Input: [ID] 351 [Entry Date] 04/21/2011 at 02:47:26 PM [Affiliation] Organization [Organization Name] Charles River Laboratories [Organization City and State] Wilmington, Massachusetts [Comments]

Output: Comment 1: Charles River Laboratories recommends that OLAW not accept the 2011 Guide in its present form. The Guide to be valuable must be clear in its recommendations, recommend practices that have a robust scientific base in the peer-reviewed literature, minimize or eliminate unintended consequences, take into account the myriad of confounding variables that may make recommendations inappropriate, and consider the impact on limited research resources. While the 2011 Guide has many positive aspects particularly in providing detailed explanations of recommended practices as well as the rationale behind them, in certain sections its guidance is unclear. The strength of some recommendations appear to exceed the robustness of the available data, and difficulties in practical application of the guidance appear not to have been appropriately considered. Previous editions, as well as the 2011 edition, leave room for professional judgment at an institutional level to apply performance standards in order to tailor practices and facilities to the needs of research animals. While the 2011 Guide acknowledges this principle, it frequently sets forth as minimum recommendations new engineering standards, new strong recommendations, and certain new prohibitions. These new standards while similar to ETS 123 do not include the same caveats as that guidance and like the standards in ETS 123 are not not adequately supported by peer-reviewed scientific studies. The level of specificity of guidance needs to be proportional to the robustness and specificity of the science supporting it. Charles River does not believe that the 2011 Guide meets this standard in several key areas. In the case of the 2011 Guide, for example, the new cage space allocations for a mother with litter for rats and mice do not appear to be supported by robust science; yet, they will have substantial unintended consequences in terms of costs for compliance, on adherence to the principles of the three Rs, and depending upon how compliance is achieved, on animal welfare. In Charles River's analysis, even if the substantial costs for implementing these new space recommendations were set aside, there is no scientifically supported proportionate benefit to the welfare of these animals that warrants these new recommendations to be considered as minimum. In some cases, not only is guidance not supported by scientific evidence, it is contradictory to other guidance such as is the case in requiring that floor space occupied by enrichment items be subtracted from the total floor area—a clear disincentive to using floor mounted rodent enrichment devices. Other unintended consequences will occur by tightening the relative humidity ranges for animal areas that is worded as a strong recommendation and is not support by scientific data, yet, will have a substantial operational and equipment cost impact on most facilities. In this case, the strength of the recommendation is disproportionate to any theoretical positive animal welfare impact. Clarification of the interpretation and application of this recommendation is not only needed but any strict application of this guidance should be justified at an institutional level based upon experience, engineering considerations, and professional judgment. Overall, Charles River recommends that OLAW gathers more detailed information on issues associated with changes in the 2011 Guide than allowed by this comment mechanism before making the final decision on acceptance. Based upon these concerns, an analysis of both scientific justification and the financial impact of new guidance should be undertaken, especially if it is to be applied as a minimum standards or strong recommendations. The decision on how the Guide will be used can then be made on a rational basis in proportion to the amount and strength of evidence supporting proposed changes in guidance. Comment 2: Charles River Laboratories believes that it is appropriate that each institution should begin to make an assessment of areas of compliance and noncompliance with new guidance as set forth in the 2011 Guide. The deadline for this evaluation as suggested by OLAW seems to be appropriate. However, Charles River strongly urges that OLAW requests that the evaluation include, in addition to a time table for compliance, a feasibility and economic impact statement for correcting areas of noncompliance. Certainly such an evaluation is in keeping with Charles River's recommendation for a more robust analysis of the new recommendations found within the 2011 Guide. Based upon this analysis, OLAW should decide if the Guide will be accepted as written and, if so, should all recommendations be implemented; and where significant economic impact is identified, should guidance be provided outlining reasonable and perhaps institutional-specific schedules for conformance or will certain recommendations require further scientific justification by an independent body such as the National Academy of Sciences perhaps using a group other than the Guide Committee assembled for this purpose. While animal welfare is an important component of biomedical research activities, recommendations for the care and use of laboratory animals need to be based on sound science and must consider the amount of resources that will be required to implement them. If such recommendations are limited or are uncertain in their established ability or level of improvement of animal welfare, if they are based principally on professional judgment, or if they do not consider all the variables that might impact their desired effect, they cannot be considered to be useful as universal guidance. Moreover, they do not warrant wide spread application or the expenditure of disproportional amounts of the ever decreasing resources available for the research community that will be required to implement them. Charles River has calculated its additional costs for implementing some of the recommendations within the Guide and has found them to conservatively exceed $100 million. Charles River believes that this level of expenditure coupled with the estimate from other rodent and rabbit breeders, as well as the costs from the research community, merits more consideration of the strength of the scientific support for these recommendations before implementation should be considered.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 352 [Entry Date] 04/21/2011 at 02:48:37 PM [Affiliation] Self [Organization Name] LSU Health Sciences Center [Organization City and State] New Orleans, LA 70112 [Comments]

Output: Comment 1: No - this should not be adopted. This will lead to additional expenses to the institution and the investigators with no real enhancement of animal welfare. This will also cause an additional paperwork burden to the investigator Comment 2: One area where this could lead to a major problem is with the requirement to use pharmaceutic preparation of drugs in animals. These steps will not increase animal welfare (particularly in the use of drugs like pentobarbital for non-survival surgery or euthanasia), but will lead to astronomical increases in the costs to the investigators.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 353 [Entry Date] 04/21/2011 at 02:49:05 PM [Affiliation] Self [Comments]

