# Mandatory Guidelines for Federal Workplace Drug Testing Programs-Oral/Fluid

> Briefs, arguments, decisions, and more.

URL: https://www.frixlaw.com/law-library/documents/fr%3A2019-22684

## Record

- **Collection:** Federal Register
- **Document type:** Rule
- **Published:** October 25, 2019
- **Citation:** 84 FR 57554

## Text

DEPARTMENT OF HEALTH AND HUMAN SERVICES
42 CFR Chapter I
[SAMHSA—4162-20-P]
RIN 0930-AA24
Mandatory Guidelines for Federal Workplace Drug Testing Programs—Oral/Fluid

AGENCY:

Substance Abuse and Mental Health Services Administration (SAMHSA), HHS.

ACTION:

Issuance of guidelines.

SUMMARY:

The Department of Health and Human Services (“HHS” or “Department”) has established scientific and technical guidelines for the inclusion of oral fluid specimens in the Mandatory Guidelines for Federal Workplace Drug Testing Programs (Guidelines).

DATES:

Effective
January 1, 2020.

FOR FURTHER INFORMATION CONTACT:

Charles LoDico, M.S., F-ABFT, Division of Workplace Programs, Center for Substance Abuse Prevention (CSAP), SAMHSA, 5600 Fishers Lane, Room 16N03A, Rockville, MD 20857, telephone (240) 276-2600 or email at
charles.lodico@samhsa.hhs.gov.

SUPPLEMENTARY INFORMATION:

The Mandatory Guidelines for Federal Workplace Drug Testing Programs using Oral Fluid (OFMG) will allow federal executive branch agencies to collect and test an oral fluid specimen as part of their drug testing programs. In addition, some agencies, such as the Department of Transportation, are required to follow the Guidelines in developing drug testing programs for their regulated industries, whereas others, such as the Nuclear Regulatory Commission (NRC), use the Guidelines as part of the regulatory basis for their drug testing programs for their regulated industries. The OFMG establish standards and technical requirements for oral fluid collection devices, initial oral fluid drug test analytes and methods, confirmatory oral fluid drug test analytes and methods, processes for review by a Medical Review Officer (MRO), and requirements for federal agency actions.

The OFMG provide flexibility for federal agency workplace drug testing programs to address testing needs and revise the requirement to collect only a urine specimen, which has existed since the Guidelines were first published in 1988. Since 1988, several products have appeared on the market making it easier for individuals to adulterate their urine specimens. The scientific basis for the use of oral fluid as an alternative specimen for drug testing has now been broadly established and the advances in the use of oral fluid in detecting drugs have made it possible for this alternative specimen to be used in federal programs with the same level of confidence that has been applied to the use of urine. For example, oral fluid collection devices and procedures have been developed that protect against biohazards, maintain the stability of analytes, and provide sufficient oral fluid for testing. Additionally, specimen volume is also much lower, saving time in collection and transport cost. Developments in analytical technologies have provided efficient and cost-effective methods with the analytical sensitivity and accuracy required for testing oral fluid specimens.

Federal agencies, MROs, and regulated industries using the OFMG will continue to adhere to all other federal standards established for workplace drug testing programs. The OFMG provide the same scientific and forensic supportability of drug test results as the Mandatory Guidelines for Federal Workplace Drug Testing Programs using Urine (UrMG).

Background

The Department of Health and Human Services, by authority of Section 503 of Public Law 100-71, 5 U.S.C. Section 7301, and Executive Order No. 12564, establishes the scientific and technical guidelines for federal workplace drug testing programs and establishes standards for certification of laboratories engaged in drug testing for federal agencies. As required, HHS originally published the Mandatory Guidelines for Federal Workplace Drug Testing Programs (Guidelines) in the
Federal Register
[FR] on April 11, 1988 [53 FR 11979]. The Substance Abuse and Mental Health Services Administration (SAMHSA) subsequently revised the Guidelines on June 9, 1994 [59 FR 29908], September 30, 1997 [62 FR 51118], November 13, 1998 [63 FR 63483], April 13, 2004 [69 FR 19644], and November 25, 2008 [73 FR 71858]. The revised Mandatory Guidelines for Federal Workplace Drug Testing Programs using Urine (UrMG) were published on January 23, 2017 [82 FR 7920] with an effective date of October 1, 2017.

The Department published the proposed Mandatory Guidelines for Federal Workplace Drug Testing Programs using Oral Fluid (OFMG) in the May 15, 2015
Federal Register
(80 FR 28054). There was a 60-day public comment period, during which 120 commenters submitted comments on the OFMG. These commenters were comprised of individuals, organizations, and private sector companies. The comments are available for public view at
http://www.regulations.gov/.
All comments were reviewed and taken into consideration in the preparation of the Guidelines. The issues and concerns raised in the public comments for the OFMG are set forth below. Similar comments are considered together in the discussion.

Summary of Public Comments and HHS's Response

The following comments were directed to the information and questions in the preamble.

Requirements for Specimen Validity Testing

The Department requested comments on requirements for federal agencies to test all oral fluid specimens for either albumin or immunoglobulin G (IgG) to determine specimen validity. Four commenters agreed with the proposed requirements. Twelve commenters disagreed with the Guidelines as written, suggesting that specimen validity testing is not needed because all oral fluid collections are observed, collection procedures require visual inspection of the mouth by the collector and a 10-minute wait period, collection devices contain a volume indicator, and there is a limited volume of oral fluid collected and this volume is needed to complete confirmatory drug tests. One commenter expressed concern over the consequences of erroneous validity test results in relation to inappropriate cutoffs being set. One commenter questioned the proposed specimen validity testing analytes and cutoffs, and proposed that volume sufficiency be determined upon receipt at the laboratory. One commenter disagreed with the proposed IgG cutoff. One commenter disagreed that specimen validity testing should be performed on all specimens, and recommended performing specimen validity testing on a randomly chosen subset. This commenter also stated that specimen validity testing must be subjected to oversight by proficiency testing and blind sample testing programs. The Department has evaluated the comments and has revised the Guidelines to allow, but not require, specimen validity testing. The Department agrees that the OFMG collection procedures greatly minimize the risks of donor attempts to tamper with the specimen, and the volume indicator requirement for oral fluid collection devices should prevent collection of insufficient volume. To avoid prohibiting use of albumin and

IgG tests, as well as other scientifically supportable oral fluid biomarker or adulterant tests that may become available, the Department is authorizing specimen validity testing upon request of the Medical Review Officer as described in Sections 3.1 and 3.5. All tests must be properly validated and include appropriate quality control samples in accordance with these Guidelines. In response to commenters' concerns about expending the limited volume of oral fluid collected, it should be noted that HHS-certified laboratories currently performing specimen validity tests for non-regulated oral fluid testing use low volumes (
i.e.,
25 mcL for albumin tests, 15 mcL for IgG tests) that would not be expected to have a significant impact on a laboratory's ability to complete testing.

Proposed Cutoff Concentrations

Nineteen commenters submitted comments on the proposed drug test cutoffs. Some were general comments, while others concerned specific drug analytes. Cutoffs for marijuana tests are discussed in the following section,
Testing for Marijuana Use.
The comments and the Department's responses concerning cutoffs for other drug tests are described below.

Two commenters agreed with all proposed analytes and cutoffs. Two deferred setting cutoffs to HHS-certified laboratories. Three disagreed with all proposed cutoffs. Two of these commenters recommended retaining the cutoffs in the proposed Guidelines of April 13, 2004 (69 FR 19673). One of these commenters believes that the technology to detect analytes at these low levels is questionable and that these cutoffs will identify employees on prescribed medications. One commenter requested the basis for changing the cutoffs from those proposed in 2004. As described in the preamble to the proposed OFMG (80 FR 28054), the Department based the proposed cutoffs for each drug on information in public comments from the April 2004 proposed Guidelines, public responses to the June 2011 Request for Information (76 FR 34086), and the recommendations of a technical workgroup consisting of subject matter experts and representatives from various stakeholder groups (
e.g.,
collection device and test kit manufacturers, oral fluid drug testing laboratories). The Department provided the recommended cutoffs with supporting scientific information to the SAMHSA Drug Testing Advisory Board (DTAB) for review and discussion and, in the preamble to the proposed OFMG of May 15, 2015 (80 FR 28054, pages 28061-28065), included reasons for the proposed cutoffs for each drug, with references to supporting scientific studies. The Department has raised the cutoffs for some drug tests to address specific comments as described below. The Department concluded that no change is needed for other analytes. The cutoffs in Section 3.4 are supported by scientific studies, and are consistent with the goals of the federal workplace drug testing programs. The National Laboratory Certification Program (NLCP) Pilot Performance Testing (PT) Program has documented that laboratories are able to meet the Guidelines requirements using the cutoffs in Section 3.4.

One commenter agreed with the proposed initial test cutoff for cocaine, and recommended that a slightly lower cutoff be used for the confirmatory test. The Department did not find scientific evidence to warrant a change to the proposed confirmatory cutoff, which is the same as that proposed in 2004.

Five commenters disagreed with the proposed codeine and morphine cutoffs. Two commenters stated that the cutoffs are too low: One expressed concern over the technology to detect analytes at the proposed low levels and both noted that the change from currently used cutoffs will increase the number of initial test positives, thereby increasing costs. Two commenters stated that the Department has not supported changing from the cutoffs proposed in 2004 (
i.e.,
40 ng/mL for both the initial and confirmatory tests), which are currently used by the industry. One commenter indicated that their test data support a cutoff of 30 ng/mL for both the initial and confirmatory tests. In the preamble to the proposed OFMG of May 15, 2015 (80 FR 28054, page 28063), the Department included reasons for the selected test cutoffs for each drug, with references supporting those cutoffs. The Department is retaining the proposed cutoffs (
i.e.,
30 ng/mL for the initial test and 15 ng/mL for the confirmatory test) and is providing further explanation below to address the comments.

Reports in the literature provide information supporting lowering the morphine initial test cutoff from 40 to 30 ng/mL. In one dosing study with doses of 20 and 10 mg of morphine sulfate, morphine concentrations in saliva peaked at 0.5 hours at 37.8 ng/mL and 10.8 ng/mL, respectively, with detection times of 24 hours using a limit of detection (LOD) of 0.6 ng/mL.
1
In another report, morphine concentrations in oral fluid of treatment patients (n=4,575) were reported to range from 2 to 3,026 ng/mL with a median concentration of 49.8 ng/mL.
2
It was also found that 25% of the specimens contained morphine less than 13.5 ng/mL. These reports of short detection times and low concentrations of morphine in oral fluid also justify lowering the confirmatory cutoff for morphine to 15 ng/mL. The NLCP Pilot PT program has demonstrated oral fluid testing laboratories' abilities to meet codeine and morphine confirmatory cutoffs of 15 ng/mL using current testing technologies.

One commenter agreed with the proposed initial test cutoffs for oxycodone, oxymorphone, hydrocodone, and hydromorphone, but recommended that the same cutoffs be used for confirmatory testing. One commenter disagreed with all proposed cutoffs for these drugs, stating that the cutoffs are too low and will identify legitimate prescription users. The Department will retain the cutoffs as proposed. In the preamble to the proposed OFMG of May 15, 2015 (80 FR 28054, pages 28064-28065), the Department included reasons for the selected test cutoffs for each drug, with references supporting those cutoffs. Considerable research and discussion were conducted regarding the complex issues surrounding the specification of each cutoff concentration. The Department solicited input from laboratories, reagent and device manufacturers, subject matter experts, and the Food and Drug Administration (FDA). The cutoff concentrations are the outcome of the lengthy discussion process and represent the best approach currently available. Furthermore, the OFMG include the same requirements as the UrMG for Medical Review Officers to interview donors to determine whether there is a legitimate medical explanation for a positive test result, and to review documentation provided by the donor to support a legitimate medical explanation.

