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Daily Rules, Proposed Rules, and Notices of the Federal Government

DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

9 CFR Part 121

[Docket No. APHIS-2009-0070]

RIN 0579-AD09

Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List; Amendments to the Select Agent and Toxin Regulations

AGENCY: Animal and Plant Health Inspection Service, USDA.
ACTION: Final rule.
SUMMARY: In accordance with the Agricultural Bioterrorism Protection Act of 2002, we are amending and republishing the list of select agents and toxins that have the potential to pose a severe threat to animal or plant health, or to animal or plant products. The Act requires the biennial review and republication of the list of select agents and toxins and the revision of the list as necessary. This action implements the findings of the third biennial review of the list. In addition, we are reorganizing the list of select agents and toxins based on the relative potential of each select agent or toxin to be misused to adversely affect human, plant, or animal health. Such tiering of the list allows for the optimization of security measures for those select agents or toxins that present the greatest risk of deliberate misuse with the most significant potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence. We are also making a number of amendments to the regulations, including the addition of definitions and clarification of language concerning security, training, biosafety, biocontainment, and incident response. These changes will increase the usability of the select agent regulations as well as provide for enhanced program oversight.
DATES: The amendments to 7 CFR 331.1 through 331.10, 331.13, and 331.16 through 331.20 and 9 CFR 121.1 through 121.10, 121.13, 121.16, 121.17, and 121.20 are effective December 4, 2012. The remaining provisions of this final rule are effective April 3, 2013.
FOR FURTHER INFORMATION CONTACT: Mr. Charles L. Divan, Acting Director, APHIS Agriculture Select Agent Program, APHIS, 4700 River Road Unit 2, Riverdale, MD 20737-1231; (301) 851-3300, option 1.
SUPPLEMENTARY INFORMATION: Executive Summary

On July 29, 2010, we published in theFederal Register(75 FR 44724-44725, Docket No. APHIS-2009-0070) an advance notice of proposed rulemaking and request for comments (ANPR)1 and On October 3, 2011, we published in theFederal Register(76 FR 61228-61244, Docket No. APHIS-2009-0070) a proposal2 regarding our intent to amend and republish the list of select agents and toxins that have the potential to pose a severe threat to animal or plant health, or to animal or plant products, reorganize the list of select agents and toxins based on the relative potential of each select agent or toxin to be misused to adversely affect human, plant, or animal health, and amend the regulations in order to add definitions and clarify language concerning security, training, biosafety, biocontainment, and incident response.

1To view the ANPR and the comments we received, go tohttp://www.regulations.gov/#!docketDetail;D=APHIS-2009-0070.

2To view the proposed rule and the comments we received, go tohttp://www.regulations.gov/#!docketDetail;D=APHIS-2009-0070.

Specifically, the ANPR solicited comments regarding whether there are other select agents or toxins that should be added to the Plant Protection and Quarantine (PPQ) and Veterinary Services (VS) lists of select agents and toxins, whether any of the select agents or toxins on the PPQ or VS lists should be removed, whether the PPQ and VS lists of select agents and toxins should be tiered based on the relative bioterrorism risk presented by each select agent or toxin, and whether the security requirements for select agents or toxins in the highest tier should be stratified based on type of use or other factors. Comments received as a result of the ANPR were used in order to inform our discussions on the content of the select agent list and our determination regarding reorganization of the list in the proposed rule. We solicited comments concerning our proposal for 60 days ending December 2, 2011. We reopened and extended the deadline for comments until January 17, 2012, in a document published in theFederal Registeron December 15, 2011 (76 FR 77914, Docket No. APHIS-2009-0070). We received 30 comments by that date. They were from researchers, scientific organizations, laboratories, and universities.

Changes to the current regulations detailed in this final rule include:

1. Modification of the select agent and toxin list:

• The following agents would no longer be considered PPQ select agents or toxins, or would be excluded from compliance with the select agent regulations: Any subspecies ofRalstonia solanacearumexcept race 3, biovar 2 and all subspecies ofSclerophthora rayssiaeexcept var.zeae, and Xylella fastidiosa,citrus variegated chlorosis (CVC) strain.

• The following agents would no longer be considered VS select agents or toxins, or would be excluded from compliance with the select agent regulations: Any low pathogenic strains of avian influenza virus, any strain of Newcastle disease virus which does not meet the criteria for virulent Newcastle disease virus, all subspeciesMycoplasma capricolumexcept subspeciescapripneumoniae(contagious caprine pleuropneumonia), and all subspeciesMycoplasma mycoidesexcept subspeciesmycoidessmall colony (MmmSC) (contagious bovine pleuropneumonia), Akabane virus; Bluetongue virus (exotic), Bovine spongiform encephalopathy agent; Camel pox virus;Ehrlichia ruminantium(Heartwater); Japanese encephalitis virus; Malignant catarrhal fever virus (Alcelaphine herpesvirus type 1); Menangle virus; and Vesicular stomatitis virus (exotic): Indiana subtypes VSV-IN2, VSV-IN3.

• The following agent would no longer be considered a VS/Department of Health and Human Services (HHS) overlap select agent: Venezuelan Equine Encephalitis Virus (subtypes ID and IE).

2. Tiering of the select agent and toxin lists:

Tier 1 select agents and toxins:

• PPQ select agents and toxins: None.

• VS select agents and toxins: Foot-and-mouth disease virus and Rinderpest virus.

• VS/HHS overlap select agents and toxins:Bacillus anthracis, Burkholderia mallei,andBurkholderia pseudomallei.

3. Establishing physical security standards for entities possessing Tier 1 select agents and toxins, including the requirement to conduct pre-access assessments and ongoing monitoring of personnel with access to Tier 1 agents and toxins;

4. Miscellaneous revisions to the regulations to clarify regulatory language concerning security, training, biosafety, and incident response.

