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PHS PolicyLast modified on June 21, 2002 OLAW Guidelines on PHS Policy (FAQs) PHS Policy (Implementation of the Health Research Extension Act of 1985, PL 99-158){3949}In 1972 the Director of NIH created the Office for Protection from Research Risks (OPRR) to ensure the welfare and safety of human and animal subjects. OPRR also had a regulatory role in monitoring the compliance of institutions with rules governing research subjects. NIH and OPRR are part of the Department of Health and Human Services (HHS). The Animal Welfare Division of OPRR is responsible for making sure that PHS-funded institutions meet requirements in addition to those specified in the AWA. This mandate was derived from the Health Research Extension Act of 1985 (PL 99-158, November 20, 1985, Animals in Research, Sec. 495(a)). This act required that the Secretary of HHS act through the Director of NIH to establish guidelines for the following:{4519}
Any institution that receives funding in the form of grants, contracts or awards from the PHS (this includes NIH) must adhere to the PHS Policy. A written assurance must be provided to OLAW that the institution will follow the "Principles for the Use of Animals" and also the Guide. The institution must have an IACUC (although who is responsible for appointing it isn't specified, unlike the Guide and 9CFR) to maintain oversight of the facilities and procedures involving animals. The IACUC must have at least 5 members who are knowledgeable in the care and use of animals.{3947} PHS Policy endorses use of the Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training. The Policy is intended to supplement and implement the Principles. A few definitions are relevant and may be different than those found elsewhere:
As an institution implements the PHS Policy, it must first submit a written Assurance. OPRR (now OLAW) approves Assurances for up to 5 years. Without an applicable, PHS-approved Assurance, no PHS-conducted or supported activity involving animals may continue. The institution’s program for animal care and use must be based on the Guide and on USDA regulations. It includes the membership list of the IACUC, a description of the occupational health program, a synopsis of the training offered to people involved with animals, and information about the square footage of the facility and the animals currently housed there. An institution must belong to either Category 1 – Accredited by the AAALAC and inspected by the IACUC every 6 months, or Category 2 – Evaluated by the IACUC every 6 months. Interestingly, the Health Research Extension Act upon which the PHS Policy is based requires only 3 members on the IACUC, of which one must be non-affiliated with the institution and one a DVM. PHS Policy, however, requires that there be 5 members, of which one is a trained DVM, one a practicing scientist experienced in research with animals, one a non-scientist, and one a non-affiliated member. The functions of the IACUC are quite similar to those listed in 9 CFR. Protocols must be reviewed and in conformance with the Guide and the AWA, and must meet the following requirements:
Protocols must be provided to all IACUC members prior to review, and any member can request a full committee review. At least one member is designated by the chair to either approve, require modifications to, or request full committee review of every protocol. If a full committee review is requested, there must be a quorum present (a majority) and a majority of those present must vote to approve the protocol in order for it to be approved. Protocols must be re-reviewed at least every 3 years. Grant or contract proposals submitted to PHS must contain the following information. Proposals from institutions with an approved Assurance must include verification that the IACUC has approved the protocol within 60 days after the receipt deadline date. If the institution does not yet have an Assurance, the signature of the official signing for the applicant is a declaration that the institution will submit an Assurance when requested by OLAW.
The institution must maintain the following records for at least 3 years, or for 3 years after the completion of the activity. This is the same requirement as in 9CFR.
