[Federal Register Volume 82, Number 12 (Thursday, January 19, 2017)]
[Rules and Regulations]
[Pages 6278-6294]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-00726]


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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: Final rule.

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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. Following the review, HHS has decided: Not to 
finalize the proposed changes to the list of select agents and toxins 
at this time; to finalize provisions to address toxin permissible 
limits and the inactivation of select agents; to finalize specific 
provisions to the section of the regulations addressing biosafety; and 
to clarify regulatory language concerning security, training, incident 
response, and records. In a companion document published in this issue 
of the Federal Register, the U.S. Department of Agriculture (USDA) has 
made parallel regulatory changes.

DATES: Effective February 21, 2017.

FOR FURTHER INFORMATION CONTACT: Dr. Samuel S. Edwin, Director, 
Division of Select Agents and Toxins, Centers for Disease Control and 
Prevention, 1600

[[Page 6279]]

Clifton Road NE., MS-A46, Atlanta, Georgia 30329. Telephone: (404) 718-
2000.

SUPPLEMENTARY INFORMATION: The preamble to this final rule is organized 
as follows:

I. Executive Summary
II. Changes to 42 CFR Part 73
    A. Modifications to the List of HHS and Overlap Select Agents 
and Toxins
    B. Responses to Other Proposed Changes
    i. Definitions
    ii. Inactivation of a Select Agent
    iii. Toxins
    iv. Exclusion Involving Patient Care
    v. Exemptions for Select Agents and Toxins
    vi. Registration
    vii. Responsible Official
    viii. Visitor Access to Select Agents and Toxins
    ix. Security, Biosafety, and Incident Response Plans
    x. Training
    xi. Records
III. Alternatives Considered
IV. Required Regulatory Analyses
    A. Executive Orders 12866 and 13563
    B. The Regulatory Flexibility Act
    C. Paperwork Reduction Act of 1995
    D. E.O. 12988: Civil Justice Reform
    E. E.O. 13132: Federalism
    F. Plain Language Act of 2010
V. References

I. Executive Summary

    On February 27, 2015 we published an Advance Notice of Proposed 
Rulemaking (ANPRM) (80 FR 10656) that initiated the required biennial 
review and republication of the HHS list of select agents and toxins. 
The ANPRM solicited public comments regarding whether any biological 
agents and toxins 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 considered appropriate.
    This notice also asked for public comment on whether HHS should 
remove the following agents from the HHS list of select agents and 
toxins: Coxiella burnetii, Rickettsia prowazekii, Bacillus anthracis 
Pasteur, Brucella abortus, B. melitensis, and B. suis.
    On January 19, 2016, we published a Notice of Proposed Rulemaking 
(NPRM) (81 FR 2805). The NPRM solicited public comments regarding 
whether any biological agents and toxins should be added or removed 
from the HHS list of select agents and toxins based on the same 
criteria used in ANPRM:
    We also invited comments on the following:
    (1) 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 as non-infectious;
    (2) Proposed changes to the aggregate amount of toxin excluded from 
the requirements of the select agent regulations;
    (3) Removal of Diacetoxyscirpenol (DAS) and T-2 from the list;
    (4) Whether seven calendar days provides a sufficient amount of 
time for the entity to destroy or transfer a select agent or toxin 
after identification;
    (5) 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; and
    (6) Alternative regulatory requirements 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.''
    (7) Whether short, paralytic alpha-conotoxins containing the 
following amino acid sequence 
(X1CCX2PACGX3X4X5
X6CX7), C. burnetii, R. prowazekii, B. anthracis 
Pasteur, B. abortus, B. melitensis, and B. suis should be removed from 
the HHS list of select agents and toxins.
    We received 22 public comments to the ANPRM and 35 public comments 
to the NPRM that addressed the composition of the HHS list of select 
agents and toxins. After carefully considering the technical input of 
subject matter experts, both within the Federal government and from 
public comments, and recommendations from Federal advisory groups, we 
have decided not to finalize the proposed changes to the list of select 
agents and toxins at this time. Upon further consideration, we may 
decide to finalize changes to the list at a future time.
    This final rule makes the following changes to current regulations:
    1. New provisions regarding the inactivation of select agents, 
specific biosafety requirements, and toxin requirements;
    2. Other revisions to the regulations to clarify regulatory 
language concerning security, training, and records.
    3. In addition, when HHS added B. cereus Biovar anthracis to the 
list of HHS select agents and toxins on September 14, 2016 by an 
interim final rule (81 FR 63138), we neglected to add the name of the 
agent to the immediate notification list for Tier 1 agents in sections 
5 and 9 of the regulations. We are correcting that error in this final 
rule.
    Costs of the Rule: The entities affected by this final rule include 
research and diagnostic facilities; Federal, State, and university 
laboratories; and private commercial and non-profit enterprises. The 
current regulations require registering for the possession, use, and 
transfer of select agents or toxins. In addition, the entity is 
currently required to ensure that the facility where the agent or toxin 
is housed has adequate biosafety and containment measures; that the 
physical security of the premises is adequate to prevent unauthorized 
access; that all individuals with approved access to select agents or 
toxins have the appropriate education, training, and/or experience to 
handle such agents or toxins; and that complete records concerning 
activities related to the select agents or toxins are maintained.
    The HHS final rule will further reduce or minimize the risk of 
misuse of select agents and toxins that have the potential to pose a 
severe threat to human health. HHS recognizes that several of the 
required measures of the regulations may impose certain operational 
costs upon affected entities. Specifically, the rule will clarify that 
an entity must use a validated method to render a select agent non-
viable or a regulated infectious nucleic acid sample non-infectious for 
future use. This means the method must be scientifically sound and 
produce consistent results each time it is used. Appropriate reporting 
and record keeping is required in order to mitigate threats to human 
health. In many cases, however, the affected entities already employ 
some or all of the required measures. Compliance costs actually 
incurred will therefore vary from one entity to the next.
    While information on the specific changes that would need to occur 
at individual sites and the associated costs was not readily available 
during proposed rulemaking, some general observations regarding the 
potential costs were presented. These general cost observations can be 
found in the Regulatory Impact Analysis. Based on the current 
recordkeeping and reporting requirements, an additional 10 to 20 hours 
per year may be required by entities. At an imputed cost of $33.40 per 
hour, this additional time

[[Page 6280]]

requirement per entity will total between $334 and $668 per year, or in 
total for all registered entities between $80,000 and $160,000.
    Benefits: The objectives of the HHS final rule are to create a 
means of ensuring enhanced oversight in the transfer, storage, and use 
of select agents and toxins; clarify that an entity must use a 
validated method to render a select agent non-viable or a regulated 
infectious nucleic acid sample non-infectious for future use; and 
require that entities in possession of such agents and toxins develop 
and implement effective means of biosafety, information security, and 
physical security. The overall benefit of the amended regulatory 
provisions will be a reduced likelihood of the accidental or 
intentional release of a select agent or toxin; and the avoidance of 
human morbidity, mortality and the economic loss associated with such a 
release. The goal of the amended regulations is to enhance the 
protection of human health and safety.

II. Changes to 42 CFR Part 73

    The table below describes the changes to the current regulation.

------------------------------------------------------------------------
      Section No.             Section title               Change
------------------------------------------------------------------------
73.0...................  Applicability and        No changes.
                          related requirements.
73.1...................  Definitions............  Adds definitions:
                                                   Validated
                                                   inactivation
                                                   procedure and
                                                   viability testing
                                                   protocol.
73.2...................  Purpose and scope......  No changes.
73.3...................  HHS select agents and    Clarifies language to
                          toxins.                  include addition of
                                                   B. cereus Biovar
                                                   anthracis and adds
                                                   new paragraphs.
73.4...................  Overlap select agents    Clarifies language to
                          and toxins.              include addition of
                                                   B. cereus Biovar
                                                   anthracis and adds
                                                   new paragraphs.
73.5...................  Exemptions for HHS       Clarifies language;
                          select agents and        redesignates
                          toxins.                  paragraph; and adds
                                                   new paragraph.
73.6...................  Exemptions for overlap   Clarifies language;
                          select agents and        redesignates
                          toxins.                  paragraph; and adds
                                                   new paragraph.
73.7...................  Registration and         Redesignates
                          related security risk    paragraphs; adds new
                          assessments.             paragraph.
73.8...................  Denial, revocation, or   No changes.
                          suspension of
                          registration.
73.9...................  Responsible Official...  Clarifies language to
                                                   include addition of
                                                   B. cereus Biovar
                                                   anthracis and adds
                                                   new paragraphs.
73.10..................  Restricting access to    Clarifies language.
                          select agents and
                          toxins; security risk
                          assessments.
73.11..................  Security...............  Clarifies language and
                                                   adds new paragraph.
73.12..................  Biosafety..............  Clarifies language.
73.13..................  Restricted experiments.  No changes.
73.14..................  Incident response......  Clarifies language.
73.15..................  Training...............  Clarifies language and
                                                   adds new paragraph.
73.16..................  Transfers..............  Clarifies language.
73.17..................  Records................  Clarifies language and
                                                   adds new paragraph.
73.18..................  Inspections............  No changes.
73.19..................  Notification of theft,   No changes.
                          loss, or release.
73.20..................  Administrative review..  No changes.
73.21..................  Civil money penalties..  No changes.
------------------------------------------------------------------------

A. Modifications to the List of HHS and Overlap Select Agents and 
Toxins

    We received 22 public comments to the ANPRM and 35 public comments 
to the NPRM that addressed the composition of the HHS list of select 
agents and toxins. After carefully considering the technical input of 
subject matter experts, both within the Federal government and from 
public comments, and recommendations from Federal advisory groups, we 
have decided not to finalize the proposed changes to the list of select 
agents and toxins at this time.