Costs of the Rule:Entities affected by the rule include research and diagnostic facilities; Federal, State, and university laboratories; and private commercial and non-profit enterprises. The regulations require registering thepossession, use, and transfer of select agents or toxins. In addition, the entity is 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, that all individuals with 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 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, animal or plant health, or to animal or plant products. APHIS and HHS recognize that several of the required measures of the regulations may impose certain operational costs upon affected entities, particularly entities that have the newly designated Tier 1 select agents and toxins. 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 Table 2 of the Regulatory Impact Analysis located at:www.regulations.govand athttp://www.selectagents.gov.

Benefits of the Rule:The objectives of the final rule is to create a means of ensuring enhanced oversight in the transfer, storage, and use of select agents and toxins; define the security procedures and suitability assessments for pre-access suitability and continual monitoring of individuals with access to Tier 1 select agents and toxins; 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 provisions will be a reduced likelihood of the accidental or intentional release of a select agent or toxin and the avoidance of costs associated with such a release. The goal of the amended regulations is to enhance the protection of human, animal, and plant health and safety.

Background

The Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (referred to below as the Bioterrorism Response Act) provides for the regulation of certain biological agents that have the potential to pose a severe threat to both human and animal health, to animal health, to plant health, or to animal and plant products. The Animal and Plant Health Inspection Service (APHIS) has the primary responsibility for implementing the provisions of the Act within the Department of Agriculture (USDA). 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. Plant Protection and Quarantine (PPQ) select agents and toxins are those that have the potential to pose a severe threat to plant health or plant products. Overlap select agents and toxins are those that have been determined to pose a severe threat to human and animal health or animal products. Overlap select agents are subject to regulation by both APHIS and the Centers for Disease Control and Prevention (CDC), which has the primary responsibility for implementing the provisions of the Act for the Department of Health and Human Services (HHS).

Subtitle B (which is cited as the “Agricultural Bioterrorism Protection Act of 2002” and referred to below as the Act), section 212(a), provides, in part, that the Secretary of Agriculture (the Secretary) must establish by regulation a list of each biological agent and each toxin that the Secretary determines has the potential to pose a severe threat to animal or plant health, or to animal or plant products. Paragraph (a)(2) of section 212 requires the Secretary to review and republish the list every 2 years and to revise the list as necessary. In this document, we are amending and republishing the list of select agents and toxins based on the findings of our third biennial review of the list.

In determining whether to include an agent or toxin on the list, the Act requires that the following criteria be considered:

• The effect of exposure to the agent or the toxin on animal and plant health, and on the production and marketability of animal or plant products;

• The pathogenicity of the agent or the toxin and the methods by which the agent or toxin is transferred to animals or plants;

• The availability and effectiveness of pharmacotherapies and prophylaxis to treat and prevent any illness or disease caused by the agent or toxin; and

• Any other criteria that the Secretary considers appropriate to protect animal or plant health, or animal or plant products.

We use the term “select agents and toxins” throughout the preamble of this final rule. Unless otherwise specified, the term “select agents and toxins” will refer to all agents or toxins listed by APHIS. When it is necessary to specify the type of select agent or toxin, we will use the following terms: “PPQ select agents and toxins” (for the plant agents and toxins listed in 7 CFR 331.3), “VS select agents and toxins” (for the animal agents and toxins listed in 9 CFR 121.3), or “overlap select agents and toxins” (for the agents and toxins listed in both 9 CFR 121.4 and 42 CFR 73.4).

On October 3, 2011, we published in theFederal Register(76 FR 61228-61244, Docket No. APHIS-2009-0070) a proposal3 to amend and republish the list of select agents and toxins that have the potential to pose a severe threat to animal or plant health, or to animal or plant products, reorganize the list of select agents and toxins based on the relative potential of each select agent or toxin to be misused to adversely affect human, plant, or animal health, and amend the regulations in order to add definitions and clarify language concerning security, training, biosafety, biocontainment, and incident response.

3To view the proposed rule and the comments we received, go tohttp://www.regulations.gov/#!docketDetail;D=APHIS-2009-0070.

We solicited comments concerning our proposal for 60 days ending December 2, 2011. We reopened and extended the deadline for comments until January 17, 2012, in a document published in theFederal Registeron December 15, 2011 (76 FR 77914, Docket No. APHIS-2009-0070). We received 30 comments by that date. They were from researchers, scientific organizations, laboratories, and universities. They are discussed below by topic.

Guidance Documents

In the proposed rule, we specifically requested comment from the regulated community and any other interested persons on the need for and desirability of guidance documents that would serve to assist regulated entities in meeting the requirements of regulations. We were particularly interested in public comment regarding Web sites, articles, or other sources useful in developing such guidance documents. We received a number of comments on the issue of guidance, which are discussed below.

Two commenters suggested the use of specific documents in creating guidance: The Laboratory Biorisk Management Standard, which wasdeveloped by the European Committee for Standardization, and the report “Guidance for Enhancing Personnel Reliability and Strengthening the Culture of Responsibility,” which was developed by the National Science Advisory Board for Biosecurity.

We agree with the commenters and have utilized both sources in developing guidance.

One commenter stated that the select agent program should develop a standardized template that addresses each item required by the regulations, both for regulated entities and inspectors. The commenter went on to say that the templates should be posted on the select agent Web site.

The National Select Agent Registry at www.selectagents.gov includes checklists, guidance documents, and templates that we have developed to aid entities in meeting the requirements of the regulations. The select agent program also conducts regular inspector training in order to standardize inspector understanding of the regulations and inspection process. We accept entity feedback regarding the inspection process and incorporate it into our training program as appropriate.

Another commenter stated that the involvement of regulated entities in the development of guidance is crucial, as it will ensure that the new regulations may be implemented without unsustainable increases in cost to those entities.

