. The HHS Guidelines require certified 

laboratories to use a pH meter for the confirmatory pH tests. 

Refractometry Urine specific 

gravity

The required test method for specific gravity analyses. A 

refractometer is used to determine the amount of solute (i.e., 

urinary total solids) in the urine by measuring the index of 

refraction. For program purposes, the refractive index is a 

measure of how much light is bent (refracted) by the urine sample 

being analyzed. The instrument manufacturer applies a formula to 

convert from refractive indices to the urine specific gravity values 

displayed by the refractometer. Laboratories and IITFs may use 

refractometers accurate to at least three decimal places to 

determine whether an initial specific gravity test is needed. The 

HHS Guidelines require certified laboratories to use 

refractometers that report and display specific gravity to four 

decimal places for the initial and confirmatory specific gravity 

tests. 

NOTE: HHS = Department of Health and Human Services; IITFs = instrumented initial test facilities; RF = 

radiofrequency.
T-4 

Table 3a. Required Comments for IITF and Laboratory Specimen Reports - Urine 

Test Result Required Comment1 Note

Negative and Dilute Creatinine = (numerical value) mg/dL & SpGr = (numerical value) IITF forwards to lab if creatinine ≤ 5.0 mg/dL

Positive (Specify drug analyte) = confirmatory test quantitative result

Positive and Dilute (Specify drug analyte) = confirmatory test quantitative result; Creatinine = (numerical

value) mg/dL & SpGr = (numerical value)

Adulterated

pH = (conf. test value) pH < 4.0 or ≥ 11.0 (within the range of controls in

the batch)

Nitrite = (confirmatory test value) mcg/mL ≥ 500 mcg/mL nitrite

Surfactant Present; dodecylbenzene sulfonate = ( confirmatory test value) mcg/mL ≥ 100 mcg/mL dodecylbenzene sulfonate

Chromium (VI) = (confirmatory test value) mcg/mL

adulterant ≥ LOQ

(Specify Halogen) = (confirmatory test value)

Glutaraldehyde = (confirmatory test value) mcg/mL

Pyridine = (confirmatory test value) mcg/mL

(Specify Adulterant) Present = (confirmatory test value)

Substituted Creatinine = (confirmatory test value) mg/dL & SpGr = ( confirmatory test value)

(Specify biomarker) = confirmatory test value

Invalid Result

Creatinine < 2 mg/dL & SpGr Acceptable SpGr > 1.0010 & < 1.0200

SpGr ≤ 1.0010 & Creatinine ≥ 2 mg/dL

Abnormal pH = (pH value supporting the invalid result) pH ≥ 4.0 & < 4.5 or pH ≥ 9.0 & < 11.0

Nitrite = (confirmatory test value) mcg/mL Nitrite ≥ 200 & < 500 mcg/mL on confirmatory 

test

Oxidant Activity = (≥ 200 mcg/mL nitrite-equivalents, ≥ 50 mcg/mL Cr VI-equivalents, 

or 

≥ halogen or other oxidant LOQ)2 

Oxidant = nitrite, chromium VI, halogen, etc.

(Specify initial drug test method) Interference2 Drug analyte(s) must not be included on reports for 

(Specify confirmatory drug test method) Interference invalid results based on assay interference 2

Possible (characterize as Aldehyde or Surfactant) Activity2

Abnormal Physical Characteristic - (Specify)2

Bottle A and Bottle B - Different Physical Appearance2

1 Remarks on CCF (Step 5a) & on electronic report for primary specimens; Remarks on CCF/Split Specimen Report & on electronic report for split specimens.

Labs and IITFs may add explanatory comments in addition to these required comments. 2 Lab shall contact the MRO to discuss the Invalid Result in accordance with the UrMG (88 Fed. Reg. 70768) section 11.19.g.