One commenter disagreed with the proposed 3 ng/mL initial test cutoff for 6-acetylmorphine (6-AM), stating that the proposed cutoff is higher than that currently used. As suggested by the commenter, and based on current 6-AM test methods and laboratory results from the NLCP Pilot PT Program, the Department has raised the proposed 6-AM initial test cutoff in Section 3.4 to 4 ng/mL (
i.e.,
the same as proposed in 2004). The same commenter recommended a higher confirmatory test cutoff (3 ng/mL vs. the proposed 2 ng/mL), and noted that their data show that using an opiates cutoff of 30 ng/mL and a 6-AM confirmatory cutoff of 3 ng/mL identifies more positive 6-AM specimens than urine testing. The comparison of 6-AM positivity rates in urine and oral fluid does not support a

change to the proposed confirmatory test cutoff. Studies have shown that 6-AM is statistically more likely to be detected in oral fluid than urine, regardless of the cutoff.
3 4 5
The Department has retained the 2 ng/mL 6-AM confirmatory test cutoff proposed in 2015, primarily for enhanced sensitivity. Studies have shown that 6-AM concentrations between 1 and 3 ng/mL are detected in the study populations.
2 3 6 7

One commenter agreed with the proposed test cutoffs for phencyclidine (PCP). Three others disagreed, recommending that the Department use the 2004 proposed cutoffs (
i.e.,
10 ng/mL for both the initial and confirmatory tests). The Department has evaluated the comments and agrees with commenters that there is an insufficient scientific basis to warrant changes from the PCP test cutoffs in the April 13, 2004 proposed Guidelines (69 FR 19673), which are currently used by many test manufacturers and laboratories. Therefore, the Department has raised the proposed cutoffs in Section 3.4 as follows: PCP cutoffs are 10 ng/mL for both the initial and confirmatory tests.

Six commenters disagreed with the proposed test cutoffs for amphetamines. Two of these commenters recommended that the Department use the 2004 proposed cutoffs (
i.e.,
50 ng/ml for both the initial and confirmatory tests). One recommended that the 2004 cutoff be used for the initial test; another recommended using the 2004 cutoff for the initial test and half of that concentration (25 ng/mL) as the confirmatory test cutoff. One commenter suggested cutoffs of 150 ng/mL or 120 ng/mL. One suggested setting cutoffs at 120 ng/mL or above to reduce the number of unverified positive initial tests. One commenter requested the basis for using different initial and confirmatory test cutoffs for methylenedioxymethamphetamine (MDMA).

The Department has evaluated the comments and agrees with commenters that, for amphetamines, there is an insufficient scientific basis to warrant changes from the initial test cutoffs in the April 13, 2004 proposed Guidelines (69 FR 19673), which are currently used by many test manufacturers and laboratories. Therefore, the Department has raised the proposed initial and confirmatory test cutoffs in Section 3.4 as follows: The initial test cutoff for amphetamines (
i.e.,
amphetamine, methamphetamine, MDMA, and MDA) is 50 ng/mL, and the confirmatory test cutoff for each amphetamine analyte is 25 ng/mL.

Testing for Marijuana Use

The Department requested comments on several topics related to testing for marijuana use. Public comments and the Department's responses are described below. After reviewing the comments, as well as the results of scientific studies published after the development of the proposed OFMG, the Department has decided to test for one marijuana analyte, delta-9-tetrahydrocannabinol (THC). THC is the primary psychoactive constituent (or cannabinoid) of the cannabis plant and is the primary intoxicant in marijuana. After careful consideration of all available evidence for THC in oral fluid, the Department has decided to retain the proposed 4 ng/mL initial test cutoff for THC in the final OFMG. Details regarding this decision are described below.

The Capability of Laboratories To Test Delta-9-Tetrahydrocannabinol-9-Carboxylic Acid (THCA) Analyte Using a Cutoff of 50 pg/mL

One commenter agreed and four commenters disagreed that laboratories were currently capable of testing THCA in oral fluid using this cutoff. One commenter stated that laboratory instrumentation required for the analysis of THCA in oral fluid is widely available and can be added to routine laboratory testing. The commenter listed examples: Two-dimensional gas chromatography/mass spectrometry (GC/MS), GC/MS/MS, and liquid chromatography (LC)/MS/MS. Three commenters disagreed, stating that it would require significant investment in more sensitive instrumentation. One commenter disagreed, stating they doubt the capabilities of the laboratories to consistently test for THCA with accuracy, sensitivity and validity. One commenter disagreed, stating that the number of laboratories with the experience in testing for THCA is limited. The Department has evaluated the comments and agrees that there is a limited number of laboratories currently testing for THCA in oral fluid. Only one commercial drug testing laboratory participating in the Oral Fluid Pilot PT program performed THCA testing. Furthermore, due to the concentration differences between THC (
i.e.,
nanogram/milliliter or ng/mL levels) and THCA (
i.e.,
picogram/milliliter or pg/mL levels), immunoassays do not have sufficient cross-reactivity to enable use of a single assay for both analytes. Initial testing for both THC and THCA would require two separate immunoassay kits or use of alternative technology. No current immunoassay has been identified that is selective for THCA only. Laboratories planning to become HHS-certified to test federal agency oral fluid specimens may already have instrumentation for confirmatory testing that could be used as an alternate technology for initial testing, but may incur additional costs to develop and validate these new initial drug tests.

The Validity of Whether THCA Can Be Established as an Accurate, Sensitive and Valid Marker for Oral Fluid Testing To Detect Marijuana Use and Whether THCA Should Be Used To Extend the Window of Detection for Marijuana Use

Four commenters agreed with THCA as a test analyte. These commenters believe that analysis of THCA may prevent or minimize the risk of positive results due to “passive exposure” (
i.e.,
a nonsmoker's exposure to secondhand marijuana smoke). One commenter stated that if both THC and THCA analytes are required to be present to constitute a rule or policy violation, this would also eliminate protracted detection of THCA. The commenter suggested that if only one of the marijuana analytes is reported, it could be addressed as a safety concern. This commenter also opposed MROs requesting THCA testing as needed and, as an alternative, suggested requiring disclosure from the donor at the time of collection (
i.e.,
the collector would ask the donor whether the donor had been exposed to marijuana recently and testing for THCA would be performed based on the donor's answer). If the donor indicated no recent exposure, the donor has waived the right to a passive inhalation defense. One commenter recommended an agency or employer should have the option to choose either test (THC or THCA), providing flexibility for employers' testing goals. One commenter noted that THCA testing, if included in the Guidelines, would be in conjunction with THC testing and expressed concerns including how to handle two test results (THC and THCA) that do not agree, additional costs, longer turnaround time, and handling of retests.

Six commenters disagreed with THCA as a test analyte. One commenter disagreed, suggesting solely testing for the active parent drug is one of the defining characteristics of oral fluid testing. Two commenters disagreed, suggesting THCA is not a reliable metabolite to be an appropriate marker for marijuana use. One commenter disagreed, stating that THCA is only present in oral fluid at very low levels. One commenter disagreed, suggesting that under realistic conditions of casual passive exposure and specimen

collection where the collection occurs outside the exposure area, a donor would not test positive for THC at the currently used initial test (3 ng/mL) and confirmatory test (1.5 ng/mL) cutoffs. One commenter disagreed, stating that more research is needed before adding THCA to the Guidelines. One commenter disagreed, indicating that, for the majority of the time, no significant THC positives are reported for samples containing THCA alone. The commenter also stated that for THCA alone (in the absence of THC) to be detected as positive in the immunoassay, the level must be at least 1,000 pg/ml, and that specimen volume is limited and should not be wasted for unnecessary tests.

The Department has evaluated the comments and decided to use THC as the sole initial and confirmatory test analyte for marijuana, with a 4 ng/mL initial test cutoff and a 2 ng/mL confirmatory test cutoff. This decision is supported by the reasons detailed below.

First, the Department is not aware of any scientific evidence to suggest that individuals would test positive for THC under the standards in these Guidelines as the result of incidental exposure to secondhand marijuana smoke. The preamble to the proposed OFMG, published on May 15, 2015, provided information on THC and THCA results from studies of subjects who were passively exposed to marijuana smoke under a variety of exposure conditions.
8-11
These studies, detailed below, were conducted under conditions of extreme marijuana smoke exposure for several hours in enclosed spaces (
i.e.,
heavy smoke in unventilated and ventilated conditions). The study data indicate that transient amounts of THC may be present in nonsmokers' oral fluid for a few hours (
i.e.,
one to three), but only under those extreme conditions, meaning exposure to smoke from multiple cannabis cigarettes in an enclosed space for an extended time period.

One 2011 study tested nonsmokers in two Dutch coffeehouses where marijuana was being smoked.
10
While some positive tests were obtained from the subjects, those samples were taken during a time of ongoing exposure to marijuana smoke in the coffeehouses, no subjects tested positive after returning for a final collection 12 to 24 hours after exposure. It should be noted that at the time of this notice's publishing, recreational and/or medical marijuana use is not permitted in places of public accommodation under either state or federal law. While this study demonstrated the types of THC oral fluid concentrations that could be obtained during exposure to secondhand marijuana smoke, the study is not directly applicable to Federal drug testing because the positive specimens collected in this study were collected during ongoing exposure to secondhand marijuana smoke, which does not approximate federal drug testing collection conditions.

A more recent study exposed nonsmokers to extreme levels of marijuana smoke under controlled conditions.
12 13
The extreme exposure in this 2015 study consisted of three different one-hour sessions in which nonsmokers were enclosed in a sealed room with six smokers who smoked cannabis cigarettes almost continually through each session. The room was a specially constructed sealed Plexiglas chamber (10 ft. by 13 ft. with a 7-ft. ceiling). Nonsmokers and smokers were seated around a table in alternating seats and the nonsmokers were continually exposed to heavy amounts of marijuana smoke. In two sessions, there was no air flow (
i.e.,
air conditioning was turned off) and in one session, the air conditioning was turned on. Heavy marijuana smoke was present in each session and the smoke caused eye irritation in the two non-ventilated sessions. Because of the extreme smoke conditions, most participants elected to wear eye goggles to reduce eye irritation. In this study, 3 of the 6 nonsmokers were negative directly after the exposure concluded (0 hours) and 4 of 6 were negative at 0.5 hours.

Some of these subjects (nonsmokers) also reported drug effects that were approximately 25% of the smokers' responses (
i.e.,
self-reported effects on a visual analog scale). The nonsmokers also exhibited detectable levels of performance impairment on some behavioral/cognitive assessments. Therefore, a reasonable donor in a safety sensitive position who is aware that he or she is in an enclosed environment with heavy levels of secondhand marijuana smoke should understand that he or she is very likely to experience the effects of inhaled marijuana smoke if he or she remains in this type of environment. Importantly, it is worth noting that exposure to the extreme levels of marijuana smoke in all three study sessions (
i.e.,
non-ventilated and ventilated) does not represent a real-world situation and, therefore, is an unlikely passive exposure situation for donors in a federal agency testing program.

The marijuana studies described above indicate that transient amounts of THC may be present in nonsmokers' oral fluid between one to three hours after prolonged, extreme exposure. Conversely, however, in two similar passive exposure studies from 2001 and 2005, none of the nonsmoking subjects tested positive using cutoffs that were lower than the OFMG THC cutoffs (
i.e.,
4 ng/mL for initial tests and 2 ng/mL for confirmatory tests).
8 9
While the exposure in the 2005 study was “extreme,” both the 2001 and 2005 studies represent more likely “real world” situations than the 2015 study.