B. Responses to Other Proposed Changes

i. Definitions
    It recently became clear that some inactivation protocols have 
failed to inactivate B. anthracis spores completely, as evidenced by 
inactivation failures that led to the inadvertent transfer of 
potentially live B. anthracis samples by the Department of Defense in 
2015. In response to this incident, new requirements were proposed to 
address the inactivation of select agents. We proposed adding 
definitions for the terms ``inactivation'' and ``kill curve'' to 
clarify the new inactivation provisions. As discussed below, we have 
removed the proposed requirement for a ``kill curve,'' and accordingly, 
we have also removed the proposed definition of ``kill curve.''
    To exclude a select agent or regulated nucleic acids that can 
produce infectious forms of any select agent virus from the 
requirements of the select agent regulations, an entity will need to 
subject the select agent or the nucleic acids to a validated 
inactivation procedure whose efficacy is confirmed through a viability 
testing protocol.
    Commenters stated that additional definitions should be provided 
for ``validated inactivation procedure,'' ``sterility testing 
protocol,'' and ``safety margin.'' We agree with the commenters and are 
defining the terms as described below. ``Validated inactivation 
procedure'' means ``a procedure, whose efficacy is confirmed by data 
generated from a viability testing protocol, to render a select agent 
non-viable but allows the select agent to retain characteristics 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.''
    Further, we have not included a separate definition for 
``inactivation'' as it is now captured in the definition of ``validated 
inactivation procedure.''
    We have changed the proposed phrase ``sterility testing protocol'' 
to ``viability testing protocol'' and defined the latter as ``a 
protocol to confirm the validated inactivation procedure by 
demonstrating the material is free of all viable select agent.'' This 
change reflects the intent that the validated inactivation procedure, 
or the procedure for removal of viable select agents from material

[[Page 6281]]

containing select agents, must render the material non-viable (i.e., 
unable to replicate). In addition, any nucleic acids that can produce 
infectious forms of any select agent virus must be rendered non-
infectious for future use.
    We are choosing to not define the term ``safety margin'' and have 
incorporated the concept of a performance standard instead.
    The new definitions will help clarify the regulatory language found 
in 42 CFR 73.3, 73.4.
ii. Inactivation of a Select Agent
    Historical inactivation failures by registered entities required us 
to focus on ways to increase the certainty that inactivated select 
agents intended for further use do not contain live agent. This is 
particularly important when the inactivation methods are tempered in 
order to avoid disrupting some of the physical characteristics of the 
agent. We proposed adding specific requirements to the exclusion 
sections of the regulations (42 CFR 73.3(d), 73.4(d)) to address the 
requirements for rendering select agents, nucleic acids that can 
produce infectious forms of any select agent virus, or extracts from 
select agents non-viable.
    Sections 73.3(d)(2) (HHS select agents and toxins) and 73.4(d)(2) 
(Overlap select agents and toxins) both provide that a non-viable 
select agent is excluded from the requirements of the select agent 
regulations. We proposed that for a select agent to be non-viable or to 
render nucleic acids that can produce infectious forms of any select 
agent virus non-infectious for future use, an entity must use a 
validated inactivation procedure. Commenters stated there is some 
confusion between inactivation validation requirements for moving 
materials to a lower containment level and inactivation validation 
requirements for waste disposal. We are clarifying that these 
provisions apply to a select agent that is inactivated for future use 
as a non-select agent and is not intended for material for waste 
disposal.
    Many commenters stated that the focus on strengthening inactivation 
requirements was being driven by an incorrect public perception of 
recent procedural errors that occurred at federally run research 
laboratories. Without commenting on what is or might be the public's 
perception with regard to inactivation problems, we disagree with these 
comments because the focus on inactivation failures with select agents 
is based on the realization that past inactivation activities have 
proved to be inadequate.
    We proposed that an entity would be required to develop a site-
specific kill curve to identify conditions of inactivation for each 
select agent. Commenters stated that although the generation of kill 
curves is appropriate for inactivation procedures using heat, 
irradiation and filtration, it is not generally applicable to 
determining infectivity of nucleic acids. Commenters stated that for 
inactivation procedures where a ``kill curve is not applicable, 
inactivation conditions are selected and then replicated to obtain 100% 
inactivation within a statistical certainty.''
    We agree with the commenters and are withdrawing the proposal to 
require a kill curve and safety margin because these would not be 
applicable to all inactivation procedures. Further, the variety of 
agents and inactivation procedures makes it likely that prescriptive 
requirements would have unintended negative consequences on research. 
We are, nonetheless, finalizing requirements for a validated 
inactivation procedure and viability testing. We are requiring that for 
a select agent or regulated nucleic acid that can produce infectious 
forms of any select agent virus to be excluded from the requirements of 
the select agent regulations, an entity will be responsible for 
achieving a certain performance standard that is confirmed through a 
viability testing protocol. Surrogate strains that are known to possess 
equivalent properties with respect to inactivation can be used to 
validate an inactivation procedure. However, if there are known strain-
to-strain variations in the resistance of a select agent to an 
inactivation procedure, then an inactivation procedure validated on a 
lesser resistant strain must also be validated on the more resistant 
strains. Additional guidance regarding this performance standard has 
been developed and is available at www.selectagents.gov.
    Many commenters asked HHS to state clearly if the standard for 
select agent inactivation is complete sterility (i.e., not a single 
viable pathogen in the entire volume of an inactivated sample), a log 
reduction in viable pathogen titer, or the limit of detection of the 
assay. We agree that it is important to specify the intent of the 
performance standard. HHS recognizes the limits of detection of the 
viability testing procedures (related to the detection assay and the 
sampling of inactivated material) and expected run-to-run variation 
when following an inactivation procedure precisely precludes 
demonstrating full sterility of inactivated material. These sources of 
error must be considered when establishing performance parameters for 
inactivation procedures. While complete sterility is not a feasible 
goal for material that is intended for further use, HHS expects that 
the risk of live agent in inactivated materials will be as low as 
realistically possible from both a safety and security perspective.
    We proposed that entities subject representative samples of an 
inactivated select agent to a validated sterility testing protocol to 
ensure that the inactivation procedure has rendered the select agent 
non-viable. Commenters stated that it is not always practical to 
conduct validation on each sample that is inactivated. Often samples 
are in limited quantities and validation studies will leave very little 
or no sample for the experimental purpose. Commenters also stated that 
the requirement to subject representative samples to sterility testing 
using a validated protocol requires further clarification. Commenters 
stated that it is reasonable to require this type of testing when the 
inactivation procedure is first established and if any changes to the 
inactivation protocol are made. However, commenters stated that it 
cannot be reasonably done on each sample in laboratory research if the 
inactivation protocol has not changed. They stated that implementing 
such a requirement would waste specimens where limited volumes are 
available, would be costly in terms of technical time and resources, 
and is scientifically unjustified.
    We agree with the commenters that the varied needs and conditions 
for inactivation preclude setting a specific standard for viability 
testing at this time. We have removed the proposed sterility testing 
requirement for select agents and nucleic acids that can produce 
infectious forms of any select agent virus and have incorporated this 
concept into the performance standard. The requirement to develop a 
validated inactivation procedure and subsequent validation data derived 
from viability testing will determine the extent of sampling required. 
This activity will provide the associated measures of uncertainty with 
the sampling protocol chosen.
    We proposed adding exclusion requirements that extracts from a 
select agent could not be excluded from the requirements of the select 
agent regulations until an individual or entity met the following 
requirements: (1) Any extract is subjected to a process that removes 
all viable cells, spores, or virus particles; (2) any extract is 
subjected to a validated sterility testing protocol; (3) any viability 
of an extract that was subjected to a validated inactivation

[[Page 6282]]

