National Institutes of Health (NIH) Office of Science Policy (OSP) Recombinant or Synthetic Nucleic Acid Research: Action Under the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines), 22286-22289 [2016-08810]

Download as PDF 22286 Federal Register / Vol. 81, No. 73 / Friday, April 15, 2016 / Notices submitted for each individual being nominated for consideration: (1) A statement that clearly states the name and affiliation of the nominee, the basis for the nomination (i.e., specific attributes such as expertise in bioethics, evidence review, public health, laboratory, maternal and child health, or clinical expertise in heritable disorders, which qualify the nominee for service in this capacity), and that the nominee is willing to serve as a member of the Committee; (2) the nominee’s name, address, and daytime telephone number and the home/or work address, telephone number, and email address; and (3) a current copy of the nominee’s curriculum vitae. Nomination packages may be summited directly by the individual being nominated or by the person/organization recommending the candidate. The Department of Health and Human Services will make every effort to ensure that the membership of the Committee is fairly balanced in terms of points of view represented. Every effort is made to ensure that individuals from a broad representation of geographic areas, gender, ethnic and minority groups, as well as individuals with disabilities are given consideration for membership. Appointments shall be made without discrimination on the basis of age, ethnicity, gender, sexual orientation, and cultural, religious, or socioeconomic status. Individuals who are selected to be considered for appointment will be required to provide detailed information regarding their financial holdings, consultancies, and research grants or contracts. Disclosure of this information is necessary in order to determine if the selected candidate is involved in any activity that may pose a potential conflict with the official duties to be performed as a member of the Committee. Jackie Painter, Director, Division of the Executive Secretariat. [FR Doc. 2016–08691 Filed 4–14–16; 8:45 am] asabaliauskas on DSK3SPTVN1PROD with NOTICES BILLING CODE 4165–15–P VerDate Sep<11>2014 17:27 Apr 14, 2016 Jkt 238001 DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institutes of Health (NIH) Office of Science Policy (OSP) Recombinant or Synthetic Nucleic Acid Research: Action Under the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) The NIH OSP is amending portions of the NIH Guidelines in order to provide investigators with biosafety guidance regarding the standards for containment of non-human primates (NHPs) in biosafety level (BL) 4 laboratories and to make such guidance consistent with the expectations articulated in the Centers for Disease Control and Prevention (CDC)/NIH Biosafety in Microbiological and Biomedical Laboratories 5th edition (BMBL). Specifically, the NIH Guidelines will allow for housing of NHPs in open caging in a dedicated animal holding room provided there are two physical barriers between that animal holding room and noncontainment space within the laboratory, the animal holding room has negative air pressure with respect to any adjacent non-containment corridors, and there are specific decontamination protocols in place before the door to the animal holding room is opened to allow for the periodic transfer of new animals into the room. These amendments do not change the current containment requirements in the NIH Guidelines but rather offer an alternative for achieving primary containment without compromising safety. In addition, the recertification requirement for biosafety cabinets in BL4 laboratories is updated in recognition of the technological standards for modern biosafety cabinets. The NIH OSP also is updating the validation requirements for equipment responsible for centralized heat decontamination of liquid effluents in laboratories working with large animals. These amendments to the NIH Guidelines will be implemented immediately upon publication in the Federal Register. These changes were developed after extensive consultation with biosafety experts, directors of and principal investigators in BL4 facilities working with NHPs, and CDC’s Division of Select Agent and Toxins (DSAT) leadership at a public workshop and discussion at a public Recombinant DNA Advisory Committee (RAC) meeting. Publication in the Federal SUMMARY: PO 00000 Frm 00079 Fmt 4703 Sfmt 4703 Register will inform the scientific and biosafety communities. FOR FURTHER INFORMATION CONTACT: If you have questions, or require additional information about these changes, please contact the NIH OSP by email at SciencePolicy@od.nih.gov, or telephone at 301–496–9838. SUPPLEMENTARY INFORMATION: The first three editions of the BMBL and the NIH Guidelines were consistent in their approach to requiring primary containment for animal work in BL4 containment laboratories. However, in the early 1990s, the BMBL was amended and the fourth edition stated that animals housed in BL4 suit laboratories (i.e., laboratories in which Class III cabinets are not used but instead personnel wear positive pressure protective suits) should be housed in a primary containment system (such as open cages covered with filtered bonnets and opened in laminar flow hoods or other equivalent containment systems). This language remains in the current BMBL (5th edition). With the change in the BMBL, primary containment caging was arguably preferred but no longer required under BL4 containment. In contrast, the NIH Guidelines have always required primary containment caging for all animals in BL4 laboratories. Non-human primates are social animals and require environmental enrichment. Researchers in several U.S. BL4 laboratories engaged in NHP research approached the NIH OSP with concerns that primary containment caging in BL4 laboratories hindered the creation of an environment that allowed animals to benefit from adequate social interaction. Also based on risk assessments and experiences comparing several primary containment caging systems, the researchers concluded that primary containment caging may actually create new hazards for laboratory workers. These findings included interference with observation of the animals from outside the room leading to more frequent entries into the BL4 animal room to monitor the animals, and exacerbation of cramped working conditions created by the additional barriers required by some containment systems, which increases the difficulty of working in inflated pressure suits as well as the potential for damage to the pressure suit. In addition, investigators stated that current BL4 laboratory designs incorporate sophisticated engineering systems, which provide biosafety protection in a dedicated animal room equivalent to the primary containment caging required under the NIH E:\FR\FM\15APN1.SGM 15APN1 asabaliauskas on DSK3SPTVN1PROD with NOTICES Federal Register / Vol. 81, No. 73 / Friday, April 15, 2016 / Notices Guidelines. On March 28, 2014, the NIH OSP, together with the CDC Division of Select Agents (DSAT), held a meeting with investigators and biosafety personnel from nine BL4 laboratories in the U.S. and five international laboratories (agenda and roster available at http://osp.od.nih.gov/officebiotechnology-activities/event/2014-0328-120000-2014-03-28-211500/primarycontainment-non-human-primatesbiosafety-level-4-laboratorieschallenges-and-best-practices). That