In the 2005 study of nonsmoking individuals exposed to marijuana smoke in an unventilated passenger van, none of the passively exposed individuals tested positive using a 3 ng/mL initial test cutoff when the oral fluid collection device was protected from exposure to contaminated surfaces.
9
In this two-part study, four non-smoking subjects sat beside four active cannabis smokers who each smoked a single cannabis cigarette containing either a low dose of THC (Study 1) or high dose of THC (Study 2). In Study 1, oral fluid was collected inside the THC-contaminated van. Maximum oral fluid THC concentrations in non-smoking subjects were 7.5 ng/mL but declined to negative levels within 45 minutes of exposure. In Study 2, oral fluid was collected outside the van. Even though the dose of THC was more than twice the dose in Study 1, the maximum concentration detected in the passively exposed subjects was 1.2 ng/mL, which is well below the initial and confirmatory THC cutoffs in these Guidelines. When potential contamination during collection was eliminated in Study 2, all non-smoking subjects were negative at both initial and confirmatory cutoff concentrations throughout the study.

In the 2001 study, subjects were administered a single dose of marijuana by smoked and oral routes, and their oral fluid and urine THC test results were compared.
8
The study used a 1 ng/mL THC initial test cutoff and a 0.5 ng/mL THC confirmatory test cutoff, both lower than the THC cutoffs in these Guidelines (
i.e.,
4 ng/mL initial test cutoff and 2 ng/mL confirmatory test cutoff). Two nonsmoking subjects were included to simulate passive exposure scenarios (
e.g.,
sitting in an unventilated room where marijuana is smoked). These subjects were positive by immunoassay using the 1 ng/mL initial test cutoff at 1- and 4-hours post-exposure but negative by the confirmatory test using a 0.5 ng/mL cutoff.

These carefully executed studies on passive exposure are considered strong evidence that exposure to secondhand marijuana smoke under normal ventilation conditions presents no risk

that an individual will have a passive exposure related positive test result under the standards used in these Guidelines.

Another reason for the Department's decision to test only for THC is that THCA cannot be reliably detected in all individuals who use marijuana. Two recent studies investigated the presence of THC and THCA in oral fluid after various routes of administration.
15 16
One study characterized marijuana analytes including THC and THCA in oral fluid of nine occasional and 11 frequent marijuana smokers after smoked, vaporized, and oral administration (
i.e.,
ingestion of a brownie containing marijuana).
15
THC was present in oral fluid specimens in all individuals from both groups, after all routes of administration, immediately after use. THC was detected above the OFMG confirmatory cutoff (
i.e.,
2 ng/mL) for 32 hours with the occasional users and 72 hours with the frequent users. Of the nine occasional users, all tested positive for THC using the OFMG confirmatory cutoff after all administration routes. However, only three occasional users tested positive for THCA (
i.e.,
at or above 15 pg/mL) after all administration routes. In a second study, drug-free subjects ate brownies containing marijuana in three separate dosing sessions, with THC concentrations of 10 mg, 25 mg, and 50 mg.
16
The appearance of THCA in oral fluid in this study was highly variable, and THCA was not present in all subjects. Within the first eight hours after marijuana ingestion, 116 oral fluid specimens were positive for either THC or THCA. Of those specimens, 23 specimens were positive for both THC and THCA, 75 were positive for THC only, and 18 were positive for THCA only. Therefore, THC was detected in approximately 84.5% of the positive oral fluid tests, while THCA was only detected in approximately 35.3%. These studies support the Department's decision to test for THC by showing that THCA cannot be as reliably detected as THC in all marijuana users.

The Department's decision to use THC as the initial and confirmatory test analyte is also supported by the differences between the detection patterns of the two analytes in occasional smokers versus chronic frequent smokers. For example, one study showed that, although THCA was detected in frequent cannabis smokers almost 100% of the time studied, occasional smokers did not consistently test positive for THCA using the previously considered confirmatory test cutoff concentration of 0.05 ng/mL.
17
Some individuals tested negative for THCA after smoking cannabis. Consequently, confirmatory testing for THCA without performing an initial test for THCA would be biased toward detecting chronic frequent cannabis smokers and would be ineffective in detecting occasional users. Such an outcome would diminish the reliability of marijuana testing using oral fluid. It is also important to note that occasional users may exhibit greater acute impairment than chronic frequent users due to the lack of tolerance to cannabis effects.
18
This consideration suggests that an oral fluid drug testing system that relies upon testing for THCA to detect marijuana use may fail to identify occasional users who could pose a safety risk to a federal agency's enterprise.

The Department believes that an immunoassay initial test with the appropriate sensitivity for testing for both THCA and THC could allow oral fluid marijuana tests to take advantage of THCA's extended detection window. The preamble to the proposed OFMG, published on May 15, 2015, noted the lack of scientific data on the time course of excretion or the detection window of THC, THCA, and conjugated THCA in oral fluid following marijuana use, especially for occasional users. It was noted that studies of daily marijuana smokers indicated that THC is detectable for up to two days, but THCA continued to be excreted in oral fluid during abstinence for several weeks in daily users.
19
Two other studies evaluated oral fluid results following cannabis smoking (
i.e.,
one cannabis cigarette containing 6.8% THC).
17 20
In a 2013 study, oral fluid was collected from 10 participants using the Quantisal
TM
(Immunalysis) oral fluid collection device over a 22-hour period.
17
The authors used a 0.5 ng/mL cutoff for THC and a 7.5 pg/mL cutoff for THCA. The mean time to last concentration and the mean last concentration was 12.3 hours and 5.1 ng/mL for THC and 14.6 hours and 42.3 pg/mL for THCA, thus providing evidence of a longer detection window for THCA. A 2012 study evaluated cannabinoid concentrations in oral fluid of chronic and occasional smokers.
20
Oral fluid was collected 19 hours before smoking to 30 hours after smoking, using the Statsure Saliva Sampler
TM
(Statsure Diagnostic Systems). The authors concluded that: (1) All specimens were THC positive for up to 13.5 hours post-smoking without significant differences between chronic and occasional smokers, (2) THCA provided longer detection times than THC in the 13.5 to 30 hour post-smoking period in all chronic smokers, and (3) THCA windows of detection for chronic cannabis smokers extended beyond 30 hours.

However, the Department has not identified immunoassay technology that is feasible as an initial test for both THC and THCA in a high-throughput laboratory environment. Such technology is necessary for the implementation of THCA testing in the federal drug testing program because: (1) THCA-only testing is not a viable option for the federal drug testing program (as discussed previously), and (2) even though THCA and THC can be tested during the confirmation phase of drug testing, the theoretical advantages of THCA's longer detection window will not be achieved unless THCA can be detected in the initial test. In other words, in the absence of a viable initial test to detect THCA, specimens positive for THCA only would not advance to confirmation testing. Therefore, until a suitable immunoassay initial test that is capable of screening for both THC and THCA is available, the Department believes that its decision to test for THC using the cutoffs established in these Guidelines provides federal agencies with an efficient, cost-effective and reliable means to detect marijuana use.

As such, it is the conclusion of the Department that a 4 ng/mL initial test cutoff for THC is supported by scientific studies and is consistent with the Department's objective of detecting the use of illicit drugs while, to the extent practicable, eliminating the risk of positive test results caused solely by the drug use of others and not caused by the drug use of the individual being tested, as directed by the SUPPORT for Patients and Communities Act, Public Law 115-271, section 8107(b).
14

Lowering the Initial Test Cutoff Concentration for THC to Either 2 or 3 ng/mL and Lowering the Confirmation Test Cutoff Concentration for THC to 1 ng/mL To Extend the Window of Detection for Marijuana Use

Three commenters recommended lowering the THC initial test and confirmatory cutoffs to extend the window of detection; one commenter recommended lowering the initial test cutoff for this reason, but keeping the proposed confirmatory cutoff. One commenter recommended a slightly lower confirmatory cutoff (
i.e.,
1.5 ng/mL). Two commenters agreed with the proposed THC cutoffs.

Two other commenters recommended increasing the initial and confirmatory THC cutoffs, so claims of positive

results due to passive exposure will not be justified.

The Department's decision on initial and confirmatory cutoffs is discussed above, but to reiterate, the Department concluded after careful review of all available scientific evidence that: (1) Credible claims of positive THC tests resulting from second-hand smoke/passive exposure are extremely unlikely, and (2) the only scenario in which there is a theoretical possibility of testing positive for THC as the result of second-hand smoke/passive exposure under these Guidelines involves sustained exposure to extreme levels of marijuana smoke. The Department is confident that under these Guidelines, only a donor's marijuana use would be identified.

Performance Requirements for an Oral Fluid Collection Device

One commenter agreed and one commenter disagreed with requiring the use of only collection devices that have been cleared by the Food and Drug Administration (FDA). One commenter suggested the requirements for collection devices should be developed by appropriate professionals after suitable scientific and stakeholder review, while another suggested the requirements be determined by laboratories and manufacturers. One commenter disagreed with the Guidelines, and suggested that only devices using “the swab technique” be required.

The Department has evaluated these comments, and maintained the requirement in Section 7.1 for oral fluid collection devices to be FDA-cleared.

Five commenters addressed proposed volume specifications. Three commenters suggested that the Department specify oral fluid collection and/or diluent volume as a percentage and not a specific volume, due to variability in commercially available devices. One commenter encouraged increasing the allowed specimen and diluent volume variance to +/− 20%. One commenter believes that the proposed 0.05 mL diluent variance is too small and not realistic. One commenter suggested that the Guidelines not specify a required volume, but emphasize that laboratories choose devices that would ensure sufficient volume is collected for initial and confirmatory testing. One commenter disagreed with the proposed variance in specimen collected and suggested that the device must collect a known volume (similar to the “European Guidelines for Workplace in Oral Fluid”). This commenter also disagreed with the 1 mL collection requirement, stating that LC/MS/MS methods use approximately 200 mcL of oral fluid and that reducing the volume will reduce the time required for collection.

The Department has evaluated these comments, and revised Section 7.3(b) to specify oral fluid collection and diluent volumes as percentages (rather than specific volumes as proposed). The Department agreed with commenters that specifying allowable diluent variance as a percentage rather than volume would allow different manufacturers to produce their oral fluid collection devices with an optimized volume of diluent while ensuring reliability across systems. The Department also changed the specimen volume variance to a percentage for consistency. Section 7.3 specifies variances of 2.5% for diluent volume and 10% for specimen volume, based on information obtained from device manufacturers. The Department also maintained the requirement to collect at least 1 mL of oral fluid. This is a reasonable collection volume that will enable sufficient specimen for testing (
e.g.,
when repeat testing or confirmatory tests for multiple drugs are required).

Four commenters addressed the proposed device requirements for recovery of ≥90% (but no more than 120%) of drug and/or drug metabolite at (or near) the initial test cutoff. The commenters disagreed with the proposed requirement of ≥90%, and suggested recovery between 80% and 120%. One commenter noted that 80% to 120% recovery is consistent with current FDA-cleared systems. One commenter cited adherence of THC to surfaces as a problem in achieving 90% recovery, and recommended either requiring ≥80% for all drugs or requiring ≥80% recovery for THC and ≥90% recovery for other drugs. One commenter agreed with specifying minimum and maximum recovery, and recommended additional emphasis on the consistency of recovery performance of the device and confirmatory methods.

The Department has evaluated these comments, and revised Section 7.3(b) to change the lower limit for drug recovery from ≥90% to ≥80%.

Two commenters addressed stability at room temperature. One commenter agreed with the requirement for stability at room temperature for at least one week, and one commenter disagreed. This commenter indicated that in-house studies found cocaine and 6-AM were unstable for that length of time and also indicated that specimens are typically received at the laboratory one to two days after collection.

The Department has evaluated these comments, and changed the stability requirement in Section 7.3(b) from one week at room temperature to five days at room temperature. Because oral fluid is collected with either a preservative buffer (
i.e.,
collection device with diluent) or preservative dry reagents (
i.e.,
neat oral fluid collection), normal transport conditions are not expected to affect stability of the drugs and/or drug metabolites. The Department will include guidance to collectors concerning proper collection and transport of oral fluid specimens in the Oral Fluid Specimen Collection Handbook.

