General Comments

To make a general comment about the BMBL 5th edition, enter your responses below in the “leave a reply” box. In your comment, please specify what information/table/figure you would suggest to be deleted, modified (how?), or added.

Your comments will be posted on this page for the committee and public to view and respond.

45 Comments

  1. Anonymous's Gravatar Anonymous
    May 20, 2016    

    The subsection of Influenza in Section VIII-Agent Summary Statements should take into consideration that bat influenza viruses (H17N10 and H18N11) do not appear to encode surface glycoproteins with demonstrated hemagglutination or neuraminidase activity, respectively. This section should be revised that influenza viruses are classified by genetic analysis and antigenic relatedness. In addition to guidance provided for non-contemporary human influenza (H2N2) strains, additional guidance should be provided for contemporary avian or mammalian influenza (H2Nx) strains. The section covering the 1918 Influenza Strain should emphasize that the pandemic 2009-lineage of influenza viruses are antigenically related to the 1918 influenza virus strain and confer protective humoral immunity. This should be factored into risk assessments. The section, Occupational Health Considerations, indicates that a medical surveillance plan that requires storage of baseline serum samples for individuals working with select agent influenza viruses. This requirement is not consistent with the occupational health program requirements specified in the select agent program regulations/guidance documents.

  2. Anonymous's Gravatar Anonymous
    May 20, 2016    

    The next addition of the BMBL should emphasize the critical importance of institutional commitment to biomedical research. This commitment should be reflected by greater oversight by an Institutional Biosafety Committee (IBC), Institutional Animal Care and Use Committee, and Occupational/Employee Health Services. Additional guidance should be provided to reflect current attention by national funding and regulatory authorities on life science research that is considered Dual Use Research of Concern or Gain of Function research. The section on biosecurity is very informative in helping an investigator create a biosecurity plan. The biosafety section should be revised in a similar fashion to indicate the essential components (i.e. roles and responsibilities, waste management practices, use and disposal of sharps, etc.) that should be included in a biosafety plan. The biosafety section should also emphasize the need to have the biosafety plan and procedures reviewed by an IBC. The role of the IBC has expanded beyond review of recombinant DNA activities, and the BMBL should reflect these additional responsibilities.

  3. Bill Homovec's Gravatar Bill Homovec
    May 20, 2016    

    Somewhere in the revised BMBL, it should be stated that a biological safety officer must be in place at institutions for their work with infectious agents at BSL-3 or higher. Appropriate training, education and creditials need to be consideration for the selection of that biological safety officer. This would be consistent with the NIH Guidelines. It would also be appropriate, given the risk assessments that would be required for Select Agents, Dual Use agents, etc. as well of the complexity of infectious disease work and appropriate containment and other requirements at these biosafety levels. For institutions doing work with infectious agents at BSL-2, a biological safety officer should be in place to support this work. Appropriate training, education and creditials should be considered for the selection of that biological safety officer.

  4. FDA ESEM's Gravatar FDA ESEM
    May 20, 2016    

    We suggest the BMBL continue to be published both electronically and in print.
    Given that BMBL is the de facto bible for biosafety (and IBCs), I think it would be extremely useful for there to be a section on risk assessment of gene modified organisms beyond the very brief couple of paragraphs in there at the moment. This is currently buried in the “Evolution of National Biosafety Guidelines” section and does little more than provide a tip of the hat to the NIH guidelines. More explicit guidance or advice on where to find it is badly needed – this is especially true with the rise of “DIY” hobbyists etc. who may be unaware that BMBL is not the right place to look.

    We also recommend the following:
    that the BMBL remain performance-based guidance
    that only minor edits to content and updates to agent summary statements are necessary

  5. Anonymous's Gravatar Anonymous
    May 19, 2016    

    Would appreciate if there was inclusion on aquatic biosafety (marine and freshwater) for fish, e.g., zebrafish, algae. If there was at minimum reference would be most appropriate.

    In addition, there would also like to see field biosafety guidance to include use of wild animals.

  6. Scott Alderman's Gravatar Scott Alderman
    May 19, 2016    

    The current BMBL section on ABSL-3 includes inconsistent language regarding eye, face and respiratory protection. Under Standard Microbiological Practices for ABSL-3, it reads, “Eye, face and respiratory protection should be used in rooms containing infected animals…”. Then in Safety Equipment for ABSL-3, it reads, “All personnel entering areas where infectious materials and/or animals are housed or manipulated wear appropriate eye, face and respiratory protection.” I suggest harmonizing the language to be more directive on noted PPE.

  7. Scott Alderman's Gravatar Scott Alderman
    May 19, 2016    

    The agent summary statement for Poxviruses currently reads, “..all persons working in or entering laboratory or animal care areas where activities with vaccinia, monkey pox, or cowpox viruses are being conducted should have evidence of satisfactory vaccination.” The package insert for the current vaccine, ACAM2000, communicates the warning, “suspected cases of myocarditis and/or pericarditis have been observed in healthy adult primary vaccinees at an approximate rate of 5.7 per 1000”. I suggest that the recommendation for vaccination be revised to something like, “Vaccination of personnel who actively handle the virus or infected animals should be evaluated for vaccination by an occupational health professional”. This modification would allow the occ health professional to properly discuss the risk of the vaccine with the worker and weigh the overall benefit before proceeding to vaccinate. Also, the modified language would remove any pressure to vaccinate workers who aren’t at risk of exposure such as someone who simply enters the lab (e.g., safety auditor) with no direct responsibility to actively handle the virus

  8. Richard W Gilpin's Gravatar Richard W Gilpin
    May 18, 2016    

    NSF/ANSI Standard 49 Appendix E Biosafety Cabinet Selection, Installation, Lifespan and Decommissioning will soon be published online to the public by NSF International, Ann Arbor, MI.
    As chair of the Appendix E revision Task Group, I suggest that the BMBL Appendix A incorporate the NSF Standard 49 Appendix E information – It is much more accurate and useful to researchers and safety personnel.

  9. Lynn Klotz's Gravatar Lynn Klotz
    May 13, 2016    

    I propose a revision to the BMBL that would allow the BMBL to deal with the new realities of dangerous research, in particular the creation of and research with live dangerous potential pandemic pathogens.”
    The proposal is too long for this Comment box, so I refer you to the following URL (http://armscontrolcenter.org/wp-content/uploads/2016/05/Comment-on-NIH-Oversight-of-Research-1.pdf) to read the proposal. The two key elements of the proposal are:
    (1) A mechanism for making decisions about research on laboratory-created potential pandemic pathogens or research. Three committees would be involved: Existing Institutional Biosafety Committee and NIH reviews, supplemented by a non-government Committee of Experts review.
    (2) If one or more of the committees recommends banning the particular research in the U.S., a final decision would be made by an Executive-branch Committee that could include members from the National Security Council, the Office of Science and Technology Policy, the Department of State, and perhaps others. This committee composition would help ensure that dual-use security concerns, biosafety risk to the community, and international ramifications are addressed

  10. Tim Baszler's Gravatar Tim Baszler
    May 12, 2016    

    It would be good to incorporate laboratory biosafety guidelines for diagnostic specimens (unknown samples) in both human and animal diagnostic laboratories. This could easily be done by referring as appropriate to a publication from a CDC-convened blue ribbon panel that thoroughly covered this topic (MMWR Supplement Vol 61, Jan 6, 2012 “Guidelines for Safe Work Practices in Human and Animal Medical Diagnostic Laboratories”. The main issue for university-based veterinary diagnostic laboratories is laboratory practices are reviewed by university-based biosafety committees, which essentially approve research protocols. As such these biosafety committee rely heavily on the BMBL, which to date focuses almost entirely as a research biosafety guideline. There is very little information in the current BMBL for how to evaluate appropriate biosafety and biocontainment for veterinary diagnostic specimens. For example, biosecurity and biosafety procedures and containment of unknown veterinary diagnostic specimens that may contain BLS3 classified agents should not mean that all diagnostic unknown specimens must be handling under BSL3 procedures and containment. What is required is some form of practical biological risk analysis that incorporates sample type, test type, species of origin, geographical region of origin etc upon which appropriate control measures can be implemented. A more clear guideline for this process in the BMBL is sorely needed.

  11. Kalpana Rengarajan's Gravatar Kalpana Rengarajan
    May 12, 2016    

    With a good risk management system in place, the practice of blaming the scientist or technician who makes a mistake should end. As long as we believe that mistakes are only caused by individuals, we deny that the overarching system has a problem. Instead, we need to understand accidents as system accidents. In a complex environment, such as a bioscience laboratory, with many different people, processes, and technologies contributing to the success or failure of the operation, any mistake is a reflection on the overall system that governs the work of the laboratory. An accident is an example of a series of small mistakes that likely have been made for a period of time that simply have not yet resulted in an accident. It is critical for management to create an environment that embraces and even rewards discussion about what doesn’t work well in the laboratory. Until we eliminate the atmosphere of blame and finger-pointing, problems, near misses, and accidents will be hidden and denied. And the lessons to be learned from the events will be lost. And the accidents will continue because the system will not change. It is essential for the BMBL to promote routine laboratory hot washes that reveal the utility and value of all of the control measures, and identify new data that can contribute to revisions of the risk assessment. The BMBL should also encourage incentives and/or rewards for those laboratory staff who identify safety issues and improvements. Finally, the BMBL should articulate the concept of the system accident, and explicitly reject the notion that individuals should be blamed for laboratory accidents.

  12. Sandia National Laboratories International Biological and Chemical Threat Reduction's Gravatar Sandia National Laboratories International Biological and Chemical Threat Reduction
    May 12, 2016    

    • There is a critical need to enhance the focus on a risk-based approach to laboratory biosafety.
    • We recommend an expansion on the very brief chapter on laboratory biosecurity. The expansion should be in alignment with more recent guidance (ex. CWA 15793, IFBA)
    • Today, there are many more considerations of risk that must be addressed in the next iteration of the BMBL. The BMBL has traditionally focused on research labs, yet other laboratory types, such as clinical, diagnostic, field, low-resource, must also be addressed. In addition, a more current assessment of risks regarding waste removal and environmental contamination, and the advancement of research and knowledge (both legitimate and dual-use) should also be considered.
    • Biorisk management (BRM) should be implemented as an organizational approach with different levels of shared responsibilities; it is not the responsibility of an individual person. The BMBL should refer to the CWA or ISO initiation of ISO35001 where this concept is stated explicitly.
    • There should be a priority focus on laboratory biosafety education, knowledge sharing, and workforce training.
    • More guidance is needed to address unknown risk specifically in the diagnostic laboratory setting (both routine and outbreak guidance).
    • The BMBL is referenced by laboratories all around the world. Consequently, we suggest the authors of this revision keep this in mind and consider structuring this document as more of an international reference document considering the various risks and circumstances in the international community.

  13. Sonia Godoy-Tundidor, PhD's Gravatar Sonia Godoy-Tundidor, PhD
    May 11, 2016    

    I’ll be happy to review the “almost final” version for language consistency, style, and typos.

  14. Anonymous's Gravatar Anonymous
    May 11, 2016    

    Given the impact of the BMBL and the changes/additions in its purpose over the years, I hope the committee will consider a complete re-thinking of the organization and content of the document. And make it easier to find things.

  15. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 11, 2016    

    Ebola probably deserves its own summary statement along with Lassa and Zika

  16. Julie Johnson's Gravatar Julie Johnson
    May 11, 2016    

    This is a comment on this process rather than on the BMBL publication:
    Given the extensive detailed material contained in the BMBL, and the weight it bears in the regulatory world, and the large amount of other regulatory revision currently ongoing that stakeholders need to absorb and comment on, the turnaround time for stakeholder to comment on the BMBL revision is quite short. There are thousands of stakeholders affected by the content of this book, and seemingly minor wording changes can end up having great impact when implemented. Would it not be better to allow additional time and advertise more broadly to stakeholders for input? This is such an important and impactful document we need to proceed with thoughtfulness and evaluation of impact so that the revision is most useful and meaningful to stakeholders.

  17. Julie Johnson's Gravatar Julie Johnson
    May 11, 2016    

    This comment is expanding on a previous comment that was submitted incomplete.

    I agree with the comment made earlier :”In the interest of brevity and to reduce confusion, I suggest eliminating redundant information between BSL-X and ABSL-X sections. ABSL requirements are fundamentally the same as BSL, but with additional enhancements. Perhaps something along the lines of “ABSL-X guidelines are to be followed with the following additional criteria:” Being concise and clear is important and would make the BMBL more efficient to use.
    It also is very important that consistent guidance is given throughout the document. Guidance in two differeent sections cannot contradict each other.
    For example:
    In Section V. under Animal Biosfaety Level 3, Section A. Standard Microbiological Practices, #15. states:
    “All wastes from the animal room (including animal tissues, carcasses, and bedding) are transported from the animal room in leak-proof containers for appropriate disposal in compliance with applicable institutional, local and state requirements. Decontaminate all potentially infectious materials before disposal using an effective method.”
    In Section V. under Animal Biosfaety Level 3, Section B. Special Practices, #5. states:
    “A method for decontaminating all infectious materials must be available within the facility, preferably within the areas where infectious materials and/or animals are housed or are manipulated (e.g., autoclave, chemical disinfection, or other approved decontamination methods).” and “Decontaminate all potential infectious materials (including animal tissues, carcasses, contaminated bedding, unused feed, sharps, and other refuse) by an appropriate method before removal from the areas where infectious materials and/or animals are housed or manipulated.”
    In Section V. under Animal Biosfaety Level 3, Section D. LAboratory Facilities, #12. states:
    “An autoclave is available which is convenient to the animal rooms where the biohazard is contained. The autoclave is utilized to decontaminate infectious materials and waste before moving it to the other areas of the facility. If not convenient to areas where infectious materials and/or animals are housed or are manipulated, special practices should be developed for transport of infectious materials to designated alternate location/s within the facility.”
    These 3 statements, all within the ABSL-3 guidance section, are not compatible and leave the user confused. It’s important that the whole publication be closely reviewed before publication so that these types of incositencies do not happen in new edition. This is a document that is used with the force of regulation, so clear guidance is essential.

  18. Julie Johnson's Gravatar Julie Johnson
    May 11, 2016    

    I agree with the comment made earlier :”In the interest of brevity and to reduce confusion, I suggest eliminating redundant information between BSL-X and ABSL-X sections. ABSL requirements are fundamentally the same as BSL, but with additional enhancements. Perhaps something along the lines of “ABSL-X guidelines are to be followed with the following additional criteria:” Being concise and clear is important and would make the BMBL more efficient to use.
    It also is very important that consistent guidance is given throughout the document. Guidance in two differeent sections cannot contradict each other.

  19. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    Agent summary statements need to be maintained electronically and referenced, separate from the published BMBL version if that still occurs, and have an approval process for updating and/or revising based on new information.

  20. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    Agency summary statements, in general, need to be updated to include all relevant information needed in performing agent-specific risk assessments, as well as information relevant to post-exposure response. Therefore, the agents summary statement format should be modified to model Health Canada’s MSDS format, or at least adopt relevant sections/topics from those documents that are not currently address consistently, including incubation period, communicability, infectious dose, Section IV – Viability (e.g., susceptibility to disinfectants, physical inactivation, and survival outside host), Section V – Medical (e.g.. post-exposure surveillance and follow-up, first aid/treatment, and prophylaxis).

  21. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    Bacterial agents are separated out by specific organism and each bacterium has its own section. This is not true for viruses where they are classified by family (ex: arbovirus, or viral hemorrhagic fevers). Many viruses in the same family have unique requirements and these should be noted.

  22. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    The BMBL and BSL concepts do not translate into low-resource environments. The international message sent by saying that it is only acceptable to work with microscopic amounts of Ebola in the US is in a BSL-4 is fitting in highly resourced countries, but in the middle of an outbreak in a low resource environment these recommendations are impractical. The BMBL is now an international document and must be able to manage biological risks wherever they occur—this is more evidence to push for a risk-based system of biosafety which can be applied internationally. It is also critical that the revision of the BMBL be aligned with the revision of the WHO’s Laboratory Biosafety Manual, which apparently is moving away from the agent-based perspective.