Finally, the institution’s IACUC must report to OLAW annually, whether there have been changes or not. If there have been no changes, a letter must state that, and give the dates of the IACUC evaluations. Changes that must be reported include any changes to the institution’s category (i.e. if AAALAC accreditation status changes), changes in the program of animal care and use, and changes in IACUC membership. If there are any actions taken by the IACUC as a result of serious or continuing noncompliance with the PHS Policy, serious deviation from the provisions of the Guide, or suspension of any activity by the IACUC, these must be promptly reported to OLAW. US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and TrainingThese Principles were developed by the Interagency Research Animal Committee (IRAC). "The development of knowledge necessary for the improvement of the health and well-being of humans as well as other animals requires in vivo experimentation with a wide variety of animal species. Whenever U.S. Government agencies develop requirements for testing, research, or training procedures involving the use of vertebrate animals, the following principles shall be considered; and whenever these agencies actually perform or sponsor such procedures, the responsible Institutional Official shall ensure that these principles are adhered to: I. The transportation, care, and use of animals should be in accordance with the Animal Welfare Act (7 U.S.C. 2131 et. seq.) and other applicable Federal laws, guidelines, and policies. II. 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. III. The animals selected for a procedure should be of an appropriate species and quality and the minimum number required to obtain valid results. Methods such as mathematical models, computer simulation, and in vitro biological systems should be considered. IV. Proper use of animals, including the avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices, is imperative. Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals. V. Procedures with animals that may cause more than momentary or slight pain or distress should be performed with appropriate sedation, analgesia, or anesthesia. Surgical or other painful procedures should not be performed on unanesthetized animals paralyzed by chemical agents. VI. Animals that would otherwise suffer severe or chronic pain or distress that cannot be relieved should be painlessly killed at the end of the procedure or, if appropriate, during the procedure. VII. The living conditions of animals should be appropriate for their species and contribute to their health and comfort. Normally, the housing, feeding, and care of all animals used for biomedical purposes must be directed by a veterinarian or other scientist trained and experienced in the proper care, handling, and use of the species being maintained or studied. In any case, veterinary care shall be provided as indicated. VIII. Investigators and other personnel shall be appropriately qualified and experienced for conducting procedures on living animals. Adequate arrangements shall be made for their in-service training, including the proper and humane care and use of laboratory animals. IX. Where exceptions are required in relation to the provisions of these Principles, the decisions should not rest with the investigators directly concerned but should be made, with due regard to Principle II, by an appropriate review group such as an institutional animal care and use committee. Such exceptions should not be made solely for the purposes of teaching or demonstration." OLAWInformation is readily available at the OLAW Web site (http://grants.nih.gov/grants/oprr/library_animal.htm) regarding their opinions about how to conduct animal research. The following is a list of FAQs that discuss important questions relating to applicability of PHS policy.{3755} Do commercial sources need an Animal Welfare Assurance? Deadlines for non-compliance reporting Do sentinels have to be covered by protocols? Employee health programs defined Major and minor deficiencies defined Do samples sent from abroad need to have a protocol? Does the IACUC need 3 or 5 members? Can we perform multiple C-sections to preserve threatened species? Do we have to track animal numbers used? 1. The Institutional Animal Care and Use
Committee at our institution is uncertain about what criteria to use in
determining what constitutes a "significant change" to an
approved research protocol, so that it can implement the appropriate review
mechanism. How should we interpret the PHS Policy in this regard? "... we have identified several kinds of significant changes that may serve as examples to guide the IACUC in its determinations. They include but are not limited to: changes in the objectives of a study; proposals to switch from nonsurvival to survival surgery; changes in the degree of invasiveness of a procedure or discomfort to an animal; changes in species or in the approximate number of animals used; changes in personnel involved in animal procedures; and changes in anesthetic agent(s), the use or withholding of analgesics, and methods of euthanasia..." 2. Our institution purchases antibodies
from commercial sources for use in various PHS-supported studies conducted in
its facilities. Does the PHS Policy require that the commercial source have an
