Listing of Public Comments on Understanding of OLAW Position Statements
Entire Comment Period: 12/01/2011 - 02/03/2012

In a December 1, 2011 Federal Register Notice (PDF - 148 KB), NIH requested public comments on their understanding of OLAW Position Statements that describe the ways in which OLAW expects institutions to implement the Guide for the Care and Use of Laboratory Animals: Eighth Edition (Guide). Link to Non-U.S. Government Site - Click for Disclaimer In May 2012, OLAW updated the original (December 2011) Position Statements following an analysis of the public’s comments. In response to those comments, OLAW clarified Position Statements: 1) Cost, 2) Housing, 2a) Nonhuman Primate Housing, 2c) Rodent Housing and 3) Non-Pharmaceutical-Grade Substances. For a summary of the changes, see the May 2012 Update Summary (PDF). For reference, an archive of the original version is available for download at December 2011 Position Statements (PDF).

NIH received a total of 44 comments: 26 responses were from those who identified themselves as individuals, 6 were from PHS Assured institutions, 2 were from animal advocacy organizations and 9 were from professional organizations.

Names of individuals or identifiable information were redacted from the comments; the symbol “*****” replaces personally identifiable information.


ID Entry Date Affiliation Organization
Name
Organization
City and State
Comment 1 Comment 2 Comment 2a Comment 2b Comment 2c Comment 2d Comment 3 Comment 4 Comment 5 Comment 6
1 01/05/2012 at 05:05:18 AM Self     The increase in the cost of rabbit cage and rodent cage is a major concern of the Indian institutes.

      Triod mating should be retain as per the previous edn. guide.

Rabbit cage size should be retain without increasing the cage height

    The surgery should be performed only by veterinarian. Non veterinarian shall not be entertained for rodent surgery particularly in India

 
2 01/12/2012 at 02:43:37 PM Self         Note: Behaviorally compatible animals must be used in socialization attempts.

In many cases compatibility issues cannot be determined beforehand, especially when introducing animals into established groups. Group dynamics will dictate weather an animal is socially acceptable to the group. To say that an animal is going to be socially compatible beforehand would be a grave mistake and a ridiculous assumption.

             
3 01/16/2012 at 11:19:51 AM Self             These new standards will impede research. Rodents are essential to scientific testing that improves human lives. Animal welfare is a much less important consideration. These guidelines will place unacceptable burdens on researchers who must either divert resources to animal housing or risk losing funding. Unless there is scientific evidence that current standards are inadequate for the purpose of furthering research, there should be no change.

         
4 01/16/2012 at 02:22:08 PM Self University of Tennessee Knoxville, TN   The housing recommendations for 1 litter/cage seems a bit excessive and does not really relate to animal welfare. Having "trios" in large cages really does not affect the animals welfare. These decisions need to be based on true science and not something that is just perceived to be "better" for the animals. All of us want to ensure the welfare of the animals but this rule seems to be an unnecessary obstacle as there is not an animal welfare issue with the current state of this type of housing.

               
5 01/18/2012 at 06:33:39 PM Self     While cost should not be the overriding factor, the OLAW and the public should realize that individual labs at universities are non-profit and most are already struggling to survive. Cost increases for experimental maintenance at this point in time will necessitate shutting down labs and firing people who are working on understanding and treating diseases such as cancer, Alzheimer's, autism, and all the other diseases the public wants us to fight.

      Any rules increasing or decreasing the recommended space for rodents should be based on experimental evidence of effects on health maintenance of the animals. A body such as the National Academy should examine the evidence or perform the appropriate experiments.

         
6 01/21/2012 at 06:03:32 PM Self         As the editor of a book on the care, housing, and psychological well-being of captive nonhuman primates, and a former member of the American Psychological Association's Committee on Animal Research and Ethics, I am pleased to see the stress on the social and behavioral needs of nonhuman primates. Limitations on how long subjects may be housed in isolation must be stringently enforced. Claims of the necessity of solitary housing should be viewed skeptically. It is more convenient to confine monkeys and apes singly, and difficult and costly to maintain suitable social housing and behavioral enrichment, but it is not in the interest of the animals to neglect their social and behavioral needs and in the long term it is not in the interest of science, because socially-deprived subjects are stressed, not normal subjects, and the generality of any findings and their application to normal populations are doubtful in the extreme.

As the editor of a book on the care, housing, and psychological well-being of captive nonhuman primates, and a former member of the American Psychological Association's Committee on Animal Research and Ethics, I am delighted to see a clear statement of the importance of environmental enrichment. This is important for all subjects, but especially important for socially-isolated subjects, who otherwise develop a variety of behavior patterns symptomatic of severe stress.

As a former member of the American Psychological Association's Committee on Animal Research and Ethics, I am pleased to see the statement that "Blanket, program-wide departures from the Guide for reasons of convenience, cost, or other non-animal welfare considerations are not acceptable." I know you are being bombarded with complaints from biomedical and biological researchers that they cannot carry on their scientific work under the Guide's specifications. If they cannot carry on research on animals in a humane way and with respect for the needs of the animal subjects, they are in the wrong field. Let them become bankers or financiers.

         
7 01/23/2012 at 02:17:58 PM Self     70% of respondents stated concern with cost of implementing the 8th Edition because it will affect their bottom line. They have gotten away with sub standard care for years and want business to continue as usual. please implement this.

i agree that that an institutions"s animal housing practices must be species_specific:appropriate for the animals and in compliance with all applicable federal and local regulartory requirements

this is logical and fair. We are 10 years behind Europe in this regard. Please implement this.

Again logical, fair and humane. Nothing you will get voluntarily from those benefiting from these animals. please implement this.

again, well stated logically thought out.

yes, you are speaking of what in another time would have been humane treatment. today that needs to be defined and sadly, legislated. please implement.

well stated please implement

please implement.ple

please implement.

Horrible that this even has to be legislated. please implement

yes, i am in support of this as well. please implement. you are hearing protests from those who profit. i wonder what percentage of objection would come from average citizens who are not employed in and profiting from the use of these animals in outdated and redundant 'scientific' process. Know that these are long overdue and take a stand knowing you are representing the majority of us who just want some modicum of decency delivered to these creatures. thank you so much.

8 01/24/2012 at 03:24:15 PM Self                 The 8th edition of the "Guide's" language requiring the use of pharmaceutical grade compounds received much comment. Almost all this comment was against this requirement. However, OLAW has decided to leave this part of the Guide essentially unchanged. This regrettable as this requirement does nothing to improve animal welfare or science, and does much harm. Alternatives to the proposed guidance exist that might achieve both OLAW's aims and not impede the improvement of human welfare through scientific discovery. The regulation requiring the use of pharmaceutical grade (by which is meant FDA approved or USP-National Formulary standards or British Pharmacopeia listed) is not a performance standard. Rather, this is a mandated requirement for which each exception must be justified. The basis for this requirement is unclear. Currently, the use of pharmaceutical grade drugs in pharmacological research in animals is rare. Problems resulting from the use of non-pharmaceutical grade drugs in animal research are equally rare. However, problems related to the use of pharmaceutical grade drugs, as defined, are likely to be pervasive. These preparations are designed for clinical use, rather than for research use. Thus, dose, volume, and vehicle cannot be rigorously controlled. Further, most approved pharmaceutical preparations contain filler products that preclude the administration of these compounds by common routes of administration in animals. Finally, many, perhaps most, of the compounds used for research purposes will not exist in any form that would be classified as pharmaceutical grade. Thus, this regulation would result in so many exceptions that it would become a mockery, while at the same time impeding needed research that will save and improve human lives. I would recommend that this guidance apply only to the clinical use of compounds (i.e., use related to maintaining the health of the animal or alleviating pain and distress), and that it not apply to the research use of compounds including non-survival studies.

     
9 01/24/2012 at 10:19:58 PM Self     While I agree that cost cannot be the overriding factor in decisions related to animal welfare in PHS-funded research, there is not scientific evidence aviailable that the new standards provide an improvement in animal welfare. A higher cost without improvement in aninmal welfare, if this is the case, could be considered ethically problematic, since without producing a benefit less potentially life-saving research potentially reducing human suffering could be performed.

      There is no clear scientific evidence showing that the new caging specifications for mice provide a benefit for the animals. NIH should fund grant studying animal welfare under different housing conditions to provide a scientific basis for the recommendation in the guide.

  A major problem for pharmacology research is that "pharmaceutical grade" drugs are designed for use in humans or animals typically larger than mice. Dosing and application requirements frequently vary for different species. Many "pharmaceutical grade drugs" can therefore simply not be used in mice. Moreover, in pharmacological research, it is imperative that the vehicle for a drug is tested as a control, not just saline if the vehicle is not saline. Indeed, the activity of valproate as an antiepileptic drug was discovered when valproate was tested separately as the vehicle control in which other experimental compounds had been dissolved. In most cases, it is impossible to obtain the "vehicles" of "pharmaceutical grade" drugs from the manufacturers.

     
10 01/25/2012 at 10:43:39 AM Self     While I as an investigator agree that cost cannot be the overriding factor in decisions related to animal welfare, it remains a fact that these new regulations require significantly more funds in order to implement new 'musts' and 'shoulds', which will in turn require more money from our funding sources. As it stands there is simply not enough time to procure this additional funding before these rules take effect. Please allow us time to make these changes.

                 
11 01/25/2012 at 04:04:04 PM Self     Although cost alone may not be an overriding factor in animal welfare decisions, it definitely needs to be taken into consideration especially for institutions that rely heavily on NIH funding to sustain a viable animal care program. One change that I see as particularly problematic is the new guideline on rodent housing. It has far reaching implications beyond just the cost of purchasing more caging, including but not limited to, the ever present concern for additional space and technical support. Where is the money going to come from to implement this change particularly in a time when funding has dropped to an abyssmal level? Most importantly,there have been no data supplied to support the new recommendations so to impose a costly change for no benefit in animal welfare makes it even more unpalatable.

                 
12 01/25/2012 at 04:09:36 PM Self     If "performance standards" are the most important component of PHS oversight of animal programs, the arbitrary changes in cage sizes for several species is inconsistent with this rhetorical goal. OLAW did not present evidence that the cage sizes approved in the previous Guide were in any way harmful to animals, or compromised animal welfare. Without evidence-based justifications for the cage size changes specified in the 8th edition of the Guide, the overall credibility of OLAW is seriously flawed.

The assumption that institutions and individual researchers should be able to finance costly cage changes without any fiscal assistance from the NIH ignores the reality of limited research dollars in a struggling economy. If research is still an NIH priority, then forcing scientists to divert precious research dollars to buy cages to satisfy a seemingly arbitrary and unjustified bureaucratic directive will erode our primary mission. In this instance, and throughout the 8th edition of the Guide, many of the changes appear designed to advance the agenda of the well-funded organizations, such as the Humane Society of America, that are opposed to any and all scientific research with animals.

If "performance standards" are the most important component of PHS oversight of animal programs, the arbitrary changes in cage sizes for several species is inconsistent with this rhetorical goal. OLAW did not present evidence that the cage sizes approved in the previous guide were in any way harmful to animals, and compromised animal welfare. Without evidence-based justifications for the cage size changes specified in the 8th edition of the guide, the overall credibility of OLAW is seriously flawed.

It appears that "outcome- based performance standards" have been ignored in formulating a position on "social housing". Individual housing has not been shown to result in abnormal behaviors suggestive of stress when appropriate environmental enrichment and visual, auditory, olfactory contact with companion animals in the room is provided. Beyond an anthropomorphic "face validity", there is no objective behavioral or hormonal evidence that "social-housing" of adult nonhuman primates improves animal welfare or "psychological wellbeing". There is considerable evidence that adult males and females may bite off fingers, toes, tails, and lacerate the companion animal. If an investigator cutoff an animals fingers, toes, and tails without anesthesia, and without post operative pain relief medication, this would be animal cruelty!!!

Does it really serve the goal of improving animal welfare to place animals at risk for such mutilations through "social housing"????????

      It was reassuring to learn that OLAW recognizes that "it is frequently necessary to use investigational compounds, veterinarian-or pharmacy-compounded drugs, and/or Schedule I controlled substances to meet scientific and research goals." However, if "performance standards" were used to formulate this new and very costly requirement, OLAW would have also recognized that there is no evidence that the use of non-pharmaceutical grade drugs over the past several decades has compromised animal health or wellbeing. Obviously, investigators have a vested interest in using study drugs that are not toxic, and do not threaten the health of the animal subject, or interfere with the interpretation of research results.

The common practice of using non-pharmaceutical grade substances in animal research has been judged to be in some way dangerous to animals without objective evidence to support this conclusion. Again, this OLAW position appears to be based primarily on cosmetic, "face validity" considerations that ignore the lack confirmatory evidence, and the unjustified increases in research costs. It appears that lobbyists for organizations such as the Humane Society of America have become increasingly skillful at persuading regulators to adopt positions designed to significantly increase the cost of conducting animal research. It is a tragedy for American science that the NIH is vulnerable to the influence of groups opposed to the use of animals in research.

     
13 01/26/2012 at 11:14:31 AM Self     I strongly concur with NABRs position that 'Principle II of the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training, which OLAW references, states, "Procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society." I believe that consideration of costs (especially unnecessary increases therein - [my addition]) is of great benefit to society and would therefore be congruent with Principle II.' It is NOT a benefit to society to require publicly-funded research institutions to spend scarce research dollars on new caging when it has not been generally accepted in the industry or the literature that the animals will actually benefit from the larger cages 'recommended.' Obfuscating the issue by saying that these new cage size 'recommendations' are merely a 'starting point' only serves to introduce more confusion to the issue. Wrong way to go. Recommend that you adopt NABRs suggestion for clarifying this Position Statement (PS).

Obfuscating the issue by saying that these new minimum cage size 'recommendations' are merely a 'starting point' only serves to introduce more confusion to the issue. Wrong way to go. Lose the murky 'starting point' terminology and adopt NABRs more clearly-written recommendation.

Adopt NABRs well-reasoned rebuttal to this regulatory over-reach.

  The world-wide literature on this issue is all over the spectrum, and there is definitely no consensus that larger cages benefit the animals. In light of the strong connection that NABR makes between Principle II (see my comment 1) and the benefit to society represented by not requiring in any way, shape or form that institutions spend scarce research dollars complying with very-poorly justified increases in cage sizes. You have to recognize that OLAW's adoption of the new Guide will cause it to rapidly assume the weight of 'regulation'! Remove the blanket prohibition to blanket exceptions. Considering the lack of agreement as to benefit to the animals and therefore the necessity of going to larger cages, if an IACUC feels that the caging in which their institution has been successfully housing and breeding rodents for years continues to be acceptable for all the reasons mentioned above, requiring them to issue serial exceptions protocol-by-protocol is disingenuous and punitive.

  Adopt NABR's recommendation to replace the words 'for research' with the words 'as medications'.

     
14 01/26/2012 at 02:27:58 PM Self     Companies and Academic institutions have plenty of resources to afford the necessary changes are justified. When an institution with it's' highly paid administrators only have themselves to blame for financial shortfalls of maintaining the program. This is do impart to facility management oversight or lack thereof, of some managers and some directors that look the other way until an inspection, upgrades or changes in the rule making process they actually at times are part of themselves. Case in point is the following recent article titled that actually fits multiple problem areas in the "Guide" that the industry is opposed to any such changes to status quo Labs Size Up New Guidelines for Rodent Cages Joseph Thulin, DVM, Director of the Biomedical Resource Center, comments on the NIH's new guidelines for rodent housing and care. National Public Radio, 1-16-2012 http://www.wbur.org/npr/145172737/labs-size-up-new-guidelines-for-rodent-cages

This institution benefits off of tax dollars big time as a PRIVATE School. They just built a new research facility 4-5 years ago complete with ALL NEW CAGING for Rodents. Full well knowing the industry changes coming down the pike, the facility leadership and institution leadership ignored and fully knew of the impending changes that were coming. Now the facility leadership (30+ years experience) notes in this NPR interview that LITTLE information is known in this area of cages sizing much less cost structures of these impacts when making business decisions and the impact on the animals. As an experienced (?) influential / authority figure in the AAALAC arena as a council member one really has to step back and ask what lack of information was used to determine the call for setting a minimum standard for cage sizing.

Housing performance standards are really behind the science. Items like corncob bedding materials is a largely used product in the industry rodent housing caging systems as a contact bedding. Though posed in the "Guide" as need to be clean, uncontaminated the industry and it's program fiduciaries (managers, AAALAC...) ignore the science of this contaminated product and its use for this purpose. By ignoring this product use has an extrapolation on the animal health and wellbeing more so than the cage sizing issue by itself. When reviewing bio burden levels of contamination within these housing systems it is noted that the bedding is contaminated before animals are housed BEFORE they are changed into a CLEAN cage. When a cage is now allowed to go 1,2,3 weeks between cage changes this bio burden continues to grow well beyond an exposure time that would mandate an FDA recall on exposure limits if they knew. The accrediting agency (AAALAC) is the same that reviews,inspects and proposes fixs' to overt health potential exposures as part of its' due diligence and accountability. How long until this is corrected?

no comment

The guide spells out the use of these beneficial objects as noted as devices that animals climb on or through, perch on, or nest in contribute to, rather than detract from, the animal's living space and need not be subtracted from the floor dimensions. As noted above there is a distinct synergy between cage size, bedding type ,amount and use, cage nesting material and location as to performance of the cage life (clean to dirty). This cage life with nesting material on the floor blocks airflow and is causal for shortened cage life increasing labor in the facility operations. Elevated platforms provide true extra space to the internal cage dimension without sacrificing floor space use. Actually some currently used caging used in the industry today can use these devices as a standard piece of equipment for that manufacturer. If ALL manufacturers interested in helping the industry should adopt this strategy for the industry instead of re-inventing a total new cage rack caging system that 60% of the industry is up in arms about costing too much.

If the individual investigator applied for and is granted a departure then the others follow suite, when does the whole facility get to the point that it becomes a blanket coverage.

Again , the above listed section is totally at the discretion of the attending Veterinarian. We used to keep track of many thousands of leaky water valves and neo-natal mouse / rat pup deaths that after years of tracking were never reported to OLAW or AAALAC council and were stopped in recording because of no need to track anymore idea. Basically this area should review all areas using the statement: IF YOU DON'T PUT THE TRUTH ON THE TABLE... THERE WILL NEVER BE A SENSE OF URGENCY TO IMPOVE.

no comment

no comment

Big issue in regards to food (like rodents) is they are born and bred on one chow to be introduced into a facility to be changed onto a completely different chow of orientation. When you study medical research progress using genetics and such could be very detrimental to the scientific data much less the repeat use of animals because of this oversight. When given preference testing of feeds there is a distinct difference in daily food consumptions. Is it a welfare concern that you feed an animal a different diet it was born and raised on in an to do research?

no comment

no comment

15 01/26/2012 at 03:34:10 PM Self     As OLAW noted, nearly 70% of individuals and institutions responding to the previous comment period raised concerns about the cost of implementing the 8th Edition of the Guide. Most of these comments were limited to examples of spending scarce research funds in the absence of reliable scientific data demonstrating that the expenditure would actually benefit animal welfare. I believe that OLAW should emphasize animal welfare and integrity of research findings as the primary factors in decisions related to the housing and use of animals in PHS-funded research.

Principle II of the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training, which OLAW references, states, "Procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society." I agree with this statement and further believe that consideration of costs is also of benefit to society and would therefore be congruent with Principle II. I recommend that OLAW revise the position statement as follows:

Animal welfare and the integrity of research findings, rather than costs alone, should be the primary factors in decisions related to assuring compliance with the recommendations in the Guide in PHS-funded research. (See U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training Principle II.) Assured institutions are responsible for compliance with the Guide. OLAW believes compliance can be best accomplished using teamwork, professional judgment, and experience. The PHS Policy and the Guide define the minimum standards ("musts") and performance standards ("shoulds") that OLAW expects of Assured institutions. OLAW recognizes there are many ways to achieve humane animal care and use. An institution may use an alternative approach if the approach satisfies the requirements of the PHS Policy as determined by OLAW. In many instances, institutions and IACUCs elect to exceed the standards. This is not required and can add expense to the program.

I believes OLAW should revise this position statement. It indicates that, "the Guide's space recommendations are a starting point for addressing space needs..." OLAW's use of the use of the phrase "starting point" in conjunction with the titles of the tables on pages 57-63, Recommended Minimum Space, are likely to cause confusion and imply the recommendations contained in the table are in fact minimum requirements ("must" statements). The position statement's use of the term "starting point" is not consistent with OLAW's preceding statement that "an institution may elect to follow a different course of action than a 'should' statement in the Guide if that action results in an equivalent outcome and is reviewed and approved by the IACUC." I recommend OLAW clarify this position statement to read as follows:

OLAW concurs with the recommendations of the Guide that performance standards are to be applied to housing issues. (See Guide pages 50-63.) Outcome-based performance standards are paramount when evaluating cage or pen space for housing animals used for research, research training, and biological testing. While the Guide's space recommendations are accepted reference points for addressing space needs, performance standards allow flexibility to improve animal welfare and scientific research. An institution's animal housing practices must be species-specific, appropriate for the animals, and in compliance with all applicable federal and local regulatory requirements.

  I would like to commend OLAW for addressing environmental enrichment in its position statements. It succinctly addresses the concerns of many of our members who also believe enrichment devices "…contribute to, rather than detract from, the animal's living space and need not be subtracted from the floor dimensions."

I believe revisions are needed to this position statement. OLAW includes the following language, "… expects institutions to use the Guide's space recommendations as a starting point." OLAW's use of the phrase "starting point" in conjunction with the titles of the tables on pages 57-63, Recommended Minimum Space, are likely to cause confusion as they appear to imply the recommendations contained in the table are in fact minimum requirements ("must" statements). The position statement's use of the term "starting point" is not consistent with OLAW's preceding statement that "an institution may elect to follow a different course of action than a 'should' statement in the Guide if that action results in an equivalent outcome and is reviewed and approved by the IACUC." I recommend that OLAW clarify this position statement to read as follows:

OLAW supports the Guide's approach to applying performance standards to achieve specified outcomes and expects institutions to use the Guide's space recommendations in that process. Adjustments to recommendations for primary enclosures may be made at the institutional level by the IACUC. The IACUC should critically evaluate objective measures of outcome-based performance. The Guide identifies examples of performance indices to assess adequacy of housing including:

  I believe revisions are needed to the position statement addressing non-pharmaceutical-grade substances. OLAW's position statement includes the following language, "The IACUC is responsible for evaluating the potential adverse consequences of such agents when used for research." I recommend OLAW clarify this position statement to read as follows:

The IACUC is responsible for evaluating the potential adverse consequences of such agents when used as medications. Doing so would reinforce the intent of the USDA Policy # 3 Pharmaceutical-Grade Compounds in Research, which states, "Investigators are expected to use pharmaceutical-grade medications whenever they are available, even in acute procedures." The inclusion of the words "in research" in the position statement implies that this policy extends to test articles which clearly should not be the intent.

     
16 01/26/2012 at 04:07:38 PM Organization University of Cincinnati Dept of Emergency Medicine Cincinnati, OH 45267-0769 Minimum standards, no matter what the cost, are an acceptable part of overhead.

    Species specific enrichment materials should be mandatory. It should be considered in acceptable housing.

    Close attention paid to pre-procedural and post-procedural analgesics as well as documented pain monitoring is a bare minimum. NOT providing analgesics for post-surgery pain, should be the exception rather than the norm. I find that investigators tend not to administer analgesics because it is inconvenient or the agents are not available.

Close monitoring of food and water deprivation and stiff fines deviations should be employed. Inattention to this matter has led to horrific cannibalism within cages.

Close attention paid to pre-procedural and post-procedural analgesics as well as documented pain monitoring is a bare minimum. NOT providing analgesics for post-surgery pain, should be the exception rather than the norm. I find that investigators tend not to administer analgesics because it is inconvenient or the agents are not available.

 
17 01/27/2012 at 02:09:24 PM Organization American Societ of Laboratory Animal Practitioners Memphis, TN       The Position Statement comments that "Animals should not be subjected to the presence of items that they find distressing or may harm them." We are concerned that emphasis of the notion that some species are upset by the introduction of novel items may result in the false impression that animals do not enjoy having novel items presented to them. Indeed, many species enjoy new items and can become bored when there is no exposure to novel items. We suggest that the Position Statement should instead offer that environmental enrichment programs identify those items that cause distress or harm to animals, and remove those items, a position which is more consistent with the discussion of environmental enrichment programs in the Guide.