Output: Comment 1: I think that it is absolutely necessary to adopt the new guidelines from the Guide for the Care and Use of Laboratory Animals (8th Edition). Not adopting them would be completely irresponsible as scientists looking to uphold the highest standards and integrity in science. The excuse that it shouldn't be adopted because it will make certain research "harder or more expensive" is a ridiculous excuse. In addition, providing research animals better conditions could actually lead to more accurate research, by reducing animal stress which could affect outcomes in certain research. Comment 2: I think that it is necessary to require institutions to complete a semiannual program and facility evaluation. In the past there have been instances of institutions not meeting the previous standards and with making the standards more extensive, more facilities will be looking at ways to get around the requirements and not adhere properly.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 354 [Entry Date] 04/21/2011 at 02:51:12 PM [Affiliation] Self [Comments]

Output: Comment 1: I hope OLAW will retain the 1996 Guide as PHS policy. A great deal of the new policy promises to significantly increase a) the expense of research, b) the paperwork burden on researchers, and c) the authority of local IACUCs to restrict already peer-reviewed research. While some of the new recommendations are based on empirical research, many are not (e.g., cage sizes, food and liquid restriction). Comment 2: I recommend at least 4 years given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 355 [Entry Date] 04/21/2011 at 02:56:11 PM [Affiliation] Self [Comments]

Output: Comment 1: As a practicing scientist, I applaud the efforts to maintain the highest levels of care for animals in research. There are a number of specific concerns, however, with the latest version of the Guide. To begin with, the new Guide is nearly twice as long as the 1996 version, and contains a great deal of new policy that promises to significantly increase (a) the expense of research, (b) the paperwork burden on researchers, and (c) the authority of local IACUCs to restrict already peer-reviewed research. Some of the new recommendations are based on empirical research, but many are not (e.g., cage sizes, food and liquid restriction). There are no reasons to suspect that these additional burdensome and costly requirements would produce any improvement in animal care and welfare, although it would likely produce erosion in the quality of research and the number of top scientists working in areas that have significant benefits for both humans and animals. Researchers care deeply about their animal subjects, and the protection and care has served science and the animals well. There is little compelling reason to adopt new guidelines when those in the 1996 Guide continue to serve the community and the animals so well. Comment 2: If the 2011 Guide is adopted as PHS policy, then the deadline for full compliance that is proposed in the Federal Register is March 31, 2012. Such a date places extreme burden and excessive costs on institutions (including government funding). At least 4 years (e.g., 2015) seems not unreasonable given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 356 [Entry Date] 04/21/2011 at 02:58:22 PM [Affiliation] Self [Comments]

Output: Comment 1: I do not think there is a need for a new version and do not think the eighth edition should be adopted. Comment 2: I recommend waiting at least 4 years (e.g., 2015) given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 357 [Entry Date] 04/21/2011 at 03:06:04 PM [Affiliation] Self [Comments]

Output: Comment 1: I find myself in agreement with the ACNP position, copied below: "NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures."

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 358 [Entry Date] 04/21/2011 at 03:09:42 PM [Affiliation] Self [Organization City and State] Sarasota, FL [Comments]

Output: Comment 1: I vote against adopting the new Guide as policy, maintaining adherence to the 1996 Guide. No substantive revisions to the existing Guide are needed. Comment 2: I recommend at least a 4-year time frame (e.g., 2015) for whatever plan is adopted. This would take into account the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 359 [Entry Date] 04/21/2011 at 03:20:23 PM [Affiliation] Self [Comments]

Output: Comment 1: I feel like these guidelines will be a positive thing for science. Such guidelines and restrictions are desperately needed in the world of research. Most labs only adhere to the bare minimum of standards and is it has stood, that simply isn't enough. Monkeys, apes, and even rats and pigeons are living creatures and deserve to live in healthy, comfortable environments, especially if they are going to be subjected to scientific tests. Comment 2: I also feel this would be beneficial to science and the animals involved.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 360 [Entry Date] 04/21/2011 at 03:28:21 PM [Affiliation] Self [Organization City and State] Charlotte, North Carolina [Comments]

Output: Comment 1: Do not adopt the eigth edition of the Guide, it would be an unecessary burden. Comment 2: This would be an necessary burden.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 361 [Entry Date] 04/21/2011 at 03:32:29 PM [Affiliation] Organization [Organization Name] University of Nevada, Reno [Organization City and State] Reno, NV [Comments]

Output: Comment 1: I do not endorse adoption of the eight edition. The new revisions do not in any way enhance treatment of existing laboratory animals and levy unnecessary expenses on scientists. The 1996 edition of the guide is more than sufficient to secure humane treatment of animals in a research context. Comment 2: I unequivocally reject the eight edition and endorse the continued use of the 1996 guide as a standard of practice.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 362 [Entry Date] 04/21/2011 at 03:37:27 PM [Affiliation] Self [Comments]

Output: Comment 1: I am against implementation of the policies as they are written. Should changes to animal housing be required, I suggest that institutions be given at least 4 years to make those changes, due to the costs and logistical difficulties of mandatory changes to housing.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 363 [Entry Date] 04/21/2011 at 03:37:54 PM [Affiliation] Organization [Organization Name] McLean Hospital [Organization City and State] Belmont, MA 02478 [Comments]

Output: Comment 1: Response: NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures. Comment 2: OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 364 [Entry Date] 04/21/2011 at 03:39:20 PM [Affiliation] Self [Comments]

Output: Comment 1: NIH should NOT adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals. This guide is too long, it will increase the expense of research, and recommendations such as limiting food and liquid restriction are NOT based on empirical research. Comment 2: NIH should NOT adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals. However, if this guide is adopted, compliance should not be required for a minimum of 4 years, given the expenses associated with compliance.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 365 [Entry Date] 04/21/2011 at 04:07:43 PM [Affiliation] Self [Comments]

Output: Comment 1: The eighth edition of the Guide should NOT be adopted. Adherance to the 1996 Guide should be maintained. Comment 2: I recommend at least 4 years (e.g., 2015) given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 366 [Entry Date] 04/21/2011 at 04:17:19 PM [Affiliation] Self [Organization Name] MPRC, University of Maryland [Organization City and State] Catonsville, Maryland [Comments]

Output: Comment 1: NO

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 367 [Entry Date] 04/21/2011 at 04:24:57 PM [Affiliation] Self [Comments]

Output: Comment 1: NIH should NOT adopt the eight edition of the "Guide for the Care and Use of Laboratory Animals (Guide)" as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals other than humans. Comment 2: NIH should NOT adopt the implementation plan which would require that institutions complete at least one semiannual program and facility evaluation using the eight edition of the Guide as the basis for evaluation by March 31, 2012.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 368 [Entry Date] 04/21/2011 at 04:27:53 PM [Affiliation] Organization [Organization Name] University of Virginia [Organization City and State] Charlottesville [Comments]

Output: Comment 1: I stand strongly AGAINST adoption of the new edition of the Guide. There is not adequate justification for supplanting the 1996 Guide as PHS Policy. There are also numerous problems with the new Guide as federal policy. In particular, I am opposed to the new guidelines for the use of medical grade compounds, newly introduced requirements for post-approval monitoring of IACUC-approved protocols and formal review of "unexpected outcomes". I also oppose the introduction of language cautioning against multiple survival surgical procedures per se on the same animal, in addition to cautioning against multiple major survival surgical procedures, as well as the section on "Food and Fluid Regulation" which requires that food and fluid consumption be recorded daily for all animals on either type of restriction. Each of these changes would force the use of more animals and/or drive up the research costs unnecessarily.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 369 [Entry Date] 04/21/2011 at 04:29:24 PM [Affiliation] Self [Comments]

Output: Comment 1: I believe that the proposed new Guide contain equirements that are not substantiated by empirical research. I strongly recommend that the 19969 standards be maintained. Comment 2: If new Guide's standards are adopted rather than retaining the 1996 standards, it is unreasonable to believe that research faciliites will be able to implement them financially and in terms of other resources in less than 1 year. New research endeavors ought to have two (2) years to implement the Guide while a four year phase in period ought to be allowed so that research protocols can be completed under the 1996 Guide's requirements when the research protocol was developed and funded.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 370 [Entry Date] 04/21/2011 at 04:34:27 PM [Affiliation] Self [Comments]

Output: Comment 1: I urge that this new addition be put on hold. It should NOT go into effect. This new addition goes a long way towards INCREASING costs, INCREASING paperwork, INCREASING roadblocks to research, INCREASING the number of animals utilized in research, and INCREASING time to conduct research. However, it will markedly DECREASE the ability to conduct research in an efficient manner. Particularly onerous is the section titled "Use of Non-Pharmaceutical Grade Chemicals and Other Substances". Not only is it unnecessary, but it will totally block new and innovative research. Rules (euphemistically called guidelines) such as these will markedly slow the progress being made in improving health for the American people and helping people live longer and healthier lives. Comment 2: Implementation plan should not be put into effect until a final version is agreed upon. Otherwise, it becomes a "fait accompli" and adds to the burden of the scientist, the institution, and research, in general.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [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]

Output: 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


Input: [ID] 372 [Entry Date] 04/21/2011 at 04:37:41 PM [Affiliation] Self [Comments]

Output: Comment 1: I recommend against the adoption of these guidelines. The science behind many of these recommendations is questionable. The added expense of the methods and the added paperwork burden on investigators and support staff will increase the cost to the taxpayer to produce less research. At a time when the US can ill afford to put itself at a disadvantage in its ability to conduct innovative biological and behavioral research, these standards are proposed. The effects on animal health and well being are questionable (at best). The effects on research, technology, innovation, and the number of bright young US researchers that choose to pursue animal research is almost assured. I strong oppose the proposed revised guidelines. Comment 2: I strongly oppose this. See prior comment for reasons supporting this opposition.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 373 [Entry Date] 04/21/2011 at 04:40:08 PM [Affiliation] Organization [Organization Name] UNT Health Science Cente [Organization City and State] Fort Worth, TX [Comments]

Output: Comment 1: 1) Newly introduced requirements for post-approval monitoring of IACUC-approved protocols (e.g., direct observation of "laboratory practices and procedures and comparisons with approved protocols") and formal review of "unexpected outcomes" of research are examples of items that require additional IACUC staffing to accomplish as well as require additional time from research team members. These are unnecessary, and more importantly ineffectual, requirements that will substantially increase cost without improving welfare. 2)The newly added section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from use of drugs provided by suppliers of high-quality drugs for research and from using such compounds provided through the NIDA drug supply program if a version of that same drug is available in a human clinical or veterinary formulation. It also fails to acknowledge the critical importance of collaborations by chemists with behavioral researchers to develop new therapeutic drugs. The statements in this section are out of touch with the realities of drug abuse research as well as research in numerous other fields. Although OLAW has published a similar set of statements on its website in recent years, the status as enforceable PHS Policy has been controversial due to their de novo introduction of the topic as an answer to a "Frequently Asked Question," (i.e., no previously published PHS Policy nor the Guide had addressed use of drugs in research). No definition of "pharmaceutical grade" is given, but two conflicting definitions are implied by citation of, first, the USDA/APHIS Policy 3, an interpretive rule for use of pharmaceutical grade "medications" to prevent pain/distress in the conduct of research; and second, the NIH policy for its intramural program on "non-pharmaceutical grade drugs." Experience with USDA/APHIS enforcement has made clear that Policy 3 is interpreted to require use of commercially prepared solutions, rather than those prepared by investigators; the first sentence of the new Guide section on this topic is consistent with this view. Yet the NIH policy defines "pharmaceutical grade" drugs as those manufactured according to USP standards, thus accommodating the practice of preparation of drug solutions in the laboratory. Yet even that intramural NIH Policy ignores the fact that the NIDA drug supply program, which has been operating to supply compounds to funded researchers for decades, does not prepare to USP standards, because they are unnecessary for research purposes. To require that they do so would result in significant increases in costs to NIH, for no valid reason, at a time when NIH funding is shrinking. Yet, as with other sections, the contradictions in guidance were not recognized by those who published the 2011 Guide. 3) The section on "Food and Fluid Regulation" requires that food and fluid consumption be recorded daily for all animals on either type of restriction, which requires abandoning automated watering systems for food-restricted, as well as water-restricted, animals; and that food consumption for fluid-restricted, as well as for food-restricted, animals be recorded daily despite the fact that each type of restriction makes the other commodity freely available. Again, these are unnecessary regulations that will be costly and ultimately ineffective, particularly as there is substantial evidence that food restricted animals are healthier due to suffering less obesity-related health disorders.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 374 [Entry Date] 04/21/2011 at 04:43:16 PM [Affiliation] Self [Comments]

Output: Comment 1: Response: NO. Many of the recommendations contained in the 2011 Guide are not based on scientific evidence, and could seriously impede progress in research that will benefit public health. Most recommendations will require significant costly alterations for institutions and investigators. Examples of recommendations that have little scientific basis and could negatively impact research progress are as follows: The recommendation for use of pharmaceutical-grade drugs: There is no evidence that pharmaceutical-grade drugs would improve animal welfare. Moreover, research could be impeded because commercially available pharmaceutical-grade formulations are often single concentrations that make it difficult or impossible to manipulate drug dose or to compare different vehicles. Moreover, pharmaceutical-grade drugs will increase the cost of pharmacological research by 500 to 1,000 times in some instances. Recommendations for Constraints on multiple procedures in animals: It is often in the best interest of science to conduct longitudinal studies in animal subjects using repeated measures in an own control design. Some nonhuman primates live for more than 25 years, and repeated measures are often necessary to answer research questions. Repeated surgeries are often necessary to repair or prolong the life of surgically implanted experimental devices. Recommendations for Paired housing for nonhuman primates: Despite the attractive "face validity" of paired housing and the opportunity for physical contact between pairs of nonhuman primates recommended in the 2011 Guide, this would place animals at risk for injury and death. Aggression in response to any surprise (a novel noise, person, etc.) may lead the dominant member of the pair to attack/kill the weaker or more submissive cage mate. Studies that require implantation of any device such as an IV catheter to evaluate medication effectiveness could not be conducted. Recommendations for Changes in cage size: There is no scientific justification for modifications in cage sizes and configurations specified in the 1996 edition of the Guide. The cost to institutions and to investigators would be astronomical! Comment 2: Response: Implementation of any changes to the 1996 Guide should be delayed for at least five years (March 2015) to allow NIH to gather scientific evidence to support or to refute the many problematic recommendations proposed in the 2011 Guide. The requirement for additional oversight will add to an already onerous regulatory burden that eventually will be unsustainable for many research institutions. The ultimate impact will be serious damage to this nation's preeminent leadership in health-related research. The NIH must recognize that lobbying efforts by groups opposed to all research with animals, such as the Humane Society of America and the Physicians for Social Responsibility, are reflected in the proposed changes to the Guide. It would be most unfortunate if NIH standards for insuring animal welfare were primarily influenced by the well-funded political agenda of those organizations opposed to all research on animals, rather than evidence-based humane concerns for animal welfare and commitment to advances in science.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 375 [Entry Date] 04/21/2011 at 04:47:59 PM [Affiliation] Organization [Organization Name] Yale University [Organization City and State] New Haven CT [Comments]

Output: Comment 1: 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


Input: [ID] 376 [Entry Date] 04/21/2011 at 04:52:45 PM [Affiliation] Self [Organization City and State] Essex Fells, nj [Comments]

Output: Comment 1: I support these changes. Comment 2: I support these changes.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 377 [Entry Date] 04/21/2011 at 04:55:16 PM [Affiliation] Self [Comments]

Output: Comment 1: I oppose the adoption of the 8th edition of the guide. This edition introduces new policies that constrain the exercise of scientific and professional judgment for both investigators and laboratory animal veterinarians. Mandatory requirements, including requirements for new cage sizes for some species (particularly for rodent breeding, apparently to conform to European standards) and mandatory requirements for social housing of all species (without leeway for practical constraints) will require large expenditures of funds to accomplish.Restrictions against using animals in multiple procedures most certainly will increase the number of animals needed in research, thus increasing costs, but also indirectly hampers the use of within-subject and single subject designs that are particularly powerful for behavioral research. The section on "Food and Fluid Regulation" requires that food and fluid consumption be recorded daily for all animals on either type of restriction, which requires abandoning automated watering systems for food-restricted, as well as water-restricted, animals; and that food consumption for fluid-restricted, as well as for food-restricted, animals be recorded daily despite the fact that each type of restriction makes the other commodity freely available. The newly added section "Use of Non-Pharmaceutical Grade Chemicals and Other Substances" is of particular concern. This section essentially bans researchers from use of drugs provided by suppliers of high-quality drugs for research and from using such compounds provided through the NIDA drug supply program if a version of that same drug is available in a human clinical or veterinary formulation. It also fails to acknowledge the critical importance of collaborations by chemists with behavioral researchers to develop new therapeutic drugs. The statements in this section are out of touch with the realities of drug abuse research as well as research in numerous other fields. Comment 2: 2011 Guide represents a significant "guidance document," as defined by the Office of Management and Budget (OMB), which "may reasonably be anticipated to lead to an annual effect on the economy of $100 million or more. . ." Therefore, an opportunity for 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


Input: [ID] 378 [Entry Date] 04/21/2011 at 05:06:14 PM [Affiliation] Self [Comments]

Output: Comment 1: I am strongly opposed to adoption of the 8th edition of the Guide in its present form. Some of the mandatory requirements (e.g. housing, use of non-pharmaceutical grade drugs) are either unreasonable or impossible to follow without a dramatic adverse impact on the integrity of certain types of behavioral science. In many ways, the new Guide represents and intrusion into second-guessing the scientific and professional judgment of investigators and veterinarians in their fields of research.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 379 [Entry Date] 04/21/2011 at 05:11:01 PM [Affiliation] Self [Comments]

Output: Comment 1: I recommend 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, professional 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 of "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: I concur 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


Input: [ID] 380 [Entry Date] 04/21/2011 at 05:17:53 PM [Affiliation] Self [Comments]

Output: Comment 1: I am AGAINST adoption of the new edition of the Guide. Guide introduces new policies that constrain the exercise of scientific and professional judgment for both investigators and laboratory animal veterinarians. Mandatory requirements relating to housing requirements and drug sourcing would result in significant increases in costs to NIH, at a time when NIH funding is shrinking.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 381 [Entry Date] 04/21/2011 at 05:27:01 PM [Affiliation] Self [Comments]

Output: Comment 1: I am against adopting the new Guide. It would create an unreasonable burden on investigators and ACUCs, and increased cost to research institutions, but no real enhancement of animal welfare. Comment 2: I am against implementing the new Guide. If it is implemented, there should be a grace period of about three years for already approved animal-study protocols.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 382 [Entry Date] 04/21/2011 at 05:29:38 PM [Affiliation] Self [Organization Name] UNCW [Organization City and State] Wilimington, NC [Comments]

Output: Comment 1: I think that the strict "guidelines" for how an institution and a researcher must alter their current practices for animal care and use is excessively restrictive. I think many of the demands placed on Institutions will require excessive oversight and paperwork, and in turn, excessive costs to maintain quality research. Additionally, I am unclear why new guidelines are required. Is there empirical evidence that current standards are resulting in undue stress or pain in animals. Are unjustified experiments taking place at alarming rates? I am a current member of IACUC, and the participation of scientists at the University in cooperation with local vets and members of the public seems to result in high standards of animal care at our university. The goal of every scientist conducting research is to have a healthy, well cared for animals. It is in our own best interest to care for our animals, and I have not witnessed any threats to animal welfare in any labs I've ever visited; at our university or any other. With the already high standards of care, I reiterate my confusion as to why we need these stricter "guidelines" (which honestly read more like mandates). I think that the unnecessary cost of implementing these unsubstantiated standards would prohibit much of my research, and I suspect many other scientists would feel the same way. Many facilities currently conducting ethical and justified research would not meet many of the standards set in the new guide, and I for one do not support shutting down good research to meet unsupported changes. I am a member of APA, and I support their official response to this request for public comment. I would not recommend adopting the guide in its current state.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 383 [Entry Date] 04/21/2011 at 05:53:01 PM [Affiliation] Self [Organization City and State] Portland, Oregon [Comments]

Output: Comment 1: NO. The new guide is supposed to be an "update" of the 1996 Guide, however the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to my research though the cost of pharmaceutical grade drugs and may preclude testing some compounds if I can not obtain the appropriate "grade" drug.However, the scientific data justifying these policy changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden with justifications in order to deviate from the new policies. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Specifically the constraints on multiple procedures, new requirements for food- or fluid-restriction, the choices of chemicals and post-approval monitoring of procedures will add to the cost of the research. Comment 2: OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 384 [Entry Date] 04/21/2011 at 06:16:32 PM [Affiliation] Self [Comments]

Output: Comment 1: I am voting against the new guide as a policy andI recommend that the 1996 Guide should be retained. Comment 2: I suggest least 4 years (e.g., 2015), given the expense of a variety of cage size and housing requirements at a time of great financial difficulty for research institutions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 385 [Entry Date] 04/21/2011 at 06:17:01 PM [Affiliation] Self [Organization Name] University of New Hampshie [Organization City and State] Durham, NH [Comments]

Output: Comment 1: I have served as Principal Investigator of grants from NIMH and NSF since the early 1960s, and the use of animals in my behavioral research complied with guidelines in effect throughout those years. The animals' health remained excellent throughout each study; many of them (pigeons) lived for more than 12 years and served in several diffeent studies. There is no need to alter the guidelines. Comment 2: If the standards are to be changed, additional funds will be required and time will be needed to meet mandated conditions. especially for animal housing.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 386 [Entry Date] 04/21/2011 at 06:25:38 PM [Affiliation] Self [Comments]

Output: Comment 1: The eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) should NOT be adopted. The 1996 guide should be maintained. Comment 2: If the eighth edition of the Guide is adopted, a period of at least 4 years (ie, 2015) should be allowed for transition to the new guidelines. Given the substantial expense of changing to new cage size and housing guidelines and the current economic strains on researchers, 2012 is NOT a reasonable goal for implementation of the eighth edition of the Guide.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 387 [Entry Date] 04/21/2011 at 06:47:40 PM [Affiliation] Self [Comments]

Output: Comment 1: No. I oppose the approval of the new guide. Compliance with the new policy statements (for example, cage sizes) will increase the expense to institutions and investigators, and result in an extraordinary increase in paperwork. However, there is little to no scientific support for the changes, and there is no identifiable improvement in animal welfare. Comment 2: Data should guide policy. Institutional compliance should not be required in the absence of scientific support.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 388 [Entry Date] 04/21/2011 at 07:19:28 PM [Affiliation] Organization [Organization Name] International Study Group for Investigating Drugs as Reinforcers [Organization City and State] Washington, D.C. [Comments]

Output: Comment 1: The College on Problems of Drug Dependence (CPDD) is the oldest U.S. scientific society on drug dependence. Originally founded in 1929 as part of the National Academy of Sciences, CPDD now is an independent scientific society comprised of ???? members.. It serves researchers, clinicians, and policy makers to promote research and facilitate the transfer of findings to improve drug abuse treatment and prevention practices. 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


Input: [ID] 389 [Entry Date] 04/21/2011 at 07:24:31 PM [Affiliation] Self [Comments]

Output: Comment 1: I am against the adoption of the eighth edition of the Guide for the Care and Use of Laboratory Animals. The new addition contains many additions/revisions from the previous version that do not improve the care or welfare of laboratory animals, but do increase costs to the NIH, researchers, and institutions. Comment 2: I am against using the new Guide as the basis of facility evaluation.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 390 [Entry Date] 04/21/2011 at 07:25:42 PM [Affiliation] Self [Comments]

Output: Comment 1: NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures. Comment 2: OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 391 [Entry Date] 04/21/2011 at 07:35:20 PM [Affiliation] Organization [Organization Name] Louisiana State University Health Sciences Center, [Organization City and State] New Orleans, LA [Comments]

Output: Comment 1: I am strongly opposed to these new guidelines as they would add an unwarranted burden to researchers using laboratory animals. If the NIH adopts the new guidelines presented in the 8th edition of the Guide for the Care and Use of Laboratory Animals, this will place an enormously increased burden upon researchers performing many types of animal experiments. For example, the guidelines suggest the use of pharmaceutical-grade chemicals (which, in the case of pentobarbital is approximately ten times the price of its non-pharmaceutical counterpart!). Although I feel it is extremely important for researchers to always be open to improvements in the care and use of laboratory animals, I was unable to find any references in the 8th edition to documentation of any specific deleterious effects (either scientific or regarding unnecessary animal suffering) arising from current guideline practices to justify these burdensome changes. Although the 8th edition guidelines do not completely preclude the use of non-pharmaceutical grade chemicals, their alternative suggestion was for researchers to give consideration to at least twelve different parameters for each chemical used, without providing specific justification for each parameter. I am very concerned that this list would leave investigators open to an extremely burdensome justification process that, as noted above, I consider to be unwarranted.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 392 [Entry Date] 04/21/2011 at 07:35:28 PM [Affiliation] Organization [Organization Name] ACADIA Pharmaceuticals [Organization City and State] San Diego, CA [Comments]

Output: Comment 1: No. Increased investigaitor burden (cost, paperwork) with no data supproting new regualtions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 393 [Entry Date] 04/21/2011 at 07:37:16 PM [Affiliation] Organization [Organization Name] Eastern Oregon University [Organization City and State] LaGrande, OR [Comments]

Output: Comment 1: NIH should NOT adopt this new policy. The 1996 policy has been sufficient and adopting the new policy will have significant impacts on research and teaching. Comment 2: No, institutions already need to have internal review by research review committees. Additional paperwork and policy will only burden this committee and hinder research and teaching.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 394 [Entry Date] 04/21/2011 at 07:39:39 PM [Affiliation] Self [Comments]

