Effective Date: January 1, 2020

Rev. 0722

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
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 (82 FR 7920) dated January 23, 2017 (effective October 1, 2017), 

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

Testing Programs using Oral Fluid (84 FR 57554) dated October 25, 2019 (effective January 1, 2020). 

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

Web site:

https://www.samhsa.gov/workplace

Previous versions of this manual are obsolete.
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Table of Contents

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

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

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

CHAPTER 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....................................................................... 2-4

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 Federal ECCF........................................................................................... 2-6

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

CHAPTER 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..................................................................................... 3-2

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

3.1.4 Specimen Validity.................................................................................... 3-4

3.1.4.1 Urine ............................................................................................ 3-4

3.1.4.2 Oral Fluid..................................................................................... 3-5

3.1.5 Testing...................................................................................................... 3-5

3.1.5.1 Urine ............................................................................................ 3-5

3.1.5.2 Oral Fluid..................................................................................... 3-7
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3.2 Test Methods ........................................................................................................ 3-9

3.2.1 Initial Drug Tests ..................................................................................... 3-9

3.2.2 Confirmatory Drug Tests ....................................................................... 3-10

3.2.3 Specimen Validity Tests........................................................................ 3-11

3.2.3.1 Urine .......................................................................................... 3-11

3.2.3.2 Oral Fluid................................................................................... 3-11

3.2.4 Split (B) Specimen Testing.................................................................... 3-11

3.2.4.1 Urine .......................................................................................... 3-11

3.2.4.2 Oral Fluid................................................................................... 3-12

3.3 IITF or Laboratory Reports ................................................................................ 3-13

3.4 Specimen and Records Storage.......................................................................... 3-14

CHAPTER 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............................................................................ 4-12

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 the 2020 and 2017 Federal CCFs ............................................... 4-18

4.2 Donor Interview................................................................................................. 4-19

4.3 Handling of Multiple Results or Multiple Collections During the Same 

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

4.4 Split Specimen Tests.......................................................................................... 4-23

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

4.8 Confidentiality ................................................................................................... 4-32

4.9 Discrepancies That May Require the MRO to Cancel a Test............................ 4-32

CHAPTER 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 Testing ............................................................. 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)................................................................................................... 5-20

5.3.1 Benzoylecgonine and Cocaine ............................................................... 5-20

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

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

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

5.3.1.4 Metabolism and Excretions........................................................ 5-23

5.3.1.5 Pharmaceuticals and Use ........................................................... 5-24
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5.4 Opioids17 (OPI) .................................................................................................. 5-25

5.4.1 Morphine and Codeine ........................................................................... 5-26

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

5.4.1.2 Background ................................................................................ 5-30

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) .......................................................................................... 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 ......................................................... 5-44

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

5.6.3.1 Background ................................................................................ 5-47

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

5.6.4 Invalid Specimens.................................................................................. 5-51
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5.6.4.1 Background ................................................................................ 5-51

5.6.4.2 MRO Actions............................................................................. 5-54

CHAPTER 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) ..................................... 6-13

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

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

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

Appendixes

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

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

C: Sample IITF Supplemental CCF.............................................................................C-1

D: Specimen Reporting Criteria.................................................................................. D-1

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

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

List of Tables

1. Immunoassay Tests ............................................................................................Tables-1

2. Examples of Specimen Validity Test Methods ..................................................Tables-2

3. Required Comments for IITF and Laboratory Reports......................................Tables-4 

4. Medical Review Officer Actions for Primary Specimen Reports (Bottle A)....Tables-6
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5. Medical Review Officer Actions for Split Specimen Reports (Bottle B)..........Tables-8

6. Some Substances That Metabolize to Amphetamines.....................................Tables-11
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CHAPTER 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 (82 FR 7920) and the Mandatory Guidelines for Federal 

Workplace Drug Testing Programs using Oral Fluid (84 FR 57554). For purposes of this 

document, Mandatory Guidelines will be used to refer to both guidelines using urine and oral 

fluid. 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 Oral Fluid Mandatory Guidelines for Federal 

Workplace Drug Testing Programs 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 
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tested at HHS-certified laboratories. The DOT program is administered separately from the 

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 (for urine) 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. 

The HHS Mandatory Guidelines for Federal Workplace Drug Testing Programs 

(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, 

and [for urine] negative/dilute and substituted); 

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

agency specimens; 

– The HHS Mandatory Guidelines for Federal Workplace Drug Testing 

Programs using urine and oral fluid specimens; 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. 
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■ 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 

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 (for urine) 

substituted test results; 

■ 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; 

■ Discuss potential invalid results with the HHS-certified laboratory to determine 

whether further testing at another HHS-certified laboratory is warranted;
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■ 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 2 years while maintaining the 

confidentiality of the information. The MRO may discard hardcopy records 6 

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

■ Conduct a medical evaluation 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; 

■ 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 Urine Mandatory Guidelines (82 FR 7920, effective October 1, 2017) and Oral 

Fluid Mandatory Guidelines (84 FR 57554, effective January 1, 2020) are on the SAMHSA 

web site: www.samhsa.gov/workplace/resources. 
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CHAPTER 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 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.

■ Electronic 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:

– 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.

– 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. 

Copies of the 2020 Federal CCF and guidance for use are on the SAMHSA web site: 

https://www.samhsa.gov/workplace/drug-testing. OMB approved the use of the 2020 Federal 

CCF as of September 1, 2020, for urine and oral fluid specimens. OMB originally extended 
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the use of the expired 2017 Federal CCF for urine specimens until August 30, 2021, and 

subsequently extended its use until August 31, 2023. The 2017 Federal CCF is not authorized 

for use with oral fluid specimens. As of August 31, 2023, the 2020 Federal CCF must be 

used for all federally regulated specimens, and the test facility (laboratory or IITF) must treat 

the use of the 2017 Federal CCF for urine specimens as a correctable discrepancy. Examples 

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

Appendix B. 

Employers are prohibited from using the Federal CCF and ECCF 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 an 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 non-federal 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. 

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. 

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. 
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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 

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

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 electronic or combination 
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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. 

2.3.1 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; 
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– 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

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 onscreen 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 

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

SAMHSA web site: 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 paper Federal CCFs and combination electronic and paper Federal 

CCFs. 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 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 facilitate linkage of the specimen package to the Federal ECCF sent 

to the test facility, the collector must either:
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– 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 is on their 

web site. 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 

may fax, courier, mail, or electronically provide this form. An example form is provided as 

Appendix C of this manual.
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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. 
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CHAPTER 3

Drug Testing

3.1 Federal Workplace Drug Testing Overview

3.1.1 Drugs 

Federal agencies must test each specimen for marijuana and cocaine (THC & COC) 

only, and are authorized to test each specimen for phencyclidine, opioids, and amphetamines 

(PCP, OPI, AMP). Appendix D lists the analytes (i.e., drugs and drug metabolites) and test 

cutoffs specified by the Urine Mandatory Guidelines and Oral Fluid Mandatory Guidelines. 

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 web site: 

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

Testing for an additional drug 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) Web site, https://www.dea.gov. 

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

for a drug or drug class other than those listed 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 an additional drug 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. 

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 
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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) Web site at: 

information/csa and a description is included in Appendix E. 

https://www.dea.gov/drug3.1.2 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. 

3.1.2.1 Urine

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). 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, this is 

considered a refusal to test. 

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 Urine Mandatory Guidelines. 

3.1.2.2 Oral Fluid

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. 
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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. 

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), 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 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 refusal to test. 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, this is considered a refusal to test.

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 Oral Fluid Mandatory Guidelines. 

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 

the Federal CCF or ECCF, 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 
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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

All specimen validity tests must be validated by the HHS-certified laboratory and 

approved by the NLCP and SAMHSA. Annual Federal Register Notices update what 

specimen validity tests may be performed by HHS-certified laboratories. 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 additional drug 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., tetrahydrocannabivarin, specimen validity 

tests using biomarkers). HHS-certified laboratories are not authorized to routinely perform 

additional drug 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 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. 

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 
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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. 

If a specimen exhibits abnormal characteristics (e.g., unusual odor or color, semisolid 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. 

Specimen validity tests must be performed for split Bottle B when a laboratory fails 

to reconfirm a drug analyte reported positive in the primary Bottle A. 

3.1.4.2 Oral Fluid

Federal agencies are authorized upon an MRO’s request to test an oral fluid specimen 

to determine specimen validity using, for example, a test for a biomarker such as albumin or 

immunoglobulin G (IgG) or a test for a specific adulterant. 

