December 1, 1998 - Proposal for Hazardous Materials: Revision to Standards for Infectious Substances and Genetically Modified Microorganisms

The ASM is the largest single life science society in the world, with over 42,000 members, representing a broad spectrum of subdisciplines in the microbiological sciences, including medical, clinical, environmental, and public health microbiology as well as infectious diseases. For nearly a century, ASM has brought its scientific, educational, and technical expertise to bear on issues surrounding the safe and appropriate study, handling, and exchange of pathogenic microorganisms. Our members work in research, clinical, industrial and government laboratories where microorganisms and infectious substances are transported on a regular basis. The ASM appreciates the opportunity to submit comments on the Department of Transportation (DOT), Research and Special Programs Administration (RSPA), Advanced Notice of Proposed Rulemaking, Hazardous Materials, Revisions to Standards for Infectious and Genetically Modified Microorganisms [Federal Register, September 2, 1998, 63: 46843-46859].

The ASM comments refer to several general problems and the following nine specific subject areas included in the RSPA proposed revisions: i) that the RSPA rules adopt World Health Organization (WHO) risk group designations for classifying infectious agents; ii) specific language used for labeling diagnostic specimens; iii) packaging and labeling requirements for other biological products; iv) labeling requirements for genetically modified organisms; v) placarding of vehicles carrying biological materials; vi) standards for transport of medical waste materials; vii) handling and labeling of waste stocks and microbial cultures; viii) segregation of infectious materials from foodstuffs, and ix) definitions for genetically modified organisms.

ASM points to one pervasive general problem being the lack of clarity that runs throughout the RSPA document, making it very difficult to understand by its intended audience. A second general problem is that RSPA uses the term "infectious substance" throughout the document to refer to a wide range of materials, sometimes etiologic agents, other times diagnostic materials, and still in other instances to materials that may be contaminated with infectious agents. Uniformly labeling all materials with this same term can be misleading and potentially meaningless.

In addition, ASM raises the following specific issues:

i) In Section II.A. of its draft standards, RSPA proposes to adopt the WHO risk group designation scheme as a way of classifying infectious disease agents when they are being transported in the United States. ASM sees several problems in this proposal.

WHO recommends that individual countries develop and use their own systems for classifying infectious disease agents. Thus, there are differences in the classification of organisms from country to country. The United States and several countries in Europe now classify the same infectious agent--for example, HIV in clinical specimens--into different WHO categories. This only becomes an issue if there are differences in packaging and labeling specified for the different risk groups.

Although the RSPA proposal recommends deferring to the Centers for Disease Control and Prevention (CDC) when assigning materials to the WHO scheme, the CDC does not routinely update its list of infectious agents. The most recent update of such a list is prepared as an appendix to the National Institutes of Health (NIH) Guidelines for Research Involving Recombinant DNA Guidelines and is incomplete.

The adoption of a standardized classification system will not, of itself, improve the safety of shipments. However, we believe that it is important to facilitate communications as a move towards global harmonization with other regulatory agencies. ASM does not consider it feasible to devise separate handling and clean-up procedures for infectious agents that might fall into one or another of the categories described in the WHO scheme for risk groups. Instead, ASM recommends a standard clean-up procedure accompanied by instructions to notify CDC about the nature of a particular spill or similar mishap and to follow ensuing CDC recommendations.

In its proposals, RSPA refers to improperly identified diagnostic specimens, but does not indicate whether those materials meet USPHS CFR 42-specified labeling and packaging requirements. ASM suggests that better enforcement of those existing requirements is preferable to developing and implementing a new set of regulations.

ii) The RSPA proposal recommends in Section II.B. the labeling of diagnostic specimens "known or suspect of containing an infectious agent" be shipped as "infectious," which is largely consistent with current USPHS requirements.

However, ASM suggests using the term, "reasonably suspect of containing" and of clarifying conditions which may cause a specimen to be "reasonably suspect," i.e., sourced from a patient with symptoms of infectious disease, sample found positive in screening assays, etc. Further, ASM agrees that specimens with a low probability of containing infectious materials should be subject to explicitly less stringent labeling and packaging requirements.

Concerns have been raised by some physicians who claim that labeling medical specimens in any way that indicates they may contain infectious materials risks compromising patient confidentiality. ASM recommends that this concern be reviewed by appropriate individuals with expertise in medical ethics.

iii) In Section II.C., RSPA proposes narrowing the current exemption for biological products that meet certain FDA or U.S. Department of Agriculture (USDA) regulations. Specifically, RSPA recommends narrowing that exemption to allow only "licensed" biological products. RSPA also is considering whether to add a new provision to except blood and blood products from existing quantity limits by aircraft when the materials are packaged in accordance with proposed Sec. 173.196.

ASM recommends retaining the current broader exemption for biological products, specifically, exempting materials which meet FDA or USDA requirements. For example, certain attenuated viruses found in biological products pose a lower risk than the wild type strains. These should not be subject to more stringent transportation requirements. Implementing the proposed changes could raise the cost of shipping such products--for example, by restricting quantities in particular shipments or by limiting such shipments to specialized carriers-- without materially improving safety. The ASM concurs with RSPA in exempting blood and blood products from existing quantity limits for air transport.

iv) In Section II.D, RSPA proposes aligning its requirements pertaining to genetically modified organisms (GMOs) with United Nations and other international provisions.

Although ASM agrees that GMOs that meet the definition of an infectious substance should be transported as infectious substances, it is concerned about the terminology used for classifying many GMOs as "hazard class 9 materials," which specifies that such agents are not infectious in the usual sense but can alter other organisms "in a way not normally the result of natural reproduction." We recommend that this wording be changed to specify that only those "GMOs reasonably suspect of being capable of altering animals, plants or microbiological substances in a way that would prove to be a hazard to health or to the environment if released" be classified as a hazard class 9.

ASM recommends that RSPA not follow these particular international provisions, which do not reflect scientifically based estimates of risk. Instead, ASM recommends that RSPA include exceptions for all materials containing microorganisms except those that carry potent infectious agents or toxins of concern to human, animal, or plant health.

v) In Section II.E, RSPA indicates it is considering requiring placards for bulk packaging, freight containers, and other transport vehicles or rail cars that contain infectious substances, including regulated medical wastes.

ASM questions the value of placarding vehicles containing any type of infectious substances. Such labels could increase the risk that the material would be stolen for illegal uses. Moreover, because placarding does not provide specific information, it would be of use only to clean-up teams. Additional containment or security measures for bulk agents or for high-risk infectious agents may be warranted, but consideration should be given to use of additional packaging safeguards.

ASM agrees that the toll free number for CDC should continue to appear on labels for infectious agents. With two phone numbers still in use, a year provides sufficient time for transition to the new number.

vi) In Section II.F., RSPA proposes new rules for labeling bulk packaging and transport vehicles carrying certain infectious or potentially infectious substances, including regulated medical waste (RMW).

ASM agrees that separate state-by-state regulations are cumbersome and that there is a need for uniform federal requirements for transporting RMW.

However, after carefully monitoring personnel who handle RMW, Environmental Protection Agency (EPA) officials concluded that RMW has not proved infectious to anyone except workers in health care settings. Moreover, EPA requires that transporters of potentially infectious medical wastes obtain special hauling permits. Thus, ASM seriously questions whether such haulers should be required to hold an additional hazardous materials permit.

vii) In Section II.H, RSPA is proposing to take a more conservative approach, on the side of safety, to the transportation of waste cultures and stocks.

ASM agrees that waste stocks and cultures that contain infectious agents falling into WHO risk groups 2,3, and 4 should be handled and transported as infectious materials unless they have been autoclaved or similarly inactivated.

viii) In Section II.I, RSPA proposes segregating some or all packages containing infectious substances from foodstuffs.

ASM does not believe that this proposed change is justified. Although many infectious agents can cause disease through exposure by the oral route, in general, a high dose of the agent is required. Moreover, few pathogens of humans are adapted to growing on foodstuffs, making it unlikely that minor contaminants could amplify in such settings to reach infective dose levels. There appears to be no scientific or historical basis for implementing this proposal.

ix) In Section 173.40, RSPA outlines criteria for defining genetically modified microorganisms and organisms and other definitions.

ASM points out that these definitions are not risk-based and that genetic modification per se does not pose a risk, as was noted by the National Academy of Sciences. Thus, packaging requirements should be based on risk, not genetic engineering per se, which would impose an additional burden and expense and would also unnecessarily alarm carriers of such packages.

In Section 173.40 (1)(ii), RSPA refers to "the potential to alter animals, plants or microbiological substances in a way not normally the result of natural reproduction." ASM notes that these criteria are not sufficient either to increase or decrease shipping requirements. The section should include exceptions for all such microorganisms except those that are potent infectious agents or carry or produce potent toxins of concern to human, animal, or plant health.

In Section 173.40 (2)(d), RSPA refers to exceptions under genetically modified organisms... " a U.S. Government agency....". The ASM would like clarification of this apparent exemption of federal agencies from these new requirements. Regulations which apply to individuals and entities which transport infectious substances should apply to all who do so without exception for place of employment.