Output: Comment 1: Yes, adopt the new guidelines immediately! It is the most correct and ethical behavior. Comment 2: Yes, adhere and comply by the earliest deadline to follow these guidelines. It is correct and ethical behavior.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 395 [Entry Date] 04/21/2011 at 08:02:11 PM [Affiliation] Self [Comments]

Output: Comment 1: Although resource intensive, stricter guidelines for the humane care and use of laboratory animals is long overdue. Please move forward with these regulations. Comment 2: Again, this is a necessary part of using live beings in laboratory research. As stated in the proposed guide: "Each institution should establish and provide sufficient resources for a Program that is managed in accord with the Guide and in compliance with applicable regulations, policies, and guidelines." Scientific research, development and application are important, but humane treatment should be non-negotiable, and evaluation of facilities would be a logical means toward fidelity of the guidelines.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 396 [Entry Date] 04/21/2011 at 10:28:36 PM [Affiliation] Self [Comments]

Output: Comment 1: I have read through much of the guide and was struck by a number of general statements that would be problematic and intrusive in daily research efforts. Many of these statements are vague and appear to make arbitrary distinctions. This sort of guidance is more likely to lead to unnecessary delays and expenses in research. As someone who studies the neural mechanisms of ingestive behavior the statement below concerns me: "In the case of conditioned-response research protocols, use of a highly preferred food or fluid as positive reinforcement, instead of restriction, is recommended." This is something that we routinely do and I can attest that animals do not always acquire tasks when given preferred food. A mild food restriction is often necessary in these studies. Most importantly, what is the basis for making this recommendation? Is there something unhealthy about mild restriction? In fact, the vast majority of research across animal phyla indicate that food restriction improves many health parameters. Even after restriction, our animal models are still heavier than a similar animal in the wild. Comment 2: No, I do think this guide, in its current from should serve as the basis for evaluation in a year. There is a need for more discussion of its implications - both financial and scientific.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 397 [Entry Date] 04/22/2011 at 12:08:32 AM [Affiliation] Self [Comments]

Output: Comment 1: It not should adopt the eighth edition of the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for evaluation of institutional programs receiving or proposing to receive Public Health Service support for activities involving animals. The advancement of science, especially in human behavior drastically benefits from animal laboratory experiments.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 398 [Entry Date] 04/22/2011 at 03:20:20 AM [Affiliation] Self [Comments]

Output: Comment 1: As a behavioral scientist, I vote against adopting the new Guide as policy,and I recommend maintaining adherence to the 1996 Guide. The new guide contains requirements that are not based on scientific evidence. These requirements will lead to costly changes that are not necessary, and these added expenses will likely lead to the loss of some laboratories. The existing standards for the IACUC oversight process are entirely adequate for the ethical use of animals for research. Comment 2: If the new guidelines are accepted, the time frame for implementation is not realistic. Additional funding would be required to meet the new standards. I recommend that at least 4 years be allowed for preparation to meet the new standards, if adopted.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 399 [Entry Date] 04/22/2011 at 03:26:23 AM [Affiliation] Self [Organization City and State] Reno, NV [Comments]

Output: Comment 1: Yes: stricter standards are needed. As a scientist, there will be limitations to such research in the future, but it is much more important that we are looking out for the "well-being" of our subjects. Comment 2: This would be a good change: again, stricter standards will lead to research that is not only in the interest of the animals involved, but also the quality of the studies that pass these tests will be of a much higher caliber than is currently the case.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 400 [Entry Date] 04/22/2011 at 07:14:08 AM [Affiliation] Organization [Organization Name] The Jackson Laboratory [Organization City and State] Bar Harbor, Maine [Comments]

Output: Comment 1: The Jackson Laboratory has long worked successfully through our IACUC to ensure appropriate implementation of the provisions of the Guide to safeguard animal welfare at our facility. The updated (8th edition) Guide contains some areas of concern. Previous comment opportunities on the new Guide pre-dated the availability of a published document. Now that it is in print, The Jackson Laboratory supports opening a comment period prior to OLAW adopting the updated Guide. Specifically, we support the use of performance standards rather than strict engineering standards as the best means of achieving optimal animal welfare within the unique environments of different institutions. The new guidelines as written could have unintended effects on research, and potentially on animal welfare. An example is the new space requirements for female mice with litters. The IACUCs are in the best position to develop appropriate performance standards, and we believe they should retain the flexibility that now allows them to make responsible animal welfare decisions at the institutional level. The fiscal impacts of the updated Guide could, depending on how the document is categorized for implementation purposes, have a major economic impact on biomedical research institutions throughout the country. For these reasons we respectfully request a more substantive opportunity for comment.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 401 [Entry Date] 04/22/2011 at 08:26:50 AM [Affiliation] Self [Comments]