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.

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 web site: www.samhsa.gov/workplace. The two types of test facilities 

allowed under the Urine Mandatory Guidelines 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.
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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— 

■ 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) test 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 review the specific gravity 

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

■ 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: 
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■ 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-by-case 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.

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 Oral Fluid 

Mandatory Guidelines 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, and 

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

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

adulterated 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, or adulterated 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 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) specimen) retest the primary specimen 

(A) for the adulterant. 

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 caseby-case 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 

case-by-case basis. 

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

donor is given an opportunity to request testing of the split (B) specimen at a second HHScertified laboratory. If a donor does not ask to have the split (B) oral fluid specimen tested, a 
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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 or adulterated 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. 

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. The method must be 

validated and accurate and reliable for testing of specimens for drugs or metabolites.1

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 

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 Urine Mandatory Guidelines and 

Oral Fluid Mandatory Guidelines 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 
Rev. 0722 

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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.

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 Urine Mandatory Guidelines and Oral Fluid 

Mandatory Guidelines 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. 
Rev. 0722 

3-11 

3.2.3 Specimen Validity Tests

3.2.3.1 Urine

The Urine Mandatory Guidelines 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 Oral Fluid Mandatory Guidelines specify that Federal agencies are authorized 

upon a Medical Review Officer’s request to test an oral fluid specimen to determine 

specimen validity using, for example, a test for a biomarker such as albumin or 

immunoglobulin G (IgG) or a test for a specific adulterant. Each invalid or adulterated 

specimen validity test result must be based on an initial specimen validity test on one aliquot 

and a confirmatory specimen validity test on a second aliquot. The Oral Fluid Mandatory 

Guidelines 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

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 
Rev. 0722 

3-12 

(LOQ)—not the HHS cutoffs. Split (B) specimen reconfirmations for adulterated and 

substituted specimens are performed at the HHS cutoffs for primary (A) specimens. 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. 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 

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 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 

HHS cutoffs for primary (A) specimens. 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, 
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3-13 

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 

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

■ 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 urine 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 (for urine) 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: 

– 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 (for urine, 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). 
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3-14 

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). 

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; 

■ (for urine) 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 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 2 years by the collector or collector employer. IITFs and laboratories must maintain 

records generated to support test results for a minimum of 2 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 2 years. See Chapter 4, Section 4.6 for 

additional information. 
Rev. 0722 

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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 6 months after conversion to electronic records. 
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CHAPTER 4

MRO Review and Reporting Procedures

The MRO must review all positive, adulterated, rejected for testing, invalid test, and (for 

urine) substituted results before reporting the results 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. 

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.
Rev. 0722 

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. 

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. 

– Step 1 contains— 

• Federal agency name and address and employer ID number (as 

appropriate); 
Rev. 0722 

4-3 

• MRO name, address (i.e., street address; not a Post Office Box 

number), telephone number, and fax number; 

• 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); 

• Testing authority (i.e., Department of Health and Human Services 

[HHS], Nuclear Regulatory Commission [NRC], Department of 

Transportation [DOT] and the specific model administration, or United 

States Coast Guard [USCG]);

• Reason for the test;

• Drug tests to be performed; and 

• Collection site information (i.e., address, telephone number, and fax 

number). 

– Step 2 documents that— 

• Specimen collected is either Urine or Oral fluid;

• 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.

• 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. 

• 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 
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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— 

• Collector’s printed name; 

• Collector’s signature; 

• Date and time of the collection; and

• 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— 

• Donor’s printed name; 

• Donor’s signature; 

• Date signed;

• Donor’s email address;

• Donor’s daytime telephone number; 

• Donor’s evening telephone number; and 

• 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 (for urine) 

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., 

teleprinter, fax, 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 
Rev. 0722 

4-5 

limit access to any data transmission, storage, and retrieval 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— 

• Laboratory or IITF accessioner’s printed name;

• Accessioner’s signature;

• Date of receipt; 

• Documentation of the primary (A) specimen (Bottle/Tube A) seal 

condition upon receipt at the test facility; 

• 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 expirations dates: 

• 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.

• For an electronic (paperless) 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— 
Rev. 0722 

4-6 

• Primary (A) specimen test results including confirmatory 

concentration (ng/mL) of each drug or drug metabolite reported for a 

Positive result; 

• Certifying technician’s or certifying scientist’s printed name;

• Certifying technician’s or certifying scientist’s signature;

• Date of result certification;

• Comments on the Remarks line (as appropriate) as follows: 

► Comments as required by HHS for specimens reported as 

adulterated, rejected for testing, invalid result or (for urine)

substituted or dilute (see Table 3); and 

► Observations or explanatory comments recorded by laboratory 

or IITF staff concerning the specimen. 

• 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— 

• Name and address of the split testing laboratory; 

• Results for the split (B) specimen, with the certifying scientist’s 

signature and printed name and the date of certification; and

• 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: 

• For RECONFIRMED drug results: the specific drug analyte(s) 

reconfirmed;

• For RECONFIRMED ADULTERATED results: adulterated with the 

measurand(s) reconfirmed; and 

• (for urine) for RECONFIRMED SUBSTITUTED: substituted with the 

creatinine and specific gravity values.

– FAILED TO RECONFIRM result(s) require the following: 
Rev. 0722 

4-7 

• For FAILED TO RECONFIRM drug results: the specific drug 

analyte(s) not reconfirmed; 

• For FAILED TO RECONFIRM adulterated results: NOT 

ADULTERATED with the measurand(s) not reconfirmed; and 

• (for urine) for FAILED TO RECONFIRM substituted results: NOT 

SUBSTITUTED.

– FAILED TO RECONFIRM drug results requires the following: 

• The specimen validity tests performed; and

• 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 (for urine) substituted with confirmatory 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
Rev. 0722 

4-8 

– Additional comments concerning the specimen’s testing and processing, as listed 

in the Remarks line of the Federal CCF.

■ 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: 

a. 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.

b. 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.

c. The collector’s signature and printed name are omitted from the Federal CCF.

d. 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.

e. 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 

documentation 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. 

f. The specimen was received at the HHS-certified laboratory or IITF without a Federal 

CCF. 

g. The specimen was collected using an unapproved ECCF system. 

h. The Federal CCF was received at the HHS-certified laboratory or IITF without a 

specimen.
Rev. 0722 

4-9 

i. The collector performed two separate collections using one Federal CCF. 

j. 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. 

k. The specimen ID number on either the primary or split specimen bottle/tube label/seal

is not unique. 

l. The collector used an expired collection device for the primary oral fluid specimen 

and Tube B cannot be redesignated as the primary (A) specimen. 

m. The entire expiration date for the oral fluid specimen device cannot be determined for 

both the primary (A) and split (B) specimen. 

n. 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: 

a. The collector failed to sign the Federal CCF (but the printed name is present). The 

laboratory must contact the collector to recover the 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.

b. 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 non-federal 

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. 

c. 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.
Rev. 0722 

4-10 

d. 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.

e. 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 collector 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 documentation may 

be provided by the collection site supervisor. 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: 

a. Incorrect laboratory or IITF name and address;

b. Incomplete/incorrect/unreadable employer name or address; 

c. MRO name is missing; 

d. Incomplete/incorrect MRO address;

e. Transposition of numbers in the donor’s social security number or ID number; 

f. Missing/incorrect telephone or fax number; 

g. A “Reason for Test” box is not marked; 
Rev. 0722 

4-11 

h. A “Drug Tests to be Performed” box is not marked; 

i. The “specimen collection” box is not marked; 

j. The “Observed” box is not marked for an observed urine collection;

k. 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.”) 

l. The collector’s printed name is missing, but the collector’s signature is properly 

recorded;

m. The time of collection is not indicated;

n. The date of collection is not indicated; 

o. Incorrect/missing name of delivery service;

p. Donor’s name included on the test facility copy of the Federal CCF or on seal labels; 

q. Signature present without printed name (i.e., of collector, accessioner, certifying 

technician, or certifying scientist);

r. The collector has changed or corrected information by crossing out the original 

information but did not date and initial the change. 

s. 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. 

t. Omitted/incorrect specimen type on Federal CCF – accessioner marks correct 

checkbox, and (if marked) lines through incorrect checkbox, initials and dates the 

edit.

u. 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). 
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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: 

a. 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.

b. There is no certifying scientist signature on the Federal CCF for a positive, 

adulterated, invalid, or (for urine) 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.

c. The electronic report from the laboratory did not contain all required data elements 

for a drug positive, adulterated, invalid, or (for urine) 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: 

a. Incorrect or outdated Federal CCF information (e.g., account number); 

b. Data entry errors due to illegible or misread Federal CCF information; 

c. Data review or transcription errors by the certifying technician or certifying scientist; 

d. A discrepancy between the Federal CCF and electronic report; 

e. The accessioner failed to identify an oral fluid collection incorrect expiration date and 

the device was not expired; or 

f. Test cancelled - the accessioner failed to identify an incorrect expiration date and the 

device was expired.