3 See NLCP Manual for further guidance: IITF Checklist Question E9 and Laboratory Question E10m, CCF Decision Trees
T-5

Table 3a. Required Comments for IITF and Laboratory Specimen Reports - Urine (continued)

Test Result Required Comment1 Note

Rejected for Testing

Fatal Flaw: Specimen ID number (Specify: mismatch; missing) ID mismatch/missing on CCF and/or either 

Bottle A or B

Fatal Flaw: No collector printed name & No signature

Fatal Flaw: No CCF

Fatal Flaw: No specimen submitted with CCF

Fatal Flaw: Two separate collections performed using one CCF

Fatal Flaw: (Specify: flaw that prevents testing or affects forensic defensibility of 

the

drug test and cannot be corrected)

Fatal Flaw: Bottle A label/seal (Specify: missing; misapplied; broken; shows

evidence of tampering)

Fatal Flaw: Bottle A seal condition not marked on CCF If redesignation is not possible

Fatal Flaw: Bottle A insufficient specimen volume (Specify reason and indicate

collector error when applicable)

Fatal Flaw: Specimen collected using an unapproved ECCF system

Fatal Flaw: Specimen ID number on bottle label/seal is not unique3 Incorrect label/seal for either the A or B

specimen

Uncorrected Flaw: Wrong CCF used3 (Specify: Expired/Non-regulated CCF; CCF 

Copy 2-5; ECCF Reprint without collector wet signature; ECCF Reprint without

collector explanation) Wait at least 5 business days before reporting if 

flaw not corrected Uncorrected Flaw: Collector signature not recovered

Uncorrected Flaw: A & B redesignation not documented by IITF

1 Remarks on CCF (Step 5a) & on electronic report for primary specimens; Remarks on CCF/Split Specimen Report & on electronic report for split specimens. 

Labs and IITFs may add explanatory comments in addition to these required comments. 2 Lab shall contact the MRO to discuss the Invalid Result in accordance with the UrMG (88 Fed. Reg. 70768) section 11.19.g. 3 See NLCP Manual for further guidance: IITF Checklist Question E9 and Laboratory Question E10m, CCF Decision Trees
T-6

Table 3b. Required Comments for Laboratory Specimen Reports - Oral Fluid

Test Result Required Comment1 Note

Positive (Specify drug analyte) = confirmatory test quantitative result

Adulterated (Specify Adulterant) Present = confirmatory test value

Substituted (Specify biomarker) = confirmatory test value

Invalid Result

(Specify initial drug test method) Interference2 Drug analyte(s) must not be included on reports for invalid 

(Specify confirmatory drug test method) Interference2 results based on assay interference

Abnormal Physical Characteristic - (Specify)2

Tube A and Tube B - Different Physical Appearance2

(Specify measurand) = confirmatory test value Examples: albumin, IgG

Rejected for Testing

Fatal Flaw: Specimen ID number (Specify: mismatch; missing) ID mismatch/missing on CCF and/or either Tube A or B

Fatal Flaw: No collector printed name & No signature

Fatal Flaw: No CCF

Fatal Flaw: No specimen submitted with CCF

Fatal Flaw: Two separate collections performed using one CCF

Fatal Flaw: (Specify: flaw that prevents testing or affects forensic defensibility of the 

drug test and cannot be corrected)

Fatal Flaw: Tube A label/seal (Specify: missing; misapplied; broken; shows evidence of 

tampering)

If redesignation is not possible Fatal Flaw: Tube A seal condition not marked on CCF

Fatal Flaw: Tube A insufficient specimen volume (Specify reason and indicate collector 

error when applicable)

Fatal Flaw: Expired device used for Tube A collection

Fatal Flaw: Tube A device expiration date cannot be determined Cannot verify device expiration date on Tube A and 

redesignation is not possible

Fatal Flaw: Device volume indicator(s) not observed This fatal flaw applies to specimens with a diluent (i.e., not a

fatal flaw for neat oral fluid specimens)

Fatal Flaw: Specimen collected using an unapproved ECCF system

Fatal Flaw: Specimen ID number on tube label/seal is not unique3 Incorrect label/seal for either the A or B specimen

Fatal Flaw: (Specify: Urine or Non-regulated CCF used)

Uncorrected Flaw: Wrong CCF used3 (Specify: CCF Copy 2-5; ECCF Reprint without 

collector wet signature; ECCF Reprint without collector explanation)

Wait at least 5 business days before reporting if flaw not 

corrected

Uncorrected Flaw: Collector signature not recovered Wait at least 5 business days before reporting if flaw not 

corrected

1 Remarks on CCF (Step 5a) & on electronic report for primary specimens; Remarks on CCF/Split Specimen Report & on electronic report for split specimens. Labs may add 

explanatory comments in addition to these required comments. 2 Lab shall contact the MRO to discuss the Invalid Result in accordance with the OFMG (88 Fed. Reg. 70814) section 11.17.f.

3 See NLCP Manual for further guidance: Laboratory Question E11k, E-11o, CCF Decision Trees
T-7

Table 4. Medical Review Officer Actions for Primary (A) Specimen Reports 

(continued)

Reported 

Primary 

(A) 

Specimen 

Result

Medical Review Officer (MRO) Action

Guideline1

UrMG 13.5

OFMG 13.5

Negative Report the negative result. Ur – a

OF – a

Negative 

and Dilute 

(for urine) 

Report the negative result and direct the Federal agency to immediately collect 

another specimen from the donor. If the recollected specimen provides a negative 

or negative/dilute result, the MRO reports a negative result to the agency, with no 

further action required. If the recollected specimen provides a result other than 

negative, follow the appropriate procedures below.

Ur – b

OF – N/A

Positive

or

(for urine) 

Positive 

and Dilute

If the laboratory reports an invalid result in conjunction with a positive, 

adulterated, or substituted result, see Invalid Results guidance below.

Report all verified positive and/or refusal to test results to the Federal agency.

Contact the donor to determine if he/she has a valid medical explanation for the 

positive result. 

• If the donor admits unauthorized use of the drug(s) that caused the 

positive result, the MRO reports the test result as positive to the agency.

The MRO must document the donor’s admission of unauthorized drug 

use in the MRO records and in the MRO’s report to the Federal agency.

• If the donor provides documentation (e.g., a valid prescription) to support 

a legitimate medical explanation for the positive result, report the test 

result as negative to the agency. 

• For a verified negative test result, if (for urine) the laboratory also reports 

the specimen is dilute, report a negative/dilute result to the agency and 

direct the Federal agency to immediately collect another specimen from 

the donor. For recollected specimens, refer to verification actions that are 

appropriate for the test result(s). 

Additional notes:

 Passive exposure to a drug (e.g., exposure to marijuana smoke) is not a 

legitimate medical explanation for a positive drug test result. 

 Ingestion of food products containing a drug (e.g., products containing 

marijuana) is not a legitimate medical explanation for a positive drug test. 

 Ingestion of food products containing a drug (poppy seeds containing codeine 

and/or morphine) is not a legitimate medical explanation for a positive urine 

drug test result. See exception for positive oral fluid codeine and/or morphine 

results below.

 A physician’s authorization or medical recommendation for a Schedule 1 

controlled substance is not a legitimate medical explanation for a positive 

drug test result. 

Ur – c, d

OF – b, c 
T-8

Table 4. Medical Review Officer Actions for Primary (A) Specimen Reports 

(continued)

Reported 

Primary 

(A) 

Specimen 

Result

Medical Review Officer (MRO) Action

Guideline1

UrMG 13.5

OFMG 13.5

 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. The MRO may inform the Federal agency’s 

designated representative 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 duties in a safety-sensitive 

occupation.

If the donor is unable to provide a legitimate medical explanation for the positive 

urine result, the MRO reports the positive result to the agency.

 If the laboratory also reports that a urine specimen is dilute, the MRO may 

choose not to report the dilute result.