  23. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    The concept that agents have defined biosafety levels (BSLs) is problematic, especially for the clinical/diagnostic laboratory community. Tightly linking agents to BSLs basically preclude the concept of a rigorous, activity-specific or protocol-specific risk assessment. Why do a risk assessment if biosafety is defined as the implementation of a BSL, and the agent tells you what BSL to use? The result is substantive risk assessments are often not conducted

  24. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    The current arrangement of chapters is not the most useful method of organizing the available information.

  25. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    The BMBL should have an updated online version where each section can be updated frequently based on new information which becomes available.

  26. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    With a good risk management system in place, the practice of blaming the scientist or technician who makes a mistake should end. As long as we believe that mistakes are only caused by individuals, we deny that the overarching system has a problem. Instead, we need to understand accidents as system accidents. In a complex environment, such as a bioscience laboratory, with many different people, processes, and technologies contributing to the success or failure of the laboratory’s operations, any mistake is a reflection on the overall system that governs the work of the laboratory. An accident is an example of a series of small mistakes that likely have been made for a period of time that simply haven’t yet resulted in an accident. It is critical for management to create an environment that embraces and even rewards discussion about what doesn’t work well in the laboratory. Until we eliminate the tendency of blame and finger-pointing, problems, near misses, and accidents will be hidden and denied. And the lessons to be learned from the events will be lost. And the accidents will continue because the system will not change. It is essential for the BMBL to promote routine laboratory hot washes that reveal the utility and value of all of the control measures, and identify new data that can contribute to revisions of the risk assessment. The BMBL should also encourage incentives and rewards for those laboratory staff who identify safety issues and improvements. Finally, the BMBL should articulate the concept of the system accident, and explicitly reject the notion that individuals should be blamed for laboratory accidents.

  27. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    The recently released GAO report on High Containment Laboratories references six elements that they identified as key for managing these types of laboratories: Incident reporting, roles and responsibilities, training, inventory control, inspections, and reference to the BMBL. Each of these elements should be reviewed in the context of the GAO report and ensure that an adequate level of guidance is provided for high containment labs. Additionally, we would recommend that the role of the Biorisk Management Standard, which also provides guidance on each of these elements, should be clarified because institutions are now faced with two separate guidance documents…one a code of conduct that can be implemented with risk-based/performance-based approach, the other a voluntary management system that can help create structure to a program. It would be helpful to have a section that clarifies how both documents can be used to complement one another.

  28. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    The BMBL basically says: define the BSL, then you’re good to go. Biosafety achieved. What the bioscience community now needs – and what is missing from the BMBL – is an explanation that biosafety must be implemented within a management system. There must be a mechanism for creating metrics – in advance of the work, based on the risk assessment – that defines how the effectiveness of the safety mitigation measures will be evaluated on a routine basis. This is often called “performance management.” This concept is well ingrained in medical diagnostic laboratories that must establish quality management systems – as well as other high-consequence industries. We do not sufficiently promote an analogous (or integrated) safety management system in the biosciences. We have no mechanisms to routinely collect information about what works and doesn’t work, and to document unexpected events in the lab, near misses, accidents, etc. This data, which should be collected on a routine (continuous) basis, should be used to regularly update the risk assessment, and to modify and improve mitigation measures before an accident happens. This is absolutely key for the future of biosafety. The BMBL must articulate a management system concept to move biosafety out of the administrative basements of bioscience laboratories – and the perception that biosafety is only the responsibility of the designated “biosafety officer” – and to create a system that invests the entire scientific staff in the performance of the safety system.

  29. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    Biosafety needs to take a management systems approach which includes risk assessment, mitigation, and performance evaluation. This information is included in the CWA Biorisk Management Standards Document. The BMBL should incorporate how to interface with both of these documents.

  30. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    Additional guidance documents and standards (e.g., MMWR Guidelines for Human and Animal Diagnostic Labs and CLSI M29-A4 – Protection of Lab Workers from Lab Acquired Infection) have been developed specifically for the clinical and diagnostic lab setting. The guidance provided in these documents compared to the existing BMBL guidance needs to be considered as they update the BMBL. The needs of the clinical/diagnostic laboratories and types evidence-based best practices appropriate for those environments may differ from biomedical/research lab setting, so that needs to be considered as the next edition of the BMBL.

  31. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    Although there is a universal understanding in the biosafety community that BSL-3 materials need to be properly inactivated before transferring to a lower BSL, the BMBL currently lacks any reference to the need for validated methods of inactivation protocols (other than for waste) in the BSL-3 guidelines, Additionally, there is no consensus on appropriate methods for validation of inactivation protocols or acknowledgement of the limitations (i.e., limits of detection) associated with validation procedures for viruses. ABSA, ASM, and APHL should work together to develop evidence-based best practices and expand guidance in the BMBL to clarify expectations (e.g., validation of inactivation methods) where appropriate. DSAT recently published draft guidance document on rendering samples free of select agents and toxins. Our institution noted some concerns with their guidance and expectations in the proposed select agent regulations, so DSAT should be involved in those discussions to ensure consistency.