Medical Review Officer (MRO) Reporting Procedures for Positive Morphine/Codeine Results

In Section 13.5, the Department proposed a concentration of 150 ng/mL for codeine and morphine to be used by the MRO to report a positive result in the absence of a legitimate medical explanation (
i.e.,
prescription), without requiring clinical evidence of illegal use, and to rule out the possibility of a positive result due to consumption of food products. The Department requested comments on the appropriateness of this concentration. One commenter agreed. Six commenters disagreed: One commenter recommended 100-120 ng/mL, one commenter recommended 50-100 ng/mL, one commenter recommended 120 ng/mL, and one commenter recommended 40 ng/mL. One commenter suggested that no additional decision point is needed because, based on scientific studies including in‐house studies, positive opiate results using a 40 ng/mL cutoff are not typical and are difficult to achieve, thus there is no justification for an MRO reversal of a codeine or morphine result less than 150 ng/mL. One commenter expressed concern that the 150 ng/mL decision point would not rule out positive codeine/morphine results due to food products and suggested that the Department use a much higher decision point or require clinical evidence of illegal drug use before an MRO verifies any opiate results as positive. Based on evaluation of these comments and examination of the data from scientific studies, the Department has concluded that no change is needed.
21-24
The 150 ng/mL concentration is higher than the highest concentration seen in study subjects at one hour and later after consumption of raw poppy seeds and products containing poppy seeds.

HHS List of FDA-Cleared Oral Fluid Collection Devices

The Department requested comments on whether HHS should publish a list of FDA-cleared oral fluid collection devices. Seven commenters agreed. One commenter disagreed, stating that it is sufficient to provide regulation on requirements and noting that the Department does not publish a list of FDA-cleared urine specimen containers. After further review, the Department has decided not to publish a list. The list might not reflect all current FDA-cleared oral fluid collection devices, and could be misconstrued as a list of SAMHSA-approved devices. Also, FDA clearance does not mean that the collection device meets OFMG requirements. The federal agency and/or the HHS-certified laboratory must ensure that the FDA-cleared device meets the device requirements in Sections 7.2 and 7.3. FDA has a searchable database on its website that can be used to identify FDA-cleared oral fluid collection devices. The Department will include a link to this database on the SAMHSA website
http://www.samhsa.gov/workplace.

Medical Review Officer (MRO) Requalification—Continuing Education Units (CEUs)

The Department requested comments on requiring MRO requalification continuing education units (CEUs) and on the optimum number of credits and the appropriate CEU accreditation bodies should CEUs be required as part of MRO requalification. Three commenters agreed with requiring MRO recertification, but disagreed with the addition of CEU requirements to the Guidelines. Two commenters disagreed with specifying the number of CEUs required. Two commenters indicated that certification entities already enforce training requirements and recommended that acceptance of CEUs be handled by MRO certification boards, not the Department. Two commenters recommended a requirement of annual CEUs: One suggested 16 CEUs and the other recommended three CEUs. One commenter recommended 12 CEUs prior to initial certification, eight CEUs every five years, and also recommended two CEUs related to the new requirements/topics within two years of implementation of the revised Guidelines. The Department has evaluated the comments and has concluded that requirements for continuing education units will remain with the MRO certification entities and will not be included in the Guidelines. The Department has removed references to MRO training entities in Sections 13.2 and 13.3, because training documentation is maintained by MRO certification entities. The Department agrees with the comment that MROs should receive training on revisions to the Guidelines and has added item Section 13.3(b) to require such training prior to the effective date of revised Guidelines, to ensure that all MROs are trained in program requirements before performing MRO duties for federal agency specimens.

Split Specimen Collection Methods

All federal agency collections are to be split specimen collections. The donor's primary (A) specimen is tested and the split (B) specimen is available for testing if the donor requests a retest at another HHS-certified laboratory. For urine, one specimen is collected from the donor, then the collector pours the collected specimen into two bottles that are then labelled as A and B specimens. Most current oral fluid collection devices collect a single specimen that cannot be divided into A and B specimens. Therefore, the Department requested comments on whether serial or simultaneous collection using two collection devices constitutes a split oral fluid collection, and recommendations for any other oral fluid collection processes that enable subdividing the collected specimen. Three commenters agreed with the proposed guidelines as written. Two cited problems with collecting expectorated oral fluid (
i.e.,
difficult to obtain a sufficient specimen, distasteful to donor and collector), and stated that collection with a device provides analyte stability, a homogenous specimen, and facilitates processing in the laboratory. The commenters noted that the split specimen requirement to identify the presence of the drug addresses any concentration differences between first and second specimens. They also noted that split collections with two devices are currently used for non-regulated testing without issue and that scientific studies support these methods. Five commenters disagreed. Some raised concerns over possible insufficient specimen volume and non-homogenous specimens leading to possible discrepant primary and split specimen results. One commenter disagreed stating that the use of two devices for each collection increases costs. One commenter believes that serial collections using two devices may increase the likelihood of collection problems (
e.g.,
collector forgets to perform the second collection; the donor may leave the collection site or be out of collector's line-of-sight between collections; the two-minute period may be exceeded). The Department has evaluated the comments and has concluded that no change is needed. Either serial or simultaneous collection using two collection devices constitutes a split oral fluid collection for federal workplace drug testing programs. These split collection procedures are described in Section 8.8. The Department revised the split specimen collection definition in Section 1.5 and revised Section 8.8(a) to clarify that the OFMG do not prohibit collection of a single specimen and subdividing the collected specimen into primary (A) and split (B) specimens. In Section 2.5, the Department clarified that the split oral fluid specimen may be collected using two devices or using one device and subdividing the specimen.

Discussion of Sections

The Department has not included a discussion in the preamble of any sections for which public comments were not submitted or where minor typographical or grammatical changes were made.

Subpart A—Applicability

1.5 What do the terms used in these Guidelines mean?

One commenter requested that “external service provider” be defined, because this is a new term included in the proposed Guidelines. The Department agrees and has added the definition “An independent entity that performs services related to federal workplace drug testing on behalf of a federal agency, a collector/collection site, an HHS‐certified laboratory, a Medical Review Officer (MRO), or, for urine, an HHS-certified Instrumented Initial Test Facility (IITF).”

Two commenters disagreed with the proposed definition for “invalid result” which indicated that an invalid result was reported only when an HHS-certified laboratory could not complete testing or obtain a valid drug test result. The Department agrees and has reinstituted wording from the definition in the Guidelines effective October 1, 2010 (73 FR 71858). The definition in Section 1.5 is “The result reported by an HHS-certified laboratory in accordance with the criteria established in Section 3.7 when a positive or negative result cannot be established for a specific drug or specimen validity test.”

To address comments described in this preamble under Section 13.1, the Department deleted the definition for “non-medical use of a drug.”

Two commenters found the definition of “specimen” confusing, because the term “sample” used in the definition

was also defined as a representative portion of a donor's specimen. The Department agrees and has reinstituted some wording for the definition of “specimen” from the Guidelines effective October 1, 2010 (73 FR 71858) for clarity. The definition in Section 1.5 is “Fluid or material collected from a donor at the collection site for the purpose of a drug test.”

The Department revised the definition of “split specimen collection (for oral fluid)” to clarify that the OFMG allow collection of a single specimen and subdividing the collected specimen into primary (A) and split (B) specimens. This is consistent with the change described in this preamble under Section 8.8(a).

For clarity, the Department added a definition for the term “undiluted (neat) oral fluid” which is used throughout the OFMG. The definition in Section 1.5 is “An oral fluid specimen to which no other solid or liquid has been added. For example, see 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.”

1.6 What is an agency required to do to protect employee records?

One commenter suggested that the non-applicability of the Health Insurance Portability and Accountability Act (HIPAA) and the Health Information Technology for Economic and Clinical Health Act (HITECH) should be clearly stated in the Guidelines. The Department has evaluated the comment and has concluded that the applicability of HIPAA and other relevant privacy laws is clearly stated in Section 1.6. Accordingly, except for minor rewording for clarity, no further revisions are necessary.

1.7 What is a refusal to take a federally regulated drug test?

The Department proposed within Section 1.7 what is a refusal to take a federally regulated drug test. Two commenters noted that this section does not include the same requirements as Section 1.7(a)(10) of the UrMG defining a refusal to test when a collector finds a device intended for the purpose of adulteration or substitution and recommended adding similar language to the OFMG. The Department has evaluated the comments, and agrees that the collector must report a refusal to test when a donor brings materials for adulterating, substituting, or diluting the specimen to the collection site, or when the collector observes a donor's clear attempt to tamper with a specimen. The Department has revised Sections 1.7, 8.3(d), and 8.4(c) accordingly. Collectors will inspect the donor's oral cavity to ensure it is free of items that may impede or interfere with the drug test as described in Section 8.3.

One commenter recommended that OFMG Section 1.7 include the same requirements as UrMG Section 1.7(a)(5) defining a refusal to test when the donor failed to provide a sufficient amount of specimen when directed, “and the required medical evaluation did not identify a legitimate medical explanation for the failure.” The Department agrees with this comment and has added a new item 4 to Section 1.7(a) consistent with the UrMG requirement.

One commenter recommended clarification that a donor's refusal to provide a split specimen will also qualify as a refusal to test. The Department has evaluated the comment and has added this as a refusal to test in Sections 1.7(a)(7) and Section 8.5(b). If the donor refuses to provide a split specimen, the collector will report this as a refusal to test.

Also in regard to Section 1.7, one commenter suggested expanding the section to include specific actions that would be classified as a refusal to test. The commenter suggested wording under the current example “disrupt the collection process” describing actions specific to OF collections “(
e.g.,
disrupt the collection process including: biting on the collection device, sucking the fluid back out of the device, failure to open mouth when directed for inspection, failure to rinse mouth when directed, failure to remove foreign object from mouth when instructed, failure to permit the observation or monitoring of the specimen collection, avoiding swabbing in-between teeth and the gum line when instructed, failure to follow the collector's instructions on swab location in the mouth, attempting to conceal chemicals or mints in the mouth, attempting to use a mouth wash immediately prior to or during the collection, attempting to chew ice during the collection, behave in a confrontational way that disrupts the collection process, fail to wash hands after being directed to do so by the collector, possess or wear a prosthetic or other device that could be used to interfere with the collection process, other failures to comply with the collector's instructions or attempt to defraud the drug test)”.

The Department has evaluated the comment and has added the failure to rinse the mouth when directed by the collector as an example of donor actions classified as a refusal to test in Sections 1.7(a)(7) and in Section 8.3(d)(2). It should be noted that Section 1.7(a)(7) lists some examples. In practice, the trained collector determines whether the donor's action is a refusal to test. Many of the commenter's described actions would disrupt the collection process and thus constitute a refusal to test under Section 1.7(a)(7). The Department will consider the commenter's suggestions during preparation of guidance which will be provided in the HHS Oral Fluid Specimen Collection Handbook.

One commenter noted that the collector does not report a refusal to test when a donor leaves the collection site before the collection process begins for a pre-employment test. The commenter recommended defining the beginning of the pre-employment collection process as the point at which the donor is asked to present photo identification. The Department agrees with the suggestion to define the beginning of the collection process specifically for this situation. However, the Department has designated the beginning as the step described in Section 8.4(a), when the collector provides or the donor selects a specimen collection device. The Department has revised Sections 1.7(a)(2) and (3) to include a reference to this section. All subsequent items in Section 1.7(a) (
i.e.,
items 4—10) apply once the donor has arrived for the pre-employment test collection.

1.8 What are the potential consequences for refusing to take a federally regulated drug test?

The Department reworded Section 1.8(b) to clarify that the requirements in this section apply to donors who fail to appear at the collection site in a reasonable time for any test (except a pre-employment test), as described in Section 1.7(a)(1).

Subpart B—Oral Fluid Specimens

2.1 What type of specimen may be collected?

Ten commenters agreed with adding oral fluid and three commenters disagreed with adding oral fluid and alternate matrices. One commenter raised questions regarding the accuracy of oral fluid testing, MRO interpretation of detection of the parent compound of a prohibited drug, and the cost of oral fluid testing. The Department has evaluated the comments, and believes the concerns raised by the commenters are not sufficient to remove oral fluid testing from the Guidelines. The Department believes that collecting and testing oral fluid specimens according to

the requirements in these Guidelines is an efficient means to detect illicit drug use and ensures that the oral fluid test results are forensically and scientifically supportable.

Numerous commenters expressed concern with the Department's urine collection policy, stating that 7 to 10% of Americans have a condition (“paruresis”), described as a social anxiety disorder which prevents a person from producing urine on demand or in the presence of other people. These commenters stated that if the government wants to seek the largest group of qualified applicants, the Guidelines should specify that a diagnosis of paruresis means non-urine (
i.e.,
oral fluid) testing will automatically be provided, and that donors should not have to attempt to provide a urine specimen first. These comments are not relevant to the OFMG. The OFMG establish the standards and technical requirements for oral fluid testing in federal workplace drug testing programs. Each federal agency will decide whether to collect urine, oral fluid, or both specimen types in their workplace testing programs.

2.2 Under what circumstances may an oral fluid specimen be collected?

One commenter recommended that oral fluid be restricted based on the reason for the test due to the short window of detection compared to urine (and hair), the benefits of observed collection, and the ability to identify the parent or active drug that was used. One commenter recognized the benefit of oral fluid with respect to fewer adulterated, substituted, and/or invalid specimens, but raised concern over the shorter window of detection in oral fluid, especially with respect to pre-employment testing. Two commenters suggested that oral fluid and hair testing be performed for pre-employment and random tests. The Department has evaluated the comments and has concluded that no change is needed. Each federal agency will decide which of the authorized specimen types it will collect and the reasons for collecting each type of specimen.

2.3 How is each oral fluid specimen collected?

One commenter noted that this section does not clearly describe a split specimen “collected either simultaneously or serially.” The Department has evaluated the comment and has revised this section to include a reference to Section 8.8, which provides clear descriptions of these split specimen collection methods.

2.4 What volume of oral fluid is collected?

2.5 How is the split oral fluid specimen collected?

Comments on these two sections (
i.e.,
Section 2.4 and Section 2.5) are addressed here. One commenter noted that Sections 2.4 and 2.5 require collection of “a known volume” of at least 1 mL undiluted oral fluid, and stated that an absorbent pad device will not meet this requirement. The commenter recommended that these sections be clarified and address all types of oral fluid collection devices. The Department has evaluated the comment and has revised Sections 2.4 and 2.5 to ensure consistent requirements for collection devices with and without a diluent (or other component, process, or method that modifies the volume of the testable specimen). The Department revised Section 2.4 to require A and B tubes to have a volume marking clearly noting a level of 1 mL if the device does not include a diluent (or other component, process, or method that modifies the volume of the testable specimen). This is consistent with requirements in Section 7.3 for devices that modify the volume of the testable specimen to have a volume indicator, to ensure that at least 1 mL of oral fluid is collected. In Section 2.5, in addition to referencing Section 8.8, the Department clarified that the split oral fluid specimen may be collected using two devices or using one device and subdividing the specimen.

Subpart C—Oral Fluid Specimen Tests

3.1 Which tests are conducted on an oral fluid specimen?

One commenter suggested changing the term “opiates” to “opioids” in the Guidelines. “Opiates” is 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. The broadly used term “opioids” includes opiates (
e.g.,
codeine, morphine, and heroin); semi-synthetic compounds (
e.g.,
hydrocodone, hydromorphone, methadone, oxycodone, and oxymorphone); and synthetic compounds (
e.g.,
fentanyl). The Department agrees with the commenter and has changed the term “opiates” to “opioids” where appropriate to refer to oxycodone, oxymorphone, hydrocodone, and hydromorphone in addition to codeine, morphine, and 6-acetylmorphine (6-AM).

In addition, as described under
Requirements for specimen validity testing
in this preamble, the Department revised Section 3.1 to allow, but not require, oral fluid specimen validity testing.

3.2 May a specimen be tested for additional drugs?

The Department reworded Section 3.2(a) to clarify the additional drug tests that may be performed on federal employee specimens.

3.3 May any of the specimens be used for other purposes?

It should be noted that, consistent with the Urine Mandatory Guidelines, Section 3.3 specifically prohibits conducting, among other types of testing, deoxyribonucleic acid (DNA) testing, on oral fluid specimens unless authorized in accordance with applicable federal law.

3.4 What are the drug test cutoff concentrations for undiluted (neat) oral fluid?

Comments concerning marijuana test cutoffs are addressed under the
Testing for Marijuana Use
section above. Comments on other drug test cutoffs are addressed under
Proposed cutoff concentrations.
To summarize, the Department revised Section 3.4 to use higher cutoffs for some drugs (
i.e.,
initial test cutoffs for 6-AM, PCP, and amphetamines; confirmatory test cutoffs for PCP and amphetamines) than in the proposed OFMG. Other comments related to Section 3.4 are addressed below.

Three commenters disagreed with testing for cocaine in oral fluid, stating that cocaine is not stable in oral fluid, especially at the pH of human oral fluid. The commenters noted that cocaine has a short half-life and hydrolyzes to benzoylecgonine, and that benzoylecgonine is present longer and at higher levels. Two of these commenters further noted that the current industry standard is to test for benzoylecgonine only in oral fluid. One stated that their in-house studies found that testing cocaine did not increase the positivity rate compared to testing only benzoylecgonine. The other commenter refuted the study cited in the preamble to the proposed OFMG that supported the inclusion of cocaine as a test analyte. The Department based the proposed analytes for each drug on the recommendations of a technical workgroup consisting of subject matter experts and representatives from various stakeholder groups (
e.g.,
collection

device and test kit manufacturers, oral fluid drug testing laboratories). In the preamble to the proposed OFMG of May 15, 2015 (80 FR 28054, page 28063), the Department included the scientific basis for including both analytes. The inclusion of both cocaine and benzoylecgonine as test analytes will increase the number of specimens that are identified as containing these cocaine analytes and, thereby, will increase the deterrent effect of the program and improve identification of employees using this drug.

One commenter disagreed with testing for hydromorphone and oxymorphone in oral fluid due to extremely low incidence and recommended testing for more prevalent metabolites. The Department has evaluated the comment and decided that no change is needed. Information provided by initial test manufacturers indicates that the proposed analytes (
i.e.,
parent drugs) are present in higher concentrations and in the absence of their metabolites.

One commenter recommended specifying D-isomers as the initial test analytes for amphetamines. The Department agrees that an antibody that is directed toward D-enantiomers in an immunoassay method should be preferred over an antibody that is non‐stereoselective, but concluded that no change is needed. The wording in this section is consistent with the UrMG, and the selection of an immunoassay kit or methodology will remain the testing laboratory's choice.

An HHS-certified laboratory may group analytes for initial testing. For clarity, the Department has defined the term “grouped analytes” where used in footnote 1 of the table in Section 3.4: “(
i.e.,
two or more analytes that are in the same drug class and have the same initial test cutoff).”

The Department proposed criteria for calibrating initial tests for grouped analytes such as opioids and amphetamines, specifying the minimum cross-reactivity to the other analyte(s) within the group. The Department also proposed including methylenedioxyamphetamine (MDA) and methylenedioxyethylamphetamine (MDEA) as initial test analytes. Four commenters stated that 80% cross-reactivity may not be possible with current immunoassay technology, so may require independent analyses (
e.g.,
hydrocodone and hydromorphone for an opiate assay; MDEA for an amphetamines assay). Two of these commenters noted concerns with additional oral fluid specimen volume needed for the independent assays. Another commenter stated that cross-reactivity specifications for hydromorphone are not necessary, based on their non-regulated testing results (
i.e.,
confirmatory test concentrations detected after using an immunoassay with 60% cross-reactivity for hydromorphone).

The Department has evaluated these comments and concluded that no change is needed for immunoassay cross-reactivity requirements. The cross-reactivity requirements in Section 3.4 are necessary to ensure consistency in testing among laboratories using different immunoassay kits, as well as those using different test methods for initial drug testing. Cross-reactivity must be demonstrated and documented by the manufacturer (
e.g.,
package insert) and by the HHS-certified laboratory (
i.e.,
assay validation studies, reagent lot verification, and batch quality control for any analyte that exhibits less than 100% cross-reactivity).

One commenter stated that the low prevalence of MDA and MDEA does not warrant the burden placed on immunoassay manufacturers and laboratories. The Department has evaluated the comment and has removed MDEA from the Guidelines (
i.e.,
MDEA is no longer included as an authorized drug in Section 3.4). The number of positive MDEA specimens reported by HHS-certified urine laboratories (
i.e.,
information provided to the Department through the NLCP) does not support testing all specimens for MDEA in federal workplace drug testing programs. Because MDEA is a Schedule I drug, a federal agency may test specimens for MDEA in accordance with Section 3.2 (
i.e.,
on a case-by-case basis for reasonable suspicion or post-accident testing, routinely with a waiver from the Secretary). The Department understands that some other analytes have a low incidence, but believes that continued testing for these analytes is warranted in a deterrent program. In particular, inclusion of MDA as an initial and confirmatory test analyte is warranted because, in addition to being a drug of abuse, it is a metabolite of MDEA and MDMA.

Also in Section 3.4, the Department did not specify the target analyte to be used to calibrate an initial test for grouped analytes such as amphetamines or opioids. Three commenters noted that when an immunoassay is calibrated with a low-reacting drug, other analytes may exhibit high cross-reactivity, leading to false initial test positives. Two of these commenters also noted that this may result in possibly different cross-reactivity profiles for some structurally unrelated and concomitantly used prescription and/or over the counter drugs. It was not the Department's intent for the laboratory to calibrate an immunoassay test using an analyte other than that specified by the manufacturer. In the preamble to the proposed OFMG, the Department described using a control containing the lowest reacting analyte at its cutoff concentration to establish the decision point (
i.e.,
when an immunoassay for grouped analytes did not demonstrate at least 80% cross-reactivity to each analyte). The Department has determined that this approach is not necessary, and will not be permitted. There are current immunoassays that meet the requirements of this section for two or more analytes in a group (
i.e.,
analytes in the same drug class that have the same initial test cutoff). As indicated in Section 3.4, the laboratory may use multiple test kits or a single kit to meet the requirements.

However, the Department has revised Section 3.4 regarding the use of alternate technology initial tests for THC and 6-AM. To ensure consistent treatment of specimens, depending on the technology, the confirmatory test cutoff (
i.e.,
2 ng/mL) must be used for THC and 6-AM. For example, because immunoassays cross-react with various marijuana constituents and metabolites, a specimen that is positive using a cutoff of 4 ng/mL for an immunoassay may not test positive using an alternate technology initial test with a 4 ng/mL cutoff for THC. When using an alternate technology initial test (
e.g.,
LC/MS/MS) that is specific for the target analyte, THC, must be tested using the confirmatory test cutoff.

3.5 May an HHS-certified laboratory perform additional drug and/or specimen validity tests on a specimen at the request of the Medical Review Officer (MRO)?

One commenter recommended that HHS maintain a list of allowable additional tests and reporting criteria (
e.g.,
threshold for reporting as positive, adulterated, substituted, and/or invalid, and a limit of detection as appropriate), to ensure consistency among laboratories and within the testing program. The Department has evaluated the comment and has concluded that no change is needed. The Department does not want to limit the analytes that may be tested, and will provide guidance to laboratories as necessary. It is also noted that the section requires all tests to meet appropriate validation and quality control requirements. The procedures and specimen records for such tests will be reviewed at NLCP inspections. The Department will continue to maintain a

list of HHS-certified laboratories that choose to perform additional tests for regulated specimens. The Department has reworded Section 3.5 in concert with revisions to Section 3.1 removing the requirement for albumin or IgG testing, as described under
Requirements for specimen validity testing
in this preamble.