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 
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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: 

a. 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. 

b. If the MRO receives a rejected for testing specimen report or identifies a fatal flaw 

during review, the MRO cancels the test. 

c. The MRO reports the cancellation and the reason to the federal agency, which then 

determines whether or not to immediately collect another specimen for the same type 

(i.e., urine or oral fluid) from the donor. 

2. When a correctable discrepancy (as defined in Section 4.1.3-2) 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. 

a. For a missing collector signature, the following may occur: 

o 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.

o 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 and notifies the federal agency of the cancelled test and the 

reason for cancellation.

b. For a regulated specimen submitted with an expired Federal CCF, the following may 

occur: 

o 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. The laboratory 

will reject the specimen if the collector did not document observation of 
Rev. 0722 

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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.

o 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.

c. For a regulated specimen submitted with an incorrect Federal CCF, the following 

may occur:

o 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. 

o 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. 

d. For a regulated specimen submitted with a non-federal form, the following may 

occur:

o If the collector provides an MFR and the specimen was tested in accordance 

with the Urine Mandatory Guidelines or Oral Fluid Mandatory Guidelines, 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.

o If the collector provides an MFR but the specimen was tested as nonregulated 

using procedures different from those specified in the Oral Fluid Mandatory 

Guidelines or the Urine Mandatory Guidelines, the laboratory or IITF must 

follow guidance provided in the NLCP Manual for Oral Fluid Laboratories 

and the NLCP Manual for Urine Laboratories (Use of Non-Regulated CCF) 

for use of a non-regulated CCF for a regulated specimen and requests to 

upgrade a non-regulated specimen to a regulated test. 

The laboratory must reanalyze the specimen using regulated procedures after 

receiving a signed request from 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 (for urine) 

IITF may send an MFR with the certification statement from the Federal CCF 

and the certifying scientist’s signatures, name, and date. 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 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 
Rev. 0722 

4-15 

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: 

o 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: 

 Laboratory MFR signed by the RP attesting that the ECCF system 

is same as the HHS-approved system; and 

 MFR from collector that explains the use of the incorrect form. 

o 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.

o 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: 

o 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: 

 Laboratory MFR signed by the RP attesting that the ECCF system 

is same as the HHS-approved system; and 

 MFR from collector that explains the use of the incorrect form. 

o 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: 

 Laboratory MFR signed by the RP attesting that the ECCF system 

is same as the HHS-approved system; 

 MFR from collector that explains the use of the incorrect form and 

explains why the authoritative copy was not sent 

Note: The laboratory must obtain Copy 1 of the CCF with the 

collector’s wet signature prior to testing the specimen. 
Rev. 0722 

4-16 

o 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. 

o 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: 

o 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 non-regulated drug test. 

o 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: 

 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.

 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 nonregulated 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.
Rev. 0722 

4-17 

e. For a regulated urine specimen received at an HHS-certified laboratory with 

redesignated primary (A) specimen (Bottle A) and split (B) specimen (Bottle B) 

bottles and no IITF explanatory comment on the Federal CCF, the laboratory must 

proceed as follows: 

o 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. 

o 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. 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 

b. 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— 

a. The MRO notifies the responsible party of the errors;
Rev. 0722 

4-18 

b. 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 

c. The MRO maintains the documentation of error notification and corrective action 

response in its records. 

d. 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 the 2020 and 2017 Federal CCFs 

The 2020 Federal CCF was implemented on August 17, 2020. Additional information is 

available at https://www.reginfo.gov/ (enter the OMB number 0930-0158 in the search area). A 

sample of the 2020 Federal CCF is available for viewing on the OMB website: (Federal Drug 

Testing Custody and Control Form (samhsa.gov). OMB granted an extension for using the 2017 

Federal CCF without an MFR as of November 23, 2021. Specimens collected using the 2017 

Federal CCF between August 30, 2021 and November 23, 2021 require an MFR explaining use 

of the 2017 form. For specimens collected on November 23, 2021 or later, laboratories and 

IITFs must accept and process federal agency specimens received with the 2017 Federal CCF 

using their routine procedures. OMB granted an extension for using the 2017 Federal CCF until 

August 31, 2023. After August 31, 2023, 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 
Rev. 0722 

4-19 

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. 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 (g) in the Urine 

Mandatory Guidelines and sections 13.5(c) through (e) in the Oral Fluid Mandatory Guidelines.) 

1. The interview process occurs as follows: 

a. 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.) 

b. 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.

c. The MRO informs the donor of the laboratory test result(s).

d. 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):
Rev. 0722 

4-20 

• 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 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.

• 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.

e. For positive, adulterated, or (for urine) 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. 

f. 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. 

g. 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. 

h. 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 Mandatory Guidelines 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 dismissal. The MRO reports a “refusal to test” to 

the federal agency in the following instances where: 

a. The donor refuses to participate at any point in the drug testing process, including: 

1) Fails to appear for any test (except a pre-employment 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; 

2) Fails to remain at the collection site until the collection process is complete with

the exception of a donor who leaves the collection site before the collection 

process begins for a pre-employment test;

3) 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 
Rev. 0722 

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regulations with the exception of a donor who leaves the collection site before the 

collection process begins for a pre-employment test; 

4) 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; 

5) Fails or decline to participate in an alternate specimen collection as directed by 

the federal agency or collector; 

6) 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/preemployment 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; 

7) 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); 

8) Brings materials to the collection site for the purpose of adulterating, substituting, 

or diluting the specimen; 

9) Attempts to adulterate, or (for urine) substitute, or dilute the specimen;

10) Admits to the collector or MRO that they have adulterated or (for urine) 

substituted the specimen; 

11) Fails to permit the observation or monitoring of provision of a urine specimen in a 

direct observed or monitored urine collection; or 

12) Possesses or wears a prosthetic or other device that could be used to interfere with 

the urine collection process. 

b. The drug test result is verified by the MRO as adulterated or (for urine) 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 (e.g., by telephone or secure fax machine). 
Rev. 0722 

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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. 

a. The MRO must report all verified positive, adulterated, “refusal to test” or (for urine) 

substituted results to the agency. 

b. 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:

a. If both specimens were verified negative, report the result as negative (single report). 

b. If one specimen was verified negative and the other was not (i.e., the specimen was 

verified as positive, adulterated, invalid, and/or (for urine) substituted or 

negative/dilute), report only the verified result(s) other than negative. 

c. 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.

d. 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 urine 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 results of all specimens have 

been received and verified. 

e. 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. The following are rules for handling split specimen requests for 

positive, adulterated, or (for urine) 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 (for urine) substituted to the 

federal agency. The donor has 72 hours from the time of his/her notification of the 
Rev. 0722 

4-23 

non-negative result to request the split 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: 

o MRO’s name and address (on MRO letterhead);

o Laboratory name and address (i.e., Laboratory A) where the primary specimen 

analysis was performed;

o Specimen ID number on the Federal CCF;

o Laboratory accession number (i.e., the number assigned by Laboratory A to 

the specimen when it was accessioned);

o Request for confirmatory testing for the drug/metabolite, adulterant, or (for 

urine) substitution reported by Laboratory A; and 

o 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 no other 

certified laboratory tests for the specific adulterant)— 

o The MRO reports to the federal agency that the test is cancelled and the 

reason for cancellation;

o The MRO directs the federal agency to immediately collect another specimen 

using (for urine) direct observation, with no notice given to the donor until 

immediately before the collection; or

o 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 
Rev. 0722 

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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., teleprinter, fax, 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 Urine Mandatory 

Guidelines or Section 14.5 of the Oral Fluid Mandatory Guidelines).

■ 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.

4.5 Interpretation and Result Verification

Chapter 5, Drug Information and Interpretation of Results, provides information on the 

drugs specified in the HHS Mandatory Guidelines for testing in federal agency workplace 

programs, including the current Controlled Substances Act (CSA) schedules, signs/symptoms of 

abuse, and metabolism information. 

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 Web site: 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 
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■ 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. 

