[Federal Register Volume 88, Number 27 (Thursday, February 9, 2023)]
[Notices]
[Pages 8428-8431]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-02730]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

[Docket No. CDC-2022-0003]


Policy Statement for Biosafety Level 4/Animal Biosafety Level 4 
Laboratory Verification; Notice of Availability

AGENCY: Centers for Disease Control and Prevention (CDC), Department of 
Health and Human Services (HHS).

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Centers for Disease Control and Prevention (CDC), in the 
Department of Health and Human Services (HHS), announces the 
availability and implementation of the final Biosafety Level 4 (BSL-4)/
Animal BSL-4 (ABSL-4) verification policy. The policy statement assists 
individuals and entities in verifying that the facility design 
parameters and operational procedures, including heating, ventilation, 
and air conditioning (HVAC) systems, in BSL-4 and/or ABSL-4 
laboratories are functioning as intended to meet the biosafety 
sufficiency requirement in the HHS/CDC select agent and toxin 
regulations.

[[Page 8429]]


DATES: The compliance date for this Policy is February 9, 2023.

FOR FURTHER INFORMATION CONTACT: Samuel S. Edwin Ph.D., Director, 
Division of Select Agents and Toxins, Centers for Disease Control and 
Prevention, 1600 Clifton Road NE, Mailstop H21-4, Atlanta, Georgia 
30329. Telephone: (404) 718-2000. Email: [email protected].

SUPPLEMENTARY INFORMATION: On January 19, 2022, CDC published a notice 
in the Federal Register (87 FR 2791) requesting public comment on a 
draft policy statement on BSL-4/ABSL-4 laboratory verifications 
standards, including HVAC, to aid individuals and entities in verifying 
that these laboratories are properly functioning. HHS/CDC received 
comment on the draft policy statement concerning BSL-4/ABSL-4 
verification requirements from seven commenters. The commenters were 
from academia, industry, city/local government, and the public.

Summary of Public Comments

    In general, commenters supported the draft policy but had specific 
suggestions on wording and revisions. Please see a summary of the 
comments and our responses below.
    Comment: One commenter suggested changing the subject to include 
BSL-3 Agriculture.
    Response: HHS/CDC notes that an established BSL-3/ABSL-3 
Verification Policy already exists (https://www.cdc.gov/cpr/ipp/docs/Policy_Import_BSL3_ABSL3_Verification.pdf). Thus, HHS/CDC made no 
changes based on this comment.
    Comment: One commenter recommended that Heating, Ventilation, and 
Air Conditioning (HVAC) be referred to as ``Building and Mechanical, 
Electrical, and Plumbing (MEP) systems.''
    Response: HHS/CDC disagreed with this recommendation because the 
term ``HVAC'' is more universally referenced. No changes were made to 
the policy due to this comment.
    Comment: HHS/CDC received comment regarding clarification and 
testing of the HVAC system only after major changes or every ten years.
    Response: HHS/CDC agreed with the commenter to provide the 
clarification and has updated the policy to state that entities must 
ensure HVAC verification is performed and documented ``after major 
changes to ensure operational parameters are maintained.'' The policy 
includes examples of major changes that can be referenced. HHS/CDC 
disagreed with the other comments regarding increasing the testing 
requirement to every ten years.
    Comment: A commenter discussed primary and secondary fans versus 
parallel HVAC fans and how setup depends on different facility 
configurations.
    Response: HHS/CDC agreed with the comment about configuration of 
HVAC fans and included ``or failure of parallel fans depending on 
facility configuration'' in the policy.
    Comment: Commenters requested that examples be provided for major 
changes and that HHS/CDC provide a list of repairs to HVAC control 
system components that require verification testing.
    Response: HHS/CDC agreed with providing examples and has updated 
the policy to include examples of major changes that can be referenced. 
Modifications include repairs or replacing a component to the HVAC to 
ensure that the system is fully operational. HHS/CDC also revised the 
policy to state ``systems'' instead of ``components.'' Entities should 
ensure all HVAC systems are operational, and because systems vary, the 
components of the system also vary from entity to entity; therefore, 
HHS/CDC will not be providing a universal list of repair of HVAC 
control system components.
    Comment: Another commenter suggested using a risk assessment-based 
approach to determine if failure testing is required after resolving a 
major problem.
    Response: HHS/CDC disagreed with the comment regarding a risk 
assessment-based approach to determine if failure testing is required 
after a major problem. As such, HHS/CDC made no updates to the policy. 
HHS/CDC understands the commenters' concerns regarding a disruption due 
to a major problem and then the need for the entity to perform HVAC 
operational verification. However, HHS/CDC believes it is essential to 
verify the system annually and after any significant modification to 
ensure operational parameters are maintained during both normal 
operating conditions and failure conditions to prevent air-flow 
reversals into non-containment areas (e.g., outside the containment 
boundary, hallways).
    Comment: A commenter requested that HHS/CDC require an HVAC design 
verification process for ``primary containment (suit and cabinet room's 
primary barrier equipment)'' instead of secondary containment.
    Response: HVAC is part of the facility safeguards, which is a 
secondary barrier; therefore, HHS/CDC will not be referring to this as 
primary containment. Secondary containment is defined by the 6th 
edition of the Biosafety in Microbiological and Biomedical Laboratories 
(BMBL) as the design and construction of the laboratory facility that 
provides a means of secondary containment of hazardous biological 
agents and toxins to protect personnel, the surrounding community, and 
the environment from possible exposure to hazardous biological agents 
and toxins.
    Comment: A commenter recommended excluding small repairs, like-for-
like replacement of smaller components, and minor automation system 
logic programming changes.
    Response: HHS/CDC made no changes to the policy and agreed with the 
commenter that minor changes and small repairs mentioned above would 
not be considered major repairs.
    Comment: Commenters suggested specific references be added to the 
list of systems to be tested/verified annually such as chemical shower, 
alarms, power source, communications, access systems, Air Pressure 
Resistant (APR) door gaskets, positive-pressure suits, water supply, 
and manual overrides tested (e.g., between mechanical and electronic 
door interlocks).
    Response: HHS/CDC agreed with the commenters and updated the policy 
to reference these items.
    Comment: Commenters requested the term ``uninterrupted power 
supply'' be changed to adequately reflect the meaning.
    Response: HHS/CDC agreed with the commenters and changed the term 
to ``automatically activated backup.''
    Comment: A commenter asked if room air pressure trend lines 
captured from the Building Automation System (BAS) could be used to 
demonstrate the absence of air reversal.
    Response: HHS/CDC agreed and revised the policy to state that 
entities may use BAS records to demonstrate no airflow reversal from 
the BSL-4/ABSL-4 laboratory during transition from normal power to the 
automatically activated backup, emergency power supply.
    Comment: Another commenter suggested the inclusion of emergency 
power stand-by systems (emergency generator and automatic transfer 
switch), uninterruptible power supply, and critical equipment with 
internal batteries (e.g., programmable logic control devices) to the 
minimum verification requirement for back-up power systems for HVAC.
    Response: HHS/CDC agreed with the comment and revised the policy to 
include ``routine maintenance programs and backup, power systems'' to