protocol is reported to the Responsible Official (RO); and (4) any 
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 by their validated sterility testing protocol, is 
reported to APHIS or CDC.
    Some commenters expressed concern with having to subject every 
extract from a select agent, such as nucleic acids, to sterility 
testing. We agree with the commenters and are replacing the term 
``extract'' with ``material containing a select agent'' to clarify that 
the requirements apply to material containing a select agent such as 
serum or liquid culture where select agents are typically removed via 
filtration without a previous inactivation step. The term ``extract'' 
is commonly used in conjunction with nucleic acids extracted from a 
select agent. We are using the term ``extract'' in the final rule to 
reflect the application of two processing steps: An inactivation step 
to destroy the select agent (e.g., lysis of select agent) and then 
another step (such as filtration), to remove any remaining viable 
select agents. Extracts from a select agent (nucleic acids, antigens, 
lysates) would be subject to the performance standard for select agents 
in the new sections 3(d)(3) and 4(d)(3) of the select agent regulations 
that includes viability testing but does not necessarily require 
viability testing on every sample. The requirement to develop a 
validated inactivation procedure and subsequent validation data derived 
from viability testing will determine the extent of sampling required. 
However, material containing select agents, as opposed to extracts 
(e.g., nucleic acids, antigens, lysates), that is subjected to a 
process to remove all viable cells, spores, or virus particles would 
require viability testing on every sample prior to treating it as a 
non-select agent. The distinguishing feature between ``material 
containing a select agent'' and an extract from a select agent is that 
in the former the select agent will only be removed and in the latter 
the select agent will be destroyed before removal. The more stringent 
requirement for viability testing of all material containing a select 
agent where the select agent was removed is warranted because of the 
lack of select agent destruction which increases the risk of viable 
select agent remaining in the material.
    We proposed that 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. We received comments asking us to clarify 
language to specify under what circumstances strain-to-strain 
differences must be validated. Commenters also stated that this is an 
unnecessary use of resources especially when agents, based on their 
morphological characteristics, are susceptible to similar inactivating 
agents. Commenters suggested at a minimum the language should state 
that this requirement only applies when there are known strain-to-
strain variations in resistance of a select agent to the inactivation 
procedure.
    We agree with the commenters and added in the term ``known'' 
strain-to-strain variation and, as stated previously, have removed the 
kill curve requirement.
    Commenters also inquired whether surrogate strains can be used to 
develop inactivation procedures. We agree with the commenters that 
surrogate strains known to possess equivalent properties with respect 
to inactivation as a select agent can be used to develop inactivation 
procedures. We have revised the requirement to include the provision 
that ``Surrogate strains that are known to possess equivalent 
properties with respect to inactivation can be used to validate an 
inactivation procedure; however, if there are known strain-to-strain 
variations in the resistance of a select agent to an inactivation 
procedure, then an inactivation procedure validated on a lesser 
resistant strain must also be validated on the more resistant 
strains.''
    Commenters were concerned about performing viability testing on 
materials such as a single diagnostic sample that is determined to 
contain a select agent and where there is a limited amount of material 
with which to work. For example, consider an entity using a 
commercially available RNA extraction kit on a diagnostic sample to 
obtain RNA for sequencing, and the sample is identified to contain 
highly pathogenic avian influenza (HPAI). In this situation, the entire 
single sample would be used when trying to demonstrate that the 
inactivation procedure was effective. We agree with the commenters. As 
noted above, surrogate select agent strains that are known to possess 
equivalent properties with respect to inactivation as the select agent 
can be used to develop validated inactivation procedures. In this 
example, low pathogenic avian influenza (LPAI) could be used to 
validate the inactivation procedure for diagnostic samples that are 
identified as containing HPAI, if LPAI possesses equivalent properties 
with respect to inactivation as HPAI. In addition, we are clarifying 
that these provisions do not apply to diagnostic samples until they are 
identified to contain a select agent and are inactivated for future use 
as a non-select agent.
    Many commenters asked who would determine the validity of an 
inactivation protocol. The responsibility for this activity remains 
with the entity, which will allow for researchers to continue to 
develop new inactivation procedures. Entities retain the responsibility 
to evaluate their inactivation procedures, to include consideration of 
the biosafety and security risks posed by the inactivated material. The 
Federal Select Agent Program (FSAP) inspectors will verify that the 
entity has developed a validated inactivation procedure and may review 
validation data during an entity's inspection. We made no changes based 
on these comments.
    Many commenters stated that the intent behind the annual review 
provisions was not clear. We agree with the commenters and modified the 
provisions to state that an entity ``Review, and revise as necessary, 
each of the entity's validated inactivation procedures or viable agent 
removal method. The review must be conducted annually or after any 
change in Principal Investigator, change in the validated inactivation 
procedure or viable agent removal method, or failure of the validated 
inactivation procedure or viable agent removal method. The review must 
be documented and training must be conducted if there are any changes 
to the validated inactivation procedure, viable agent removal method, 
or viability testing protocol.'' We made these changes because the 
annual review of an entity's validated inactivation procedures or 
viable agent removal method is key to a successful inactivation 
program. The annual review requirement does not necessarily involve 
revalidating inactivation procedures. This review could simply be the 
evaluation of the site-specific standard operating procedures for 
validated inactivation of select agents to ensure the inactivating 
conditions used and upper agent concentration limits found in 
validation data are consistent, and that entity staff are following the 
site-specific standard operating procedures for validated inactivation 
of select agents.
    However, sometimes an entity will need to revalidate inactivation 
procedures during the annual review. For example, if the entity 
identifies that staff are not adhering to standard operating procedures 
for validated inactivation of select agents, or if the entity wants to 
deviate from the validated inactivation procedure, the

[[Page 6283]]

entity will need to revalidate the inactivation procedures during the 
annual review. Further, in this final rule, we have consolidated the 
review provisions into one provision, clarified that the reviews must 
be documented, and moved this provision into the requirements for the 
RO as they will be the individual responsible for these review 
activities.
    Many commenters stated that the intent of the inactivation failure 
reporting requirements was not clear and reporting every inactivation 
failure to CDC or APHIS was burdensome. We agree with the commenters 
and have modified reporting requirements to require the RO to 
``Investigate to determine the reason for any failure of a validated 
inactivation procedure or any failure to remove viable agent from 
material. If the Responsible Official is unable to determine the cause 
of a deviation from a validated inactivation procedure or a viable 
agent removal method; or receives a report of any inactivation failure 
after the movement of material to another location, the Responsible 
Official must report immediately by telephone or email the inactivation 
failure or viable agent removal method failure to CDC or APHIS.'' The 
intent of this modification is to create an environment at the entity 
where inactivation or select agent removal failures are investigated to 
determine the reason for the failure as opposed to merely re-subjecting 
the material to the inactivation or select agent removal method. It is 
the position of the FSAP that each failure represents either human 
error in conducting the validated procedure or an inadequate 
inactivation method or an inadequate select agent removal method if no 
human error can be discovered. Both situations demand careful attention 
by the entity to ensure training and/or reevaluation of the 
inactivation procedure in order to minimize the likelihood that the 
situation would reoccur in the future. The revised regulatory language 
only requires reporting of inactivation or select agent removal 
failures to FSAP when the RO cannot establish that the failure resulted 
from human error or when an entity receives a report of any 
inactivation failure after the movement of material to another 
location.
    We also proposed that written records be kept for select agents 
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 
incapable of producing infectious forms of any select agent virus. Some 
commenters stated that the proposal was not clear how long these 
records must be kept and who is responsible for keeping these records. 
We made no changes based on these comments as these records are subject 
to the records retention requirement in section 17 of the select agent 
regulations and must be kept for three years by a registered individual 
or entity.
    Some commenters asked about the conditions of submitting a waiver 
to the inactivation provisions of the select agent regulations. An 
entity may submit a request to FSAP to apply an alternative 
inactivation procedure. The entity is to provide justification 
regarding the alternative procedure including a description of what 
material is to be waived, the inactivation protocol and viability test 
to be used, validation data, and any other supporting information/
references, such as scientific references. Accordingly, we revised the 
provision found in sections 3(d)(6) and 4(d)(6) to include information 
on how to apply for a waiver that reads ``. . . To apply for such a 
determination a registered individual or entity must submit a written 
request and supporting scientific information to FSAP. A written 
decision granting or denying the request will be issued.'' Additional 
guidance has been developed and is available at: www.selectagents.gov.
iii. Toxins
    To ensure the language is consistent with the exclusion language 
found in 73.3(e) which describes the exclusion of toxins that have been 
modified to be less potent or toxic, we are making a technical change 
to the regulation and revising the terms ``nonfunctional'' toxin to 
``nontoxic'' toxin and ``functional form(s) of any of the toxins'' to 
``toxic form(s) of any of the toxins.'' This change is being made to 
clarify the intent of the regulations as the terms ``nonfunctional'' 
and ``functional'' are broad and have led to confusion. The intention 
behind the original provisions was to exclude toxins that can no longer 
exert their toxic effect and cause disease and regulate those that can. 
For example, Botulinum neurotoxin has three functional domains--binding 
domain, translocation domain and catalytic domain. Each functional 
domain solely can be manipulated such that the toxin is no longer toxic 
and does not cause diseases even though the other two domains may be 
functional.
Due Diligence
    We are adding a more specific documentation requirement to the 
toxin exclusion provision found in section 73.3(d)(3)(i) of the select 
agent regulations to require the transferor of an unregulated amount of 
a select toxin 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 recipient. The name of the toxin 
and the total amount transferred must also be documented. Identity 
information of the person requesting and using the toxins must include 
the individual's name, institution name, address, telephone number, and 
email address. We received one comment requesting to include language 
for transfers of toxins within an institution. We made no changes based 
on this comment because intra-entity transfers, where the sender and 
the recipient are covered by the same certificate of registration, are 
already addressed in section 17(3)(viii) of the regulations.
Toxin Permissible Limits
    As proposed, we are increasing the toxin exclusion aggregate 
amounts. We received 10 comments supporting the increase in the toxin 
exclusion aggregate amounts. We received three general comments 
opposing the increase of the exclusion aggregate amounts and two 
additional comments opposing the increase of the ricin exclusion 
aggregate amount. One commenter stated that no changes were necessary. 
Another commenter had concerns regarding whether the risk assessment 
scenarios were relevant to the goal of reducing any significant harm 
able to be caused by illegitimate use of any lethal amounts of toxin. 
We are making no changes based on these comments.
    DHS developed toxin parameters and attack scenarios for potential 
inhalation and ingestion exposures to select toxins to protect the 
homeland against the potential release of weaponized biological toxins. 
The DHS group analyzed a range of release sizes (in mg) for each select 
toxin in order to estimate the number of people that would be exposed 
to each toxin amount by ingestion of milk (using published TD[50] or 
LD[50]) and/or indoor inhalation (using published LD[50]). Revised 
toxin exclusion aggregate amounts were proposed based on the data 
generated by the models to expose <10 or <100 people by inhalation or 
ingestion to the LD[50] or TD[50] levels of toxin. A commenter stated 
that (1) the scenarios proposed appear to consider a high-consequence 
event or exposure to a given toxin and that the interpretation of what 
constitutes a high-consequence event or exposure is impacted not only 
in the number of people affected but in

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the attention afforded by news media and the public and (2) a revision 
of these exclusion limits should also consider amounts that would be 
sufficient for research purposes. We are making no changes based on 
these comments because we do not believe the impact the news media may 
have if an exposure occurs is an appropriate consideration for the 
listing of a biological agent or toxin. Further, the consideration of 
amounts sufficient for research purposes is a subjective assessment as 
smaller academic laboratories have differing needs than an entity that 
is developing detection assays. The comments specific to ricin raised 
concerns that the increased exclusion aggregate amounts would increase 
the risk of (1) exposure to laboratory workers and (2) that individuals 
would have access to greater amounts of material to use for nefarious 
purposes. We are making no changes based on these comments. We do not 
agree that the increased permissible limits will increase the risk of 
laboratory worker exposure. The new proposed exclusion amount is less 
than an oral lethal dose for a single person weighing more than 50 kg, 
based on 20 mg/kg-body weight (Ref. 1), thus a single fatality would 
require consuming more than all of the ricin in the laboratory. Ricin 
does display a higher toxicity when administered intravenously or by 
inhalation, but these two routes of exposure require either injection 
or manipulation to generate particles capable of reaching the lower 
respiratory tract, respectively, two processes not likely to occur 
accidentally. Also, entities that produce ricin typically do so in 
liquid, as opposed to lyophilized powder formulations, thus decreasing 
the risk of ingestion or aerosol exposure. Additionally, the increased 
exclusion aggregate amounts would allow entities to more efficiently 
produce and store ricin preparations which are typically frozen in 
aliquots until the need to use the material arises. Finally, while 
increasing the permissible limits allows individuals with nefarious 
purposes access to greater amounts of toxin, we do not believe access 
to the revised amounts poses a severe threat to public health and 
safety based on the reasons stated above.
Toxins: Exclusion of an HHS Select Toxin Identified in an Original Food 
Samples and Clinical Samples
    As proposed, we are excluding from the requirements of the 
regulations a select toxin identified in an original food sample 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 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, our proposal to exclude select toxin identified in 
an original food sample or clinical sample identified is consistent 
with the rationale for the current exclusion for animals exposed to 
toxins (42 CFR 73.3(d)(4)). This exclusion was based on recommendations 
by toxin subject matter experts. We received one comment that supported 
this exclusion.
Exclusion of Botulinum Neurotoxin Produced as a Byproduct
    In the NPRM, we proposed to exclude all toxins that are only 
produced as a byproduct of a study of the toxin producing host organism 
so long as the toxin had not been intentionally collected, purified, or 
otherwise extracted, and the material containing the toxin was 
inactivated and properly disposed of within 30 days of the initiation 
of the culture. Based on the input from subject matter experts, the 
final regulatory language narrows the exception to only Botulinum 
neurotoxin produced as a byproduct in the study of Botulinum neurotoxin 
producing species of Clostridium. Work with that organism is already 
regulated, thus providing regulatory oversight of the material during 
the 30 day time frame, as opposed to an agent like Staphylococcus 
aureus, the organism that produces Staphylococcal enterotoxins, which 
is not regulated. One commenter stated that clarification was needed in 
the ``exclusion of toxin produced as a by-product'' and inquired 
whether this provision applies to material held in long term storage or 
cell lysates or culture supernatants kept for diagnostic or research 
purposes other than toxin work. Since the situations described by the 
commenter referred to material held in long term storage (longer than 
30 days) this exclusion would not apply.
iv. Exclusion Involving 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, we proposed that waste generated during the delivery of 
patient care is not considered regulated under the select agent 
regulations. One commenter recommended that we define patient care as 
part of the diagnosis definition. Specifically, the commenter suggested 
we define diagnosis as ``the analysis of specimens for the purpose of 
identifying or confirming the presence or characteristics of a select 
agent or toxin provided that such analysis is associated with the 
determination or provision of patient treatment in a patient care 
setting, or directly related to protecting the public health or safety, 
animal health or animal products, or plant health or plant products. 
Clinical or diagnostic specimen retention times as required for patient 
treatment are included within the determination of the point in time 
when patient care has concluded.'' Another commenter stated ``the 
challenges of differentiating between patient care and experimental 
research when treating infectious diseases are complex and nuanced and 
any effort to introduce regulation of medical care involving select 
agents and toxins has the potential to introduce inconsistencies and 
confusion.'' The proposed exclusion language in the NPRM was ``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.'' We 
revised the proposed language based on the two comments to state: 
``Waste generated during the delivery of patient care by health care 
professionals from a patient diagnosed with an illness or condition 
associated with a select agent, where such waste is, within seven days 
of the conclusion of patient care, decontaminated, or transferred for 
destruction in compliance with state and Federal regulations.''
    We revised the proposed exemption language in 42 CFR 73.5(a)(3), 
and 42 CFR 73.6(a)(3) to provide that, unless otherwise directed by the 
HHS Secretary or APHIS Administrator, as appropriate, ``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 by health care professionals has 
concluded.''
    For specimens generated from the patient, the specimens are not 
subject to the select agent regulations for only the period that they 
are directly associated with the diagnosis. In accordance with sections 
five and six of the select agent regulations, within seven calendar 
days after identification, a specimen is subject to the select agent 
regulations

[[Page 6285]]

and must be transferred in accordance with section 73.16 or destroyed 
on-site by a recognized sterilization or inactivation process. Since 
the material would be excluded from the regulations, there would be no 
requirement to document the transfer or destructions. A specimen must 
be secured against theft, loss, or release during the period between 
identification and transfer or destruction, and any theft, loss, or 
release of the specimen must be reported. All specimens generated from 
the patient and kept more than seven days after acute patient care 
concludes would be subject to the select agent regulations.
v. Exemptions for Select Agents and Toxins
Informing Specimen Provider
    Since a registered or reference laboratory typically confirms the 
identification of a select agent or toxin for public health and 
agriculture, we proposed to require that a registered or reference 
laboratory inform the specimen provider of the identification as a 
condition for a clinical or diagnostic laboratory to maintain their 
exemption under 42 CFR 73.5(a), and 42 CFR 73.6(a). Two commenters 
stated they did not believe basic good practices require regulations. 
We made no changes based on these comments because this provision will 
ensure that the reference laboratory notifies the specimen provider of 
the identification of the select agent or toxin. It is important 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 
(e.g., cannot maintain possession of the select agent or toxin, must 
destroy or get approval for a transfer, and report a theft, loss, or 
release).
Identification of Toxin
    In the current select agent regulations, in order for clinical or 
diagnostic laboratories to maintain their exemption under 42 CFR 
73.5(a), and 42 CFR 73.6(a), the clinical or diagnostic laboratory 
must, either immediately or within seven calendar days, report the 
identification of a select agent or toxin to APHIS or CDC unless 
directed otherwise by HHS Secretary or APHIS Administrator. In the 
NPRM, we proposed to amend the language in 42 CFR 73.5(a), and 42 CFR 
73.6(a) to state: ``Unless directed otherwise by the Secretary, within 
seven calendar days after identification of the select agent or toxin 
(except for Botulinum neurotoxin (BoNT) and/or Staphylococcal 
enterotoxins (Subtypes A-E)), or within 30 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.'' We sought comments concerning 
(1) the extension of 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, and 
(2) whether seven calendar days provided sufficient amount of time for 
the entity to destroy or transfer other select agents or toxins after 
identification. We received one comment to extend the amount of time 
for other select agents or toxins to 10 calendar days since destruction 
may not occur on-site, therefore allowing the secure transport to the 
ultimate site of disposition. We made no changes to adjust the seven 
calendar day requirement for agents or toxins other than BoNT and 
Staphylococcal enterotoxin (Subtypes A-E) because the other agents or 
toxins do not involve the identification of both agent and toxin as 
part of diagnosis. Therefore, these situations are not as complicated 
and do not warrant additional time for reporting identification.
vi. Registration
    We are codifying in regulation the current FSAP policy that an 
entity is required to meet all of the regulatory requirements for those 
select agents and toxins listed on an entity's registration regardless 
of whether the select agent or toxin is in the actual possession of an 
entity, and without regard to the actual amounts of toxins in the 
possession of an entity. We received no comments regarding this 
proposal and have made no changes to the language in the proposed rule.
vii. Responsible Official
    Section 73.9(a)(6) of the select agent regulations currently states 
that the RO 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 proposed adding a requirement that the RO must also 
document the corrective actions taken by the entity to address any 
identified deficiencies. We received one comment that supported this 
proposed requirement and are finalizing the requirement as proposed.
HHS or USDA Office of the Inspector General Hotline
    In its December 2014 report, the Federal Experts Security Advisory 
Panel (FESAP) recommended adding a specific regulatory requirement 
addressing how individuals are informed of the availability of 
procedures for accessing the HHS or USDA Office of Inspector General 
Hotlines to anonymously report a safety or security concern. In 
response to that recommendation, we proposed adding a requirement that 
the RO must ensure that individuals at their entity are provided the 
contact information of the HHS Office of Inspector General Hotline and 
USDA Office of Inspector General Hotline so that an individual is able 
to anonymously report a biosafety or security concern related to select 
agents and toxins. We received no comments regarding this proposed 
addition and are finalizing the requirement as proposed.
viii. 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 RO, 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 person with 
approved access at a registered entity to have approved access to a 
select agent at another registered entity. To ensure that the RO of the 
entity hosting such a visitor is aware if a visiting individual loses 
access approval to select agents and toxins, we added a requirement 
that the RO at the home entity must immediately notify the RO of the 
visiting entity if a person's access to select agents or toxins has 
been terminated. We received one comment that supported this addition 
to the regulations and are finalizing the requirement as proposed.
ix. 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 and toxins they handle. These are:
     A security plan that provides for measures sufficient to 
safeguard a select agent or toxin against unauthorized access, theft, 
loss, or release (42 CFR 73.11);

[[Page 6286]]

     A biosafety plan that provides for measures sufficient to 
contain a select agent or toxin (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, or others. (42 CFR 73.14).
    The select agent regulations require that drills or exercises must 
be conducted at least annually to test and evaluate the effectiveness 
of the plans, and that the plans must be reviewed and revised, as 
necessary, after any drill or exercise, and after any incident. We 
proposed 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. 
Three commenters stated that there was no need to codify the 
documentation of how a drill or exercise evaluated a plan and 
corrective actions in regulations because they believed this 
requirement is already being documented. We are making no changes based 
on the comments because this requirement will provide a more thorough 
accounting of required activities via testing and entity-directed 
improvements.
    Another commenter requested clarification regarding the recording 
of the names of individuals who participate in drills or exercises. The 
commenter believed the requirement should be limited to registered 
entity personnel and not include first responders or other non-entity 
participants, but list only the participating external agencies (e.g., 
emergency management, emergency medical services, or fire department). 
We agreed with the commenter and have amended the proposed regulatory 
language to clarify that an entity only needs to document the names of 
individuals at the registered entity. An entity may choose to list the 
external agencies who participated in the drill or exercise.
    Similar to the existing requirement for the security plan, we 
proposed to add a requirement that the biosafety and incident response 
plans be submitted for initial registration, renewal of registration, 
or when requested by FSAP. We received two comments regarding these 
proposals which supported this requirement. However, one commenter 
questioned the need for additional requirements as this is already done 
routinely. While we agreed with the commenter that some, or even most, 
entities already provide the plans routinely, we are making no changes 
to the proposed language so that all entities will be required to 
submit their biosafety and incidence response plans, consistent with 
the existing requirement for the security plan.
Security
    We proposed amending the requirement that a 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 add a requirement 
that the security plan must include a description of centralized access 
control management systems (e.g., keycards) and/or key management 
(e.g., mechanical keys). We proposed this requirement because during 
our inspections of registered entities we have observed that the 
central access control management system in some instances is 
controlled, either on- or off-site, by individuals who (1) have not 
received access approval from HHS Secretary or APHIS Administrator, and 
(2) have the ability to assign people access or override access 
controls without the knowledge of the entity's RO. Three commenters 
suggested that access management processes are sensitive and a greater 
security risk may result from having too detailed information available 
in a single document. One commenter recommended we include a definition 
of what an access control system is and what components need to be 
included in the security plan. After considering the comments and 
reconsidering the purpose of the proposed language, we are not 
finalizing the proposed revision. Our concerns about unauthorized 
persons either having access or granting access without the knowledge 
of the entity RO can be addressed by the current provisions found in 
subsections (c)(1) and (c)(2) of section 11 (security) of the select 
agent regulations, which make the RO responsible to ensure access 
controls, irrespective of the type of security system in place.
    Paragraphs (d)(7)(i) through (d)(7)(v) of section 11 (security) of 
the select agent regulations encompass a list of events that 
individuals with access approval from the HHS Secretary or the APHIS 
Administrator must immediately report to the RO. We proposed to add a 
new requirement that the RO 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 received 
one comment requesting clarification on the time frame for 
notification. We made no changes based on the comment since the 
regulations under subsection (d) already provide that notification must 
be immediate. The notification will facilitate notification of the 
Federal Bureau of Investigation (FBI) if deemed necessary by the RO as 
the loss of such equipment may be criminal in nature.
Biosafety
    We proposed amending the regulatory language in section 73.12 of 
the select agent regulations to update the name change of the National 
Institutes of Health (NIH) ``Guidelines for Research Involving 
Recombinant or Synthetic Nucleic Acid Molecules'' (Ref. 2). We received 
no comments and are finalizing this change as proposed.
    The biosafety section of the select agent regulations contains a 
reference to the Occupational Safety and Health Administration (OSHA) 
regulations found in 29 CFR 1910.1200 and 1910.1450. These sections 
provide specific requirements for handling hazardous chemicals in the 
laboratories. These regulations also provide recommendations for safely 
working with chemicals including toxins and give non-mandatory 
recommendations for prudent practices in laboratories handling chemical 
hazards. Since the current edition of the CDC/NIH ``Biosafety in 
Microbiological and Biomedical Laboratories'' Appendix I (Ref. 3) now 
provides guidelines for work with toxins of biological origin, we 
proposed removal of the reference to these OSHA regulations. We note, 
however, that regulated entities are still required to meet the OSHA 
regulatory requirements where applicable. We received no comments and 
are finalizing this change as proposed.
    In the NPRM, we proposed adding the requirement that ``biosafety 
and containment procedures specific to each registered laboratory must 
be available to each individual working in that laboratory.'' We 
proposed adding this language to ensure that laboratory personnel 
working with select agents and toxins have access to relevant biosafety 
information and are therefore aware of the risks associated with these 
agents. One commenter requested clarification regarding the term 
``laboratory'' and whether the term referred to a single room or a 
building or to a group of rooms (e.g., laboratory, animal room, 
necropsy) used by a Principal Investigator for a research project. The 
commenter also requested

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clarification on the language ``must be available to each individual 
working in the laboratory'' and whether this implied that there must be 
a specific biosafety manual for each room. We also received three 
comments that questioned the need for a new requirement since the 
commenters believe a laboratory-specific biosafety manual was already 
accessible to individuals. We are not adding the proposed provision to 
the regulations because upon further reflection we agree with the 
commenters that individuals already have access to their biosafety 
plan.
    In the NPRM, we proposed adding specific provisions to the 
biosafety section that would require (1) a written risk assessment for 
each registered select agent or toxin; (2) written safety procedures to 
protect entity personnel, the public, and the environment from exposure 
to the select agent or toxin; (3) written decontamination procedures; 
and (4) written waste management procedures. We received 13 comments 
that stated that ``risk assessments'' should be defined and the 
proposed requirement of having these for each procedure involving a 
select agent or toxin that addresses the hazards associated with the 
agent or toxin must be clarified because risk assessments are completed 
through institutional review committees by collaborative processes with 
Principal Investigators and biosafety professionals. One commenter 
stated that a risk assessment was always a requirement. We agree with 
the commenters that ``risk assessment for each procedure'' should not 
be required and agreed that having a risk assessment was already 
addressed in the regulations as outlined in Section 12(a) that ``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.'' However, 
we have clarified in the final regulatory language found in section 
12(a)(1) of the select agent regulations that the biosafety plan 
include ``the hazardous characteristics of each agent or toxin listed 
on the entity's registration and the biosafety risk associated with 
laboratory procedures related to the select agent or toxin.''
    The majority of the commenters stated that the approach outlined in 
the NPRM discussion of section 12(a) would lead to decreased compliance 
and an increase in paperwork burden. One commenter stated that many 
biosafety plans are already upwards of 50 pages, and increasing the 
length further may greatly decrease the likelihood that researchers 
will continue to read these plans and use them as a resource. Another 
commenter stated that regulatory language should be omitted to prevent 
creating a redundant process such as those provisions already covered 
under training and incident response. We agree with commenters and have 
removed the training and incident response language that was noted in 
the NPRM because these provisions are already covered by other sections 
in the regulations (i.e., incident response and training sections). We 
combined other provisions to reduce the seven provisions listed in the 
NPRM to four provisions in the final rule.
    One commenter stated we should consider requiring the adoption of 
shared algorithms developed by the American Society for Microbiology 
(ASM) for use by clinical laboratories. These algorithms are presented 
as frequently asked questions (FAQs) from ASM to assist laboratories. 
We made no changes based on this comment because FSAP already provides 
FAQs to assist entities with meeting the biosafety requirements of the 
regulations.
    Another commenter recommended that we also offer the suggestion 
that entities consider implementing programs whereby personnel are 
required to work with another trained person (i.e., a ``buddy'' system 
or dual authentication) as an appropriate and effective proactive 
method for the prevention of laboratory acquired infections and 
accidental releases of select agents. We made no changes based on this 
comment as it is essential for entities to develop their own biosafety 
initiatives to meet their own needs. The commenter continued that many 
of these issues come down to the culture of safety in an entity, and 
adherence to established protocols and training. The commenters wanted 
the regulatory provisions to reflect an improved safety culture. Two 
commenters requested that we consider leaving the current provisions in 
place and develop guidance to assist entities that would include risk 
assessment, use of safety equipment, personal protective equipment, 
containment devices, and occupational health consideration. Another 
commenter stated that the new section appears redundant with the risk 
assessment(s) performed during review of work registrations by an 
Institutional Biosafety Committee. We agree with the commenters that 
the provisions focus on the hazards and risks associated with the 
select agents and toxins and the safety practices put in place by the 
entity to protect entity personnel, the public, and the environment. We 
have revised the proposed language to state that the biosafety plan 
must include the provisions found in section 12(a) of the select agent 
regulations (see Sec.  73.12(a)(1)-(4)). To address the commenters' 
suggestion that FSAP develop a guidance document regarding biosafety, 
additional guidance has been developed and is available at: http://www.selectagents.gov.
x. Training
    We proposed to amend section 15 of the select agent regulations to 
require that training be completed within 12 months of that 
individual's anniversary of receiving access approval from the HHS 
Secretary or the APHIS Administrator, 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 ensure 
that individuals at registered entities receive timely training. We 
received no specific comments regarding this proposed change. However, 
seven commenters stated that we should include a description of the 
level of training necessary for personnel in varying positions with 
highly disparate job duties and responsibilities. The commenters 
requested that we clarify that the required training will be conducted 
at a level appropriate to the registered person's role and level of 
access to select agents. We made no changes based on this comment 
because the current regulatory language is clear that ``the training 
must address the particular needs of the individual, the work they will 
do, and the risks posed by the select agents or toxins.'' The training 
for the individuals should be determined by the entity based on at the 
level of which the individual will have access to select agents or 
toxins. The training that each person receives should be designed to 
ensure that they can carry out their responsibilities without causing 
harm to themselves, or to their fellow co[hyphen]workers, or to the 
public. We did clarify the regulatory language regarding training for 
an individual who must be escorted to specify that their training must 
be accomplished prior to the individual's entry into a registered area.
    One commenter also asked that we consider making ``training a pre-
requisite for access to select agents and toxins, and not a requirement 
for just being FSAP approved.'' The regulations in 42 CFR 73.15(a)(1) 
already requires that each approved individual receive information and 
training on biosafety, security (including security awareness), and 
incident response before that individual has access to any select 
agents and toxins. The same commenter

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asked that we clearly specify the requirements for both initial and 
annual training. While we made no changes to our regulatory language 
based on this comment, the document, ``Guidance for Meeting the 
Training Requirements of the Select Agent Regulations,'' found at 
http://www.selectagents.gov/guidance-training.html, has been amended to 
provide further detail and assistance regarding the content of initial 
and annual training. The same commenter stated that in two instances an 
employee's annual training deadline occurred in the middle of an 
extended medical leave during which it was not possible to complete the 
training, and the entity had to choose to either let the training 
become overdue, or to remove the individual from the registration and 
completely start over with the security risk assessment (SRA) approval 
process once the individual was back to work. The commenter stated that 
``SRA approved personnel could commonly be on other types of extended 
leave such as maternity leave, or on sabbatical doing research at 
another institution but still employed and SRA approved at their home 
institution.'' While we made no changes to our regulatory language 
based on this comment, we have updated our guidance, ``Guidance for 
Meeting the Training Requirements of the Select Agent Regulations,'' 
which is available at www.selectagents.gov, to include information on 
how to deal with situations regarding individuals that have extended 
absences from the laboratory.
xi. Records
    Based on our inspections of registered entities, we observed that 
not all entities maintain records of the final disposition of select 
agents when consumed or destroyed, and this impedes validation of 
inventory holdings. Section 73.17 of the select agent regulations 
currently does not include a requirement for documenting the final 
disposition of a select agent. To ensure the proper tracking of a 
select agent from acquisition to final disposition, we are adding a 
requirement for entity records to include the final disposition 
(including destruction) for each select agent that has been held in 
long-term storage. One commenter expressed concern that a requirement 
for a record of destruction of select agents would place an undue 
burden on investigators and recommended that this requirement be 
excluded from the final rule. However, the commenter did agree that an 
entity should be required to maintain a current and accurate inventory 
of all select agents in their possession and document when an agent is 
no longer in their possession. We agree with the commenter that final 
disposition needs to be part of the entity's recordkeeping requirement. 
We disagree with the commenter that this will place undue burden on 
investigators because this information can be included with an entity's 
existing recordkeeping system (e.g., inventory spreadsheet). Therefore, 
to clarify the regulatory language, we have revised the proposed 
regulatory language to provide that the record will need to include 
``the select agent used, purpose of use, and, when applicable, final 
disposition.''
    Section 73.17 of the select agent regulations currently states that 
records and databases need to be accurate. To ensure that the accuracy 
of handwritten records can be verified, we proposed to clarify that a 
handwritten record must be legible (i.e., capable of being read). We 
received one comment requesting that we define the term ``legible 
handwritten records.'' We made no changes based on this comment because 
we are using the term ``legible'' in its ordinary meaning.
    We proposed to expand the scope of records required to be 
maintained to include any records that contain information related to 
the requirements of the regulations. We received five comments that 
expressed concerns about the information being kept in laboratory 
notes. The commenters stated that the information is ``proprietary in 
nature,'' contains intellectual property information and should not be 
required to be provided to FSAP inspectors. We understand the concerns 
of the commenters and clarified the language to indicate that it is 
only information related to requirements of the select agent 
regulations that must be produced on request. Such information may be 
found in the biocontainment certifications, laboratory notebooks, 
institutional biosafety and/or animal use committee minutes and 
approved protocols, and records associated with occupational health and 
suitability programs. Accordingly, we will only review relevant 
portions of any laboratory notebooks or documents, and only if they 
contain information related to any requirements of the regulations 
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. Two commenters stated 
that certain records are ``protected under the HIPAA Privacy Rule.'' 
FSAP would expect any information provided to FSAP regarding an 
individual's health would be provided in accord with the HIPAA Privacy 
Rule, including the use and disclosure of protected health information 
to public health authorities authorized by law to collect or receive 
such information for preventing or controlling disease, injury, or 
disability.
Records for Long-Term Storage
    In the NPRM we also solicited information and ideas as to how a 
regulatory requirement could be constructed such that a registered 
entity would know whether a select agent or toxin had been lost or 
stolen, without that registered entity first having ``an accurate, 
current inventory for each select agent . . . held in long-term 
storage.'' In addition, we requested ideas as to how the current 
regulations could be amended to address the threat of the theft of a 
select agent from a container held in long-term storage. We received 
three comments that addressed this request. One commenter suggested 
that FSAP inspectors review the record of select agents held in long-
term storage and accept the attestation of the responsible 
investigators of their accuracy. Another commenter stated we should 
continue with FSAP's current select agent practices to allow for these 
stocks to be maintained in tamper-evident containers (e.g., security 
ties on freezer boxes) so that vials are not individually removed, 
thawed, and measured. The third commenter recommended dual 
authentication coupled with required entity inventory reviews. We 
appreciate the comments and will continue to consider how the 
recognition of theft and loss might be addressed through alternative 
approaches.

III. Alternatives Considered

    The Public Health Security and Bioterrorism Preparedness and 
Response Act of 2002 requires HHS and USDA to review and republish the 
list of select agents and toxins every two years. In drafting this 
final rule, we considered the action proposed in the NPRM of removing 
the six select agents and one toxin where its costs and benefits were 
discussed. If those policies were adopted, it would result in savings 
ranging from approximately $15,300 for a small commercial BSL-3 
laboratory to approximately $165,000 for a larger university with BSL-
2/3 laboratories for laboratories no longer regulated. Based on the 
review of FSAP database, approximately eleven small entities would no 
longer be regulated and would not be required to register with FSAP. If 
the entities withdrew their registration, it would result in an 
estimated saving of $168,300 annually. On the other hand, this policy 
could increase the likelihood of entities working with these removed 
select agents and toxin not having the

[[Page 6289]]

appropriate biosafety and security provisions in place to prevent an 
accidental or intentional release of a select agent or toxin. The 
intentional release could adversely affect the public health and 
safety. Recent events concerning the accidental transfer of select 
agents that had not been fully inactivated, leading to the inadvertent 
release of select agents, caused us to also look at provisions in this 
regulation. After carefully considering the technical input of subject 
matter experts, both within the Federal government and from public 
comments, and recommendations from Federal advisory groups, we have 
decided not to finalize the proposed changes to the list of select 
agents and toxins at this time.