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 (for urine) substituted 

result (see Section 4.3 above), this is a separate result that does not refer to the validity of the 
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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: and oral fluid specimens with 

concentrations of biomarkers like albumin or IgG that are not consistent with human oral fluid. 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.

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 (for 

urine) 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 (for urine) 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 
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of invalid results. Certain antibiotics and nonsteroidal anti-inflammatory 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 

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.” 
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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 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. 
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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. 

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 safety-sensitive, healthsensitive, 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. 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.48

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 

The MRO may change a previously verified test result 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. 
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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. 

The Mandatory Guidelines require MROs to retain drug test records for a minimum of 2 

years from the date of collection. Hardcopy records may be discarded 6 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).
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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

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 or mail or use 

various electronic means (e.g., teleprinter, fax, 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 
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■ 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). 

4.8 Confidentiality

The Mandatory Guidelines require the MRO to— 

■ 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 (for urine) 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 
Rev. 0722 

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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.
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CHAPTER 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 specimen for marijuana and cocaine (THC & 

COC), and may also test each specimen for phencyclidine, opioids, and amphetamines (PCP, 

OPI, AMP). With the exception of 6-acetylmorphine (a metabolite of heroin), benzoylecgonine 

(a metabolite of cocaine), and Δ9- tetrahydrocannabinol-9- carboxylic acid (a metabolite of 

marijuana), the analytes detected are primarily parent compounds. Appendix D lists the analytes 

(i.e., drugs and drug metabolites) and test cutoffs specified by the Mandatory Guidelines for 

urine and oral fluid testing. 

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.53,54 Positivity rates for oral fluid reported for nonregulated 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.55 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.56 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-protein bound and nonionized drug in plasma can diffuse into saliva. Consequently, oral fluid drug concentrations are 

closely related to the free, unbound drug in blood (plasma). 
Rev. 0722 

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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.34,35 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.37

Drug residues can initially be deposited in high concentration in oral fluid during active drug 

administration by oral, transmucosal, smoked, inhaled, and insufflated routes.34,35,57 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. 

The Department of Health and Human Services (HHS) instituted the following urine 

assay validation and reporting requirements that prevent the possibility of false positive 

methamphetamine results:
Rev. 0722 

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■ Laboratories are required to quantitate at least 100 ng/mL amphetamine in a urine 

specimen in order to report a positive methamphetamine result. As described 

previously, methamphetamine metabolizes to amphetamine. This occurs quickly, via 

a simple demethylation reaction. Because the sympathomimetic amines are not 

converted to amphetamine, the presence of amphetamine is supporting evidence for 

methamphetamine use.

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

o 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. 

o 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 

o Mass spectrometry: The test method must use an analytical method 

combining chromatographic separation and mass spectrometric 
Rev. 0722 

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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

(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,

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(ng/mL)

Amphetamine/ Methamphetamine 500 Amphetamine

Methamphetamine

250 

250 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(ng/mL)

Amphetamine/ Methamphetamine 50 Amphetamine

Methamphetamine

25 

25
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■ 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. 

5.1.1.2 Enantiomer Drug Testing 

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 L-methamphetamine 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 L-methamphetamine and/or Lamphetamine.

(Comment: Enantiomer test results aid in result interpretation.2

 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 
Rev. 0722 

5-6 

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 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 L-isomers 

have distinct pharmacological properties. In this case, the D-isomer of each substance has a 

strong central nervous system stimulant effect while the L-isomer of each substance has 

primarily a peripheral action. Illegally manufactured amphetamine and methamphetamine are 

principally found as the D-isomer; however, significant amounts of the L-isomer of each 

substance may be present depending on the starting materials used by the clandestine 

laboratories.

5.1.1.4 Routes of Administration

■ Amphetamine—oral (i.e., tablets or capsules), intravenous injection, smoking, and 

intranasal (i.e., snorting). 
Rev. 0722 

5-7 

■ Methamphetamine—oral (i.e., tablets or capsules), intravenous injection, smoking, 

and intranasal (i.e., snorting). 

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 is demethylated to amphetamine and its metabolites. Amphetamine is excreted as 

both unchanged amphetamine and as hydroxylated metabolites. Typically, about one-quarter of 

an administered dose is excreted as unchanged amphetamine, but this varies widely with urinary 

pH; the drug stays in the body longer when urine is alkaline, allowing reabsorption and thus 

allowing more of it to be metabolized. In 24 hours, about 74% of a dose will be excreted 

unchanged if urine is acidic, while 1 to 2 % is excreted if urine is alkaline. 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.25

Methamphetamine and its metabolite, amphetamine, also appear rapidly in oral fluid with 

methamphetamine as the major constituent.26,27 Both amphetamine and methamphetamine 

appearance in oral fluid are affected by pH. Amphetamine and methamphetamine detection in 

oral fluid is generally one day.59

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 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 
Rev. 0722 

5-8 

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.7

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 Lmethamphetamine and L-amphetamine. Another example is benzphetamine (Didrex®). 

Benzphetamine is metabolized to D-methamphetamine and D-amphetamine. A D-isomer and Lisomer 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 

methamphetamine and amphetamine. Specimens containing sympathomimetic amines will not 

be reported positive by the laboratory after conducting the confirmatory test. Some over-thecounter (OTC) products (e.g., inhalers) contain L-methamphetamine (also called L-
Rev. 0722 

5-9 

desoxyephedrine 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) added substituted phenethylamines 

to the performance testing (PT) program to ensure all certified laboratories were distinguishing 

those from the MDMA and MDA. 
Rev. 0722 

5-10 

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

o 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. 

o 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 

o 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 

Concentration

(ng/mL)

MDMA/MDA 500 

MDMA

MDA

250 

250 
Rev. 0722 

5-11 

(b) Oral Fluid

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(ng/mL)

MDMA/MDA 50

MDMA

MDA

25 

25

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.
Rev. 0722 

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 dihydroxy- derivatives. 

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.28

Limited studies have shown MDMA and MDA detectable in oral fluid for 71 and 47 hours, 

respectively, in oral fluid.58

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 users to take a second 

dose of the drug as the effects of the first dose begin to fade. These effects include feelings of 
Rev. 0722 

5-13 

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-

tetrahydrocannabinol-9-carboxylic acid [THCA] for urine and ∆-9-

tetrahydrocannabinol [(THC] for oral fluid).
Rev. 0722 

5-14 

– 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 

Concentration

(ng/mL)

Marijuana (THCA) 50 THCA 15 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(ng/mL)

Marijuana (THC) 4 THC 2 
Rev. 0722 

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).8

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. 
Rev. 0722 

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 

also is 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.29 THC appears at its highest 

concentration in oral fluid immediately after smoking marijuana.30,31,32,33 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 

dronabinol, the MRO should allow the donor the opportunity to provide the supporting 
Rev. 0722 

5-17 

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.49,50 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.9,10,11 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 CBD-enriched 

product for the control of intractable epilepsy in children. Epidiolex is cannabidiol (CBD) and 

contains trace THC. Therefore, this compound may 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 cannabidiol (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 Web 

Oil is being advertised in Colorado for similar symptoms. That product appears to be a marijuana 
Rev. 0722 

5-18 

extract enriched with higher ratios of CBD to THC. The product might give a positive THCA 

test result. 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.3

(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. 

(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 
Rev. 0722 

5-19 

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.12 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.64 

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 non-FDAapproved drug products made from cannabis.13 “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).51 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 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. 48 
Rev. 0722 

5-20 

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. 

The subject of cannabinoid isomers is rapidly evolving and may outpace the publication 

schedules for the MRO Manual. MRO’s should look for program updates as they become 

available from SAMHSA, the DOT, and MRO professional associations. 

5.3 Cocaine (COC)

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 
Rev. 0722 

5-21 

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

o 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. 

o 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., 100 ng/mL for urine 

benzoylecgonine). 

■ Confirmatory Test 

o 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. 
Rev. 0722 

5-22 

(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: 

■ 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.

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(ng/mL)

Cocaine metabolite 

(Benzoylecgonine)

150 Benzoylecgonine 100 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(ng/mL)

Cocaine/Benzoylecgonine 15

Cocaine

Benzoylecgonine

8 

8
Rev. 0722 

5-23 

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 urine drug testing program requires analysis for the cocaine metabolite 

benzoylecgonine. 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.15

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.