One commenter asked whether an MRO could submit a blanket request to perform additional testing (
e.g.,
additional opioid metabolites) for all confirmatory specimens (
i.e.,
would laboratories be permitted to monitor the additional compounds in all confirmatory test assays?). The Department believes that testing all specimens for additional analytes may not be appropriate for some tests, especially hydrocodone, hydromorphone, oxycodone and oxymorphone. Recent studies show that testing for norhydrocodone and/or noroxycodone is not necessary for the interpretation of all results.
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Norhydrocodone and noroxycodone metabolites may be helpful for the MRO to interpret test results only when a donor's prescription does not support the test results. The presence of norhydrocodone metabolite would support the use of hydrocodone and validate the donor's prescription. The same could be said for interpreting test results following an oxycodone dose. The presence of noroxycodone metabolite would support the use of oxycodone and validate the donor's prescription. The Department will provide guidance on these and other additional tests that may provide useful information for the MRO in the Medical Review Officer Guidance Manual for Federal Workplace Drug Testing Programs. The Department has revised Section 3.5 to clarify that HHS-certified laboratories are authorized to perform additional tests upon MRO request on a case-by-case basis, but are not authorized to routinely perform such tests without prior authorization from the Secretary or designated HHS representative, with the exception of the determination of D,L stereoisomers of amphetamine and methamphetamine. The Department will continue to allow HHS-certified laboratories to test for D,L amphetamine and methamphetamine routinely or upon MRO request. The Department will provide guidance on these and other additional tests that may provide useful information for the MRO (
e.g.,
tetrahydrocannabivarin) in the Medical Review Officer Guidance Manual for Federal Workplace Drug Testing Programs.

Additional drug and specimen validity testing under Section 3.5 does not include DNA testing.

3.7 What criteria are used to report an invalid result for an oral fluid specimen?

One commenter disagreed and recommended deleting Sections 3.7(a-c) and 3.7(g) from the Guidelines due to observed collections by trained collectors. As described under
Requirements for specimen validity testing
in this preamble, the Department has revised the Guidelines to allow, but not require, specimen validity testing. Section 3.7 has been revised accordingly.

Subpart D—Collectors

4.1 Who may collect a specimen?

One commenter questioned why the Department prohibits supervisors or hiring officials from collecting oral fluid specimens (unless no other collector is available). The commenter cited fewer privacy concerns in collecting oral fluid versus urine, and indicated that having supervisors collect specimens would be particularly useful in remote locations and/or for post-accident tests. The Department has evaluated the comments and has concluded that no change is needed. The Department will continue to prohibit routine collections by a supervisor, to avoid potential conflicts of interest due to the employee-supervisor relationship as much as possible. The Guidelines permit collections by a supervisor who has been trained as a collector when no other trained collector is available.

4.2 Who may not collect a specimen?

One commenter expressed concern that this section as written may unintentionally prevent the use of valid collection methods (
i.e.,
preventing the donor from collecting their own specimen may prohibit the donor from holding the collection device). The Department has evaluated the comments and has concluded that no change is needed to Section 4.2, which includes general language concerning the entire collection process. Section 8.4 describes steps the collector takes before the donor provides the oral fluid specimen, including reviewing with the donor the manufacturer's instructions for oral fluid collection using the specimen collection device. Section 8.5 describes the collection procedure, including the requirement for the donor to position the device for collection, and for the collector and donor to complete the collection in accordance with the manufacturer's instructions for the collection device. However, the Department has revised the wording in Section 8.5(a)(1) to address all types of oral fluid collection devices allowed by the OFMG (
i.e.,
including those that are not placed in the mouth).

Subpart E—Collection Sites

5.2 What are the requirements for a collection site?

One commenter suggested that the Department require restricted access only to be applicable during a collection period, and allow supplies and records to be stored in nearby secured areas. The Department has evaluated the comments and has concluded that no change is needed. The section clearly describes the requirements and addresses the commenter's concerns.

Subpart F—Federal Drug Testing Custody and Control Form (CCF)

6.1 What federal form is used to document custody and control?

6.2 What happens if the correct OMB-approved Federal CCF is not available or is not used?

Comments on these two sections (Sections 6.1 and 6.2) are addressed here. Three commenters recommended that the Federal Custody and Control Form (CCF) be revised to address oral fluid specimens. The Department will revise the Federal CCF when Guidelines allowing oral fluid become effective.

The Department reworded items 6.2(b) and (c) for clarity.

Subpart G—Oral Fluid Specimen Collection Devices

7.3 What are the minimum performance requirements for a collection device?

The Department reworded Section 7.3(a) in reference to oral fluid collection volume, as described under Sections 2.4 and 2.5 above, and revised Section 7.3(b) in response to public comments, as described under
Performance requirements for an oral fluid collection device
above.

Subpart H—Oral Fluid Specimen Collection Procedure

8.2 What must the collector ensure at the collection site before starting an oral fluid specimen collection?

One commenter stated that this section requires the collector to deter adulteration or substitution at the collection site, but does not provide any information on how this is to be done. The commenter recommended that Section 8.2 be deleted or, alternatively, that additional information be added to the section. The Department has

evaluated the comments and has concluded that no change is needed. The section provides the general requirement; the Department will provide more specific guidance as needed in the HHS Oral Fluid Specimen Collection Handbook, which will be issued after these Guidelines become effective.

8.3 What are the preliminary steps in the oral fluid specimen collection procedure?

In response to comments described under Sections 1.7 and 8.4 in this preamble, the Department revised Section 8.3(d) to require the collector to report a refusal to test when a donor brings materials for adulterating, substituting, or diluting a specimen to the collection site.

One commenter requested that the Guidelines clarify (possibly using a flowchart) the different waiting periods in Sections 8.3 and 8.6 (
i.e.,
if multiple waiting periods are required, do they run concurrently or consecutively?). The Department has evaluated the comments and has concluded that no change is needed. The Department will consider the commenter's suggestion during preparation of the HHS Oral Fluid Specimen Collection Handbook.

Several comments concerned Section 8.3 collection procedures regarding rinsing or drinking. One commenter disagreed with the requirement to have tobacco users rinse their mouth prior to an oral fluid collection, noting it is an inconvenience for the collector to provide a place for the donor to spit out the liquid. One commenter requested clarification on oral fluid collection procedures for tobacco users (
e.g.,
is the collector required to ask, is it a refusal if a tobacco user doesn't rinse their mouth, is the donor required to rinse with water, what if the donor uses more than 4 oz. of liquid to rinse?). The Department removed the reference to tobacco users in 8.3(d)(2) because there is no need for all tobacco users to rinse their mouths. The proposed procedure for tobacco users was due to the dark brown color of tobacco juice. The issue is that any discoloration may interfere with initial testing (
i.e.,
not just tobacco juice). The Department reworded this section to include abnormally colored saliva as a reason for the collector to give water to the donor for rinsing their mouth.

One commenter recommended that the Guidelines clarify that if the donor drinks water, the water must not be provided by the donor. For clarity, the Department revised Section 8.3(d)(2) to require the collector to give the donor water (for example, up to 4 oz.) to rinse the donor's mouth when the collector's inspection of the oral cavity identifies any items that could impede or interfere with the collection of an oral fluid specimen. If the donor refuses to rinse, this is a refusal to test. Rinsing with more than 4 oz. of water does not invalidate the collection, so this amount was given as an example rather than a requirement.

One commenter indicated that some collection devices specifically instruct against offering the donor anything to rinse with or drink. This commenter suggested modifying Section 8.3 to make offering of water conditionally allowed, depending on the collection device manufacturer's instructions. The Department has evaluated these comments and concluded that no change is needed. The Department believes that rinsing the oral cavity with water prior to a 10-minute wait period is a reasonable part of the oral fluid collection protocol. The wait period is sufficient to comply with the device instructions, and will not dilute the collected oral fluid.

Several comments concerned Section 8.3 collection procedures regarding inspection of the donor's mouth. One commenter requested clarification on what items need to be removed from a donor's mouth prior to an oral fluid collection (tobacco, food, gum, or mints versus retainers and piercings). One commenter requested clarification of whether “dental retainer” refers to a temporary or permanent device (or both), should the device be removed and, if so, where the device should be placed during the oral fluid collection. The Department has evaluated the comments and concluded that only one change is needed: Removal of “dental retainer” from the examples of items that must be removed based on a collector's inspection of the donor's mouth in Section 8.3(d). A donor is not required to remove dental appliances such as a retainer. The Department will provide additional information in the Oral Fluid Specimen Collection Handbook to clarify items that may impede or interfere with the collection.

One commenter recommended that the Guidelines address the situation where a donor may have a medical condition that prevents them from opening their mouth for the collector to inspect. The Department agrees with the commenter and has revised Section 8.3(d) to address this situation. The collector will proceed with the same steps as when a donor is unable to provide an oral fluid specimen, as described in Section 8.6(b)(2), and the MRO will follow the steps in Section 13.6(b) requiring a medical evaluation of the donor.

8.4 What steps does the collector take in the collection procedure before the donor provides an oral fluid specimen?

Two commenters believe that if the collector finds an adulterant or substitution product, this should be a refusal to test. As noted under Sections 1.7 and 8.3 in this preamble, the Department agrees that the collector must report a refusal to test when a donor brings materials for adulterating, substituting, or diluting a specimen to the collection site, or when the collector observes a donor's clear attempt to tamper with a specimen. The Department has revised Section 8.4(c) accordingly.

The Department deleted Section 8.4(b)(1) for consistency with Section 8.6(b). The deleted item stated that the collector may set “a reasonable time for a collection based on the device used, not to exceed 15 minutes.” Section 8.6(b) states that the donor demonstrates their inability to provide a specimen when, after 15 minutes of using the collection device, there is insufficient volume or no oral fluid collected using the device.

8.5 What steps does the collector take during and after the oral fluid specimen collection procedure?

One commenter suggested that the section should state that the collector be present and maintain visual contact with the donor and collection device during the procedures outlined in this section. The Department has evaluated the comment and has concluded that no change is needed: Sections 8.4(a) and 8.5(a) clearly require the collector to keep the unwrapped collection devices and the donor in view at all times during the collection.

One commenter asked if there was a limit to the number of times a collection could be restarted due to collection device failures. The Department has evaluated the comment and has reworded Section 8.5 for clarity. Section 8.5(a)(1) was revised to indicate that a failure to provide a specimen (which may or may not be due to device failure) prompts recollection using a new device and that the collector documents the failed collection attempt on the Federal CCF. The Department also reworded Section 8.5(b) to clarify that a donor's refusal to begin the collection process after a failure to collect the specimen is a refusal to test. The Department did not set a limit for the number of attempts because there may be different reasons for failing to collect the specimen from the donor. However, the Department

revised the section to require the collector to follow the procedure in Section 8.6 “after multiple attempts to collect the specimen.”

One commenter stated that HHS should clarify that a donor's refusal to provide a split specimen will also qualify as a refusal to test. The Department agrees with the comment and has revised Section 8.5(b) to include the refusal to provide a split oral fluid specimen as a refusal to test.

Additionally, as described under Section 4.2 above, the Department revised Section 8.5(a)(1) to address all types of collection devices allowed by the OFMG (including those that are not placed in the mouth).

8.6 What procedure is used when the donor states that they are unable to provide an oral fluid specimen?

Three commenters disagreed with the requirement for the collector to contact the agency representative for authorization to collect an alternate specimen each time a donor is unable to provide a sufficient volume. These commenters suggested that the Guidelines allow this to be addressed in established standard protocols for the agency. The Department agrees with the commenters. Each federal agency may decide whether to require notification in each case or whether to provide a standard protocol for collectors to follow. Section 8.6 has been revised accordingly.

Also in regard to Section 8.6, one commenter requested additional information on donor hydration during an oral fluid specimen collection (
i.e.,
asking if there is evidence that hydration improves the ability to provide a specimen and whether hydration dilutes the specimen). One commenter indicated that the volume of oral fluid collected does not appear to be directly related to fluid intake and suggested that, because some donors may not be able to provide a sufficient specimen even after the one hour wait time, a urine specimen should be collected immediately. One commenter disagreed with the one hour period allowed for an oral fluid collection, and indicated that there is no evidence provided that dry mouth is eliminated by waiting one hour. The commenter indicated that this extra time allotted costs the employer unnecessary time and money, and maintained that a waiting period of 10 minutes after consumption of 8 oz. of water is sufficient. The Department has evaluated the comments and concluded that no change is needed to Section 8.6. The proposed procedure sets a reasonable time limit within which most donors would be able to provide an acceptable specimen volume (
i.e.,
10 minutes between attempts to provide the oral fluid specimen, up to one hour), and the section clearly states that the donor is not required to drink any fluids during the wait time. The Guidelines clearly describe the limited circumstances in which the collector offers the donor fluids. However, the Department has revised Section 8.8(a)(2) to expressly prohibit rinsing or drinking between the collection of the primary and split specimens when serially collected.

8.7 If the donor is unable to provide an oral fluid specimen, may another specimen type be collected for testing?

One commenter disagreed with the Guidelines as written and suggested that when a donor cannot provide the primary specimen type, an alternate specimen should be collected immediately. The commenter cited the additional time and cost as well as the fact that the collector may not know the agency's policy on alternate specimen types. The Department has concluded that no change is needed for Section 8.7 in response to this comment. The Guidelines will continue to require that the donor be allowed reasonable attempts to provide an oral fluid specimen as described in Sections 8.5 and 8.6. The Department has revised Section 8.6 to allow a federal agency to either require notification in each case or provide a standard protocol for collectors to follow when the donor is unable to provide an oral fluid specimen. The Department has reworded this section to state “Yes, if. . .” rather than “No, unless. . .” in response to a federal agency's comment and to enhance clarity. The meaning of this section remains the same.

8.8 How does the collector prepare the oral fluid specimens?

One commenter requested clarification of the “simultaneous” oral fluid collections. The Department has evaluated the comment and has concluded that no change is needed. Section 8.8(a)(1) describes “Two specimens collected simultaneously with two separate collection devices.”

One commenter expressed concern that the requirement for a serial collection of a split specimen to begin within two minutes of the first collection may be difficult to monitor and may lead to differences between the two specimens. This commenter requested clarification on how this process will be monitored. One commenter agreed with the two-minute maximum time between serial collections of a split specimen. The Department has evaluated the comments and agrees with the second commenter that no change is needed. The proposed procedure in Section 8.8 sets a reasonable time within which the collector can take the first collection device from the donor and record the time on the Federal CCF, while the donor positions the second device for the collection. Because the collector works with one donor at a time, the collector should have no difficulty monitoring the time between primary and split collections. Furthermore, the Department believes this timing would not affect results of the primary and split oral fluid specimens.

One commenter disagreed with the proposed two-minute maximum time between serial collections of a split specimen and suggested that the time be increased to 10 minutes (so as not to rush the collector in completing chain of custody forms). This commenter suggested that a second specimen should only be collected after an initial test result is obtained (which the commenter indicates can usually be done in 10 minutes). The Department has evaluated the comments and has concluded that no change is needed. The collector is not required to complete the Federal CCF until both the primary and split specimens have been collected. Point of collection testing is not allowed under these Guidelines. That is, all testing must be performed at an HHS-certified test facility.

One commenter asked whether hydration would be allowed between serial split collections. The Department revised Section 8.8(a)(2) to expressly prohibit rinsing or drinking between the collection of the primary and split specimens when serially collected. Prohibiting rinsing or drinking will better ensure consistency of the primary and split specimens.

The Department added an additional item under Section 8.8(a) to clarify that the OFMG allow collection of a single specimen and subdividing the collected specimen into primary (A) and split (B) specimens. A similar change was made to the definition of “split specimen collection (for oral fluid)” in Section 1.5.

The Department also removed the word “known” in Section 8.8(b) in reference to oral fluid collection volume, as described under Sections 2.4 and 2.5 above.

In response to a federal agency comment, the Department deleted a sentence in item 8.8(h) that required the collector to send a copy of the Federal CCF to the HHS-certified laboratory. The Department agreed with the federal

agency that this instruction is redundant because item 8.8(g) instructs the collector to distribute copies of the Federal CCF as required.

Subpart I—HHS-Certification of Laboratories

9.5 What are the qualitative and quantitative specifications of performance testing (PT) samples?

One commenter noted that, because proposed initial test requirements allow calibration with a low-reacting analyte, PT schemes would likely need to be designed based on the specific implementation at each laboratory. The commenter provided an example: When an immunoassay is calibrated with a drug/metabolite that exhibits 50% cross-reactivity, the intended target analyte (“calibrant”) at the cutoff concentration would elicit a response well in excess of the cutoff. This could result in inaccurate initial test results (
i.e.,
a positive initial test result for a specimen containing the calibrant at a concentration below the cutoff). The commenter stated that this result could be scored as a “false positive” PT result. The Department has evaluated the comment and has concluded that no change is needed. As noted above regarding Section 3.4, it was not the Department's intent for the laboratory to calibrate an immunoassay test using an analyte other than that specified by the manufacturer. NLCP PT schemes are designed based on known cross-reactivity profiles of the initial tests used by HHS-certified laboratories.

Also in regard to proposed Section 9.5, one commenter suggested that the Guidelines use the same wording as in the Guidelines effective October 1, 2010 (73 FR 71858) for retest PT sample specifications (
i.e.,
“. . . may be as low as . . .” rather than the proposed wording “. . . may be less than . . .”). The Department agrees and has reinstituted wording from Section 9.3 of the Guidelines effective October 1, 2010 (73 FR 71858) into Section 9.5(a)(1)(ii).

As described under
Requirements for specimen validity testing
in this preamble, the Department has revised the Guidelines to allow, but not require, specimen validity testing. Section 9.5 has been revised accordingly.

9.6 What are the PT requirements for an applicant laboratory?

9.7 What are the PT requirements for an HHS-certified oral fluid laboratory?

Comments on these two sections (Sections 9.6 and 9.7) are addressed here. As described under
Requirements for specimen validity testing
in this preamble, the Department has revised the Guidelines to allow, but not require, specimen validity testing. Sections 9.6 and 9.7 have been revised accordingly.

Subpart J—Blind Samples Submitted by an Agency

10.1 What are the requirements for federal agencies to submit blind samples to HHS-certified laboratories?

Two commenters disagreed with the proposed limit to the number of blind samples required (
i.e.,
a maximum of 400 blind samples per year) in Section 10.1(b). The commenters indicated that for a large agency, there is a very large difference between 3% and 400 samples and suggested keeping only the 3% requirement. Another commenter disagreed with the 3% requirement for blind samples and requested that the amount to be lowered to 1% to lessen the burden on employers. The Department has evaluated the comments and has concluded that no change is needed. The 400 sample limit was added to reduce the burden on large agencies based on the Department's review of agencies' blind testing programs.

One commenter suggested that the wording be modified to clarify that employers are responsible for ensuring blind samples are sent to the laboratories, but that collectors are tasked with submitting the blind samples. The Department has evaluated the comment and has concluded that no change is needed. The wording in Section 10.1(a) clearly describes the responsibilities of the federal agency and the role of the collector in blind sample submission; however, the Department reworded Section 10.3(a) for clarity as described below.

10.3 How is a blind sample submitted to an HHS-certified laboratory?

The Department has reworded Section 10.3(a) to clarify that the collector sends a blind sample to a laboratory as a split specimen (
i.e.,
specimens A and B).

Subpart K—Laboratory

11.9 What are the requirements for an initial drug test?

One commenter noted that HHS previously required initial and confirmatory testing using different techniques, and asked whether this requirement had been removed with allowance of technologies other than immunoassay for initial testing. The commenter expressed concern that an error in the initial drug test could be repeated in the confirmatory drug test using the same method. The Department has evaluated the comment and has concluded that no change is needed. The Guidelines maintain the requirement for initial and confirmatory tests on two separate aliquots to report a result other than negative. The NLCP will review validation and quality control records, as well as specimen records, to ensure that the initial and confirmatory testing methods meet Guidelines requirements and provide scientifically and forensically supportable results.

11.10 What must an HHS-certified laboratory do to validate an initial drug test?

One commenter noted that Section 11.10 provides general information on validation requirements, and asked where detailed requirements can be found. The Department has evaluated the comment and has concluded that no change is needed. The Department will continue to provide details for applicant and certified test facilities through the NLCP.

One commenter asked whether the requirement in 11.10(c) for periodic verification of “each initial drug test using an alternate technology” applied to immunoassay tests used differently than originally cleared by the FDA or other laboratory developed tests. The Department has evaluated the comment and has concluded that no change is needed. This section clearly distinguishes initial tests using immunoassay from those using an alternate technology. Furthermore, Section 1.5 includes the definition for “alternate technology initial drug test.”

11.11 What are the batch quality control requirements when conducting an initial drug test?

Seven commenters disagreed with the requirement for an initial test control targeted at 25% above the cutoff. The commenters noted that drug concentrations are much lower in oral fluid than in urine, and stated that assays are unlikely to perform robustly with current immunoassay technology. One commenter also noted that oral fluid is diluted three- to four-fold. One commenter suggested requiring a control targeted at 50% above the cutoff, consistent with current FDA-cleared assays. The Department has evaluated the comments and has concluded that no change is needed. Consistent with the urine program requirements, laboratories must have the ability to apply the program cutoffs to regulated specimens, and document that ability by analyzing a control targeted at 25% above the cutoff in each batch.

One commenter asked whether the inclusion of “additional compounds as target analytes” for amphetamine and

opioid assays affect quality control content requirements. The Department has evaluated the comment and has concluded that no change is needed. The initial drug test quality control requirements in the Guidelines apply to each analyte used to calibrate the test (
i.e.,
immunoassay or alternate technology initial drug test). When a single immunoassay test is used for two or more analytes in a drug class, the HHS-certified laboratory must include a control in accordance with item 11.11(a)(2) for each analyte that has less than 100% cross-reactivity with the assay, to demonstrate that the requirement for at least 80% cross-reactivity has been met.

11.14 What are the batch quality control requirements when conducting a confirmatory drug test?

One commenter stated that analyzing quality control samples with concentrations of a drug or metabolite targeted at less than 40% of the proposed cutoffs would be an analytical challenge for high volume laboratories utilizing GC/MS or LC/MS/MS. The Department has evaluated the comments and has concluded that no change is needed. The NLCP Pilot PT Program has documented the capability of laboratories to meet the proposed OFMG requirements.

Also in regard to the proposed quality control requirements for an initial drug test in Section 11.11 and for a confirmatory drug test in Section 11.14, one commenter requested clarification for the requirement for a drug-free control (
i.e.,
whether the control should contain no drug or whether the control should not contain the specific analyte for that test). The Department has evaluated the comment and has concluded that no change is needed. These Guidelines sections list the requirement for “at least one control certified to contain no drug or drug metabolite,” meaning that the control must contain no regulated drug analytes.

11.15 What are the analytical and quality control requirements for conducting specimen validity tests?

The Department has reworded Section 11.15(a) for clarity, to correctly reflect requirements.

11.17 What are the requirements for an HHS-certified laboratory to report a test result?

One commenter suggested that the Department remove the requirement for an executed CCF as the official report for “non-negative” specimens and permit the use of an electronic report with the required information. The Department has evaluated the comment and has concluded that no change is needed. The Federal CCF establishes the chain of custody for the specimen from the time of collection until receipt by the laboratory and also contains the certification statement signed by the certifying scientist. The Federal CCF may be paper or electronic.

As described under
Requirements for specimen validity testing
in this preamble, the Department has revised the Guidelines to allow, but not require, specimen validity testing. Section 11.17 has been revised accordingly.

11.21 What HHS-certified laboratory information is available to a federal agency?

As described under
Requirements for specimen validity
testing in this preamble, the Department has revised the Guidelines to allow, but not require, specimen validity testing. The list of items provided in a standard documentation package for an oral fluid specimen has been revised accordingly [
i.e.,
Section 11.21(b)(4)].

11.22 What HHS-certified laboratory information is available to a federal employee?

One commenter asked why the proposed Guidelines include a requirement for a copy of the semiannual statistical summary report to be sent to the Secretary or designated HHS representative. The Department included the requirement to facilitate compilation of statistical information for the federal drug-free workplace program. This will not place an additional burden on the laboratory other than transmission of the report. The Department will continue to evaluate the effectiveness of this requirement.

Subpart L—Instrumented Initial Test Facility (IITF)

12.1 May an IITF test oral fluid specimens for a federal agency's workplace drug testing program?

One commenter disagreed with prohibiting IITFs for oral fluid. This commenter considers the current HHS-certified urine IITF to be a success in Canada and stated that prohibiting oral fluid IITFs would result in less enthusiasm for regulated procedures and impact workplace safety. At this time, as stated in the preamble to the proposed OFMG, IITFs are not practical and will not be allowed due primarily to the limited specimen volume of oral fluid collected from the donor. The Department will continue to monitor developments in oral fluid drug testing after this new specimen type has been implemented in federal workplace programs, and may reassess the feasibility of allowing IITFs for oral fluid in the future.

Subpart M—Medical Review Officer (MRO)

13.1 Who may serve as an MRO?

Three commenters disagreed with the term “nonmedical use of a drug” used in Section 13.1 (and defined in Section 1.5) and indicated that the term changes the role of an MRO from review, verify and “report a non-negative result” to review, verify and “interpret before reporting a result as negative or nonmedical use of a drug.” Two commenters disagreed with use of “interpretation of results” to supplant “alternative medical explanation.” One commenter noted that this perceived change in the MRO's role represents an unjustified shifting of risk to the MRO. One commenter believes the term presents a possible legal flaw to Guidelines, stating that this term is legally different from “safety concern” and places MROs in the position of being in conflict with the prescribing physician and subject to lawsuits. This commenter stated that even a lack of a finding of nonmedical use could be an issue if the donor subsequently had an accident after using the drug. The same commenter submitted five recommendations related to inclusion of prescription drugs in federal workplace drug testing programs, to address the commenter's concerns with the proposed Guidelines. These five specific recommendations pertain to matters that are outside the scope of these Guidelines, and therefore are not addressed in the Department's response below.

The responsibilities of an MRO to interpret results have largely remained the same between the Guidelines effective October 1, 2010 (73 FR 71858) and these Guidelines. As stated in Section 13.5(c) of these Guidelines, “if the donor provides a legitimate medical explanation (
e.g.,
a valid prescription) for the positive result, the MRO reports the test result as negative to the agency.” Accordingly, the intent of the Guidelines, in this context, is to confirm whether a positive drug test is the result of drug use under a valid prescription. Furthermore, the term “alternate medical explanation” has never been used in the Guidelines, but has been used in the HHS Medical Review Officer Manual for Federal Workplace Drug Testing Programs.

For the reasons above, the Department believes that the definition of “nonmedical use of a drug” and the requirement for a physician serving as an MRO to have knowledge of this topic do not fundamentally change the MRO's responsibilities. However, to address the commenters' concerns, the Department has removed this term from the Guidelines (
i.e.,
revised Sections 1.5 and 13.1).

One commenter requested clarification that it is the federal agency's burden to ensure that the MRO is certified. One commenter asked how the laboratory will be informed that an MRO has met requirements for re-qualification. The Department evaluated the comments and concluded that no change is needed. The MRO is an employee or a contractor of the agency. Therefore, it is the agency's responsibility to ensure that the MRO meets the Guidelines qualification requirements.

Two commenters disagreed with the requirement for MRO recertification every five years, and recommended that MROs complete training every three years. Five commenters stated support for five year requalification and examination requirements. The Department has evaluated the comments and has concluded that no change is needed. The Department will keep the five-year requalification requirement as proposed. This is consistent with the MRO requalification requirement in the UrMG.

13.2 How are nationally recognized entities or subspecialty boards that certify MROs approved?

One commenter agreed with MRO certification/training entities submitting the delivery method and content of the MRO examination as applicable along with other required documents. One commenter agreed with extending time from one to two years for approved MRO certification/training entities' resubmission of qualifications for HHS approval. The commenter noted that they would support further extension to 3 years.

One commenter recommended that approval of MRO educational courses and content be at the discretion of the MRO certification entities, not HHS. Since the certification entities and their examinations are subject to HHS oversight and approval, the commenter noted that it may be burdensome for HHS to review and approve the courses and content, and be a disincentive to development of new courses. One commenter recommended that examinations be allowed to be in-person or online with appropriate security precautions for each delivery method. The Department has evaluated the comments and agrees that the submission of training materials to HHS would possibly discourage the development of new training courses. Therefore, the review of MRO educational courses and content will not be part of the approval process for MRO certification entities. As described under
Medical Review Officer (MRO) requalification—continuing education units (CEUs)
in this preamble, the Department has removed references to MRO training entities in Section 13.2, because training documentation is maintained by MRO certification entities. The Department will only require the MRO certification entities to submit their examination and any other necessary supporting examination materials (
e.g.,
answers, examination statistics or background information on questions) that will help in the Department's evaluation of the examination. The Department has revised Section 13.2 accordingly.

The Department will review and evaluate the examination delivery method (
e.g.,
in-person or online) when reviewing submitted materials to ensure that the delivery method employs appropriate security and identification procedures.

13.3 What training is required before a physician may serve as an MRO?

Five commenters disagreed and one commenter agreed with the added requirement for MRO training to include information about how to discuss substance misuse and abuse and how to access those services. The Department has evaluated the comments and has revised Section 13.3 to remove this requirement. Federal agencies may provide this information to employees and applicants to facilitate their access to effective treatment and support recovery. The Department provides information to the public on help and treatment for substance misuse and abuse, and how to access those services, on the SAMHSA website
http://www.samhsa.gov/
.

One commenter stated that the Department should add a requirement for MRO training on what constitutes a refusal to test. One commenter suggested that the Department should add a requirement for MRO training on when and how to report safety concerns to employers when prescription and/or over-the-counter medications may affect performance. The Department has evaluated the comments and has concluded that no change is needed. Criteria for reporting a refusal to test are covered under the topics listed in Section 13.3 such as items (a)(4) training on the Guidelines and (a)(5) procedures for interpretation, review, and reporting of results. When a donor provides a legitimate medical explanation for a positive drug test (
e.g.,
a valid prescription), the Guidelines do not require MROs to contact federal agency employers for the purpose of reporting a safety concern. Accordingly, MRO training related to reporting “safety concerns” does not relate to a mandatory function under the Guidelines and, therefore, is not an essential component of required MRO training. The Department will provide additional guidance in the HHS Medical Review Officer Guidance Manual for Federal Workplace Drug Testing Programs.

In addition, the Department revised Section 13.3 as described under
Medical Review Officer (MRO) requalification—continuing education units (CEUs)
in this preamble. The Department removed references to MRO training entities because training documentation is maintained by MRO certification entities, and added item 13.3(b) to require MRO training on revised Guidelines prior to their effective date.

13.4 What are the responsibilities of an MRO?

One commenter suggested creating a subset of medical professionals trained specifically to determine fitness for duty since an MRO cannot determine fitness for duty over the telephone. The Department has evaluated the comment and has concluded that no change is needed. Fitness for duty evaluations fall outside the purview of the Guidelines.

13.5 What must an MRO do when reviewing an oral fluid specimen's test results?

The Department has revised Section 13.5(c)(1) to include “a valid prescription” as an example of documentation to support a medical explanation for a positive drug test result.

As described under
Testing for Marijuana Use
in this preamble, the Department has revised Section 13.5(c)(1) to reflect the Department's policy that passive exposure to a drug (
e.g.,
exposure to secondhand marijuana smoke) and ingestion of food products containing marijuana are not legitimate medical explanations for a positive drug test result.

In Section 13.5(c)(2)(i), the Department clarified that the requirement for “clinical evidence of illegal use” does not apply if the laboratory confirms the presence of 6-

acetylmorphine (
i.e.,
the presence of this metabolite is proof of heroin use).

13.6 What action does the MRO take when the collector reports that the donor did not provide a sufficient amount of oral fluid for a drug test?

One commenter requested definition of “appropriate expertise” in medical issues raised by a donor's failure to provide a specimen. The same commenter requested medical referral information on the employer's actions when a donor could not provide a urine specimen and then could not provide an oral fluid specimen. The Department has evaluated the comments and has concluded that no change is needed. A physician who is a trained MRO will have the knowledge necessary to identify another physician with appropriate expertise for the medical evaluation. The Department will provide additional guidance in the HHS Medical Review Officer Guidance Manual for Federal Workplace Drug Testing Programs as appropriate when oral fluid is allowed in federal workplace drug testing programs.

The Department clarified the definition of “permanent or long-term medical conditions” in Section 13.6(b)(1) based on a federal agency comment.

Subpart O—Criteria for Rejecting a Specimen for Testing

15.1 What discrepancies require an HHS-certified laboratory to report a specimen as rejected for testing?

The Department revised wording in items a and b of this section, and included three additional fatal flaws as items f-h, to reflect fatal flaws for regulated donor specimens that have been identified by HHS-certified laboratories. These fatal flaws were addressed in NLCP guidance sent to all HHS-certified and applicant laboratories and IITFs on August 9, 2016. In addition, the Department revised this section to include an additional item i to allow a laboratory to reject a specimen when they identify a flaw that prevents testing or affects the forensic defensibility of the drug test, and cannot be corrected. This general item enables laboratories to reject specimens with fatal flaws that may be rare, but do occur. It is not possible to list all such flaws in the Guidelines.

15.3 What discrepancies are not sufficient to require an HHS-certified laboratory to reject an oral fluid specimen for testing or an MRO to cancel a test?

Two commenters indicated that inclusion of some items as insignificant discrepancies contradicts guidance provided to HHS-certified laboratories and IITFs in NLCP Notices, which required laboratories to attempt to recover missing information. One of these commenters suggested that if these items are important, they should be removed from the “insignificant” list. Two commenters disagreed with the Guidelines designating the listed omissions and discrepancies as “insignificant only when they occur no more than once per month.” The Department has evaluated the comments. The listed discrepancies would not result in rejection or cancellation. NLCP Notices requiring laboratory action are consistent with this section. However, the Department has reworded section 15.3 to not classify these errors as insignificant. While these types of errors do not warrant laboratory rejection of a specimen or MRO cancellation of a test, as noted in section 15.3(c), corrective action must be initiated when they occur more than once a month.

The commenters indicated that this section implies that the MRO must keep a log of insignificant errors by laboratory and by collection site in order to track frequency. The commenters noted that this is an unenforceable policy, that this should be a duty of inspectors of laboratories and collection sites, and that requiring MROs to keep these types of logs would create significant extra costs. One commenter suggested that item 15.3(c) be modified for the MRO to advise the collector or laboratory to retrain staff on relevant procedures to ensure that collections are completed correctly (rather than directing them to immediately take corrective action). The Department has evaluated the comments and has concluded that no change is needed. This section is the same as in the Guidelines effective October 1, 2010 (73 FR 71858).

One commenter suggested modifying 15.3(a)(5) to read “donor identification number” which would include a social security number or an employee identification number since many employers no longer use social security numbers for employee identification. The Department agrees and has revised Section 15.3(a)(5) to include “employee identification number” in addition to “Social Security Number.”

15.4 What discrepancies may require

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Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/fr%3A2019-22684. Public record. Not legal advice.