  32. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    The BMBL was written for research laboratories that (generally) know what agent they work with. Diagnostic laboratories generally don’t know the agent; the purpose of their work is to identify the agent or to help explain the cause of the disease or malady. The BMBL really provides inadequate biosafety guidance for laboratories that must diagnose unknowns. Should there be a new or separate document for diagnostic clinical laboratories? Some hospitals and clinical laboratories in the US refused to test suspect Ebola samples because of the BMBL. The implications with a more ubiquitous infectious disease could be extremely challenging, even perhaps disastrous.

  33. Association of Public Health Laboratories (Member Contributions)'s Gravatar Association of Public Health Laboratories (Member Contributions)
    May 10, 2016    

    Many of the bacterial specific guidance specify which biosafety level precautions to use based on the purpose (diagnostic vs. culture). This is not specified for viral work and should be.

  34. Anonymous's Gravatar Anonymous
    May 9, 2016    

    Similar to a previous comment, guidelines for inactivation of pathogens should be included in the BMBL. However, I don’t think it is the place for a non-regulatory guidance document to be too proscriptive about outlining requirements for demonstrating sterility of samples. This should be the purview of the IBC as they are (or certainly should be) the responsible entity at a given institution.

    I also agree with Dr. Spindler that there needs to be a more effective means for amending information between versions of the BMBL. In order to address the specific issue that she had, would ArboCat be an appropriate location for verifying appropriate containment for pathogens? SALS should be able to update this document. Does the BMBL need a guidance committee so that decisions to not depend specifically on Dr. Wilson or whomever is involved at CDC?

    In the interest of brevity and to reduce confusion, I suggest eliminating redundant information between BSL-X and ABSL-X sections. ABSL requirements are fundamentally the same as BSL, but with additional enhancements. Perhaps something along the lines of “ABSL-X guidelines are to be followed with the following additional criteria:”

    General comments:
    P12: Not to split hairs, but there is no recombinant DNA in most RG3 and RG4 viruses. These are typically RNA viruses.

    P23: First paragraph “Facility Design and Construction: Change first sentence to read “…from infectious agents to prevent release from the laboratory”

    P26, second ¶: Change to “Crimean-Congo HF”

    P31, 5a and throughout: There are a number of instances where the recapping of needles is necessary. This bullet should stipulate that needles may be recapped using appropriate mechanical devices in accordance with the appropriate safety manual.

    P32, 5d and throughout: Indicate …”forceps or other mechanical device.”

    P44, bullet 10: Please clarify sentence regarding class III BSCs and connection to a second HEPA. Where is the first? Is the second to be attached to the BSC or outside of the laboratory space? Similar clarifications required in the discussion of A/BSL4 cabinet labs.

    P48, 7: “must”

    P52, bullet 7 and elsewhere. Clarify here and in ABSL4 section that house vacuum should not be connected to lower level containment laboratory unless 2x in-line HEPA filters are in place and outside the containment space.

    P53, bullet 10: If a thimble connection is used, please clarify that 2x HEPA filtration is required after the thimble. BSC HEPAs don’t count.

    P55, bullet 1, 2nd ¶: Change to indicate entry from clean to dirty.

    P58, bullet 13: First sentence says “cabinet laboratory”. This section refers to a “suit laboratory”.

    P 81, bullet #4: Add in “procedures may require use of double-gloves, cut-resistant gloves, or puncture-resistant gloves as appropriate.

    P84, bullet 11: Include standards for downdraft or backdraft tables. Clarify use of thimble in respect to HEPA filters as mentioned earlier.

    P85, bullet #2: Animals “should” be house in ventilated enclosures, as appropriate. A risk assessment should be performed to justify deviation from this standard.

    P86, bullet #2: Re-write for clarification

    P89, bullet #1: This is better written than the comparable BSL-4 section. See comment above about redundant and inconsistent information in the BSL-X vs ABSL-X sections.

    P94, bullet #1, 2nd ¶: Re-write clean to dirty. Also specify “ABSL-4 cabinet laboratory”

    P96, bullet #7: See comment above regarding vacuum systems

    P101, bullet #13: Says “cabinet” lab in “suit” lab section

    Agent summaries: I would include a link to the Select Agent list rather than include a separate select agent section for different agents. This list has changed over the past 10 years with a number of pathogens removed, some added and the division into “Tier 1” and “Tier Other” sections.

    P216: Update polio type II destruction of lab stocks

    P224: Add MERS-CoV

    Table 6: Change Oropouche to BSL-2

  35. CSHEMA Biosafety Community of Practice's Gravatar CSHEMA Biosafety Community of Practice
    May 9, 2016    

    It would be helpful if the 6th edition covered issues related to Dual Use Research of Concern and viral vector safety.

  36. Anonymous's Gravatar Anonymous
    May 9, 2016    

    Detailed information needs to be added regarding inactivation and sterility testing of microorganisms:

    Inactivation and Sterility Testing of Microorganisms
    Biocontainment laboratories are finding it increasingly necessary to inactivate microorganisms in order to handle them at lower containment levels, but guidance on effective methods for the inactivation of infectious pathogens and toxins while still preserving nucleic acid (for molecular assays), ultrastructure (for electron microscopy studies), and tissue architecture is scarce. Reports of incomplete inactivation or inadequate methods in recent years calls to action the need to discuss best practices when it comes to these high-consequence procedures [1].
    Currently there are no federal regulations or national consensus standards regarding microorganism inactivation methods. Laboratories should be aware of the lack of consistency when accepting samples that have purportedly inactivated by other laboratories, and may find it prudent to perform their own sterility testing on samples accepted from other institutions.
    Selection of Inactivation Method
    Laboratories may choose and inactivation method based on both the target agent and the requirements of the end product. Physical sterilization methods include heating, radiation or filtering, and amongst chemical sterilants labs may select fixatives such as guanidine thiocyanate or universal fixative). Not all laboratories will have access to an irradiator, and if examination via electron microscopy is the end process desired, then physically filtering a sample will remove all morphological features and objects of interest, so selection of an inactivation method is dependent on resources and reasons for inactivation.