5.3.1.4 Metabolism and Excretions 

(a) Urine

Cocaine is rapidly and extensively metabolized by liver and plasma enzymes to its major 

metabolite, benzoylecgonine.16 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 using a test 

cutoff of 300 ng/mL. 
Rev. 0722 

5-24 

(b) Oral Fluid

Cocaine appears in oral fluid within minutes after use following intravenous, nasal and 

smoked administration. 34 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.60

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: 

■ 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.52 When a donor claims that the positive benzoylecgonine test was due to 

passive inhalation, the MRO should allow the donor to describe the circumstances 
Rev. 0722 

5-25 

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 Opioids17 (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”). 

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.18 In 

the United States, the problem of diverted pharmaceutical opioids is reaching crisis proportions. 
Rev. 0722 

5-26 

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.19 In 15 states, the number of deaths from 

prescription medications now exceeds the number of traffic fatalities.

Effective October 1, 2017, HHS revised the Mandatory Guidelines to include the 

semisynthetic opioids oxycodone, oxymorphone, hydrocodone, and hydromorphone as 

analytes. Opioids included in the drug testing panel confirm correctly and independently of 

other synthetic opioids. 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 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 information from the laboratory for any other opioid analytes (i.e., 

morphine, codeine, 6-acetylmorphine (6-AM), oxycodone, hydrocodone, oxymorphone, 

hydromorphone) that are present below the cutoff. 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.

5.4.1 Morphine and Codeine 

A positive test for codeine or morphine would be comprised of any or all analytes with a 

confirmed urine concentration equal to or greater than 2000 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). These opioids are 

differentiated during testing and will not be misidentified using a confirmatory test as required 

by the Mandatory Guidelines. 
Rev. 0722 

5-27 

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. There is 

limited information in the scientific literature on the codeine and/or morphine 

concentrations seen in oral fluid after consumption of poppy seed food products. 

Therefore, the Department is proposing a conservative concentration of 150 ng/mL 

(i.e., 10 times the confirmatory test cutoff) as the decision point. 

■ A positive result for any of the opioid analytes (with the exception of 6-AM) may be 

from legitimate use of a drug product. 

■ The presence of both codeine and morphine in urine indicates the recent use of 

codeine; however, morphine alone may be detected as a remnant of codeine that has 

been completely metabolized.

The MRO must assess the laboratory result and the information from the donor to verify 

the drug test positive. 

HHS included additional criteria in the Mandatory Guidelines to distinguish between 

specimens testing positive due to opioids abuse and specimens testing positive due to food 

sources or legitimate medical use. The criteria are as follows:

■ When a laboratory reports a specimen as positive for codeine and/or morphine and 

the quantitative urine results for both codeine and morphine are less than 15,000 

ng/mL (or less than 150 ng/mL for oral fluid) — 

– If there is clinical evidence of illicit use of any opium or opium derivative (e.g., 

morphine or codeine) listed in the Controlled Substances Act (CSA) Schedule I or 

II, the MRO verifies the result as positive; or 

– If there is no clinical evidence of illicit use, the MRO verifies the result as 

negative. However, this requirement does not apply if the laboratory confirms the 

presence of 6-acetylmorphine (i.e., the presence of this metabolite is proof of 

heroin use). 

■ When a laboratory reports a specimen as positive for codeine and/or morphine and 

the codeine and/or morphine urine result is greater than or equal to 15,000 ng/mL (or 

greater than or equal to 150 ng/mL for oral fluid)— 

– If the donor does not present a legitimate medical explanation for the presence of 

morphine or codeine (e.g., a valid prescription), the MRO verifies the result as 

positive. Consumption of food products is not a legitimate medical explanation 

for the donor having morphine or codeine at or above this concentration; or 
Rev. 0722 

5-28 

– If the donor presents a legitimate medical explanation for the presence of 

morphine or codeine (e.g., a valid prescription), the MRO verifies the result as 

negative.

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.
Rev. 0722 

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, 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 

Concentration

(ng/mL)

Codeine/Morphine 2000 Codeine 

Morphine

2000 

2000 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(ng/mL)

Codeine/Morphine

30 Codeine 

Morphine

15 

15
Rev. 0722 

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-
Rev. 0722 

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.35,36 Morphine detected in oral fluid following ingestion of poppy seeds indicated 

that morphine was positive for a shorter intervals of 1-2 hours.37,61 Single dose studies of codeine 

demonstrated codeine is detected in oral fluid within an hour but morphine was not detected.38

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 and confirmatory cutoffs for morphine and codeine at 2000 ng/mL. 

Note: Heroin contaminated with acetylcodeine may produce positive test results for 

morphine, and codeine in addition to 6-acetylmorphine. 
Rev. 0722 

5-32 

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, 

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.
Rev. 0722 

5-33 

■ 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 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(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 

Concentration

(ng/mL)

Hydrocodone/Hydromorphone 30 Hydrocodone 

Hydromorphone

15 

15

Oxycodone/Oxymorphone 30 Oxycodone 

Oxymorphone 

15 

15 
Rev. 0722 

5-34 

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 

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 for 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 0-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). 
Rev. 0722 

5-35 

■ Oxymorphone—oral (i.e., tablet or extended-release tablet). 

Abusers may use in a variety of methods, including intravenous injection and smoking. 

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.38,39,40 

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.5

 

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 
Rev. 0722 

5-36 

cutoff concentration of 50 ng/mL, detection times were approximately 30 hours for oxycodone 

and oxymorphone. Some final specimens at relatively low concentrations contained only 

oxymorphone. Using 100 ng/mL as the cutoff, the study shows that hydrocodone and 

hydromorphone are generally detectable in urine for one day.4

 

(b) Oral Fluid

Both oxycodone and oxymorphone have been reported to be readily detectable in oral 

fluid specimens collected from pain patients.41,42 Oxycodone is metabolized in relatively minor 

amounts to oxymorphone.43 Oxymorphone is a potent analgesic used for pain relief orally and 

parenterally, and is primarily metabolized by conjugation.44 Hydromorphone appears rapidly in 

oral fluid following intravenous administration.45 

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.62 

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.63
Rev. 0722 

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 initial testing and confirmatory cutoffs for morphine and codeine at 2000 ng/mL. 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.

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 
Rev. 0722 

5-38 

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

– 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 
Rev. 0722 

5-39 

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 

Concentration

(ng/mL)

6-Acetylmorphine 10 6-Acetylmorphine 10 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(ng/mL)

6-Acetylmorphine 4 6-Acetylmorphine 2
Rev. 0722 

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. 
Rev. 0722 

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.35 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)

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. 
Rev. 0722 

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

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(ng/mL)

Phencyclidine 25 Phencyclidine 25 

Initial Test Analyte

Initial Test 

Cutoff 

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(ng/mL)

Phencyclidine 10 Phencyclidine 10
Rev. 0722 

5-43 

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 

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.

23 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.24

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. 
Rev. 0722 

5-44 

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 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.46,47 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

5.6.1 Dilute Specimens

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 

■ 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. 
Rev. 0722 

5-45 

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 positive or negative. These MRO actions are shown in Table 4, Medical Review Officer

Actions for Primary (A) Specimen Reports.

5.6.2 Substituted Urine Specimens

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. 

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 drugfree 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 
Rev. 0722 

5-46 

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.

■ 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. 
Rev. 0722 

5-47 

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

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 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 
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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 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: 
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■ 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 6 months of age. 

■ Occupational exposure. Workers in explosives and pharmaceuticals manufacturing 

may be exposed to nitrates. 

■ Medications. Organic nitrate and nitro compound drugs (e.g., used for angina, 

congestive heart failure, ulcers) metabolize to inorganic nitrite ion. Inorganic 

nitrite/nitrate salts have limited medical uses (e.g., used for cyanide poisoning). 

■ Endogenous production. The enzyme nitric oxide synthase (NOS) catalyzes the 

endogenous formation of nitric oxide radical, which oxidizes to nitrite and nitrate. 

This may result in normal human urine containing a small amount of nitrate with an 

extremely small ratio of nitrite.

■ Pathological conditions. Some infectious and inflammatory conditions (e.g., sepsis, 

asthma, rheumatoid arthritis, tuberculosis, inflammatory bowel disease, Alzheimer’s 

disease, multiple sclerosis) induce another enzyme (i.e., inducible NOS) that 

catalyzes the formation of nitric oxide radical.

■ Medical treatments. Some medical treatments (e.g., Interleukin-2 in cancer 

treatment) can induce NOS and result in nitrite in the urine.

■ Urinary tract infections. Some urinary tract infections are caused by bacteria that, if 

present in large numbers, may reduce nitrate to nitrite by microbial action.