 

If the donor is unable to provide a legitimate medical explanation for the positive 

oral fluid result, the MRO reports a positive result to the agency for all drugs 

except codeine and/or morphine as follows: 

 For oral fluid codeine and morphine less than 150 ng/mL, the MRO must 

report the result as negative to the agency unless the donor admits 

unauthorized use of the drug(s) that cause the positive result.

For oral fluid codeine and/or morphine equal to or greater than 150 ng/mL and no 

legitimate medical explanation, the MRO shall report a positive result to the agency. 

Consumption of food products must not be considered a legitimate medical 

explanation for the donor having oral fluid morphine or codeine at or above this 

concentration.

Substituted If the laboratory reports an invalid result in conjunction with a positive, 

adulterated, or substituted result, see Invalid Results guidance below.

Contact the donor to determine if he/she has a valid medical explanation for the 

substituted result. If the donor provides a legitimate medical explanation for the 

substituted result, report a negative result to the Federal agency. If the donor is 

unable to provide a legitimate explanation, report a “refusal to test” (substituted) 

to the Federal agency.

Ur – e

OF – d 

Adulterated If the laboratory reports an invalid result in conjunction with a positive, 

adulterated, or substituted result, see Invalid Results guidance below.

Contact the donor to determine if he/she has a valid medical explanation for the 

adulterated result. If the donor provides a legitimate medical explanation for the 

adulterated result, report a negative result to the Federal agency. If the donor is 

unable to provide a legitimate explanation, report a “refusal to test” (adulterated) 

to the Federal agency.

Ur – e

OF – d 
T-9

Table 4. Medical Review Officer Actions for Primary (A) Specimen Reports

(continued)

Reported 

Primary 

(A) 

Specimen 

Result

Medical Review Officer (MRO) Action

Guideline1

UrMG 13.5

OFMG 13.5

Invalid 

Result

If the laboratory reports an invalid result in conjunction with a positive, 

adulterated, or substituted result, do not report the verified invalid result to the 

Federal agency at this time. The MRO takes action for the verified invalid result(s) 

for the primary (A) specimen only when:

• the MRO verifies the positive, adulterated, or substituted results as 

negative based upon a legitimate medical explanation, or for oral fluid 

codeine and/or morphine concentrations less than 150 ng/mL, or

• the split B specimen is tested and reported as a failure to reconfirm the 

positive, adulterated, or substituted result.

Prior to reporting an invalid result to the MRO, the laboratory must contact the 

MRO to decide whether additional/different testing would be of use to obtain a 

definitive result EXCEPT when (for urine) the invalid result is based on creatinine 

and specific gravity, pH, or a confirmatory nitrite test result greater than or equal 

to 200 mcg/mL and less than 500 mcg/mL.

Contact the donor to determine if he/she has a legitimate medical explanation for 

the invalid result. For urine pH results in the 9.0 to 9.5 invalid range, MROs may 

contact the collection site, laboratory, or IITF to discuss time and temperature issues 

(e.g., time elapsed from collection to receipt at the testing facility, likely 

temperature conditions between the time of the collection and transportation to the 

testing facility, specimen storage conditions). If the donor provides documentation 

(e.g., a valid prescription) or the MRO determines that time and temperature 

account for a urine pH in the 9.0 to 9.5 range to support a legitimate medical 

explanation for the invalid result, report a test cancelled result with the reason for 

the invalid result and inform the Federal agency that a recollection is not required 

because there is a legitimate explanation for the invalid result.

Exception note: a Federal agency plan may require a negative drug test result 

based on the reason for testing (e.g., Federal agency applicant/pre-employment, 

return to duty, follow-up). 

If the donor is unable to provide a legitimate explanation or the MRO determines 

that time and temperature fail to account for the urine pH in the 9.0—9.5 range, 

report a test cancelled result with the reason for the invalid result and direct the 

Federal agency to immediately collect another specimen from the donor using a 

direct observed collection. 

If the second specimen collected provides an invalid result, report this specimen as 

test cancelled and recommend that the agency collect another authorized specimen 

type (e.g., oral fluid or urine). If the Federal agency does not authorize collection 

of another specimen type, the MRO consults with the agency to arrange a clinical 

evaluation to determine whether there is a legitimate medical reason for the 

invalid result.

See also required MRO actions in the MRO Manual Chapter 5.6.4, items 3 and 4 

for invalid specimens.

Ur – c, d, f, 

g 

OF – b, c, e 
T-10

Table 4. Medical Review Officer Actions for Primary (A) Specimen Reports

(continued)

Reported 

Primary 

(A) 

Specimen 

Result

Medical Review Officer (MRO) Action

Guideline1

UrMG 13.5

OFMG 13.5

Multiple 

Reported 

Results

If the laboratory reports an invalid result in conjunction with a positive, 

adulterated, or substituted result, see Invalid Results guidance above.

When the laboratory reports multiple results for the primary (A) specimen, follow 

the preceding verification procedures as appropriate for each reported result. 

Report all verified positive and/or “refusal to test” results to the Federal agency. 

When two separate specimens are collected during the same testing event and sent 

to the laboratory or IITF for testing (e.g., the collector sent a urine specimen out of 

temperature range and the subsequently collected specimen—urine or another 

authorized specimen type), report all verified positive and/or “refusal to test” 

results to the Federal agency and:

 If both specimens were verified negative, report the result as negative.

 If one specimen was verified negative and the other was not (i.e., the 

specimen was verified as positive, adulterated, invalid, substituted or [for 

urine] negative/dilute.), report only the verified result(s) other than negative. 

– For example, if you verified one specimen as 

negative and the other as a refusal to test because the 

specimen was substituted, report only the refusal to 

the Federal agency.

 If both specimens were verified as positive, adulterated, and/or substituted, 

report all results. 

– For example, if you verified one specimen as positive 

and the other as a refusal to test because the specimen 

was adulterated, report the positive and the refusal 

results to the Federal agency.

 If one specimen has been verified and the laboratory has not reported the 

result(s) of the other specimen:

– Immediately report verified result(s) of positive, 

adulterated, or substituted and do not wait to receive 

the result(s) of the other specimen.

– Do not report a verified result of negative, invalid or 

(for urine) negative/dilute for the first specimen to the 

Federal agency. Hold the report until results of both 

specimens have been received and verified. Do not 

report invalid results for the primary (A) specimen 

unless the split (B) specimen is tested and reported as 

a failure to reconfirm.

Ur – c, d-f, g

OF – b, c-f 
T-11

Table 4. Medical Review Officer Actions for Primary (A) Specimen Reports

1 Ur - Mandatory Guidelines for Federal Workplace Drug Testing Programs, section 13.5; OF - Mandatory Guidelines for Federal Workplace Drug Testing Programs— Oral

Fluid, section 13.5

Reported 

Primary 

(A) 

Specimen 

Result

Medical Review Officer (MRO) Action

Guideline1

UrMG 13.5

OFMG 13.5

Rejected 

for Testing

When the laboratory or IITF reports a rejected for testing result for the primary 

(A) specimen, report a test cancelled result and recommend that the Federal 

agency collect another specimen of the same type (i.e., urine or oral fluid) from 

the donor.

Ur – h

OF – f 
T-12

When Laboratory A reports multiple results (i.e., drug positive, adulterated, substituted) for the primary (A) specimen 

and Laboratory B reconfirms some (but not all) of the results for the split (B) specimen, the MRO takes the 

following action(s):

• Report to the agency all reconfirmed results (specify drug[s]/adulterant/substituted) and all results that failed 

to reconfirm (specify drug[s]/adulterant/not substituted).