Animal Welfare Assurance on file with the OLAW? "In the case that standard reagent antibodies (e.g. mouse-antihuman) are produced by a commercial supplier using their own resources and offering them for general sale, for example, through a catalogue, the institution may consider the antibodies to be "off-the-shelf" reagents, and the supplier is not required to file an Assurance with OLAW. If, on the other hand, a supplier or contractor produces custom antibodies using antigen(s) provided by or at the request of a principal investigator, the antibodies are considered "customized" and the vendor or subcontractor must file an Assurance with OLAW. When both the PHS Grantee and its Contractor hold OLAW-approved Assurances, some latitude is allowed in determining which IACUC (if not both) will review the proposal. However, the institution which subcontracts or subgrants any animal activity retains partial accountability for providing effective oversight mechanisms to ensure compliance with the PHS Policy. Part of that responsibility includes ensuring that subgranted/subcontracted animal-related activities are conducted only at an Assured institution." 3. Our institution receives funding from PHS and non-PHS sources. Must we
include those programs, projects, and facilities which are not supported by the
PHS in our Assurance of Compliance? "OLAW advises institutions that the maintenance of uniform and consistent standards is an essential ingredient in the development and implementation of a quality animal care and use program. Only when an institution can document that the animal care and use program funded by a non-PHS source is entirely separate and distinct, physically and programmatically, from PHS-supported activities will OLAW consider its exclusion from the Institutional Assurance. .." 4. How extensive must the animal care and use
training program be in our small institution, and at what frequency should it
be offered? "Each Assured Institution is responsible for training its staff to meet the performance requirements cited in paragraph IV.C.1.a.- g. of the PHS Policy, and guidelines have been developed to assist institutions to meet these objectives... At a minimum, however, the Policy requires institutions to ensure that individuals who use or provide care for animals are trained and qualified in the appropriate, species-specific housing methods, husbandry procedures, and handling techniques. The institution must ensure that research staff members performing experimental manipulation, including anesthesia and surgery, are qualified through training or experience to accomplish such procedures humanely and in a scientifically acceptable fashion. They must also provide training or instruction in research and testing methods that minimize the number of animals required to obtain valid results and minimize animal distress. Institutions must also ensure that professional staff whose work involves hazardous biological, chemical, or physical agents have training or experience to assess potential dangers and select and oversee the implementation of appropriate safeguards. Finally, OLAW strongly recommends that institutions offer their staff access to training leading to certification in animal technology such as that available from AALAS or a formally designated academic program. Institutions should also know and ensure compliance with any initial and continuing education State requirements for the licensing of veterinary or animal health technicians." 5. In the event that our IACUC
reports a serious noncompliance with the PHS Policy or deviation from the Guide,
we understand that the report must fully explain the circumstances and actions
taken to correct the situation. How soon after the noncompliance or deviation
is identified must we submit the report? How closely is our institution held to
meeting its self-imposed schedule for correction? "...Examples of noncompliance and deviations include: conducting an animal-related activity without appropriate IACUC review and approval; the temporary or permanent interruption of an activity involving animals by the IACUC; and conditions that jeopardize the health or well-being of an animal. The USDA's Animal Welfare Regulations are more specific, requiring institutions report such matters to the Animal Plant and Health Inspection Service (APHIS) and the funding agency if not resolved within 15 business days of the completion date specified in the IACUC's initial corrective plan and schedule. The IACUC should use the interval to investigate and develop a definitive corrective plan and a schedule for implementation. In many cases, it also provides ample opportunity for total resolution of the problem. One should note, however, that solution of the problem does not dismiss the institution's obligation to file a report with OLAW and APHIS. When the IACUC cannot completely resolve the noncompliance or deviation within the allotted time, the institution must present a specific and reasonable corrective plan and schedule. If the situation directly involves animals and threatens their health and safety, such plans are to contain interim measures, including possible relocation of the animals at risk. OLAW's acceptance of a plan and schedule is usually conditioned on notification when the corrective action is complete. It is recognized that circumstances which are beyond the institution's control may arise and prevent the scheduled completion of the plan. In such cases, OLAW will consider requests to extend the schedule if the circumstances are adequately described and the proposed new deadline is reasonable." 6. Our institution uses animals as sentinels in the
animal disease surveillance program, in breeding programs, and as donors for
blood and blood products. Since these animals are not used in research per se,
is it necessary to develop protocols for the review and approval of our IACUC? "PHS Policy applicability is not limited to research. It also includes all activities involving animals including testing and teaching..." 7. Could you describe the kind and