Because low levels of nitrite may be present in human urine due to the reasons listed 

above, HHS set a cutoff level 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 
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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) 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 
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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.

5.6.4 Invalid Specimens

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 
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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 

immunoassay or alternate technology 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; 

■ 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.
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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 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. HHS-certified 

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 to determine specimen validity using, 

for example, a test for a biomarker such as the albumin concentration or immunoglobulin G 

(IgG) concentration or a test for a specific 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 

HHS 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 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) oral fluid specimen as an invalid 

result when: 

■ Interference with testing
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– Interference occurs on the initial drug tests on two separate aliquots (i.e., valid 

immunoassay or alternate technology 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; 

■ 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

■ The concentration of an MRO-requested biomarker (e.g., albumin or IgG) is not 

consistent with that established for human oral fluid for both the initial (first) test and 

the second test on two separate aliquots. 

The Mandatory Guidelines using oral fluid do not require routine specimen validity 

testing for oral fluid testing. The MRO must request biomarker testing for oral fluid. 

Invalid 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.

5.6.4.2 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 specimens invalid due to a possible adulterant or for specimens 

with an abnormal physical characteristic. 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. 

For invalid urine results based on pH of greater than or equal to 9.0 to 9.5, the MRO must 

consider if time and warm temperature could account for the result.6 The MRO must contact the 

collection site, IITF, and/or laboratory to investigate the conditions of shipping and storage. The 

procedures to follow are described in Table 4. 

The MRO must take the following actions for a specimen with an invalid result: 

1. If the donor’s explanation is medically legitimate OR if time and temperature

conditions appear to account for urine pH in the 9.0–9.5 range, report the test as

cancelled with the reason for the invalid result and inform the federal agency that a 
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recollection is not required because there is an acceptable reason 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. 

2. If the donor’s explanation is not medically legitimate OR if time and temperature

conditions do not appear to account for urine pH in the 9.0–9.5 range, report the test as

cancelled with the reason for the invalid result and direct the federal agency to

immediately collect another specimen using (for urine) a direct observed collection

procedure. If the urine specimen recollected under direct observation is valid, the 

result is reported in accord with Chapter 5 and Table 4 of this manual. 

3. If a specimen is recollected using direct observation and is invalid for— 

a. The same reason reported for the first specimen, report the test as cancelled with 

the reason for the invalid result and inform the federal agency that a recollection 

is not required because there is an acceptable reason 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 in 

Item 4 below; or

b. A different reason than reported for the first specimen, do not contact the donor. 

Report the test as cancelled with the reason for the invalid result and direct the 

federal agency to immediately collect another specimen using (for urine) a direct 

observed collection procedure. Review and report the test based on the reported 

result of the specimen from the second observed collection using the above 

procedures. If the specimen from the second observed collection is reported as 

invalid for a different reason than the specimen from the first observed collection 

and there is no acceptable explanation, follow procedures as described in Item 4 

below. 

4. Determine if there is clinical evidence that the donor is a current illicit drug user 

when— 

a. The donor has an invalid result with an acceptable explanation as described in 

section 5.6.4.2-1 above, and a negative result is required (e.g., for a federal

agency applicant/pre-employment, return to duty, or follow-up test); 

b. The donor has two specimens reported as invalid for the same reason as described 

in section 5.6.4.2-3(a) above, and a negative result is required (e.g., for a federal

agency applicant/pre-employment, return to duty, or follow-up test); or 

c. The donor’s second urine specimen collected under direct observation as described

in section 5.6.4.2-3(b) above is invalid for a different reason than the urine 

specimen from the first observed collection and there is no acceptable explanation 

(e.g., time and temperature that account for pH in the 9.0–9.5 range).

5. If needed under Item 4 above, arrange for a medical evaluation of the donor as 

follows: 
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a. The MRO must personally conduct the medical evaluation or ensure that the 

medical evaluation is conducted by another licensed physician that is acceptable 

to the MRO. If appropriate, the MRO may also consult with the donor’s physician 

to gather information needed to make the determination. 

b. The physician conducting the medical evaluation may conduct medically 

approved procedures to determine clinical evidence of current drug use. 

c. 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 

specimen impossible; and

• The basis for determining that no signs and symptoms of drug 

use exist; and 

• Recommend that the agency authorize collection of an 

alternative specimen type (e.g., urine or oral fluid) for any 

subsequent collections. 

Or 

■ “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) of the donor: 

• The basis for the determination that a permanent or long-term 

medical condition exists, making provision of a sufficient 

specimen impossible; and

• The basis 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. 

 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 
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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.
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CHAPTER 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 Mandatory Guidelines using urine and oral fluid include requirements for blind 

samples as follows:

Urine:

■ A blind sample that is positive must be prepared with one or more of the drugs or 

metabolites specified in the Mandatory Guidelines at a concentration 1.5–2 times the 

initial drug test cutoff (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 
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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).

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 with one or more of the drugs or 

metabolites specified in the Mandatory Guidelines at a concentration 1.5–2 times the 

initial drug test cutoff (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 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 
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sample is a “blind sample” where the donor would normally provide a signature (Step 5 on Copy 

2 of the Federal CCF).

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 alternative 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 MRO must 
Rev. 0722 

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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 alternative specimen. When the federal 

agency did not authorize the collection of an alternative 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 (e.g., urinary system dysfunction) 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 urine during the 

collection. 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. Examples include the following: 

■ Destruction of the glomerular filtration system leading to renal failure;

■ Unrepaired traumatic disruption of the urinary tract; 

■ 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 
Rev. 0722 

6-5 

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 

at least 45 mL of urine as required for the test); 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 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 urine. The MRO reports a refusal to test to the 

federal agency; or 

■ 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 donor from providing urine, but is highly likely 

to prevent the employee from providing a sufficient amount of urine for a very long 

or indefinite period. In the case the result is needed for the agency, the MRO follows 

section 6.2.1.1 below. Otherwise, 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 Urine Mandatory Guidelines Section 13.7 as appropriate. If 

Section 13.7 is not applicable, you report a test cancelled result to the federal agency 
Rev. 0722 

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and recommend that the agency authorize collection of an alternative specimen type 

(e.g., oral fluid) for any subsequent drug tests for the donor. 

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 alternative 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., Mandatory Guidelines using oral fluid specimen 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 alternative specimen (e.g., 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 donor’s 
Rev. 0722 

6-7 

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 alternative 

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) 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 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. 
Rev. 0722 

6-8 

If the insufficient oral fluid volume is due to a limited collection that was not noted, the MRO 

will implement the medical evaluation procedure.

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 alternative 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 alternative 

specimen. When the federal agency did not authorize the collection of an alternative 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 urine for a federally regulated drug test but was unable to provide 

at least 1 mL of neat oral fluid as required for the test); 

■ 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.) 
Rev. 0722 

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 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; or 

■ 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 donor from providing oral fluid, but is highly 

likely to prevent the employee from providing a sufficient amount of oral fluid for a 

very long or indefinite period. In the case the result is needed for the agency, the 

MRO follows paragraph 6.2.2.1 below. Otherwise, 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 oral fluid for a very long or indefinite period of time. As the MRO, you 

must follow the requirements of Oral Fluid Mandatory Guidelines 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 alternative 

specimen type (e.g., urine) for any subsequent drug tests for the donor. 

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 alternative 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., Mandatory Guidelines using urine specimen 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
Rev. 0722 

6-10 

■ 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.

6.2.2.1 Permanent or Long-Term Medical Condition and Required Negative Test 

Additional actions are required when the federal agency does not authorize collection of 

an alternative specimen (e.g., urine), the MRO determines that a donor has a permanent or longterm 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: 

• The basis for the determination that a permanent or long-term medical 

condition exists, making provision of a sufficient oral fluid specimen 

impossible; 

• The basis for determining that no signs and symptoms of drug use 

exist; and 

• Recommend that the agency authorize collection of an alternative 

specimen type (e.g., urine) for any subsequent collections. 

Or 

■ “Test cancelled” when the medical evaluation reveals clinical evidence of drug use. 
Rev. 0722 

6-11 

– 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 oral fluid specimen 

impossible; and

• The basis for determining that signs and symptoms of drug use exist.

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 
Rev. 0722 

6-12 

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. 

6.4 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.
Rev. 0722 

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6.5 Protection of Personally Identifiable Information (PII)

Personally identifiable information (PII) is information that can be used to distinguish or 

trace an individual’s identity alone or when combined with other personal identifying 

information that is linked or 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. 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 (e.g., collectors, test facilities, 

MROs) 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. 