• For specimens with at least one reconfirmed positive drug, inform the agency that it may take action based 

on the reconfirmed drug result(s) regardless of:

 Laboratory B’s failure to reconfirm the other drug(s) reported positive in the primary (A) specimen;

 Whether Laboratory B found the split specimen to be adulterated, invalid, or substituted when 

performing specimen validity testing after failing to reconfirm a drug; or

 Whether Laboratory B reported the failure to reconfirm a drug because the laboratory was unable to 

obtain valid confirmatory test results.

• Notify the appropriate regulatory office of the test results for the specimen.

For adulterated and substituted results, donor actions may impact actions the MRO takes after receiving the split (B) 

specimen result from the second laboratory (Laboratory B):

• If the donor provides a legitimate medical explanation for an adulterated and/or a substituted result or if the 

primary specimen was only reported as adulterated and/or substituted (but not positive for any drugs):

 Report to the agency as failed to reconfirm result (specify drug[s]); and

 Cancel both tests.

• If there is no legitimate medical explanation:

 Report to the agency as “refusal to test” (specify adulterant and/or substituted);

 Give the donor 72 hours to request that Laboratory A:

o for adulterated, request that Laboratory A retest the primary (A) specimen for the adulterant; 

o for substituted based on biomarker testing, request that Laboratory A test the primary (A) specimen 

using its confirmatory test for the biomarker; or 

o for substituted based upon urine creatinine and specific gravity, review the creatinine and specific 

gravity results for the primary (A) specimen.

 When the donor requests that Laboratory A retest the primary (A) specimen for the adulterant or 

biomarker or that Laboratory A review the urine creatinine and specific gravity results for the primary 

(A) specimen:

o If Laboratory A reconfirms the adulterant, biomarker and/or (for urine) the review of Laboratory A 

original primary (A) specimen results for creatinine and specific gravity confirms the specimen was 

substituted:

• Report to the agency as “refusal to test” (specify adulterant or substituted).

o If Laboratory A fails to reconfirm the adulterant, biomarker and/or (for urine) the review of 

Laboratory A original primary (A) specimen results for creatinine and specific gravity fails to 

confirm the specimen was substituted:

• Cancel both tests;

• Direct the agency to immediately collect another specimen using a direct observation collection 

procedure; and

• Notify the appropriate drug-free workplace regulatory office regarding the failed to reconfirm 

and cancelled test.

Subject to donor request for original specimen (A) retest and review actions described for adulterated and substituted 

results (above), the following are examples of MRO actions for combinations of reconfirmed results, failed to 

reconfirm results for drug(s), adulteration, invalid, and substituted.
T-13

Table 5. Medical Review Officer Actions for Split (B) Specimen Reports

Reported Split Specimen Result Medical Review Officer (MRO) Action2,3,4 Guideline5 

UrMG 14.6

OFMG 14.6 

Reconfirmed Failed to 

Reconfirm

Additional 

Testing Results1 

Drug(s)  Report to the agency a reconfirmed result (specify 

drug[s]).

Ur – a

OF – a

Adulterated  Report to the agency a reconfirmed result 

(adulterated [specify adulterant]).

Ur – a

OF – a

Substituted  Report to the agency a reconfirmed result 

(substituted).

Ur – a

OF – a

Drug(s) Adulterated  If the donor provides a legitimate medical 

explanation, report to the agency a failed to 

reconfirm result (specify drugs[s]) and cancel 

both tests. 

 If there is no legitimate medical explanation, 

report to the agency a failed to reconfirm result 

(specify drugs[s]) and a “refusal to test” (specify 

drug[s] and that adulterant is present.

 (see above for donor request for Lab A primary 

(A) specimen retest)

Ur – b

OF - b 

Drug(s) Substituted  If the donor provides a legitimate medical 

explanation, report to the agency a failed to 

reconfirm result (specify drugs[s]) and cancel 

both tests. 

 If there is no legitimate medical explanation, 

report a failed to reconfirm (specifying the 

drug[s]) and a refusal to test (substituted) to the 

agency. 

