Webinar Follow-up: Clarifying “Exceptions” and “Departures” – How to Identify, Track, and Report

The Guide for the Care and Use of Laboratory Animals and the Animal Welfare Act Regulations describe rules and best practices for animal care and use professionals to follow in order to ensure that high welfare standards are upheld for animals used in research. When an IACUC finds something that diverges from these regulations and standards, it can be a challenge to know whether and where to report the issue. To complicate matters, OLAW and USDA APHIS use differing terminology to describe these occurrences, and have different requirements for reporting. A solid, systematic framework for understanding, sorting, and managing “exceptions” and “departures” can help IACUC administrators more effectively sort through complex issues of compliance.

In January 2018, PRIM&R hosted a webinar, Clarifying “Exceptions” and “Departures”: How to Identify, Track, and Report, to offer actionable strategies and illuminate best practices for handling exceptions, departures, and deviations. The speaker panel comprised three experts in the oversight of research involving animals: Alice Huang, PhD, CPIA, the deputy for IACUC guidance in the Office of the Chief Veterinary Medical Officer, Office of Research and Development, Department of Veterans Affairs; Elizabeth Meek, DVM, MPH, assistant director for the USDA APHIS Animal Care; and Richelle Scales, CPIA, research compliance analyst in the Office of Animal Care and Use at the University of California Berkeley.

After the webinar, Dr. Huang and Ms. Scales responded to some of the attendee questions time didn’t permit us to address live. We’re pleased to share those responses with the readers of Ampersand.

Can you re-clarify the difference between a departure and a deviation (in regards to PHS sponsored activity)?
Alice Huang (AH): With regard to OLAW’s requirements, a “deviation” is anything that is different from the way the regulatory language says it ought to be. Most commonly, the “OLAW requirements” involved are provisions of the Guide. If there are provisions in the Guide that allow for the difference (provisions such as specifically described “exceptions”, or well-established performance standards), the “deviation” is just a “deviation” and nothing more. If there are no provisions in the Guide that cover the “deviation” in question, OLAW considers the “deviation” a “departure,” and requires some kind of action on the part of the IACUC (approval on the basis of scientific, veterinary medical, or animal welfare justification, and then inclusion as an “approved departure” in the semiannual report to the IO; or determination as to whether the noncompliance is reportable, and then reporting as needed).

OLAW Deviation [Flow Chart]: The response indicating that if a deviation is needed for the purposes of the scientific study, it is not reported on the semiannual report to the IO, does not appear to match the flow chart. Please clarify.
AH: The specific example that was under discussion was a deviation from the statement that “social animals should be housed in stable pairs or groups of compatible individuals” (Guide, p. 51).  For OLAW deviations from this particular “should” statement, there is an “exception specifically described in the Guide” (p. 51): “unless they must be housed alone for experimental reasons or because of social incompatibility.” This means that single housing is a deviation, and is not a departure, if, for example, it is scientifically necessary to monitor individual food intake because of the experimental design, because “experimental reasons” are covered in the stated exception to this “should” statement. Such a deviation is not a departure, so there is no need to include it on the semiannual report to the IO.

This does not apply to every deviation that the IACUC approves for scientific reasons, because some “must” or “should” statements in the Guide do not have explicitly stated exceptions for “experimental reasons.” For example, Table 3.3 on p. 59 of the Guide gives “Recommended Minimum Space for Rabbits, Cats, and Dogs Housed in Pairs or Groups” and includes a comment for dogs, that “cage height should be sufficient for the animals to comfortably stand erect with their feet on the floor.” No exceptions are mentioned. If then, for example, the IACUC approves housing of a dog in a shorter cage for a few days after surgery that the experimental design requires, in order to limit its physical activity to allow for healing, this would be a deviation for an “experimental reason” that is not covered by a specifically described exception. As such, it would be a “departure” approved by the IACUC for a scientific/veterinary medical/animal welfare reason, and is to be included on the semiannual report to the IO.