  The OLAW position statement indicates that "OLAW recognizes the necessity of cost-efficiency and the valid concerns of the community about program cost, but those concerns must be balanced with animal welfare." ASLAP is concerned that, as worded, the position statement gives the false impression that program efficiency can be, or always is, at odds with animal welfare. Programs can operate efficiently and maintain excellent animal welfare standards. Federally funded programs should be encouraged to operate efficiently and balance animal welfare standards. We recommend removal of wording which suggest that concerns related to cost and efficiency are incompatible with the goal of animal welfare.

Whereas OLAW's position statement states, "The IACUC is responsible for evaluating the potential adverse consequences of such agents when used for research," ASLAP recommends that OLAW clarify this position statement to read as follows: "The IACUC is responsible for evaluating the potential adverse consequences of such agents when used as medications." This revision would provide clarification relevant to the safe and judicious use of compounds in research animals. Further, doing so would reinforce the intent of the USDA Policy # 3 Pharmaceutical-Grade Compounds in Research, which states, "Investigators are expected to use pharmaceutical-grade medications whenever they are available, even in acute procedures." The inclusion of the words "for research" implies that the OLAW policy extends to test articles which clearly should not be the intent.

     
18 01/27/2012 at 02:25:48 PM Organization Johns Hopkins University Baltimore, MD         Cage space: The Guide and OLAW's position statement on cage floor space for female mice with litters is confusing. The Guide clearly says that a female with a litter will require a minimum of 51 square inches of space, but it then comments that "other breeding configurations may require more space and will be dependent on considerations such as number of adults and litters, and size and age of litters". No reference is provided for this space requirement of more space for females with litters, and in fact, some of the references cited to support space needs state that mice may do better when given less space then, more. The need to provide a female with a litter a specific amount of floor space has nothing to do with the breeding configuration that is being used to produce that litter. Until the female delivers her litter, her space requirement if housed in a group, is determined by her body weight. It appears that this space requirement has been incorrectly copied from the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes. The European convention states that the minimum enclosure size for breeding mice is 330 sq cm, which is equivalent to 51.15 square inches. It further says that this amount of space is "for a monogamous pair (outbred/inbred) or a trio (inbred). For each additional female plus litter 180 sq cm should be added".

In its position statement OLAW states that "Rodent cages of the size commonly used in the United States may be appropriate for trio breeding. The 8th Edition of the guide does not add specific, additional engineering standards for breeding configurations. This empowers institutions to determine appropriate housing." While this statement is correct, it is erroneous, because a female with a litter is not a breeding configuration and the new space requirement for a female with a litter is clearly a new engineering standard which OLAW has further stated is a "starting point for addressing space needs".

Robert J. Adams DVM Johns Hopkins University

         
19 01/27/2012 at 04:39:30 PM Organization Taconic Hudson NY Adoption of the new Guide as planned by NIH is likely to have a significant economic impact on PHS-assured institutions. Research institutions are already under extreme financial strain that may be compounded by continued NIH budget pressures in FY 2012 and beyond.

Since rats and mice are utilized as a research model by the tens of millions, the proposed change in breeding cage size will materially alter the budgetary impact of NIH grants. We are concerned about the magnitude of the following financial consequences of the new Guide. The new Guide will dramatically increase the cost of research animals: As previously expressed by the Laboratory Animal Breeders Association of North America in comments on the pre-publication version, the new Guide's breeding cage requirements will have a major impact on their businesses. They estimate their total initial capital investment for changes will be approximately $500 million. Their recurring annual operating cost is calculated to be $155 million. These dramatic increases will be passed on to their research institution customers, including the NIH intramural program, in the form of higher research animal prices. PHS grants as well as the NIH budget will be affected. The new Guide will increase PHS grant expenses beyond the direct cost of laboratory animals. The cost of rats and mice will certainly increase as breeders pass on the additional cost of meeting the new recommendations for breeding cages. In addition, the per diem charged to principal investigators for animal care by PHS-assured institutions will increase. In order to meet these new recommendations, institutions like ours will either need to change the existing caging systems or increase the number of cages in use, thereby increasing per diem charges. While the cost impact of addressing the many new and revised recommendations is unclear at this time, there are certain to be other costs associated with programmatic changes resulting from the new Guide that will be passed on to the investigators. We believe strongly the above concerns must be addressed before the 2011 Guide is adopted and implemented by NIH. Taconic requests that the agency clarify the provisions in the new Guide are not binding on PHS-assured institutions and alternative approaches to those specified in the Guide may be acceptable. We strongly urge NIH to state clearly and unambiguously that adherence to all of the provisions in the Guide is not mandatory. We further recommend NIH re-issue a notice for public comment that permits an opportunity to provide meaningful comments on the substantive provisions in the Guide so the full effects on the animal research community are fully understood. Only after such information is made available can NIH make an informed decision on the best manner in which to implement the Guide.

Excellent new reference information from the peer-reviewed scientific literature has been added to the 2011 Guide in support of many subject areas. However, scientific evidence is lacking for changes in at least one major subject, the "recommended minimum space" for animals by species (Tables 3.2 - 3.6). In the Preface of the 8th Edition, the Committee acknowledges that scientific information is insufficient when it comes to space and housing needs of laboratory species, yet still includes new requirements that will have a significant impact on the research community. While acknowledging that many variables must be considered when housing animals in the laboratory, the new Guide offers no justification from the scientific literature as to why minimum space requirements have been changed and why specific increases in dimensions were selected. Because the minimum cage sizes are expressed in exact dimensions by species in the Guide, they amount to fixed engineering standards with which PHS-assured institutions must comply. The revision of minimum space for laboratory rodents (Table 3.2) is causing the greatest concern for Taconic. For the first time the new Guide indicates recommended space for a "Female + litter" for both mice and rats, specifying a floor area of 51 in sq (330 cm sq) for the former housing group and 124 in sq (800 cm sq) for the latter. This designation would exclude the current practice of housing rodent pairs (male and female) and trios (one male, 2 females) together continuously for breeding purposes in the standard cage used by most facilities. The new European Directive for the Protection of Animals Used in Scientific Procedures (2010/63/EU) indicates the same floor space requirements, but uses the term "breeding" cages for rodent pair/trio housing, thus permitting the practice of housing breeding pairs and trios in existing cages (See Attachment 1). Because the new Guide will require larger caging for standard breeding practices, PHS-assured institutions and NIH contractors will be faced with the prospect of replacing existing cages for breeding pairs and trios with larger cages. Further complicating the situation is the fact that the 2011 Guide states (p 60-61), "Floor space taken up by food bowls, water containers, litter boxes and enrichment devices (e.g. novel objects, toys, foraging devices) should not be considered part of the floor space." There are significant operational, logistical, physical plant and financial issues associated with these recommendations, which should be commented upon in more detail by individual institutions and commercial laboratory animal breeders. The issue related to rodent breeding cages was raised in comments on the pre-publication version of the Guide released in June 2010. The final version of the Eighth Edition published in January of this year, only added an asterisk to the title of Table 3.2 with the related note: "* The interpretation of this table should take into consideration the performance indices described in the text beginning on page 55." OLAW currently has a "frequently asked questions" section published on its website that leads us to believe the flexibility of institutions to use performance based standards in determining a policy on cage sizes will be more limited than implied by the language beginning on page 55 of the Guide. The text of that posting appears below: May the IACUC approve deviations from the Guide for rodent (mice and rats) cage density? - OLAW supports the Guide's approach to applying performance standards to achieve specified outcomes, and expects institutions to use the Guide's engineering standards as a baseline. The Guide clearly states that the need for adjustments to the recommendations for primary space enclosures should be made at the institutional level by the Institutional Animal Care and Use Committee (IACUC) and should be based on performance outcomes. The Guide further identifies examples of performance indices to assess adequacy of housing, including health, reproduction, growth, behavior, activity, and use of space (Guide, pages 25-26). IACUC determinations of the need for adjustments in the space recommendations should be based on veterinary considerations or scientific justification relative to the nature of the protocol and its requirements. Blanket, program-wide deviations from the Guide for reasons of convenience, cost, facility capacity, and other non-animal welfare considerations are not acceptable. IACUC approved deviations from the Guide must be clearly documented and reflect the scientific or veterinary justification relevant to the action. For example, the Guide notes that space allocations should be reviewed and modified as necessary to address individual housing situations and animal needs such as prenatal and postnatal care. One way to address housing for maternally dependent litters of mice and rats is to consider them as single entities with their parent(s) until the pups begin actively moving about the cage, at which point multiple parental/litter groups should then be housed according to housing conditions recommended in the Guide.

               
20 01/27/2012 at 04:45:55 PM Self     Adoption of the new Guide as planned by NIH is likely to have a significant economic impact on PHS-assured institutions. Research institutions are already under extreme financial strain that may be compounded by continued NIH budget pressures in FY 2012 and beyond.

Since rats and mice are utilized as a research model by the tens of millions, the proposed change in breeding cage size will materially alter the budgetary impact of NIH grants. I am concerned about the magnitude of the following financial consequences of the new Guide. The new Guide will dramatically increase the cost of research animals: As previously expressed by the Laboratory Animal Breeders Association of North America in comments on the pre-publication version, the new Guide's breeding cage requirements will have a major impact on their businesses. They estimate their total initial capital investment for changes will be approximately $500 million. Their recurring annual operating cost is calculated to be $155 million. These dramatic increases will be passed on to their research institution customers, including the NIH intramural program, in the form of higher research animal prices. PHS grants as well as the NIH budget will be affected. The new Guide will increase PHS grant expenses beyond the direct cost of laboratory animals. The cost of rats and mice will certainly increase as breeders pass on the additional cost of meeting the new recommendations for breeding cages. In addition, the per diem charged to principal investigators for animal care by PHS-assured institutions will increase. In order to meet these new recommendations, institutions will either need to change the existing caging systems or increase the number of cages in use, thereby increasing per diem charges. While the cost impact of addressing the many new and revised recommendations is unclear at this time, there are certain to be other costs associated with programmatic changes resulting from the new Guide that will be passed on to the investigators. I believe strongly the above concerns must be addressed before the 2011 Guide is adopted and implemented by NIH. I am requesting that the agency clarify the provisions in the new Guide are not binding on PHS-assured institutions and alternative approaches to those specified in the Guide may be acceptable. I strongly urge NIH to state clearly and unambiguously that adherence to all of the provisions in the Guide is not mandatory. I further recommend NIH re-issue a notice for public comment that permits an opportunity to provide meaningful comments on the substantive provisions in the Guide so the full effects on the animal research community are fully understood. Only after such information is made available can NIH make an informed decision on the best manner in which to implement the Guide.

