The Beacon Volume 3, Issue 1


USDA LogoUSDA Inspection

The United States Department of Agriculture typically conducts its annual inspection of Yale’s animal facilities and laboratories from April through July.  In order to be inspection-ready, please focus on the following items in preparation for the upcoming inspection.

Consideration of Alternatives to Potentially Painful or Distressful Procedures

  • When writing your protocols and considering whether a procedure is painful or distressful, consider all parts of that procedure, e.g., cutdown for jugular catheterization, etc. 
  • Please contact your Department’s assigned librarian in YSM or FAS for guidance and assistance in conducting a painful procedures alternatives search.  If you have any questions about this specific topic or any other protocol-related topics, please do not hesitate to contact your Department’s Protocol Liaison.

Expired Compounds (drugs, food and supplies)

  • These items are consistently identified as one of the top three deficiencies found during IACUC semi-annual self-assessments of vivaria and PI-managed facilities and laboratories. 
  • Please check supplies frequently to ensure that all items are within date that are in use or are intended for use in live vertebrate animals.
  • Label and segregate any expired compounds.
  • If you have any questions about this specific topic or any other post-approval requirements, please do not hesitate to contact your Department’s Research Support Specialist.

Record-Keeping

  • Any animal-related records can be a focus of attention by the Veterinary Medical Officer (VMO), but surgical records and post-operative monitoring are always a hot topic. 
  • If you have any questions about this specific topic or any other post-approval requirements, please do not hesitate to contact your Department’s Research Support Specialist.

Summary of common findings on PAM visits and Semi-annual Lab Assessments

When Post-Approval Monitoring (PAM) Specialists visit laboratories where animals are used, we often notice trends in issues that need improvement to ensure compliance.  Trending issues in the past year included:

  • Record keeping:
    • Intra-op and/or post-op records did not include appropriate documentation of analgesia administration.
    • Intra-op records did not include documentation of lack of response to noxious stimulus prior to incision and/or every 15 minutes thereafter.  Please note that this documentation is also required for terminal procedures such as perfusion.
    • Monitoring every 15 minutes during immediate post-op recovery (the time between when the surgery ends and the animal achieves sternal recumbency) is not being noted on the surgical record.
  • Expired drugs, drug storage and labeling- Common findings include:
    • Drugs/fluids/topicals being used after expiration:  this is a deficiency that carries the highest risk for the institution.  Please refer to the Beacon Volume 2, Issue 1 for recommended best practices for managing expiration.  In addition, since the expiration date on tube crimps are difficult to read, please consider writing the expiration date on the tube when you open boxes of topical medications.
    • Dilutions of injectable drugs stored in falcon tubes: in order to maintain sterility, dilutions or mixtures should be stored in sterile empty vials or red-top vacutainer tubes.
    • Inappropriate labeling of drug dilutions or mixtures: vials must be labeled with the name of the drug and either the date mixed or the date of expiration (one month after the date mixed).  Whichever date is used, the label should include the appropriate descriptor (mixed/made/diluted or expired).
  • Waste Anesthetic Canisters:  as per manufacturer specifications, these canisters should be weighed prior to initial use and the weight recorded on the canister.  These should be re-weighed/weight recorded prior to each subsequent use.  The canister(s) should be discarded when the weight exceeds the manufacturer specifications.
  • Variances from approved protocols regarding anesthetic and or analgesic administration:  all staff should be familiar with the drugs, dosages and frequency of administration for these agents prior to initiating studies.
  • Sanitation:  frequent findings include dust, spilled feces and bedding or fur on counters.  Animal use areas should be clutter free for ease of cleaning which should be done before and after each use to prevent inadvertent exposure to animal allergens or cross contamination of housing rooms.
  • Emergency Response Instructions are not posted in animal use areas.  All personnel actively working with animals must be aware of procedures to follow in the event of an emergency see: Emergency Response Instructions.

AAALAC_logo

AAALAC accreditation is a voluntary process by which the University demonstrates a high standard of care and use by assuring compliance with federal laws and policies governing the care and use of laboratory animals.  

The site visit will be any time from mid-September through the beginning of December–we won’t know when exactly until late August. During the site visit, AAALAC visitors will evaluate animal facilities and laboratories, as well as review animal protocols and animal use records. To help labs prepare for the site visit, the Office of Animal Research Support (OARS) Specialists will begin visiting laboratories more frequently than the routine comparative review and lab assessment schedule. Throughout the spring and summer, additional information about the site visit will be communicated with the research community. In the meantime, please begin to prepare for the site visit by assuring completion of the following items:

Census Carryover

The PHS Policy implicitly requires that institutions establish mechanisms to document and monitor numbers of animals acquired and used, including any animals that are euthanized because they are not needed.  Institutions have employed a variety of administrative, electronic and manual mechanism to meet both institutional needs and PHS Policy Requirements.

To meet this requirement, the Yale Animal Program accounts for the number of animals that remain on census at time of 3-year renewal.

Here is how it works:

  • As of 4/7/17, the Yale Animal Resources Center (YARC) eSirius database calculates adjustments, i.e. at time of approval, the number of cages which is multiplied by a proxy number of animals.

How to address in the protocol:

  • The number of animals that remain in the facility (at the 3-year renewal of the protocol) have previously been justified, approved, and counted and it is understood that these animals will complete experiments until their endpoint.  Therefore, investigators will need to account for these animals within each experiment.  The protocol liaisons can assist in how best to account for these animals in the electronic protocol system MAPS. 
  • For established rodent colonies, protocols likely have a consistent month-to-month census, thus having consistent carryover. 

