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CHALLENGES IN OUTSOURCING STUDIES An Academic Perspective James Macy A paradigm shift is beginning to occur with regard to academic collabora- tions across borders. Historically there has been a lot of collaboration between US academic institutions and those in the United Kingdom, Canada, and Europe. There was certainly a comfort zone in these interactions in terms of animal care and use regulations—they are not the same in each area, but clearly they func- tionally accomplished the same things. More recently, countries such as China and India have the scientific and the physical infrastructure to perform cutting-edge science. With China as an example, there is technology developed there that is innovative and when at- tached to an NIH individual or program project application makes it very attrac- tive for funding. So the academic agency has to determine how to best collabo- rate with this other institution. Unlike a CRO, it is not necessarily a choice of the institution but a choice of the research. The problem is that our academic institutions do not have much experi- ence with the local animal care and use regulations, especially in countries like China and India. Thus the two central questions that need to be considered are: Is the animal care and use being performed under reasonably appropriate condi- tions in a humane and ethical way? And are the resulting data of acceptable quality and integrity? There have been some recent updates in regulations re- garding human clinical studies, which center on the last point and probably ap- ply to animal studies as well. In an academic institution, oftentimes most of the funding is predicated on the US Public Health Service (PHS). The following is a scenario outlining the institution’s responsibility when there is a PHS award with a foreign component. That foreign component is usually executed through a subaward or subcontract. A foreign component is defined as performing a significant element of the pro- ject outside the United States. It is performed either by the grantee or an indi- vidual working for the foreign institution, and funds do not necessarily change 232

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An Academic Perspective 233 hands. For example, an investigator may be listed as key personnel under a grant. Even though the investigator might not be getting paid for it, it still can be a foreign component as long as there is a significant element in the work that is being performed for that project. So a foreign component involves human or animal subjects. It also includes what we would consider field studies, if some- body is going to a foreign site and collecting samples from animals. If the inves- tigator is acting as a consultant, the institutions must grapple with that, because consultants are not included in the NIH foreign component entity. Looking at the terms or conditions of a subaward or subcontract language related to animals, there are several points to consider. One is that the foreign entity must file a PHS assurance or provide evidence that acceptable standards for the humane care and use of animals will be met. All performance sites have to be operating under an assurance and there has to be verification of an IACUC approval. What does the foreign assurance entail? It is essentially a one-page document with three major components: a statement that the institution must comply with whatever the local regulations are; the institution needs to be guided by the International Guiding Principles for Biomedical Research Involv- ing Animals issued by the Council for International Organizations of Medical Sciences (CIOMS), which are very similar to the US Government Principles; and the institution has to make a reasonable effort to ensure that the people do- ing the work understand the regulations and their responsibilities. The foreign assurance is now in the process of revision. In contrast to a domestic assurance, the foreign assurance does not have a statement about the Animal Welfare Act, does not mention the need for accordance with the Guide for the Care and Use of Laboratory Animals, does not address lines of authority for administering a program, does not ask for the qualifications of the veterinar- ian, and does not have reporting requirements. The IACUC review, reporting and understanding the qualifications, falls to the primary recipient, which is the institution receiving the grant. From an institutional perspective, the initial challenge is knowing that there is a grant with a foreign component. In an IACUC protocol, the investiga- tor may forget to check the box for off-site research or may forget to indicate all the locations where the research will be done. There also may be some confu- sion as to whether the work being performed off-site has to be listed in the IACUC protocol. The IACUC protocol is often one way to monitor off-site research, but the key is to ensure that your institution is doing a congruency review, i.e., certify- ing that what is in the grant matches the IACUC protocol. When doing a con- gruency review, the person reviewing the grant will see the subcontract includ- ing a description of the work and the justification for having it done off-site. The reviewer will determine whether there are procedures in the grant that are not in the IACUC protocol. So this is a very good protection mechanism that needs to occur. Another important issue to consider is export control, not necessarily with respect to animals but other things that can go back and forth. This is highly