 (see above for donor request for Lab A primary 

(A) specimen retest)

Ur – c

OF - c 

Drug(s) Not adulterated

or

Not substituted

 Report to the agency a failed to reconfirm result 

(specify drug[s]);

 Cancel both tests; 

 Notify the HHS office responsible for 

coordination of the drug-free workplace program

Ur – d

OF - d 

Drug(s) Invalid If the invalid result cannot be resolved—

 Report a failed to reconfirm result (specify 

drug[s]) and give the reason for the invalid result; 

 Cancel both tests;

 Direct the Federal agency to immediately collect 

another specimen. If this was a urine test, direct 

the Federal agency to immediately collect another 

specimen using a direct observed collection 

procedure; and

 Notify the HHS office responsible for 

coordination of the drug-free workplace program.

Ur – e

OF – e 

(continued)
T-14

Table 5. Medical Review Officer Actions for Split (B) Specimen Reports

Reported Split Specimen Result Medical Review Officer (MRO) Action2,3,4 Guideline5 

UrMG 14.6

OFMG 14.6 

Reconfirmed Failed to 

Reconfirm

Additional 

Testing Results1 

Drug(s) Drug(s) Adulterated  Report to the agency a reconfirmed result (specify 

drug[s]) and a failed to reconfirm result (specify 

drug[s]);

 Tell the agency it may take action based on the 

reconfirmed drug(s) although Laboratory B failed 

to reconfirm one or more drugs and found that the 

specimen was adulterated; and

 Notify the HHS office responsible for 

coordination of the drug-free workplace program

Ur – f

OF – f 

Drug(s) Drug(s) Substituted  Report to the agency a reconfirmed result (specify 

drug[s]) and a failed to reconfirm result (specify 

drug[s]);

 Tell the agency it may take action based on the 

reconfirmed drug(s) although Laboratory B failed 

to reconfirm one or more drugs and found that the 

specimen was substituted; and

 Notify the appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – g

OF – g 

Drug(s) Drug(s) Not Adulterated 

Not Substituted

 Report to the agency a reconfirmed result (specify 

drug[s]) and a failed to reconfirm result (specify 

drug[s]);

 Tell the agency it may take action based on the 

reconfirmed drug(s) although Laboratory B failed 

to reconfirm one or more drugs; and

 Notify the appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – h

OF – h

Drug(s) Drug(s) Invalid If the invalid result cannot be resolved—

 Report to the agency a reconfirmed result (specify 

drug[s]) and a failed to reconfirm result (specify 

drug[s]);

 Tell the agency it may take action based on the 

reconfirmed drug(s) although Laboratory B failed 

to reconfirm one or more drugs and reported an 

invalid result; and

 Notify the appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – i

OF – i 

Adulterated 

or 

Substituted 

 Report to the agency a failed to reconfirm result 

(not adulterated: specify adulterant [pH for urine] 

or not substituted);

 Cancel both tests; and

 Notify the appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – j

OF – j 

(continued)
T-15

Table 5. Medical Review Officer Actions for Split (B) Specimen Reports

Reported Split Specimen Result Medical Review Officer (MRO) Action2,3,4

Guideline5 

UrMG 14.6

OFMG 14.6 

Reconfirmed Failed to 

Reconfirm

Additional 

Testing 

Results1

Adulterated 

or 

Substituted 

Invalid  Report to the agency a failed to reconfirm result 

(not adulterated: specify adulterant [pH for urine] 

or not substituted, and the reason for the invalid 

result);

 Cancel both tests; and

 Direct the Federal agency to immediately collect 

another specimen. If this was a urine test, direct the 

Federal agency to immediately collect another 

specimen using a direct observed collection 

procedure; and

 Notify the appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – k

OF – k 

Adulterated 

or

Substituted

(urine)

Drug(s)  Report to the agency a reconfirmed result 

(adulterated or substituted) and a failed to 

reconfirm result (specify drug[s] and

 Tell the agency it may take action based on the 

reconfirmed result (adulterated or substituted) 

although Laboratory B failed to reconfirm the 

drug(s) result.