IV. Required Regulatory Analyses

A. Executive Orders 12866 and 13563

    Under Executive Order (E.O.) 12866, Regulatory Planning and Review 
(58 FR 51735, October 4, 1993), 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 (E.O.). E.O. 12866 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 
E.O. 12866.
    E.O. 13563, Improving Regulation and Regulatory Review, (76 FR 
3821, January 21, 2011), updates some of the provisions of E.O. 12866 
in order to promote more streamlined regulatory actions. This E.O. 
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.
    We have prepared an economic analysis for this rule. The economic 
analysis provides a cost-benefit analysis, as required by E.O. 12866, 
and a final regulatory flexibility analysis (See Section III.B. of this 
Preamble) that examines the potential economic effects of this rule on 
small entities, as required by the Regulatory Flexibility Act. The 
economic analysis is summarized below. Copies of the full analysis are 
available in the docket at www.regulations.gov or at www.select 
agents.gov.
    We have determined that this final rule is significant for the 
purposes of Executive Order 12866 and, therefore, this final rule has 
been reviewed by OMB.
Summary of the Regulatory Impact Analysis
    The Public Health Security and Bioterrorism Preparedness and 
Response Act of 2002 (Pub. L. 107-188) provides for the regulation of 
certain biological agents and toxins that have the potential to pose a 
severe threat to human, animal, or plant health, or to animal or plant 
products. APHIS and CDC have primary responsibility for implementing 
the provisions of the Act within the Department of Agriculture and the 
Department of Health and Human Services, respectively. Within APHIS, 
Veterinary Services (VS) select agents and toxins are those that have 
been determined to have the potential to pose a severe threat to animal 
health or animal products, and Plant Protection and Quarantine (PPQ) 
select agents and toxins are those that have been determined to have 
the potential to pose a severe threat to plant health or plant 
products. HHS select agents and toxins are those that have been 
determined to have the potential to pose a severe threat to human 
health. APHIS and CDC coordinate regulatory activities for overlap 
select agents and toxins that have been determined to pose a severe 
threat to human and animal health or products.
    Sections 201 and 212(a)(2) of the Act require a biennial review and 
republication of the select agent and toxin list, with revisions as 
appropriate in accordance with this law. These final rules will 
implement the recommendations of the fourth biennial review of select 
agent regulations and have finalized changes that will increase their 
usability as well as provide for enhanced program oversight. These 
amendments include new provisions regarding the inactivation of select 
agents, specific biosafety and toxin requirements and clarification of 
regulatory language concerning security, training, and records.
    The final rule will require that entities develop validated 
inactivation procedures for select agents or regulated infectious 
nucleic acid and maintain written records of having done so. Costs of 
complying with this amendment are expected to be modest.
    Currently, there are 286 entities registered with APHIS and CDC 
including 91 academic, 53 commercial, 81 State government, 45 Federal 
government, and 16 private (non-profit) institutions, most of which are 
considered to be small entities. Based on current record keeping and 
reporting requirements, an additional 10 to 20 hours per year may be 
required for maintaining records associated with select agents or 
material containing select agents or regulated nucleic acids that can 
produce infectious forms of any select agent virus that have been 
subjected to a validated inactivation procedure or a procedure for 
removal of viable select agents. At an imputed cost of $33.40 per hour 
(GS-12, step 2), this additional time requirement per entity will cost 
between $334 and $668 per year, or in total for all registered entities 
between $80,000 and $160,000. The final rule will not have a 
significant economic impact on a substantial number of small entities. 
Costs associated with this rule do not include costs related to 
training, overhead, updates to facilities, etc. We assume in this rule 
that all costs associated with such factors for entities performing 
inactivation procedures have already been incurred prior to rulemaking.
    The benefits of strengthened safeguards against the unintentional 
or deliberate release of a select agent or toxin greatly exceed 
compliance costs of the rules. As an example of losses that can occur, 
the October 2001 anthrax attacks caused five fatalities and 17 
illnesses, disrupted business and government activities (including $2 
billion in lost revenues for the Postal Service), and required more 
than $23 million to decontaminate one Senate office building and $3 
billion to decontaminate postal facilities and procure mail-sanitizing 
equipment. Deliberate introduction greatly increases the probability of 
a select agent becoming established and causing wide-ranging and 
devastating impacts to the economy, other disruptions to society, and 
diminished confidence in public and private institutions.
    The amended regulations will enhance the protection of human, 
animal, and plant health and safety. The final rules will reduce 
likelihood of the accidental or intentional release of a

[[Page 6290]]

select agent or toxin. Benefits of the rules will derive from the 
greater probability that a release will be prevented from occurring.

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 RFA (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, RFA, as amended by the Small Business Regulatory 
Enforcement Fairness Act (SBREFA), requires agencies to analyze 
regulatory 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 because these registered 
entities are already required to comply with the select agent 
regulations. The small entities would only incur some costs if they are 
performing inactivation procedures and are not maintaining records. The 
additional costs that may be incurred are small in comparison to the 
long-term benefits of additional protection against the release of 
select agents and toxins that would result in devastating effects to 
the economy.
    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.), 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 (Possession, Use, and Transfer of Select Agents and Toxins (42 CFR 
73), Expiration 12/31/2018).

D. E.O. 12988: Civil Justice Reform

    This rule has been reviewed under E.O. 12988, Civil Justice Reform. 
Once the final rule is in effect, 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. E.O. 13132: Federalism

    HHS/CDC has reviewed this final rule in accordance with E.O. 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.''

F. Plain Language Act of 2010

    Under the Plain Language Act of 2010 (Pub. 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.

V. References

1. D.R. Franz and N.K. Jaax (1997). Defense Against Toxin Weapons 
(Chapter 30). In Textbook of Military Medicine: Medical Aspects of 
Chemical and Biological Warfare, Borden Institute, Walter Reed Army 
Medical Center, Washington, DC. 631-642.
2. U.S. Department of Health and Human Services, National Institutes 
of Health. (2013). NIH Guidelines for Research Involving Recombinant 
Or Synthetic Nucleic Acid Molecules (NIH Guidelines). Retrieved from 
http://osp.od.nih.gov/sites/default/files/NIH_Guidelines.html.
3. U.S. Department of Health and Human Services, Centers for Disease 
Control and Prevention and National Institutes of Health. (2009). 
Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th 
Edition. Retrieved from http://www.cdc.gov/biosafety/publications/bmbl5/index.htm.

List of Subjects in 42 CFR Part 73

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

    For the reasons discussed in the preamble, we 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 validated inactivation procedure and viability testing protocol to 
read as set forth below.


Sec.  73.1  Definitions.

* * * * *
    Validated inactivation procedure means a procedure, whose efficacy 
is confirmed by data generated from a viability testing protocol, to 
render a select agent non-viable but allows the select agent to retain 
characteristics 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.
* * * * *
    Viability testing protocol means a protocol to confirm the 
validated inactivation procedure by demonstrating the material is free 
of all viable select agent.
* * * * *

0
3. Section 73.3 is amended as follows:
0
a. By revising paragraph (b).
0
b. By removing ``functional'' and adding in its place ``toxic'' in 
paragraph (c)(2).
0
c. By revising paragraph (d)(2).
0
d. By redesignating paragraph (d)(3) as (d)(7) and revising 
redesignated paragraphs (d)(7) introductory text and (d)(7)(i).
0
e. By redesignating paragraph (d)(4) as paragraph (d)(8).
0
f. By redesignating paragraph (d)(5) as paragraph (d)(12).
0
g. By adding new paragraphs (d)(3), (d)(4), (d)(5), (d)(6), (d)(9), 
(d)(10) and (d)(11).
0
h. By adding paragraph (e)(3).
0
i. By adding ``Bacillus cereus Biovar anthracis,'' before ``Botulinum 
neurotoxins'' in paragraph (f)(3)(i).
    The additions and revisions read as follows:


Sec.  73.3  HHS select agents and toxins.

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

Abrin
Bacillus cereus Biovar anthracis*
Botulinum neurotoxins*
Botulinum neurotoxin producing species of Clostridium*
Conotoxins (Short, paralytic alpha conotoxins containing the following

[[Page 6291]]

amino acid sequence 
X1CCX2PACGX3X4X5X
6CX7) \1\
---------------------------------------------------------------------------

    \1\ C = Cysteine residues are all present as disulfides, with 
the 1st and 3rd Cysteine, and the 2nd and 4th Cysteine forming 
specific disulfide bridges; The consensus sequence includes known 
toxins [alpha]-MI and [alpha]-GI (shown above) as well as [alpha]-
GIA, Ac1.1a, [alpha]-CnIA, [alpha]-CnIB; X1 = any amino acid(s) or 
Des-X; X2 = Asparagine or Histidine; P = Proline; A = Alanine; G = 
Glycine; X3 = Arginine or Lysine; X4 = Asparagine, Histidine, 
Lysine, Arginine, Tyrosine, Phenylalanine or Tryptophan; X5 = 
Tyrosine, Phenylalanine, or Tryptophan; X6 = Serine, Threonine, 
Glutamate, Aspartate, Glutamine, or Asparagine; X7 = Any amino 
acid(s) or Des X and; ``Des X'' = ``an amino acid does not have to 
be present at this position.'' For example if a peptide sequence 
were XCCHPA then the related peptide CCHPA would be designated as 
Des-X.
---------------------------------------------------------------------------

Coxiella burnetii
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 virus containing any portion of the coding regions of all 
eight gene segments (Reconstructed 1918 influenza virus)
Ricin
Rickettsia prowazekii
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 nontoxic HHS toxins.
    (3) A select agent or toxin that has been subjected to 
decontamination or a destruction procedure when intended for waste 
disposal.
    (4) 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 procedure that is confirmed through a viability 
testing protocol. Surrogate strains that are known to possess 
equivalent properties with respect to inactivation can be used to 
validate an inactivation procedure; however, if there are known strain-
to-strain variations in the resistance of a select agent to an 
inactivation procedure, then an inactivation procedure validated on a 
lesser resistant strain must also be validated on the more resistant 
strains.
    (5) Material containing a select agent that is subjected to a 
procedure that removes all viable select agent cells, spores, or virus 
particles if the material is subjected to a viability testing protocol 
to ensure that the removal method has rendered the material free of all 
viable select agent.
    (6) A select agent or regulated nucleic acids that can produce 
infectious forms of any select agent virus not subjected to a validated 
inactivation procedure or material containing a select agent not 
subjected to a procedure that removes all viable select agent cells, 
spores, or virus particles if the material is determined by the HHS 
Secretary to be effectively inactivated or effectively removed. To 
apply for a determination an individual or entity must submit a written 
request and supporting scientific information to CDC. A written 
decision granting or denying the request will be issued.
    (7) 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; 100 mg of Conotoxins (Short, paralytic 
alpha conotoxins containing the following amino acid sequence 
X1CCX2PACGX3X4X5X
6CX7); 10,000 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. 
Provided that,
    (i) The toxin is transferred only after the transferor uses due 
diligence and documents the identification of the recipient and the 
legitimate need (e.g., 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.
* * * * *
    (9) An HHS select toxin identified in an original food sample or 
clinical sample.
    (10) For those laboratories that are not exempt under Sec.  73.5(a) 
and Sec.  73.6(a), Botulinum neurotoxin that is produced as a byproduct 
in the study of Botulinum neurotoxin producing species of Clostridium 
so long as the toxin has not been intentionally cultivated, collected, 
purified, or otherwise extracted, and the material containing the toxin 
is rendered non-toxic and disposed of within 30 days of the initiation 
of the culture.
    (11) Waste generated during the delivery of patient care by health 
care professionals from a patient diagnosed with an illness or 
condition associated with a select agent, where that waste is 
decontaminated or transferred for destruction by complying with state 
and Federal regulations 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 removing ``functional'' and adding in its place ``toxic'' in 
paragraph (c)(2).
0
c. By revising paragraph (d)(2).
0
d. By redesignating paragraph (d)(3) as (d)(9).
0
e. By adding new paragraphs (d)(3), (d)(4), (d)(5), (d)(6), (d)(7) and 
(d)(8).
0
f. 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 *
Bacillus anthracis Pasteur strain

[[Page 6292]]

Brucella abortus
Brucella melitensis
Brucella suis
Burkholderia mallei *
Burkholderia pseudomallei *
Hendra virus
Nipah virus
Rift Valley fever virus
Venezuelan equine encephalitis virus
* * * * *
    (d) * * *
    (2) Non-viable overlap select agents or nontoxic overlap toxins.
    (3) A select agent or toxin that has been subjected to 
decontamination or a destruction procedure when intended for waste 
disposal.
    (4) 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 procedure that is confirmed through a viability 
testing protocol. Surrogate strains that are known to possess 
equivalent properties with respect to inactivation can be used to 
validate an inactivation procedure; however, if there are known strain-
to-strain variations in the resistance of a select agent to an 
inactivation procedure, then an inactivation procedure validated on a 
lesser resistant strain must also be validated on the more resistant 
strains.
    (5) Material containing a select agent that is subjected to a 
procedure that removes all viable select agent cells, spores, or virus 
particles if the material is subjected to a viability testing protocol 
to ensure that the removal method has rendered the material free of all 
viable select agent.
    (6) A select agent or regulated nucleic acids that can produce 
infectious forms of any select agent virus not subjected to a validated 
inactivation procedure or material containing a select agent not 
subjected to a procedure that removes all viable select agent cells, 
spores, or virus particles if the material is determined by the HHS 
Secretary or Administrator to be effectively inactivated or effectively 
removed. To apply for a determination an individual or entity must 
submit a written request and supporting scientific information to CDC 
or APHIS. A written decision granting or denying the request will be 
issued.
    (7) An overlap select toxin identified in an original food sample 
or clinical sample.
    (8) Waste generated during the delivery of patient care by health 
care professionals from a patient diagnosed with an illness or 
condition associated with a select agent, where that waste is 
decontaminated or transferred for destruction by complying with state 
and Federal regulations 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 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 Administrator will grant or deny the 
request for reconsideration as promptly as circumstances allow and will 
state, in writing, the reasons for the decision.
* * * * *

0
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).
0
d. By adding ``Bacillus cereus Biovar anthracis,'' before ``Botulinum 
neurotoxins'' in paragraph (a)(3)(i).
    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 or toxin (except 
for Botulinum neurotoxin and/or Staphylococcal enterotoxin (Subtypes A-
E)), or within 30 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 
calendar days after delivery of patient care by health care 
professionals 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 seven 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 new 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 calendar days after delivery of 
patient care by health care professionals 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 seven 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 its 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 paragraphs (a)(7), (a)(8) and (a)(9) to read as set forth 
below.

[[Page 6293]]

0
c. By adding ``Bacillus cereus Biovar anthracis,'' after ``Bacillus 
anthracis,'' in paragraph (c)(1).


Sec.  73.9  Responsible Official.

    (a) * * *
    (7) Ensure that individuals are provided the contact information 
for the HHS Office of Inspector General Hotline and the USDA Office of 
Inspector General Hotline so that they may anonymously report any 
biosafety or security concerns related to select agents and toxins.
    (8) Investigate to determine the reason for any failure of a 
validated inactivation procedure or any failure to remove viable select 
agent from material. If the Responsible Official is unable to determine 
the cause of a deviation from a validated inactivation procedure or a 
viable select agent removal method; or receives a report of any 
inactivation failure after the movement of material to another 
location, the Responsible Official must report immediately by telephone 
or email the inactivation or viable agent removal method failure to CDC 
or APHIS.
    (9) Review, and revise as necessary, each of the entity's validated 
inactivation procedures or viable select agent removal methods. The 
review must be conducted annually or after any change in Principal 
Investigator, change in the validated inactivation procedure or viable 
select agent removal method, or failure of the validated inactivation 
procedure or viable select agent removal method. The review must be 
documented and training must be conducted if there are any changes to 
the validated inactivation procedure, viable select agent removal 
method, or viability testing protocol.
* * * * *

0
9. Section 73.10 is amended as follows:
0
a. By a 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 (d)(7)(vi).
0
c. By adding a sentence to the end of paragraph (h).
    The additions read as follows:


Sec.  73.11  Security.

* * * * *
    (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 the names of registered 
entity personnel participants.

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. The current biosafety plan must be 
submitted for initial registration, renewal of registration, or when 
requested. The biosafety plan must include the following provisions:
    (1) The hazardous characteristics of each agent or toxin listed on 
the entity's registration and the biosafety risk associated with 
laboratory procedures related to the select agent or toxin;
    (2) Safeguards in place with associated work practices to protect 
entity personnel, the public, and the environment from exposure to the 
select agent or toxin including, but not limited to: Personal 
protective equipment and other safety equipment; containment equipment 
including, but not limited to, biological safety cabinets, animal 
caging systems, and centrifuge safety containers; and engineering 
controls and other facility safeguards;
    (3) Written procedures for each validated method used for 
disinfection, decontamination or destruction, as appropriate, of all 
contaminated or presumptively 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 (if applicable), animal carcasses or extracted tissues and 
fluids (if applicable), laboratory surfaces and equipment, and effluent 
material; and
    (4) Procedures for the handling of select agents and toxins in the 
same spaces with non-select agents and toxins 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 the names of registered 
entity personnel participants.

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 the names of registered 
entity personnel participants.

0
13. Section 73.15 is amended as follows:
0
a. Revising paragraph (a) to read as set forth below.
0
b. By adding paragraph (e) to read as set forth below.


Sec.  73.15  Training.

    (a) An individual or entity required to register under this part 
must provide information and training on biocontainment, biosafety, 
security (including security awareness), and incident response to:
    (1) Each individual with access approval from the HHS Secretary or

[[Page 6294]]

Administrator. The training must address the particular needs of the 
individual, the work they will do, and the risks posed by the select 
agents or toxins. The training must be accomplished prior to the 
individual's entry into an area where a select agent is handled or 
stored, or within 12 months of the date the individual was approved by 
the HHS Secretary or the Administrator for access, whichever is 
earlier.
    (2) Each individual not approved for access to select agents and 
toxins by the HHS Secretary or Administrator before that individual 
enters areas under escort where select agents or toxins are handled or 
stored (e.g., laboratories, growth chambers, animal rooms, greenhouses, 
storage areas, shipping/receiving areas, production facilities, etc.). 
Training for escorted personnel must be based on the risk associated 
with accessing areas where select agents and toxins are used and/or 
stored. The training must be accomplished prior to the individual's 
entry into where select agents or toxins are handled or stored (e.g., 
laboratories, growth chambers, animal rooms, greenhouses, storage 
areas, shipping/receiving areas, production facilities, etc.).
* * * * *
    (e) The Responsible Official must ensure and document that 
individuals are provided the contact information of the HHS Office of 
Inspector General Hotline and the 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 (e.g., 
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 revising paragraph (a)(1)(v).
0
c. By adding paragraph (a)(8).
0
d . By revising paragraph (b).
0
e. By revising paragraph (c).
    The revision and additions read as follows:


Sec.  73.17  Records.

    (a) * * *
    (1) * * *
    (v) The select agent used, purpose of use, and, when applicable, 
final disposition,
* * * * *
    (8) For select agents or material containing select agents or 
regulated nucleic acids that can produce infectious forms of any select 
agent virus that have been subjected to a validated inactivation 
procedure or a procedure for removal of viable select agent:
    (i) A written description of the validated inactivation procedure 
or viable select agent removal method used, including validation data;
    (ii) A written description of the viability testing protocol used;
    (iii) A written description of the investigation conducted by the 
entity Responsible Official involving an inactivation or viable select 
agent removal failure and the corrective actions taken;
    (iv) The name of each individual performing the validated 
inactivation or viable select agent removal method;
    (v) The date(s) the validated inactivation or viable select agent 
removal method was completed;
    (vi) The location where the validated inactivation or viable select 
agent removal method was performed; and
    (vii) A certificate, signed by the Principal Investigator, that 
includes the date of inactivation or viable select agent removal, the 
validated inactivation or viable select agent removal method used, and 
the name of the Principal Investigator. A copy of the certificate must 
accompany any transfer of inactivated or select agent removed material.
* * * * *
    (b) The individual or entity must implement a system to ensure that 
all records and data bases created under this part are accurate and 
legible, have controlled access, and authenticity may be verified.
    (c) The individual or entity must promptly produce upon request any 
information that is related to the requirements of this part but is not 
otherwise contained in a record required to be kept by this section. 
The location of such information may include, but is 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. All records created under this part must be maintained for 3 
years.

    Dated: January 9, 2017.
Sylvia M. Burwell,
Secretary.
[FR Doc. 2017-00726 Filed 1-18-17; 8:45 am]
 BILLING CODE 4163-18-P