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234 Animal Research in a Global Environment: Meeting the Challenges regulated by the US State Department, the Commerce Department, and the Treasury Department. Although most of these regulations do not apply here, and it is a low-risk situation, the consequences are very high if they are not followed. There may be fines up to a million dollars and imprisonment up to ten years. So it is critically important to determine that if there are to be animal-related items or products going back and forth, they are not on the commerce control list or part of any other export regulations. Once an institution enters into an agreement to perform animal research at a foreign site, there needs to be a risk assessment to determine what the institu- tion needs to do for monitoring and oversight. What kind of oversight is there? Is the institution AAALAC accredited? Are there local regulations? What infra- structure is available? What is the physical plant like? Are the human resources skilled or unskilled? What are the reporting lines of authority? There are also concerns about conflict of interest, e.g., is the person in charge of animal welfare reporting to the investigator doing the work? Also, the species involved may matter—the higher the species the more concern. Other concerns surround whether the procedures are invasive or noninvasive, the appropriateness of the number of animals, and whether the study is large or small. It is important to know whether the institution has a track record of collaborating with other insti- tutions and whether any of their work has been published. If so, what does the materials and methods section say in the paper? This information can give a lot of insight into how the institution conducts its work. After the risk assessment, a monitoring program needs to be implemented. There is an auditing clause in the subaward or subcontract, which primarily in- volves following the money to see how it is spent. However, it also gives the primary institution the ability to audit any documents related to regulations. In addition, the auditing clause allows the primary recipient to audit many aspects of the project according to the terms and conditions of the subcontract. The terms of auditing need to be very clear. If the institution wants to perform a spe- cific document review, it needs to specify which documents should be kept and the frequency of the audit review. Physical monitoring of the facility is the best option. There are multiple ways to do this, but the best is a site visit at least initially. Physical monitoring may also be done by requesting pictures and videos, or by looking through webcams. These methods all have security issues but as it has been said be- fore, a picture is worth a thousand words, and going there is probably worth 10,000 words. What happens if through the monitoring review noncompliance is ob- served? Who reports? Recall that the foreign assurance does not require that institution to report; reporting is the responsibility of the primary grant recipient. Who is held accountable for investigation and correction? Since the foreign country is out of OLAW’s jurisdiction, the main responsibility is on the primary institution. On the OLAW website there is a document that describes what hap- pens during progressive noncompliance. Certainly one repercussion would be

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An Academic Perspective 235 cessation of the financial support to the foreign institution if noncompliance was not resolved. The last thing I wish to address is the recent trend with clinical trials. The FDA has put out new standards for the conduct of clinical trials. The new stan- dards mandate that foreign clinical trials must now have an independent ethical committee and must be in compliance with the FDA’s good clinical practice. In the past, the standards were similar to what the requirements are for the foreign assurance now, i.e., the work must follow an international guideline. However, the stringency has increased to ensure that the data are reproducible and of ap- propriate quality to support a New Drug Application. In an academic collaboration the onus is on the primary recipient to make sure that all of these things are occurring. If issues arise that are numerous and serious enough, it may be that this kind of regulation for animals will follow.

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Perspective from China Alex Zhang To begin, I would like to say that I am not a specialist in laboratory ani- mals but rather a biologist, with a specialty in stem cells. For the past eight years I have been working in a medical university in Beijing and I am currently in- volved in an effort to build a primate research facility in China from the ground up. I would like to tell our story of how to build such a facility. In the past few days, almost all the talks mention China, and yet I am the only person who came from China, and I am not even a specialist in this particu- lar area. At the end of my presentation, I would like to offer suggestions for those who are either planning on or now working with Chinese entities on scien- tific projects. In 2003, most of my research [on stem cell therapy] was with mice. Before going to human trials I wanted to move to nonhuman primates. At that time the SARS epidemic rampaged through China and all animal transportation was stopped throughout the country. Consequently I wanted to find out where it might be possible to do NHP studies in China, i.e., where the monkeys were, where the good facilities were. Most of the monkey breeders are in southern China; almost all the Chinese rhesus colonies or breeders are to the southwest. The area north of Vietnam is where many of the breeders of cynomolgus monkeys are located. In visiting the area, I found many monkey breeders. For the bigger ones, the basic unit is 10,000, so they have 10,000 or 20,000 or 30,000 monkeys. But there were no good research facilities at all, and certainly not the type of facility we would like to have to do stem cell cultures or brain surgeries. So we decided to build our own. We chose the city of Nanning for two reasons. One is that it is a small city by Chinese standards, with a million people, but the air is good, there is no traf- fic, and there are many direct flights to the big cities like Beijing, Shanghai, and Guangzhou. A second reason is that there are many good breeders in that gen- eral area, and most of them provide high-quality cynomolgus monkeys. Most of these facilities sell the monkeys abroad. 236