Ur – l

OF – l 

Drug(s)

Adulterated 

or 

Substituted 

 Report to the agency a failed to reconfirm result 

(specify drug[s] and not adulterated: specify 

adulterant [pH for urine] or not substituted);

 Cancel both tests; and

 Notify the appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – m

OF – m 

Drug(s)

Adulterated

Drug(s)  Report to the agency a reconfirmed result (specify 

drug[s] and adulterated) and a failed to reconfirm 

result (specify drug[s]); and

 Tell the agency it may take action based on the 

reconfirmed drug(s) and reconfirmed adulterated 

result although Laboratory B failed to reconfirm 

one or more drugs.

Ur – n

OF – n 

Drug(s) Drug(s) 

Adulterated

 Report to the agency a reconfirmed result (specify 

drug[s]) and a failed to reconfirm result (specify 

drug[s] and not adulterated: specifying the 

adulterant [pH for urine]);

 Tell the agency it may take action based on the 

reconfirmed result (specify drug[s] although 

Laboratory B failed to reconfirm one or more 

drugs and failed to reconfirm the adulterated result.

Ur – o

OF – o 

(continued)
T-16

Table 5. Medical Review Officer Actions for Split (B) Specimen Reports

Reported Split Specimen Result Medical Review Officer (MRO) Action2,3,4 Guideline5 

UrMG 14.6

Reconfirmed OFMG 14.6 Failed to 

Reconfirm

Additional 

Testing Results1

Adulterated

and

Substituted

 Report to the agency a failed to reconfirm result 

not adulterated specifying the adulterant [pH for 

urine] and not substituted);

 Cancel both tests; and

 Notify the appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – p

OF – p 

Substituted Adulterated  Report to the agency a reconfirmed result 

(substituted) and a failed to reconfirm result (not 

adulterated: specifying the adulterant [pH for 

urine]); and

 Tell the agency it may take action based on the 

reconfirmed result (substituted) although 

Laboratory B failed to reconfirm the adulterated 

result.

Ur – q

OF – q 

Adulterated Substituted  Report to the agency a reconfirmed result 

(adulterated) and a failed to reconfirm result (not 

substituted); and

 Tell the agency it may take action based on the 

reconfirmed result (adulterated) although 

Laboratory B failed to reconfirm the substituted 

result.

Ur – r

OF – r 

1 For urine: Laboratory B conducts specimen validity tests to determine whether the failure to reconfirm the drug(s) 

is because the split specimen is adulterated, substituted, or invalid.

2 See additional MRO actions (in chart above) if 1) the donor provides a legitimate medical explanation for 

adulterated and/or substituted results or 2) requests Laboratory A to retest (adulterant) or review original results 

(substituted) for the original primary (A) specimen.

3 Prior to reporting a failed to reconfirm result to the MRO, if the laboratory believes the drug may be present, the 

laboratory must contact the MRO to decide whether testing at a third laboratory would be useful.

4 Prior to reporting a failed to reconfirm and invalid result to the MRO, the laboratory must contact the MRO to 

decide whether testing at a third laboratory would be useful.

5 Ur - Mandatory Guidelines for Federal Workplace Drug Testing Programs, section 14.6; OF - Mandatory 

Guidelines for Federal Workplace Drug Testing Programs— Oral/Fluid, section 14.6
T-17

Table 6. Some Substances That Metabolize to Amphetamine and Methamphetamine

Category Substance

Substances known to metabolize to 

methamphetamine (and amphetamine)

Benzphetamine 

Dimethylamphetamine

Famprofazone

Fencamine

Furfenorex

Selegiline 

Substances known to metabolize to amphetamine Amphetaminil

Clobenzorex 

Ethylamphetamine

Fenethylline 

Fenproporex 

Mefenorex 

Mesocarb

Prenylamine
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