extent of the employee health program required by the PHS Policy? "Principal requirements for an institutional occupational health program are outlined in the Guide for the Care and Use of Laboratory Animals. .. Thus, the institution must base their health program on an assessment of the risks present in its particular animal research program, including those in cagewashing and other support activities. Basic elements of any health program, however, should provide: a pre-employment medical evaluation and history; immunization against tetanus; detailed training on how to perform required procedures safely; instruction in personal hygiene, zoonoses, and precautions for pregnant women and others at risk; protective clothing and devices; instruction in first aid procedures appropriate to potential hazards; and access to medical attention for the treatment of animal bites, scratches, allergies and other job-related injuries or illnesses. When there is risk of exposure to rabies through the use of random-source dogs and cats and certain wildlife species, the institution should offer pre-exposure immunization, and should regularly schedule tuberculin testing for all personnel exposed to nonhuman primates. The institution should have precautions in place and a zoonoses surveillance mechanism established when work involves exposure to nonhuman primates and species likely to harbor the causative agents of diseases such as Q fever, tularemia, hantavirus pulmonary syndrome, and plague. When research involves infectious diseases, such as hepatitis B, for which there are safe and effective vaccines, the use of prophylactic immunizations should also be considered. A health program is required not only for persons having "frequent contact with animals," but for all "personnel who work in laboratory animal facilities." These include not only animal caretakers, technicians, students, volunteers, investigators, and veterinarians but facilities maintenance engineers, housekeepers, security, and other staff. OLAW recommends that the foregoing phrases be interpreted in the context of the potential risks to which the persons are exposed..." More FAQs were addressed in 1997 in another journal:{3759} 1. Could you provide examples of
"significant" and "minor" deficiencies and suggest
appropriate methods for reporting them in the Institutional Semiannual and
Annual Reports? "The term "significant deficiency," ... refers to any facility or program deficiency that is or may be a threat to the health or safety of animals. Program or facility deficiencies, including accidents and natural disasters, which cause injury, death, or severe distress to animals, are, by definition, "significant." ...Some illustrations of significant facility deficiencies include failures in heating, ventilating, and air conditioning systems and their associated electrical systems; inoperative watering systems; and general power failures of sufficient duration to affect critical areas such as isolators, barriers, surgical suites, and intensive care units. Minor deficiencies in animal facilities include infrequent findings of peeling or chipped paint, burnt-out light bulbs, missing floor drain covers, and similar problems for which immediate solutions generally are not necessary to protect life or prevent distress. Repeated detection of minor, area-specific problems, however, should suggest to management that there are substantial program deficiencies resulting in failure to develop effective policies or plans or to take corrective actions to prevent recurrences." 2. Investigators at our institution often
collaborate with scientists in other countries and sometimes go abroad to
collect samples from captive wild animals maintained in zoological collections
and in research colonies. Is it necessary for our IACUC to review and approve
their protocols? What about samples that are obtained by citizens of the
foreign country and sent to our institution? "All animal activities supported by the PHS must be reviewed by the IACUC of the domestic-assured awardee institution that receives such support. Foreign institutions that serve as performance sites must also have Assurances on file with OLAW.... In the specific case of sample collection, the review should take into account the species involved, nature of the specimen, and the degree of invasiveness of the procedure, giving appropriate consideration to the use of anesthetics and analgesics. In cases in which samples are obtained directly by citizens of a foreign country for subsequent shipment, recipient PHS-supported investigators should determine the proposed methods of collection and present that information to their IACUC for review... OLAW strongly recommends that each awardee institution consult with other agencies of the U.S. government concerning importation requirements. Depending on the species involved and the nature of the specimen, the following may be of assistance: the U.S. Fish and Wildlife Service, Department of the Interior (for compliance with the International Convention on Trade in Endangered Species of Fauna and Flora [CITES]), APHIS, U.S. Department of Agriculture (regarding potential animal pathogens), and the Centers for Disease Control and Prevention (concerning importation of nonhuman primates and potential pathogens of human beings)." 3. The PHS Policy requires that the IACUC consist
of at least 5 members, whereas the Health Research Extension Act states that
the committee be composed of at least 3 members. Regulations of the Animal
Welfare Act are consistent with the latter. In constituting our committee, which
requirement should we adhere to? Also, would you explain the difference between