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Perspective from China 237 We talked to local people and rented space from them to set up our own facility. We immediately faced a problem that has already been discussed and that is an overall lack of awareness of animal welfare. Things have improved in the past two or three years, but it is still a problem. Also, there is a lack of exper- tise in veterinary care and technical skills. This is now recognized as a problem, and some remote education programs or lecture series have become available in China, but unfortunately at that time there were none. Also, the quality of the animals is variable. Most of the breeders that sell to foreign countries are very good, but others are not, so we must stringently screen those animals. All this is quite understandable. A quote from a commentary in Cell [129(6):1033-1036] published last year says: “There are 135 million Chinese living on less than $1 a day, which the World Bank defines as abject poverty. In comparison, ‘monkeys listen to music, have toys to play with and drink purified water’ in Wincon’s AAALAC-accredited lab.…” Even with the economic boom in the past few years, there are still many people at a very low standard of living. In such places it is difficult to provide care for our monkeys in such a way that they listen to music, have toys to play with, and drink purified water. With re- gard to purified water, I have a relevant personal experience. When we decided to install water purification systems for our monkeys, our technician came to me and asked if we could install a faucet in the office for the staff: people do not have purified drinking water—they normally boil the tap water for drinking. This small anecdote provides a view into the situation in China. In developing our program, we decided to adopt a high standard, starting with the Guide. While this was a very good decision, in the beginning it was a very tough plan to carry through. Staff, including myself, had no experience with the Guide. It is embarrassing to say here that I became aware of AAALAC only in 2004. However, since we decided to go for this particular standard and apply for AAALAC accreditation, it has forced us to do everything properly and acceptably to the international community. We were very fortunate to develop a collaboration with the University of Wisconsin, National Primate Research Center, and with Joe Kemnitz in particu- lar. The center sends staff to our facility for days and sometimes weeks to help us implement the Guide in our facility and laboratories. This activity is continu- ing, but now people come not just to tell us what to do but also to collaborate with us on scientific experiments. The third piece of developing our program involved the implementation of continuing education for our staff. The final aspect of our program development was working with the local government to educate them and the local community. These efforts serve to bring support from the local community and funds from the local government. It has been amazing how quickly things have progressed. In 2003 I visited Nanning and we were able to convince some local business people and the local government to put in some modest investment to rent a space on the second floor of a building beside a breeder, a big monkey farm. In 2004 we decided to

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238 Animal Research in a Global Environment: Meeting the Challenges work toward the standards set by the Guide, and in 2005 we had laboratory ani- mal professionals from the University of Wisconsin come in to help us. By the end of 2005 we were able to apply for AAALAC accreditation, and we received it in 2006. Since then everything has been progressing even faster, like everything in China nowadays. First, we immediately started getting phone calls from various pharmaceutical companies about our company. Second, we suddenly received investment money to build a new facility, which is to be completed by next year. Third, on a personal level, I have become one of the bigger clients of this com- pany but am no longer involved with it. A large portion of my research grant goes into this company to support my study. But I feel happy about the outcome because I am a scientist, not a businessman. Finally, I would like to offer a few additional suggestions for those plan- ning to work with Chinese entities. The first is that it is important to spend more time going to China, and not just for site visits. It is important to spend time with the people who work there and this will help to solve a lot of problems such as language. Even though the English language capability of Chinese staff is not great, much may be accomplished just by working side by side. Also, it helps to build trust. Once everyone knows each other, it is possible to determine their trustworthiness, which is something that cannot be done by teleconference or videoconference. Another consideration is that flying human primates is cheaper than flying nonhuman primates, given the restrictions with transportation. Even though travel to China is expensive, it is worth it, especially if one is working with non- human primates. An additional suggestion is that people coming from abroad should work with the Chinese government, which, at the local or federal state level, is very receptive to advice from abroad and is also receptive to collaborations. In the last few years we were able to convince a major science funding agency in China to add requirements for major grants, mandating that facilities doing ani- mal studies must comply with international standards, either by AAALAC ac- creditation or adherence to the Guide. Finally, we are lobbying the Chinese government to support sequencing of the cynomolgus monkey genome so that we can compare the various sub- species as well as do genomic comparisons of Chinese and Indian rhesus. Working with the government may require additional effort, but it helps to tap into government resources.