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 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 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. 
Rev. 0722 

6-14 

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 related to 

regulated drug testing. For example, an MRO, MRO employer, or MRO group (i.e., MRO 

organization with more than one MRO), 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 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 another MRO within its organization as responsible for the 

external service provider’s compliance with the Guidelines. 

To ensure that MROs are properly identified (on Federal CCFs), MROs, MRO 

employers, or MRO groups should provide federal agencies with documentation that designates 

a specific MRO 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 Urine Mandatory 

Guidelines and Oral Fluid Mandatory Guidelines. 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. 
Rev. 0722 

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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 2 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 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. 
Rev. 0722 

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 October 1, 2017) 

and the HHS Mandatory Guidelines for Federal Workplace Drug Testing Programs using Oral 

Fluid (OFMG, Effective January 1, 2020), 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 an endogenous substance. 

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 HHScertified 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. 

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.
Rev. 0722 

A-2 

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 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 urine specimen.

Collection Site. The location where specimens are collected.

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 a specimen validity test result.
Rev. 0722 

A-3 

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 or drug metabolite concentration) used as the 

decision point to determine a result (e.g., negative; positive; adulterated; invalid; or [for urine] 

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. 

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 HHScertified laboratory; a Medical Review Officer (MRO); or an HHS-certified Instrumented Initial 

Test Facility (IITF).

Failed to Reconfirm. The result reported for a split (B) specimen when a second HHScertified 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 (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 

invalid, adulterated, or (for urine) diluted or substituted. 
Rev. 0722 

A-4 

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 3.7 of the OFMG) when a 

positive or negative 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. 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. 

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 
Rev. 0722 

A-5 

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 HHS-certified 

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 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. 
Rev. 0722 

A-6 

• 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.

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 HHS-certified 

laboratory corroborates the original result reported for the primary (A) specimen. 

Rejected for Testing. The result reported by an HHS-certified laboratory or HHS-certified 

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.
Rev. 0722 

A-7 

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. 

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 urine, 

as evidenced by creatinine and specific gravity values that are outside the physiologically 

producible ranges of human urine. 

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. 
Rev. 0722 

B-1 

APPENDIX B: 

SAMPLE OF CCF—TEST FACILITY COPY (1) AND MRO COPY (2)

(Note reduced size)
Rev. 0722 

B-2 
Rev. 0722 

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

 
Rev. 0722 

D-1 

APPENDIX D: 

URINE SPECIMEN REPORTING CRITERIA

Initial Test Analyte

Initial Test 

Cutoff 1

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(ng/mL)

Marijuana metabolites 

(THCA)2

50 3 THCA 15 

Cocaine metabolite 

(Benzoylecgonine) 

(BZE)

150 3 Benzoylecgonine 100 

Codeine/Morphine 

(COD/MOR)

2000 Codeine 

Morphine 

2000 

2000 

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. 
Rev. 0722 

D-2 

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)

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 

NOTE: 

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). 
Rev. 0722 

D-3 

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.

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; 

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.

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. 
Rev. 0722 

D-4 

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. 

■ 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 plasmamass spectrometry). 

■ A halogen (e.g., bleach [chlorine], iodine, fluorine) 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 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 sulfonateequivalent 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). 
Rev. 0722 

D-5 

■ 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).

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). 
Rev. 0722 

D-6 

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).

5. The possible presence of a halogen (e.g., bleach [chlorine], 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 Medical Review Officer (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. The concentration of a biomarker is not consistent with that established for human urine. 

A laboratory will report an invalid result for a urine specimen when the laboratory identifies an abnormal 

physical characteristic and— 

■ The laboratory cannot test the specimen due to the abnormal physical characteristic; 

■ The physical appearance of the specimen is such that testing the specimen may damage the 

laboratory’s instruments; 
Rev. 0722 

D-7 

■ 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; 

■ 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. 
Rev. 0722 

D-8 

ORAL FLUID SPECIMEN REPORTING CRITERIA

Initial Test Analyte

Initial Test 

Cutoff 1

(ng/mL)

Confirmatory 

Test Analyte

Confirmatory 

Test Cutoff 

Concentration

(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 
Rev. 0722 

D-9 

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)

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/ 

Methylenedioxyamphetamine 

1 “THC” or “delta-9-tetrahydrocannabinol” for the confirmatory analyte 

NOTE: 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). 
Rev. 0722 

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.

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/drug metabolite.

Adulterated Result

A laboratory reports a primary (A) oral fluid specimen as an 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 two separate aliquots meet one 

of the following criteria: 

■ Interference with the initial drug test occurs on two separate aliquots (i.e., valid immunoassay 

or alternate technology initial drug test results cannot be obtained); 

■ Interference with the drug confirmatory drug test occurs on two separate aliquots of the 

specimen and the laboratory is unable to identify the interfering substance; or

■ The concentration of an MRO-requested biomarker (e.g., albumin or IgG) is not consistent 

with that established for human oral fluid for both the initial (first) test and the second test on 

two separate aliquots. 

A laboratory will report an invalid result for an oral fluid specimen when the laboratory identifies an 

abnormal physical characteristic and- 

■ 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 laboratory tests A tube).
Rev. 0722 

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) Web site (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.

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.
Rev. 0722 

F-1 

APPENDIX F:

MRO VERIFICATION STATEMENT FOR EXTERNAL SERVICE PROVIDER

I, the undersigned, have or My employer/MRO 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)
Rev. 0722 

Tables-1 

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 EnzymeLinked Immunosorbent 

Assay

ELISA

A competitive binding enzyme immunoassay using drugspecific antibodies that are immobilized in the wells of a 

microplate. 

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.
Rev. 0722 

Tables-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. Measureand 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)
Rev. 0722 

Tables-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 

measurand-specific 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.
Rev. 0722 

Tables-4 

Table 3a. Required Comments for IITF and Laboratory Specimen Reports -Urine

NOTE: CCF = Custody and Control Form; HHS = Department of Health and Human Services; ID = identification; IITF = instrumented initial test facility; LOQ = limit of 

quantification; MFR = Memorandum for the record; MRO = Medical Review Officer; NLCP = National Laboratory Certification Program; SpGr = specific gravity. 

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 = (conf. test value) mcg/mL ≥ 500 mcg/mL nitrite

Surfactant Present; dodecylbenzene sulfonate = (conf. test value) mcg/mL ≥ 100 mcg/mL dodecylbenzene sulfonate

Chromium (VI) = (conf. test value) mcg/mL

adulterant ≥ LOQ

(Specify Halogen) = (conf. test value)

Glutaraldehyde = (conf. test value) mcg/mL

Pyridine = (conf. test value) mcg/mL

(Specify Adulterant) Present = (conf. test value)

Substituted Creatinine = (conf. test value) mg/dL & SpGr = (conf. 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 = (conf. 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 confirmatory drug test method) interference2 Drug analyte(s) must not be included on reports for invalid 

(Specify initial drug test method) Interference 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

(Specify biomarker) = (conf. test value)

1 Remarks on CCF (Step 5a) & on elec. report for primary specimens; Remarks on CCF/Split Specimen Report & on elec. 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 HHS Guidelines (82 Fed. Reg. 7920) section 11.19.g. 3 See NLCP Urine Manual for further guidance: IITF Checklist Question E9 and Laboratory Question E10, CCF Decision Trees.
Rev. 0722 

Tables-5 

Table 3a. Required Comments for IITF and Laboratory Specimen Reports - Urine (continued)

NOTE: CCF = Custody and Control Form; HHS = Department of Health and Human Services; ID = identification; IITF = instrumented initial test facility; LOQ = limit of 

quantification; MFR = Memorandum for the record; MRO = Medical Review Officer; NLCP = National Laboratory Certification Program; SpGr = specific gravity.

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 on either the A or B specimen

Uncorrected Flaw: Wrong CCF used3 (Specify: Expired/Non-Federal 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 elec. report for primary specimens; Remarks on CCF/Split Specimen Report & on elec. 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 HHS Guidelines (82 Fed. Reg. 7920) section 11.19.g.

3 See NLCP Urine Manual for further guidance: IITF Checklist E9 and Laboratory Question E10, CCF Decision Trees
Rev. 0722 

Tables-6 

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

NOTE: CCF = Custody and Control Form; HHS = Department of Health and Human Services; ID = identification; IITF = instrumented initial test facility; LOQ = limit of 

quantification; MFR = Memorandum for the record; MRO = Medical Review Officer; NLCP = National Laboratory Certification Program; SpGr = specific gravity. 