The guidance documents developed in conjunction with this rule are, in part, a response to the questions and issues raised by the commenters regarding various aspects of the proposed rule. We also consulted HHS and USDA subject matter experts and other sources including National Science Advisory Board for Biosecurity, the National Academies, the Department of Defense Security Engineering Facilities Planning Manual, and Director of Central Intelligence Directive Number 6/9. Regarding the commenter's cost concerns, the guidance developed by the select agent program does not set out a prescriptive series of procedures that must be followed by all regulated entities; rather, it establishes examples of ways in which an entity may choose to meet the requirements of the regulations. We have purposefully left the regulations in their general state in order to allow for the wide variety of regulated entities to meet the regulatory standard in a way that is most cost-effective for each.

PPQ Select Agents and Toxins

We proposed to amend the list of PPQ select agents and toxins listed in 7 CFR 331.3 by removingXylella fastidiosa,citrus variegated chlorosis (CVC) strain, from the list as it no longer meets the criteria for use as an agroterrorism agent.

One commenter stated that the scientific basis for the removal ofXylella fastidiosafrom the list was unclear and requested clarification concerning our decision. The commenter additionally stated that if the review process for such removal were to be transparent, with expert opinion from the public and private sector, including a sound scientific analysis and an assessment of the biosecurity risk of each agent, other plant pathogens on the list of select agents and toxins could potentially be removed.

We are making no changes as a result of this comment. Each agent on the select agent and toxin list was considered for retention or removal based on a variety of factors, including, but not limited to, the scientific concerns cited by the commenter. Further, the select agent program did employ subject-matter experts as part of the decision-making process as recommended by the commenter in addition to soliciting public comment. Experts in the biology of these agents and toxins evaluated their “potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence.” This evaluation included assessments of morbidity and mortality, communicability, low infectious dose, availability of countermeasures, and economic impact of a potential attack. Each agent and toxin was then assessed for its “risk of deliberate misuse,” including its history of weaponization and/or known interest by State or non-State adversaries. These evaluations, combined with input received as a result of the publication of an advance notice of proposed rulemaking and request for comments (ANPR)4 in theFederal Registeron July 29, 2010, and relevant findings in recent government and non-government reports, formed the basis for deliberations concerning which agents should constitute the list. It is important to note that removal of pathogens from the list of select agents and toxins does not mean that they are not of potential concern, but rather that the risk they represent has been reevaluated using the above criteria. Reduction of the list is meant to decrease the burden on researchers and focus attention on agents and toxins judged to be of greatest biosecurity concern.

4To view the ANPR and the comments we received, go tohttp://www.regulations.gov/#!docketDetail;D=APHIS-2009-0070.

The list of PPQ select agents and toxins includes an entry forXanthomonas oryzae.While we did not propose any changes to the entry forXanthomonas oryzae,one commenter stated that it should be removed from the list of select agents and toxins and offered a number of arguments, which are discussed below.

The commenter proposed the removal ofXanthomonas oryzaebased on the assertion thatXanthomonas oryzaepopulations are adapted only to local conditions and do not persist upon introduction to new environments. Given that the major natural host forXanthomonas oryzaeis rice, the commenter also compared cultivation practices utilized in domestic commercial rice production with those utilized in Asian commercial rice production. The commenter argued that domestic commercial cultivation practices eliminate transmission of the pathogen since rice seeds are directly planted whereas in Asia rice seedlings are cultivated elsewhere and then transplanted, and wounds created during such handling and transplant are important modes of transmission for the pathogen to healthy seedlings. In addition, the commenter said that domestic weather patterns are not conducive to dissemination and that quarantines can prevent seed-borne disease. The commenter claimed that field-to-field spread ofXanthomonas oryzaein Asia is largely dependent on the strong winds and driving rains that occur frequently during typhoon season.

We are making no changes to the regulations as a result of this comment. Natural spread or persistence of the pathogen in a particular location is not at issue; it is the risk of deliberate misuse leading to the most significant potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence. The issue of standard commercial planting practices for rice in a domestic versus Asian setting is not relevant to the discussion ofXanthomonas oryzae's potential for use as a biological weapon. APHIS analyzed and assessed this pathogen using the criteria discussed earlier in this document. Based on that analysis and assessment and the knowledge thatXanthomonas oryzaehas been modified for use as a biological weapon in the past, it has been retained on the list of PPQ select agents and toxins.

The commenter also stated thatXanthomonas oryzaeshould beremoved from the list of select agents and toxins because it is endemic in the United States and any foreign strains introduced in the future would prove unlikely to establish and spread.

While we disagree with the commenter's assertion regardingXanthomonas oryzae's pathogenicity, these arguments are unrelated to the work of the select agent program as a whole as the select agent regulations do not allow for the environmental release of listed agents and toxins. Whether or not a given select agent or toxin is endemic in the United States is not the only determining factor in the select agent or toxin's inclusion on the list. The regulations govern use of listed select agents and toxins in laboratory settings only. In this regard, the case for maintainingXanthomonas oryzaeon the list of those select agents and toxins whose deliberate misuse represents the most significant potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence, is compelling as work was done onXanthomonas oryzaein the 1970s which led to its classification as a bioterrorism agent by the security community.

The list of PPQ select agents and toxins includes an entry forRalstonia solanacearum,race 3, biovar 2. While we did not propose any changes to the entry forRalstonia solanacearum,race 3, biovar 2, five commenters stated that it should be removed from the list of select agents and toxins.

The commenters argued that, based on the biological and historical climate data for North America,Ralstonia solanacearum,race 3, biovar 2 does not have the potential to pose a severe threat to plant health or plant products in the context of U.S. agriculture. The commenters stated thatRalstonia solanacearum,race 3, biovar 2 is only a serious problem in the developing world in those areas of cool highland tropics where annual temperature profiles differ significantly from those found in the major potato growing regions in the United States (i.e., Colorado, Idaho, Maine, Minnesota, North Dakota, and Wisconsin). The commenters argued that, unlike the northern States, the cool highland tropics experience few hard freezes and no long winters. Since, the commenters claimed, epidemiological and laboratory research data show thatRalstonia solanacearum,race 3, biovar 2 is intolerant of freezing and freeze-thaw cycles and does not generally survive winters in regions with sustained low temperatures, the bacterium is unlikely to become established in the northern U.S. where potatoes are commercially grown.

We disagree with the commenters' claim thatRalstonia solanacearum,race 3, biovar 2 is only a serious pathogen in the developing world as the bacterium has been shown to establish itself in northern Europe by over-wintering in weeds, thereby posing a severe threat toSolanaceaespecies (e.g., potato, eggplant, and tomato) in cool climates such as those found both in northern Europe and North America. In addition, as discussed earlier in this document, the evaluation process for select agents includes broad criteria that not only focus on the biological characteristics of a given pathogen, but also that pathogen's ability to produce a devastating effect on the economy and the threat that pathogen represents if it were to be used as a biological weapon. We are making no changes as a result of these comments.

The commenters also stated that retainingRalstonia solanacearum,race 3, biovar 2 on the list of select agents and toxins would further constrain research in the field ofRalstoniaresearch. The commenters attributed such listing with registration time for use, transfer, or possession of select agents and toxins in excess of 18 months prior to the initiation of research and difficulty in meeting the registration requirements.

We are making no changes in response to these comments. While there are added requirements concerning physical security, personnel authorization, recordkeeping, biocontainment, and site inspections, we do not believe these requirements will impede research as, in many cases these regulations serve to codify systems and procedures already in use by a majority of regulated entities. Further, entity registration for use, transfer, or possession of select agents and toxins does not take, nor has ever taken, 18 months. On average, new entity registration takes 6 months from the date the request is received by the select agent program and the issuance of the registration certificate. The security risk assessment (SRA) takes less than 45 days and runs parallel to the entity registration process. These timeframes are all based on the assumption that the entity registration submission and the SRA submission are complete and accurate for select agent program review prior to the required on-site inspection.

Commenters additionally stated thatRalstonia solanacearum,race 3, biovar 2 should be removed from the list for the same reasons that were cited for the proposed removal ofXylella fastidiosa,CVC strain.

We are making no changes as a result of these comments. The decision to remove the CVC strain from the list of select agents and toxins was based on the completion of extensive review and analysis of the criteria for inclusion on the list. In particular, the creation of detection methods and the use of geostatistical analysis with relation to monitoring in order to facilitate a response to any purposeful introduction are both key components in our decision to delist CVC. As discussed earlier in this document, the evaluation process for select agents includes a broad number of criteria that not only focus on the biological characteristics of a given pathogen but also that pathogen's ability to produce a devastating effect on the economy and the threat that pathogen represents if it were to be used as a biological weapon. Based on that analysis and assessmentRalstonia solanacearum,race 3, biovar 2 will remain on the list of select agents and toxins.

Commenters said that eradicatingRalstonia solanacearum,race 3, biovar 2 introduced into the United States through infected geraniums cost commercial greenhouses and importers millions of dollars as a direct result of its presence on the list of select agents and toxins.

We are making no changes as a result of these comments. The presence ofRalstonia solanacearum,race 3, biovar 2 on the list of select agents and toxins had no bearing on the eradication program instituted by APHIS. The cost of this eradication program to commercial greenhouses and importers was the same as the cost of eradicating any other quarantine plant pathogen not known to be present in the United States.

Identification of Strains

The list of VS select agents and toxins includes an entry for virulent Newcastle disease virus. While we did not propose any changes to the entry for virulent Newcastle disease virus, one commenter stated that, by not considering all forms of Newcastle disease virus as select agents, APHIS has created a period of uncertainty prior to the completion of the sequencing necessary to identify whether a form of Newcastle disease virus is virulent or not. The commenter requested clarification as to whether laboratories would be required to treat uncharacterized Newcastle disease virus as a select agent given this uncertainty.

We agree with the commenter's point. We have therefore revised the list of VS only select agents and toxins in order to list certain select agents and toxins not by specific strains but by the generictaxonomic classifications for those select agents. The specific VS only select agents and toxins affected are: Avian influenza virus (highly pathogenic),mycoplasma capricolumsubspeciescapripneumoniae(contagious caprine pleuropneumonia),mycoplasma mycoidessubspeciesmycoidessmall colony (MmmSC) (contagious bovine pleuropneumonia), and virulent Newcastle disease virus, which we have altered to read avian influenza virus,mycoplasma capricolum, mycoplasma mycoides,and Newcastle disease virus, respectively. In order to capture the applicable strains, subtypes, or pathogenicity levels we have also added exemptions for those strains, subtypes, or pathogenicity levels of certain select agents and toxins which are not considered to have the potential to pose a severe threat to animal health or animal products.

The list of overlap select agents and toxins contains an entry for Venezuelan equine encephalitis. One commenter stated that, by not considering all subtypes of Venezuelan equine encephalitis as select agents, APHIS has created a period of uncertainty prior to the completion of the typing necessary to identify whether a form of Venezuelan equine encephalitis is among the subtypes classified by APHIS as select agents. The commenter requested clarification as to whether laboratories would be required to treat untyped Venezuelan equine encephalitis as a select agent given this uncertainty.

We agree with the commenter's point. As stated previously, we have therefore revised the list of overlap select agents and toxins in order to list certain select agents and toxins not by specific strains but by the generic taxonomic classifications for those select agents. The specific overlap select agent is Venezuelan equine encephalitis virus: Epizootic Subtypes IAB, IC, which we have altered to read Venezuelan equine encephalitis virus. In order to capture the applicable strains, subtypes, or pathogenicity levels we have also added exemptions for those strains, subtypes, or pathogenicity levels of certain select agents and toxins which are not considered to have the potential to pose a severe threat to animal or human health or animal products. We do note that we have specifically includedBacillus anthracis(Pasteur strain) in the list of overlap select agents and toxins. This is necessary in order to distinguish this strain, which we do not consider to be a Tier 1 select agent, from all other strains ofBacillus anthracis,which are classified as Tier 1 select agents.

Although we did not receive any comments on this issue as it concerns PPQ only select agents and toxins, in order to strengthen the regulations as discussed previously as well as to maintain parity between the VS and PPQ regulations, we are revising the list of PPQ only select agents and toxins in order to list certain select agents and toxins not by specific strains but by the generic taxonomic classifications for those select agents. The specific PPQ only select agents and toxins affected are:Ralstonia solanacearum,race 3, biovar 2 andSclerophthora rayssiaevar.zeaewhich we have altered to readRalstonia solanacearumandSclerophthora rayssiae,respectively. In order to capture the applicable strains, subtypes, or pathogenicity levels we have also added exemptions for those strains, subtypes, or pathogenicity levels of certain select agents and toxins which are not considered to have the potential to pose a severe threat to plant health or plant products.

With the changes described above, we clearly establish that when an agent or toxin is initially identified to a taxonomic level, in the case of an agent, or by its toxicological properties, in the case of a toxin, it is regulated under the select agent regulations until further testing is accomplished to exclude the particular agent by strain, subtype, pathogenicity levels, or a particular toxin by properties. We believe it is important that laboratories treat these agents as select agents until further testing can be conducted to verify whether the agent is of a strain, subtype, or pathogenicity level that presents a higher level of danger to animal health and safety. These changes will not have any impact on the exemption for diagnostic laboratories or alter the process of receiving diagnostic samples and forwarding any potentially identified select agents for further testing. They also do not change the reporting criteria for those agents confirmed to be select agents. Finally, they do not change the current lists of select agents and toxins but alters the fashion in which select agents and toxins are listed with specific exemptions included to ensure that appropriate verification of the agents by strains, subtypes, or pathogenicity level occurs.

VS Select Agents and Toxins

We proposed to remove nine VS select agents and toxins from the list set out in § 121.3(b). Specifically, we proposed to remove the following: Akabane virus; Bluetongue virus (exotic), Bovine spongiform encephalopathy agent; Camel pox virus;Ehrlichia ruminantium(Heartwater); Japanese encephalitis virus; Malignant catarrhal fever virus (Alcelaphine herpesvirus type 1); Menangle virus; and Vesicular stomatitis virus (exotic): Indiana subtypes VSV-IN2, VSV-IN3.

One commenter recommended that we exclude the Texas GB strain of Newcastle disease virus from select agent status. The commenter stated that the exclusion is warranted since, although Newcastle disease virus is widespread in the environment, there is little illness if a flock is exposed because nearly all commercial poultry is vaccinated against the disease. The commenter observed that the Texas GB strain of Newcastle disease virus is used by vaccine manufacturers as the challenge organism to verify the potency of Newcastle disease virus vaccines and this fact gives poultry producers a high degree of assurance that their flocks are protected against the Texas GB strain. Given these factors, the commenter concluded that the Texas GB strain is not a biosecurity threat to the domestic poultry industry, and the strain should be excluded from APHIS's definition of virulent Newcastle disease virus.

We are making no change in this final rule as a result of this comment. Texas GB strain of Newcastle disease virus is a highly virulent form of Newcastle disease virus and, as such, is appropriately included in the general category of “virulent Newcastle disease virus.” While vaccine manufacturers do use the Texas GB strain of Newcastle disease virus as a challenge organism for Newcastle disease virus vaccines, this is on account of its high level of virulence. A vaccine effective against the Texas GB strain of Newcastle disease virus can therefore be assumed to be effective against less virulent forms of Newcastle disease virus.

The list of VS select agents and toxins includes an entry for avian influenza virus (highly pathogenic) (HPAI). While we did not propose any changes to the entry for HPAI, one commenter proposed that we change the guidance by which influenza strains are categorized as HPAI. The commenter argued that extensive evidence has been obtained to support the conclusion that, while the HA polybasic cleavage site is the primary determinant for HPAI strains, strains with removed HA polybasic cleavage sites have been created, tested, and ultimately excluded from select agent status. The commenter stated that, as a result of these experiments and history, APHIS should specify that avian influenza strains without the HA polybasic cleavage site are not HPAI viruses and, therefore, not subject to the select agent regulations.

The commenter further argued that continuing to consider strains of avian influenza with removed HA polybasic cleavage sites as select agents until such time as an exclusion is granted would impede vaccine availability in the event of an HPAI pandemic in either the human or avian population. The commenter stated that the lead candidates for the seed viruses that would be used to make vaccines against HPAI viruses during such an event will likely be attenuated strains with mutated polybasic cleavage sites. The commenter stated that the current process by which avian influenza strains that lack the polybasic cleavage site are granted exclusions takes weeks or months, an untenable timeline in the event of an HPAI pandemic.

We are making no changes in response to this comment. APHIS standards are based on existing internationally recognized requirements established by the World Animal Health Organization (OIE). In the event of a future HPAI pandemic such as the one described by the commenter, APHIS would work in conjunction with HHS to address any vaccine availability issues. Finally, attenuated strains of select agents officially approved for human vaccination purposes by the Food and Drug Administration (FDA) or other recognized national or international organizations continue to be exempt from the select agent regulations as specified by the regulations in § 121.5(c) and (d).

Overlap Select Agents and Toxins

We proposed to modify the list of overlap select agents and toxins by removing certain subtypes of Venezuelan equine encephalitis virus from the list of overlap select agents and toxins set out in 9 CFR 121.4(b), and to clarify that only Venezuelan equine encephalitis subtypes IAB and IC would remain on the list. These subtypes contain the only recognized strains of Venezuelan equine encephalitis that can suddenly affect a large number of animals over a large area (i.e., epizootic). The remaining subtypes, ID and IE, are strains prevalent among existing animal populations (i.e., enzootic) and do not represent the same type of risk. Other viruses within the Venezuelan equine encephalitis complex (subtypes IF and II through IV) are separate viruses and are not included in the list of overlap select agents and toxins.

Another commenter recommended that we remove Venezuelan equine encephalitis strain 3014 from the list of select agents and toxins. The commenter argued that, although strain 3014 was derived from a 1AB isolate, this molecularly cloned strain has properties that render it incapable of causing epizootic or epidemic transmission. The commenter stated that mutations selected after only a handful of passages make the virus avirulent in adult mice and dramatically increases its clearance from the bloodstream of mice following intravenous inoculation. Further, the vanishingly low titers of strain 3014 consist of envelope glycoprotein gene mutations, which allow the strain to bind heparin sulfate; such binding is also associated with the attenuated phenotype of Venezuelan equine encephalitis strain TC-83, which is also derived from the 1AB Trinidad donkey strain by passage in culture that has already been excluded from select agent status.

We are making no changes as a result of this comment. Since Venezuelan equine encephalitis strain 3014 is derived from a listed overlap select agent, the commenter's proposal for its removal is more appropriately addressed via the exclusion process for overlap select agents and toxins as detailed in 9 CFR 121.6. We have contacted the commenter and provided guidance regarding how they may initiate this process.

We proposed to designateBacillus anthracisas a Tier 1 select agent. A number of commenters objected to such a blanket designation, arguing instead that theBacillus anthracisPasteur strain should be exempted from consideration both as a Tier 1 select agent and as a select agent in general.

One commenter argued that given the fact that Laboratory Response Network (LRN) laboratories maintain live cultures of non-pathogenicBacillus anthracisPasteur strain for use in quality control testing, designation ofBacillus anthracisas a Tier 1 select agent therefore has the potential to impact the willingness or ability of LRN laboratories to maintain inventories ofBacillus anthracisPasteur strain due to the regulatory and financial burdens associated with possession of Tier 1 select agents and toxins. The commenter went on to state that this situation could potentially impact national health and safety given that the potential use ofBacillus anthracisspores as a bioweapon remains a viable threat and increased burdens, particularly on small laboratories, could lead to the overall decrease in the number of laboratories that would otherwise serve to ensure that the LRN has sufficient capacity to detect and respond to a deliberate release ofBacillus anthracis.

Three commenters stated that theBacillus anthracisPasteur strain is analogous to theBacillus anthracisSterne strain, which is excluded since it was determined not to pose a severe threat to public health and safety, animal health, or animal products. The commenter argued thatBacillus anthracisPasteur strain should not be considered as a select agent given that the only way to create an agent that poses a severe threat would be via combination of the Pasteur strain with a non-regulated strain. The commenter pointed out that other agents that pose little harm individually, but could be modified genetically to become harmful are not included on the select agent list because of this potential threat.

Another commenter claimed that the designation ofBacillus anthracisPasteur strain as a select agent would not serve to prevent an authorized person from intentionally or accidentally facilitating the combination of plasmids from Sterne and Pasteur types of strains to create a wild type phenotype. The commenter stated that combination of these two strains can be accomplished no matter what sort of physical security may be employed to prevent access, theft, loss, or release of the agent. The commenter concluded that more effective preventive measures can be achieved through training and educating microbiologists on how to avoid accidentally combining these two strains and by penalizing any individuals who intentionally try to combine them.

We agree with the commenters thatBacillus anthracisPasteur strain is attenuated and poses a significantly lower risk than wild typeBacillus anthracisstrains. We also agree that the Pasteur strain is not likely to have the potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence and therefore does not meet the criteria used to apply the Tier 1 designation. In addition, we note that the Pasteur strain has been used successfully as a veterinary and human vaccine, which further demonstrates the attenuation of this strain. Therefore we have determined that theBacillus anthracisPasteur strain should not be designated as a Tier 1 select agent.

While we agree that theBacillus anthracisPasteur strain does not meet the criteria for inclusion as a Tier 1 select agent, we do not agree with the argument that regulating theBacillus anthracisPasteur strain would not serve to prevent the accidental (or intentional) generation of a wild typeBacillus anthracisstrain by the combination of theBacillus anthracisPasteur strain with theBacillus anthracispXO1+/pXO2- Sterne strain. Retaining the Bacillus anthracisPasteur strain as a select agent will allow for continued oversight of laboratories in which the accidental (or intentional) combination of this strain with theBacillus anthracisSterne strain could occur to produce the wild type phenotype ofBacillus anthracisde novo. Failure to retain theBacillus anthracisPasteur strain as a select agent could result in an environment in which the probability of creation of virulent wild typeBacillus anthracisstrains by the combination of non-regulated strains would be enhanced. Therefore, we have chosen not to exclude theBacillus anthracisPasteur strain from the list of select agents in this rulemaking. We will continue to evaluate exclusion requests as additional information becomes available in this area.

As explained above under the heading “VS Select Agents and Toxins,” avian influenza virus (highly pathogenic) is currently on the list of VS only select agents and toxins. One commenter recommended that, in light of recent studies whereby researchers have generated derivatives of influenza virus A (H5N1) capable of efficient aerosol transmission, we add “Replication competent forms of influenza virus A (H5N1) capable of efficient aerosol transmission in ferrets or primates containing any portion of the coding regions of all eight gene segments [influenza virus A (H5N1) capable of efficient aerosol transmission in ferrets or primates]” to the list of overlap select agents and toxins. The commenter also recommended that this type of avian influenza virus be classified as a Tier 1 agent given the historical 50 percent case-fatality rate of avian influenza virus A (H5N1) in humans.

The select agent program is currently in discussions regarding this issue and may address it in future rulemaking. Given the stage these discussions are in, however, we are not making any changes in this final rule based on this comment.

Reorganization of the Current List of Select Agents and Toxins

We proposed to establish a number of select agents and toxins as “Tier 1” select agents and toxins within the lists of VS and overlap select agents and toxins. Specifically, we proposed to list foot-and-mouth disease (FMD) virus and rinderpest virus as Tier 1 VS select agents and toxins andBacillus anthracis, Burkholderia mallei,andBurkholderia pseudomalleias Tier 1 overlap select agents and toxins. We did not include PPQ select agents and toxins in this proposed reorganization because none of the PPQ select agents and toxins met the minimumcriteria for inclusion on the proposed Tier 1 select agents and toxins list. All other select agents and toxins would continue to be subject to the current requirements concerning select agents and toxins.

