Summary of Changes to the Biosafety in Microbiological and Biomedical Laboratories 6th Edition (BMBL-6)

This Summary of Changes was prepared by the ABSA International Technical and Regulatory Review Committee (TRR). May 2021

This Summary of Changes is not to be used as a substitute for the CDC/NIH BMBL-6 edition.

Table of Contents

Appendix C – Transportation of Infectious Substances (pages 415-421)

Changes of note include updates to reflect new ICAO & IATA requirements , updates to outdated contact information and weblinks, and modifications to verbiage for flow, not content. Structurally, this section is very similar to the BMBL-5 with the one major change, shipment of Select Agents has become its own, stand-alone subtitle.

Appendix D – Biosafety and Biocontainment for Pathogens Affecting Agricultural Animals and Animals that are Loose-Housed or in Open Penning (pages 423-456)

Appendix D of the BMBL-6 is substantially different from that in the BMBL-5, starting with a more informative title. As the expanded introduction states, this appendix “…focuses primarily on in vitro and in vivo research and diagnostic activities involving pathogens that primarily affect agricultural animals and other animal species that cannot be housed in primary containment isolators or an equivalent means of primary containment following challenge.”

TheBMBL-5 provided a description of facility and work practice enhancements added to ABSL-3 to become BSL-3Ag, as well as potential facility enhancements to BSL-3 and ABSL-3 for agriculture agent permitting. TheBMBL-6 includes guidance for performing risk assessments to ensure appropriate biosafety and biocontainment practices are in place. In addition, there has been both a change in terminology, Animal Biosafety Level-3 Agriculture (ABSL-3Ag) replacing BSL-3-Ag, and an addition of new terminology: ABSL-2Ag and ABSL-4Ag. Potential enhancements to non-agriculture biosafety levels for conducting research with animal pathogens for work conducted in primary containment now includes BSL/ABSL-2 and BSL/ABSL-4, in addition to BSL/ABSL-3 found in the previous edition. Similarly, potential enhancements for work with animal pathogens outside primary containment now includes ABSL-2Ag and ABSL-4Ag in addition to ABSL-3Ag. The most important, and welcome, changes found in the new edition are the sections describing potential enhancements. Not only have these been rewritten (or written for the new sections) for clarity in guidance and better applicability, but they are also presented in a logical order from lower to higher biosafety levels. The final change in this appendix is the replacement of agent summaries with tables of an expanded list of agents and recommended containment levels. These tables also include natural host range, natural routes of transmission, and environmental stability information for each agent.

Appendix E – Arthropod Containment Guidelines (pages 458-459)

This section includes changes with an increased focus on risk assessment and containment levels. In addition, Appendix E in the BMBL-6 includes a citation of the most recent publication and revisions to the Arthropod Containment Guidelines, Version 3.2 published in 2019 by the American Committee of Medical Entomology, a subcommittee of the American Society of Tropical Medicine and Hygiene, included as the 2nd reference for this Appendix.

Appendix F – Select Agents and Toxins (page 460)

The Public Health Security and Bioterrorism Preparedness and Response Act of 2002 and Agricultural Bioterrorism Protection Act of 2002 requires the Department of Health and Human Services and U.S. Department of Agriculture to regulate the possession, use, and transfer of select biological agents and toxins that have the potential to pose a severe threat to public health and safety and animal and plant health or products. The Federal Select Agent Program (FSAP) oversees these activities and is jointly run by the Centers for Disease Control and Prevention’s Division of Select Agents ( 42 CFR Part 73) and Toxins and the Animal and Plant Health Inspection Service’s Agriculture Select Agent Services (7 CFR 331 and 9 CFR Part 121).

The key safety and security elements of the regulations include: required registration with FSAP; security risk assessment of registered personnel, enforcement actions for violations; designation of Responsible Officials at entities; development of various plans (security, incident response, and biosafety); requirement for approval of certain experiments; training requirements, duty to report various situations; approval of all transfer; maintenance of records and documentation; authority to inspect entities; specific exemptions and exclusions; and requirement to validate inactivation procedures.

Appendix G – Integrated Pest Management (pages 463-465)

This appendix describes the importance and design of an integrated pest management program to laboratory management. This section is almost identical to its counterpart in the BMBL-5 except for minor verbiage modifications. The only addition not found in the BMBL-5 is under the FACILITY DESIGN header, where the use of the NIH Design Requirements Manual was specifically mentioned as a resource.

Appendix H – Working with Human, NHP, and Other Mammalian Cells and Tissues (pages 466-468)

The BMBL-6 Appendix H provides a more detailed guidance for working with clinical or research samples which may contain bloodborne pathogens including risk assessment and risk mitigation precautions presented in six new sections: The Bloodborne pathogens and risk assessment related to material source and type provides a basic description of bloodborne pathogens with several common examples as a basis for the risk assessment to be performed when working with human or NHP blood or other potentially infectious materials, as well as a reference to the USA OSHA Bloodborne pathogen standard. Factors to consider during the risk assessment include Tissue source (human pathogens and zoonotic agents); Cell or tissue type (cells from different tissues and sources present different risks for oncogenesis); Culture Type (potential of cells maintained in culture for harboring undetected pathogens or viral genomes which may present a risk to personnel using primary cultures or cell lines permissive to various viruses known to be pathogenic to humans).

Additional considerations for handling human and NHP source materials include endogenous pathogens present in the specimens or which may have been introduced for experimental purposes when developing the risk assessment. Lastly, the Risk Mitigation section describes the use of universal precautions (BSL-2 practices, engineering controls, use of a BSC, and PPE) for handling RG-2 pathogens or samples with no known infectious agents. RG-3 and RG-4 pathogens need to be handled using higher level of containment practices and engineering controls.