Test Result Required Comment1 Note

Positive (Specify drug analyte) = confirmatory test quantitative result

Adulterated (Specify Adulterant) Present = (conf. 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) interference results based upon assay interference 2

Abnormal Physical Characteristic – (Specify)2

Tube A and Tube B – Different Physical Appearance2

(Specify biomarker) = (conf. test value) Examples: albumin, IgG

Rejected for Testing

Fatal Flaw: Specimen ID number (Specify: missing; mismatch) 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: Device volume indicator(s) not observed This flaw applies to specimens with a diluent (i.e., this is 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 on either the A or B specimen

Fatal Flaw: (Specify: Urine or Non-regulated CCF used) (see NLCP Manual E-11o)

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 flaw if not 

corrected Uncorrected Flaw: Collector signature not recovered 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 HHS Guidelines (84 Fed. Reg. 57554) section 11.17.d. 3 See NLCP Manual for further guidance: Question E-11, CCF Decision Trees
Rev. 0722 

Tables-7 

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

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 (for urine) 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 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 marijuana smoke or ingestion of food products 

containing marijuana are not a legitimate medical explanation for a positive 

THC or THCA result.

 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, report a 

positive result to the agency for all drugs except codeine and/or morphine as 

follows. 

 If the laboratory also reports that a urine specimen is dilute, the MRO may 

choose not to report the dilute result.

 For codeine and/or morphine less than 15,000 ng/mL in urine (150 ng/mL in 

oral fluid) and there is clinical evidence of illegal use (in addition to the drug 

test result), report the positive result to the agency. If there is no clinical 

evidence of illegal use, report the result as negative to the agency. This 

reporting requirement does not apply if the laboratory confirms the presence 

of 6-acetylmorphine (i.e., the presence of this metabolite is proof of heroin 

Ur – d 

OF – c 
Rev. 0722 

Tables-8 

use).

 For codeine and/or morphine equal to or greater than 15,000 ng/mL in urine 

(150 ng/mL in oral fluid) and there is no legitimate medical explanation, 

report the result as positive to the agency. Consumption of food products must 

not be considered a legitimate medical explanation for the donor having 

morphine or codeine at or above these concentrations. 

Substituted 

(for urine) 

If the laboratory reports an invalid result in conjunction with a positive, 

adulterated, or (for urine) 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 – N/A

Adulterated If the laboratory reports an invalid result in conjunction with a positive, 

adulterated, or (for urine) 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 

Invalid 

Result

If the laboratory reports an invalid result in conjunction with a positive, 

adulterated, or (for urine) substituted result, do not report the verified invalid result 

to the federal agency at this time. Report the verified invalid result(s) for the 

primary (A) specimen only if the split specimen is tested and reported as a failure 

to reconfirm.

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 prescription medication) 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 and (for 

urine) using a direct observed collection. If the second specimen collected 

provides an invalid result, report this specimen as test cancelled and recommend 

Ur – c, f, g

OF – b, e
Rev. 0722 

Tables-9 

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

that the agency collect another authorized specimen type (e.g., oral fluid or urine). 

See also required MRO actions in the MRO Manual Chapter 5.6.4, items 3 and 4 

for invalid specimens.

Multiple 

Reported 

Results

If the laboratory reports an invalid result in conjunction with a positive, 

adulterated, or (for urine) 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. 

If an invalid result was reported in conjunction with a positive, adulterated, or (for 

urine) substituted result, see Invalid Results guidance above. 

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, or [for urine] 

negative/dilute or substituted), report only the verified result(s) other than 

negative. 

– For example (for urine), 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 (for urine) 

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 (for 

urine) 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 – g 

OF – not 

provided

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 
Rev. 0722 

Tables-10 

When Laboratory A reports multiple results (i.e., drug positive, adulterated, [for urine] 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/[for urine]substituted) and all 

results that failed to reconfirm (specify drug[s]/adulterant/[for urine]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 (for urine) 

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 (for urine) 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 (for urine) a 

substituted result or if the primary specimen was only reported as adulterated and/or (for urine) 

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 [for urine] substituted);

 Give the donor 72 hours to request that Laboratory A: retest primary (A) specimen for the 

adulterant; or (for substituted urine) 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 

and/or (for urine) that Laboratory A review the creatinine and specific gravity results for the 

primary (A) specimen:

o If Laboratory A reconfirms the adulterant 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 and/or [for urine] 

substituted).

o If Laboratory A fails to reconfirm the adulterant 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 (for urine) 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 (for 

urine) 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 (for urine) substituted.
Rev. 0722 

Tables-11 

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 14.5

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 

(urine)

 Report to the agency (for urine) a reconfirmed 

result (substituted).

Ur – a 

OF – N/A

Drug(s) Adulterated

or

Substituted

(urine)



 Report to the agency a failed to reconfirm result 

(specify drug[s]) 

 If the donor provides a legitimate medical 

explanation for the adulterated result, cancel both 

tests. If there is no legitimate medical 

explanation, report a “refusal to test” (specify 

adulterant and/or [for urine] substituted).(see 

above for donor request for Lab A primary (A) 

specimen retest)

Ur – b,c

OF - b 

Drug(s) Not adulterated

or

Not substituted

(urine)

or

Not invalid

 Report to the agency a failed to reconfirm result 

(specify drug[s]);

 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 appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – d 

OF - c 

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 appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – e 

OF – d 

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 appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – f 

OF – e 
Rev. 0722 

Tables-12 

Reported Split Specimen Result Medical Review Officer (MRO) Action2,3,4 Guideline5 

UrMG 14.6

OFMG 14.5

Reconfirmed Failed to 

Reconfirm

Additional 

Testing Results1 

Drug(s) Drug(s) Substituted 

(urine)

 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 – N/A

Drug(s) Drug(s) Not Adulterated 

Not Substituted

(urine)

 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 – f 

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.

r – i 

OF – g 

Adulterated 

or 

Substituted 

(urine)

 Report to the agency a failed to reconfirm result 

(specify adulterant or [for urine] not substituted);

 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 appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – j 

OF – h 

Adulterated 

or

Substituted

(urine)

Drug(s)  Report to the agency a reconfirmed adulterated 

result ( specify adulterant and/or [for urine] 

substituted) result and a failed to reconfirm result 

(specify drug[s]); and

 Tell the agency it may take action based on the 

reconfirmed result (adulterated or [for urine] 

substituted) although Laboratory B failed to 

reconfirm the drug(s) result.

Ur – k 

OF – i 
Rev. 0722 

Tables-13 

Reported Split Specimen Result Medical Review Officer (MRO) Action2,3,4 Guideline5 

UrMG 14.6

OFMG 14.5

Reconfirmed Failed to 

Reconfirm

Additional 

Testing Results1 

Drug(s)

Adulterated 

or 

Substituted 

(urine)

 Report to the agency a failed to reconfirm result 

(specify drug[s] and specify adulterant and/or [for 

urine] substituted);

 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 appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – l 

OF – j 

Drug(s)

Adulterated

Drug(s)  Report to the agency a reconfirmed result (specify 

drug[s] and specify adulterant) 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 – m 

OF – k 

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 specify adulterant);

 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 – n 

OF – l 

Adulterated

and

Substituted

(urine)

 Report to the agency a failed to reconfirm result 

([specify adulterant] and [for urine] not 

substituted);

 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 appropriate drug-free workplace 

regulatory office regarding the test results for the 

specimen.

Ur – o 

OF – not 

provided

Substituted

(urine)

Adulterated  Report to the agency a reconfirmed result ([for 

urine] substituted) and a failed to reconfirm result 

(specify adulterant); and

 Tell the agency it may take action based on the 

reconfirmed result (substituted) although 

Laboratory B failed to reconfirm the adulterated 

result.

Ur – p 

OF – N/A
Rev. 0722 

Tables-14 

Reported Split Specimen Result Medical Review Officer (MRO) Action2,3,4 Guideline5 

UrMG 14.6

OFMG 14.5

Reconfirmed Failed to 

Reconfirm

Additional 

Testing Results1 

Adulterated Substituted

(urine)

 Report to the agency a reconfirmed result 

(adulterated) and a failed to reconfirm result ([for 

urine] not substituted); and

 Tell the agency it may take action based on the 

reconfirmed result (adulterated) although 

Laboratory B failed to reconfirm the [for urine] 

substituted result.

Ur – q 

OF – N/A

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 14.5
Rev. 0722 

Tables-15 

 

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 
Rev. 0722 

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