    Types of Inactivation Verification
    Once a laboratory has selected an inactivation method, it must be decided whether the laboratory will perform sterility testing on the samples. Research institutions may choose to test all or a portion of the samples to be removed from BSL-3 and or BSL-4, or they may choose not to conduct sterility testing at all.
    (1) Agent inactivation with sterility testing. The most reliable method for verifying agent inactivation is performing sterility testing every time on every sample that is inactivated. Samples are subjected to the process and a significant portion (at least 10% of the inactivated sample) is sacrificed for testing. The remaining sample is set aside pending the results of the sterility testing. Note: Containers re-opened following the removal of the portion for testing must be re-tested as it has been exposed again to the containment environment). The sacrifice sample undergoes the logical method for sterility testing, and is monitored for suspicious growth. In this context, removal of agent from a biocontainment laboratory, no microbial growth should be tolerated. Once the tested sample has been deemed sterile, the portion remaining in quarantine may be removed from the containment lab and handled safely at a lower biosafety level.
    (2) Agent inactivation with no sterility testing. As there is currently no published guidance on the requirement to sterility test samples (excepting virulent Bacillus anthracis per DSAT guidance), the option exists for laboratories to decline to sterility test at all. Common sense dictates that in this vein, one should choose their method wisely, which leaves us with three logical paths:
    a. Rely on published literature
    There has been some published literature regarding inactivation methods for viruses[2, 3], bacteria[4] and even more sparsely, rickettsia[5]. Personnel choosing to adopt methods from published literature should consider the validity of the data:
    • Whether the literature was published in a peer-reviewed journal. Is it a reasonable method with replicates and sound data?
    • The circumstances of the data generated – was the inactivation performed in a pure culture, while the samples you would like to inactivate in a mixed culture? Is there a direct correlation between the two – titers of virus, pfu of bacteria all may matter when choosing a method without a subsequent sterility test.
    • Can you find other published data utilizing the methods?
    b. Rely on a validated (in house) method
    It may be that your laboratory chooses to develop an in-house inactivation method. When developing a method, it would be best practice to validate it in house, generating your own data to ensure that the method you have chosen both inactivates the agent reliably as well as preserves what is needed for further assay.
    c. A combination of the above
    Choosing an inactivation method developed from an outside resource and then replicating (validating) in house with your own materials and personnel is the best practice amongst any method chosen without sterility testing. You have the benefits of data gathered from an outside source (a starting history) as well as generating your own data.
    Validating an Inactivation Method
    The objective of any method validation is to produce consistent, reliable data. In the science of agent inactivation, several points should be considered when developing a validation plan for microorganisms:
    The scope of the inactivation method. Is this method intended to be used for just one organism? A family of organisms? When are the organisms so unlike one another you have trouble justifying data including all of them when you have only tested two species out of thousands? For example, there are many species included in the family Herpesviridae, but if you tested only HSV-1, could you say that the inactivation method is valid for murine CMV? Is it valid for all enveloped DNA viruses? Surrogate organisms are not recommended in certain instances (e.g., biological indicator Bacillus pumilus is not considered an especially resistant organism to irradiation)[6].
    • Without regulations, this decision is left solely to each institution which lead to inconsistent policies and practices.
    • The method should be codified in a detailed protocol such as SOP. The SOP (and the validation) should specifically account for variations in agent concentration or titer, organic load in a sample or type of tissue (as in fixative penetration). The environment, matrix and materials are variables that should be taken into consideration when developing a validation protocol, and may be reason enough to perform additional validations to account for those variables. Example: In an institution developing a radiation dose curve for a gamma irradiator, the protocol will not translate to other irradiation sources as the curve is specific to the institution’s irradiator, and sources suggest best practice is specific to species of agent as well [7].
    • Agent stability should also be evaluated; Care should be taken to prove that the agent remains viable just prior to the inactivation assay, as well as through the duration of the assay by running a positive control. For example, one should grow and enumerate a previously frozen bacterial culture prior to running an inactivation validation assay, and also run a positive control throughout the duration of the inactivation protocol.
    • The method should account for the intended result: as stated previously, validating a method that destroys nucleic acids when end interest is in molecular assays is obviously counter-productive. Conversely, the desired endpoint may be inactivation of the agent itself as well as denaturation of genetic materials, and design of the protocol should demonstrate what is intended by the validation procedure.
    • The protocol should also account for the fact that in dealing with biological organisms, variations amongst species is also expected, including resistant organisms. One cannot depend strictly on a survival curve, as data has suggested survival times of microorganisms are not necessarily distributed normally. Consideration for a reasonable “safety-margin” allowing for outliers is necessary.