Excellent new reference information from the peer-reviewed scientific literature has been added to the 2011 Guide in support of many subject areas. However, scientific evidence is lacking for changes in at least one major subject, the "recommended minimum space" for animals by species (Tables 3.2 - 3.6). In the Preface of the 8th Edition, the Committee acknowledges that scientific information is insufficient when it comes to space and housing needs of laboratory species, yet still includes new requirements that will have a significant impact on the research community. While acknowledging that many variables must be considered when housing animals in the laboratory, the new Guide offers no justification from the scientific literature as to why minimum space requirements have been changed and why specific increases in dimensions were selected. Because the minimum cage sizes are expressed in exact dimensions by species in the Guide, they amount to fixed engineering standards with which PHS-assured institutions must comply. The revision of minimum space for laboratory rodents (Table 3.2) is causing the greatest concern. For the first time the new Guide indicates recommended space for a "Female + litter" for both mice and rats, specifying a floor area of 51 in sq (330 cm sq) for the former housing group and 124 in sq (800 cm sq) for the latter. This designation would exclude the current practice of housing rodent pairs (male and female) and trios (one male, 2 females) together continuously for breeding purposes in the standard cage used by most facilities. The new European Directive for the Protection of Animals Used in Scientific Procedures (2010/63/EU) indicates the same floor space requirements, but uses the term "breeding" cages for rodent pair/trio housing, thus permitting the practice of housing breeding pairs and trios in existing cages (See Attachment 1). Because the new Guide will require larger caging for standard breeding practices, PHS-assured institutions and NIH contractors will be faced with the prospect of replacing existing cages for breeding pairs and trios with larger cages. Further complicating the situation is the fact that the 2011 Guide states (p 60-61), "Floor space taken up by food bowls, water containers, litter boxes and enrichment devices (e.g. novel objects, toys, foraging devices) should not be considered part of the floor space." There are significant operational, logistical, physical plant and financial issues associated with these recommendations, which should be commented upon in more detail by individual institutions and commercial laboratory animal breeders. The issue related to rodent breeding cages was raised in comments on the pre-publication version of the Guide released in June 2010. The final version of the Eighth Edition published in January of this year, only added an asterisk to the title of Table 3.2 with the related note: "* The interpretation of this table should take into consideration the performance indices described in the text beginning on page 55." OLAW currently has a "frequently asked questions" section published on its website that leads us to believe the flexibility of institutions to use performance based standards in determining a policy on cage sizes will be more limited than implied by the language beginning on page 55 of the Guide. The text of that posting appears below: May the IACUC approve deviations from the Guide for rodent (mice and rats) cage density? - OLAW supports the Guide's approach to applying performance standards to achieve specified outcomes, and expects institutions to use the Guide's engineering standards as a baseline. The Guide clearly states that the need for adjustments to the recommendations for primary space enclosures should be made at the institutional level by the Institutional Animal Care and Use Committee (IACUC) and should be based on performance outcomes. The Guide further identifies examples of performance indices to assess adequacy of housing, including health, reproduction, growth, behavior, activity, and use of space (Guide, pages 25-26). IACUC determinations of the need for adjustments in the space recommendations should be based on veterinary considerations or scientific justification relative to the nature of the protocol and its requirements. Blanket, program-wide deviations from the Guide for reasons of convenience, cost, facility capacity, and other non-animal welfare considerations are not acceptable. IACUC approved deviations from the Guide must be clearly documented and reflect the scientific or veterinary justification relevant to the action. For example, the Guide notes that space allocations should be reviewed and modified as necessary to address individual housing situations and animal needs such as prenatal and postnatal care. One way to address housing for maternally dependent litters of mice and rats is to consider them as single entities with their parent(s) until the pups begin actively moving about the cage, at which point multiple parental/litter groups should then be housed according to housing conditions recommended in the Guide.

               
21 01/30/2012 at 12:18:36 PM Organization Council on Governmental Relations (COGR) Washington DC The Council on Governmental Relations (COGR) appreciates the reaffirmation of OLAW's support and high regard for performance standards developed by the research community. We acknowledge that cost cannot be an overriding factor in decisions related to animal welfare and do not believe any assured institution would use costs as a factor at the expense of the health and welfare of animals under their control. However, an institutional plan and schedule for implementation of the 8th Edition of the Guide, required by December 31, 2012, may reflect the management of any related costs.

COGR recognizes the distinction being made between the use of "must" versus "should" statements; a minimum standard in the former case, a performance standard in the latter. It is and will be important that inspectors or site visitors from OLAW recognize that distinction when reviewing an institution's program of care and use. The consistent application of the Guide and policy will ensure a fair and effective evaluation of an institution's compliance.

COGR is concerned that OLAW's endorsement of the Guide's space recommendations as a "starting point" effectively establishes a minimum requirement for cage and pen space and directly undermines OLAW's stated support of outcomes-based standards. We recommend changing the sentence to read "While the Guide's space recommendations are USEFUL REFERENCE POINTS for addressing space needs, performance standards allow flexibility to improve animal welfare and scientific research."

    COGR is concerned that OLAW's "expectation" that institutions will use the Guide's rodent housing recommendations "as a starting point" establishes a minimum requirement for rodent housing and directly undermines OLAW's stated support of outcomes-based performance standards.

The reliance on performance standards is particularly acute in the Guide and OLAW's treatment of cage floor space for females with litters. As we noted in our original comment, some of the scientific citations used to support the space requirement conflict with the recommendation. Furthermore, the distinction in the configuration for breeding may not be appropriate for a "female with litter." Thus, the need to resolve this confusion will require a judgment by the IACUC.

COGR recommends that OLAW affirm its support of outcome-based performance standards by revising the first sentence of the statement to read: "OLAW supports the Guide's approach to applying performance standards to achieve specified outcomes and ENCOURAGES INSTITUTIONS TO USE THE GUIDE'S SPACE RECOMMENDATIONS IN ITS DETERMINATION OF APPROPRIATE STANDARDS."

  COGR urges OLAW to clarify the position statement concerning non pharmaceutical-grade substances to align with the cited USDA Animal Care Manual Policy 3 by affirming the IACUC's responsibility for evaluating adverse consequence of the use of non-pharmaceutical-grade substances when used as MEDICATIONS. This approach would be consistent with the USDA policy and avoid the implication that the position statement extends to test or research articles which, we believe, should not be the intent.

     
22 01/30/2012 at 12:30:54 PM Organization The Jackson Laboratory Bar Harbor, Maine         The Jackson Laboratory wishes to confirm our support of OLAW's position statement in the use of formal performance standards to achieve specified outcomes when establishing standards for housing rodents in breeding groups. It is our understanding that, when OLAW states, "Adjustments to recommendations for primary enclosures may be made at the institutional level by the IACUC", the approval of any protocol requesting deviation from Guide-recommended group housing densities be based upon the professional judgment and experience of voting members of the IACUC in light of performance indices described in the Guide, such as health and reproductive behavior, as they are established at each institution. We believe in OLAW's emphasis on the need for scientific evidence to buttress regulatory changes. Charles E. Hewett, Ph.D., Institutional Official

         
23 01/30/2012 at 03:34:56 PM Organization American Society for Pharmacology & Experimental Therapeutics Bethesda, Maryland             The Association for Pharmacology and Experimental Therapeutics (ASPET) comprises 4800 members who are experts in research across a wide range of pharmacology specialties, as indicated by the names of its divisions: Behavioral Pharmacology, Cardiovascular Pharmacology, Drug Discovery & Development Drug Metabolism, Molecular Pharmacology, Neuropharmacology, Toxicology, and Translational & Clinical Pharmacology.

ASPET appreciates OLAW's response to the 2010 public comment period in drafting a position statement to amplify its guidance on the research use of "Non-Pharmaceutical-Grade Substances." The position statement is helpful in a number of respects: (1) in explicitly recognizing that the use of investigational compounds and Schedule I controlled substances frequently is necessary to meet research goals, (2) in advising that IACUCs may establish acceptable scientific criteria within their institutions for use of non-pharmaceutical grade agents, rather than requiring IACUC review and approval on a case-by-case basis; and (3) in providing a definition of a pharmaceutical grade compound.

Though the position statement was responsive to concerns about the paperwork and review burden that a strict interpretation of the 8th edition of the Guide on this topic imposes, it still reflects a view of pharmacology research that is at variance with the realities and practice of the science. We are concerned that unless these issues are clarified for IACUCs and scientists alike, research that uses drugs and other chemicals in laboratory animals will be unnecessarily, and likely inadvertently, impeded. The far-reaching importance of this issue is clear given that pharmacology research in laboratory animals is a part of the portfolio of virtually every NIH Institute.

Below are specific comments on Position Statement 3.

Differentiation of clinical and research use of drugs:

The statement that OLAW and USDA agree that pharmaceutical grade chemicals must be used to avoid toxicity or side effects, as written, implies that the USDA has precluded use of 'non-pharmaceutical grade" chemicals in research procedures. To our knowledge, this is not the case. Rather, policies in the USDA/APHIS Policy Manual are restricted to interpretation of the Animal Welfare Act (AWA) Regulations with respect to covered species. Their Policy 3 interprets 9 CFR, Part 2, Section 2.31 "(d). (1). . . . Further, the IACUC shall determine that the proposed activities or significant changes in ongoing activities meet the following requirements:. . . . (i.v.) Procedures that may cause more than momentary or slight pain or distress to the animal will: (A) Be performed with appropriate sedatives, analgesics or anesthetics, unless withholding such agents is justified for scientific reasons, in writing, by the principal investigator and will continue for only the necessary period of time . . . . "

Thus we conclude that USDA Policy 3 covers only "sedatives, analgesics, or anesthetics" used to prevent pain/distress with species covered under the AWA. It does not pertain to those situations in which a drug is being used as a research tool or to study its effects, which is implied by the current wording in the OLAW position statement and in the 8th edition of the Guide itself. We urge that OLAW clarify a distinction in policy between drugs for clinical use in research animals and those selected for use to accomplish the scientific aims of the research.

Implications that drugs not formulated for clinical use are inferior for research use:

The first sentence of Position Statement 3 that ". . . pharmaceutical grade chemicals and other substances, when available, must be used to avoid toxicity or side effects that may threaten the health and welfare of vertebrate animals and/or interfere with the interpretation of research results," followed by "However, it is frequently necessary to use investigational compounds, veterinarian- or pharmacy-compounded drugs, and/or Schedule I controlled substances to meet scientific and research needs" attributes liabilities and risks to research compounds that do not apply. In fact, researchers are particularly sensitive to assuring that variables that would jeopardize the research and its interpretation are identified and controlled.

Furthermore, were researchers to attempt to use a preparation sold for clinical use for dose-effect evaluations, which are central to pharmacology research, they inevitably must manipulate that solution in ways that might indeed introduce the toxicity and uncontrolled variables that are the topics of OLAW's concern to the research. Specific problems with clinical use solutions for pharmacology research were covered in our submission during the comment period. We urge that the position statement wording be changed to remove the implication that drugs selected for research purposes will necessarily be inferior to those that have been formulated for clinical use.

We appreciate the inclusion of reference to Schedule I controlled substances as those that may be used in research, and also that footnote 3 also states that Schedule II-V drugs may be used in biomedical research. It would be helpful to include the reference to Schedules II-V in the body of the position statement. In addition, it would be reasonable to acknowledge the NIH/NIDA drug supply programs for funded researchers as a recognized source of drugs for animal research.

The definition of a pharmaceutical grade drug footnote 1 is an important step forward, and we appreciate that this has been adapted from guidance prepared by the NIH intramural research program. Given the concerns implied in the position statement regarding drug quality, we believe that the position statement should bring the issue of drug purity prominently into the discussion of the types of compounds that may be used appropriately in research. In fact, there are companies that, for decades, have been highly regarded vendors of compounds of excellent quality for laboratory animal research. These companies typically supply technical information on purity and other qualities of the compounds with each purchase. In many cases, these products are of equal or higher purity as those manufactured as USP grade. Exclusion of mention of such sources and their dependability could be taken by IACUCs to mean that their products are inferior for research needs, when, in fact, they are often the best quality for a research purpose.

Expertise necessary to formulate drugs for research use:

The position statement includes the possibility that research "drugs," (presumably solutions) may be compounded by a veterinarian. This suggests that researchers should be encouraged to turn their investigational drugs over to a veterinarian for preparation for research use. We suspect this is not what was intended. The link supplied to the AVMA website (in footnote 2 of the position statement) indicates that this AVMA policy was generated to permit veterinarians in clinical practice to prepare a drug from powder in case the one that was needed for clinical use were to be unavailable commercially, which is consistent with the policy expressed in USDA/APHIS Policy 3 regarding medications that are unavailable. We suggest that it would be inappropriate (and likely unwelcome) to ask institutional veterinarians to prepare research compounds for investigators.

The position statement also seems to urge researchers to turn powder forms of drugs over to a pharmacy for preparation of solutions, which is problematic. In addition to the practical and cost-related issues, the individuals most qualified to determine how to prepare and store compounds for a particular research use are most often the investigators themselves. Many research compounds must be used within a short period of time after being solubilized and/or stored under special conditions, and it is unrealistic to imply to IACUCs that locating a compounding pharmacy is a first choice for preparation of solutions for research. Investigators who carry out drug research typically are well versed in the considerations relevant to the compounds they are using; and have equipped their laboratories with the analytical balances, stirrers, pH meters, sonicators, etc. necessary for drug preparation. In fact, even with respect to medications for sedation, analgesia, and anesthesia that are unavailable in clinical use formulations, an investigator's laboratory may be better experienced and equipped to prepare these appropriately than are veterinary facilities at many research institutions.

With respect to compounds legally scheduled under the Controlled Substances Act, researchers who obtain these drugs by virtue of their approved DEA and state registrations have committed to procedures for secure storage, record-keeping and supervision of use by limited numbers of individuals. Turning such compounds over to another entity for formulation of solutions raises unnecessary legal complications in addition to those described above.

We agree with the position statement comment in the paragraph on non-survival studies that "professional judgment" of the investigator is the key element to determine that scientific issues are appropriately addressed in choice of formulation for a research study. We urge that the wording that implies that only veterinarians and pharmacists are qualified to prepare drugs for administration be revised to focus on the importance of the expertise of the investigator with respect to selection, handling, and use of compounds in research as the primary consideration.

