f6098d8b__and_Use_of_Laboratory_Animals__Comments
[ID] 371 [Entry Date] 04/21/2011 at 04:36:42 PM [Affiliation] Self [Organization Name] UAMS [Organization City and State] Little Rock, AR [Comments] 
Comment 1: I am a member of the College on Problems of Drug Dependence (CPDD), from whom I am sure you have heard already. CPDD welcomes the opportunity to comment on whether the 8th edition of the "Guide for the Care and Use of Laboratory Animals" should supplant the 7th edition as PHS Policy. CPDD recommends that the 8th edition not be adopted as PHS Policy. While it contains some useful new information (e.g., on care of aquatic species), there are numerous problems with the 8th edition as federal policy that will govern PHS-funded researchers. Instead, the 8th edition can function, as do other National Academy publications, as a useful reference volume on certain issues relating to animal husbandry. The 8th edition departs significantly from the 7th, which has served us well since 1996. Of particular concern is the extent to which the 8th edition introduces new policies that go beyond the earlier edition. Many of these new policies constrain the exercise of scientific and professional judgment and add significantly to the paperwork burden for investigators and IACUCs. Many of these will result in higher costs to grants and to institutions. Mandatory requirements for new cage sizes for some species (particularly rodent breeding) and for social housing of all species will require large expenditures. Newly introduced requirements for post-approval monitoring of protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" are examples of items requiring additional IACUC staffing and researcher effort. A major change in the Guide is the introduction of language cautioning against multiple survival surgery procedures in addition to the previous caution against multiple major survival surgeries. This echoes a newly introduced caution against animal reuse as a "reduction" strategy. Restrictions against using animals in multiple procedures surely increases the number of animals needed, thus increasing research costs as well as the number of animals used in research. These restrictions fail to take into account the value of within-subject and single subject designs, which are particularly powerful for behavioral research. Further, the Guide oversteps the bounds of its mandates by outlining policies and guidelines for other Executive Branch agencies (e.g., OSHA and DEA). It steps out of the PHS Policy to cover vertebrates used in research in stating "The Guide does not address in detail agricultural animals … or invertebrate animals (e.g., cephalopods) used in research, but establishes general principles and ethical considerations that are also applicable to these species and situations." The section on "Food and Fluid Regulation" requires daily recording of food and fluid consumption for all animals on either type of restriction, which ignores the fact that animals for which one commodity is restricted have unrestricted access to the other. This requirement will necessitate use of calibrated water bottles or flow-meters rather than the now common automated watering systems, thus incurring additional equipment costs; and will require a method of weighing the unrestricted food given to fluid-restricted animals. Guidance to use "treats" for behavioral training with the assumption that this avoids food restriction is counter to the information in two of the scholarly reviews cited in that same Guide paragraph. These examples may represent only imprecise drafting, rather than intent, but this is only one example of how the 8th edition is unsuitable as federal policy. The new section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from using standard source drugs for research,(e.g., compounds from the NIDA drug supply program; reliable private vendors; chemists) or requires additional paperwork burden to justify and detail their use if a version of that same drug is available in a human clinical or veterinary formulation. It also is written in a way that assumes that clinical preparations are available for most laboratory animal research, when this is seldom true. Further, clinical formulations are generally bad choices for research as these can make dose manipulations and vehicle comparisons difficult. No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of the USDA/APHIS Policy 3, an interpretive rule for use "medications" to prevent pain/distress and the intramural NIH program policy on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement makes clear that Policy 3 is interpreted as requiring use of commercially prepared solutions, rather than investigator-prepared;, and the first sentence of the new Guide section on this topic is consistent with this. Yet the intramural policy defines "pharmaceutical grade" as manufactured according to USP standards, thus accommodating investigator-prepared solutions. Even the intramural Policy ignores that the NIDA drug supply program and other standard sources do not prepare to USP standards, as these have more to do with documenting drug manufacture than drug quality. As with other sections, the contradictions in guidance are problematic. Reconciling definitions is one obstacle to interpretation, but the clear requirement that investigators justify the use of certain types of compounds and provide elaborate detail on their preparation and characteristics for IACUC review is only one example of the new Guide's intrusion into the realm of the scientific and professional judgment of NIH-funded researchers. Comment 2: CPDD concurs with the National Association for Biomedical Research that the 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, a meaningful opportunity to comment in greater detail on the substance of the new Guide and its financial consequences is necessary before a decision on Guide adoption and implementation strategy can be made.
Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals