42 C.F.R. PART 73—SELECT AGENTS AND TOXINS
Title 42 - Public Health
Authority: 42 U.S.C. 262a; sections 201–204, 221 and 231 of Title II of Public Law 107–188, 116 Stat. 637 (42 U.S.C. 262a).
Source: 70 FR 13316, Mar. 18, 2005, unless otherwise noted.
For purposes of this part: Administrator means the Administrator, Animal and Plant Health Inspection Service, or any person authorized to act for the Administrator. Animal and Plant Health Inspection Service (APHIS) means the Animal and Plant Health Inspection Service of the U.S. Department of Agriculture. Attorney General means the Attorney General of the United States or any person authorized to act for the Attorney General. Biological agent means any microorganism (including, but not limited to, bacteria, viruses, fungi, rickettsiae, or protozoa), or infectious substance, or any naturally occurring, bioengineered, or synthesized component of any such microorganism or infectious substance, capable of causing death, disease, or other biological malfunction in a human, an animal, a plant, or another living organism; deterioration of food, water, equipment, supplies, or material of any kind; or deleterious alteration of the environment. CDC means Centers for Disease Control and Prevention of the Department of Health and Human Services. Diagnosis means 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 directly related to protecting the public health or safety, animal health or animal products, or plant health or plant products. Entity means any government agency (Federal, State, or local), academic institution, corporation, company, partnership, society, association, firm, sole proprietorship, or other legal entity. HHS means the Department of Health and Human Services. HHS Secretary means the Secretary of the Department of Health and Human Services or his or her designee, unless otherwise specified. HHS select agent and/or toxin means a biological agent or toxin included in §73.3. Overlap select agent and/or toxin means a biological agent or toxin listed in §73.4 and 9 CFR part 121.4. Principal investigator means the one individual who is designated by the entity to direct a project or program and who is responsible to the entity for the scientific and technical direction of that project or program. Proficiency testing means the process of determining the competency of an individual or laboratory to perform a specified test or procedure. Responsible Official means the individual designated by an entity with the authority and control to ensure compliance with the regulations in this part. Select agent and/or toxin means unless otherwise specified, all of the biological agents or toxins listed in §§73.3 and 73.4. Specimen means samples of material from humans, animals, plants or the environment or isolates or cultures from such samples for the diagnosis, verification, or proficiency testing. State means any of the several States of the United States, the Commonwealth of the Northern Mariana Islands, the Commonwealth of Puerto Rico, the District of Columbia, Guam, the Virgin Islands of the United States, or any other territory or possession of the United States. Toxin means the toxic material or product of plants, animals, microorganisms (including, but not limited to, bacteria, viruses, fungi, rickettsiae, or protozoa), or infectious substances, or a recombinant or synthesized molecule, whatever their origin and method of production, and includes any poisonous substance or biological product that may be engineered as a result of biotechnology, produced by a living organism; or any poisonous isomer or biological product, homolog, or derivative of such a substance. United States means all of the States. USDA means the United States Department of Agriculture. Verification means the demonstration of obtaining established performance (e.g., accuracy, precision, and the analytical sensitivity and specificity) specifications for any procedure used for diagnosis. This part implements the provisions of the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 setting forth the requirements for possession, use, and transfer of select agents and toxins. The biological agents and toxins listed in this part have the potential to pose a severe threat to public health and safety, to animal health, or to animal products. Overlap select agents and toxins are subject to regulation by both CDC and APHIS. (a) Except for exclusions under paragraphs (d) and (e) of this section, the HHS Secretary has determined that the biological agents and toxins listed in this section have the potential to pose a severe threat to public health and safety. (b) HHS select agents and toxins:
Abrin Cercopithecine herpesvirus 1 (Herpes B virus) Coccidioides posadasii Conotoxins Crimean-Congo haemorrhagic fever virus Diacetoxyscirpenol Ebola viruses Lassa fever 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. Ricin Rickettsia prowazekii Rickettsia rickettsii Saxitoxin Shiga-like ribosome inactivating proteins South American Haemorrhagic Fever viruses (Junin, Machupo, Sabia, Flexal, Guanarito) Tetrodotoxin Tick-borne encephalitis complex (flavi) viruses (Central European Tick-borne encephalitis, Far Eastern Tick-borne encephalitis [Russian Spring and Summer encephalitis, Kyasanur Forest disease, Omsk Hemorrhagic Fever]) Variola major virus (Smallpox virus) and Variola minor virus (Alastrim) Yersinia pestis (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent viruses listed in paragraph (b) of this section. (2) Recombinant nucleic acids that encode for the functional form(s) of any of the toxins listed in paragraph (b) of this section if the nucleic acids: (i) Can be expressed in vivo or in vitro, or (ii) Are in a vector or recombinant host genome and can be expressed in vivo or in vitro. (3) HHS select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d) HHS select agents or toxins that meet any of the following criteria are excluded from the requirements of this part: (1) Any HHS select agent or toxin that is in its naturally occurring environment provided the select agent or toxin has not been intentionally introduced, cultivated, collected, or otherwise extracted from its natural source. (2) Non-viable HHS select agents or nonfunctional HHS toxins. (3) HHS toxins under the control of a principal investigator, treating physician or veterinarian, or commercial manufacturer or distributor, if the aggregate amount does not, at any time, exceed the following amounts: 100 mg of Abrin; 100 mg of Conotoxins; 1,000 mg of Diacetoxyscirpenol; 100 mg of Ricin; 100 mg of Saxitoxin; 100 mg of Shiga-like ribosome inactivating proteins; or 100 mg of Tetrodotoxin. (e) An attenuated strain of a HHS select agent or toxin may be excluded from the requirements of this part based upon a determination that the attenuated strain does not pose a severe threat to public health and safety. (1) To apply for an exclusion, an individual or entity must submit a written request and supporting scientific information. A written decision granting or denying the request will be issued. An exclusion will be effective upon notification to the applicant. Exclusions will be published periodically in the notice section of the (2) If an excluded attenuated strain is subjected to any manipulation that restores or enhances its virulence, the resulting select agent or toxin will be subject to the requirements of this part. (3) An individual or entity may make a written request to the HHS Secretary for reconsideration of a decision denying an exclusion application. 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. (f) Any HHS select agent or toxin seized by a Federal law enforcement agency will be excluded from the requirements of this part during the period between seizure of the select agent or toxin and the transfer or destruction of such agent or toxin provided that: (1) As soon as practicable, the Federal law enforcement agency transfers the seized select agent or toxin to an entity eligible to receive such agent or toxin or destroys the agent or toxin by a recognized sterilization or inactivation process, (2) The Federal law enforcement agency safeguards and secures the seized select agent or toxin against theft, loss, or release, and reports any theft, loss, or release of such agent or toxin, and (3) The Federal law enforcement agency reports the seizure of the select agent or toxin to CDC or APHIS. (i) The seizure of Ebola viruses, Lassa fever virus, Marburg virus, South American Haemorrhagic Fever virus (Junin, Machupo, Sabia, Flexal, Guanarito), Variola major virus (Smallpox virus), Variola minor (Alastrim), or Yersinia pestis must be reported within 24 hours by telephone, facsimile, or e-mail. This report must be followed by submission of APHIS/CDC Form 4 within seven calendar days after seizure of the select agent or toxin. (ii) For all other HHS select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after seizure of the agent or toxin. (iii) A copy of APHIS/CDC Form 4 must be maintained for three years. (4) The Federal law enforcement agency reports the final disposition of the select agent or toxin by submission of APHIS/CDC Form 4. A copy of the completed form must be maintained for three years. [70 FR 13316, Mar. 18, 2005, as amended at 70 FR 61049, Oct. 20, 2005] (a) Except for exclusions under paragraphs (d) and (e) of this section, the HHS Secretary has determined that the biological agents and toxins listed in this section have the potential to pose a severe threat to public health and safety, to animal health, or to animal products. (b) Overlap select agents and toxins:
Bacillus anthracis Botulinum neurotoxins Botulinum neurotoxin producing species of Clostridium Brucella abortus Brucella melitensis Brucella suis Burkholderia mallei (formerly Pseudomonas mallei) Burkholderia pseudomallei (formerly Pseudomonas pseudomallei) Clostridium perfringens epsilon toxin Coccidioides immitis Coxiella burnetii Eastern Equine Encephalitis virus Francisella tularensis Hendra virus Nipah virus Rift Valley fever virus Shigatoxin Staphylococcal enterotoxins T–2 toxin Venezuelan Equine Encephalitis virus (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms: (1) Nucleic acids that can produce infectious forms of any of the overlap select agent viruses listed in paragraph (b) of this section. (2) Recombinant nucleic acids that encode for the functional form(s) of any overlap toxins listed in paragraph (b) of this section if the nucleic acids: (i) Can be expressed in vivo or in vitro, or (ii) Are in a vector or recombinant host genome and can be expressed in vivo or in vitro. (3) Overlap select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d) Overlap select agents or toxins that meet any of the following criteria are excluded from the requirements of this part: (1) Any overlap select agent or toxin that is in its naturally occurring environment provided that the select agent or toxin has not been intentionally introduced, cultivated, collected, or otherwise extracted from its natural source. (2) Non-viable overlap select agents or nonfunctional overlap toxins. (3) Overlap toxins under the control of a principal investigator, treating physician or veterinarian, or commercial manufacturer or distributor, if the aggregate amount does not, at any time, exceed the following amounts: 0.5 mg of Botulinum neurotoxins; 100 mg of Clostridium perfringens epsilon toxin; 100 mg of Shigatoxin; 5 mg of Staphylococcal enterotoxins; or 1,000 mg of T–2 toxin. (e) An attenuated strain of an overlap select agent or toxin may be excluded from the requirements of this part based upon a determination that the attenuated strain does not pose a severe threat to public health and safety, to animal health, or to animal products. (1) To apply for an exclusion, an individual or entity must submit a written request and supporting scientific information. A written decision granting or denying the request will be issued. An exclusion will be effective upon notification to the applicant. Exclusions will be published periodically in the notice section of the (2) If an excluded attenuated strain is subjected to any manipulation that restores or enhances its virulence, the resulting overlap select agent or toxin will be subject to the requirements of this part. (3) An individual or entity may make a written request to the HHS Secretary for reconsideration of a decision denying an exclusion application. 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. (f) Any overlap select agent or toxin seized by a Federal law enforcement agency will be excluded from the requirements of this part during the period between seizure of the select agent or toxin and the transfer or destruction of such agent or toxin provided that: (1) As soon as practicable, the Federal law enforcement agency transfers the seized select agent or toxin to an entity eligible to receive such agent or toxin or destroys the agent or toxin by a recognized sterilization or inactivation process, (2) The Federal law enforcement agency safeguards and secures the seized select agent or toxin against theft, loss, or release, and reports any theft, loss, or release of such agent or toxin, and (3) The Federal law enforcement agency reports the seizure of the overlap select agent or toxin to CDC or APHIS. (i) The seizure of Bacillus anthracis, Botulinum neurotoxins, Brucella melitensis, Francisella tularensis, Hendra virus, Nipah virus, Rift Valley fever virus, or Venezuelan equine encephalitis virus must be reported within 24 hours by telephone, facsimile, or e-mail. This report must be followed by submission of APHIS/CDC Form 4 within seven calendar days after seizure of the select agent or toxin. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after seizure of the select agent or toxin. (iii) A copy of APHIS/CDC Form 4 must be maintained for three years. (4) The Federal law enforcement agency reports the final disposition of the overlap select agent or toxin by the submission of APHIS/CDC Form 4. A copy of the completed form must be maintained for three years. (a) Clinical or diagnostic laboratories and other entities that possess, use, or transfer a HHS select agent or toxin that is contained in a specimen presented for diagnosis or verification will be exempt from the requirements of this part for such agent or toxin contained in the specimen, provided that: (1) Unless directed otherwise by the HHS Secretary, within seven calendar days after identification, the select agent or toxin is transferred in accordance with §73.16 or destroyed on-site by a recognized sterilization or inactivation process, (2) The select agent or toxin is secured against theft, loss, or release during the period between identification of the select agent or toxin and transfer or destruction of such agent or toxin, and any theft, loss, or release of such agent or toxin is reported, and (3) The identification of the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law. (i) The identification of any of the following HHS select agents or toxins must be immediately reported by telephone, facsimile, or e-mail: Ebola viruses, Lassa fever virus, Marburg virus, South American Haemorrhagic Fever viruses (Junin, Machupo, Sabia, Flexal, Guanarito), Variola major virus (Smallpox virus), Variola minor (Alastrim), or Yersinia pestis. This report must be followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other HHS select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after identification. (iii) Less stringent reporting may be required based on extraordinary circumstances, such as a widespread outbreak. (iv) A copy of APHIS/CDC Form 4 must be maintained for three years. (b) Clinical or diagnostic laboratories and other entities that possess, use, or transfer a HHS select agent or toxin that is contained in a specimen presented for proficiency testing will be exempt from the requirements of this part for such agent or toxin contained in the specimen, provided that: (1) Unless directed otherwise by the HHS Secretary, within 90 calendar days of receipt, the select agent or toxin is transferred in accordance with §73.16 or destroyed on-site by a recognized sterilization or inactivation process, (2) The select agent or toxin is secured against theft, loss, or release during the period between identification of the select agent or toxin and transfer or destruction of such agent or toxin, and the theft, loss, or release of such agent or toxin is reported, and (3) The identification of the select agent or toxin, and its derivative, is reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law. To report the identification of a select agent or toxin, APHIS/CDC Form 4 must be submitted within 90 calendar days of receipt of the select agent or toxin. A copy of the completed form must be maintained for three years. (c) Unless the HHS Secretary issues an order making specific provisions of this part applicable to protect public health and safety, products that are, bear, or contain listed select agents or toxins that are cleared, approved, licensed, or registered under any of the following laws, are exempt from the provisions of this part insofar as their use meets the requirements of such laws: (1) The Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301 et seq.), (2) Section 351 of the Public Health Service Act pertaining to biological products (42 U.S.C. 262), (3) The Act commonly known as the Virus-Serum-Toxin Act (21 U.S.C. 151–159), or (4) The Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 136 et seq.). (d) The HHS Secretary may exempt from the requirements of this part an investigational product that is, bears, or contains a select agent or toxin, when such product is being used in an investigation authorized under any Federal Act and additional regulation under this part is not necessary to protect public health and safety. (1) To apply for an exemption, an individual or entity must submit a completed APHIS/CDC Form 5. (2) The HHS Secretary shall make a determination regarding the application within 14 calendar days after receipt, provided the application meets all of the requirements of this section and the application establishes that the investigation has been authorized under the cited Act. A written decision granting or denying the request will be issued. (3) The applicant must notify CDC or APHIS when an authorization for an investigation no longer exists. This exemption automatically terminates when such authorization is no longer in effect. (e) The HHS Secretary may temporarily exempt an individual or entity from the requirements of this part based on a determination that the exemption is necessary to provide for the timely participation of the individual or entity in response to a domestic or foreign public health emergency. With respect to the emergency involved, the exemption may not exceed 30 calendar days, except that one extension of an additional 30 calendar days may be granted. To apply for an exemption or an extension of an exemption, an individual or entity must submit a completed APHIS/CDC Form 5 establishing the need to provide for the timely participation of the individual or entity in a response to a domestic or foreign public health emergency. A written decision granting or denying the request will be issued. (a) Clinical or diagnostic laboratories and other entities that possess, use, or transfer an overlap select agent or toxin that is contained in a specimen presented for diagnosis or verification will be exempt from the requirements of this part for such agent or toxin contained in the specimen, provided that: (1) Unless directed otherwise by the HHS Secretary or Administrator, within seven calendar days after identification, the select agent or toxin is transferred in accordance with §73.16 or 9 CFR part 121.16 or destroyed on-site by a recognized sterilization or inactivation process, (2) The select agent or toxin is secured against theft, loss, or release during the period between identification of the select agent or toxin and transfer or destruction of such agent or toxin, and any theft, loss, or release of such agent or toxin is reported, and (3) The identification of the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law. (i) The identification of any of the following overlap select agents or toxins must be immediately reported by telephone, facsimile, or e-mail: Bacillus anthracis, Botulinum neurotoxins, Brucella melitensis, Francisella tularensis, Hendra virus, Nipah virus, Rift Valley fever virus, or Venezuelan equine encephalitis virus. This report must be followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after identification. (iii) Less stringent reporting may be required based on extraordinary circumstances, such as a widespread outbreak. (iv) A copy of APHIS/CDC Form 4 must be maintained for three years. (b) Clinical or diagnostic laboratories and other entities that possess, use, or transfer an overlap select agent or toxin that is contained in a specimen presented for proficiency testing will be exempt from the requirements of this part for such agent or toxin contained in the specimen, provided that: (1) Unless directed otherwise by the HHS Secretary or Administrator, within 90 calendar days of receipt, the select agent or toxin is transferred in accordance with §73.16 or 9 CFR part 121.16 or destroyed on-site by a recognized sterilization or inactivation process, (2) The select agent or toxin is secured against theft, loss, or release during the period between identification of the select agent or toxin and transfer or destruction of such agent or toxin, and the theft, loss, or release of such agent or toxin is reported, and (3) The identification of the select agent or toxin, and its derivative, is reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law. To report the identification of an overlap select agent or toxin, APHIS/CDC Form 4 must be submitted within 90 calendar days of receipt of the select agent or toxin. A copy of the completed form must be maintained for three years. (c) Unless the HHS Secretary issues an order making specific provisions of this part applicable to protect public health and safety, products that are, bear, or contain listed select agents or toxins that are cleared, approved, licensed, or registered under any of the following laws, are exempt from the provisions of this part insofar as their use meets the requirements of such laws: (1) The Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301 et seq.), (2) Section 351 of the Public Health Service Act pertaining to biological products (42 U.S.C. 262), (3) The Act commonly known as the Virus-Serum-Toxin Act (21 U.S.C. 151–159), or (4) The Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 136 et seq.). (d) The HHS Secretary, after consultation with Administrator, may exempt from the requirements of this part an investigational product that is, bears, or contains an overlap select agent or toxin, may be exempted when such product is being used in an investigation authorized under any Federal Act and additional regulation under this part is not necessary to protect public health and safety. (1) To apply for an exemption, an individual or entity must submit a completed APHIS/CDC Form 5. (2) The HHS Secretary shall make a determination regarding the application within 14 calendar days after receipt, provided the application meets all of the requirements of this section and the application establishes that the investigation has been authorized under the cited Act. A written decision granting or denying the request will be issued. (3) The applicant must notify CDC or APHIS when an authorization for an investigation no longer exists. This exemption automatically terminates when such authorization is no longer in effect. (e) The HHS Secretary may temporarily exempt an individual or entity from the requirements of this part based on a determination that the exemption is necessary to provide for the timely participation of the individual or entity in response to a domestic or foreign public health emergency. With respect to the emergency involved, the exemption may not exceed 30 calendar days, except that one extension of an additional 30 calendar days may be granted. To apply for an exemption or an extension of an exemption, an individual or entity must submit a completed APHIS/CDC Form 5 establishing the need to provide for the timely participation of the individual or entity in a response to a domestic or foreign public health emergency. A written decision granting or denying the request will be issued. (f) Upon request of the Administrator, the HHS Secretary may exempt an individual or entity from the requirements of this part, for 30 calendar days if the Administrator has granted the exemption for agricultural emergency. The HHS Secretary may extend the exemption once for an additional 30 calendar days. (a) Unless exempted under §73.5, an individual or entity shall not possess, use, or transfer any HHS select agent or toxin without a certificate of registration issued by the HHS Secretary. Unless exempted under §73.6 or 9 CFR part 121.6, an individual or entity shall not possess, use, or transfer overlap select agents or toxins, without a certificate of registration issued by the HHS Secretary and Administrator. (b) As a condition of registration, each entity must designate an individual to be its Responsible Official. While most registrants are likely to be entities, in the event that an individual applies for and is granted a certificate of registration, the individual will be considered the Responsible Official. (c)(1) As a condition of registration, the following must be approved by the HHS Secretary or Administrator based on a security risk assessment by the Attorney General: (i) The individual or entity, (ii) The Responsible Official, and (iii) Unless otherwise exempted under this section, any individual who owns or controls the entity. (2) Federal, State, or local governmental agencies, including public accredited academic institutions, are exempt from the security risk assessments for the entity and the individual who owns or controls such entity. (3) An individual will be deemed to own or control an entity under the following conditions:1 1 These conditions may apply to more than one individual. (i) For a private institution of higher education, an individual will be deemed to own or control the entity if the individual is in a managerial or executive capacity with regard to the entity's select agents or toxins or with regard to the individuals with access to the select agents or toxins possessed, used, or transferred by the entity. (ii) For entities other than institutions of higher education, an individual will be deemed to own or control the entity if the individual: (A) Owns 50 percent or more of the entity, or is a holder or owner of 50 percent or more of its voting stock, or (B) Is in a managerial or executive capacity with regard to the entity's select agents or toxins or with regard to the individuals with access to the select agents or toxins possessed, used, or transferred by the entity. (4) An entity will be considered to be an institution of higher education if it is an institution of higher education as defined in section 101(a) of the Higher Education Act of 1965 (20 U.S.C. 1001(a)), or is an organization described in 501(c)(3) of the Internal Revenue Code of 1986, as amended (26 U.S.C. 501(c)(3)). (5) To obtain a security risk assessment, an individual or entity must submit the information necessary to conduct a security risk assessment to the Attorney General. (d) To apply for a certificate of registration that covers only HHS select agents or toxins, an individual or entity must submit the information requested in the registration application package (APHIS/CDC Form 1) to CDC. To apply for a certificate of registration that does not cover only HHS select agents or toxins (i.e., covers at least one overlap select agent and/or toxin, or covers any combination of HHS select agents and/or toxins and USDA select agents and/or toxins), an individual or entity must submit the information requested in the registration application package (APHIS/CDC Form 1) to CDC or APHIS, but not both. (e) Prior to the issuance of a certificate of registration, the Responsible Official must promptly provide notification of any changes to the application for registration by submitting the relevant page(s) of the registration application. (f) The issuance of a certificate of registration may be contingent upon inspection or submission of additional information, such as the security plan, biosafety plan, incident response plan, or any other documents required to be prepared under this part. (g) A certificate of registration will be valid for one physical location (a room, a building, or a group of buildings) where the Responsible Official will be able to perform the responsibilities required in this part, for specific select agents or toxins, and for specific activities. (h) A certificate of registration may be amended to reflect changes in circumstances (e.g., replacement of the Responsible Official or other personnel changes, changes in ownership or control of the entity, changes in the activities involving any select agents or toxins, or the addition or removal of select agents or toxins). (1) Prior to any change, the Responsible Official must apply for an amendment to a certificate of registration by submitting the relevant page(s) of the registration application. (2) The Responsible Official will be notified in writing if an application to amend a certificate of registration has been approved. Approval of the amendment may be contingent upon an inspection or submission of additional information, such as the security plan, biosafety plan, incident response plan, or any other documents required to be prepared under this part. (3) No change may be made without such approval. (i) An entity must immediately notify CDC or APHIS if it loses the services of its Responsible Official. In the event that an entity loses the services of its Responsible Official, an entity may continue to possess or use select agents or toxins only if it appoints as the Responsible Official another individual who has been approved by the HHS Secretary or Administrator following a security risk assessment by the Attorney General and who meets the requirements of this part. (j) A certificate of registration will be terminated upon the written request of the entity if the entity no longer possesses or uses any select agents or toxins and no longer wishes to be registered. (k) A certificate of registration will be valid for a maximum of three years. (a) An application may be denied or a certificate of registration revoked or suspended if: (1) The individual or entity, the Responsible Official, or an individual who owns or controls the entity is within any of the categories described in 18 U.S.C. 175b, (2) The individual or entity, the Responsible Official, or an individual who owns or controls the entity as reasonably suspected by any Federal law enforcement or intelligence agency of: (i) Committing a crime specified in 18 U.S.C. 2332b(g)(5), (ii) Knowing involvement with an organization that engages in domestic or international terrorism (as defined in 18 U.S.C. 2331) or with any other organization that engages in intentional crimes of violence, or (iii) Being an agent of a foreign power (as defined in 50 U.S.C. 1801). (3) The individual or entity does not meet the requirements of this part, or (4) It is determined that such action is necessary to protect public health and safety. (b) Upon revocation or suspension of a certificate of registration, the individual or entity must: (1) Immediately stop all use of each select agent or toxin covered by the revocation or suspension order, (2) Immediately safeguard and secure each select agent or toxin covered by the revocation or suspension order from theft, loss, or release, and (3) Comply with all disposition instructions issued by the HHS Secretary for the select agent or toxin covered by the revocation or suspension. (c) Denial of an application for registration and revocation of registration may be appealed under §73.20. However, any denial of an application for registration or revocation of a certificate of registration will remain in effect until a final agency decision has been rendered. (a) An individual or entity required to register under this part must designate an individual to be the Responsible Official. The Responsible Official must: (1) Be approved by the HHS Secretary or Administrator following a security risk assessment by the Attorney General, (2) Be familiar with the requirements of this part, (3) Have authority and responsibility to act on behalf of the entity, (4) Ensure compliance with the requirements of this part, and (5) Ensure that annual inspections are conducted for each laboratory where select agents or toxins are stored or used in order to determine compliance with the requirements of this part. The results of each inspection must be documented, and any deficiencies identified during an inspection must be corrected. (b) An entity may designate one or more individuals to be an alternate Responsible Official, who may act for the Responsible Official in his/her absence. These individuals must have the authority and control to ensure compliance with the regulations when acting as the Responsible Official. (c) The Responsible Official must report the identification and final disposition of any select agent or toxin contained in a specimen presented for diagnosis or verification. (1) The identification of any of the following select agents or toxins must be immediately reported by telephone, facsimile, or e-mail: Bacillus anthracis, Botulinum neurotoxins, Brucella melitensis, Francisella tularensis, Ebola viruses, Hendra virus, Marburg virus, Lassa fever virus, Nipah virus, Rift Valley fever virus, South American Haemorrhagic Fever viruses (Junin, Machupo, Sabia, Flexal, Guanarito), Variola major virus (Smallpox virus), Variola minor (Alastrim), Venezuelan equine encephalitis virus, or Yersinia pestis. The final disposition of the agent or toxin must be reported by submission of APHIS/CDC Form 4 within seven calendar days after identification. A copy of the completed form must be maintained for three years. (2) To report the identification and final disposition of any other select agent or toxin, APHIS/CDC Form 4 must be submitted within seven calendar days after identification. A copy of the completed form must be maintained for three years. (3) Less stringent reporting may be required based on extraordinary circumstances, such as a widespread outbreak. (d) The Responsible Official must report the identification and final disposition of any select agent or toxin contained in a specimen presented for proficiency testing. To report the identification and final disposition of a select agent or toxin, APHIS/CDC Form 4 must be submitted within 90 calendar days of receipt of the agent or toxin. A copy of the completed form must be maintained for three years. (a) An individual or entity required to register under this part may not provide an individual access to a select agent or toxin, and an individual may not access a select agent or toxin, unless the individual is approved by the HHS Secretary or Administrator, following a security risk assessment by the Attorney General. (b) An individual will be deemed to have access at any point in time if the individual has possession of a select agent or toxin (e.g., ability to carry, use, or manipulate) or the ability to gain possession of a select agent or toxin. (c) Each individual with access to select agents or toxins must have the appropriate education, training, and/or experience to handle or use such agents or toxins. (d) To apply for access approval, each individual must submit the information necessary to conduct a security risk assessment to the Attorney General. (e) An individual's security risk assessment may be expedited upon written request by the Responsible Official and a showing of good cause (e.g., public health or agricultural emergencies, national security, or a short term visit by a prominent researcher). A written decision granting or denying the request will be issued. (f) An individual's access approval will be denied or revoked if the individual is within any of the categories described in 18 U.S.C. 175b, (g) An individual's access approval may be denied, limited, or revoked if: (1) The individual is reasonably suspected by any Federal law enforcement or intelligence agency of committing a crime specified in 18 U.S.C. 2332b(g)(5), knowing involvement with an organization that engages in domestic or international terrorism (as defined in 18 U.S.C. 2331) or with any other organization that engages in intentional crimes of violence, or being an agent of a foreign power (as defined in 50 U.S.C. 1801), or (2) It is determined such action is necessary to protect public health and safety. (h) An individual may appeal the HHS Secretary's decision to deny, limit, or revoke access approval under §73.20. (i) Access approval is valid for a maximum of five years. (j) The Responsible Official must immediately notify CDC or APHIS when an individual's access to select agents or toxins is terminated by the entity and the reasons therefore. (a) An individual or entity required to register under this part must develop and implement a written security plan. The security plan must be sufficient to safeguard the select agent or toxin against unauthorized access, theft, loss, or release. (b) The security plan must be designed according to a site-specific risk assessment and must provide graded protection in accordance with the risk of the select agent or toxin, given its intended use. The security plan must be submitted upon request. (c) The security plan must: (1) Describe procedures for physical security, inventory control, and information systems control, (2) Contain provisions for the control of access to select agents and toxins, (3) Contain provisions for routine cleaning, maintenance, and repairs, (4) Establish procedures for removing unauthorized or suspicious persons, (5) Describe procedures for addressing loss or compromise of keys, passwords, combinations, etc. and protocols for changing access numbers or locks following staff changes, (6) Contain procedures for reporting unauthorized or suspicious persons or activities, loss or theft of select agents or toxins, release of select agents or toxins, or alteration of inventory records, and (7) Contain provisions for ensuring that all individuals with access approval from the HHS Secretary or Administrator understand and comply with the security procedures. (d) An individual or entity must adhere to the following security requirements or implement measures to achieve an equivalent or greater level of security: (1) Allow access only to individuals with access approval from the HHS Secretary or Administrator, (2) Allow individuals not approved for access from the HHS Secretary or Administrator to conduct routine cleaning, maintenance, repairs, or other activities not related to select agents or toxins only when continuously escorted by an approved individual, (3) Provide for the control of select agents and toxins by requiring freezers, refrigerators, cabinets, and other containers where select agents or toxins are stored to be secured against unauthorized access (e.g., card access system, lock boxes), (4) Inspect all suspicious packages before they are brought into or removed from the area where select agents or toxins are used or stored, (5) Establish a protocol for intra-entity transfers under the supervision of an individual with access approval from the HHS Secretary or Administrator, including chain-of-custody documents and provisions for safeguarding against theft, loss, or release, (6) Require that individuals with access approval from the HHS Secretary or Administrator refrain from sharing with any other person their unique means of accessing a select agent or toxin (e.g., keycards or passwords), (7) Require that individuals with access approval from the HHS Secretary or Administrator immediately report any of the following to the Responsible Official: (i) Any loss or compromise of keys, passwords, combination, etc., (ii) Any suspicious persons or activities, (iii) Any loss or theft of select agents or toxins, (iv) Any release of a select agent or toxin, and (v) Any sign that inventory or use records for select agents or toxins have been altered or otherwise compromised, and (8) Separate areas where select agents and toxins are stored or used from the public areas of the building. (e) In developing a security plan, an entity or individual should consider, the document entitled “Laboratory Security and Emergency Response Guidance for Laboratories Working with Select Agents. Morbidity and Mortality Weekly Report December 6, 2002; 51:RR–19:1–6.” The document is available on the Internet at: http://www.cdc.gov/mmwr. (f) The plan must be reviewed annually and revised as necessary. Drills or exercises must be conducted at least annually to test and evaluate the effectiveness of the plan. The plan must be reviewed and revised, as necessary, after any drill or exercise and after any incident. (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 agent or toxin, given its intended use. The biosafety plan must contain sufficient information and documentation to describe the biosafety and containment procedures. (b) The biosafety and containment procedures must be sufficient to contain the select agent or toxin (e.g., physical structure and features of the entity, and operational and procedural safeguards). (c) In developing a biosafety plan, an individual or entity should consider: (1) The CDC/NIH publication, “Biosafety in Microbiological and Biomedical Laboratories”, including all appendices. Copies may be obtained from the Superintendent of Documents, U.S. Government Printing Office, Post Office Box 371954, Pittsburgh, Pennsylvania, 75250–7954 or from the CDC Web site at http://www.cdc.gov/. Copies may be inspected at the Centers for Disease Control and Prevention, 1600 Clifton Road, Mail Stop E–79, Atlanta, Georgia. (2) The Occupational Safety and Health Administration (OSHA) regulations in 29 CFR parts 1910.1200 and 1910.1450. (3) The “NIH Guidelines for Research Involving Recombinant DNA Molecules,” (NIH Guidelines). Copies may be obtained from the Centers for Disease Control and Prevention, 1600 Clifton Road, Mail Stop E–79, Atlanta, Georgia, 30333 or from the CDC Web site at http://www.cdc.gov/. Copies may be inspected at the Centers for Disease Control and Prevention, 1600 Clifton Road, Mail Stop E–79, Atlanta, Georgia. (d) The plan must be reviewed annually and revised as necessary. Drills or exercises must be conducted at least annually to test and evaluate the effectiveness of the plan. The plan must be reviewed and revised, as necessary, after any drill or exercise and after any incident. (a) An individual or entity may not conduct a restricted experiment with a HHS select agent or toxin unless approved by and conducted in accordance with any conditions prescribed by the HHS Secretary. In addition, an individual or entity may not conduct a restricted experiment with an overlap select agent or toxin unless approved by and conducted in accordance with any conditions prescribed by the HHS Secretary, after consultation with Administrator. (b) Restricted experiments: (1) Experiments utilizing recombinant DNA that involve the deliberate transfer of a drug resistance trait to select agents that are not known to acquire the trait naturally, if such acquisition could compromise the use of the drug to control disease agents in humans, veterinary medicine, or agriculture. (2) Experiments involving the deliberate formation of recombinant DNA containing genes for the biosynthesis of select toxins lethal for vertebrates at an LD50 < 100 ng/kg body weight. (c) The HHS Secretary may revoke approval to conduct any of the experiments in paragraph (b) of this section, or revoke or suspend a certificate of registration, if the individual or entity fails to comply with the requirements of this part. (d) To apply for approval to conduct any of the experiments in paragraph (a) of this section, an individual or entity must submit a written request and supporting scientific information. A written decision granting or denying the request will be issued. (a) An individual or entity required to register under this part must develop and implement a written incident response plan.2 2 Nothing in this section is meant to supersede or preempt incident response requirements imposed by other statutes or regulations. (b) The incident response plan must fully describe the entity's response procedures for the 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, suspicious packages, and emergencies such as fire, gas leak, explosion, power outage, etc. The response procedures must account for hazards associated with the select agent and toxin and appropriate actions to contain such select agent or toxin. (c) The incident response plan must also contain the following information: (1) The name and contact information (e.g., home and work) for the individual or entity (e.g., responsible official, alternate responsible official(s), biosafety officer, etc.), (2) The name and contact information for the building owner and/or manager, where applicable, (3) The name and contact information for tenant offices, where applicable, (4) The name and contact information for the physical security official for the building, where applicable, (5) Personnel roles and lines of authority and communication, (6) Planning and coordination with local emergency responders, (7) Procedures to be followed by employees performing rescue or medical duties, (8) Emergency medical treatment and first aid, (9) A list of personal protective and emergency equipment, and their locations, (10) Site security and control, (11) Procedures for emergency evacuation, including type of evacuation, exit route assignments, safe distances, and places of refuge, and (12) Decontamination procedures. (d) The plan must be reviewed annually and revised as necessary. Drills or exercises must be conducted at least annually to test and evaluate the effectiveness of the plan. The plan must be reviewed and revised, as necessary, after any drill or exercise and after any incident. (a) An individual or entity required to register under this part must provide information and training on biosafety and security to each individual with access approval from the HHS Secretary or Administrator before he/she has such access.3 3 The training need not duplicate training provided under the OSHA Bloodborne Pathogen Standard set forth at 29 CFR 1910.1030. (b) Refresher training must be provided annually. (c) A record of the training provided to each individual must be maintained. The record must include the name of the individual, the date of the training, a description of the training provided, and the means used to verify that the employee understood the training. (a) Except as provided in paragraphs (c) and (d) of this section, a select agent or toxin may only be transferred to individuals or entities registered to possess, use, or transfer that agent or toxin. A select agent or toxin may only be transferred under the conditions of this section and must be authorized by CDC or APHIS prior to the transfer.4 4 This section does not cover transfers within an entity when the sender and the recipient are covered by the same certificate of registration. (b) A transfer may be authorized if: (1) The sender: (i) Has at the time of transfer a certificate of registration that covers the particular select agent or toxin to be transferred and meets all requirements in this part, (ii) Meets the exemption requirements for the particular select agent or toxin to be transferred, or (iii) Is transferring the select agent or toxin from outside the United States and meets all import requirements. (2) At the time of transfer, the recipient has a certificate of registration that includes the particular select agent or toxin to be transferred and meets all of the requirements of this part. (c) A select agent or toxin that is contained in a specimen for proficiency testing may be transferred without prior authorization from CDC or APHIS provided that, at least seven calendar days prior to the transfer, the sender reports to CDC or APHIS the select agent or toxin to be transferred and the name and address of the recipient. (d) On a case-by-case basis, the HHS Secretary may authorize a transfer of a select agent or toxin, not otherwise eligible for transfer under this part under conditions prescribed by the HHS Secretary. (e) To obtain authorization for transfer, APHIS/CDC Form 2 must be submitted. (f) The recipient must submit a completed APHIS/CDC Form 2 within two business days of receipt of a select agent or toxin. (g) The recipient must immediately notify CDC or APHIS if the select agent or toxin has not been received within 48 hours after the expected delivery time, or if the package containing select agents or toxins has been damaged to the extent that a release of the select agent or toxin may have occurred. (h) An authorization for a transfer shall be valid only for 30 calendar days after issuance, except that such an authorization becomes immediately null and void if any facts supporting the authorization change (e.g., change in the certificate of registration for the sender or recipient, change in the application for transfer). (i) The sender must comply with all applicable laws concerning packaging and shipping. (a) An individual or entity required to register under this part must maintain complete records relating to the activities covered by this part. Such records must include: (1) Accurate, current inventory for each select agent (including viral genetic elements, recombinant nucleic acids, and recombinant organisms) held in long-term storage (placement in a system designed to ensure viability for future use, such as in a freezer or lyophilized materials), including: (i) The name and characteristics (e.g., strain designation, GenBank Accession number, etc.), (ii) The quantity acquired from another individual or entity (e.g., containers, vials, tubes, etc.), date of acquisition, and the source, (iii) Where stored (e.g., building, room, and freezer), (iv) When moved from storage and by whom and when returned to storage and by whom, (v) The select agent used and purpose of use, (vi) Records created under §73.16 and 9 CFR 121.16 (Transfers), (vii) For intra-entity transfers (sender and the recipient are covered by the same certificate of registration), the select agent, the quantity transferred, the date of transfer, the sender, and the recipient, and (viii) Records created under §73.19 and 9 CFR part 121.19 (Notification of theft, loss, or release), (2) Accurate, current inventory for each toxin held, including: (i) The name and characteristics, (ii) The quantity acquired from another individual or entity (e.g., containers, vials, tubes, etc.), date of acquisition, and the source, (iii) The initial and current quantity amount (e.g., milligrams, milliliters, grams, etc.), (iv) The toxin used and purpose of use, quantity, date(s) of the use and by whom, (v) Where stored (e.g., building, room, and freezer), (vi) When moved from storage and by whom and when returned to storage and by whom including quantity amount, (vii) Records created under §73.16 and 9 CFR part 121.16 (Transfers), (viii) For intra-entity transfers (sender and the recipient are covered by the same certificate of registration), the toxin, the quantity transferred, the date of transfer, the sender, and the recipient, (ix) Records created under §73.19 and 9 CFR part 121.19 (Notification of theft, loss, or release), and (x) If destroyed, the quantity of toxin destroyed, the date of such action, and by whom, (3) A current list of all individuals that have been granted access approval from the HHS Secretary or Administrator, (4) Information about all entries into areas containing select agents or toxins, including the name of the individual, name of the escort (if applicable), and date and time of entry, (5) Accurate, current records created under §73.9 and 9 CFR part 121.9 (Responsible Official), §73.11 and 9 CFR part 121.11 (Security), §73.12 and 9 CFR part 121.12 (Biosafety), §73.14 and 9 CFR part 121. 14 (Incident response), and §73.15 and 9 CFR part 121.15 (Training), and (6) A written explanation of any discrepancies. (b) The individual or entity must implement a system to ensure that all records and data bases created under this part are accurate, have controlled access, and that their authenticity may be verified. (c) All records created under this part must be maintained for three years and promptly produced upon request. (a) Without prior notification, the HHS Secretary, shall be allowed to inspect any site at which activities regulated by this part are conducted and shall be allowed to inspect and copy any records relating to the activities covered by this part. (b) Prior to issuing a certificate of registration to an individual or entity, the HHS Secretary may inspect and evaluate the premises and records to ensure compliance with this part. (a) Upon discovery of the theft or loss of a select agent or toxin, an individual or entity must immediately notify CDC or APHIS and appropriate Federal, State, or local law enforcement agencies. Thefts or losses must be reported even if the select agent or toxin is subsequently recovered or the responsible parties are identified. (1) The theft or loss of a select agent or toxin must be reported immediately by telephone, facsimile, or e-mail. The following information must be provided: (i) The name of the select agent or toxin and any identifying information (e.g., strain or other characterization information), (ii) An estimate of the quantity lost or stolen, (iii) An estimate of the time during which the theft or loss occurred, (iv) The location (building, room) from which the theft or loss occurred, and (v) The list of Federal, State, or local law enforcement agencies to which the individual or entity reported, or intends to report the theft or loss. (2) A completed APHIS/CDC Form 3 must submitted within seven calendar days. (b) Upon discovery of a release of an agent or toxin causing occupational exposure or release of a select agent or toxin outside of the primary barriers of the biocontainment area, an individual or entity must immediately notify CDC or APHIS. (1) The release of a select agent or toxin must be reported by telephone, facsimile, or e-mail. The following information must be provided: (i) The name of the select agent or toxin and any identifying information (e.g., strain or other characterization information), (ii) An estimate of the quantity released, (iii) The time and duration of the release, (iv) The environment into which the release occurred (e.g., in building or outside of building, waste system), (v) The location (building, room) from which the release occurred, (vi) The number of individuals potentially exposed at the entity, (vii) Actions taken to respond to the release, and (viii) Hazards posed by the release. (2) A completed APHIS/CDC Form 3 must be submitted within seven calendar days. An individual or entity may appeal a denial, revocation, or suspension of registration under this part. An individual may appeal a denial, limitation, or revocation of access approval under this part. The appeal must be in writing, state the factual basis for the appeal, and be submitted to the HHS Secretary within 30 calendar days of the decision. Where the denial, revocation, or suspension of registration or the denial, limitation, or revocation of an individual's access approval is based upon an identification by the Attorney General, the request for review will be forwarded to the Attorney General. The HHS Secretary's decision constitutes final agency action. (a) The Inspector General of the Department of Health and Human Services is delegated authority to conduct investigations and to impose civil money penalties against any individual or entity in accordance with regulations in 42 CFR part 1003 for violations of the regulations in this part, as authorized by the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (Pub. L. 107–188). The delegation of authority includes all powers contained in section 6 of the Inspector General Act of 1978 (5 U.S.C. App.). (b) The administrative law judges in, assigned to, or detailed to the Departmental Appeals Board have been delegated authority to conduct hearings and to render decisions in accordance with 42 CFR part 1005 with respect to the imposition of civil money penalties, as authorized by the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (Pub. L. 107–188). This delegation includes, but is not limited to, the authority to administer oaths and affirmations, to subpoena witnesses and documents, to examine witnesses, to exclude or receive and give appropriate weight to materials and testimony offered as evidence, to make findings of fact and conclusions of law, and to determine the civil money penalties to be imposed. (c) The Departmental Appeals Board of the Department of Health and Human Services is delegated authority to make final determinations with respect to the imposition of civil money penalties for violations of the regulations of this part.
Title 42: Public Health
PART 73—SELECT AGENTS AND TOXINS
Section Contents
§ 73.1 Definitions.
§ 73.2 Purpose and scope.
§ 73.3 HHS select agents and toxins.
§ 73.4 Overlap select agents and toxins.
§ 73.5 Exemptions for HHS select agents and toxins.
§ 73.6 Exemptions for overlap select agents and toxins.
§ 73.7 Registration and related security risk assessments.
§ 73.8 Denial, revocation, or suspension of registration.
§ 73.9 Responsible Official.
§ 73.10 Restricting access to select agents and toxins; security risk assessments.
§ 73.11 Security.
§ 73.12 Biosafety.
§ 73.13 Restricted experiments.
§ 73.14 Incident response.
§ 73.15 Training.
§ 73.16 Transfers.
§ 73.17 Records.
§ 73.18 Inspections.
§ 73.19 Notification of theft, loss, or release.
§ 73.20 Administrative review.
§ 73.21 Civil money penalties.
§ 73.1 Definitions.
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§ 73.2 Purpose and scope.
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§ 73.3 HHS select agents and toxins.
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§ 73.4 Overlap select agents and toxins.
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§ 73.5 Exemptions for HHS select agents and toxins.
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§ 73.6 Exemptions for overlap select agents and toxins.
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§ 73.7 Registration and related security risk assessments.
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§ 73.8 Denial, revocation, or suspension of registration.
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§ 73.9 Responsible Official.
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§ 73.10 Restricting access to select agents and toxins; security risk assessments.
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§ 73.11 Security.
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§ 73.12 Biosafety.
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§ 73.13 Restricted experiments.
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§ 73.14 Incident response.
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§ 73.15 Training.
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§ 73.16 Transfers.
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§ 73.17 Records.
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§ 73.18 Inspections.
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§ 73.19 Notification of theft, loss, or release.
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§ 73.20 Administrative review.
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§ 73.21 Civil money penalties.
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