Cost considerations and animal welfare:

We agree with OLAW that it is critical to take animal welfare into consideration in making choices of procedures and materials to use in laboratory animal research. Certainly one should not make poor choices of drugs based on cost. However, we are concerned that the position statement, as well as the previous FAQ and the Guide itself, impose requirements to choose a more expensive option when a less expensive option will indeed be entirely appropriate for the research and for the welfare of the animal. Given that funds for purchase of chemicals and drugs for research within NIH and at Assured institutions come from federal research budgets, we urge OLAW to recognize that, other considerations being equal, cost savings are an important consideration in making choices for research materials.

Conclusion:

We acknowledge that the 8th edition of the Guide did indeed incorporate a position that OLAW had taken with its publication of an FAQ in Lab Animal in 2003, and regret that we and others did not formally address this issue several years ago. However, our focus on it in the context of the adoption of the 8th edition of the Guide is, to some extent, now usefully informed by experience with IACUC approaches to compliance with the FAQ statements themselves.

We appreciate this opportunity to comment on behalf of our membership. We hope that OLAW will feel welcome to contact ASPET for discussion of any of the concerns related to use of drugs and other chemicals in laboratory animals as it reviews our and other comments on this position statement.

     
24 01/30/2012 at 03:35:24 PM Organization American Psychological Association Washington, DC January 30, 2012

Francis S. Collins, MD, PhD Director, National Institutes of Health Building One, 126 Shannon One Center Drive Bethesda, MD 20892

RE: OLAW Position Statements on the Eighth Edition of the Guide for the Care and Use of Laboratory Animals

Sent via U.S. Mail and submitted online at the OLAW Website

Dear Dr. Collins:

The American Psychological Association (APA) submits these comments to the National Institutes of Health (NIH) Office of Laboratory Animal Welfare (OLAW) regarding its understanding of the Position Statements on the Eighth Edition of the Guide for the Care and Use of Laboratory Animals (Guide), as requested on December 1, 2011 (76 Fed. Reg. 74803). The APA Committee on Animal Research & Ethics (CARE) has reviewed the Position Statements and assessed the potential impact of these interpretations of the Public Health Service (PHS) Policy on the conduct of nonhuman animal research in psychology. As a standing committee of APA committed to the humane treatment of laboratory animals for over 85 years and representing a membership of over 154,000 researchers, educators, clinicians, consultants, and students, CARE has been involved in developing and updating guidelines for the humane care and treatment of nonhuman animals in research. Because research with laboratory animals is an integral component of the science of behavior, APA has strongly supported past efforts to improve laboratory animal welfare while ensuring that proposed policies do not compromise scientific research.

APA appreciates OLAW's efforts to address important issues raised by the research community at large during the initial comment period. As we noted then, it is not cost per se that the research community objected to, but it was increased cost in the absence of any demonstrable improvement in the welfare of laboratory animals. APA recognizes that OLAW released these position statements to clarify the use of the Guide in assessing compliance with PHS policies. We hope that the final position statements will provide institutions with the flexibility necessary to tailor the guidelines to their individual animal care and use programs. APA's specific comments addressing OLAW's Position Statements on the Guide are as follows:

1. Position Statement: Cost

As OLAW noted, nearly 70% of respondents in the initial comment period raised concerns about the cost of implementing the 8th Edition of the Guide. Many comments noted examples of spending scarce research funds in the absence of scientific data demonstrating that the expenses would significantly improve laboratory animal welfare. APA believes that OLAW decisions related to the housing and use of nonhuman animals in PHS-funded research should be evidence-based to ensure both actual improvement in the welfare of the research animals as well as integrity of research findings.

Principle II of the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training, referenced by OLAW, states, "Procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society." APA agrees with this statement and further believes that consideration of costs is also of benefit to society and would therefore be congruent with Principle II. APA recommends that the position statement be revised as follows:

Animal welfare and the integrity of research findings, rather than costs alone, should be the primary factors in decisions related to assuring compliance with the recommendations in the Guide in PHS-funded research. (See U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training Principle II.) Assured institutions are responsible for compliance with the Guide. OLAW believes compliance can be best accomplished using teamwork, professional judgment, and experience. The PHS Policy and the Guide define the minimum standards ("musts") and performance standards ("shoulds") that OLAW expects of Assured institutions. OLAW recognizes there are many ways to achieve humane laboratory animal care and use. An institution may use an alternative approach if the approach satisfies the requirements of the PHS Policy as determined by OLAW. In many instances, institutions and IACUCs elect to exceed the standards. This is not required and can add expense to the program.

2. Position Statement: Housing

APA believes that this position statement should be revised. The position statement states, "the Guide's space recommendations are a starting point for addressing space needs..." APA believes the use of the phrase "starting point" in conjunction with the titles of the tables on pages 57-63, "Recommended Minimum Space," are likely to cause confusion and also imply the recommendations contained in the table are in fact minimum requirements ("must" statements). In addition, the use of the term "starting point" is inconsistent with OLAW's preceding position statement that "an institution may elect to follow a different course of action than a 'should' statement in the Guide if that action results in an equivalent outcome and is reviewed and approved by the IACUC." Therefore, APA recommends clarifying this position statement to read as follows:

OLAW concurs with the recommendations of the Guide that performance standards are to be applied to housing issues. (See Guide pages 50-63.) Outcome-based performance standards are paramount when evaluating cage or pen space for housing laboratory animals used for research, research training, and biological testing.

While the Guide's space recommendations are accepted reference points for addressing space needs, performance standards allow flexibility to improve laboratory animal welfare and scientific research.

An institution's laboratory animal housing practices must be species-specific, appropriate for the animals, and in compliance with all applicable federal and local regulatory requirements.

2a. Position Statement: Nonhuman Primate Housing

APA believes revisions are needed to this position statement to ensure consistency with USDA's Animal Welfare Regulations. The position statement states, "Housing of nonhuman primates in social settings (pairs or groups) is the requirement of the USDA regulations (9 CFR Ch. 1, Part 3, Subpart D)…" However, Section 3.81 of the Animal Welfare Regulations actually requires that, "The environment plan must include specific provisions to address the social needs of nonhuman primates of species known to exist in social groups in nature." According to the Federal Register Vol. 56, No. 32 on February 15, 1991, "The regulations as proposed do not specifically call for group housing of nonhuman primates" (emphasis added). Therefore, OLAW's position statement should be revised to accurately reflect the language in the regulations. APA recommends revising the third paragraph to read as follows:

Institutions are encouraged to consult the Animal Welfare Act and Regulations on primate housing requirements. Compliance with the USDA regulations is an absolute requirement of this [PHS] Policy. (See PHS Policy footnote 2.) Exemptions to the social housing requirement must be based on strong scientific justification approved by the IACUC or for a specific veterinary medical or behavioral reason. Lack of appropriate caging does not constitute an acceptable justification for exemption.

In addition, the last paragraph should be deleted because FAQ F14 does not accurately reflect the history that led to the current regulatory language.

2b. Position Statement: Environmental Enrichment

APA commends OLAW for addressing environmental enrichment in its position statements. We also believe that enrichment devices "…contribute to, rather than detract from, the animal's living space and need not be subtracted from the floor dimensions."

2c. Position Statement: Rodent Housing

APA believes that this position statement should be revised. The position statement states, "the Guide's space recommendations are a starting point for addressing space needs..." As noted above, APA believes the use of the phrase "starting point" in conjunction with the titles of the tables on pages 57-63, "Recommended Minimum Space," are likely to cause confusion and also imply the recommendations contained in the table are in fact minimum requirements ("must" statements). In addition, the use of the term "starting point" is inconsistent with OLAW's preceding position statement that "an institution may elect to follow a different course of action than a 'should' statement in the Guide if that action results in an equivalent outcome and is reviewed and approved by the IACUC." Therefore, APA recommends clarifying this position statement to read as follows:

OLAW supports the Guide's approach to applying performance standards to achieve specified outcomes and expects institutions to use the Guide's space recommendations in that process. Adjustments to recommendations for primary enclosures may be made at the institutional level by the IACUC. The IACUC should critically evaluate objective measures of outcome-based performance. The Guide identifies examples of performance indices to assess adequacy of housing including health, reproduction, growth, behavior, activity, and use of space.

2d. Position Statement: Rabbit Housing

APA commends OLAW for addressing this issue in its position statements.

3. Position Statement: Non-Pharmaceutical-Grade Substances

APA believes revisions are needed to the position statement addressing non-pharmaceutical-grade substances. The position statement states, "The IACUC is responsible for evaluating the potential adverse consequences of such agents when used for research." APA recommends clarifying this position statement to read as follows:

The IACUC is responsible for evaluating the potential adverse consequences of such agents when used as medications.

The revised statement would reinforce the intent of the USDA Policy # 3 Pharmaceutical-Grade Compounds in Research, which states, "Investigators are expected to use pharmaceutical-grade medications whenever they are available, even in acute procedures." The inclusion of the words "in research" in the position statement implies that this policy extends to test articles which clearly should not be the intent.

4. Position Statement: Food and Fluid Restriction/Use of Preferred Foods

APA commends OLAW for the clarity with which it addressed this issue and for the emphasis on the use of performance standards based on the level of restriction.

5. Position Statement: Multiple Surgical Procedures

APA commends OLAW for the clarity with which it addressed this issue and for the emphasis on the use of performance standards to define the nature of the surgical procedure. The position statement addressing multiple surgical procedures, along with changes to FAQ F9, has helped to clarify this issue.

APA thanks NIH for this opportunity to share our comments on the position statements released by OLAW. We recognize the importance of the Guide in ensuring the humane care and treatment of nonhuman animals in research and we offer our concerns and suggestions in order to ensure that the Guide retains its current flexibility as a guidance document, as opposed to functioning like regulations. If you have any questions, or if we can provide any further information, please feel free to contact me at 202-336-6000, or by email at sbreckler@apa.org.

Sincerely,

Steven J. Breckler, PhD Executive Director for Science American Psychological Association

cc Patricia Brown, VMD Director, Office of Laboratory Animal Welfare Office of Extramural Research, National Institutes of Health RKL1, Suite 3601, Mail Stop 7982 6705 Rockledge Drive Bethesda, MD 20892-7982

 
25 01/30/2012 at 05:10:16 PM Self ****** Brown City MI 48416         Requirement for research institutions at leading universities to justify their current density practices wrongly assumes OLAW based on solid data. Unfortunate that in a time when practicing physicians like me are [rightly] encouraged to practice evidence-based medicine, NIH stands ready to impose odious regulatory burdens on the same research and teaching institutions which could provide the basis for meaningful study of optimal conditions regarding humane and cost-effective use of laboratory animals.

         
26 01/30/2012 at 07:01:02 PM Organization Animal Legal Defense Fund Cotati, California The Animal Legal Defense Fund supports, in part, Position Statement (1), which states that "[c]ost cannot be the overriding factor in decisions related to animal welfare." ALDF is concerned, however, that this principle is compromised by OLAW's simultaneous willingness to permit institutions to use less expensive and less humane approaches than those required by the Guide. As discussed in more detail below, ALDF urges OLAW to require organizations to comply with the measurable standards in the Guide, rather than allowing institutions to develop their own work-around solutions that use cost as a deciding factor.

Federal regulations require that facilities receiving federal funds comply with the Guide. 42 C.F.R. 52b.14(d)(5). Despite this clear requirement, PHS has adopted a policy of "enforced self-regulation," in which oversight is left to internal review committees and facilities must merely provide "assurances" of animal welfare. This policy makes it difficult for PHS and OLAW to ensure that regulated laboratories are meeting the requirements of the Guide. This militates in favor of establishing clear, quantifiable standards at the outset. Combining "enforced self-regulation" with the loose "performance standards" advocated in this position statement is a recipe for disaster: it provides laboratories with an unchecked incentive to find that deviations from quantifiable standards are permissible, thus compromising animal welfare.

    ALDF is concerned that Position Statement 2(c) retreats from the precise space standards for rodent housing articulated in the Guide in favor of amorphous "performance standards" that would allow institutions to avoid updating their facilities. OLAW states in Position Statement 2(c) that institutions should use the space recommendations contained in Table 3.2 as "a starting point." OLAW should clarify that under the Guide, these recommendations are a minimum. Any departure from these baselines must be authorized by the IACUC, and OLAW must clarify that this cannot be done as a matter of routine, nor can it be done for cost-saving purposes or convenience. As is evident from their public comments, laboratories' unwillingness to adopt the Guide's recommendations in Table 3.2 stems entirely from concerns about the cost and inconvenience of doing so. Because the new standards in the Guide for rodent housing provide a clear directive to institutions that would result in improved living conditions for laboratory animals, we urge OLAW to retract its Position Statement 2(c) and instead clarify its expectation that labs meet the Guide's minimum space recommendations in Table 3.2.

Again, ALDF is concerned about the disastrous combination of imprecise performance standards with self-regulation, and urges OLAW to adopt as written the Guide's requirement that rabbit cages be at least 16 inches in height. (Guide at 59, Table 3.3). OLAW's Position Statement (2)(d) states that IACUCs may consider the use of a rabbit cage that is 14 inches high if performance standards are met. Permitting amorphous "performance indices" in this context is unnecessary and will result in reduced animal welfare. Given that 16 inches for cage height is a minimum, OLAW should retract its endorsement of institutional use of 14 inch cages. OLAW has repeatedly stated that "[c]ost saving or convenience alone is not sufficient justification to approve a departure from the minimum standards of the Guide." (OLAW Adoption and Implementation Plan). OLAW's willingness to accept reduced cage heights for rabbits in Position Statement (2)(d) because of "the necessity of cost-efficiency and the valid concerns of the community about program cost" conflicts with OLAW's stated purpose in administering the updated version of the Guide. The European Union requires that rabbits under 10 weeks of age be provided with a minimum cage height of 15.7 inches, rabbits over ten weeks of age be provided with a minimum cage height of 17.7 inches, and rabbits weighing over 5 kilograms to be given 23.6 inches of cage height. OLAW's suggestion that rabbits can be comfortably housed in cages at 14 inches is incongruous not only with OLAW's stated purpose to improve animal welfare, but also with the updated edition of the Guide and international standards. Accordingly, ALDF urges OLAW to retract Position Statement 2(d), and instead require institutions to comply with the minimum cage height requirements for rabbits in Table 3.3.

       
27 01/31/2012 at 10:44:30 AM Organization Association for Research in Vision & Ophthalmology Rockville, MD ARVO is a member of the National Association for Biomedical Research (NABR) and supports the following statement. "NABR believes that OLAW should emphasize animal welfare and integrity of research findings as the primary factors in decisions related to the housing and use of animals in PHS-funded research."

AAALAC as well as most of the laboratory animal research community made it clear that outcome-based performance standards are the best guide for housing parameters. We think housing requirements need to be flexible to accommodate institution-specific requirements. If the Guide recommendations are interpreted as guidelines rather than standards, there should be no major issues with Guide implementation.

Social housing of non-human primates should be based on scientific justification and should be approved by the IACUC in a context dependent manner. Social housing is a very important enrichment for social animals. Several factors need to be considered, including colony age, social compatibility of the animals, type of research being performed, and the availability of personnel that can carry out the socialization program. Strong scientific justification approved by the IACUC should take care of any concerns around this issue.

We agree with OLAW's position on environmental enrichment. Institutions can be creative about environmental enrichment without incurring too much cost. So, this should not have much impact.

Our committee members either agree with this statement or have no comments.

We agree with the OLAW statement. However, a strong IACUC process would be required if the exceptions are to be deemed appropriate at the institutions.

We agree that pharmaceutical-grade chemicals and other substances, when available, should be used "for agents when used [delete: "for research"]and [replace with "as medications"].

Our committee members either agree with this statement or have no comments.

We think that multiple major survival surgeries should only be permitted when there is strong scientific justification.

This statement seems appropriate.

28 01/31/2012 at 12:50:07 PM Organization The National Institutes of Health, Intramural Research Program Bethesda, Maryland       The NIH IRP submits the following comment for consideration: The last two sentences seem ambiguous and do not appear to add value to the position statement. Suggest deleting these two sentences.

[Delete] "Some species are upset by the introduction of novel items. Animals should not be subjected to the presence of items that they find distressing."

    The NIH IRP submits the following comments for consideration: 1) Add 'or better grade' to the first sentence. In some cases there are higher quality compounds, with lower levels of impurities, than pharmaceutical grade, and in those circumstances no further justification should be needed to meet the requirements of this practice standard.

"OLAW and USDA agree that pharmaceutical-grade or better grade chemicals..."

2) The statement: '...it is frequently necessary to use investigational compounds, veterinarian- or pharmacy-compounded drugs...' has left some concerned that compounding must be performed by a pharmacist. Request clarification regarding the ACUC's latitude to allow investigators to perform their own compounding, as has been routinely approved in the past. Often the investigator is the primary individual that has the expertise and knowledge to compound drugs in a manner that ensures the tenets of this regulatory standard are met.

     
29 02/01/2012 at 12:29:34 PM Organization Association of American Medical Colleges Washington, DC   We urge that OLAW explicitly state that institutions may use alternative approaches to achieve humane care and use, as long as the approach satisfies the requirements of the PHS Policy as determined by OLAW. We also agree with NABR that the position statement concerning rodent housing

    In particular, we urge that OLAW explicitly state that institutions may use alternative approaches to achieve humane care and use, as long as the approach satisfies the requirements of the PHS Policy as determined by OLAW. We also agree with NABR that the position statement concerning rodent housing should be further clarified to make it clear that the Guide's table regarding space is not a minimum requirement (a "must" statement). Rather, it is a "should" statement, which OLAW earlier noted allows an institution to "elect to follow a different course of action… if that action results in an equivalent outcome and is reviewed and approved by the IACUC."

         
30 02/01/2012 at 01:22:28 PM Organization Animals in Research Committee of the College on Problems of Drug Dependence Philadelphia, PA             The Committee on Animals in Research of the College on Problems of Drug Dependence (CPDD) wishes to respond to OLAW position statement on the research use of "Non-Pharmaceutical-Grade Substances" as outlined in the 8th edition of the "Guide for the Care and Use of Laboratory Animals." We believe there is still the possibility of confusion in interpretation of this directive even with the new "position statement" of OLAW. The capacity to be able to test investigational compounds is a hallmark of biomedical research. Introduction of a regulation, which in its wording could be interpreted to mean that use of such compounds by research laboratories is prohibited or infringed by requiring collaboration with a veterinarian or a pharmacy to formulate the drug for injection in animals, runs contrary to the essence of what transpires in a working research laboratory. The rule could also be misinterpreted in a way that would disqualify compounds purchased from legitimate and highly qualified vendors. In addition, drugs supplied by NIH/NIDA to funded researchers should be recognized as an acceptable source of drugs for animal research. Further, controlled substances that need to be administered to animals for research must be under the control of the person licensed to receive and dispense them. The process of formulating them could not be delegated to a veterinarian or a pharmacist without significant legal problems. We urge: 1. That the wording that implies that only veterinarians and pharmacists are qualified to prepare drugs for administration to animals be extensively revised to make it clear that an investigator can prepare and use such compounds as part of their research. 2. That the wording state explicitly that Schedule I-V drugs are exempt from the classification as "Non-Pharmaceutical-Grade Substances" if they are being used for research purposes, and that NIDA supplied drugs are acceptable. 3. That it be explicitly stated that compounds purchased from legitimate supply companies can be used in animal research.

     
31 02/01/2012 at 02:33:42 PM Self LSU Health Sciences Center in Shreveport               I am concerned since the wording implies that only veterinarians and pharmacists are qualified to prepare drugs for administration to animals. This needs to be revised. I am a pharmacologist (not a pharmacist) and a scientist who has been conducting drug studies in rats for 30 years. It would be cost prohibitive and time constraining to have to wait for a veterinarian or pharmacist to prepare all of our drug solutions. Perhaps the wording could include something about the training of scientists in the use of drugs in animals if this is a concern. The wording must be extensively revised to make it explicitly clear that an investigator can prepare and use compounds as part of their research.

The wording should also explicitly that Schedule I-V drugs are exempt from the classification as "Non-Pharmaceutical-Grade Substances" if they are being used for research purposes, and that NIDA supplied drugs are acceptable. The wording should also state clearly that compounds purchased from legitimate supply companies can be used in animal research.

     
32 02/01/2012 at 02:39:53 PM Self   Philadelphia, PA             This policy will unnecessarily hamper research and will do little to protect animals. I feel that the policy should be modified as follows: or a pharmacist without significant legal problems. We urge: 1. That the wording state explicitly that Schedule I-V drugs are exempt from the classification as "Non-Pharmaceutical-Grade Substances" if they are being used for research purposes, and that drugs supplied by NIH are acceptable. 2. That extensive revisions be made to the wording that implies that only veterinarians and pharmacists are qualified to prepare drugs for administration to animals; it should be made clear that an investigator can prepare and use such compounds as part of their research. 3. That it be explicitly stated that compounds purchased from legitimate supply companies can be used in animal research.

     
33 02/02/2012 at 10:11:49 AM Organization American College of Neuropsychopharmacology Nashville, TN             The American College of Neuropsychopharmacology (ACNP) is a professional organization of more than 900 leading scientists, including three Nobel Laureates, whose mission is to further research and education in neuropsychopharmacology and related fields. Membership in ACNP is open only to those from around the world who have made major and significant research and/or clinical contributions in this field. Members of ACNP Council have reviewed the Comments to OLAW Regarding Adoption of the Guide for the Care and Use of Laboratory Animals: Eighth Edition regarding Non-Pharmaceutical Grade Substances that were submitted by ASPET. Our members share the concerns addressed in the ASPET comments and agree with their conclusions and recommendations. We are writing to urge OLAW to give careful consideration to the ASPET statement and to adopt recommendations they made.

     
34 02/02/2012 at 11:15:02 AM Self     With the lowest pay lines in recent history at NIH, decreased state budgets, a shrinking of private (pharmaceutical companies) investment in certain types of research, the costs investigators will incur if the new Guide is adopted will further stifle US research laboratories.

Changes in housing specifications are not empirically supported, will not obviously improve on already excellent care of animals, and will burden institutions and investigators with huge costs.

Many non-human primates are not suited to group housing and they do not cohabitate that way in their natural environment. The social hierarchy in the wild can be violent and lethal although in the wild subordinate animals have the opportunity to flee. Not only is this guideline unfounded ethologically, it will be terribly disruptive to many types of research that use special instrumentation, special dietary conditions, and drug administration. It is difficult to imagine that truly knowledgeable people were consulted on this matter -- there is no question that the only possible outocomes of implementing this policy for some non-human primates are serious injury to animals and/or elimination of research in non-human primates.

Within reason, enrichment can only improve the quality of research. The issue at hand is whether the recommendations are empirically based, feasible, and in the best interest of animals, researchers, and research.

    The large majority of drug research does not use USP or BP certified drugs, although most of those non-certified drugs are of a quality that is as high or higher than USP or BP standards. It is unclear why this policy is moving forward. Is there any evidence that current practice is not appropriate? This appears to be another layer of bureauracy that has no justification. The individuals conducting the research are usually the experts...why would you task veterinarians (who have little training in chemistry or pharmacology) with drug preparations? That realighment of responsibility would be very costly in time and money, particularly when considering use of controlled substances. This appears to be trying to create a problem where there isn't one. Again, if the strictest interpretation of this guidline is implemented, it will shut down valuable research.

It would appear as though IACUC already does this.

Under appropriate conditions animals should be used for multiple surgical procedures -- the alternative is to use of more animals at much greater expense (e.g., training new animals for every procedure/condition)or significantly restrict research. The Guide should PROMOTE research within humane guidelines -- not restrict research in a manner that impedes progress. It is absolutely unclear why this revision was initiated -- is there evidence that there was a problem that needed addressing???

 
35 02/02/2012 at 12:27:51 PM Organization College on Problems of Drug Dependence Philadelphia, PA             The College on Problems of Drug Dependence (CPDD) wishes to respond to OLAW position statement on the research use of "Non-Pharmaceutical-Grade Substances" as outlined in the 8th edition of the "Guide for the Care and Use of Laboratory Animals." We believe there is still the possibility of confusion in interpretation of this directive even with the new "position statement" of OLAW. The capacity to be able to test investigational compounds is a hallmark of biomedical research. Introduction of a regulation, which in its wording could be interpreted to mean that use of such compounds by research laboratories is prohibited or infringed by requiring collaboration with a veterinarian or a pharmacy to formulate the drug for injection in animals, runs contrary to the essence of what transpires in a working research laboratory. The rule could also be misinterpreted in a way that would disqualify compounds purchased from legitimate and highly qualified vendors. In addition, drugs supplied by NIH/NIDA to funded researchers should be recognized as an acceptable source of drugs for animal research. Further, controlled substances that need to be administered to animals must be under the control of the person licensed to receive and dispense them. The process of formulating them could not be delegated to a veterinarian or a pharmacist without significant legal problems. We urge: 1. That the wording that implies that only veterinarians and pharmacists are qualified to prepare drugs for administration to animals be extensively revised to make it clear that an investigator can prepare and use such compounds as part of their research. 2. That the wording state explicitly that Schedule I-V drugs are exempt from the classification as "Non-Pharmaceutical-Grade Substances" if they are being used for research purposes, and that NIDA supplied drugs are acceptable. 3. That it be explicitly stated that compounds purchased from legitimate supply companies can be used in animal research.

     
36 02/03/2012 at 10:02:58 AM Self   Gainesville FL             The capacity to be able to test investigational compounds is a hallmark of biomedical research in the field of aging. Introduction of a regulation, which in its wording could be interpreted to mean that use of such compounds by research laboratories is prohibited or infringed by requiring collaboration with a veterinarian or a pharmacy to formulate the drug for injection in animals, runs contrary to the essence of what transpires in a working research laboratory. The rule could also be misinterpreted in a way that would disqualify compounds purchased from legitimate and highly qualified vendors. I urge: 1. Remove statements regarding veterinarians and pharmacists being the only ones qualified to prepare drugs for administration to animals and/or extensively revised to make it clear that an researcher can prepare and use such compounds as part of their program. 2. That it be explicitly stated that compounds purchased from legitimate supply companies can be used in animal research.

     
37 02/03/2012 at 11:53:40 AM Organization The Humane Society of the United States Washington, DC The Humane Society of the United States (HSUS), on behalf of its more than 11 million supporters, supports OLAW's statement that cost cannot be the deciding factor in making decisions about animal welfare in PHS-funded research. The fact that the majority of commenters felt it appropriate to mention concerns with cost makes it even more imperative that OLAW strongly clarify that cost cannot be a reason not to address animal welfare. However, OLAW's mention that "In many instances, institutions and IACUCs elect to exceed the standards... [which] is not required and can add expense to the program," could be interpreted by some institutions as discouragement from exceeding the standards. We urge OLAW to add a supplemental statement that, while it is not required, OLAW does not discourage institutions from exceeding the standards.

The Humane Society of the United States (HSUS), on behalf of its more than 11 million supporters, urges OLAW to strictly enforce new housing standards in the 2011 Guide. The qualified Guide committee members must have been compelled to add these new housing suggestions to the 2011 Guide for valid reasons. However, when performance standards are applied to housing, The HSUS further supports the statement that "outcome-based performance standards are paramount." The HSUS is concerned, however, that the ability to utilize performance standards will be used as way for institutions to maintain the status quo and claim positive outcomes, but without true evidence of such. Therefore, it is essential that OLAW verify that institutions have clearly defined outcome measures and that success is monitored regularly. Without defining measurable outcomes, performance standards provide too much flexibility, not enough guidance, and inadequate protection for animal welfare and quality of science.

Furthermore, where performance outcomes are adopted for housing, institutions should collect data on performance outcomes, such as scoring animals in terms of pain and distress, performance of species-typical behaviors, and assessing their preferences (such as how hard the animals will work to gain access to something or avoid something). The data collection would not only serve to demonstrate institutional compliance but allow for continual improvement in reaching expected outcomes.

The Humane Society of the United States (HSUS), on behalf of its more than 11 million supporters, is glad to see the emphasis of social housing of nonhuman primates in OLAW's position statement. The HSUS supports OLAW's clarification that protected tactile contact is considered single housing, and also that lack of caging is not a justified reason for not socially housing primates.

The Humane Society of the United States (HSUS), on behalf of its more than 11 million supporters, supports OLAW's statement that the purpose of environmental enrichment is to enhance animal well-being (rather than focusing on preventing negative behaviors). Unfortunately, there has been a wide range of environmental enhancement plan implementation and results amongst facilities due to a lack of appropriate and uniform measures of success, as well as a more prominent focus on minimizing abhorrent behavior rather than maximizing species-typical behavior. The HSUS urges OLAW to clarify a definition of, and means of measuring, the success of efforts related to promoting the psychological well-being of animals through environmental enrichment.

The Humane Society of the United States (HSUS), on behalf of its more than 11 million supporters, urges OLAW to strictly uphold new housing requirements for rodents. Millions of mice are bred and used in PHS-funded research every year, so increased space requirements for these animals in particular, is of special concern. The HSUS is concerned that the ability to utilize performance standards will be used as way for institutions to continue with the status quo and claim positive outcomes without true, measurable evidence. Therefore, it is essential that OLAW verify that institutions have clearly defined outcome measures and that success it monitored regularly. Without defining measurable outcomes, performance standards provide too much flexibility, not enough guidance, and inadequate protection for animal welfare and quality of science. Furthermore, we support OLAW's statement that departures from the Guide for convenience, cost or non-animal welfare reasons will not be acceptable and urge OLAW to be vigilant of institutions that may try to do so.

The Humane Society of the United States (HSUS), on behalf of its more than 11 million supporters, urges OLAW to strictly uphold the new height suggestions for rabbit housing and supports the clarification that rabbits should be able to hold their ears upright without touching the cage ceiling. The HSUS is, however, concerned that the ability to utilize performance standards will be used as way for institutions to continue with the old rabbit cage height and claim positive outcomes without evidence of such outcomes. Therefore, it is essential that OLAW verify that institutions have clearly defined outcome measures and that success is monitored regularly. Without defining measurable outcomes, performance standards provide too much flexibility, not enough guidance, and inadequate protection for animal welfare and quality of science.

The Humane Society of the United States (HSUS), on behalf of its more than 11 million supporters, supports OLAW's statement that "procedures that may cause more than momentary or slight pain or distress to the animals must be performed with sedation, analgesia, or anesthesia agents using veterinary or human pharmaceutical-grade compounds…" We further urge OLAW to closely scrutinize and ensure solid justification for the use of non-veterinary or non-human pharmaceutical-grade compounds for sedation, analgesia, and anesthesia in procedures involving more than momentary or slight pain or distress to animals.

The Humane Society of the United States (HSUS), on behalf of its more than 11 million supporters, urges OLAW to closely scrutinize any use of food or fluid restriction. For example, in terms of studies that involve performance of behavioral task, there are many cases in which animals will engage in these tasks for supplemental food or fluids and don't need their regular intake to be restricted. Food and fluid restriction seem readily used without true justification. When food and fluid restriction are used, we urge OLAW to add a statement of clarification on the importance of staff communication during such restriction studies. Recording increments of food and water intake over time requires staff to be attentive and organized in order to obtain accurate totals to then ensure optimal animal welfare.

The Humane Society of the United States (HSUS), on behalf of its more than 11 million supporters urges OLAW to closely scrutinize and ensure that PIs are providing the IACUC with solid justification for conducting multiple survival surgeries on animals. In keeping in line with the 3R's, justification should also include proof that there are no available alternatives; we urge OLAW to add a statement on this issue to this position statement.

 
38 02/03/2012 at 12:18:50 PM Self                 It seems that there would be considerable logistical, administrative, scientific, and possibly legal problems should veterinary/pharmacy compounding be required for "non-pharmaceutical-grade" drugs. From a logistical and scientific standpoint, such a requirement would practically preclude any work with drugs that must be made fresh (on the order of minutes to hours) on a daily basis, or that are particularly difficult to get into solution, without having a pharmacist "on call". There would also be significant administrative challenges when such drugs require compounding on a daily basis. Finally, given the strict legal requirements for storage and handling of controlled substances, it does not seem feasible to transfer such substances to other individuals for compounding.

     
39 02/03/2012 at 02:16:43 PM Self         Though veterinary staff would completely agree that social housing of NHPs should be the norm, it may be detrimental to the animals to expect institutions to comply with these expectations within the coming year or two. The norm for so many years and in so many institutions has been to single-house NHPs. Many, if not most, institutions are not appropriately staffed nor trained to conduct large-scale movement to social housing. Aged NHPs who have been single-housed require close follow-up and evaluation to determine if social housing is most appropriate for those individual NHPs. My concern is that Institutions will respond to meet the requirement of the Guide while possibly failing to see what is safest and least stressful for each NHP. Further guidance should be given in this position statment to stress a strong behavioral evaluation program and efforts made to train staff.

             
40 02/03/2012 at 02:45:41 PM Organization National Association for Biomedical Research (NABR) Washington, DC February 3, 2012 Francis S. Collins, MD, PhD Director, National Institutes of Health Building One, 126 Shannon One Center Drive Bethesda, MD 20892

RE: OLAW Position Statements on the Eighth Edition of the Guide for the Care and Use of Laboratory Animals

Sent via U.S. Mail and submitted online at the OLAW Website

Dear Dr. Collins:

The National Association for Biomedical Research (NABR) represents more than 325 public and private universities, medical and veterinary schools, teaching hospitals, voluntary health organizations, professional societies, pharmaceutical and biotechnology companies and promotes sound public policy for the humane care and use of laboratory animals in biomedical research. On behalf of its member institutions, NABR appreciates the opportunity to provide comments regarding its understanding of the Position Statements on the Eighth Edition of the Guide for the Care and Use of Laboratory Animals (Guide) developed by the Office of Laboratory Animal Welfare (OLAW), as requested on December 1, 2011. (76 Fed. Reg. 74803). NABR appreciates OLAW's efforts to address important issues raised by the Association and other organizations during the initial comment period and recognizes that OLAW's clarifications regarding the nature and use of the Guide in assessing compliance with PHS assurance policies provides institutions with increased flexibility to tailor the guidelines provided in the Guide to their individual animal care and use programs. However, in light of the fundamental changes to the Eighth Edition that have shifted its emphasis from professional judgment towards a greater reliance on prescriptive requirements, NABR continues to be concerned about how the Guide will be interpreted and applied in the future, as expressed in our comment letter of May 24, 2011. NABR's specific comments addressing OLAW's publicly posted Position Statements on the Guide are as follows:

1. Position Statement: Cost

As OLAW noted, nearly 70% of individuals and institutions responding to the previous comment period raised concerns about the cost of implementing the 8th Edition of the Guide. Most of these comments, like NABR's own, were limited to examples of spending scarce research funds in the absence of reliable scientific data demonstrating that the expenditure would actually benefit animal welfare. NABR believes that OLAW should emphasize animal welfare and integrity of research findings as the primary factors in decisions related to the housing and use of animals in PHS-funded research.

Principle II of the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training, which OLAW references, states, "Procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society." NABR agrees with this statement and further believes that consideration of costs is also of benefit to society and would therefore be congruent with Principle II. Other considerations being equal, cost savings are an important consideration in decisions related to the conduct of research. NABR recommends that OLAW revise the position statement as follows:

Animal welfare and the integrity of research findings, rather than costs alone, should be the primary factors in decisions related to assuring compliance with the recommendations in the Guide in PHS-funded research. (See U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training Principle II.) Assured institutions are responsible for compliance with the Guide. OLAW believes compliance can be best accomplished using teamwork, professional judgment, and experience. The PHS Policy and the Guide define the minimum standards ("musts") and performance standards ("shoulds") that OLAW expects of Assured institutions. OLAW recognizes there are many ways to achieve humane animal care and use. An institution may use an alternative approach if the approach satisfies the requirements of the PHS Policy as determined by OLAW. In many instances, institutions and IACUCs elect to exceed the standards. This is not required and can add expense to the program.

2. Position Statement: Housing

NABR believes OLAW should revise this position statement. It indicates that, "the Guide's space recommendations are a starting point for addressing space needs..." OLAW's use of the use of the phrase "starting point" in conjunction with the titles of the tables on pages 57-63, Recommended Minimum Space, are likely to cause confusion and imply the recommendations contained in the table are in fact minimum requirements ("must" statements). The position statement's use of the term "starting point" is not consistent with OLAW's preceding statement that "an institution may elect to follow a different course of action than a 'should' statement in the Guide if that action results in an equivalent outcome and is reviewed and approved by the IACUC." NABR recommends OLAW clarify this position statement to read as follows:

OLAW concurs with the recommendations of the Guide that performance standards are to be applied to housing issues. (See Guide pages 50-63.) Outcome-based performance standards are paramount when evaluating cage or pen space for housing animals used for research, research training, and biological testing. The Guide's space recommendations should be used to develop performance standards which allow flexibility to improve animal welfare and scientific research while addressing the space needs of the animals. An institution's animal housing practices must be species-specific, appropriate for the animals, and in compliance with all applicable federal and local regulatory requirements.

