[Federal Register Volume 81, Number 11 (Tuesday, January 19, 2016)]
[Proposed Rules]
[Pages 2805-2818]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-00758]



[[Page 2805]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Docket No. CDC-2015-0006]

42 CFR Part 73

RIN 0920-AA59


Possession, Use, and Transfer of Select Agents and Toxins; 
Biennial Review of the List of Select Agents and Toxins and Enhanced 
Biosafety Requirements

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

ACTION: Notice of Proposed Rulemaking (NPRM).

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SUMMARY: In accordance with the Public Health Security and Bioterrorism 
Preparedness and Response Act of 2002 (the Bioterrorism Response Act), 
the Centers for Disease Control and Prevention (CDC) in the Department 
of Health and Human Services (HHS) has reviewed the list of biological 
agents and toxins that have the potential to pose a severe threat to 
public health and safety and proposes to amend and republish the list. 
Specifically, we are proposing to remove six biological agents; add 
provisions to address the inactivation of select agents; add specific 
provisions to the section of the regulations addressing biosafety; and 
clarify regulatory language concerning security, training, incident 
response, and records.

DATES: Submit written or electronic comments by March 21, 2016.

ADDRESSES: You may submit comments, identified by Docket No. CDC-2015-
0006 or RIN 0920-AA59 by any of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
     Mail: Division of Select Agents and Toxins, Centers for 
Disease Control and Prevention, 1600 Clifton Road NE., MS-A46, Atlanta, 
Georgia 30329, Attn: Docket CDC-2015-0006.
    Instructions: All submissions received must include the agency name 
and docket number or Regulatory Information Number (RIN) for this 
rulemaking. All relevant comments received will be posted without 
change to http://regulations.gov, including any personal information 
provided. For access to the docket to read background documents or 
comments received, go to http://www.regulations.gov.
    Comments will also be available for public inspection from Monday 
through Friday, except for legal holidays, from 9 a.m. to 5 p.m., 
Eastern Time, at 1600 Clifton Road NE., Atlanta, Georgia, 30329. Please 
call ahead to (404) 718-2000 and ask for a representative from the 
Division of Select Agents and Toxins to schedule your visit.

FOR FURTHER INFORMATION CONTACT: Dr. Dan Sosin, Acting Director, 
Division of Select Agents and Toxins, Centers for Disease Control and 
Prevention, 1600 Clifton Road NE., MS-A46, Atlanta, Georgia 30329. 
Telephone: (404) 718-2000.

SUPPLEMENTARY INFORMATION: 
    The NPRM is organized as follows:

I. Public Participation
II. Background
    A. Legal Authority
    B. Historical background to this rulemaking
III. Summary of Proposed Changes to 42 CFR part 73
    A. Definitions
    B. Proposed changes to the list of select agents
    C. Inactivation of a Select Agent
    D. Toxins
    E. Exemptions for select agents and toxins
    F. Registration
    G. Responsible Official
    H. Visitor Access to Select Agents and Toxins
    I. Security, Biosafety, and Incident Response Plans
    J. Training
    K. Records
IV. Alternatives Considered
V. Required Regulatory Analyses
    A. Executive Orders 12866 and 13563
    B. The Regulatory Flexibility Act
    C. Paperwork Reduction Act of 1995
    D. EO 12988: Civil Justice Reform
    E. EO 13132: Federalism
    F. Plain Language Act of 2010
VI. References

I. Public Participation

    Interested persons or organizations are invited to participate in 
this rulemaking by submitting written views, recommendations, and data. 
Comments are invited on any topic related to this rulemaking.
    In addition, HHS/CDC invites comments specifically as to whether 
there are biological agents or toxins that should be added or removed 
from the HHS list of select agents and toxins based on the following 
criteria:
    (1) The effect on human health of exposure to the agent or toxin;
    (2) The degree of contagiousness of the agent or toxin and the 
methods by which the agent or toxin is transferred to humans;
    (3) The availability and effectiveness of pharmacotherapies and 
immunizations to treat and prevent any illness resulting from infection 
by the agent or exposure to the toxin; and
    (4) Any other criteria, including the needs of children and other 
vulnerable populations that the commenter considers appropriate.
    HHS/CDC also invites comments on the following questions:
    (1) Are there other methods that should be required to validate the 
rendering of a select agent non-viable or regulated nucleic acids that 
can produce infectious forms of any select agent virus non-infectious?
    (2) Should there be changes to the toxin permissible limits for 
excluded toxins?
    (3) Should Diacetoxyscirpenol (DAS) and T-2 be removed from the 
select toxin list because they do not have the potential to pose a 
severe threat to public health and safety?
    (4) Does seven calendar days provide a sufficient amount of time 
for the entity to destroy or transfer the select agents or toxins after 
identification?
    (5) Are there any specific biosafety measures that should be 
required to prevent laboratory acquired infections (LAIs) or accidental 
release of the select agents and toxins from an entity into the 
community?
    (6) What alternative regulatory requirement could be constructed 
such that a registered entity would know whether it had a theft or loss 
of a select agent or toxin without that registered entity first having 
``an accurate, current inventory for each select agent . . . held in 
long term storage''?
    Comments received, including attachments and other supporting 
materials, are part of the public record and subject to public 
disclosure. Do not include any information in your comment or 
supporting materials that you consider confidential or inappropriate 
for public disclosure. HHS/CDC will carefully consider all comments 
submitted in preparation of a final rule.

II. Background

A. Legal Authority

    HHS/CDC is promulgating this rule under the authority of sections 
201-204 and 221 of Title II of Public Law 107-188, 116 Stat 637 (42 
U.S.C. 262a).

B. Historical Background to This Rulemaking

    Subtitle A of the Public Health Security and Bioterrorism 
Preparedness and Response Act of 2002, (42 U.S.C. 262a), requires HHS 
to regulate the possession, use, and transfer of biological agents or 
toxins that have the potential to pose a severe threat to public health 
and safety (select agents and toxins). Subtitle B of the Public Health 
Security and Bioterrorism Preparedness and Response Act of 2002

[[Page 2806]]

(which may be cited as the Agricultural Bioterrorism Protection Act of 
2002), (7 U.S.C. 8401), requires the United States Department of 
Agriculture (USDA) to regulate the possession, use, and transfer of 
biological agents or toxins that have the potential to pose a severe 
threat to animal or plant health, or animal or plant products (select 
agents and toxins). Accordingly, HHS and USDA have promulgated 
regulations requiring individuals or entities that possess, use, or 
transfer select agents and toxins to register with the CDC or the 
Animal and Plant Health Inspection Service (APHIS). See 42 CFR part 73, 
7 CFR part 331, and 9 CFR part 121 (the select agent regulations). The 
Federal Select Agent Program (FSAP) is the collaboration of the CDC, 
Division of Select Agents and Toxins (DSAT) and the APHIS Agriculture 
Select Agent Services (AgSAS) to administer the select agent 
regulations in a manner that minimizes the administrative burden on 
persons subject to the select agent regulations. The FSAP administers 
the select agent regulations in close coordination with the Federal 
Bureau of Investigation's Criminal Justice Information Services 
Division (CJIS).
    The Bioterrorism Response Act also requires the HHS Secretary to 
establish by regulation a list of biological agents and toxins that 
have the potential to pose a severe threat to public health and safety. 
In determining whether to include an agent or toxin on the list, the 
HHS Secretary considers criteria such as the effect on human health of 
exposure to an agent or toxin; the degree of contagiousness of the 
agent and the methods by which the agent or toxin is transferred to 
humans; the availability and effectiveness of pharmacotherapies and 
immunizations to treat and prevent illnesses resulting from an agent or 
toxin; and the needs of children and other vulnerable populations. The 
current list of HHS select agents and toxins can be found at 42 CFR 
73.3 (HHS select agents and toxins) and 42 CFR 73.4 (Overlap select 
agents and toxins). The list of HHS and Overlap select agents and 
toxins is also available at: http://www.selectagents.gov/SelectAgentsandToxinsList.html.
    The HHS Secretary last republished the list of HHS select agents 
and toxins in the Federal Register on October 5, 2012 (77 FR 61084). 
The list of HHS select agents and toxins is divided into two sections. 
The select agents and toxins listed in section 73.3 (HHS select agents 
and toxins) are those regulated only by HHS under the authority of the 
Bioterrorism Response Act (42 U.S.C. 262a). The select agents and 
toxins listed in section 73.4 (Overlap select agents and toxins) are 
those regulated by HHS under the authority of the Bioterrorism Response 
Act and also regulated by the U.S. Department of Agriculture under the 
authority of the Agricultural Bioterrorism Protection Act of 2002 (7 
U.S.C. 8401).
    The Bioterrorism Response Act requires the HHS Secretary to review 
and republish the list of select agents and toxins on at least a 
biennial basis. Using government subject matter experts, HHS/CDC 
conducts the biennial review process in consultation with the HHS/CDC 
Intragovernmental Select Agents and Toxins Technical Advisory Committee 
(ISATTAC). The ISATTAC is comprised of Federal government employees 
from CDC, Biomedical Advanced Research and Development Authority 
(BARDA) within the Office of the Assistant Secretary for Preparedness 
and Response, the National Institutes of Health (NIH), the Food and 
Drug Administration (FDA), the Department of Homeland Security (DHS), 
the Department of Defense (DOD), the USDA/Animal and Plant Health 
Inspection Service (APHIS), USDA/Agricultural Research Service (ARS), 
and USDA Center for Veterinary Biologics (CVB). Based on the criteria 
outlined in the Bioterrorism Response Act, the ISATTAC considered the 
following criteria in their review of the HHS and Overlap lists of 
select agents and toxins: The degree of pathogenicity (ability of an 
organism to cause disease), communicability (ability to spread from 
infected to susceptible hosts), ease of dissemination, route of 
exposure, environmental stability, ease of production in the 
laboratory, ability to genetically manipulate or alter, long-term 
health effects, acute morbidity (illness), mortality, available 
treatment, status of host immunity, vulnerability of special 
populations, and the burden or impact on the health care system.
    On February 27, 2015, HHS/CDC published an advance notice of 
proposed rulemaking (80 FR 10656) in which we requested public comment 
on (1) whether there are biological agents or toxins that should be 
added or removed from the HHS list of select agents and toxins; and (2) 
whether HHS/CDC should remove the following six select agents from the 
HHS list of select agents and toxins: Coxiella burnetti, Rickettsia 
prowazekii, Bacillus anthracis Pasteur strain, Brucella abortus, 
Brucella melitensis, and Brucella suis.