In either situation, if the investigator claims that the deviation is needed for scientific reasons, but does not clearly justify this need in the protocol, the deviation would be a “departure” that the IACUC would not be able to approve. If implemented anyway, the deviation would be noncompliance, and the IACUC would have to determine whether it is a “serious” or “continuing” noncompliance, which must be reported to OLAW.

Can you clarify whether singly housed mice are considered a “deviation”?
AH: The speaker misspoke in saying that singly housing mice because of incompatibility is not a “deviation.” Single housing of mice is always a “deviation,” but if it is done because of incompatibility (an exception specifically described in the Guide) the deviation is not a “departure.”

Richelle Scales (RS): Single housing of mice due to incompatibility is a deviation but is not reportable on the semi-annual program review. Here’s why—page 64 of the Guide states:

“Not all members of a social species are necessarily socially compatible. Social housing of incompatible animals can induce chronic stress, injury, and even death. In some species, social incompatibility may be sex biased; for example, male mice are generally more prone to aggression than female mice, and female hamsters are generally more aggressive than male hamsters. Risks of social incompatibility are greatly reduced if the animals to be grouped are raised together from a young age, if group composition remains stable, and if the design of the animals’ enclosure and their environmental enrichment facilitate the avoidance of social conflicts. Social stability should be carefully monitored; in cases of severe or prolonged aggression, incompatible individuals need to be separated.”

These statements in the Guide give the justification for individual housing of social species that are incompatible with others of the same species.

Would it be possible to receive an example of an Excel spreadsheet that records the deviations?
AH: Many have tried to compile neat lists of “deviations” and “exceptions” in the Guide, but I am not aware of any definitive complete list anywhere. An example of a “deviation” that is covered by a Guide “exception,” and an example of a “deviation” that is not covered by any Guide “exception” but is approved by the IACUC on the basis of a scientific justification, are given in the response to the previous question. Careful reading of the Guide itself is your best bet.

USDA Departure flow chart: What is an example of a departure that is not specifically provided for in the Regulations & Standards?
AH: §3.83 of the Animal Welfare Act (AWA) Regulations and Standards (CFR 9 Chapter 1) is an example of a standard that does include a specific provision (italics added below) for a departure.  It addresses watering of nonhuman primates, and states:

Potable water must be provided in sufficient quantity to every nonhuman primate housed at facility. If potable water is not continually available to the nonhuman primates, it must be offered to them as often as necessary to ensure their health and well-being, but no less than twice daily for at least l hour each time, unless otherwise required by the attending veterinarian, or as required by the research proposal approved by the Committee at research facilities.

In contrast, §3.76 (c) of CFR 9 Chapter 1 addresses lighting for primates, and contains no explicit provisions for departures:

Indoor housing facilities must be lighted well enough to permit routine inspection and cleaning of the facility, and observation of the nonhuman primates. Animal areas must be provided a regular diurnal lighting cycle of either natural or artificial light. Lighting must be uniformly diffused throughout animal facilities and provide sufficient illumination to aid in maintaining good housekeeping practices, adequate cleaning, adequate inspection of animals, and for the well-being of the animals. Primary enclosures must be placed in the housing facility so as to protect the nonhuman primates from excessive light.

Accordingly, if the IACUC approves of providing potable water to nonhuman primates intermittently, as described by the provision in §3.83, this is considered an “approved exception” that is not to be included on the USDA annual report. But if the IACUC approves of a departure from the lighting standard in §3.76 (c), this is considered an “approved departure” that is to be included on the annual report, because the AWA standards do not specifically provide for such departures. 

The specific provisions for departures in the AWA Regulations and Standards (CFR 9, Chapter 1, Parts 2 and 3) are designated by various cues. Besides the “if” passage discussed above, some provisions are indicated by the word “provided” – for example, §2.33(a)(3), states:

The attending veterinarian shall be a voting member of the IACUC; Provided however, That a research facility with more than one Doctor of Veterinary Medicine (DVM) may appoint to the IACUC another DVM with delegated program responsibility for activities involving animals at the research facility.