Institutional Official and Chief Executive Officer (CEO)? "When your institution is a recipient of PHS support for animal-related activities, its IACUC must consist of at least 5 members who are appointed by the institution's CEO... At a minimum, IACUCs must include a veterinarian, a practicing scientist experienced in animal research, a person whose primary concerns are in nonscientific areas, and a person who is unaffiliated with the institution except as a member of the IACUC. ..Although an individual who qualifies to fill more than one of the aforementioned categories may be appointed to do so, it is still required that the committee consist of 5 members. For purposes of the PHS Policy, the institutional official is that person in the organization having the administrative and operational authority to commit institutional resources to ensure that the animal care and use program will comply with requirements of the PHS Policy. In some institutions, the institutional official and the CEO may be one and the same, whereas in other institutions, particularly large ones, the CEO may be further removed from the day-to-day program oversight." 5. Our IACUC has
received a proposal in which nonhuman primates from our institution's breeding
colonies would be subjected to multiple cesarean sections in order to obtain
viable offspring and to maximize cost effectiveness and the reproductive utility
of the colony of a threatened species. Because cesarean sections commonly are
performed in other species such as companion animals, will our IACUC have to
consider the proposal in the context of a multiple survival surgery? "...the Guide states that the IACUC may consider special circumstances involving requests to do so. An example of a potentially justifiable request given in the Guide involves performing multiple procedures on an animal when the procedures are related components of a research project. The USDA Animal Welfare Regulations, which are applicable under the PHS Policy, provide further guidance on this matter. Under the regulations, multiple major operative procedures are permitted when 1) scientifically justified by the investigator... and approved by the IACUC or 2) when needed as a routine veterinary procedure or to protect the health and well-being of an animal... Proposals that involve exposing an animal to multiple major surgery under conditions not covered by items 1 or 2 must receive prior authorization by the Administrator, APHIS, USDA. When considering proposals such as the one described, specific requests should be made to APHIS on a case-by-case basis. ...The IACUC must understand that it was the intent of Congress to prohibit subjecting animals to multiple major (survival) surgeries in unrelated research protocols, and that species that are threatened or endangered were not distinguished from those that are not on a threatened or endangered list." 7. Is it necessary for our IACUC to
track the numbers of animals used in the various protocols it has approved to
ensure that the numbers do not exceed those that were approved in the proposal
review process? If so, could you provide guidance on the best means for
accomplishing this? "Although neither the PHS Policy nor the USDA regulations explicitly require an institutional mechanism to track animal usage by investigators under IACUC-approved activities, both require that proposals to the IACUC specify and include a rationale for the approximate number of animals proposed to be used. These provisions implicitly require that institutions establish mechanisms to monitor and document the number of animals acquired and used in approved activities. .." 8. In conducting its semiannual facility
reviews, is it necessary for our IACUC to consider laboratories or other sites
where animal procedures or holding activities are conducted only sporadically
or for periods of less than 24 h? How does our IACUC determine whether to
follow the requirements of the PHS or the USDA regarding the definition of
"study area?" "Each assured institution, acting through its IACUC or facility veterinarian, is responsible for all animal-related activities at the institution regardless of where the animals are maintained or the duration of their stay. The degree, frequency, and method of IACUC oversight often depends on the nature of the activity. For example, satellite holding facilities and areas in which surgical manipulations are performed must always be included in semiannual reviews, whereas laboratories in which only routine immunization, dosing, and weighing take place may be monitored by other means such as random site visits and evaluations. Regardless of whether such laboratories are included in the semiannual review process or are monitored by other means, the IACUC must have reasonable access to them for the purpose of verifying that activities involving animals are being conducted in accordance with the proposal approved by the IACUC. The PHS Policy requires compliance with the USDA regulations regarding areas where USDA-covered species are maintained for any purpose for more than 12 hours. The term "satellite facility", as defined in the PHS Policy, remains unchanged and is applicable to the housing or holding facilities provided for all vertebrate animals. It is important to keep in mind that the institution is accountable for all activities involving animals, regardless of technical differences in definitions and time limits, and that institutional policies should be designed to obtain the desired outcome of both the PHS Policy and the Animal Welfare Act (namely, the appropriate, humane care of all animals at each institution)." |
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©1999, Janet Becker Rodgers, DVM, MS, DipACLAM, MRCVS All rights reserved. Comments? Send an email to janet.rodgers@vet.ox.ac.uk |