2a. Position Statement: Nonhuman Primate Housing

NABR believes revisions are needed to this position statement to ensure it is consistent with USDA's Animal Welfare Regulations. OLAW's position statement contains the following statement, "Housing of nonhuman primates in social settings (pairs or groups) is the requirement of the USDA regulations (9 CFR Ch. 1, Part 3, Subpart D)…" Section 3.81 of the Animal Welfare Regulations actually requires that, "The environment plan must include specific provisions to address the social needs of nonhuman primates of species known to exist in social groups in nature." This language was included in the regulations following an extensive review and comment period on the proposed regulations. A record of these comments can be found in the Federal Register Vol. 56, No. 32 on February 15, 1991, along with the Final Rule as it relates to Section 3.81. On page 6472, the following language appears:

A large number of commenters urged that the regulations include specific requirements for exercise and social grouping of nonhuman primates, as proposed in our original proposal. We disagree with the commenters that it be in the best interest of nonhuman primates to impose uniform rigid standards on all facilities.

Further down the page USDA continues, "A number of commenters stated that social housing should not be mandatory but rather should be one of the possible methods of enriching the animals' environment…The regulations as proposed do not specifically call for group housing of nonhuman primates." 56 Fed. Reg. 6426 at 6472 (emphasis added). OLAW's position statement should be revised to accurately reflect the language in the regulations. This could be done by revising the third paragraph to read as follows:

Institutions are encouraged to consult the Animal Welfare Act and Regulations on primate housing requirements. Compliance with the USDA regulations is an absolute requirement of this [PHS] Policy. (See PHS Policy footnote 2.) Exemptions to the social housing requirement must be based on strong scientific justification approved by the IACUC or for a specific veterinary medical or behavioral reason. Lack of appropriate caging does not constitute an acceptable justification for exemption.

In addition, the last paragraph should be deleted because FAQ F14 does not accurately reflect the current regulatory language or regulatory history that led to the current regulatory language.

NABR commends OLAW for addressing environmental enrichment in its position statements. It succinctly addresses the concerns of many of our members who also believe enrichment devices "…contribute to, rather than detract from, the animal's living space and need not be subtracted from the floor dimensions."

NABR believes revisions are needed to this position statement. OLAW includes the following language, "… expects institutions to use the Guide's space recommendations as a starting point." OLAW's use of the phrase "starting point" in conjunction with the titles of the tables on pages 57-63, Recommended Minimum Space, are likely to cause confusion as they appear to imply the recommendations contained in the table are in fact minimum requirements ("must" statements). The position statement's use of the term "starting point" is not consistent with OLAW's preceding statement that "an institution may elect to follow a different course of action than a 'should' statement in the Guide if that action results in an equivalent outcome and is reviewed and approved by the IACUC." NABR recommends that OLAW clarify this position statement to read as follows:

OLAW supports the Guide's approach to applying performance standards to achieve specified outcomes and expects institutions to use the Guide's space recommendations in that process. Adjustments to recommendations for primary enclosures may be made at the institutional level by the IACUC. The IACUC should critically evaluate objective measures of outcome-based performance. The Guide identifies examples of performance indices to assess adequacy of housing including:

NABR commends OLAW for addressing this issue in its position statements.

3. Position Statement: Non-Pharmaceutical-Grade Substances

NABR believes revisions are needed to the position statement addressing non-pharmaceutical-grade substances. OLAW's position statement includes the following language, "The IACUC is responsible for evaluating the potential adverse consequences of such agents when used for research." NABR recommends OLAW clarify this position statement to read as follows:

The IACUC is responsible for evaluating the potential adverse consequences of such agents when used as medications.

Doing so would reinforce the intent of USDA Policy # 3 Pharmaceutical-Grade Compounds in Research, which states, "Investigators are expected to use pharmaceutical-grade medications whenever they are available, even in acute procedures." The inclusion of the words "in research" in the position statement implies that this policy extends to test articles which clearly should not be the intent.

NABR also commends the comments of the Association for Pharmacology and Experimental Therapeutics (ASPET) to your attention.

NABR commends OLAW for the clarity with which it addressed this issue and for the emphasis on the use of performance standards based on the level of restriction.

5. Position Statement: Multiple Surgical Procedures

NABR commends OLAW for the clarity with which it addressed this issue and for the emphasis on the use of performance standards to define the nature of the surgical procedure. The position statement addressing multiple surgical procedures, along with changes to FAQ F9, has helped to clarify this issue.

Thank you for your consideration of our comments and please contact me if you have any questions.

Sincerely, Frankie L. Trull President

cc Patricia Brown, VMD Director, Office of Laboratory Animal Welfare Office of Extramural Research, National Institutes of Health RKL1, Suite 3601, Mail Stop 7982 6705 Rockledge Drive Bethesda, MD 20892-7982

 
41 02/03/2012 at 03:10:01 PM Organization Johns Hopkins University Baltimore, MD             We appreciate the clarifications of the policy that the position statement provides. We understand that a distinction is made between drugs/chemicals that are being used for clinical purposes and those that are being used as research tools or are the object of study themselves (e.g., Schedule I drugs or those in the development process). That is, that preparations used for a clinical purpose, such as for anesthesia or analgesia, ideally should be those that have been formulated and made available commercially for that purpose. We understand that, as in the AVMA policy link provided, OLAW recognizes that there are situations in which the preferred form of the medication is essentially unavailable due to business decisions of the manufacturer. In those situations, alternative forms of the drug may be obtained and prepared for clinical use. This is consistent with the APHIS Policy Manual's Policy 3, though the OLAW position statement goes further in noting various aspects of formulations that may need to be considered if information is not readily available on the appropriate preparation of the compound for administration. We understand that these same qualities are relevant to formulations prepared for research use as well.

We appreciate that the position statement clarifies that IACUCs may prepare guidance statements that inform researchers about the various considerations in choices of drugs/chemicals and their preparation for use in laboratory animals. We understand that OLAW does not require that IACUCs review the technical details of preparation of compounds on a protocol-by-protocol basis. We believe that an emphasis on training and expertise in selection, preparation, and use of chemical compounds is important to include in such an institutional policy, which is consistent with the emphasis on training for other aspects of research with laboratory animals.

The inclusion in the position statement of a definition of a pharmaceutical grade compound is useful, but we ask that it be revised to emphasize drug purity per se rather than be couched in terms of having been approved by FDA and/or manufactured according to USP or BP standards. It's possible that OLAW intended this definition to apply to drugs used for clinical purposes, since the vast majority of drugs used for experimental purposes would not necessarily be approved by FDA or be manufactured according to USP manufacturing process. However, purity is the characteristic that is the most critical element from both a clinical and a research standpoint. Many drugs that are commercially available for research use (e.g., from Sigma/Aldrich, Tocris, and other trusted sources) are equivalent to or higher in purity than USP standards. We believe IACUCs would find it useful for the position statement to use wording that explicitly says that the first choice for a formulation for a clinical purpose is one that has been commercially prepared and sold for that purpose rather than couching this in terms of FDA approval or USP/BP standards. Then, an emphasis on purity for chemicals for experimental use can be made, with perhaps a reference to USP or BP or higher standards, without the implication that a drug not manufactured to USP standards is unacceptable per se.

We thank OLAW for this opportunity to comment on the position statement, and for its consideration of comments during the 2011 public comment period.

     
42 02/03/2012 at 04:51:00 PM Self     Regarding the use of chimpanzees for scientific study, I find the breeding of chimps for study, as is taking place at the Southwest National Primate Center in San Antonio, Texas ethically abhorant and it should never be supported in any manner by Federal funds. This will save costs.

  I am completely against the use of non human primates for study especially now that there are alternatives such as induced pluripotent stem cells made from human peripheral blood samples

             
43 02/03/2012 at 05:28:11 PM Self     What are the practical solutions for institutions and/or investigators through grants pay for new equipment designed to adhere to the guide requirements? With funding levels at new lows, the idea that cost cannot be a consideration is unfeasible, essentially shutting down labs, and therefore, important research. I don't think this is a desirable outcome for anyone.

Performance standards should be applied only if they are evidence-based. For example, some of the evidence cited in the guide for foot lesions in rats being housed in wire cages were studies done in rabbits.

  The guide does not define "well-being", therefore, the criteria for environmental enrichment policies are unclear, making it impossible for the IACUCs to determine what is necessary and/or sufficient. There needs to a good quantifiable and consistent definition.

The guide specifications are written in such general language that it provides no practical means for IACUCs to determine optimal housing. There should be species-specific guides.

    There is no specific definition of "health and well-being" of animals. These should be species specific and clearly defined.

   
44 02/03/2012 at 06:28:49 PM Organization Arizona State University Tempe, AZ Response: ASU agrees that cost in and of itself should not be the overriding factor in decisions related to animal welfare. However, cost is also a consideration in the design of an experiment and its benefit to society. We echo NABR's recommendation that Position Statement 1 be revised to read as follows:

"Animal welfare and the integrity of research findings, rather than costs alone, should be the primary factors in decisions related to assuring compliance with the recommendations in the Guide in PHS-funded research. (See U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training Principle II.) Assured institutions are responsible for compliance with the Guide. OLAW believes compliance can be best accomplished using teamwork, professional judgment, and experience. The PHS Policy and the Guide define the minimum standards ("musts") and performance standards ("shoulds") that OLAW expects of Assured institutions. OLAW recognizes there are many ways to achieve humane animal care and use. An institution may use an alternative approach if the approach satisfies the requirements of the PHS Policy as determined by OLAW. In many instances, institutions and IACUCs elect to exceed the standards. This is not required and can add expense to the program."

ASU agrees that performance based standards are ideal and we suggest clarifying the language for this standard to read as follows: "…the Guide's space recommendations are accepted reference points for addressing space needs. Performance standards allow flexibility to improve animal welfare and scientific research. …"; as it now stands, OLAW's use of the term "starting point" is inconsistent with your previous statement that "institutions may elect to follow a different course of action than a 'should' statement in the Guide if that action results in an equivalent outcome and is reviewed and approved by the IACUC."

ASU believes that this principle is inconsistent with the USDA's Animal Welfare Regulations (Section 3.81) and thus needs to be revised. As originally drafted by NABR, we recommend revising the 3rd paragraph of this Position Statement as follows:

"Institutions are encouraged to consult the Animal Welfare Act and Regulations on primate housing requirements. Compliance with the USDA regulations is an absolute requirement of this [PHS] Policy. (See PHS Policy footnote 2.) Exemptions to the social housing requirement must be based on strong scientific justification approved by the IACUC or for a specific veterinary medical or behavioral reason. Lack of appropriate caging does not constitute an acceptable justification for exemption."

The corresponding FAQ 14 would need to be revised as well.

The use of the terms "starting point" and "may elect" are confusing as they infer that the recommendations are minimum requirements. They are inconsistent with the preceding statement that "an institution may elect to follow a different course of action than a 'should' statement in the Guide if that action results in an equivalent outcome and is reviewed and approved by the IACUC". We recommend that you clarify this Position Statement via use of NABR's suggested language:

"OLAW supports the Guide's approach to applying performance standards to achieve specified outcomes and expects institutions to use the Guide's space recommendations in that process. Adjustments to recommendations for primary enclosures may be made at the institutional level by the IACUC. The IACUC should critically evaluate objective measures of outcome-based performance. The Guide identifies examples of performance indices to assess adequacy of housing including:"

In the new requirement for cage floor space for breeding rodents we do not see enough data to support the new requirement. We recommend this not be required by OLAW until there is a satisfactory body of knowledge to better understand the requirements for breeding rodents from a scientific standpoint.

We note that there is a difference in the height of the rabbit cages between the Guide and the AWA. We recommend consistency and suggest a uniform position between the AWA and the Guide. In reality, the height of the cage should be based on the size of the rabbit – the cage should allow enough height so that the rabbit can sit comfortably and not have its ears touching the top of the cage (or some other type of qualitative or quantitative standard).

       



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