The U.S. Army’s new biomedical regulations

The October 2001 anthrax event attracted considerable attention to the safety and security of microbiology research and diagnostic programs, particularly those operating at high-containment laboratories. This scrutiny, although not undue, has resulted in a great deal of caution–and subsequently, delays–within U.S. government departments and agencies responsible for conducting research on infectious disease. The Health and Human Services Department’s Rule on the Possession, Use, and Transfer of Select Agents and Toxins, better known as the Select Agent Rule, may be the most notable exception.

The Select Agent Rule represents a critical step in addressing domestic accountability for the possession and transfer of certain dangerous pathogens; however, it falls short of being the comprehensive security regulation that many organizations and advocates have called for. In order to address shortfalls in the Select Agent Rule, the U.S. Army has proactively implemented changes to its safety and security programs–first by issuing guidelines on responsibility and oversight of dangerous biological agents in July 2008 and then, in May, effecting major revisions to Department of the Army Pamphlet 385-69: Safety Standards for Microbiological and Biomedical Laboratories. Pamphlet 385-69 establishes army safety guidelines for the U.S. biological defense program and implements several changes to army biosafety policies in an effort to enhance pathogen accountability and containment.

The most significant aspect of Pamphlet 385-69 is that it makes the published Centers for Disease Control and Prevention biosafety guidelines, “Biosafety in Microbiological and Biomedical Laboratories” (BMBL), mandatory across army clinical diagnostic, biomedical, and veterinary research programs. The BMBL often is regarded internationally as a compendium of global best practices and is emulated, with some local modifications, by several countries with active biomedical research agendas (e.g., the former Soviet republics, Pakistan, India, and Singapore). However, the BMBL isn’t a prescriptive regulation; rather, it’s a set of continuously evolving guidelines that are meant to be flexible and that adapt to the discovery of new or emerging infectious diseases with complex or unknown causes. Because the BMBL is a flexible and nuanced document, it often leaves certain details to the discretion of a competent biosafety officer and institutional biosafety committee. Thus, Pamphlet 385-69 seeks to remove some of the ambiguity in how the BMBL should be implemented within the U.S. Army.

Another prominent revision to Pamphlet 385-69 comes in its clarifications of biosafety program standards, including the academic and internal U.S. Army credentials required of biosafety officers. Additionally, Pamphlet 385-69 mandates that clinical laboratories supporting the U.S. Army Medical Department have qualified biosafety officers assigned, if not as an in-house asset then through a regional support function. As a result, diagnostic facilities that are less likely to handle highly pathogenic agents and are therefore less likely to have qualified individuals on their staff will have access to trained persons in their area.

Pamphlet 385-69 also elaborates on the BMBL risk-assessment methodologies, which don’t direct laboratory investigators or biosafety officers to take a particular approach to determining the risk posed by research or diagnostic activities. Nor do they require the participation of specific laboratory or institute personnel. Thus, Pamphlet 385-69 directs specific personnel, including the biosafety officer and the institutional biosafety committee, to perform a specific risk assessment for every research and diagnostic activity, in particular recommending the use of army risk-assessment methodology to support the assessment’s required documentation.

Although Pamphlet 385-69 falls far short of being a decisive monograph on the practice of biosafety, it does provide a more rigorously defined biosecurity framework than the BMBL alone. This in itself is laudable and meets the current expectations for greater accountability when operating existing high-containment laboratories in the United States or commissioning new ones. Nevertheless, there are some limitations to the current document, which, however subtle, may be worth considering as U.S. Army and Defense Department joint research efforts evolve.

Pamphlet 385-69 does not, in this revision, specifically address army labs located in foreign countries or army-sponsored programs conducted in foreign-owned-and-operated labs, which are key components of U.S. science and clinical research on emerging and exotic infectious diseases. Therefore, there is some ambiguity as to whether provisions in Pamphlet 385-69 should apply to foreign research programs. Admittedly, in situations where the army and foreign entities conducting research in support of army programs have control over facilities and laboratory personnel qualifications, there probably will not be conflicts or the need for significant deviations from army policy. After all, Pamphlet 385-69 is written using language that allows for differences between foreign design and materials so not to complicate compliance with relevant design and commissioning requirements. But an issue such as immunization of laboratory workers, for example, may pose a problem for foreign nationals if locally available vaccines aren’t familiar to army medical officers, aren’t FDA licensed, or don’t meet army standards. Even if the use of new foreign vaccines under established USDA protocols may be reasonable, the use of U.S. vaccines in foreign nationals working in army research programs must be handled carefully and with the consultation of national physicians.

The application of Pamphlet 385-69 to external biodefense research that is funded by or conducted with materials provided by the army also deserves clarification. A large part of army biodefense research is conducted by extramural investigators at federally funded research-and-development centers, government-owned and contractor-operated national labs, private industrial labs, private research foundations, and state or private universities. Pamphlet 385-69 clearly states that its provisions apply to all of these entities when they conduct research for the army, but it doesn’t specify whether the same regulations apply if army reagents are used in research that is funded by other government agencies or private sources. Additionally, if army standards are significantly more stringent than the BMBL or other prevailing biosafety guidelines for civilian research entities, the implementation of the revised army guidelines may pose a problem for external biodefense research.

Already, some of the changes to Pamphlet 385-69 represent costly enhancements. For example, new biosafety officer experience and qualification standards may force external biodefense labs to hire primary duty biosafety officers, whereas in the past, these positions were collateral duties held by research staff. An army policy that is overly stringent relative to government and industrial biosafety best practices may jeopardize important extramural research programs thereby limiting these programs’ benefit to U.S. biodefense efforts.

Pamphlet 385-69 undoubtedly clarifies several key BMBL guidelines that use vague language–presumably easing problems the army has encountered during implementation. Although it’s appropriate that the army adopt clarifying language in its own pamphlet, army research programs may require additional resources to support the investigators, biosafety officers, and institutional biosafety committees in implementing the revised requirements in civilian and foreign laboratories.