[[Page 8430]]

succinctly summarize the minimum verification requirements.
    Comment: Commenters requested term ``power failure'' be changed to 
adequately reflect the meaning.
    Response: HHS/CDC agreed with commenters and changed the term to 
``emergency power status.''
    Comment: A commenter stated that ``only modifications in the 
programming sequence that affect how the laboratory reacts in failure 
conditions should be required to be re-tested.'' The commenter further 
suggested that changes or updates such as ``tuning PID loops, updates 
on coefficients that are imbedded in the sequence of operation, or the 
optimization of the logic to reduce the traffic of data in the system, 
should not require re-verification.''
    Response: HHS/CDC made no changes based on this comment. HHS/CDC is 
primarily interested in ensuring that all systems are working as 
designed after any major changes, which is a normal practice to ensure 
the system is fully operational.
    Comment: A commenter suggested that the addition or removal of 
hard-ducted equipment (e.g., biological safety cabinets [BSCs], Class 
III BSC, or decontamination systems) without affecting the airflow 
balance of the room does not affect the operations, therefore no re-
verification should be required.
    Response: HHS/CDC made no changes based on the comment. Additions 
or removals should be tested to ensure repairs were effective even if 
one component was replaced.
    Comment: A commenter stated that the methods for verification of 
primary containment integrity is unclear and needs to be clarified 
(specifically for primary containment of centrifuges and animal caging 
systems). The commenter further requested that the policy state what 
documentation or testing is needed for the verification.
    Response: HHS/CDC made no changes to the policy based on the 
comment since there are no specific tests to determine integrity. 
Centrifuges need to have safety cups and no leaks in the washers to 
ensure integrity of primary containment inside the centrifuge (BMBL 6th 
edition, Inadvertent Toxin Aerosols). Animal cages need to be designed 
to allow recirculation of air into the room after high-efficiency 
particulate air (HEPA) filtration (BMBL 6th edition, Part 3: Biological 
Safety Cabinets). While there are no specific tests to determine 
integrity, HHS/CDC recommends that the entity verifies the animal 
caging systems and centrifuge, and its components, are working as 
designed.
    Comment: Commenters requested to clarify the meaning of BSCs with 
an HVAC connection ``not working properly.'' A commenter asserted that 
the observation or evidence that the BSC is not working properly is 
more of an issue with the certification and maintenance of the 
equipment and not the HVAC system, therefore, it is not a major problem 
and does not require re-verification.
    Response: HHS/CDC agreed with the commenters to clarify the meaning 
of ``not working properly'' and revised the policy to read 
``observation or evidence that BSCs with an HVAC connection (hard duct 
or thimble) are not working as designed.'' HHS/CDC disagreed with the 
commenter regarding reverification. When major repairs are made to the 
BSC including replacing components of the BSC, the entity should test 
the system to ensure repair was effective and does not compromise the 
functionality of the HVAC system.
    Comment: Commenters requested clarification on verifying BAS-
programmed alarm communication as part of the BSL-4/ABSL-4 facility 
verification. One commenter recommended that verification of BAS 
programmed alarms should be tested only initially.
    Response: HHS/CDC did not make any changes based on the comments. 
Verification of the BAS-programmed alarm communication should include 
assurance that if an alarm occurs, the strobes, lights, or audibles are 
activated. Testing annually ensures all parameters that are important 
to maintain containment have a functioning alarm.
    Comment: A commenter provided editorial changes for clarity to 
paragraph A, Effluent, tissue, autoclave, and decontamination systems, 
under section 3 (confirmation that decontamination systems are 
operating as designed [e.g., autoclave, room decontamination systems, 
tissue digesters, liquid effluent systems, and chemical showers]). 
Specifically, the commenter recommended:
     3. A. i: Change to Annual verification that system 
operational parameters have not changed from biologically validated 
conditions (e.g., volume, pressure, temperature settings)
     3. A. iii: Change to Annual certification testing of 
associated HEPA filters, if applicable (e.g., operating vent, pressure 
relief vent, chamber effluent/vent)
     3. A. iv: Change to Annual verification that system 
failure, emergency communication systems are operating as designed 
(e.g., alarms, leak detection)
     3. A. v: Change to Verify appropriate filter media is 
selected and maintained annually (e.g., HEPA, polytetrafluoroethylene 
[PTFE])
    Another commenter agreed that 3. A. v. should be rewritten for 
clarity and stated that the sentence should refer to ``HEPA, however, 
it should instead be revised in terms of efficiency and particle size 
since HEPA filters are at least 99.97% of airport particles 0.3 
micrometers, while PTFE filters have 99.99% efficiency of airborne 
particles 2.5micrometers in diameter.''
     3. A. vi: Another commenter stated that this was unclear 
and needs to be clarified to state specifically what document/test 
needs to be provided to meet this requirement.
    Response: HHS/CDC agreed with the editorial changes, updated the 
policy based on these changes, and clarified 3. A. v. to read ``v. 
Verify appropriate filter media is selected and maintained annually 
(e.g., HEPA, PTFE).'' However, HHS/CDC disagreed with suggestion to 
revise 3. A. iv. ``annual verification that system failure alarms are 
operating as designed'' because the language is clear as written and 
communication is more encompassing than alarms. HHS/CDC agreed with the 
commenter to clarify 3. A. vi. to read, ``Implementation of risk-based 
preventative maintenance for other equipment that is critical to 
containment components, but is not specifically included above (e.g., 
cook tanks, etc.).''
    Comment: A commenter requested to clarify decontamination systems 
by adding decontamination rooms and chambers.
    Response: HHS/CDC made no changes to the policy based on the 
comment because some facilities may not have these rooms or chambers.
    Comment: A commenter responded that room decontamination should be 
validated upon each use and not rely on annual verifications as a 
substitution, since parameters can shift slightly from use to use 
(i.e., atmospheric moisture or room temperature).
    Response: HHS/CDC agreed with commenter; however, no changes were 
made based on this comment since the policy notes that this is an 
annual verification of the room decontamination system and biological 
indicators are already mentioned for this reason.
    Comment: Commenters suggested wording changes for annual 
verification requirement for certification of laboratory HVAC, plumbing 
vent line, and decontamination system filters, stating that there are 
no written standards by which to certify BSL-4/ABSL-4 laboratories.

[[Page 8431]]

    Response: HHS/CDC agreed with the commenters and made the change to 
the policy.
    Comment: A commenter requested that ``established'' specifications 
be changed to ``approved design'' specifications.
    Response: HHS/CDC agreed with the commenter and revised the policy.
    Comment: Commenters requested adding the verification requirement 
for ``pressure decay testing.''
    Response: HHS/CDC agreed with the commenters and included that 
pressure decay testing may be used to identify and confirm proper 
operation of various BSL-4/ABSL-4 containment boundary points of 
failure (e.g., penetrations, cracks, breaks, APR doors, HEPA isolation 
dampers, etc.).

Where can this document be found?

    This policy document is available at the Federal Select Agent 
Program website at www.selectagents.gov.

Legal Authority

    HHS/CDC is issuing this policy under the authority of sections 201-
204 and 221 of Title II of Public Law 107-188, (42 U.S.C. 262a).

Tiffany Brown,
Acting Executive Secretary, Centers for Disease Control and Prevention.
[FR Doc. 2023-02730 Filed 2-8-23; 8:45 am]
BILLING CODE 4163-18-P