meeting was followed by a discussion at the June 11, 2014, meeting of the NIH RAC regarding housing of NHPs in BL4 laboratories (a webcast of that discussion is available at http:// videocast.nih.gov/ summary.asp?Live=14300&bhcp=1.) As a result of these discussions and after consultation with CDC DSAT, the NIH OSP is amending the NIH Guidelines to allow the housing of NHP in open cages in a dedicated animal room provided certain conditions as articulated below are met. In addition, OSP is updating the requirement for testing and certification of Class I and II biosafety cabinets at BL4 from every six months to annually, recognizing the technological advances in biosafety cabinet design and engineering that have occurred over the period since this performance measure was originally implemented. Finally, Appendix Q of the NIH Guidelines currently requires that the centralized heat treatment catch tank system in BL4 large animal laboratories be validated every 30 days. To carry out this testing effectively, the system should be near capacity (i.e. ‘‘under load’’). Some laboratories do not use their catch tank systems on a regular basis; therefore, a mandatory 30 day validation would require them to demonstrate that the equipment is functioning when it is not in use or is not at capacity. This will not serve the intended purpose of demonstrating that the equipment is functioning as intended. Therefore, validation intervals will need to be set based on the utilization of the system provided it is done at least once a year. To implement these changes, the following sections of the NIH Guidelines are to be amended: Appendix G–II–D–2–l. currently states: Appendix G–II–D–2–l. Laboratory animals involved in experiments requiring BL4 level physical containment shall be housed either in cages contained in Class III cabinets or in partial containment caging systems, such as Horsfall units (see Appendix G–III–K, Footnotes and References of Appendix G), open cages placed in ventilated enclosures, VerDate Sep<11>2014 17:27 Apr 14, 2016 Jkt 238001 or solid-wall and -bottom cages placed on holding racks equipped with ultraviolet irradiation lamps and reflectors that are located in a specially designed area in which all personnel are required to wear one-piece positive pressure suits. Appendix G–II–D–2–1 is amended as follows with the addition of a new Appendix G–II–D–2–1–(2) that will address housing of NHPs: Appendix G–II–D–2–l. Containment for Animal Research Appendix G–II–D–2–l–(1). Laboratory animals involved in experiments requiring BL4 level physical containment shall be housed either in cages contained in Class III cabinets or in partial containment caging systems, such as Horsfall units (see Appendix G– III–K, Footnotes and References of Appendix G), open cages placed in ventilated enclosures, or solid-wall and -bottom cages placed on holding racks equipped with ultraviolet irradiation lamps and reflectors that are located in a specially designed area in which all personnel are required to wear onepiece positive pressure suits. Appendix G–II–D–2–l–(2). Nonhuman primates (NHP) may be housed (1) under the containment conditions described in Appendix G–II–D–2–l–(1) above, or (2) in open cages within a dedicated animal holding room that serves as the primary barrier and in which all personnel are required to wear one-piece positive pressure suits. A room serving as a primary barrier must be air-tight and capable of being decontaminated using fumigation. If NHPs are to be contained in a dedicated animal holding room serving as the primary barrier, the following conditions shall be met: (i) Access to the animal holding room from service corridors outside of the BL4 containment space shall require passage through two sets of doors, and the inner most door must be an air pressure resistant (APR) door; (ii) For any animal holding room considered to be a primary barrier, APR door(s) providing direct ingress from the exterior service corridor shall be fitted with appropriate and redundant lockout mechanisms to prevent access when the animal holding room is contaminated and in use. There should be more than one mechanism to ensure that this primary barrier door cannot be opened when the animal room is contaminated and the APR door shall not serve as an emergency exit from the BL4 laboratory. The APR door shall be appropriately tested to demonstrate that in the closed, locked-out mode, the door provides an air-tight barrier proven by PO 00000 Frm 00080 Fmt 4703 Sfmt 4703 22287 pressure decay testing or other equivalent method; (iii) Any door(s) allowing access into a corridor from which there is direct ingress to an animal holding room must be fitted with either (1) an APR door or (2) a non-APR door, providing directional airflow is maintained from the laboratory corridor space into the animal room. For the purpose of fumigation, animal rooms equipped with non-APR doors opening into the adjacent interior corridors shall be considered one space (i.e., areas between air-tight doors shall be fumigated together). (iv) Any door(s) used for access to the service corridor (the secondary barrier) shall be self-closing and of solid construction, designed not to corrode, split or warp; (v) Access to the service corridor inside the secondary barrier shall be restricted and strictly controlled when animal rooms are in use. Whenever possible, the secondary barrier door(s) should be fitted with safety interlock switches designed to prevent it from opening when an animal holding room door (the primary barrier) is opened following room decontamination; if interlock devices cannot be used, specific administrative procedures shall be implemented to control access to the service corridor; (vi) The service corridor shall maintain a negative pressure (inward directional airflow) relative to adjoining traffic corridors; (vii) Prior to fumigation of the animal holding room, cages should be removed for autoclaving or chemical decontamination. (viii) Caging should be chosen to reduce the amount of animal detritus that can be thrown out of the cage and onto the floor of the animal holding room; (ix) The flow of personnel, material and equipment should be directed in order to minimize the spread of contamination from the animal holding room into adjacent areas of the laboratory. (x) Following animal room decontamination, safeguards involving the use of personal protective equipment and appropriate administrative controls shall be implemented for the safe retrieval of biological indicators in order to prevent the spread of infectious agents in the event of a decontamination failure. With regard to the frequency of class II biosafety cabinet recertification and testing, the NIH Guidelines require recertification/testing of biosafety cabinets at six-month intervals. However, modern biosafety cabinet E:\FR\FM\15APN1.SGM 15APN1 22288 Federal Register / Vol. 81, No. 73 / Friday, April 15, 2016 / Notices design specifications incorporate continuous electronic and physical monitoring systems that track multiple operational parameters such as pressure differential, air flow velocity and plenum pressure with added capabilities for remote control and monitoring. Continuous performance monitoring and redundant safety features obviate the need for frequent testing of modern biosafety cabinets under normal conditions of use. Also the testing of biosafety cabinets in biomedical high containment (BL4) laboratories entails a complete shutdown of the laboratory for decontamination with appropriate sterilants to allow technicians to access the equipment safely. This procedure increases risks to laboratory staff working with the sterilants (often in the form of toxic gasses) and requires a halt to all research activities for an extended period of time depending on the number of cabinets to be tested or recertified. The NIH is in agreement with the recommendation of the BMBL that class II biosafety cabinets be tested and certified at least annually, with the understanding that retesting may have to be performed as needed at the discretion of the Institutional Biosafety Committee (IBC), if for example, equipment is moved or subject to unusual conditions of use. Appendix G–II–D–4–p currently states: asabaliauskas on DSK3SPTVN1PROD with NOTICES Appendix G–II–D–4–p. The treated exhaust air from Class I and II biological safety cabinets may be discharged into the laboratory room environment or the outside through the facility air exhaust system. If exhaust air from Class I or II biological safety cabinets is discharged into the laboratory the cabinets are tested and certified at six-month intervals. The exhaust air from Class III biological safety cabinets is discharged, without recirculation through two sets of high efficiency particulate air/HEPA filters in series, via the facility exhaust air system. If the treated exhaust air from any of these cabinets is discharged to the outside through the facility exhaust air system, it is connected to this system in a manner (e.g., thimble unit connection (see Appendix G–III–L, Footnotes and References of Appendix G)) that avoids any interference with the air balance of the cabinets or the facility exhaust air system. Appendix G–II–D–4–p is amended as follows: Appendix G–II–D–4–p. The treated exhaust air from Class I and II biological safety cabinets may be discharged into the laboratory room environment or the outside through the facility air exhaust system. If exhaust air from Class I or II biological safety cabinets is discharged into the laboratory the cabinets are tested and certified at minimum on a yearly basis. More frequent testing and VerDate Sep<11>2014 17:27 Apr 14, 2016 Jkt 238001 certification, based on the amount of use or other safety factors, shall be left to the discretion of the IBC. The exhaust air from Class III biological safety cabinets is discharged, without recirculation through two sets of high efficiency particulate air/HEPA filters in series, via the facility exhaust air system. If the treated exhaust air from any of these cabinets is discharged to the outside through the facility exhaust air system, it is connected to this system in a manner (e.g., thimble unit connection (see Appendix G–III–L, Footnotes and References of Appendix G)) that avoids any interference with the air balance of the cabinets or the facility exhaust air system. With regard to the periodic biologic validation of the centralized heat treatment process for all BL3 and BL4 facilities, the NIH Guidelines requires that this process be performed every 30 days while the BMBL recommends at least an annual biological validation. Similar to biosafety cabinets, modern catch tank systems for heat treatment of all laboratory effluents have also become more sophisticated and now incorporate redundant monitoring systems to track temperature and pressure parameters during each heat treatment cycle. In addition it should be noted that proper validation of the heat treatment catch tank system requires that testing be performed when the system is at or near capacity (i.e. ‘‘under load’’)—more frequent validation of a heat treatment system that is below capacity may not serve the intended purpose of demonstrating that the equipment is functioning as intended. An additional margin of safety is achieved by monitoring sterilization cycle parameters on a routine basis. We are, therefore, in agreement with the recommendation of the BMBL that validation be performed as frequently as necessary at the discretion of the IBC and at least once annually to ensure that the centralized effluent heat treatment system is performing as intended under the established process parameters. This amendment shall apply to heat treatment systems used in both large animal BL3 and BL4 facilities. For large animal BL3 laboratories, the requirement for decontamination and inactivation (BL3–N) found at Appendix Q–II–C–1–b–(5) currently states: Appendix Q–II–C–1–b–(5). Liquid effluent from containment equipment, sinks, biological safety cabinets, animal rooms, primary barriers, floor drains, and sterilizers shall be decontaminated by heat treatment before being released into the sanitary system. The procedure used for heat decontamination of liquid wastes shall be monitored with a recording thermometer. PO 00000 Frm 00081 Fmt 4703 Sfmt 4703 The effectiveness of the heat decontamination process system shall be revalidated every 30 days with an indicator organism. Appendix Q–II–C–1–b–(5) is amended as follows: Appendix Q–II–C–1–b–(5). Liquid effluent from containment equipment, sinks, biological safety cabinets, animal rooms, primary barriers, floor drains, and sterilizers shall be decontaminated by heat treatment before being released into the sanitary system. The procedure used for heat decontamination of liquid wastes shall be monitored with a recording thermometer. The effectiveness of the heat decontamination process system shall be revalidated at minimum on a yearly basis with an indicator organism. More frequent validation, based on the amount of use or other safety factors, shall be left to the discretion of the IBC. For large animal BL3 laboratories, the requirement for animal facilities (BL3– N) found at Appendix Q–II–C–2–h currently states: Appendix Q–II–C–2–h. Liquid effluent from containment equipment, sinks, biological safety cabinets, animal rooms, primary barriers, floor drains, and sterilizers shall be decontaminated by heat treatment before being released into the sanitary system. The procedure used for heat decontamination of liquid wastes shall be monitored with a recording thermometer. The effectiveness of the heat decontamination process system shall be revalidated every 30 days with an indicator organism. Appendix Q–II–C–2–h is amended as follows: Appendix Q–II–C–2–h. Liquid effluent from containment equipment, sinks, biological safety cabinets, animal rooms, primary barriers, floor drains, and sterilizers shall be decontaminated by heat treatment before being released into the sanitary system. The procedure used for heat decontamination of liquid wastes shall be monitored with a recording thermometer. The effectiveness of the heat decontamination process system shall be revalidated at minimum on a yearly basis with an indicator organism. More frequent validation, based on the amount of use or other safety factors, shall be left to the discretion of the IBC. For large animal BL4 laboratories, the requirement for decontamination and inactivation (BL4–N) found at Appendix Q–II–D–1–b–(9) currently states: Appendix Q–II–D–1–b–(9). Liquid effluent from containment equipment, sinks, biological safety cabinets, animal rooms, primary barriers, floor drains, and sterilizers shall be decontaminated by heat treatment before being released into the sanitary E:\FR\FM\15APN1.SGM 15APN1 Federal Register / Vol. 81, No. 73 / Friday, April 15, 2016 / Notices system. Liquid wastes from shower rooms and toilets shall be decontaminated with chemical disinfectants or heat by methods demonstrated to be effective. The procedure used for heat decontamination of liquid wastes shall be monitored with a recording thermometer. The effectiveness of the heat decontamination process system shall be revalidated every 30 days with an indicator organism. Liquid wastes from the shower shall be chemically decontaminated using an Environmental Protection Agency-approved germicide. The efficacy of the chemical treatment process shall be validated with an indicator organism. Chemical disinfectants shall be neutralized or diluted before release into general effluent waste systems. asabaliauskas on DSK3SPTVN1PROD with NOTICES Appendix Q–II–D–1–b–(9) is amended as follows: Appendix Q–II–D–1–b–(9). Liquid effluent from containment equipment, sinks, biological safety cabinets, animal rooms, primary barriers, floor drains, and sterilizers shall be decontaminated by heat treatment before being released into the sanitary system. If required by design, regulation, local ordinance or policy, liquid wastes from shower rooms and toilets shall be decontaminated with chemical disinfectants or heat by methods demonstrated to be effective. The procedure used for heat decontamination of liquid wastes shall be monitored with a recording thermometer. The effectiveness of the heat decontamination process system shall be revalidated at minimum on a yearly basis with an indicator organism. More frequent validation, based on the amount of use or other safety factors, shall be left to the discretion of the IBC. If required by design, regulation, local ordinance or policy, liquid wastes from the shower shall be chemically decontaminated using an Environmental Protection Agency-approved germicide. The efficacy of the chemical treatment process shall be validated with an indicator organism. Chemical disinfectants shall be neutralized or diluted before release into general effluent waste systems. For large animal BL4 laboratories, the requirement for animal facilities (BL4– N) found at Appendix Q–II–D–2–i currently states: Appendix Q–II–D–2–i. Liquid effluent from containment equipment, sinks, biological safety cabinets, animal rooms, primary barriers, floor drains, and sterilizers shall be decontaminated by heat treatment before being released into the sanitary system. Liquid wastes from shower rooms and toilets shall be decontaminated with chemical disinfectants or heat by methods demonstrated to be effective. The procedure used for heat decontamination of liquid wastes shall be monitored with a recording thermometer. The effectiveness of the heat decontamination process system shall be VerDate Sep<11>2014 17:27 Apr 14, 2016 Jkt 238001 revalidated every 30 days with an indicator organism. Liquid wastes from the shower shall be chemically decontaminated using an Environmental Protection Agency-approved germicide. The efficacy of the chemical treatment process shall be validated with an indicator organism. Chemical disinfectants shall be neutralized or diluted before release into general effluent waste systems. Appendix Q–II–D–2–i is amended as follows: Appendix Q–II–D–2–i. Liquid effluent from containment equipment, sinks, biological safety cabinets, animal rooms, primary barriers, floor drains, and sterilizers shall be decontaminated by heat treatment before being released into the sanitary system. If required by design, regulation, local ordinance or policy, liquid wastes from shower rooms and toilets shall be decontaminated with chemical disinfectants or heat by methods demonstrated to be effective. The procedure used for heat decontamination of liquid wastes shall be monitored with a recording thermometer. The effectiveness of the heat decontamination process system shall be revalidated at minimum on a yearly basis with an indicator organism. More frequent validation, based on the amount of use or other safety factors, shall be left to the discretion of the IBC. If required by design, regulation, local ordinance or policy, liquid wastes from the shower shall be chemically decontaminated using an Environmental Protection Agency-approved germicide. The efficacy of the chemical treatment process shall be validated with an indicator organism. Chemical disinfectants shall be neutralized or diluted before release into general effluent waste systems. Dated: April 9, 2016. Lawrence A. Tabak, Deputy Director, National Institutes of Health. [FR Doc. 2016–08810 Filed 4–14–16; 8:45 am] BILLING CODE 4140–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; 60-Day Comment Request; NLM PEOPLE LOCATOR® System Summary: In compliance with the requirement of Section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995, for opportunity for public comment on proposed data collection projects, the National Library of Medicine (NLM), National Institutes of Health (NIH), will publish periodic summaries of proposed PO 00000 Frm 00082 Fmt 4703 Sfmt 4703 22289 projects to be submitted to the Office of Management and Budget (OMB) for review and approval. Written comments and/or suggestions from the public and affected agencies are invited on one or more of the following points: (1) Whether the proposed collection of information is necessary for the proper performance of the function of the agency, including whether the information will have practical utility; (2) The accuracy of the agency’s estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) Ways to enhance the quality, utility, and clarity of the information to be collected; and (4) Ways to minimize the burden of the collection of information on those who are to respond, including the use of appropriate automated, electronic, mechanical, or other technological collection techniques or other forms of information technology. To Submit Comments and For Further Information: To obtain a copy of the data collection plans and instruments, submit comments in writing, or request more information on the proposed project, contact: David Sharlip, NLM Project Clearance Liaison, Office of Administrative and Management Analysis Services, OAMAS, NLM, NIH, Building 38A, Room B2N12, 8600 Rockville Pike, Bethesda, MD 20894, or call non-toll-free number (301) 496– 5441, or Email your request, including your address to: sharlipd@mail.nih.gov. Formal requests for additional plans and instruments must be requested in writing. Comment Due Date: Comments regarding this information collection are best assured of having their full effect if received within 60 days of the date of this publication. Proposed Collection: NLM People Locator System 0925–0612, Expiration Date: 07/31/2016, EXTENSION, National Library of Medicine (NLM), National Institutes of Health (NIH). Need and Use of Information Collection: This collection of data is intended to assist in the reunification of family members and friends who are separated during a disaster. Experience in operational drills and during realworld disasters such as the January 2010 earthquakes in Haiti demonstrates that family members and loved ones are often separated during disasters and have significant difficulty determining each other’s safety, condition, and location. Reunification can not only improve their emotional well-being during the recovery period, but also improve the chances that injured victims will be cared for once they are E:\FR\FM\15APN1.SGM 15APN1

Agencies

[Federal Register Volume 81, Number 73 (Friday, April 15, 2016)]
[Notices]
[Pages 22286-22289]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-08810]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Institutes of Health (NIH) Office of Science Policy 
(OSP) Recombinant or Synthetic Nucleic Acid Research: Action Under the 
NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic 
Acid Molecules (NIH Guidelines)

SUMMARY: The NIH OSP is amending portions of the NIH Guidelines in 
order to provide investigators with biosafety guidance regarding the 
standards for containment of non-human primates (NHPs) in biosafety 
level (BL) 4 laboratories and to make such guidance consistent with the 
expectations articulated in the Centers for Disease Control and 
Prevention (CDC)/NIH Biosafety in Microbiological and Biomedical 
Laboratories 5th edition (BMBL). Specifically, the NIH Guidelines will 
allow for housing of NHPs in open caging in a dedicated animal holding 
room provided there are two physical barriers between that animal 
holding room and non-containment space within the laboratory, the 
animal holding room has negative air pressure with respect to any 
adjacent non-containment corridors, and there are specific 
decontamination protocols in place before the door to the animal 
holding room is opened to allow for the periodic transfer of new 
animals into the room. These amendments do not change the current 
containment requirements in the NIH Guidelines but rather offer an 
alternative for achieving primary containment without compromising 
safety.
    In addition, the recertification requirement for biosafety cabinets 
in BL4 laboratories is updated in recognition of the technological 
standards for modern biosafety cabinets. The NIH OSP also is updating 
the validation requirements for equipment responsible for centralized 
heat decontamination of liquid effluents in laboratories working with 
large animals.
    These amendments to the NIH Guidelines will be implemented 
immediately upon publication in the Federal Register. These changes 
were developed after extensive consultation with biosafety experts, 
directors of and principal investigators in BL4 facilities working with 
NHPs, and CDC's Division of Select Agent and Toxins (DSAT) leadership 
at a public workshop and discussion at a public Recombinant DNA 
Advisory Committee (RAC) meeting. Publication in the Federal Register 
will inform the scientific and biosafety communities.

FOR FURTHER INFORMATION CONTACT: If you have questions, or require 
additional information about these changes, please contact the NIH OSP 
by email at SciencePolicy@od.nih.gov, or telephone at 301-496-9838.

SUPPLEMENTARY INFORMATION: The first three editions of the BMBL and the 
NIH Guidelines were consistent in their approach to requiring primary 
containment for animal work in BL4 containment laboratories. However, 
in the early 1990s, the BMBL was amended and the fourth edition stated 
that animals housed in BL4 suit laboratories (i.e., laboratories in 
which Class III cabinets are not used but instead personnel wear 
positive pressure protective suits) should be housed in a primary 
containment system (such as open cages covered with filtered bonnets 
and opened in laminar flow hoods or other equivalent containment 
systems). This language remains in the current BMBL (5th edition). With 
the change in the BMBL, primary containment caging was arguably 
preferred but no longer required under BL4 containment. In contrast, 
the NIH Guidelines have always required primary containment caging for 
all animals in BL4 laboratories.
    Non-human primates are social animals and require environmental 
enrichment. Researchers in several U.S. BL4 laboratories engaged in NHP 
research approached the NIH OSP with concerns that primary containment 
caging in BL4 laboratories hindered the creation of an environment that 
allowed animals to benefit from adequate social interaction. Also based 
on risk assessments and experiences comparing several primary 
containment caging systems, the researchers concluded that primary 
containment caging may actually create new hazards for laboratory 
workers. These findings included interference with observation of the 
animals from outside the room leading to more frequent entries into the 
BL4 animal room to monitor the animals, and exacerbation of cramped 
working conditions created by the additional barriers required by some 
containment systems, which increases the difficulty of working in 
inflated pressure suits as well as the potential for damage to the 
pressure suit. In addition, investigators stated that current BL4 
laboratory designs incorporate sophisticated engineering systems, which 
provide biosafety protection in a dedicated animal room equivalent to 
the primary containment caging required under the NIH

[[Page 22287]]

Guidelines. On March 28, 2014, the NIH OSP, together with the CDC 
Division of Select Agents (DSAT), held a meeting with investigators and 
biosafety personnel from nine BL4 laboratories in the U.S. and five 
international laboratories (agenda and roster available at http://osp.od.nih.gov/office-biotechnology-activities/event/2014-03-28-120000-2014-03-28-211500/primary-containment-non-human-primates-biosafety-level-4-laboratories-challenges-and-best-practices). That meeting was 
followed by a discussion at the June 11, 2014, meeting of the NIH RAC 
regarding housing of NHPs in BL4 laboratories (a webcast of that 
discussion is available at http://videocast.nih.gov/summary.asp?Live=14300&bhcp=1.)
    As a result of these discussions and after consultation with CDC 
DSAT, the NIH OSP is amending the NIH Guidelines to allow the housing 
of NHP in open cages in a dedicated animal room provided certain 
conditions as articulated below are met.
    In addition, OSP is updating the requirement for testing and 
certification of Class I and II biosafety cabinets at BL4 from every 
six months to annually, recognizing the technological advances in 
biosafety cabinet design and engineering that have occurred over the 
period since this performance measure was originally implemented.
    Finally, Appendix Q of the NIH Guidelines currently requires that 
the centralized heat treatment catch tank system in BL4 large animal 
laboratories be validated every 30 days. To carry out this testing 
effectively, the system should be near capacity (i.e. ``under load''). 
Some laboratories do not use their catch tank systems on a regular 
basis; therefore, a mandatory 30 day validation would require them to 
demonstrate that the equipment is functioning when it is not in use or 
is not at capacity. This will not serve the intended purpose of 
demonstrating that the equipment is functioning as intended. Therefore, 
validation intervals will need to be set based on the utilization of 
the system provided it is done at least once a year.
    To implement these changes, the following sections of the NIH 
Guidelines are to be amended:
    Appendix G-II-D-2-l. currently states:

    Appendix G-II-D-2-l. Laboratory animals involved in experiments 
requiring BL4 level physical containment shall be housed either in 
cages contained in Class III cabinets or in partial containment 
caging systems, such as Horsfall units (see Appendix G-III-K, 
Footnotes and References of Appendix G), open cages placed in 
ventilated enclosures, or solid-wall and -bottom cages placed on 
holding racks equipped with ultraviolet irradiation lamps and 
reflectors that are located in a specially designed area in which 
all personnel are required to wear one-piece positive pressure 
suits.

    Appendix G-II-D-2-1 is amended as follows with the addition of a 
new Appendix G-II-D-2-1-(2) that will address housing of NHPs:

Appendix G-II-D-2-l. Containment for Animal Research

    Appendix G-II-D-2-l-(1). Laboratory animals involved in experiments 
requiring BL4 level physical containment shall be housed either in 
cages contained in Class III cabinets or in partial containment caging 
systems, such as Horsfall units (see Appendix G-III-K, Footnotes and 
References of Appendix G), open cages placed in ventilated enclosures, 
or solid-wall and -bottom cages placed on holding racks equipped with 
ultraviolet irradiation lamps and reflectors that are located in a 
specially designed area in which all personnel are required to wear 
one-piece positive pressure suits.
    Appendix G-II-D-2-l-(2). Non-human primates (NHP) may be housed (1) 
under the containment conditions described in Appendix G-II-D-2-l-(1) 
above, or (2) in open cages within a dedicated animal holding room that 
serves as the primary barrier and in which all personnel are required 
to wear one-piece positive pressure suits. A room serving as a primary 
barrier must be air-tight and capable of being decontaminated using 
fumigation. If NHPs are to be contained in a dedicated animal holding 
room serving as the primary barrier, the following conditions shall be 
met:
    (i) Access to the animal holding room from service corridors 
outside of the BL4 containment space shall require passage through two 
sets of doors, and the inner most door must be an air pressure 
resistant (APR) door;
    (ii) For any animal holding room considered to be a primary 
barrier, APR door(s) providing direct ingress from the exterior service 
corridor shall be fitted with appropriate and redundant lock-out 
mechanisms to prevent access when the animal holding room is 
contaminated and in use. There should be more than one mechanism to 
ensure that this primary barrier door cannot be opened when the animal 
room is contaminated and the APR door shall not serve as an emergency 
exit from the BL4 laboratory. The APR door shall be appropriately 
tested to demonstrate that in the closed, locked-out mode, the door 
provides an air-tight barrier proven by pressure decay testing or other 
equivalent method;
    (iii) Any door(s) allowing access into a corridor from which there 
is direct ingress to an animal holding room must be fitted with either 
(1) an APR door or (2) a non-APR door, providing directional airflow is 
maintained from the laboratory corridor space into the animal room. For 
the purpose of fumigation, animal rooms equipped with non-APR doors 
opening into the adjacent interior corridors shall be considered one 
space (i.e., areas between air-tight doors shall be fumigated 
together).
    (iv) Any door(s) used for access to the service corridor (the 
secondary barrier) shall be self-closing and of solid construction, 
designed not to corrode, split or warp;
    (v) Access to the service corridor inside the secondary barrier 
shall be restricted and strictly controlled when animal rooms are in 
use. Whenever possible, the secondary barrier door(s) should be fitted 
with safety interlock switches designed to prevent it from opening when 
an animal holding room door (the primary barrier) is opened following 
room decontamination; if interlock devices cannot be used, specific 
administrative procedures shall be implemented to control access to the 
service corridor;
    (vi) The service corridor shall maintain a negative pressure 
(inward directional airflow) relative to adjoining traffic corridors;
    (vii) Prior to fumigation of the animal holding room, cages should 
be removed for autoclaving or chemical decontamination.
    (viii) Caging should be chosen to reduce the amount of animal 
detritus that can be thrown out of the cage and onto the floor of the 
animal holding room;
    (ix) The flow of personnel, material and equipment should be 
directed in order to minimize the spread of contamination from the 
animal holding room into adjacent areas of the laboratory.
    (x) Following animal room decontamination, safeguards involving the 
use of personal protective equipment and appropriate administrative 
controls shall be implemented for the safe retrieval of biological 
indicators in order to prevent the spread of infectious agents in the 
event of a decontamination failure.
    With regard to the frequency of class II biosafety cabinet 
recertification and testing, the NIH Guidelines require 
recertification/testing of biosafety cabinets at six-month intervals. 
However, modern biosafety cabinet

[[Page 22288]]

design specifications incorporate continuous electronic and physical 
monitoring systems that track multiple operational parameters such as 
pressure differential, air flow velocity and plenum pressure with added 
capabilities for remote control and monitoring. Continuous performance 
monitoring and redundant safety features obviate the need for frequent 
testing of modern biosafety cabinets under normal conditions of use. 
Also the testing of biosafety cabinets in biomedical high containment 
(BL4) laboratories entails a complete shutdown of the laboratory for 
decontamination with appropriate sterilants to allow technicians to 
access the equipment safely. This procedure increases risks to 
laboratory staff working with the sterilants (often in the form of 
toxic gasses) and requires a halt to all research activities for an 
extended period of time depending on the number of cabinets to be 
tested or recertified. The NIH is in agreement with the recommendation 
of the BMBL that class II biosafety cabinets be tested and certified at 
least annually, with the understanding that retesting may have to be 
performed as needed at the discretion of the Institutional Biosafety 
Committee (IBC), if for example, equipment is moved or subject to 
unusual conditions of use.
    Appendix G-II-D-4-p currently states:

    Appendix G-II-D-4-p. The treated exhaust air from Class I and II 
biological safety cabinets may be discharged into the laboratory 
room environment or the outside through the facility air exhaust 
system. If exhaust air from Class I or II biological safety cabinets 
is discharged into the laboratory the cabinets are tested and 
certified at six-month intervals. The exhaust air from Class III 
biological safety cabinets is discharged, without recirculation 
through two sets of high efficiency particulate air/HEPA filters in 
series, via the facility exhaust air system. If the treated exhaust 
air from any of these cabinets is discharged to the outside through 
the facility exhaust air system, it is connected to this system in a 
manner (e.g., thimble unit connection (see Appendix G-III-L, 
Footnotes and References of Appendix G)) that avoids any 
interference with the air balance of the cabinets or the facility 
exhaust air system.

    Appendix G-II-D-4-p is amended as follows:
    Appendix G-II-D-4-p. The treated exhaust air from Class I and II 
biological safety cabinets may be discharged into the laboratory room 
environment or the outside through the facility air exhaust system. If 
exhaust air from Class I or II biological safety cabinets is discharged 
into the laboratory the cabinets are tested and certified at minimum on 
a yearly basis. More frequent testing and certification, based on the 
amount of use or other safety factors, shall be left to the discretion 
of the IBC. The exhaust air from Class III biological safety cabinets 
is discharged, without recirculation through two sets of high 
efficiency particulate air/HEPA filters in series, via the facility 
exhaust air system. If the treated exhaust air from any of these 
cabinets is discharged to the outside through the facility exhaust air 
system, it is connected to this system in a manner (e.g., thimble unit 
connection (see Appendix G-III-L, Footnotes and References of Appendix 
G)) that avoids any interference with the air balance of the cabinets 
or the facility exhaust air system.
    With regard to the periodic biologic validation of the centralized 
heat treatment process for all BL3 and BL4 facilities, the NIH 
Guidelines requires that this process be performed every 30 days while 
the BMBL recommends at least an annual biological validation. Similar 
to biosafety cabinets, modern catch tank systems for heat treatment of 
all laboratory effluents have also become more sophisticated and now 
incorporate redundant monitoring systems to track temperature and 
pressure parameters during each heat treatment cycle. In addition it 
should be noted that proper validation of the heat treatment catch tank 
system requires that testing be performed when the system is at or near 
capacity (i.e. ``under load'')--more frequent validation of a heat 
treatment system that is below capacity may not serve the intended 
purpose of demonstrating that the equipment is functioning as intended. 
An additional margin of safety is achieved by monitoring sterilization 
cycle parameters on a routine basis. We are, therefore, in agreement 
with the recommendation of the BMBL that validation be performed as 
frequently as necessary at the discretion of the IBC and at least once 
annually to ensure that the centralized effluent heat treatment system 
is performing as intended under the established process parameters. 
This amendment shall apply to heat treatment systems used in both large 
animal BL3 and BL4 facilities.
    For large animal BL3 laboratories, the requirement for 
decontamination and inactivation (BL3-N) found at Appendix Q-II-C-1-b-
(5) currently states:

    Appendix Q-II-C-1-b-(5). Liquid effluent from containment 
equipment, sinks, biological safety cabinets, animal rooms, primary 
barriers, floor drains, and sterilizers shall be decontaminated by 
heat treatment before being released into the sanitary system. The 
procedure used for heat decontamination of liquid wastes shall be 
monitored with a recording thermometer. The effectiveness of the 
heat decontamination process system shall be revalidated every 30 
days with an indicator organism.

    Appendix Q-II-C-1-b-(5) is amended as follows:
    Appendix Q-II-C-1-b-(5). Liquid effluent from containment 
equipment, sinks, biological safety cabinets, animal rooms, primary 
barriers, floor drains, and sterilizers shall be decontaminated by heat 
treatment before being released into the sanitary system. The procedure 
used for heat decontamination of liquid wastes shall be monitored with 
a recording thermometer. The effectiveness of the heat decontamination 
process system shall be revalidated at minimum on a yearly basis with 
an indicator organism. More frequent validation, based on the amount of 
use or other safety factors, shall be left to the discretion of the 
IBC.
    For large animal BL3 laboratories, the requirement for animal 
facilities (BL3-N) found at Appendix Q-II-C-2-h currently states:

    Appendix Q-II-C-2-h. Liquid effluent from containment equipment, 
sinks, biological safety cabinets, animal rooms, primary barriers, 
floor drains, and sterilizers shall be decontaminated by heat 
treatment before being released into the sanitary system. The 
procedure used for heat decontamination of liquid wastes shall be 
monitored with a recording thermometer. The effectiveness of the 
heat decontamination process system shall be revalidated every 30 
days with an indicator organism.

    Appendix Q-II-C-2-h is amended as follows:
    Appendix Q-II-C-2-h. Liquid effluent from containment equipment, 
sinks, biological safety cabinets, animal rooms, primary barriers, 
floor drains, and sterilizers shall be decontaminated by heat treatment 
before being released into the sanitary system. The procedure used for 
heat decontamination of liquid wastes shall be monitored with a 
recording thermometer. The effectiveness of the heat decontamination 
process system shall be revalidated at minimum on a yearly basis with 
an indicator organism. More frequent validation, based on the amount of 
use or other safety factors, shall be left to the discretion of the 
IBC.
    For large animal BL4 laboratories, the requirement for 
decontamination and inactivation (BL4-N) found at Appendix Q-II-D-1-b-
(9) currently states:

    Appendix Q-II-D-1-b-(9). Liquid effluent from containment 
equipment, sinks, biological safety cabinets, animal rooms, primary 
barriers, floor drains, and sterilizers shall be decontaminated by 
heat treatment before being released into the sanitary

[[Page 22289]]

system. Liquid wastes from shower rooms and toilets shall be 
decontaminated with chemical disinfectants or heat by methods 
demonstrated to be effective. The procedure used for heat 
decontamination of liquid wastes shall be monitored with a recording 
thermometer. The effectiveness of the heat decontamination process 
system shall be revalidated every 30 days with an indicator 
organism. Liquid wastes from the shower shall be chemically 
decontaminated using an Environmental Protection Agency-approved 
germicide. The efficacy of the chemical treatment process shall be 
validated with an indicator organism. Chemical disinfectants shall 
be neutralized or diluted before release into general effluent waste 
systems.

    Appendix Q-II-D-1-b-(9) is amended as follows:
    Appendix Q-II-D-1-b-(9). Liquid effluent from containment 
equipment, sinks, biological safety cabinets, animal rooms, primary 
barriers, floor drains, and sterilizers shall be decontaminated by heat 
treatment before being released into the sanitary system. If required 
by design, regulation, local ordinance or policy, liquid wastes from 
shower rooms and toilets shall be decontaminated with chemical 
disinfectants or heat by methods demonstrated to be effective. The 
procedure used for heat decontamination of liquid wastes shall be 
monitored with a recording thermometer. The effectiveness of the heat 
decontamination process system shall be revalidated at minimum on a 
yearly basis with an indicator organism. More frequent validation, 
based on the amount of use or other safety factors, shall be left to 
the discretion of the IBC. If required by design, regulation, local 
ordinance or policy, liquid wastes from the shower shall be chemically 
decontaminated using an Environmental Protection Agency-approved 
germicide. The efficacy of the chemical treatment process shall be 
validated with an indicator organism. Chemical disinfectants shall be 
neutralized or diluted before release into general effluent waste 
systems.
    For large animal BL4 laboratories, the requirement for animal 
facilities (BL4-N) found at Appendix Q-II-D-2-i currently states:

    Appendix Q-II-D-2-i. Liquid effluent from containment equipment, 
sinks, biological safety cabinets, animal rooms, primary barriers, 
floor drains, and sterilizers shall be decontaminated by heat 
treatment before being released into the sanitary system. Liquid 
wastes from shower rooms and toilets shall be decontaminated with 
chemical disinfectants or heat by methods demonstrated to be 
effective. The procedure used for heat decontamination of liquid 
wastes shall be monitored with a recording thermometer. The 
effectiveness of the heat decontamination process system shall be 
revalidated every 30 days with an indicator organism. Liquid wastes 
from the shower shall be chemically decontaminated using an 
Environmental Protection Agency-approved germicide. The efficacy of 
the chemical treatment process shall be validated with an indicator 
organism. Chemical disinfectants shall be neutralized or diluted 
before release into general effluent waste systems.

    Appendix Q-II-D-2-i is amended as follows:
    Appendix Q-II-D-2-i. Liquid effluent from containment equipment, 
sinks, biological safety cabinets, animal rooms, primary barriers, 
floor drains, and sterilizers shall be decontaminated by heat treatment 
before being released into the sanitary system. If required by design, 
regulation, local ordinance or policy, liquid wastes from shower rooms 
and toilets shall be decontaminated with chemical disinfectants or heat 
by methods demonstrated to be effective. The procedure used for heat 
decontamination of liquid wastes shall be monitored with a recording 
thermometer. The effectiveness of the heat decontamination process 
system shall be revalidated at minimum on a yearly basis with an 
indicator organism. More frequent validation, based on the amount of 
use or other safety factors, shall be left to the discretion of the 
IBC. If required by design, regulation, local ordinance or policy, 
liquid wastes from the shower shall be chemically decontaminated using 
an Environmental Protection Agency-approved germicide. The efficacy of 
the chemical treatment process shall be validated with an indicator 
organism. Chemical disinfectants shall be neutralized or diluted before 
release into general effluent waste systems.

     Dated: April 9, 2016.
Lawrence A. Tabak,
Deputy Director, National Institutes of Health.
[FR Doc. 2016-08810 Filed 4-14-16; 8:45 am]
 BILLING CODE 4140-01-P