The biodefense industry has reached a critical point in its evolution. To accelerate product development for biodefense-related diagnostics, therapeutics, and reagents, we urgently need biological consensus standards - which generally do not exist. These standards can have an impact on overall R&D productivity and quality as profound as any technological advance, a fact readily acknowledged by biodefense leaders.
Within biodefense-related R&D, standard biological materials and processes are critical in three general areas. First, standards help properly validate instruments and assays used in measuring, producing, or testing products for biodefense applications. For example, scientists need standard microorganisms to validate an instrument designed to identify threat agents from environmental samples in the field. Second, we need standard biodefense-related materials and protocols to train personnel and confirm the capabilities of a biodefense laboratory; standards are invaluable for evaluating an individual's or laboratory's performance at identifying or assaying particular bioagents. Third, standards help compare experimental results among different researchers and different laboratories, enabling groups across the hall or across the globe to weigh results meaningfully. This enables high-quality and efficient research and testing, and it also stimulates innovation.
Standards are most effective when developed by the cadre of people who have the most to gain by their use. A provision of the National Technology Transfer and Advancement Act (1996; P.L. 104-113) states: Wherever possible, groups should use voluntary consensus standards developed by a community of interested stakeholders, rather than federally mandated regulations.
To jumpstart development of these standards, the American Type Culture Collection (ATCC) convened the Expert Panel on the Development of Standards for Biodefense in Washington, DC, in early April. The meeting represented a launching point for a process that will culminate in the development of voluntary consensus standards for critical materials and protocols for biodefense-related research and product development. A group of approximately 60 experienced biodefense experts gathered from a range of government agencies, academic institutions, and private companies.
Instead of writing specific standards, participants first delineated the areas of need for biodefense materials and processes. In discussion over the course of the two-day meeting, a broad agreement was reached on a handful of areas of need for biodefense standards. Participants also generated even more questions and issues that still require resolution. The areas of need include:
>> Standard reference materials - Participants strongly agreed that a major unmet need exists for universally accepted reference standard biological materials, including microorganisms posing public health threats. Such reference materials would be used as benchmarks in the study and testing of bioagents. Discussion at the meeting, however, focused more on how to define a reference material than on which bioagents should have standards. To define a material as a reference standard, what characteristics of the organisms constitute required knowledge? Much consideration and decision-making remains before, for example, experts can establish a reference standard Bacillus anthracis Ames strain. Nonetheless, meeting participants acknowledged that the set of information should include genetic profile, phylogenic position, microbe source, purity, and chain of custody.
>> Standard measurement protocols - Once a set of requisite information is established, the next critical step is to define and agree to measurement protocols for each piece of information, the participants reasoned. For example, how should the purity of cultures and reagents be assessed, and what levels of impurity, if any, would be acceptable? How should one measure infectivity, virulence, or stability of an organism in various environments? Any group setting out to develop standard measurement protocols must consider what types of measurement devices and instruments on which to seek agreement, as well as what levels of specificity vs. sensitivity are acceptable. As a sample problem, what would be the criteria for successful decontamination of an area where a bioagent was detected? Panelists suggested that experts set standards on methods of bioagent characterization, and managing the information associated with the biological materials as well as evaluating countermeasures.
>> Harmonization of terms - Biodefense experts from academia, industry, and government alike strongly endorsed the concept of harmonizing definitions of key terms, and agreeing on a set of common biodefense-related terminology. Standardized definitions for key terms were viewed almost as a prerequisite to standards development. More work is needed in this area, but some of the terms identified by the group as needing common definitions included: sensitivity, specificity, shelf life, inactivation, limits of detection, and validation. The panel advocated obtaining help in this area from such organizations as International Standards Organization (ISO) and Clinical Laboratory Standards Institute (CLSI).
>> Standardized communication methods - The group clearly saw a need for a standard set of information and standard format for communicating and reporting descriptions of biomaterials, modeled after materials safety data sheets (MSDS) for chemicals. In addition, the group felt that experts should develop a standard format for certificates of analyses (C of A).
>> Standard surrogates - Even after taking extensive and redundant precautions, biodefense-related organisms, by definition, carry hazards even to experienced laboratory professionals. Consequently, the meeting participants agreed that a substantial need exists for standardized surrogates. These materials would be useful as models for biodefense-threat organisms in research and product development, but would not pose the same level of threat.
>> Standard animal models - Testing biodefense prophylactic and therapeutic products pose some obvious major challenges to manufacturers - namely, that human testing is virtually impossible. As a result, vaccines, drugs, or diagnostics require robust and specific animal models for testing, and panelists agreed that the biodefense industry needs standardized animal models of biodefense-related diseases. These models would bolster confidence in research results by allowing valid comparisons and experimental reproducibility. Future work in this area will need to determine the best models for various bioagents and different environments.
>> Standard handling protocols - Panelists also saw a significant demand for standard methods for manipulating and working with biomaterials. Important areas lacking standards include: protocols for handling, storage, transport, inactivation, and disposal of biomaterials.
Special needs for end-user groups
The panel acknowledged that certain standards - such as transport - could be of general use, while others, such as limits of sensitivity and specificity, would be specific to different end-user groups. They acknowledged the reality that biodefense standards would be employed by different groups with potentially different needs, including groups involved with food and water testing, environmental surveillance, diagnostics, or forensics. As a result, standards must address the differences in needs for the various end-user communities.
Meeting materials, an attendee list, slides from the presentations, and notes from the discussion sessions are available online at the conference Web site: www.biodefensestandards.org. To move toward developing voluntary consensus standards, a wider group of stakeholders will be assembled to sustain momentum and maximize participant buy-in. In the next year, a series of follow-up conferences to the April expert panel gathering will be held in order to begin development of specific biodefense standards.
Scott Jenkins is a science writer at ATCC. Joseph Perrone is the vice president for standards and certification at ATCC and chaired the Expert Panel. firstname.lastname@example.org