III. Summary of Proposed Changes

    The following changes to the list of HHS select agents and toxins 
are proposed based on comments received to the advance notice of 
proposed rulemaking (80 FR 10656) referenced above, recommendations 
from the ISATTAC, information from the DHS Material Threat 
Determinations (DHS-MTD) of biological agents and toxins (https://www.medicalcountermeasures.gov/phemce/dhs.aspx), and the expertise of 
federal agencies and staff responsible for the oversight of the 
possession, use, and transfer of select agents and toxins. We are also 
proposing specific changes to the current regulations, as discussed 
below, addressing biosafety; clarifying regulatory language concerning 
security, training, incident response, and records; correcting an 
omission from the technical amendment (appeal process for exclusion); 
and revision of the select agent list with current taxonomic names.

A. Definitions

    We are proposing to add two new terms to section 73.1 (Definitions) 
of the regulations. We are proposing to define the term 
``Inactivation'' as ``a method to render a select agent non-viable but 
retain characteristic of interest for future use, or to render any 
nucleic acids that can produce infectious forms of any select agent 
virus non-infectious for future use.'' We are also proposing to define 
the term ``Kill curve'' as ``the results of a dose-response experiment 
where a select agent is subjected to increasing amounts of the 
inactivating treatment to determine the minimum conditions required to 
render it non-viable or to render any nucleic acids that can produce 
infectious forms of any select agent virus as non-infectious.'' The new 
definitions will help clarify proposed regulatory language in section 
73.12 (Biosafety).

B. Proposed Changes to the List of Select Agents

    On February 27, 2015, HHS/CDC published an advance notice of 
proposed rulemaking (ANPRM) (80 FR 10656) in which we requested public 
comment specifically on whether there are biological agents or toxins 
that should be added or removed from the HHS list of select agents and 
toxins.
    In that same docket, HHS/CDC also requested public comments as to 
whether biological agents specifically listed in the February 27, 2015 
ANPRM should be removed or remain on the list. The listed agents were 
Coxiella burnetti, Rickettsia prowazekii, Bacillus anthracis Pasteur 
strain, Brucella abortus, Brucella melitensis, and Brucella suis. We 
are now proposing that these agents be removed from the

[[Page 2807]]

HHS list of select agents based on the twenty-two comments received in 
response to the February 27, 2015 ANPRM, recommendations from the 
ISATTAC, and our review of current scientific data regarding these 
biological agents.
Coxiella burnetii (42 CFR 73.3)
    In response to the February 27, 2015 ANPRM, we received 11 comments 
concerning Coxiella burnetii. Only two commenters recommended that C. 
burnetii remain on the list because ``antibiotic treatment should not 
be considered for removing the agent.'' The other nine commenters 
argued that C. burnetii should not be included as a select agent based 
on the following assertions:
     Five commenters stated it is not easily transmitted from 
person to person.
     Three commenters referenced that even in the absence of 
antibiotic treatment, Q fever (the disease with acute and chronic 
stages caused by the bacteria C. burnetii) is generally a self-limited 
flu-like illness with low mortality (Ref. 1).
     All commenters acknowledged that most infections are 
inapparent and most seropositive individuals cannot remember an 
infection consistent with Q fever.
     Six commenters agreed that Coxiella is susceptible to a 
number of readily available antibiotics. Preferred treatments include 
tetracycline or doxycycline. Quinolones have also been used 
successfully and Co-trimoxazole is recommended in specific situations 
such as pregnancy.
    The ISATTAC recommended the removal of C. burnetii from the HHS 
list of select agents and toxins because:
     It has a low mortality rate with antibiotic treatment and 
most seropositive individuals cannot remember an infection consistent 
with Q fever (Ref. 2); and
     A whole-cell killed vaccine (Q-Vax) with nearly 100% 
efficacy is licensed in Australia and has been used to vaccinate U.S. 
researchers whom were at risk (Ref. 3).
    We are now proposing to remove C. burnetii from the HHS list of 
select agents (42 CFR 73.3). As discussed above, our proposal is 
supported by comments we received in response to the February 27, 2015 
ANPRM and the recommendations of the ISATTAC. Both the commenters and 
the ISATTAC supported their recommendations with the scientific 
references noted above. We further conclude that, based on recent 
information provided by DHS-MTD, C. burnetii does not pose a severe 
threat to public health and safety. We are, however, still seeking 
comment from those who may believe that C. burnetii remains a severe 
threat to public health and safety and accordingly should be retained 
as a HHS select agent.
Rickettsia prowazekii (42 CFR 73.3)
    In response to the February 27, 2015 ANPRM, we received eight 
comments concerning Rickettsia prowazekii. Only one commenter 
recommended to retain Rickettsia prowazekii because ``antibiotic 
treatment should not be considered for removing the agent.'' The other 
seven commenters supported removal based on the following reasons:
     The risk of mass casualties is low because R. prowazekii 
can be treated with a single dose of doxycycline when symptoms are 
present;
     Transmissibility from person to person is low due to the 
fact that R. prowazekii is usually transmitted via blood, although it 
can be spread through inhalation of louse feces;
     The agent has poor environmental stability; and
     The difficulty in growing and purifying substantial 
quantities of these agents in vitro.
    The ISATTAC recommended the removal of R. prowazekii from the HHS 
list of select agents and toxins because:
     It is treatable with available antibiotics (Ref. 4 and 5);
     The risk of mass casualties is low because R. prowazekii 
can be treated with a single dose of doxycycline when symptoms are 
present (Ref. 4 and 5); and
     Transmissibility from person to person is low due to the 
fact that R. prowazekii is usually transmitted via blood, although it 
can be spread through inhalation of louse feces (Ref. 5).
    We are now proposing to remove R. prowazekii from the HHS list of 
select agents (42 CFR 73.3). As discussed above, our proposal is 
supported by the comments we received in response to the February 27, 
2015 ANPRM and the recommendations of the ISATTAC. Both the commenters 
and the ISATTAC supported their recommendations with the scientific 
references noted above. We further conclude that, based on recent 
information provided by DHS-MTD, R. prowazekii does not pose a severe 
threat to public health and safety. We are, however, still seeking 
comment from those who may believe that R. prowazekii remains a severe 
threat to public health and safety and accordingly should be retained 
as a HHS select agent.
Bacillus anthracis Pasteur Strain (42 CFR 73.4)
    We received six comments to the February 27, 2015 ANPRM with all 
commenters agreeing that Bacillus anthracis Pasteur strain should not 
be included as a select agent based on B. anthracis Pasteur strain 
lacks the plasmid that encodes the toxin genes causing disease. The B. 
anthracis Sterne strain, which lacks the plasmid that encodes for the 
capsule, was excluded from the requirements of the regulations 
effective on February 27, 2003.
    The ISATTAC recommended the removal of B. anthracis Pasteur strain 
from the overlap list of select agents and toxins because:
     B. anthracis Pasteur strain lacks the plasmid that encodes 
the toxin genes causing disease (Ref. 6);
     B. anthracis Sterne strain, which lacks the plasmid that 
encodes for the capsule, was excluded from the requirements of the 
regulations effective on February 27, 2003 (Ref. 7-8); and
     Historically, the B. anthracis Pasteur strain has been 
retained as a select agent to allow for continued oversight of 
laboratories in which the accidental (or intentional) combination of 
this strain with the Sterne strain could occur to produce de novo the 
wild type phenotype B. anthracis. However, a recent study indicates 
that bacterial transformation of B. subtilis with plasmid DNA is 
inefficient; indicating that transformation with plasmid pXO1 into 
closely related bacteria such as the Bacillus anthracis Pasteur strain 
would also be inefficient (Ref. 9).
    We agreed with the commenters and ISATTAC. We propose to remove B. 
anthracis Pasteur strain because the transformation of a virulence 
plasmid from one Bacillus strain to another is difficult.
Brucella abortus, B. melitensis, and B. suis (42 CFR 73.4)
    Responses were received from 16 commenters to the February 27, 2015 
ANPRM, that addressed the retention of the three Brucella species (B. 
abortus, B. melitensis, and B. suis) currently on the overlap select 
agent list. Only two commenters recommended to retain these species 
because ``antibiotic treatment should not be considered for removing 
the agent.'' The other 14 commenters supported removal based on the 
rationale provided in the ANPRM.
    The ISATTAC recommended the removal of B. abortus, B. melitensis, 
and B. suis from the overlap list of select agents and toxins because:
     B. abortus has a low human mortality rate (Ref. 10);

[[Page 2808]]

     B. abortus, B. melitensis, and B. suis are treatable with 
antibiotics (Ref. 10); and
     Human-to-human transmission is extremely rare, and 
wildlife carriers in the United States often come into contact with 
humans without significant transmission (Ref. 10).
    We agreed with the commenters and ISATTAC. We propose to remove B. 
abortus, B. melitensis, and B. suis because although Brucella has a low 
infectious dose, it is treated, mortality is low, efficacy of treatment 
is good for all three Brucella strains.

C. Inactivation of a Select Agent

    We are proposing to add specific requirements to the biosafety 
section of the regulations (42 CFR 73.12) to address the requirements 
for rendering a select agent or an nucleic acids that can produce 
infectious forms of any select agent virus ``non-viable.''
    Sections 73.3 (HHS select agents and toxins) and 73.4 (Overlap 
select agents and toxins) both provide that a ``non-viable'' select 
agent is excluded from the requirements of the select agent 
regulations. We are proposing that for an agent to be ``non-viable,'' 
or to render a nucleic acids that can produce infectious forms of any 
select agent virus non-infectious for future use, an entity must use a 
validated method. A validated method means that the method must be 
scientifically sound such that method will produce consistent results 
each time the method is used. As outlined in our guidance for ``Non-
viable Select Agents and Nonfunctional Select Toxins and Rendering 
Samples Free of Select Agents and Toxins'' (http://www.selectagents.gov/guidance-nonviable.html), an inactivation 
procedure may include (1) use of the exact conditions of an accepted 
method that has been validated, such as autoclaving, (2) a published 
method with adherence to the exact published conditions, or (3) for in-
house methods, validation testing should include the specific 
conditions used and appropriate controls.
    As part of the inactivation procedure, an entity would be required 
to develop a site specific kill curve to identify conditions of 
inactivation for each select agent or regulated nucleic acids that can 
produce infectious forms of any select agent virus. If there are 
strain-to-strain variations in resistance of a select agent to the 
inactivation procedure, then a specific kill curve would be required to 
be developed for each strain that undergoes the inactivation procedure. 
A new kill curve would also be required to be created upon any change 
in procedure or inactivation equipment. In addition, a validated 
sterility testing protocol to ensure that the inactivation method has 
rendered a select agent non-viable or regulated nucleic acids that can 
produce infectious forms of any select agent virus non-infectious would 
be required to be conducted.9ij
    We are also proposing that written records be kept for a select 
agent or extracts that have been subjected to a procedure to render 
them non-viable or regulated nucleic acids that can produce infectious 
forms of any select agent virus that have been subjected to a procedure 
to render them non-infectious.
    We are also soliciting ideas as to whether there are other methods 
that should be required to validate the rendering of a select agent 
non-viable or regulated nucleic acids that can produce infectious forms 
of any select agent virus non-infectious.

D. Toxins

Due Diligence
    Section 73.3(d)(3) of the select agent regulations (42 CFR 
73.(d)(3))specifies the select toxin amounts under the control of a 
principal investigator, treating physician or veterinarian, or 
commercial manufacturer or distributor that are excluded from the 
requirements of the select agent regulations. However, this exclusion 
applies to the transfer of select toxins ``only after the transferor 
uses due diligence and documents that the recipient has a legitimate 
need . . . to handle or use such toxins'' (42 CFR 73.3(d)(3)(i)). This 
provision was added to the select agent regulations to address the 
concern that someone might be able to covertly stockpile toxins by 
receiving multiple orders below the excluded amount. The toxin ``due 
diligence'' provision requires a person transferring toxins in amounts 
which would otherwise be excluded from the provisions to: (1) Use due 
diligence to assure that the recipient has a legitimate need to handle 
or use such toxins; and (2) report to the FSAP if they detect a known 
or suspected violation of Federal law or become aware of suspicious 
activity related to the toxin.
    ``Due diligence'' is generally understood to be such a measure of 
prudence, activity, or assiduity, as is properly to be expected from, 
and ordinarily exercised by, a reasonable and prudent person under the 
particular circumstances; not measured by any absolute standard, but 
depending on the relative facts of the specific case.
    We are proposing to add a more specific documentation requirement 
to the toxin exclusion provision to require the transferor to document 
the identity of the recipient and the legitimate need (i.e., 
prophylactic, protective, bona fide research, or other peaceful 
purpose) claimed by the transferee. Information required to be 
documented would also include the name of the toxin and the total 
amount transferred. Identity information of the person requesting and 
using the toxins would include the individual's name, institution name, 
address, telephone number, and email address.
Toxin Permissible Limits
    In conjunction with this biennial review, the FSAP solicited input 
from biological toxin subject matter experts to review the listed 
exclusion limits for select toxins in the HHS select agent regulations. 
To assess the amount necessary to weaponize a biological toxin, DHS 
developed toxin parameters and attack scenarios for potential 
inhalation and ingestion exposures to select toxins. DHS used the 
formulas described below to estimate ingestion scenarios while 
employing the ``NIST CONTAM Multizone Modeling'' software (http://www.bfrl.nist.gov/IAQanalysis/) for inhalation scenarios. To estimate 
the amount of toxin for each scenario, DHS analyzed a range of release 
sizes (in mg) for each biological toxin in order to estimate the number 
of people that would be exposed to LD-50 (lethal dose, 50% or median 
lethal dose, the amount of the substance required (usually per body 
weight) to kill 50% of the test population); or TD-50 (the median toxic 
dose of a toxin is the dose at which toxicity occurs in 50% of cases) 
levels of each toxin amount by ingestion of milk (using published TD-50 
or LD-50) and/or indoor inhalation (using published LD-50). The 
inhalation models analyzed toxin releases in three different indoor 
public facilities that experience heavy commuter volume (population 
details for these facilities are given in Table 1). One hundred 
scenarios were generated for each facility using 1-10[micro]m particle 
sizes. The models used 10 random locations within each facility 
(potential release locations and population evenly spaced throughout 
occupied area) at 10 random times. The inhalation models assumed:
     No immediate symptoms, so no changes in population 
movement due to attack
     Respiration rate 10L/min
     All people assumed to have the same mass = 70 kg (e.g., 
did not account for lower doses required for children)

[[Page 2809]]



                           Table 1--Summary of Facility Population and Residence Times
----------------------------------------------------------------------------------------------------------------
                                                                                                    Simulation
                                                                    2008 Annual     Simulation       transient
                            Facility                                 passenger       transient        average
                                                                      traffic         hourly      residence time
                                                                     (people)       population       (minutes)
----------------------------------------------------------------------------------------------------------------
High throughput transportation facilities.......................     255,500,000          43,750              10
High throughput transportation facilities.......................     219,000,000          37,500              15
High throughput transportation facilities.......................      64,300,000          11,005              60
----------------------------------------------------------------------------------------------------------------

    The ingestion models investigated biological toxins introduced into 
a fluid (e.g., milk) that was purchased and consumed by consumers over 
a two day period. Production details and specifics of how the toxins 
were introduced were not considered. In particular, the largest 
scenarios involve contaminating greater than ten million servings, 
which was determined to be implausible in practice. The ingestion 
models made the following assumptions:
     Milk containing specified quantity of active toxin (1 mg 
to 1 kg) reaches store shelves.
     Milk is consumed over six days at a uniform rate.
     Contaminated milk is consumed daily until supply is 
depleted or a health advisory is issued.
     Milk contamination discovered and health advisory issued a 
minimum of one day, and a maximum of >1 week post attack (at which 
point all contaminated milk has been consumed).
     For toxins other than saxitoxin and tetrodotoxin, the 
attacker chooses a toxin concentration such that a person in the 45+ 
years old age group will consume 1 LD-50 (or TD-50) over 6 day 
consumption period.
     Since saxitoxin and tetrodotoxin are largely excreted in 
approximately one day after consumption, the attacker chooses a 
saxitoxin or tetrodotoxin concentration such that a person in the 45+ 
years old age group will consume 1 LD-50 (or TD-50) over a one day 
consumption period.
     Total volume of milk contaminated equals the number of 
grams of toxin available divided by the toxin concentration (i.e., 
total volume of milk contaminated depends on the mass of toxin assumed 
to be available (which varies from 1 mg to 1 kg) and the toxin 
ingestion LD-50 (or TD-50)).
     If the toxin ingestion LD-50 (or TD-50) is given by a 
range, the geometric mean of this range is used.
     Range of total volumes of milk contaminated is less than 1 
L to approximately 10\8\ L.
     The amount of milk contaminated is assumed to depend on 
how much toxin the attacker has available (i.e., the total volume of 
milk contaminated equals the number of grams of toxin available divided 
by the toxin concentration). For example, for a 1 g attack, with a 
toxin that has an LD-50 of 1mg/kg, the volume of milk contaminated 
would be 1000 mg/(0.056 mg/mL*1000 mL/L) = 18 L of milk.
     For small attack sizes, it is assumed the attacker would 
target appropriately-sized small holding tanks or containers, while for 
large attack sizes, the attacker would target large holding tanks or 
silos.
     If the toxin is degraded due to pasteurization or storage, 
the amount of toxin introduced pre-processing would have to be 
correspondingly larger than these masses.
Proposed Increase of Regulatory Exclusion Limits
    Based on the data generated by the models described above, we are 
proposing the following exclusion limits based on the amounts estimated 
to expose less than 10 people by inhalation or less than 100 people by 
ingestion to the LD-50 or TD-50 levels of toxin:
     Increase the regulatory exclusion limit of Botulinum 
neurotoxin (BoNT) from 0.5 mg to 1 mg;
     Increase the regulatory exclusion limit of Staphylococcal 
enterotoxins from 5 mg to 100 mg;
     Increase the regulatory exclusion limit of saxitoxin from 
100 mg to 500 mg;
     Increase the regulatory exclusion limit of tetrodotoxin 
from 100 mg to 500 mg;
     Increase the regulatory exclusion limit of abrin from 100 
mg to 1,000 mg;
     Increase the regulatory exclusion limit of ricin from 100 
mg to 1,000 mg; and
     Increase the regulatory exclusion limit of DAS from 1,000 
mg to 10,000 mg.
     Increase the regulatory exclusion limit of T-2 from 1,000 
mg to 10,000 mg.
    We are, however, still seeking comment from those who may believe 
that we should retain the current exclusion limits. In addition, we are 
interested in receiving comments from the public on whether DAS and T-2 
have the potential to pose a severe threat to public health and safety 
or whether these two toxins should be removed from the select toxin 
list given the high exclusion limit for DAS and T-2.
Proposed Removal of Select Toxins
Short, Paralytic Alpha-Conotoxins
    We are proposing short, paralytic alpha-conotoxins containing the 
following amino acid sequence 
(X1CCX2PACGX3X4X5
X6CX7) be removed as a select toxin for the 
following reasons:
     The DHS model reported LD-50 value for inhalation delivery 
of alpha-conotoxin is 20 [micro]g/kg, which is a low toxicity compared 
to other select toxins;
     A regulatory exclusion limit of 10,000 mg would require 
the depletion of the cone snail population to achieve this quantity.
    Therefore, based on the low toxicity of short, paralytic alpha-
conotoxins and the high dosage required for inhalation exposure, we are 
proposing that the alpha-conotoxin be removed from the select toxin 
list (Ref. 32).
Toxins: Exclusion of Original Food Samples and Clinical Samples
    Original food samples and clinical samples are those specimens that 
are submitted to laboratories for diagnosis or verification purposes to 
identify or verify a biological agent or toxin. For example, an 
original food sample could be a container of potato salad or juice. An 
original clinical sample could be serum or stool from a patient. 
Laboratories that test food sample and clinical samples for the 
presence of toxins generally do not know the level of toxin in a sample 
and do not extract and purify a toxin as part of their studies. 
Therefore, we are proposing to exclude the original food sample or 
clinical sample identified to contain an HHS select toxin to be 
consistent with the rationale for the current exclusion for animals 
exposed to toxins (42 CFR 73.3(d)(4)). The proposed exclusion is based 
upon input from biological toxin subject matter experts and our 
determination that quantifying the

[[Page 2810]]

amount of toxin in these samples is problematic because (1) the amount 
of toxin is highly variable, which would require large amounts of food 
and clinical samples to quantify or purify, (2) laboratory procedures 
to extract toxin from samples are inefficient with most extractions 
producing low yields; (3) the resources that would be required to 
quantify toxins in clinical samples and food samples make sample 
quantification prohibitively expensive; and (4) procedures in these 
laboratories, based on the requirements of their public health mission, 
are designed only for toxin detection and not for purification and 
quantification. Therefore, we are interested in comments regarding our 
rationale that the original food sample or clinical sample identified 
to contain an HHS select toxin should be excluded from the select agent 
regulation.
Exclusion of Toxin Produced as a Byproduct
    Laboratories that are only registered for BoNT-producing species of 
Clostridium do not normally have a need to account for BoNT produced 
during the culturing of Clostridium since studying the toxin is not 
part of their work objective. Therefore, we propose to exclude toxins 
that are produced only as a byproduct to a study of the toxin producing 
host organism so long as the toxin has not been intentionally 
collected, purified, or otherwise extracted, and the material 
containing the toxin is inactivated and properly disposed of within 30 
days of the initiation of the culture. The 30 day disposal time was 
recommended by biological toxin subject matter experts based on the 
time it would take to grow the organism and perform the extraction 
process. This exclusion allows laboratories whose purpose does not 
include purification of the toxin to more effectively conduct outbreak 
investigations, food studies, and molecular characterization of agents 
which produce toxin. In the case of BoNT, these laboratories would 
still be regulated for the BoNT-producing species of Clostridium and in 
the case of all other HHS select toxins the laboratories would be 
regulated if they wished to keep the material containing toxins for 
longer than 30 days from the initiation of culture of the toxin 
producing host organism. If at any time an entity manipulated the 
material that contains the select toxin, such as intentional 
collection, purification or extraction of the toxin from culture 
supernatant, such activities would void this exemption, and the entity 
would be required to be registered for the select toxin and meet all 
applicable select agent and toxin regulatory requirements.

E. Exemptions for Select Agents and Toxins

Informing Specimen Provider
    Since a registered or certified reference laboratory typically 
confirms the identification of a select agent or toxin for public 
health and agriculture, clinical and diagnostic laboratories, we are 
proposing to require the registered or certified reference laboratory 
inform the specimen provider of the identification. This will ensure 
that the reference laboratory notifies the specimen provider of the 
identification of the select agent or toxin so that the specimen 
provider is aware that they are in possession of the agent or toxin and 
must meet the requirements outlined in 42 CFR 73.5, 73.6.
Identification of Toxin
    Once a clinical or diagnostic laboratory has identified a select 
toxin-positive specimen, an APHIS/CDC Form 4 (Report of the 
Identification of a Select Agent or Toxin) must be submitted to the 
FSAP. The select agent regulations currently require the laboratory to 
transfer or destroy the material within seven days of identification 
(42 CFR 73.5(a), 73.6(a)) because we determined through input from 
technical experts that the seven calendar days provides a sufficient 
amount of time for the entity to destroy or transfer the select agents 
or toxins after identification. In the past, we have received comments 
that argued that the seven day requirement for transferring or 
destroying select agents or toxins used for diagnosis or testing is too 
short a time limit. Therefore, we are seeking comments to determine if 
seven calendar days provides a sufficient amount of time for the entity 
to destroy or transfer the select agents or toxins after 
identification.
    In addition, we are seeking comments to extend the exemption time 
period to 30 days for BoNT and Staphylococcal enterotoxin (Subtypes A-
E) to allow clinical and diagnostic laboratories sufficient time to 
complete their investigations without having to transfer or destroy the 
sample. Laboratories would still be required to report the 
identification of BoNT immediately and Staphylococcal enterotoxin 
(Subtypes A-E) within seven days. We are proposing to amend the 
language in 42 CFR 73.5(a), and 42 CFR 73.6(a)to read: ``Unless 
directed otherwise by the HHS Secretary, within seven calendar days 
after identification of the select agent and toxin (except for 
Botulinum neurotoxin and/or Staphylococcal enterotoxin (Subtypes A-E)), 
or within thirty calendar days after identification of Botulinum 
neurotoxin and/or Staphylococcal enterotoxin (Subtypes A-E), the select 
agent or toxin is transferred in accordance with Sec.  73.16 or 
destroyed on-site by a recognized sterilization or inactivation 
process,''
Patient Care
    To clarify how the select agent regulations apply to activities 
associated with the diagnosis and care for individuals infected with a 
select agent or exposure to a select toxin, we are proposing to add 
provisions that HHS/CDC will not regulate material containing a select 
agent or toxin when it is in a patient care setting and is not being 
otherwise collected, tested or retained for non-patient care purposes. 
However, once delivery of patient care for an illness associated with a 
select agent or toxin has concluded these specimens would become 
subject to the regulatory requirements. An entity unable to meet all of 
the regulatory requirements necessary to retain the material will then 
have the option of transferring the material containing the select 
agent or toxin in accord with the select agent regulations or 
destroying the materials within seven calendar days of the conclusion 
of patient care.
    We also are proposing to clarify that FSAP does not regulate waste 
generated during the delivery of patient care.

F. Registration

    We are codifying in regulations the current FSAP policy that an 
entity is required to meet all of the regulatory requirements for those 
select agents and toxins listed on the entity's registration regardless 
of whether the select agent or toxin is in the actual possession of the 
entity; and without regard to the actual amounts of toxins in the 
possession of the entity.

G. Responsible Official (RO)

    Section 73.9(a)(6) of the select agent regulations currently states 
that the Responsible Official must ensure that an annual inspection is 
conducted for each laboratory where select agents and toxins are stored 
or used. This requirement also provides that the results of each 
inspection must be documented, and any deficiencies identified during 
an inspection must be corrected. We are adding a requirement that the 
Responsible Official must also document the corrective actions taken by 
the entity to address any identified deficiencies.

[[Page 2811]]

HHS or USDA Office of the Inspector General Hotline
    In response to a recommendation in the December 2014 Federal 
Experts Security Advisory Panel report, we are adding a requirement 
that the Responsible Official must ensure that individuals are provided 
the contact information of the HHS or USDA Office of Inspector General 
Hotline so that individuals are able to anonymously report a safety or 
security concern related to select agents and toxins. In its December 
2014 report, the Federal Experts Security Advisory Panel recommended 
adding a specific requirement to include how individuals are informed 
so that they can access the HHS or USDA Office of Inspector General 
Hotline to anonymously report a safety or security concern.

H. Visitor Access to Select Agents and Toxins

    Section 73.10(e) of the select agent regulations currently provides 
that a person with a valid approval from the HHS Secretary or APHIS 
Administrator to have access to select agents and toxins may request, 
through his or her Responsible Official, that the HHS Secretary or 
APHIS Administrator provide their approved access status to another 
registered individual or entity for a specified period of time. This 
allows a scientist registered to work with a select agent at a 
registered entity to work with the select agent at another registered 
entity. To ensure that the Responsible Official of the entity hosting 
the visitor is aware if a visiting individual loses approval for access 
to select agents and toxins, we are proposing to add a requirement that 
the Responsible Official at the home entity must immediately notify the 
Responsible Official of the visiting entity if the person's access to 
select agents or toxins has been terminated.

I. Security, Biosafety, and Incident Response Plans

    The select agent regulations require a registered entity to develop 
and implement a number of plans in order to ensure the safety and 
security of the select agents they handle. These are:
     A security plan that provides for measures sufficient to 
safeguard the select agent or toxin against unauthorized access, theft, 
loss, or release (42 CFR 73.11);
     A biosafety plan that provides for measures sufficient to 
contain the select agent or toxin (e.g., physical structure and 
features of the entity, and operational and procedural safeguards) (42 
CFR 73.12); and
     An incident response plan that provides for measures that 
the registered entity will implement in the event of theft, loss, or 
release of a select agent or toxin; inventory discrepancies; security 
breaches (including information systems); severe weather and other 
natural disasters; workplace violence; bomb threats and suspicious 
packages; and emergencies such as fire, gas leak, explosion, power 
outage, etc. The response procedures must account for hazards 
associated with the select agent or toxin and appropriate actions to 
contain such agent or toxin. (42 CFR 73.14)
    Drills or exercises must be conducted at least annually to test and 
evaluate the effectiveness of the plans. The plans must be reviewed and 
revised, as necessary, after any drill or exercise and after any 
incident. We are proposing to require that these drills or exercises be 
documented to include how the drill or exercise tested and evaluated 
the plan, any problems identified and corrective actions that were 
taken, and the names of the individuals who participated in the drill 
or exercise. This will provide a more thorough accounting of required 
activities via testing and entity-directed improvements.
    Similar to the existing requirement for the security plan, we are 
also proposing to add a requirement that the biosafety and incident 
response plans be submitted for initial registration, renewal of 
registration, or when requested by FSAP.
Biosafety
    We are proposing to amend the regulatory language in section 73.12 
to update the name change of the National Institutes of Health (NIH) 
Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid 
Molecules (Ref. 31).
    Prior to the publication of the 5th edition of CDC/NIH Biosafety in 
Microbiological and Biomedical Laboratories (Ref. 3), the Occupational 
Safety and Health Administration (OSHA) regulations in 29 CFR 1910.1200 
and 1910.1450 provided specific requirements for handling hazardous 
chemicals in the laboratories. This regulation also provided 
recommendations for safely working with chemical including toxins and 
gave non-mandatory recommendations for prudent practices in 
laboratories handling chemical hazards. As such, we included this 
reference for entities to consider when developing biosafety plans for 
those facilities working with toxins. Since the current edition of the 
CDC/NIH Biosafety in Microbiological and Biomedical Laboratories 
Appendix I provides guidelines for work with toxins of biological 
origin, we have removed the reference to the OSHA regulations in 29 CFR 
1910.1200 and 1910.1450. It should be noted that regulated entities 
must still meet the OSHA regulatory requirements where applicable.
    In addition, we want to ensure that laboratory personnel that are 
working with select agents and toxins are aware of the risks associated 
with these agents. As such, we are proposing to add a requirement that 
a laboratory-specific biosafety manual must be accessible to 
individuals. This is consistent with guidance provided by the CDC/NIH 
publication, Biosafety in Microbiological and Biomedical Laboratories. 
This requirement is proposed to foster an enhanced culture of 
responsibility by ensuring that appropriate biosafety resources are 
available to all staff with access to select agents and toxins within a 
select agent laboratory.
    The current regulations require that the biosafety plan be written 
using performance standards. In the aftermath of recent biosafety 
incidents involving select agents, we are proposing that the biosafety 
plan should be designed according to a site-specific risk assessment in 
accordance with the risk of a select agent, given its intended use by 
adding specific provisions to the biosafety section that would require 
a written risk assessment for each registered select agent or toxin; 
written safety procedures to protect entity personnel, the public, and 
the environment from exposure to the select agent or toxin; written 
decontamination procedures; and written waste management procedures.
    The FSAP would also like to solicit ideas regarding any specific 
biosafety measures that should be required to prevent LAIs or 
accidental or intentional release of the select agents and toxins from 
an entity into the community.
Security
    We are proposing to amend the requirement that the security plan 
contain a description of how the entity authorizes the means of entry 
into areas where select agents or toxins are stored or used, to include 
a requirement that the security plan must include a description of 
centralized access control management systems (e.g., keycards) and/or 
key management (mechanical keys).
    Paragraphs (d)(7)(i) through (d)(7)(v) of section 11 of the select 
agent regulations encompass a list of events that individuals with 
access approval from the APHIS Administrator or the

[[Page 2812]]

HHS Secretary must immediately report to the Responsible Official. We 
are proposing to add a new requirement that the Responsible Official 
must be notified of any loss of computer, hard drive, or other data 
storage device containing information that could be used to gain access 
to select agents or toxins. We believe that such notification will 
facilitate notification of the Federal Bureau of Investigation if 
deemed necessary by the Responsible Official as the loss of such 
equipment may be criminal in nature.

J. Training

    We are proposing to amend section 15 of the select agent 
regulations which concerns the provision of training for staff and 
visitors who work in or visit areas where select agents or toxins are 
handled or stored. Since individuals need to understand hazards 
associated with the select agents and toxins that they will be working 
with in the laboratory or are in the area they will be visiting, we are 
proposing to require that all individuals who have received approval to 
have access to select agents and toxins have training that address the 
particular needs of the individual and the risks posed by the select 
agent or toxin regardless of whether they have access to the select 
agents or toxins. The training would have to be completed within 12 
months of that individual's anniversary of receiving access approval or 
prior to his or her entry into an area where any select agents and 
toxins are used or stored, whichever occurs first. This change is 
necessary in order to codify our policy regarding which individuals at 
registered entities are required to receive training.
    We are also proposing to add a new paragraph (e) to section 15, 
which would require the entity's Responsible Official to provide 
contact information for the USDA or HHS Office of the Inspector General 
Hotline. Details of the proposed addition may be found under the 
heading ``Responsible Official.''

K. Records

    Based on inspections of registered entities, we observed that 
entities are maintaining records of the destruction of select agents 
even though section 73.17 of the select agent regulations currently 
does not include a requirement for documenting when a select agent is 
destroyed. To ensure the proper tracking of a select agent from 
acquisition to destruction and to incorporate into the regulations what 
entities are currently doing, we are proposing to add the requirement 
for records to be created and maintained for the destruction of a 
select agent held in long-term storage to include the quantity (i.e., 
number of vials) of select agent destroyed, the date of such action, 
and by whom.
    Section 73.17 of the select agent regulations currently states that 
records and databases need to be accurate. To ensure that handwritten 
records are accurate, we are proposing to clarify that hand-written 
record must be legible (i.e., capable of being read).
    We are proposing to expand the scope of records required to be 
maintained to include any records that contain information related to 
the requirements of the regulations. Such records may include, but 
would not limited to, biocontainment certifications, laboratory 
notebooks, institutional biosafety and/or animal use committee minutes 
and approved protocols, and records associated with occupational health 
and suitability programs. We propose revision to the regulations will 
enhance the ability of FSAP to evaluate biosafety, security, and 
incident response programs and includes any record created under 
sections 73.5, 73.7, 73.9, 73.11, 73.12, 73.14, 73.15, 73.16, 73.17, 
and 73.19 of the select agent regulations.
Records for Long-term Storage
    The FSAP continues to receive comments that are critical of that 
portion of the select agent regulations that require a registered 
entity to maintain ``an accurate, current inventory for each select 
agent . . . held in long term storage.'' The comments typically focus 
on the belief that a container based inventory requirement is not 
useful to track inventory of biological agents of which small amounts 
of samples from the container could be stolen without detection and 
used to grow larger quantities. In the Public Health Security and 
Bioterrorism Preparedness and Response Act of 2002, Congress requires 
the Secretaries of Health and Human Services and Agriculture to include 
in the select agent regulations a requirement for ``the prompt 
notification of the Secretary, and appropriate Federal, State, and 
local law enforcement agencies, of the theft or loss of listed agents 
and toxins.'' HHS/CDC is soliciting ideas on any alternative regulatory 
requirement that could be constructed such that a registered entity 
would know whether it had a theft or loss of a select agent or toxin 
without that registered entity first having ``an accurate, current 
inventory for each select agent . . . held in long term storage.''