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Transportation Issues with Nonhuman Primates Saverio Capuano I am going to focus on the transportation issues surrounding nonhuman primates (NHP). It is important to remember that almost 27,000 monkeys came into the United States in 2007.1 Even though there is a financial crunch and there is not as much money for research and fewer carriers are flying animals, there were still 27,000 monkeys that came into this country—and I am still worried about transporting animals. Not only are there fewer carriers flying animals but there is no air trans- port within the US. We are converting to ground transport internally, and there are several companies that are very good at it. It has been said previously at this conference that there are very few deaths during transport of NHP. But every year about 200 deaths occur in quar- antine and it should not be considered a successful transport until the animals get out of quarantine. While some of these animals travel huge distances, even thousands of miles, a 1% death rate is still unacceptable. Facilities should be examined to find out why, if the animals are preconditioned and healthy before transportation, 1% of those animals die in quarantine. There is a veritable cornucopia of laws and governing bodies that must be dealt with in order to move animals domestically or internationally and various agencies to enforce these laws and guidelines. Many times these regulations contradict each other and there may be [a lot of] ambiguity. Sometimes it is very difficult to know what the rules are. In addition, it is necessary to deal with offi- cials at every one of these governing bodies and their interpretation of the laws. My plea to all of the attendees here is to get together and work with the agencies to develop an interagency agreement. The goal of such an agreement would be to bring all the documents together to give us better guidelines. The difficulty in finding air carriers that will transport NHP has already been discussed. The profit margin for airlines to carry the animals is very low, 1 Data from G. Gale Galland, Nonhuman primate importation and quarantine, United States: 2007. 35th Annual Workshop of the Association of Primate Veterinarians. Octo- ber 11-13, 2007; Charlotte, North Carolina. 239

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240 Animal Research in a Global Environment: Meeting the Challenges and it costs them money to train their employees, put them at risk, and deal with the public relations aspect of it. It is likely that in the future there will be even fewer carriers that will transport these animals. Good transport practices are based on common sense, on experience, and on knowledge of the animals. It is important to know the inspectors, know the rules, know all the officials, and know your shipping company, especially when it is a large or long shipment. Know what is going to happen with those animals every step of the way. Remember that regardless of how the animals are cared for in your facility, once they leave it they are under the control of others. One thing is to anticipate the weather, particularly in the summer, when there is cause for worry because of potentially high temperatures. Another consideration is space allocation. While the animals are housed in a facility more space may be better, but during transport small is much better. Large spaces mean more chance of animals falling, of rolling, of problems with motion in transport. Food and water of course must be considered. Anorexia and adipsia may occur during transport. It is not prudent to include large volumes of water because it causes changes in temperature and bad sanitation in your trans- port. With regard to handling, it is extremely important to precondition and ac- climate the animals. They should be prepared by becoming acclimated to the transport cages and to the food they will eat during the trip. It is prudent to instruct the driver or whoever might be moving or handling the animals about how to act with them, what behaviors to look for, and to be careful with them, remembering that the transporter likely has little or no knowledge about the animals. It is important to provide for a way to monitor the animals throughout the trip and to prepare emergency procedures for a worst-case scenario, such as the truck breaking down or the need to euthanize an animal. It may be necessary to have alternate places for the animals to go if the unexpected happens. Other issues that should be considered are training, shipping containers, and biosecurity. Initial training and continuing education should be given to transporters. With regard to shipping containers, ideally each container should have an overcarrier, but this may not be feasible. However, it is necessary to ensure that the container will endure a trip of thousands of miles. This is particu- larly true when it comes to biosecurity. If urine or feces were to penetrate to the outside of the container, workers may be exposed to infectious agents the pri- mate might be carrying. This also raises the issue of having the workers wear personal protective equipment. Ideally, they should, but doing so might raise concerns among the public who see them. The workers should ideally also be aware of biocontainment issues, but without specific training it is unlikely that they would be. In summary, it is important to consider all of these issues before transport- ing animals in order to make it safe, especially for the animals.