    A robust validation allows for the normal variation of processes that involve humans. Ensuring a process generates the same result whether the assay is completed by different personnel following the same written procedure, with the same tools is key to a scientifically sound method. Can a research assistant following the same SOP produce the same end result as a senior scientist performing the identical procedure? The greater number of personnel participating in the validation, the greater the variation (in personnel and in microorganisms) and the more robust successful data becomes.

    Sterility Testing
    When choosing to sterility test, one should follow a growth protocol known to support the target organism’s growth preferences and/or requirements. Useful references for growth support can be found reference books on clinical microbiology procedure or in a literature search.
    For laboratories intending to remove samples from a containment laboratory, best practice suggests sterility testing not just for target agent (i.e., the agent contained in the culture) but also concurrently testing the sample using a general media that would support growth of contaminants. For example, if your target agent is Francisella tularensis, you would want to consider using both a selective media such as chocolate agar (to select for the target agent) as well as a general media such as sheep blood agar. For virus growth, passage on cells known to support the growth of the target microorganism. One should also consider the persistence of other agents utilized in the laboratory (such as spore-formers) and target accordingly. Sterility testing should show no evidence of any growth, including that of contaminants. The addition of chaotropic agents such as guanidine isothiocyanate frequently used in the process of RNA and DNA extraction is also known to inactivate viruses through the protein denaturing process[2]. This chemical is also toxic to cells, prohibiting sterility testing without the removal of the toxic chemicals first. Performing a proper sterility test may also mean devising a way to remove chemicals used in the inactivation process.
    Complicating Factors
    Inactivation and sterility testing is not a straight-forward process. There are numerous variables and thousands of agents. As stated above, even sterility tests can present a problem as the inactivating nature of a chemical may prove toxic to the cells needed to support a sterility test. For inactivation of agent in different matrices (such as animal tissues or in thick serum), penetration times become a concern and should be evaluated in a validation method accordingly. The nature of the agent and whether testing a representative is “good enough” must be decided by professional judgement within an institution in partnership with governing bodies.
    The benefits to manipulating microorganisms at lower containment levels is obvious: It is ultimately safer, less cumbersome, and less expensive to handle sterilized pathogens outside of a high or maximum containment lab. A reliable inactivation method prevents the need to have staff enter containment as well as the cost of populating containment laboratories with expensive equipment like Transmission Electron Microscopes or equipment for molecular assays. This also prevents the need to either bring technical staff into a containment lab to service the equipment, or develop a method to decontaminate equipment out of the laboratory to be shipped off site of servicing (a time-consuming and expensive prospect which can sometimes damage the equipment in question).

    1. Review of CDC Anthrax Incident, in Energy and Commerce Subcommitee on Oversight and Investigations2014: Washington, DC.
    2. Blow, J.A., et al., Virus inactivation by nucleic acid extraction reagents. J Virol Methods, 2004. 119(2): p. 195-8.
    3. Jonathan S. Towner, T.K.S., Thomas G. Ksiazek and Stuart T. Nichol and High-Throughput Molecular Detection of Hemorrhagic Fever Virus Threats with Applications for Outbreak Settings. Emerging Infectious Diseases, 2007. 196 ((Supplement 2)): p. S205-S212.
    4. Brantner, C.A., et al., Inactivation and Ultrastructure Analysis of Bacillus spp. and Clostridium perfringens Spores. Microsc Microanal, 2014. 20(1): p. 238-44.
    5. Frickmann, H. and G. Dobler, Inactivation of rickettsiae. Eur J Microbiol Immunol (Bp), 2013. 3(3): p. 188-93.
    6. Block, S.S., Disinfection, Sterilization and Preservation. 5th ed, ed. S.S. Block. 1918, Philadelphia: Lippincott, Williams and Wilkens. 1481.
    7. Defense, D.o., Review Committee Report: Inadvertant Shipment of Live Bacillus anthracis Spores by DOD. 2015.

  37. Anonymous's Gravatar Anonymous
    May 9, 2016    

    Add a section on the importance of developing a strong safety culture:

    High containment, biological laboratories have received considerable negative publicity in the recent past related to errors, mistakes, and general systematic process breakdowns that have resulted in loss of containment and potential human exposures to biological select agents and toxins (BSAT). In each case, the lack of a strong culture of safety was identified as a contributing factor. As a high hazard facilities, the biological containment laboratories should strive to provide the largest possible margin for safety to help ensure work conducted with BSAT does not represent a level of risk that cannot be successfully mitigated. A key component for maintaining this acceptable safety margin and thus the basis necessary to prevent significant mishaps from occurring is the creation of a strong safety culture. Additionally, a strong safety culture also represents a key aspect for reducing the significance of a mishap if it were to occur.
    The importance of a good safety culture is becoming widely accepted as a necessary part of an operational environment. The nuclear industry, often seen as a leader in operational safety, has long recognized the development of a strong safety culture as a critical component of the operational environment. This is demonstrated by the Institute of Nuclear Power Operations (INPO) publishing documentation on the principles for a strong nuclear safety culture. The Occupational Safety and Health Administration has also recognized the importance of safety cultures in the work place and has published guidance that companies can use in developing a strong safety culture in their work places.
    In recognition of the important role of a strong safety culture plays in prevention and mitigation of biological risks, any revision to the BMBL should address this important issue.

  38. Anonymous's Gravatar Anonymous
    May 9, 2016    

    Add a section on the importance of hiring and using a credentialed biosafety professional as part of your everyday activities:

    The Biosafety Professional
    A biosafety professional develops and participates in programs to promote safe microbiological practices, procedures, and proper use of containment equipment and facilities; stimulates responsible activities among workers; and provides advice on laboratory design.

    A biosafety professional is a person who, based on education and/or experience has subject area expertise in the principles of microbiology, epidemiology, disease transmission patterns, risk-assessment and risk management, disinfection and sterilization, disease prevention, aerobiology and environmental control. (from ABSA website). He or she serves as subject matter expert in biosafety practices and principals to investigators, animal care technicians, research assistants and other laboratory staff.

    Practicing Biosafety Officers are strongly encouraged by the American Biological safety Association and the American Society of Microbiologists (ASM) to achieve and maintain the credentials of either Certified Biosafety Professional (CBSP) or Registered Biosafety Professional (RBP).

  39. Rajesh Parmar's Gravatar Rajesh Parmar
    May 3, 2016    

    BMBL – 5th edition has lots of good information.
    It would be nice to have easy to understand flow charts for certain things (like how to clean up a spill), pictures of infectious agents (e.g how anthrax looks under the scope or on blood agar), ideal contents of a spill kits, examples of biohazard symbols and signs labs need to have on their doors, how to conduct a safety audit, checklist and areas that need to focus on, how to conduct initial and annual safety training and what should be covered in the training, and stuff like that.

    Thanks
    Rajesh

  40. Scott Patlovich's Gravatar Scott Patlovich
    May 3, 2016    

    Although no compendium of field associated infections currently exists similar to the Sulkin/Pike and Harding/Byers reports on LAIs, these events have been documented during field research activities. We should consider including an appendix dedicated to creating awareness of risks associated with the field collection of potentially infectious biological specimens. Recommended controls should be discussed within this section. See reference: Patlovich, S., Emery, R.J., Whitehead, L., Brown, E.L., Flores, R. Assessing the Biological Safety Profession’s Evaluation and Control of Risks Associated with the Field Collection of Potentially Infectious Specimens. Applied Biosafety, Volume 20, Number 1, 2015.

  41. Barbara Johnson's Gravatar Barbara Johnson
    April 21, 2016    

    Gain-of-Function and Dual Use Research of Concern policy and recommendations should be included as a new appendix. A new section or appendix that discusses the importance of sterility testing/verification of materials before moving samples to lower BSL’s would be of value. It should include a referenced discussion of means of inactivating agents as well as methods for sterility testing to provide lab staff with a place to start when validating a method at their lab. Add CRISPR biosafety recommendations and viral vector safety (new section?).

  42. Katherine Spindler's Gravatar Katherine Spindler
    April 20, 2016    

    There should be an easy way to get biological agents’ biosafety levels reconsidered and amended between BMBL editions, and such reconsideration should happen in a timely manner. I strongly recommend that such a system take advantage of electronic submission of such requests and electronic publication of interim updates of approvals. I was able to get SALS to recommend changing a virus’ (Oropouche) category from BSL3 to BSL2 at their meeting at ASTMH in November 2013. However, despite phone calls, emails, and entreaties directly and indirectly to the chair of that committee, that recommendation was never acted on in a way that would enable me to submit something to my local IBC. (My local IBC required that there be something official at the “BMBL level” in order for them to consider allowing us to do experiments at BSL2). Finally, after more than 2 years, I had success with the fifth or sixth tactic I tried over two years to get SALS’ decision to be made official: I was able to get Deborah Wilson at NIH to help me; she looked at all the communications, SALS committee decisions (multiple ones, including a new Risk Assessment, etc.) and she wrote a letter to my local IBC committee in January 2016 indicating that OROV work at BSL2 is approved. Thus my lab is now able to work on OROV at BSL2. However this change still needs to be codified in the next BMBL. Moreover, in the interim, there should be a way to make it public so that other labs around the country/world can also work on OROV at BSL2. It shouldn’t be this hard to get documentation that something is approved for a different biosafety level from what is published in the BMBL. More than one person should be able to act on such SALS (or other) committee decisions, so that one person cannot be a bottleneck that can hold up investigators’ research (at a practical, cost-effective appropriate biosafety level) for more than two years.

  43. J. Paul Jennette, MS, PE, RBP's Gravatar J. Paul Jennette, MS, PE, RBP
    April 15, 2016    

    Please change references to “BSL-_ agents” appearing at:
    Page 37, third & fourth paragraphs
    Page 46, Item B.5
    Page 53, Item B.5
    Page 134, introduction
    Page 248, Table 1
    to something more technically accurate such as “Risk Group-__agents” or “agents being manipulated at BSL-_” since many agents, particularly in Risk Groups 2 and 3, are commonly worked with at BSL-2 or BSL-3 depending on the amounts, manipulations, etc. involved.

  44. Shamsul Arfin Qasmi's Gravatar Shamsul Arfin Qasmi
    April 15, 2016    

    It will be worthwhile to add a chapter on waste management, as there are many questions on CBSP examination conducted by NRCM for professional certification. it will be a comprehensive document if it is added in the next edition.

  45. Stephen Morash's Gravatar Stephen Morash
    April 7, 2016    

    In the 4th addition, Appendix F dealt with Emergency Response. In the 5th addition there is no mention of emergency response. this has been eliminated.

    WHY?!?

    Now more than ever, emergency response planning and emergency response and consequence management must be put back in to the BMBL

    As we in emergency management say, it’s now if, it’s when. Accidents, and incidents will happen. It’s a matter of time.