V. Required Regulatory Analyses

A. Executive Orders 12866 and 13563

    Under Executive Order 12866 (EO 12866), Regulatory Planning and 
Review (58 FR 51735, October 4, 1993) HHS/CDC is required to determine 
whether this regulatory action would be ``significant'' and therefore 
subject to review by the Office of Management and Budget (OMB) and the 
requirements of the Executive Orders. This order defines ``significant 
regulatory action'' as any regulatory action that is likely to result 
in a rule that may:
     Have an annual effect on the economy of $100 million or 
more or adversely affect in a material way the economy, a sector of the 
economy, productivity, competition, jobs, the environment, public 
health or safety, or state, local, or tribal governments or 
communities;
     Create a serious inconsistency or otherwise interfere with 
an action taken or planned by another agency;
     Materially alter the budgetary impact of entitlements, 
grants, user fees, or loan programs or the rights and obligations of 
recipients; or,
     Raise novel legal or policy issues arising out of legal 
mandates, the President's priorities, or the principles set forth in EO 
12866.
    Executive Order 13563 (EO 13563), Improving Regulation and 
Regulatory Review, (76 FR 3821, January 21, 2011), updates some of the 
provisions of EO 12866 in order to promote more streamlined regulatory 
actions. This EO charges, in part, that, while protecting ``public 
health, welfare, safety, and our environment'' that regulations must 
also ``promote predictability and reduce uncertainty'' in order to 
promote economic growth. Further, regulations must be written in plain 
language and be easy to understand.
    HHS/CDC has determined that this NPRM is a significant regulatory 
action as defined in EO 12866. However, the Office of Management and 
Budget has waived their review of the document.

B. The Regulatory Flexibility Act (RFA), as Amended by the Small 
Business Regulatory Enforcement Fairness Act (SBREFA)

    We have examined the impacts of the proposed rule under the 
Regulatory Flexibility Act (5 U.S.C. 601-612). Unless we certify that 
the proposed rule is not expected to have a significant economic impact 
on a substantial number of small entities, the Regulatory Flexibility 
Act (RFA), as amended by the Small Business Regulatory Enforcement 
Fairness Act (SBREFA), requires agencies to analyze regulatory

[[Page 2813]]

options that would minimize any significant economic impact of a rule 
on small entities. We certify that this proposed rule will not have a 
significant economic impact on a substantial number of small entities 
within the meaning of the RFA.
    This regulatory action is not a major rule as defined by Sec. 804 
of the Small Business Regulatory Enforcement Fairness Act of 1996. This 
proposed rule will not result in an annual effect on the economy of 
$100,000,000 or more; a major increase in cost or prices; or 
significant adverse effects on competition, employment, investment, 
productivity, innovation, or on the ability of United States-based 
companies to compete with foreign-based companies in domestic and 
export markets.

C. Paperwork Reduction Act of 1995

    In accordance with section 3507(d) of the Paperwork Reduction Act 
of 1995 (44 U.S.C. 3501 et seq.), HHS/CDC has determined that the 
Paperwork Reduction Act does apply to information collection and 
recordkeeping requirements included in this rule. We note that the 
information collection and recordkeeping requirements are already 
approved by the Office of Management and Budget (OMB) under OMB Control 
Number 0920-0576.

D. EO 12988: Civil Justice Reform

    This rule has been reviewed under E.O. 12988, Civil Justice Reform. 
Once the final rule is in effect, HHS/CDC notes that: (1) All State and 
local laws and regulations that are inconsistent with this rule will be 
preempted; (2) No retroactive effect will be given to this rule; and 
(3) Administrative proceedings will not be required before parties may 
file suit in court challenging this rule.

E. EO 13132: Federalism

    HHS/CDC has reviewed this proposed rule in accordance with 
Executive Order 13132 regarding Federalism, and has determined that it 
does not have ``federalism implications.'' The rule does not ``have 
substantial direct effects on the States, on the relationship between 
the national government and the States, or on the distribution of power 
and responsibilities among the various levels of government.''
    In accordance with section 361(e) of the PHSA [42 U.S.C. 264(e)], 
nothing in this rule would supersede any provisions of State or local 
law except to the extent that such a provision conflicts with this 
rule.

F. Plain Language Act of 2010

    Under the Plain Language Act of 2010 (P.L. 111-274, October 13, 
2010), executive Departments and Agencies are required to use plain 
language in documents that explain to the public how to comply with a 
requirement the Federal Government administers or enforces. HHS/CDC has 
attempted to use plain language in promulgating this rule consistent 
with the Federal Plain Writing Act guidelines.

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Toxicology and Pharmacology, July 2014. 70: 197-202.

[[Page 2814]]

List of Subjects in 42 CFR Part 73

    Biologics, Packaging and containers, Penalties, Reporting and 
recordkeeping requirements, Transportation.

    For the reasons discussed in the preamble, we propose to amend 42 
CFR part 73 as follows:

PART 73--SELECT AGENTS AND TOXINS

0
1. The authority citation for part 73 continues to read as follows:

    Authority:  42 U.S.C. 262a; sections 201-2014, 221 and 231 of 
Title II of Public Law 107-188, 116 Stat 637 (42 U.S.C. 262a).

0
2. Section 73.1 is amended by adding in alphabetical order, definitions 
of inactivation and kill curve to read as set forth below.


Sec.  73.1  Definitions.

* * * * *
    Inactivation means a method to render a select agent non-viable but 
retain characteristic of interest for future use, or to render any 
nucleic acids that can produce infectious forms of any select agent 
virus non-infectious for future use.
* * * * *
    Kill curve means the results of a dose-response experiment where a 
select agent is subjected to increasing amounts of the inactivating 
treatment to determine the minimum conditions required to render it 
non-viable or to render any nucleic acids that can produce infectious 
forms of any select agent virus as non-infectious.
* * * * *
0
3. Section 73.3 is amended as follows:
0
a. By revising paragraph (b).
0
b. By adding new paragraphs (d)(2)(i), (ii), and (iii).
0
c. By revising paragraphs (d)(3) introductory text and (d)(3)(i).
0
d. By redesignating paragraph (d)(5) as paragraph (d)(7).
0
e. By adding new paragraphs (d)(5), (d)(6), and (d)(8).
0
f. By adding paragraph (e)(3) to read as set forth below.
    The additions and revisions read as follows:


Sec.  73.3  HHS select agents and toxins.

* * * * *
    (b) HHS select agents and toxins:

Abrin
Botulinum neurotoxins*
Botulinum neurotoxin producing species of Clostridium*
Crimean-Congo hemorrhagic fever virus
Diacetoxyscirpenol
Eastern equine encephalitis virus
Ebola virus*
Francisella tularensis*
Lassa fever virus
Lujo virus
Marburg virus*
Monkeypox virus
Reconstructed replication competent forms of the 1918 pandemic 
influenza A virus containing any portion of the coding regions of all 
eight gene segments (Reconstructed 1918 influenza A virus)
Ricin
SARS coronavirus (SARS-CoV)
Saxitoxin
South American hemorrhagic fever viruses:
Chapare
Guanarito
Junin
Machupo
Sabia
Staphylococcal enterotoxins (subtypes A-E)
T-2 toxin
Tetrodotoxin
Tick-borne encephalitis virus
    Far Eastern subtype
    Siberian subtype
Kyasanur Forest disease virus
Omsk haemorrhagic fever virus
Variola major virus (Smallpox virus) *
Variola minor virus (Alastrim) *
Yersinia pestis*
* * * * *
    (d)* * *
    (2) Non-viable HHS select agents or nonfunctional HHS toxins.
    (i) Unless waived by the HHS Secretary, a select agent or regulated 
nucleic acids that can produce infectious forms of any select agent 
virus that has been subjected to a validated inactivation process to 
remove viability or infectious form (i.e., the ability to reproduce or 
produce disease, while maintaining cellular structure) is not excluded 
from the requirements of this part until an individual or entity:
    (A) Develops a site-specific kill curve to define conditions of 
inactivation for each select agent or regulated nucleic acids that can 
produce infectious forms of any select agent virus. If there are 
strain-to-strain variations in resistance of a select agent to the 
inactivation procedure, then a specific kill curve must be developed 
for each strain that undergoes the inactivation procedure. A new kill 
curve must be created upon any change in procedure or inactivation 
equipment.
    (B) Develops site-specific standard operating inactivation 
procedures to ensure that the material is inactivated by a safety 
margin determined by the kill curve.
    (C) Subjects representative samples of inactivated select agents or 
any nucleic acids that can produce infectious forms of any select agent 
viruses to a validated sterility testing protocol to ensure that the 
inactivation method has rendered the select agent non-viable or 
regulated nucleic acids non-infectious.
    (D) Any viability of a select agent or infectivity of regulated 
nucleic acids that can produce infectious forms of any select agent 
virus that was subjected to a validated inactivation protocol is 
reported to APHIS or CDC.
    (E) Reviews annually, and revises as necessary, the following:
    (1) The kill curve procedure and results;
    (2) Site-specific standard operating procedures to ensure that 
select agents or regulated nucleic acids that can produce infectious 
forms of any select agent virus are inactivated by a safety margin; and
    (3) The validated sterility testing protocol used to ensure that 
the inactivation method has rendered a select agent non-viable or 
regulated nucleic acids that can produce infectious forms of any select 
agent virus sample non-infectious.
    (F) Reviews, and revises as necessary, documents listed in 
paragraph (d)(2)(i)(E) of this section after any change in principal 
investigator, change in protocol, or any reported viability of a select 
agent or infectivity of regulated nucleic acids that can produce 
infectious forms of any select agent viruses previously assessed as 
inactive.
    (ii) Unless waived by the HHS Secretary, an extract from a select 
agent is not excluded from the requirements of this part until an 
individual or entity meets the following requirements:
    (A) Any extract is subjected to a process that removes all viable 
cells, spores, or virus particles.
    (B) Any extract is subjected to a validated sterility testing 
protocol to ensure that the inactivation method has rendered the 
extract free of a select agent.
    (C) Any viability of an extract that was subjected to a validated 
inactivation protocol is reported to the Responsible Official.
    (D) Any viability of a select agent or infectivity of regulated 
nucleic acids that can produce infectious forms of any select agent 
virus that was previously assessed as inactive by their validated 
sterility testing protocol is reported to APHIS or CDC.
    (3) Except as required in Sec.  73.16(l), the aggregate amount of 
the toxin under the control of a principal investigator, treating 
physician or veterinarian, or commercial manufacturer or distributor 
does not, at any time, exceed the following amounts: 1000 mg of Abrin; 
1 mg of Botulinum neurotoxins; 10,000

[[Page 2815]]

mg of Diacetoxyscirpenol; 1000 mg of Ricin; 500 mg of Saxitoxin; 100 mg 
of Staphylococcal enterotoxins (subtypes A-E); 10,000 mg of T-2 toxin; 
or 500 mg of Tetrodotoxin.
    (i) The toxin is transferred only after the transferor uses due 
diligence and documents the identification of the recipient and the 
legitimate need (i.e., prophylactic, protective, bona fide research, or 
other peaceful purpose) claimed by the recipient to use such toxin. 
Information to be documented includes, but is not limited to, the 
recipient identity information, including the recipient's name, 
institution name, address, telephone number and email address; name of 
the toxin and the total amount transferred, and the legitimate need 
claimed by the recipient. Notwithstanding the provisions of paragraph 
(d) of this section, the HHS Secretary retains the authority to, 
without prior notification, inspect and copy or request the submission 
of the due diligence documentation to the CDC.
* * * * *
    (5) An HHS select toxin identified in an original food sample or 
clinical sample.
    (6) Select toxins that are produced as a byproduct in the study of 
the toxin producing host organism so long as the toxin has not been 
intentionally cultivated, collected, purified, or otherwise extracted, 
and the material containing the toxin is rendered non-functional and 
disposed of within 30 days of the initiation of the culture.
* * * * *
    (8) Waste generated during the delivery of patient care from a 
patient infected with a select agent that is decontaminated with a 
validated method within seven calendar days of the conclusion of 
patient care,
    (e) * * *
    (3) An individual or entity may make a written request to the HHS 
Secretary for reconsideration of a decision denying an application for 
the exclusion of an attenuated strain of a select agent or a select 
toxin modified to be less potent or toxic. The written request for 
reconsideration must state the facts and reasoning upon which the 
individual or entity relies to show the decision was incorrect. The HHS 
Secretary will grant or deny the request for reconsideration as 
promptly as circumstances allow and will state, in writing, the reasons 
for the decision.
* * * * *
0
4. Section 73.4 is amended as follows:
0
a. By revising paragraph (b).
0
b. By adding new paragraphs (d)(2)(i), (ii), and (iii).
0
c. By adding paragraph (d)(4).
0
d. By adding paragraph (e)(3).
    The revision and additions read as follows:


Sec.  73.4  Overlap select agents and toxins.

* * * * *
    (b) Overlap select agents and toxins:
Bacillus anthracis*
Burkholderia mallei*
Burkholderia pseudomallei*
Hendra virus
Nipah virus
Rift Valley fever virus
Venezuelan equine encephalitis virus
* * * * *
    (d) * * *
    (2) * * *
    (i) Unless waived by the APHIS Administrator or HHS Secretary, a 
select agent or regulated nucleic acids that can produce infectious 
forms of any select agent virus that has been subjected to a validated 
inactivation process to remove viability or infectious form (i.e., the 
ability to reproduce or produce disease, while maintaining cellular 
structure) is not excluded from the requirements of this part until an 
individual or entity:
    (A) Develops a site-specific kill curve to define conditions of 
inactivation for each select agent or regulated nucleic acids that can 
produce infectious forms of any select agent viruses. If there are 
strain-to-strain variations in resistance of a select agent to the 
inactivation procedure, then a specific kill curve must be developed 
for each strain that undergoes the inactivation procedure. A new kill 
curve must be created upon any change in procedure or inactivation 
equipment.
    (B) Develops site-specific standard operating inactivation 
procedures to ensure that the material is inactivated by a safety 
margin determined by the kill curve.
    (C) Subjects representative samples of inactivated select agents or 
nucleic acids that can produce infectious forms of any select agent 
viruses to a validated sterility testing protocol to ensure that the 
inactivation method has rendered a select agent non-viable or regulated 
nucleic acids non-infectious.
    (D) Reports any viability of a select agent or infectivity of 
regulated nucleic acids that can produce infectious forms of any select 
agent virus that was subjected to a validated inactivation protocol to 
the Responsible Official.
    (E) Reviews annually, and revises as necessary, the following:
    (1) The kill curve procedure and results;
    (2) Site-specific standard operating procedures to ensure that 
select agents or regulated nucleic acids that can produce infectious 
forms of any select agent viruses are inactivated by a safety margin; 
and
    (3) The validated sterility testing protocol used to ensure that 
the inactivation method has rendered a select agent non-viable or 
regulated nucleic acids that can produce infectious forms of any select 
agent viruses non-infectious.
    (F) Reviews, and revises as necessary, documents listed in 
paragraph (d)(2)(i)(E) of this section after any change in principal 
investigator, change in protocol, or any reported viability of a select 
agent or infectivity of regulated nucleic acids that can produce 
infectious forms of any select agent virus previously assessed as 
inactive.
    (ii) Unless waived by the APHIS Administrator or HHS Secretary, an 
extract from a select agent is not excluded from the requirements of 
this part until an individual or entity meets the following 
requirements:
    (A) Any extract is subjected to a process that removes all viable 
cells, spores, or virus particles.
    (B) Any extract is subjected to a validated sterility testing 
protocol to ensure that the inactivation method has rendered the 
extract free of a select agent.
    (C) Any viability of an extract that was subjected to a validated 
inactivation protocol is reported to the Responsible Official.
    (D) Any viability of a select agent or infectivity of regulated 
nucleic acids that can produce infectious forms of any select agent 
virus that was previously assessed as inactive by the validated 
sterility testing protocol is reported to APHIS or CDC.
    (d) * * *
    (4) Waste generated during the delivery of patient care from a 
patient infected with a select agent that is decontaminated with a 
validated method within seven calendar days of the conclusion of 
patient care.
    (e) * * *
    (3) An individual or entity may make a written request to the HHS 
Secretary or APHIS Administrator for reconsideration of a decision 
denying an application for the exclusion of an attenuated strain of a 
select agent or a select toxin modified to be less potent or toxic. The 
written request for reconsideration must state the facts and reasoning 
upon which the individual or entity relies to show the decision was 
incorrect. The HHS Secretary or APHIS Administrator will grant or deny 
the request for reconsideration as promptly as circumstances allow and 
will state, in writing, the reasons for the decision.
* * * * *

[[Page 2816]]

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5. Section 73.5 is amended as follows:
0
a. By revising paragraph (a)(1).
0
b. By redesignating paragraph (a)(3) as paragraph (a)(4) and revising 
newly redesignated paragraph (a)(4).
0
c. By adding new paragraph (a)(3).
    The revisions and addition read as follows:


Sec.  73.5  Exemptions for HHS select agents and toxins.

    (a) * * *
    (1) Unless directed otherwise by the HHS Secretary, within seven 
calendar days after identification of the select agent and toxin 
(except for Botulinum neurotoxin and/or Staphylococcal enterotoxin 
(Subtypes A-E)), or within thirty calendar days after identification of 
Botulinum neurotoxin and/or Staphylococcal enterotoxin (Subtypes A-E), 
the select agent or toxin is transferred in accordance with Sec.  73.16 
or destroyed on-site by a recognized sterilization or inactivation 
process,
* * * * *
    (3) Unless otherwise directed by the HHS Secretary, the clinical or 
diagnostic specimens collected from a patient infected with a select 
agent are transferred in accordance with Sec.  73.16 or destroyed on-
site by a recognized sterilization or inactivation process within seven 
days after delivery of patient care has concluded, and
    (4) The identification of the agent or toxin is reported to CDC or 
APHIS, the specimen provider, and to other appropriate authorities when 
required by Federal, State, or local law by telephone, facsimile, or 
email. This report must be followed by submission of APHIS/CDC Form 4 
to APHIS or CDC within 7 calendar days after identification.
* * * * *
0
6. Section 73.6 is amended as follows:
0
a. By redesignating paragraph (a)(3) as paragraph (a)(4) and revising 
newly redesignated paragraph (a)(4).
0
b. By adding paragraph (a)(3).
    The revision and addition read as follows:


Sec.  73.6  Exemptions for overlap select agents and toxins.

    (a) * * *
    (3) Unless otherwise directed by the HHS Secretary or 
Administrator, the clinical or diagnostic specimens collected from a 
patient infected with a select agent are transferred in accordance with 
Sec.  73.16 or destroyed on-site by a recognized sterilization or 
inactivation process within seven days after delivery of patient care 
has concluded, and
    (4) The identification of the agent or toxin is reported to CDC or 
APHIS, the specimen provider, and to other appropriate authorities when 
required by Federal, State, or local law by telephone, facsimile, or 
email. This report must be followed by submission of APHIS/CDC Form 4 
to APHIS or CDC within 7 calendar days after identification.
* * * * *
0
7. Section 73.7 is amended as follows:
0
a. By redesignating paragraphs (b) through (k) as paragraphs (c) 
through (l), respectively.
0
b. By adding a new paragraph (b) to read as follows:


Sec.  73.7  Registration and related security risk assessments.

* * * * *
    (b) As a condition of registration, each entity is required to be 
in compliance with the requirements of this part for select agents and 
toxins listed on the registration regardless of whether the entity is 
in actual possession of the select agent or toxin. With regard to 
toxins, the entity registered for possession, use or transfer of a 
toxin must be in compliance with the requirements of this part 
regardless of the amount of toxin currently in possession.
* * * * *
0
8. Section 73.9 is amended as follows:
0
a. In paragraph (a)(6) by removing ``laboratory'' and adding in its 
place ``registered space'' and adding ``and the corrections 
documented'' after ``corrected'' at the end of the sentence.
0
b. By adding paragraph (a)(7) to read as set forth below.


Sec.  73.9  Responsible Official.

    (a) * * *
    (7) Ensure that individuals are provided the contact information 
for the HHS or USDA Office of Inspector General Hotline so that they 
may anonymously report any safety or security concerns related to 
select agents and toxins.
* * * * *
0
9. Section 73.10 is amended by adding a new sentence to the end of 
paragraph (e) to read as follows:


Sec.  73.10  Restricting access to select agents and toxins; security 
risk assessments.

* * * * *
    (e) * * * A Responsible Official must immediately notify the 
Responsible Official of the visited entity if the person's access to 
select agents and toxins has been terminated.
* * * * *
0
10. Section 73.11 is amended as follows:
0
a. In paragraph (c)(5) by adding ``keycards,'' between ``keys,'' and 
``passwords'' and removing ``numbers'' and adding in its place 
``permissions''.
0
b. By adding paragraph (c)(11).
0
c. By adding paragraph (d)(7)(vi).
0
d. By adding a sentence to the end of paragraph (h).
    The additions read as follows:


Sec.  73.11  Security.

* * * * *
    (c) * * *
    (11) Describe how the entity authorizes the means of entry into 
areas where select agents or toxins are stored or used, to include 
centralized access control management systems (e.g., keycards) and/or 
mechanical key management.
    (d) * * *
    (7) * * *
    (vi) Any loss of computer, hard drive or other data storage device 
containing information that could be used to gain access to select 
agents or toxins.
* * * * *
    (h) * * * Drills or exercises must be documented to include how the 
drill or exercise tested and evaluated the plan, any problems that were 
identified and corrective action(s) taken, and all individuals who 
participated in the drill or exercise.
0
11. Section 73.12 is amended as follows:
0
a. By revising paragraph (a).
0
b. By removing paragraph (c)(2), redesignating paragraph (c)(3) as 
(c)(2), and in newly redesignated paragraph (c)(2), removing ``NIH 
Guidelines for Research Involving Recombinant DNA Molecules'' and 
adding in its place ``NIH Guidelines for Research Involving Recombinant 
or Synthetic Nucleic Acid Molecules''.
0
c. By adding a new sentence to the end of paragraph (e).
    The revision and addition read as follows:


Sec.  73.12  Biosafety.

    (a) An individual or entity required to register under this part 
must develop and implement a written biosafety plan that is 
commensurate with the risk of the select agent or toxin, given its 
intended use. The biosafety plan must contain sufficient information 
and documentation to describe the biosafety and containment procedures 
for the select agent or toxin, including any animals (including 
arthropods) or plants intentionally or accidentally exposed to or 
infected with a select agent. Biosafety and containment procedures 
specific to each registered laboratory must be available to each 
individual working in that laboratory. The current biosafety plan must 
be submitted for initial registration, renewal of registration, or

[[Page 2817]]

when requested. The biosafety plan must include the following 
provisions:
    (1) A written risk assessment for each procedure involving a select 
agent or toxin that addresses the hazards associated with the agent or 
toxin.
    (i) The hazardous characteristics of each agent or toxin listed on 
the entity's registration, including probable routes of transmission in 
the laboratory and in the environment, infective dose (if known), 
stability in the environment, host range, contribution of any genetic 
manipulations, and endemicity.
    (ii) Hazards associated with laboratory procedures related to the 
select agent or toxin;
    (2) Safeguards in place with associated work practices to protect 
registered entity personnel, the public, and the environment from 
exposure to the select agent or toxin including, but not limited to: 
Safety training requirements for registered entity personnel performing 
the procedure; required personal protective equipment and other safety 
equipment; required containment equipment including, but not limited 
to, biological safety cabinets, animal caging systems, and centrifuge 
safety containers; and required engineering controls and other facility 
safeguards.
    (3) Written procedures for decontamination with a validated method, 
of all contaminated or potentially contaminated materials including, 
but not limited to: Cultures and other materials related to the 
propagation of select agents or toxins, items related to the analysis 
of select agents and toxins, personal protective equipment, animal 
caging systems and bedding, and animal carcasses or extracted tissues.
    (4) Written procedures for decontamination, with a validated 
method, of laboratory surfaces and equipment using manufacturer's 
specification.
    (5) Effluent decontamination procedures, with a validated method, 
that describe the treatment of effluent material contaminated with 
select agents and toxins.
    (6) Procedures to respond to emergencies such as spills, sharps 
injury, or animal bites involving select agents and toxins.
    (7) Procedures for the handling of select agents and toxins in the 
same spaces with non-select agents and toxins in order to prevent 
unintentional contamination.
* * * * *
    (e) * * * Drills or exercises must be documented to include how the 
drill or exercise tested and evaluated the plan, any problems that were 
identified and corrective action(s) taken, and all individuals who 
participated in the drill or exercise.
0
12. Section 73.14 is amended as follows:
0
a. By adding a new sentence to the end of paragraph (a).
0
b. By adding a new sentence to the end of paragraph (f).
    The additions read as follows:


Sec.  73.14  Incident response.

    (a) * * * The current incident response plan must be submitted for 
initial registration, renewal of registration, or when requested.
* * * * *
    (f) * * * Drills or exercises must be documented to include how the 
drill or exercise tested and evaluated the plan, any problems that were 
identified and corrective action(s) taken, and all individuals who 
participated in the drill or exercise.
0
13. Section 73.15 is amended as follows:
0
a. In paragraph (a)(1) by removing ``before that individual has such 
access to select agents and toxins'' and adding in its place ``, within 
12 months of that individual's anniversary of receiving such approval 
or prior to his or her entry into an area where select agents or toxins 
are used or stored, whichever occurs first.''.
0
b. By adding paragraph (e) to read as set forth below.


Sec.  73.15  Training.

* * * * *
    (e) The Responsible Official must ensure and document that 
individuals are provided the contact information of the HHS or USDA 
Office of Inspector General Hotline so that they may anonymously report 
any safety or security concerns related to select agents and toxins.
0
14. Section 73.16 is amended by revising paragraph (l)(1) to read as 
follows:


Sec.  73.16  Transfers.

* * * * *
    (l) * * *
    (1) Transfer the amounts only after the transferor uses due 
diligence and documents that the recipient has a legitimate need (i.e., 
prophylactic, protective, bona fide research, or other peaceful 
purpose) to handle or use such toxins. Information to be documented 
includes, but is not limited, to the recipient information, toxin and 
amount transferred, and declaration that the recipient has legitimate 
purpose to store and use such toxins.
* * * * *
0
15. Section 73.17 is amended as follows:
0
a. In paragraphs (a)(1)(iii) and (a)(3)(v) by adding ``or other storage 
container'' after ``freezer''.
0
b. By adding paragraph (a)(1)(ix).
0
c. By adding paragraph (a)(8).
0
d . In paragraph (b) by adding ``legible,'' after ``are''.
0
e. By revising paragraph (c).
    The revision and additions read as follows:


Sec.  73.17  Records.

    (a) * * *
    (1) * * *
    (ix) If destroyed, the quantity (e.g., containers, vials, tubes, 
etc.) of select agent destroyed, the date of such action, and by whom.
* * * * *
    (8) For a select agent or an extract from a select agent that has 
been rendered non-viable or regulated nucleic acids that can produce 
infectious forms of any select agent virus that have been rendered non-
infectious through inactivation:
    (i) A written description of the inactivation process used for 
rendering a select agent non-viable or regulated nucleic acids that can 
produce infectious forms of any select agent virus non-infectious;
    (ii) The sterility testing protocol used to verify non-viability of 
a select agent or non-infectivity of regulated nucleic acids that can 
produce infectious forms of any select agent virus and the results of 
the test, including investigation, of any inactivation process failures 
and the corrective actions taken;
    (iii) The name of each individual performing the inactivation 
method and sterility testing protocols;
    (iv) The date(s) the inactivation method and sterility testing 
protocols were completed;
    (v) The location where the inactivated method and sterility testing 
protocols were performed; and
    (vi) An inactivation certificate that includes the date of 
inactivation, method of inactivation, date of final sterility testing 
protocol result, and the Principal Investigator. A copy of the 
inactivation certificate must accompany any transfer of inactivated 
material.
* * * * *
    (c) Any records that contain information related to the 
requirements of the regulations. Such records may include, but are not 
limited to, biocontainment certifications, laboratory notebooks, 
institutional biosafety and/or animal use committee minutes and 
approved protocols, and records associated with occupational

[[Page 2818]]

health and suitability programs. All records created under this part 
must be maintained for 3 years.
* * * * *

    Dated: January 12, 2016.
Sylvia M. Burwell,
Secretary.
[FR Doc. 2016-00758 Filed 1-14-16; 4:15 pm]
 BILLING CODE 4163-18-P