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The Future of the Use of Nonhuman Primates in the UK Judy MacArthur Clark This presentation will focus on what we have recently been doing in the UK in terms of reviewing the use of nonhuman primates and whether such use can be justified. It will consider the Weatherall report,1 including the goal of that review, the methodologies, conclusions, and recommendations in the report, and the responses to the report. I will end with some personal ideas in terms of the way forward. I am taking the place of Professor Roger Lemmon who was unfor- tunately not able to be here. A snapshot of primate use in the United Kingdom (from 2007 UK Home Office statistics) shows that use of primates is significantly less than in the United States. We performed about 4,000 procedures on primates in 2007, which constitutes about 0.1% of all procedures. The actual number of primates used was about 3,125, and most of those would have been Old World macaques, with a much smaller number of New World monkeys, primarily common mar- mosets. The number of animals and the number of procedures differ slightly because some animals are used in more than one procedure and are thus counted more than once. The statistics indicate that 87% of animals used are in regulatory toxicol- ogy and about 13% in basic or applied research, which was the area of greatest interest to the authors of the Weatherall report; thus I will not say much about regulatory toxicology. The ratio of rhesus to cynomolgus macaques in the UK is slightly different from that in the US, where rhesus monkeys are used in most basic and applied research. The data show that the use of Old World monkeys has stayed relatively stable from 1995 to 2007. On the other hand, the number of New World monkeys seems to be on the decline. The background to the generation of the Weatherall report was a report from the Boyd Group in 2002. The Boyd Group is a very diverse group of indi- 1 The Use of Non-Human Primates in Research and Testing (2002). Jane A. Smith and Kenneth M. Boyd, ed.; the Boyd Group. Leicester: The British Psychological Society. 241

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242 Animal Research in a Global Environment: Meeting the Challenges viduals from a range of backgrounds, including science, government, welfare, and antivivisection organizations. In 2002, they produced a report on the use of nonhuman primates in research and testing.2 That information was also then taken into consideration by the Nuffield Council on Bioethics, which was also a very interesting group of which I was privileged to be a member. We produced a report in 2005 on the ethics of re- search involving animals.3 I recommend that report to provide a breadth of un- derstanding of the ethics of use of animals in research, which is an excellent starting point. Arising from the realization in the Nuffield Council report that there were significant views being expressed about the ethics of using primates in research, the Royal Society and others in the UK set up the Weatherall Committee. It re- ported in December 2006 on the use of nonhuman primates in research. The focus of the report, however, was much more on the scientific justification as opposed to ethics. The sponsors of the report were the Royal Society, which is somewhat the equivalent of the National Academies, the UK Academy of Medical Sciences, the Wellcome Trust, and the Medical Research Council, the last two being the major funders of basic and applied research involving primates. It was focused on hypothesis-driven research in academia and looked at the use of primates in communicable disease research, neuroscience, and reproductive biology. There was a small amount about fetal development research and aging, as well as a brief consideration of drug discovery and development. The report also consid- ered alternatives, welfare issues, and ethics to an extent, but those were not ma- jor components. The central goal of this study was to examine the scientific case for the use of nonhuman primates for research into the prevention and treatment of disease or for fundamental research that has the long-term potential for achieving the same end. This was a fairly unique approach to looking at the use of primates and justification for their use in research. The methodology was to set up an “independent” committee. This means that all members of the nine-person committee were nonusers of primates in research, although some of them were academic researchers, including those from overseas, and there was also representation from lay people. There was a public call for evidence to which 62 responses were received. In addition the committee took oral evidence from 35 witnesses. Both breeding and using sites were visited by the committee. The committee sat for some 18 months, and took a fairly rigorous approach to writing the report. 2 The Use of Non-Human Primates in Research (2006). A working group report chaired by Sir David Weatherall. London: The Royal Society, Academy of Medical Sci- ences, Medical Research Council, Wellcome Trust. 3 The Ethics of Research Involving Animals (2005). London: Nuffield Council on Bio- ethics.