One commenter argued thatBurkholderia malleiandBurkholderia pseudomalleishould not be classified as Tier 1 select agents. The commenter stated that these two select agents do not represent the same level of concern as the other select agents proposed for inclusion in Tier 1 and should therefore be assigned non-Tier 1 status.

Another commenter observed thatBacillus anthracisis less virulent than eitherYersinia pestisorFrancisella tularensis, which are on the list of HHS only select agents and toxins. The commenter additionally stated that the virulence of all three is far less than that of the hemorrhagic fever viruses and the encephalitis viruses that were not proposed for inclusion on the list of Tier 1 select agents and toxins. The commenter stated that significant advances have been made in the development of products for environmental decontamination and prophylaxis against inhalation ofBacillus anthracis.

We are making no changes to the regulations as a result of these comments. The process by which we determined which select agents and toxins should be designated as Tier 1 was multi-faceted and we are confident in the results of that process. Our determinations were not based on one aspect of each of the proposed select agents or toxins only. In order to determine which select agents and toxins should be given Tier 1 status, a two-part risk analysis was conducted on each. First, experts in the biology of these agents and toxins evaluated their potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence. This process included assessments of morbidity and mortality, communicability, low infectious dose, availability of countermeasures, and economic impact of a potential attack. Second, each select agent and toxin was assessed for its risk of deliberate misuse, including its history of weaponization and/or known interest by State or non-State adversaries. These evaluations, combined with input from public comments received on our July 2010 ANPR and relevant findings in recent government and non-government reports, formed thebasis for deliberations on which agents should constitute the Tier list. Agents that scored highly on both the public health and biothreat sets of criteria were judged to be those that were appropriately given a Tier 1 designation.

Two commenters pointed out that the categorization of select agents and toxins has already been carefully stratified into four biological safety levels (BSL) as specified by the CDC, with each BSL based on infectivity, virulence, and ease of transmission of the material in question. The commenters further observed that the Tier 1 designation implies the existence of a Tier 2 category which would require less attention to security. The commenters concluded that the process of tiering will only add confusion and administrative and financial burden to the current BSL grouping of select agents and toxins.

Two additional commenters stated that the proposed rule did not do enough to reduce the regulatory burden associated with non-Tier 1 agents. The commenters said that reduced levels of security requirements for personnel and facilities should be considered for non-Tier 1 agents.

In designating certain select agents and toxins as “Tier 1,” the select agent program considered and rejected the idea of designating the remaining select agents and toxins as “Tier 2.” The aim of establishing the Tier 1 category is to account for and respond to the particular risks associated with the agents and toxins in this category by increasing their handling and security requirements accordingly. The establishment of the Tier 1 category is in no way intended to imply that the non-Tier 1 select agents and toxins pose a lesser risk to public health and safety than they have previously. In accordance with that fact, we have not decreased the handling and security requirements for those non-Tier 1 agents. Biosafety levels describe the required combination of lab practices and techniques, safety equipment, and lab facilities appropriate for the operations being performed using potentially harmful materials such as select agents and toxins while the Tier 1 designation institutes security measures applicable to the agents and toxins themselves. For this reason there is no conflict that exists between BSL classifications and Tier 1 select agents and toxins.

Two commenters expressed concern regarding the proposal to list rinderpest virus as a Tier 1 agent, given that there are already special conditions in place as contained in §§ 121.3(f)(3)(i), 121.5(a)(3)(i), and 121.9(c)(1) concerning its handling and tracking. The commenters suggested that an alternative approach would be for APHIS to designate rinderpest virus asa pathogen with very special handling requirements that is not considered to be part of either category of select agents. The commenters argued that this approach is justified due to the fact that rinderpest has now been officially eradicated worldwide.

We disagree with the commenters' suggestion to classify rinderpest virus as a separate type of agent apart from either of the select agent categories of designation. While it is true that rinderpest was declared to be officially eradicated by the OIE on May 25, 2011, this development does not render the disease any less of a concern as a select agent with potential formisuse. Enacting the suggestion that rinderpest virus be treated as a pathogen with “very special handling requirements” and not as either a Tier 1 or non-Tier 1 select agent would only serve to create a further level of required administrative oversight for regulated entities.

One commenter stated that the proposed tiering system poses significant questions as to the nature of the risk assessment process. Specifically, the commenter questioned listing as Tier 1 agents bacterial diseases that are treated with licensed antibiotics, that are not commonly spread person to person, and that are present in the environment of the United States, while viruses that have no known therapy and that pose extreme risk to Western populations are absent. The commenter further stated that the 20 criteria used for evaluation of each select agent and toxin should be made available to the regulated community for review and assessment.

We are making no changes as a result of this comment. The relative ease by which exposure to a select agent or toxin may be treated is only one aspect considered by the select agent program when determining the tier status of each. The 20 criteria referenced by the commenter are those employed by the Federal Experts Security Advisory Panel (FESAP) in providing recommendations to the select agent program. The criteria that the FESAP used in its risk assessment process are:

1. The relative ease with which a select agent or toxin might be acquired from a laboratory or commercial source;

2. The relative ease of production of a select agent or toxin;

3. The relative ease by which a select agent or toxin might be modified in order to enhance its pathogenicity, transmissibility, or ability to evade medical and non-medical countermeasures;

4. The potential for easy deliberate dissemination;

5. The potential for creating disease or illness;

6. The relative environmental stability of a select agent or toxin by itself and how well it survives in the environment in which it is formulated or disseminated;

7. The amount of select agent or toxin necessary to induce illness;

8. The relative ease with which a particular select agent or toxin might be disseminated or transmitted from one animal or person to another or into the environment where it could produce a deleterious effect upon animal, plant, or human health;

9. Whether the target population has innate immunity to the select agent or toxin or whether immunity has been acquired from a source such as vaccines;

10. The potential for the select agent or toxin to create morbidity (i.e., any non-fatal illness that renders partial dysfunction to an animal or human lasting weeks or months that will eventually resolve with medical, veterinary, and/or supportive care);

11. The burden placed on the human, veterinary, or plant health system by the deliberate release of the select agent or toxin;

12. The ability to detect a release of the select agent or toxin into the environment, food, water, or soil;

13. The ability of the human and agricultural health authorities to accurately and rapidly diagnose and treat the disease presented by a release of the select agent or toxin;

14. The existence of countermeasures to prevent, treat, or mitigate the symptoms of a disease caused by the release of a select agent or toxin and/or its spread through a population;

15. The potential for high animal, plant, or human mortality rates with delivery of medical countermeasures;

16. The potential for high animal, plant, or human mortality rates without delivery of medical countermeasures;

17. The short-term economic impact of a single outbreak of a disease or release of a toxin;

18. The human, monetary, and other resource costs of making an area, building, industrial plant, farm, or field safe for humans, animals or plants to inhabit following the release of the select agent or toxin;

19. The pathogen's ability to persist in the environment or to find a reservoir that makes its recurrence more likely; and

20. The long-term health or economic consequences caused by a single release of the select agent or toxin.

We believe that the process by which determinations were made regarding the Tier 1 or non-Tier 1 status of the select agents and toxins was responsive to regulated community concerns received during the comment period for the advance notice of proposed rulemaking as well as for the proposed rule.

One commenter asked why the requirements for working with plant pathogens had not been lessened. The commenter stated that a transparent process does not exist that is inclusive of expert opinion from both the private and public sectors to determine which agents should be removed or added to the list of select agents and toxins.

We are making no changes as a result of this comment. In creating the Tier 1 class of agents, the Select Agent Program considered and rejected the idea of designating the remaining agents as “Tier 2.” The aim of establishing the Tier 1 category is to account for and respond to the particular risks associated with the agents and toxins in this category by increasing their handling and security requirements accordingly. The establishment of the Tier 1 category is in no way intended to imply that the non-Tier 1 agents pose a lesser risk to public health and safety than they have previously. In accordance with that fact, we have not decreased the handling and security requirements for those non-Tier 1 agents. Further, we determined that the establishment of more varying levels of risk would serve to create the need for increased administrative oversight and complication for regulated entities. We believe that the process by which these determinations were made was sensitive to public and expert opinion via the comment period on the initial advance notice of proposed rulemaking as well as on the proposed rule.

Security Measures for Tier 1 Select Agents or Toxins

We also proposed additions to the VS regulations that would allow for the optimization of security measures for those select agents or toxins that are designated as Tier 1. These requirements included:

• Additions regarding the assessment of persons prior to their access to Tier 1 select agents and toxins that would be made to the security plan currently required to be developed by all entities seeking approval for the possession, use, and transfer of select agents and toxins; ongoing oversight of those persons with access to Tier 1 select agents and toxins; and the role of the entity's responsible official in coordinating and assuring the security of Tier 1 select agents and toxins;

• Security enhancements that include provisions for security barriers, intrusion detection and monitoring,delay/response force, access control, and information security;

• Additions to the biosafety plan currently required to be developed by all entities seeking approval for the possession, use, and transfer of select agents and toxins that would describe implementation of an occupational health program for individuals with access to Tier 1 select agents and toxins;

• Development of security policies and procedures describing the entity's response to a failure of an intrusion detection or alarm system and notification procedures for the Federal Bureau of Investigation (FBI) in the event of theft or suspicious activity that may be criminal in nature involving a Tier 1 select agent or toxin. These policies and procedures would be required as part of the entity's incident response plan; and

• Required annual insider threat awareness briefings focused on how to identify and report suspicious behaviors.

We have made changes to some of these proposed requirements, which are discussed in detail below.

Many commenters had questions or concerns regarding the additions to the security plan for those entities possessing a Tier 1 select agent or toxin as proposed in 9 CFR 121.11(e). Specific issues addressed by the commenters included: Conduct of pre-access suitability assessments, ongoing suitability assessments, and self- and peer-reporting of incidents or conditions that could affect an individual's ability to safely have access to or work with select agents and toxins. Commenters generally fell into two categories in their responses to the proposed additions: Some felt that the requirements were too vague to prove useful, creating administrative burden without improving the overall security of Tier 1 select agents and toxins, while others felt that the requirements could or would require entities to behave in a manner contrary to local laws, privacy laws, or union contracts.

For the most part, we anticipate that these requirements are already being met and that these regulations will merely require those entities possessing a Tier 1 select agent or toxin to codify and document the systems and processes currently in place. It should be noted that many of the specific concerns raised by commenters regarding potential violation of laws or union contracts arose as a result of the commenters' examination of those recommendations given to the select agent program by the FESAP. As a matter of clarification, the select agent program considered the FESAP recommendations, as well as recommendations from other sources (e.g.,National Science Advisory Board for Biosecurity), in developing the proposed rule and suitability assessment guidance documents; however, we are not adopting all of the specific recommendations found in these studies. While we have created specific guidance to aid in compliance with this section of the revised regulations, we are deliberately leaving the regulatory text in its broadly-written state in order to allow entities a measure of flexibility in how they meet the requirements. Given our experience with the select agent and toxin regulations and the wide variety of regulated entities the regulations cover, we have found this to be the most effective approach. The guidance document developed in conjunction with this rule is, in part, a response to the questions and issues raised by the commenters. Issues addressed in this document include, but are not limited to:

• Understanding the risks and reasons for suitability assessments;

• Delineating the roles and responsibilities of individuals to ensure optimal security;

• Requesting information about individuals in a standardized manner and assessing individuals in the context of safety and security;

• Responding to reports in a consistent, prompt, and confidential manner; and

• Providing training for recognizing and reporting suspicious behavior.

Full guidance on this and other issues may be found on the National Select Agent Registry atwww.selectagents.gov.

In 9 CFR