Other provisions are identified as “exemptions” – for example, §3.8 addresses exercise in dogs, and (d) states:

Exemptions. (1) If, in the opinion of the attending veterinarian, it is inappropriate for certain dogs to exercise because of their health, condition, or well-being, the dealer, exhibitor, or research facility may be exempted from meeting the requirements of this section for those dogs.

USDA departures that are not covered by any explicit provisions in the Regulations or Standards require attention from the IACUC.  As shown on the flow chart, they may be departures that have been approved by the IACUC, which means that they are to be included on the Annual Report to USDA APHIS, or they may be deficiencies, which have to be documented in the IACUC minutes and in some cases in reports to USDA APHIS.

If a PI has an IACUC approved exemption, how often does it need to be reviewed?
AH: An “IACUC approved exception/exemption” refers to departures from USDA regulatory language that have been approved by the IACUC for protocol or scientific purposes. These should be reviewed by the IACUC whenever the applicable protocol or policy is being reviewed.

Is it an OLAW “departure” from the Guide, when the scientific design involves non-standard husbandry?
AH: This question typically comes up with regard to feed, water, lighting, humidity, etc. It is important to keep in mind that the Guide describes the requirements for standard husbandry, and does not address limits on how that husbandry may be modified when the study of a modification is the objective of the research. This means that scientific interventions such as adding a test agent to the drinking water, in order to test the effect of that agent, or changing the light-dark cycle to 24 hours of light, or 12 hours of white light and 12 hours of red light, to test the effects of such light cycles, are not even deviations from the Guide. They would be deviations that are departures if they were not themselves the focus of study (which may be approved by the IACUC for scientific, veterinary medical, or animal welfare reasons), or if the modified husbandry only reflects failure to provide standard husbandry when standard husbandry is appropriate (if implemented without IACUC approval, these would be noncompliant departures, and the IACUC would have to determine whether they are “serious” or “continuing” and therefore require reporting).

What special circumstances are involved if our species is not actually covered under the AWA?
AH: For species that are not regulated by USDA, the regulatory language of USDA APHIS does not apply, so nothing about the care and use of those species would ever differ from what the USDA APHIS regulatory language says it ought to be. If the species meets the definition of “animal” used by PHS Policy, and the institution has a PHS Assurance, OLAW’s regulatory language would still apply.

RS: You would not have to concern yourself with USDA requirements, but you would still be expected to follow the Guide for the Care and Use of Laboratory Animals.

We have recently hired a compliance coordinator/PAM. They have been asked to review protocols that have finished the IACUC review process to identify and correct inconsistencies or address remaining questions. The protocol will not have been officially approved at this point. After the PI has corrected or supplied additional information to clarify the protocol contents, do you think the protocol should go back to the IACUC or is it OK to approve the protocol?  We think if any revisions are minor clarifications, then the protocol can get approved. But if a clarification results in a large change to the protocol, that it would be distributed back to the IACUC for a continued review period of 48 hours.
AH: PHS policy requires that IACUC approval of protocols be granted only by one of two mechanisms: full-committee review (FCR), or designated member review (DMR). If the IACUC determines that revisions are required before the protocol can be approved (Requires Modifications to Secure Approval [RMSA]), the investigator may certainly accept assistance from anyone (including the compliance coordinator) with relevant expertise to “identify and correct inconsistencies or address remaining questions,” but the expectation is that the committee will have identified and informed the PI of the issues that it requires the PI to modify. Requiring the investigator to satisfy separate requirements of the compliance coordinator would be a self-imposed local expansion of the regulatory requirements.

If substantive changes are made in a protocol, regardless of whether they were made in response to comments from the IACUC or instructions from the compliance coordinator, only the IACUC has the authority to approve the revised protocol, and the IACUC can do so only by FCR or DMR. The compliance coordinator has no authority to grant IACUC approval. The only changes that can be made administratively are changes such as typographical corrections or updates of contact information. These can be made without IACUC review after the IACUC has granted approval to the protocol, and are not relevant to the approval status of the protocol.

RS: If the IACUC completed its reviews but hasn’t officially approved the protocol, the protocol would need to go back to the IACUC for final approval after all issues have been addressed.

PRIM&R thanks the speakers for sharing their expertise!

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