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The Future of the Use of Nonhuman Primates in the UK 243 This is an appropriate place to state that the UK regulatory control system is very stringent, with a requirement for three licenses for any primate use. There are also local ethical review processes. Many recommendations emerged in this report. First, it concluded there was a strong scientific case for the carefully regulated use of nonhuman primates when there are no other means to address clearly defined questions of particular biological or medical importance. The second recommendation reiterates that point in relation to the fields considered in the study—communicable diseases, neuroscience, and reproduc- tive biology—confirming that nonhuman primates were needed at least for the immediate future. There is a sense in this report that there are developments occurring all the time that may or may not affect the justification for the use of primates in the longer term. The third recommendation is that major specialist organizations should regularly collate information involving their fields, and the information should be disseminated to funding bodies, ethics committees, and regulatory agencies. Fourth, the major funding organizations should undertake a systematic re- view of the outcome of all research using nonhuman primates supported over the last decade. That is being done by examining the benefits resulting from funding those areas of research. The fifth recommendation refers to the development of alternatives, and there is strong support for greater funding to develop alternatives to the use of nonhuman primates both in research and in toxicology. Funders should expand their support for research into refining nonhuman primate research practices particularly in behavioral neurosciences. A sixth recommendation related to retrospective reporting of severity of procedures. This would entail introducing a system to report severity actually incurred during procedures, either to a local ethical committee or more cen- trally. Obviously such reporting would take place after the procedures have been performed. The next recommendation called for improvements in the training of re- search workers in nonhuman primate research. The committee also addressed housing issues, specifically minimum cage sizes, avoidance of single housing, and how cage fittings and conditions can be accommodated to the purpose of the experiment, thereby relating the housing to the purpose of the research. They also called for better assessments of the advan- tages of things like access to outdoors and the general need for visual stimula- tion for primates. The next three recommendations relate to regulatory toxicology, particu- larly in areas where alternatives may be feasible, and pursuing regulators to con- sider what may be unnecessary tests or duplication of tests.

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244 Animal Research in a Global Environment: Meeting the Challenges There was a recommendation toward the end of the report that looked at the creation of UK centers of excellence, which I will address further when I talk about future activities. The Weatherall report was produced in December 2006, and in June 2007 there was a flurry of activity in response to the report. The funders and govern- ment produced a combined response that was generally supportive of the rec- ommendations and gave commitment to take them forward and to work together on the strategy of how to move forward. Shortly thereafter, the UK National Center for the Three Rs (NC3Rs) pub- lished a critique of the report. It was a constructive critique that sought a more rigorous review and analysis of the use of primates in research. It talked about the need for a national strategy, which is something now being explored. It also mentioned that the NC3Rs has set up an annual meeting on the welfare of pri- mates, which has been serving a very useful purpose. It draws a very diverse audience and serves as a very useful forum for comparing best practice across the community that is involved and interested in research using primates. What is next then? We are embarking in various areas on thematic re- views of the use of primates. One area that needs to be explored is the use of primates in neuroscience. My team of inspectors in the UK looks at how the cost-benefit assessment is applied in those studies and how we can help our licensees to adopt best practice. Looking at retrospective severity is also an interesting exercise, including options for alternatives and how effectively those are being applied. In addition, there are moves toward development of a national primate strategy, including determining the need for centers of excellence. In the UK there are far fewer centers that use primates than in the United States. Some question whether it is necessary to develop new centers of excellence rather than have existing centers become better networked together. The national primate strategy will also look at things like training and sourcing, which were not ad- dressed in the Weatherall report but are nevertheless very important. Also, it will be important to heed the recommendations from [the] Weatherall [report] about media and public understanding about why primates are used. But as already stated, the use of primates is a global issue, not solely a UK issue nor a US issue. While we do some small-scale breeding of primates in the UK, many of our primates are sourced from overseas, primarily China, Vietnam, and Mauritius. It’s clear we have to think of primates as a global resource. We are cur- rently competing with other countries for our needs; we should not be in compe- tition but rather exploring the needs of science together. There are significant transport and welfare issues to consider as well. And there are significant oppor- tunities to share best practice, especially between countries, such as the US and UK, with well-established programs of primate research and those that are emerging scientifically in this field.

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The Future of the Use of Nonhuman Primates in the UK 245 Those are just some of the issues that come with the fact that the use of primates in research is not only a highly sensitive issue but also something that has global impact. My conclusion is that this is an ideal opportunity for global collaboration and harmonization, so that we are not competing for use of these animals but truly ensuring that this global resource is being used as effectively as possible. We must achieve this by sharing our ideas and by sharing access to those re- sources.

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Proposed International NHP Plan Joseph Kemnitz In lieu of the last item on the agenda for this afternoon in terms of presen- tations,1 I will simply mention that the ILAR Council and staff would like to capture the content and the spirit of this afternoon’s session and use it to launch an international primate plan to enable the best use of global resources to maxi- mize research progress that requires the use of nonhuman primates while mini- mizing the numbers used and the negative consequences for the animals. We have a draft plan that is not completely polished. Our hope is to launch it within the year. We need some additional resources in order to do so. Then we have a time line that would call for completion of a written plan within two years. Finally, I thank all of you who participated in this conference, especially the speakers, and very especially Joanne Zurlo and the ILAR staff as well as the sponsors of this meeting. Text of Joseph Kemnitz’s Slides on the Proposed International NHP Plan Background First primate plan developed in 1978 by the Interagency Primate Steering Committee established by the Director of the National Institutes of Health (NIH). Recommendations were made to ensure: • Expansion of domestic production of nonhuman primates (NHP) • Action to ensure effective use of NHP 1 This session reached the end of its allotted time and eclipsed Dr. Kemnitz’s presenta- tion about the International Primate Plan; the text of the slides he prepared for presenta- tion is included here. 246

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Proposed International NHP Plan 247 • Stable supply and long-term availability of NHP from countries of origin The 1978 Plan was quickly outdated (e.g., ban on exportation from India, AIDS crisis). Great pressure was put on Indian-derived rhesus monkey re- sources. A workshop on International Perspectives: The Future of Nonhuman Pri- mates Resources was convened by ILAR in 2002. • Reports on NHP resources and programs in 16 countries • Updates on issues such as nutrition, genetics, microbiology and trans- portation A companion workshop, Rhesus Monkey Demands in Biomedical Re- search, was convened by NIH’s Office of AIDS Research (OAR) and National Center for Research Resources (NCRR). • Emphasized pressure on Indian rhesus monkey supply • Encouraged use of alternative species • Develop a comprehensive plan to preserve and expand resources for biomedical research using NHP models Rationale for a New Plan • Increasing need for human disease research and testing • Disease threats that compromise quality and supply of NHP • Globalization of research • Need for conservation • Need for renewed investment in infrastructure Overall Scope To address the current and future needs of NHP supply and use in bio- medical research on a global level with consideration of multiple issues Scope 1. Supply and demand issues based on input from countries and facilities that are major producers and/or users of NHP • Projections for NHP demand in the US over the next ten years will be determined in part by examination of US Department of Agriculture data and import/quarantine information from the last 10–15 years and in part by examina- tion of trends and anticipated future trajectories of those trends.

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248 Animal Research in a Global Environment: Meeting the Challenges • Assessment of needs for NHP in other countries by enlisting expertise from these countries in the project. 2. Factors affecting the breeding of various species of NHP used in re- search • This will include breeding of NHP both in the US and abroad, and will address issues such as nutrition, age of dams, pregnancy success rates, genetic management. 3. Infectious diseases affecting NHP and the standardization of microbial characterization of individuals and colonies with a focus on quality control and the development and use of reference reagents to minimize variability among laboratories and facilities. 4. Genetic management of animals including either genetic diversity or genetic similarity, depending on the needs of the research with recommenda- tions for standardizing practices. 5. Behavioral management of the animals with recommendations for best practice in maintaining psychological well-being, optimal housing conditions and colony management. 6. Transportation issues specific to NHP, including the control of micro- environment of the animals during shipping, transport of biological samples from NHP, and current international regulatory obstacles to importation and transportation of animals. 7. Training of individuals involved with the care and use of NHP, includ- ing research and husbandry staff, and addressing the shortage of veterinarians specializing in NHP medicine. 8. Recommendations for the conservation of NHP resources, including the creation of formal mechanisms to facilitate sharing of samples and animals, de- tailed databases of genomic information on individual animals and development of small animal models to replace NHP where appropriate. Some additional issues to be addressed: • Elaborate on the translational value of research on NHP to human disease • Identify priority areas of basic research for which NHP resources will be essential