Output: Comment 1: As a physician and NIH-funded researcher, I am greatly concerned with the changes that are proposed to be implemented in the new Guide. While my concerns are many and deep, below are the points that I feel are most concerning. I strongly request that the changes in the Guide not be implemented until a careful consideration has been given to their multiple detrimental impacts and substantial changes made. 1. There is no indication that wholesale changes needed to be made in the Guide. There were only a few areas that needed updating in the previous edition. 2. Many (~60) of the changes aren't "guidelines," they are mandatory changes that will need to be made, removing investigator and IACUC scientific judgment from the process. 3. There is no scientific justification (and often conflicting evidence) for many of the changes suggested. This is especially true for the cage sizes. Implementing these changes for rodents will cost several hundred million dollars in direct (infrastructure) and indirect (impaired research) costs. 4. Implementation of regulatory guidelines like these that are projected to cost >$100,000,000 should receive more careful consideration as to their benefits and costs, and be backed by accepted scientific findings. 5. Strongly discouraging multiple use of animals (even for a "within subject design") will have the unintended consequence of driving up animal use and associated expenses. This is a direct conflict with the "Reduce" part of the "3-R's", which is a guiding fundamental animal use in research. 6. Recommending that positive reinforcement rather than mild food restriction be used in conditioned response experiments ignores substantial data that positive reinforcement does not work well to train behaviors such as self administration. 7. The introduction of the requirement that IACUC approve the use of non-pharmaceutical grade chemicals including formulation and a host of details that are required for FDA approval of drug administration to humans is unworkable, inappropriately transfers responsibility from the investigator to the IACUC (who generally lack the expertise to make these evaluations), and ignores the fact that the data required to implement this requirement is lacking for most drugs that would be administered to animals. 8. Additional duties assigned to the IACUC are excessively burdensome to the IACUC members and to the experimenter, again slowing down research and increasing the administrative burden, with no measurable benefit to the experimental animals. The most onerous of these is direct comparison of approved protocols to what is being done in the lab, and "formal review" of unexpected outcomes. Comment 2: Semiannual investigations are fine, basing them on the eighth edition is not. (Since the 8th edition is fundamentally flawed.)

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 402 [Entry Date] 04/22/2011 at 08:35:28 AM [Affiliation] Self [Comments]

Output: Comment 1: I am AGAINST adoption of the new edition of the Guide for the Care and Use of Laboratory Animals. This new 8th edition departs significantly from the 7th. 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.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 403 [Entry Date] 04/22/2011 at 08:50:54 AM [Affiliation] Self [Comments]

Output: Comment 1: NO. I concur with the response offered by the ACNP, which is restated here. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures. Comment 2: I concur with the response of the ACNP, which is that OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 404 [Entry Date] 04/22/2011 at 09:17:21 AM [Affiliation] Self [Organization Name] Binghamton University (SUNY) [Organization City and State] NY [Comments]

Output: Comment 1: I am againts the the edition of the guide

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 405 [Entry Date] 04/22/2011 at 09:18:16 AM [Affiliation] Self [Organization Name] University of Massachusetts [Organization City and State] Amherst, MA [Comments]

Output: Comment 1: In especially these times of fiscal constraints, the imposition of additional and unneeded regulations is unwarranted. In addition to their adverse consequences for research, the proposed regulations would pose further difficulties for the conduct of laboratory sections of academic courses, Please simply reaffirm the 1996 regulations. Thank you.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 406 [Entry Date] 04/22/2011 at 09:30:39 AM [Affiliation] Self [Comments]

Output: Comment 1: The 8th edition of the Guide should not be adopted. It too stringent and impedes the progress of scientific research. Comment 2: Program and facilities evaluations are necessary and I support them, however, I do not support the use of the 8th edition of the Guide as the the basis for evaluations.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals


Input: [ID] 407 [Entry Date] 04/22/2011 at 09:42:55 AM [Affiliation] Self [Comments]

Output: Comment 1: The College on Problems of Drug Dependence (CPDD) is the oldest U.S. scientific society on drug dependence. Originally founded in 1929 as part of the National Academy of Sciences, CPDD now is an independent scientific society comprised of 5997 members. It serves researchers, clinicians, and policy makers to promote research and facilitate the transfer of findings to improve drug abuse treatment and prevention practices. 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


Input: [ID] 408 [Entry Date] 04/22/2011 at 10:10:00 AM [Affiliation] Organization [Organization Name] Tufts University [Organization City and State] Medford, MA [Comments]

Output: Comment 1: NO. The new guide was originally supposed to be an "update" of the 1996 Guide, however, the final product is twice as long and contains a great deal of new "policy." Compliance with these new "policy" statements may increase the expense to institutions (e.g., cage size) and expense to investigators (e.g., drugs). However, the scientific data justifying these expense changes is non-existent. Adherence to the 2011 Guide will require large increase in paperwork burden (all deviations from "should" statements contained in the new Guide will need to be justified). Adoption of the new guide may also negate the opportunity to diminish the burden resulting from over reactions to issues for which institutions already have "overregulated." Moreover, the new "Guide" policies Increased infringement on scientific decision-making by PHS grantees, contractors and IRGs. The policy changes implemented by the new Guide will result in significant additional expenses to the institution and the investigator with no real enhancement of animal welfare. Some specific examples include constraints on multiple procedures in animals, constraints on multiple surgeries (per se), new requirements for food- or fluid-restriction, naïve and constraining section on choices of "chemicals and other substances" to give animals and specific guidance on "post-approval" monitoring (e.g., observation of procedures). In addition the new "Guide" requires an increased level of intra and post-operative surgical procedures. Comment 2: OLAW should require institutional compliance with the new Guide no sooner than March, 2015 to allow for the collection of relevant data. It is the data that should guide policy decisions.

Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals