Mandatory Guidelines for Federal Workplace Drug Testing Programs-Authorized Testing Panels, 4662-4668 [2025-00425]

Agencies

• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 90, Number 10 (Thursday, January 16, 2025)]
[Rules and Regulations]
[Pages 4662-4668]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-00425]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

42 CFR Chapter 1


Mandatory Guidelines for Federal Workplace Drug Testing 
Programs--Authorized Testing Panels

AGENCY: Substance Abuse and Mental Health Services Administration 
(SAMHSA), Department of Health and Human Services (HHS)

ACTION: Issuance of authorized drug testing panels.

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SUMMARY: The Department of Health and Human Services (``HHS'' or 
``Department'') herein publishes the panels of Schedule I and II drugs 
and biomarkers authorized for testing in Federal workplace drug testing 
programs. The Department has revised the drug testing panels for both 
urine and oral fluid, and revised required nomenclature for laboratory 
and Medical Review Officer Reports.

DATES: The authorized drug testing panels and required report 
nomenclature are effective July 7, 2025.

FOR FURTHER INFORMATION CONTACT: Eugene D. Hayes, Ph.D., MBA, SAMHSA, 
CSAP, DWP; 5600 Fishers Lane, Room 16N02, Rockville, MD 20857, by 
telephone (240) 276-1459 or by email at [email protected].

SUPPLEMENTARY INFORMATION: The drug testing panels in this Notification 
specify the analytes and cutoffs for Federal agency workplace drug 
testing specimens and the nomenclature (i.e., analyte names and 
abbreviations) that must be used to report Federal workplace drug test 
results, in accordance with Subpart C of the Mandatory Guidelines for 
Federal Workplace Drug Testing Programs using Urine (UrMG, 88 FR 70768) 
and the Mandatory Guidelines for Federal Workplace Drug Testing 
Programs using Oral Fluid (OFMG, 88 FR 70814). Section 3.4 of Subpart C 
calls upon the Secretary of HHS (Secretary) to ``publish the drug and 
biomarker test analytes and cutoffs (i.e., the `drug testing panel' and 
`biomarker testing panel') for initial and confirmatory drug and 
biomarker tests in the Federal Register each year,'' and make them 
available on the internet at https://www.samhsa.gov/workplace. Section 
3.4 of the UrMG and the OFMG also requires HHS-certified laboratories, 
instrumented initial test facilities (IITFs, urine only), and Medical 
Review Officers (MROs) to use the nomenclature (i.e., analyte names and 
abbreviations) published with the drug and biomarker testing panels to 
report Federal workplace drug test results.
    This Federal Register Notification (FRN) contains only the drug 
testing panel because, to date, HHS has not approved any biomarker 
tests for use with Federal workplace drug testing specimens. The drug 
testing panels in Section 3.4 of the UrMG and OFMG will remain in 
effect until July 7, 2025.

Background

    HHS, by the authority of section 503 of Public Law 100-71, 5 
U.S.C., and Executive Order 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. In addition, the Department specifies the 
drugs and biomarkers for which Federal employees may be tested. To 
facilitate timely analyte and cutoff changes based on the state of the 
science, the Department publishes the HHS authorized drug and biomarker 
testing panels separately from the Mandatory Guidelines.
    Analyte changes are based on a thorough review of relevant 
information, including drug prevalence estimates, the current state of 
the science, laboratory capabilities, costs associated with the change, 
and benefits of the change to Federal agencies. To identify panel 
changes needed, the Department solicits review and input from subject 
matter experts such as Responsible Persons (RPs) of HHS-certified 
laboratories, Medical Review Officers (MROs), research scientists, and 
manufacturers of collection devices and/or immunoassay kits, as well as 
Federal partners such as the Department of Transportation (DOT), the 
Food and Drug Administration (FDA), the Department of Defense (DOD), 
and the Drug Enforcement Administration (DEA). The Department also 
seeks public comment to inform decisions related to analyte changes.

[[Page 4663]]

    Using this process for recommending changes to the analyte table, 
the Department proposed the removal of methylenedioxyamphetamine (MDA) 
and methylenedioxymethamphetamine (MDMA) and the addition of fentanyl 
in the notice for the December 5, 2023, Drug Testing Advisory Board 
(DTAB) meeting published in the November 17, 2023, Federal Register. 
The meeting notice included supporting information for the proposed 
changes and a request for public comment, along with the January 4, 
2024, due date for public comments and the methods for comment 
submission. During the December 5th, 2023, DTAB meeting, the Department 
presented the basis for the proposed changes including technical and 
scientific support.
    The Department received and reviewed 176 comments from 118 
commenters. All comments were reviewed and taken into consideration in 
the preparation of draft final drug testing panels. During the DTAB 
meeting on March 5, 2024, the Department presented a summary of the 
public comments, along with additional supporting information for the 
proposed changes including workplace testing prevalence information, 
cost estimates and areas of agreement and concerns The comments are 
available for public view on the SAMHSA website at https://www.samhsa.gov/meetings/dtab-meeting-december-2023 and https://www.samhsa.gov/meetings/dtab-meeting-march-2024. During the June 4-5, 
2024, DTAB meeting, the Department provided updated information on 
fentanyl positivity in workplace testing (urine and oral fluid). DTAB 
members agreed with the proposed changes.
    The Department continued to assess the proposed testing panel 
changes and as described below, has decided not to remove MDMA and MDA 
from the urine and oral fluid drug testing panels at this time.

Summary of Public Comments and HHS's Response

    The following provides the basis for the changes to nomenclature 
and the drug testing panel. The issues and concerns raised in public 
comments and HHS responses are set forth under each topic.

Nomenclature

    For consistency and to avoid misinterpretation of test results, the 
UrMG and OFMG require HHS-certified test facilities and MROs to report 
results using the nomenclature (i.e., analyte names and abbreviations) 
in the drug and biomarker testing panels published in the Federal 
Register.
    The drug testing panel includes revised abbreviations for marijuana 
test analytes, consistent with current scientific nomenclature. The 
Department previously used the abbreviation THC for [Delta]-9-
tetrahydrocannabinol and THCA for [Delta]-9-tetrahydrocannabinol-9-
carboxylic acid. The new abbreviations are [Delta]9THC in place of THC 
and [Delta]9THCC in place of THCA. Including ``[Delta]9'' in these 
abbreviations distinguishes them from other compounds (e.g., [Delta]-8-
tetrahydrocannabinol-9-carboxylic acid and [Delta]-8-
tetrahydrocannabinol). The revised abbreviation [Delta]9THCC also 
distinguishes this marijuana metabolite from [Delta]9-
tetrahydrocannabinolic acid, a non-psychoactive cannabinoid in the 
cannabis plant that is also commonly abbreviated as THCA. This plant 
compound is an important precursor integral to the growth, definition, 
and production of legal hemp as defined by the US Department of 
Agriculture (USDA).1 2

Drug Testing Panel

    Note: Oral fluid cutoffs in the authorized drug testing panel 
are based on undiluted (neat) oral fluid.

Removed Drugs: Methylenedioxyamphetamine (MDA) and 
Methylenedioxymethamphetamine (MDMA)

    The Department proposed to remove MDA and MDMA from the drug 
testing panel because the number of positive specimens reported by HHS-
certified laboratories did not seem to support testing all specimens 
for MDA and MDMA in Federal workplace drug testing programs. 
Information provided to the Department through the National Laboratory 
Certification Program (NLCP) in 2024 shows the MDMA positivity rate for 
the past three years (2021-2023) has been at or below 0.002% and a 
review of the results indicates that >25% of the positive specimens are 
likely agency blind samples. A further review of the NLCP data shows 
that almost 40% of MDMA positive urine specimens are also positive for 
another drug to include amphetamines (7%), benzoylecgonine (9%) and THC 
(21%), indicating that these specimens would be identified as drug 
positive by other means. MDMA accounts for only 0.28% of the drugs 
identified in exhibits submitted to crime laboratories. Tablets sold as 
MDMA on the street often do not contain MDMA and instead contain 
another phenethylamine compound such as dipentylone.3 4 In 
addition, the NLCP information shows that MDA has a significantly lower 
positivity rate (0.00008% of tested specimens) than MDMA, with only six 
specimens identified as containing MDA without MDMA in 2023, and both 
analytes have lower positivity rates than phencyclidine (PCP). While 
PCP has an overall positivity rate nearly as low as MDMA, there are 
regional differences in the positivity of PCP in federally regulated 
and general workplace drug testing populations with some areas of the 
country having much higher rates, so the Department has determined that 
PCP remains a regulated test analyte.\5\
    A total of 10 commenters addressed the removal of MDMA and MDA from 
the testing panel. Of these, four agreed with removal of these drugs, 
while six disagreed.
    Four commenters who disagreed noted that, because drug testing 
deters use, MDMA and MDA use may increase after removal from the panel. 
Another commenter who disagreed with removal stated that growing 
interest in MDMA use for post-traumatic stress disorder and anxiety may 
lead to increased MDMA use. This commenter also noted that the National 
Survey on Drug Use and Health (NSDUH) showed adults' self-reported use 
of MDMA (i.e., Ecstasy) was higher than for phencyclidine (PCP).\6\ A 
commenter who agreed with removal noted that SAMHSA might consider 
removing MDA and keeping MDMA on the testing panel with amphetamine and 
methamphetamine, based on current amphetamines immunoassay cross-
reactivity to MDMA.
    Three commenters stated that MDMA/MDA positivity rates in DOT-
regulated programs have remained steady over time. One of these agreed 
with removal and had no safety concerns, while the other two commenters 
cited this as a reason for continuing to test these drugs.
    The Department considered all comments and has decided that the 
removal of MDMA and MDA from the urine and oral fluid drug testing 
panels requires further study, and therefore, MDMA/MDA will not be 
removed from the drug testing panels at this time. The Department will 
continue to monitor MDMA/MDA prevalence and will engage with the DTAB 
and continue to assess the costs and benefits of removing one or both 
analytes in the future.

Added Drugs: Fentanyl and Norfentanyl

    After declaring the opioid crisis, a public health emergency in 
2017, former President Trump signed the SUPPORT for Patients and 
Communities Act (SUPPORT Act) into law on October 24, 2018. Section 
8105 of the Fighting Opioid Abuse in Transportation Act,

[[Page 4664]]

included in the SUPPORT Act, required the Secretary to determine 
whether it is justified, based on the reliability and cost-
effectiveness of testing, to revise the Mandatory Guidelines for 
Federal Workplace Drug Testing Programs to include fentanyl.\7\ Section 
8105 additionally required the Secretary to consider whether to include 
any other drugs or other substances listed in Schedule I and II of 
Controlled Substances Act (CSA).\8\ Norfentanyl is a metabolite of 
fentanyl. Because it is also an immediate precursor used in the illicit 
manufacture of fentanyl, it is a Schedule II substance under the CSA.
    Fentanyl was considered for inclusion in the proposed Mandatory 
Guidelines of May 2015. At that time, fentanyl was primarily found as a 
mixture with heroin. Because the heroin metabolite 6-acetylmorphine was 
already included in the Mandatory Guidelines, it was decided that the 
addition of fentanyl was not needed to identify fentanyl use. However, 
the illicit drug market and epidemiological data on drug use and 
overdose have changed since that time: fentanyl, primarily illicitly 
made fentanyl, is involved in a large percentage of overdose deaths in 
the United States and is therefore an important public safety 
concern.9 10 Furthermore, illicitly made fentanyl is 
increasingly used as a stand-alone substance among people who use 
drugs, not in conjunction with heroin and other substances.\3\ 
According to the National Forensic Laboratory Information System 
(NFLIS) 2022 Annual Report, fentanyl was the 3rd most frequently 
identified drug and accounted for 13.81% of all drugs reported by 
forensic laboratories.
    The Department conducted studies to determine the prevalence of 
fentanyl in regulated drug testing specimens and examined the current 
state of the technology available to HHS-certified laboratories for 
initial and confirmatory testing of fentanyl and norfentanyl. A review 
of the literature was conducted to identify peer-reviewed publications 
that reported concentrations of fentanyl and/or norfentanyl in urine 
and oral fluid, to determine whether the current initial and 
confirmatory test technologies available in HHS-certified laboratories 
are appropriate for testing for fentanyl and/or norfentanyl and to 
assist in decisions regarding appropriate cutoff concentrations.

Fentanyl Prevalence

    When the Department assessed fentanyl prevalence, two HHS-certified 
laboratories offered urine testing for fentanyl upon request of a 
Federal agency or an MRO. Data from the NLCP included six laboratory-
reported positive test results from 52 requests for fentanyl testing 
from January 1, 2017, through December 31, 2022. Three of the specimens 
were also positive for at least one other drug: two specimens were 
positive for [Delta]9THCC, and one was positive for other opioids 
(i.e., hydrocodone, hydromorphone) in addition to fentanyl.
    The Department also gathered information through a query of HHS-
certified laboratories that perform fentanyl and norfentanyl testing 
(urine and/or oral fluid) for non-regulated clients (e.g., workplace 
testing, compliance testing of healthcare providers) and through pulse 
testing studies (i.e., retesting several deidentified federally 
regulated urine specimens using the laboratory's fentanyl and 
norfentanyl testing procedures). Based on information from non-
regulated workplace drug testing and the pulse testing studies, it is 
estimated that approximately 0.27-0.37% of submitted Federal workplace 
urine specimens will screen positive during initial testing and 0.1 to 
0.3% will confirm positive for fentanyl and/or its primary metabolite 
norfentanyl. Additionally, a recent pulse testing study showed that 
norfentanyl was 36% more prevalent than 6-acetylmorphine in specimens 
with a positive opiate initial test.
    Of the total 118 commenters, 115 supported the addition of fentanyl 
to the authorized drug testing panels. Most commenters noted the 
prevalence of fentanyl use and overdoses, based on their professional 
or personal experience, and the threat to workplace and public safety, 
particularly in transportation industries. Of the three individuals who 
disagreed: one incorrectly stated that fentanyl would be detected and 
reported using current opioid tests for Federal agency urine specimens; 
one incorrectly indicated that fentanyl would only be detected within a 
few hours of use; and the third disagreed with any additional Federal 
regulations for truck drivers.
    The Department considered all comments and has added fentanyl to 
the urine and oral fluid drug testing panels and added its metabolite 
norfentanyl to the urine drug testing panel. Until the effective date 
of the new drug testing panel, fentanyl and/or norfentanyl can be 
analyzed under the Mandatory Guidelines only upon request of a Federal 
agency for a reasonable suspicion or post-accident specimen or 
routinely with a waiver from the Secretary (in accordance with Section 
3.2 of the UrMG and OFMG). A detailed discussion is provided below.

Fentanyl Analyte Selection and Cutoff Determination--Urine

    Information provided by HHS-certified laboratories in 2023 
indicated that a majority (84%) of the laboratories analyzed non-
regulated workplace specimens for fentanyl and/or norfentanyl, and that 
all had the ability to analyze urine specimens for fentanyl with 
sufficiently sensitive detection limits using commercially available 
immunoassay kits and confirmatory test instrumentation commonly used in 
HHS-certified laboratories. The laboratories' initial test cutoffs 
ranged from 0.5 to 2 ng/mL for fentanyl and confirmatory test cutoffs 
for fentanyl and norfentanyl ranged from 0.5 to 2 ng/mL for fentanyl 
and 0.5 to 5 ng/mL for norfentanyl.
    Fentanyl and norfentanyl prevalence and concentrations appear to 
vary considerably depending on the population studied and the applied 
cutoff. Laboratory data from non-regulated workplace drug testing are 
around 1% fentanyl positivity in urine. The median, mean and max 
fentanyl concentrations were 12.6 ng/mL, 257.5 ng/mL and 36,199 ng/mL, 
respectively. Norfentanyl concentrations were reported to be around 4 
times higher than those of fentanyl.\11\ A recent pulse testing study 
on regulated urine workplace specimens showed that norfentanyl 
concentrations were 5.5 times higher than fentanyl concentrations 
(median, Q1-Q3, 2.5-13.3 times higher).\12\ The median fentanyl and 
norfentanyl concentrations were 159 and 1,521 ng/mL, respectively. In a 
large study of 1 million urine specimens conducted by healthcare 
professionals for routine care, the positivity rate for fentanyl was 
1.4% (13,770 specimens) using cutoffs of 2 ng/mL for fentanyl and 8 ng/
mL for norfentanyl.\13\ Using immunoassay screening and a GC-MS 
confirmatory test cutoff of 1 ng/mL, fentanyl was positive in 4.2% (458 
specimens) of specimens among patients being treated for pain 
conditions.\14\ The median, mean, and range of fentanyl concentrations 
were 23 ng/mL, 87 ng/mL, and 1 to 2382 ng/mL, respectively. Another 
study of patients with chronic pain demonstrated that norfentanyl can 
be an important component of identifying people who use fentanyl when 
urine is the specimen matrix.\15\ The authors showed that including 
norfentanyl increased the number of positive specimens by 42% over 
analyzing for fentanyl alone. The fentanyl median, mean and range 
concentrations were 22 ng/ml, 59.2 ng/mL, and 0.5 to 596 ng/mL, 
respectively.

[[Page 4665]]

Norfentanyl median, mean and range concentrations were 25.5 ng/mL, 134 
ng/mL, and 0.5 to 1,772 ng/ml, respectively. A study of 77,018 urine 
specimens from patients treated with fentanyl using a transdermal patch 
reported median and mean fentanyl concentration of 37 and 88 ng/mL.\16\ 
When comparing doses of 12 and 100 [micro]g/h, the mean fentanyl 
concentration increased from 32 to 137 ng/mL, and the norfentanyl mean 
concentration increased from 176 to 695 ng/mL, illustrating the dose-
response relationships.
    Based on this information, the Department originally proposed a 1 
ng/mL initial test cutoff for both fentanyl and norfentanyl in urine, 
with a 0.5 ng/mL confirmatory test cutoff for both analytes.
    Ten commenters disagreed with adding norfentanyl as an initial test 
analyte for urine. Nine of these specifically disagreed with 
norfentanyl as an initial test analyte, noting that no current FDA-
cleared immunoassay has sufficient cross-reactivity for fentanyl and 
norfentanyl to meet the program requirement for grouped analytes (i.e., 
at least 80% cross-reactivity to the non-target analyte). One commenter 
suggested that the Department lower the cross-reactivity requirement to 
5%, noting that norfentanyl is often at higher concentrations than 
fentanyl. One suggested including fentanyl as the initial test analyte 
and norfentanyl only as a confirmatory test analyte, noting it is a 
Schedule II drug because it is used in the synthesis of fentanyl, and 
is not a pharmacologically active metabolite or a separate drug of 
misuse.
    Nine commenters addressed the proposed 1 ng/mL fentanyl initial 
test cutoff for urine. Of these, one agreed with the fentanyl cutoff, 
noting that current FDA-cleared immunoassays used for initial testing 
can meet this cutoff. Eight commenters disagreed, stating that a 1 ng/
mL cutoff is beyond the limits of traditional immunoassay technologies, 
and that laboratories would not be able to meet the UrMG requirement 
for initial test controls targeted at 25% above and below the cutoff. 
One commenter suggested a lower cutoff (0.75 ng/mL) but did not provide 
supporting information. The Department notes that there is a commercial 
immunoassay at this cutoff.
    Regarding the proposed confirmatory test analytes and cutoffs, one 
commenter agreed with testing both fentanyl and norfentanyl using the 
proposed 0.5 ng/mL cutoff. Two other commenters agreed with norfentanyl 
as a confirmatory test analyte but disagreed with the proposed cutoff. 
One of these commenters provided 2022-2023 data from non-regulated drug 
testing showing that only 1.6% of specimens had results below 1.0 ng/
mL, while more than 50% had results above 100 ng/mL for fentanyl and 
above 1000 ng/mL for norfentanyl. The commenter did not indicate the 
initial test cutoff(s) used for these specimens. An initial test cutoff 
of 1 or 2 ng/mL could explain the low percentage of confirmatory test 
results below 1 ng/mL.
    One commenter disagreed with the proposed fentanyl cutoffs for both 
initial and confirmatory testing, stating the cutoffs were too low and 
would present legal challenges due to long elimination times in urine 
following fentanyl use. The commenter noted that there are no 
controlled studies in the literature on this topic. Concerns were based 
on a laboratory's reports of six cases involving norfentanyl >0.5 ng/mL 
for at least one month after self-reported cessation of fentanyl use, 
and two other studies indicating possible long elimination time based 
on positive results after self-reported cessation of fentanyl use by 
individuals with opioid use disorder.\17\
    The Department considered all comments. Regarding initial test 
analyte selection, the Department agrees with commenters that, at the 
time of this writing, most commercial immunoassays for fentanyl in 
urine are calibrated to fentanyl and exhibit little cross-reactivity to 
norfentanyl. The Department is aware of one immunoassay for fentanyl 
that has 5-7% cross-reactivity to norfentanyl and another immunoassay 
for norfentanyl in urine with a 5 ng/mL cutoff (i.e., above the cutoff 
specified in the drug testing panel). As detailed above, HHS-certified 
laboratory test information, the pulse testing study, and review of 
fentanyl and norfentanyl concentrations from other tested populations 
demonstrate the importance of testing for norfentanyl.
    To facilitate implementation of fentanyl testing into Federal 
workplace drug testing programs, the Department has decided to include 
only fentanyl (not norfentanyl) as the sole initial test analyte for 
urine at a cutoff of 1 ng/mL and require a fentanyl immunoassay initial 
test to exhibit at least 5% cross-reactivity for norfentanyl. The 
Department also increased the proposed 0.5 ng/mL confirmatory test 
cutoffs to 1 ng/mL for both fentanyl and norfentanyl. These changes are 
consistent with the current initial and confirmatory test technologies 
already available in HHS-certified laboratories and detailed in the 
current scientific literature.

Fentanyl Analyte Selection and Cutoff Determination--Oral Fluid

    Information provided by HHS-certified urine laboratories in 2023 
indicated that 43% offered oral fluid testing to non-regulated 
workplace clients and that 71% of these laboratories offered testing 
for fentanyl. These laboratories indicated they had the ability to 
analyze oral fluid specimens for fentanyl with sufficiently sensitive 
detection limits using commercially available immunoassay kits and 
confirmatory test instrumentation commonly used in HHS-certified 
laboratories. The laboratories' initial test cutoffs ranged from 1 to 4 
ng/mL for fentanyl and confirmatory test cutoffs for fentanyl ranged 
from 0.5 to 1 ng/mL for fentanyl.
    Fentanyl has been detected in oral fluid in non-regulated workplace 
drug testing, patients receiving pain management, overdose cases, and 
driving under the influence of drugs (DUID) cases. Laboratory data from 
non-regulated workplace drug testing show around 4% fentanyl positivity 
in oral fluid. The median, mean and max fentanyl concentrations were 
8.6 ng/mL, 55.7 ng/mL and 17,409 ng/mL, respectively.\11\ The median 
norfentanyl concentration was 4.5 ng/mL. For DUID testing, cutoffs of 1 
ng/mL for the initial test and 0.5 ng/mL for the confirmatory test have 
been recommended for fentanyl in oral fluid.\18\ In a study of people 
arrested for DUID, 59% of oral fluid specimens had concentrations above 
20 ng/mL.\19\ In a large study, oral fluid specimens were collected 
from 6,441 patients receiving pain care and screened by immunoassay (1 
ng/mL fentanyl cutoff) and confirmed by LC-MS/MS.\20\ Of the collected 
specimens, 6.9% screened positive (443 specimens) and 98.4% of those 
(436 specimens) were confirmed positive. The fentanyl, median, mean, 
and range concentrations were, 6.6, 49.8, and 0.2 to 5,341.3 ng/mL, 
respectively. For the 148 confirmed positive norfentanyl specimens, the 
norfentanyl median, mean, and range concentrations were 1.6, 4.7, and 
0.5 to 125 ng/mL, respectively. In a study of patients treated with 
buprenorphine, the prevalence of fentanyl in oral fluid was 2.9% 
(n=146) with a median concentration of 1.3 ng/mL (Q1-Q3, 0.4-10.4).\21\ 
In a study of patients wearing fentanyl patches (n=162), the median 
fentanyl concentration was around 5 ng/mL, range 0.012-38.4 ng/mL.\22\
    Based on this information and review of the scientific literature, 
the Department originally proposed fentanyl as the only analyte for 
oral

[[Page 4666]]

fluid, with a 1 ng/mL initial test cutoff and a 0.5 ng/mL confirmatory 
test cutoff.
    Three commenters disagreed with testing fentanyl in oral fluid 
noting that, because there are no FDA-cleared immunoassays meeting 
program requirements, inclusion of fentanyl would delay implementation 
of oral fluid into Federal workplace drug testing programs. One of 
these commenters raised concern that the added burden and cost to 
develop and implement an alternate technology initial test (e.g., LC-
MS/MS) would deter some laboratories from applying for oral fluid 
certification. Another commenter noted that, unless the regulatory 
process is streamlined, HHS will not be able to respond quickly to 
changes in drug use.
    One commenter agreed with the proposed 1 ng/mL fentanyl initial 
test cutoff for oral fluid, while 10 commenters disagreed. Most 
commenters were concerned that the cutoff was too low, stating that 
oral fluid collection devices containing a buffer (i.e., diluting the 
oral fluid) would not be able to meet program analytical requirements 
(e.g., controls at 25% above and below the initial test cutoff). Many 
of the commenters indicated that a higher cutoff is supported by drug 
test results. One commenter suggested raising the cutoff: suggesting 
that the Department select a cutoff between 2 and 4 ng/mL. Two 
commenters requested research supporting the proposed 1 ng/mL initial 
test cutoff and 0.5 confirmatory test cutoff. This information is 
provided above. One commenter recommended a lower initial test cutoff 
(0.75 ng/mL) and a higher confirmatory cutoff (5 ng/mL), with no 
scientific support.
    The Department has considered all comments and has decided to 
increase the initial test cutoff to 4 ng/mL and the confirmatory test 
cutoff for fentanyl to 1 ng/mL. Based on information provided by the 
public, review of the scientific literature, and current methods and 
technologies used for oral fluid drug testing, the Department has 
determined that these fentanyl cutoffs are appropriate for initial and 
confirmatory tests.

Revised Criteria for Grouped Analytes Using an Alternate Technology 
Initial Drug Test

    The Department defines grouped initial test analytes as two or more 
analytes that are in the same drug class and have the same initial drug 
test cutoff. Footnote 1 of the drug testing panel specifies 
requirements for initial tests using immunoassay and those using an 
alternate technology (e.g., liquid chromatography-tandem mass 
spectrometry, LC-MS/MS). The Department has revised Footnote 1 of the 
Section 3.4 tables in the UrMG and OFMG to include more specific and 
updated criteria for alternate technology initial drug tests, based on 
current technology and program experience.
    For a technology other than immunoassay that measures a response 
from the entire group without differentiating between analytes (e.g., 
an activity-based assay, a mass spectrometric assay that does not 
differentiate isobaric compounds), the laboratory must compare the 
result to the initial test cutoff. In the case of an alternate 
technology that differentiates and quantifies each analyte in the 
group, the laboratory must compare each analyte's result to the 
confirmatory test cutoff and reflex specimens with a positive initial 
test result to confirmatory testing.

Biomarker Testing Panel

    Section 3.4 of the UrMG and OFMG call upon the Secretary to add 
biomarkers to the biomarker testing panel; however, at the time of this 
writing, no biomarkers have been approved for Federal workplace drug 
testing. The Department will review and approve biomarkers based on 
laboratory data and support from the scientific and medical literature 
and add them to the biomarker testing panel in a subsequent FRN.
    A biomarker is defined in Section 1.5 of the UrMG and OFMG as ``an 
endogenous substance used to validate a biological specimen''. While 
creatinine in urine meets this definition, it is not sufficient as a 
sole analyte. The UrMG include requirements for testing both creatinine 
and specific gravity to report a specimen as dilute, invalid, or 
substituted.

Costs and Benefits

    HHS-certified test facilities and MROs will incur initial costs for 
administrative and programming changes for the addition of fentanyl 
and/or norfentanyl.
    Laboratories that already offer fentanyl and norfentanyl testing 
and use the same cutoff(s) for their non-regulated clients may 
experience some savings compared to laboratories that do not test for 
these analytes. Estimated costs for testing for fentanyl range from 
$0.23 to $5.00 (for initial testing) and $8.00 to $25.00 (for 
confirmatory testing) per specimen tested. Total laboratory costs for 
fentanyl confirmatory testing of Federal employee specimens are 
estimated to range from $577-$4,750. Based on the number of tests 
performed on Federal employees, the added cost for fentanyl 
confirmatory testing will be $0.0152 to $0.125 per submitted specimen, 
and the total cost for adding fentanyl will range from $9,317 to 
$194,750, based on these estimates.
    MROs may experience increased costs when an agency chooses to test 
their federal job applicants and employees for the added analytes, as 
fentanyl analytes are expected to have high positivity rates and, in 
addition, fentanyl is a Schedule II drug with approved therapeutic uses 
requiring the MRO to review potential medical explanations. Additional 
costs for testing and MRO review will be incorporated into the overall 
costs for the Federal agency submitting the specimen to the laboratory. 
Added costs to MROs would be expected to shift to Federal agencies over 
time, as existing contracts expire, and new contract terms are 
negotiated.
    Currently, the Department does not require HHS-certified test 
facilities to implement authorized biomarker tests. Each laboratory and 
IITF should conduct their own cost analysis when deciding whether to 
offer biomarker testing to federally regulated clients. The Department 
will consider costs when deciding whether to require all certified test 
facilities to test for a specific biomarker.

References

1. Agriculture Improvement Act of 2018, Public Law 115-334 (2018). 
115th Congress. https://www.congress.gov/115/plaws/publ334/PLAW-115publ334.pdf.
2. Agricultural Marketing Service. (2021). Establishment of a 
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(SAMHSA). (2023). National Survey on Drug Use and Health (NSDUH). 
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Health and Human Services, https://www.samhsa.gov/data/data-we-collect/nsduh-national-survey-drug-use-and-health.
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and Treatment for Patients and Communities Act or the SUPPORT for 
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``Deaths involving fentanyl, fentanyl analogues, and U-47700--10 
states, July-December 2016, Weekly/November 3, 2017/66(43); 1197-
1202,'' Centers for Disease Control and Prevention, Atlanta, GA.
10. Trecki J, Gerona RR, Ellison R, Thomas C, Mileusnic-Polchan D. 
Notes from the Field: Increased Incidence of Fentanyl-Related Deaths 
Involving Para-fluorofentanyl or Metonitazene--Knox County, 
Tennessee, November 2020-August 2021. MMWR Morb Mortal Wkly Rep 
2022;71:153-155. doi: https://dx.doi.org/10.15585/mmwr.mm7104a3.
11. Kuntz, D. (2024, March 5). CRL testing experience for fentanyl 
in urine and oral fluids. DTAB Meeting. https://www.samhsa.gov/sites/default/files/meeting/documents/crl-testing-experience-fentanyl-urine-oral-fluids.pdf.
12. Vikingsson, S. (2023, March 7). Summary of pulse testing studies 
for fentanyl in opioids initial test positive and [Delta]8-HC in 
THCA initial test positive specimens. DTAB Meeting. https://www.samhsa.gov/sites/default/files/meeting/documents/dtab-summary-of-pulse-testing-2023.pdf
13. LaRue, L., Twillman, R.K., Dawson, E., Whitley, P., Frasco, 
M.A., Huskey, A., & Guevara, M.G. (2019). Rate of fentanyl 
positivity among urine drug test results positive for Cocaine or 
Methamphetamine. JAMA Network Open, 2(4), e192851. https://doi.org/10.1001/jamanetworkopen.2019.2851.
14. Cone, E.J., Caplan, Y.H., Black, D.L., Robert, T., & Moser, F. 
(2008). Urine drug testing of chronic pain patients: Licit and 
illicit drug patterns. Journal of Analytical Toxicology, 32(8), 530-
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T., Moser, F., Caplan, Y.H., & Cone, E.J. (2010). Urine drug testing 
of chronic pain patients. III. Normetabolites as biomarkers of 
synthetic opioid use. Journal of Analytical Toxicology, 34(8), 444-
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16. Cummings, O.T., Enders, J.R., & McIntire, G.L., Backer, R., & 
Poklis, A. (2016). Fentanyl-Norfentanyl concentrations during 
transdermal patch application: LC-MS-MS urine analysis. Journal of 
Analytical Toxicology, 40(8), 595-600. https://doi.org/10.1093/jat/bkw067.
17. Walker, N., Dawson, G.B., Rana, S., 2023. Challenges with 
fentanyl renewed use interpretation. Society of Forensic 
Toxicologists (SOFT) 2023 Meeting, Denver, CO. soft-tox.org/assets/Denver/2023ProgramBook-Digital.pdf.
18. D'Orazio, A.L., Mohr, A.L.A., Chan-Hosokawa, A., Harper, C., 
Huestis, M.A., Limoges, J.F., Miles, A.K., Scarneo, C.E., Kerrigan, 
S., Liddicoat, L.J., Scott, K.S., Logan, B.K. (2021). 
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Analytical. Toxicology, 45(6), 529-536. https://doi.org/10.1093/jat/bkab064.
19. Harper, C.E., Mata, D.C., & Lee, D. (2023). The impact of 
fentanyl on DUIDs and traffic fatalities: Blood and oral fluid data. 
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20. Heltsley, R., DePriest, A., Black, D.L., Robert, T., Marshall, 
L., Meadors, V.M., Caplan, Y.H., & Cone, E.J. (2011). Oral fluid 
drug testing of chronic pain patients. I. Positive prevalence rates 
of licit and illicit drugs. Journal of Analytical. Toxicology, 
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                       Report Nomenclature--Urine
------------------------------------------------------------------------
                                  Urine
-------------------------------------------------------------------------
              Abbreviation                           Analyte
------------------------------------------------------------------------
[Delta]9THCC...........................  [Delta]-9-tetrahydrocannabinol-
                                          9-carboxylic acid.
BZE....................................  Benzoylecgonine.
COD....................................  Codeine.
MOR....................................  Morphine.
HYC....................................  Hydrocodone.
HYM....................................  Hydromorphone.
OXYC...................................  Oxycodone.
OXYM...................................  Oxymorphone.
6-AM...................................  6-Acetylmorphine.
PCP....................................  Phencyclidine.
FENT...................................  Fentanyl.
NFENT..................................  Norfentanyl.
AMP....................................  Amphetamine.
MAMP...................................  Methamphetamine.
MDMA...................................  Methylenedioxymethamphetamine.
MDA....................................  Methylenedioxyamphetamine.
------------------------------------------------------------------------


                                          HHS Drug Testing Panel--Urine
----------------------------------------------------------------------------------------------------------------
                                                                  Confirmatory test        Confirmatory  test
       Initial test analyte         Initial  test cutoff \1\           analyte                   cutoff
----------------------------------------------------------------------------------------------------------------
Marijuana metabolite               50 ng/mL.                  [Delta]9THCC............  15 ng/mL.
 ([Delta]9THCC).
Cocaine metabolite                 150 ng/mL.\2\              Benzoylecgonine.........  100 ng/mL.
 (Benzoylecgonine).
Codeine/Morphine.................  2,000 ng/mL.               Codeine.................  2,000 ng/mL.
                                                              Morphine................  4,000 ng/mL.
Hydrocodone/Hydromorphone........  300 ng/mL.                 Hydrocodone.............  100 ng/mL.
                                                              Hydromorphone...........  100 ng/mL.
Oxycodone/Oxymorphone............  100 ng/mL.                 Oxycodone...............  100 ng/mL.
                                                              Oxymorphone.............  100 ng/mL.
6-Acetylmorphine.................  10 ng/mL.                  6-Acetylmorphine........  10 ng/mL.
Phencyclidine....................  25 ng/mL.                  Phencyclidine...........  25 ng/mL.
Fentanyl \3\.....................  1 ng/mL.                   Fentanyl................  1 ng/mL.
                                                              Norfentanyl.............  1 ng/mL.
Amphetamine/Methamphetamine......  500 ng/mL.                 Amphetamine.............  250 ng/mL.
                                                              Methamphetamine.........  250 ng/mL.
MDMA/MDA.........................  500 ng/mL.                 Methylenedioxymethamphet  250 ng/mL.
                                                               amine.                   250 ng/mL.
                                                              Methylenedioxyamphetamin
                                                               e.
----------------------------------------------------------------------------------------------------------------
\1\ For grouped analytes (i.e., two or more analytes that are in the same drug class and have the same initial
  test cutoff):
Immunoassay: The test must be calibrated with one analyte from the group identified as the target analyte. The
  cross-reactivity of the immunoassay to the other analyte(s) within the group must be 80 percent or greater; if
  not, separate immunoassays must be used for the analytes within the group.

[[Page 4668]]

 
Alternate technology: Either one analyte or all analytes from the group must be used for calibration, depending
  on the technology. For a technology that measures a response from the entire group without differentiating
  between analytes (e.g., an activity-based assay, a mass spectrometric assay that does not differentiate
  isobaric compounds), the laboratory must compare the result to the initial test cutoff. In the case of an
  alternate technology that differentiates and quantifies each analyte in the group, the laboratory must compare
  each analyte's result to the confirmatory test cutoff and reflex specimens with a positive initial test result
  to confirmatory testing.
\2\ Alternate technology (BZE): The confirmatory test cutoff must be used for an alternate technology initial
  test that is specific for the target analyte (i.e., 100 ng/mL for benzoylecgonine).
\3\ A fentanyl immunoassay must have at least 5% cross-reactivity to norfentanyl.

HHS Biomarker Testing Panel--Urine

    SAMHSA has not yet authorized routine testing for any biomarker in 
urine. HHS-certified laboratories and instrumented initial test 
facilities (IITFs) may request authorization to test Federal agency 
specimens for a biomarker upon Medical Review Officer (MRO) request by 
submitting supporting documentation and assay validation records to the 
National Laboratory Certification Program (NLCP) for SAMHSA review and 
approval.

                     Report Nomenclature--Oral Fluid
------------------------------------------------------------------------
                               Oral fluid
-------------------------------------------------------------------------
              Abbreviation                           Analyte
------------------------------------------------------------------------
[Delta]9THC............................  [Delta]-9-tetrahydrocannabinol.
COC....................................  Cocaine.
BZE....................................  Benzoylecgonine.
COD....................................  Codeine.
MOR....................................  Morphine.
HYC....................................  Hydrocodone.
HYM....................................  Hydromorphone.
OXYC...................................  Oxycodone.
OXYM...................................  Oxymorphone.
6-AM...................................  6-Acetylmorphine.
PCP....................................  Phencyclidine.
FENT...................................  Fentanyl.
AMP....................................  Amphetamine.
MAMP...................................  Methamphetamine.
MDMA...................................  Methylenedioxymethamphetamine.
MDA....................................  Methylenedioxyamphetamine.
------------------------------------------------------------------------


                                       HHS Drug Testing Panel--Oral Fluid
----------------------------------------------------------------------------------------------------------------
                               HHS drug testing panel--undiluted (neat) oral fluid
-----------------------------------------------------------------------------------------------------------------
                                                                  Confirmatory test        Confirmatory  test
       Initial test analyte         Initial  test cutoff \1\           analyte                   cutoff
----------------------------------------------------------------------------------------------------------------
Marijuana ([Delta]9THC)..........  4 ng/mL.                   [Delta]9THC.............  2 ng/mL.
Cocaine/Benzoylecgonine..........  15 ng/mL.                  Cocaine.................  8 ng/mL.
                                                              Benzoylecgonine.........  8 ng/mL.
Codeine/Morphine.................  30 ng/mL.                  Codeine.................  15 ng/mL.
                                                              Morphine................  15 ng/mL.
Hydrocodone/Hydromorphone........  30 ng/mL.                  Hydrocodone.............  15 ng/mL.
                                                              Hydromorphone...........  15 ng/mL.
Oxycodone/Oxymorphone............  30 ng/mL.                  Oxycodone...............  15 ng/mL.
                                                              Oxymorphone.............  15 ng/mL.
6-Acetylmorphine.................  4 ng/mL.\2\                6-Acetylmorphine........  2 ng/mL.
Phencyclidine....................  10 ng/mL.                  Phencyclidine...........  10 ng/mL.
Fentanyl.........................  4 ng/mL.                   Fentanyl................  1 ng/mL.
Amphetamine/Methamphetamine......  50 ng/mL.                  Amphetamine.............  25 ng/mL.
                                                              Methamphetamine.........  25 ng/mL.
MDMA/MDA.........................  50 ng/mL.                  Methylenedioxymethamphet  25 ng/mL.
                                                               amine.                   25 ng/mL.
                                                              Methylenedioxyamphetamin
                                                               e.
----------------------------------------------------------------------------------------------------------------
\1\ For grouped analytes (i.e., two or more analytes that are in the same drug class and have the same initial
  test cutoff):
Immunoassay: The test must be calibrated with one analyte from the group identified as the target analyte. The
  cross reactivity of the immunoassay to the other analyte(s) within the group must be 80 percent or greater; if
  not, separate immunoassays must be used for the analytes within the group.
Alternate technology: Either one analyte or all analytes from the group must be used for calibration, depending
  on the technology. For a technology that measures a response from the entire group without differentiating
  between analytes (e.g., an activity-based assay, a mass spectrometric assay that does not differentiate
  isobaric compounds), the laboratory must compare the result to the initial test cutoff. In the case of an
  alternate technology that differentiates and quantifies each analyte in the group, the laboratory must compare
  each analyte's result to the confirmatory test cutoff and reflex specimens with a positive initial test result
  to confirmatory testing.
\2\ Alternate technology (6-AM): The confirmatory test cutoff must be used for an alternate technology initial
  test that is specific for the target analyte (i.e., 2 ng/mL for 6-AM).

HHS Biomarker Testing Panel--Oral Fluid

    SAMHSA has not yet authorized routine testing for any biomarker in 
oral fluid. HHS-certified laboratories may request authorization to 
test Federal agency specimens for a biomarker by submitting supporting 
documentation and assay validation records to the National Laboratory 
Certification Program (NLCP) for SAMHSA review and approval. Authorized 
biomarker test cutoffs for oral fluid will be based on undiluted (neat) 
oral fluid.

Xavier Becerra,
Secretary, Department of Health and Human Services.
[FR Doc. 2025-00425 Filed 1-15-25; 8:45 am]
BILLING CODE 4162-20-P