Policy and Standard Procedure Updates

IACUC Policy Updates

The following policy updates have been recently approved by the IACUC. For policy questions, please contact the Office of Animal Research Support (OARS) at (203) 785-5992.  For animal health questions, please contact Veterinary Clinical Services (VCS) at (203) 785-2501. 

Animal Acquisition (Revised)

Changes to this policy include:

  • Dogs and cats may only be procured through a Class A dealer/vendor.
  • A new section describing the requirements and considerations for transferring animals between Yale protocols has been added.

Transportation of Animals (Inter-Institutional) (Revised)

Changes to this policy include:

  • A section describing the regulations was added to more clearly define the reason for this policy.
  • The Policy section was revised to be more descriptive.
  • The requirements for importing and exporting animals was combined into one section and updated. It describes the following:
    • Rodents to/from Domestic Institutions
    • Other Species to/from Domestic Institutions
    • All Species to/from International Institutions
  • The Export Controls section was removed. However, a link has been inserted for situations when the Office of Sponsored Projects needs to be contacted for any questions regarding Export Controls.
  • The section describing Material Transfer Agreements and Commercial Licenses has been removed.

Housing Policy (New)

This is a new policy relating to animals housed in YARC-managed or YARC-authorized enclosures. This policy will take the place of the individual housing policies for dogs, hamsters, and guinea pigs. The housing policies for mice, rats, and aquatic species will remain stand-alone documents for the time being. This policy describes the following topics:

  • The recommendations and standards for providing appropriate housing described in the Guide for Care and Use of Laboratory Animals (Guide), the Animal Welfare Regulations (AWAR), and the Public Health Service Policy (PHSP).
  • The general guidelines for space requirements and the links for the Guide and AWAR to reference species-specific space and housing densities.
  • A section describing Social Housing and a link to the IACUC approved Social Housing Policy.
  • A section describing Environmental Enrichment and the standards that are expected.

Regulated Food and/or Fluids in NHPs (Revised)

Changes to this policy include:

  • A section describing the regulations was added to more clearly define the reason for this policy.
  • The Policy section was revised to be more descriptive.
  • Note that the language for several definitions has been modified. This includes:
    • Food scheduling
    • Food restriction
    • Ad libitum
    • Non-regulated (fluid consumption)
    • Average daily fluid consumption (New)
  • The section describing food restriction (4437.4) is now more concise and the language is easier to understand.
  • The requirements for socially housing animals on food restriction is now stated as such:
    • No additional monitoring is required if cage-mates of food restricted animals consume their normal daily food allotment.
  • The health monitoring of a food restricted animal now states the weight loss of > 10% of restricted body weight may be an indication of a health problem associated with food restriction and must be immediately reported to VCS.
  • Section 4437.5 describing fluid restriction has been updated.
  • A description about food availability for animals on fluid restriction.
  • A more specific requirement for establishing an average daily unrestricted fluid consumption.
  • A modified way to establish DTB is described, and a new requirement for adjusting DTB that states: DTB must be reevaluated at a minimum of every 6 months for juveniles (<5 years of age) to change the DTB as the animal grows. Each time the DTB is re-established it must be demonstrated and documented that the animal will not test for a higher mean DTB.
  • New requirements for cage mates that are NOT on fluid restriction now must:
    • have water offered to the unregulated cage mate for at least two hours daily
    • be monitored monthly for hydration by body weights or at least one subjective and one objective measurement (described in section for monitoring hydration)

Non-Pharmaceutical Grade Experimental Agents Use and Approval for Classes of Drugs (Revised)

Changes to this policy include:

  • NEW guidelines have been added to section 4454.4 describing instances when chemical -grade reagents may be used instead of an existing pharmaceutical-grade agent. Those guidelines include:
  • An equivalent veterinary or human drug is available for experimental use; however, the chemical-grade reagent is required to replicate methods from previous studies because results are directly compared to those of replicated studies.
  • The available human or veterinary drug is not concentrated enough to meet experimental requirements or the correct formulation for the route of administration.
  • The available human or veterinary drug contains preservatives or inactive ingredients which confound the research goals of the study.
  • Other justifications will be considered on a case by case basis by the IACUC.
  • An additional factor to be considered by the IACUC and investigators for new compounds or compounds in which the effects or actions are yet to be determined is described as the following:
    • Non-pharmaceutical grade compounds may contain endotoxins such as LPS or may not be at physiological pH. Impurities could have unexpected impactful consequences, resulting in using more animals than necessary.
  • Section 4454.5 includes a more concise list of criteria for approval for use of a class of drugs.

Tumor Policy: Mice and Rats (Revised)

Changes to this policy include:

  • A section describing the regulations was added to more clearly define the reason for this policy.
  • The Policy section was revised to be more descriptive.
  • Section 4445.3 provides more information on pathogen testing requirements.
  • The guidelines section now includes a much more robust description on pain and distress classification.
  • The requirement for monitoring frequency of a tumor once growth is evident has changed from 72 hours to at least three times weekly.
  • It is now recommended that body weight should be used in conjunction with body condition scoring for non-palpable tumors.
  • A note on necrosis was added under the section on monitoring tumor progression, which states:
    • In some studies, the use of therapeutic or experimental agents may result in necrosis of tumor tissue which may be exhibited by a cavitation greater than 1mm in depth.  Expectation of necrosis as well as endpoints must be fully described in the IACUC protocol with animals assigned to category E.

Acclimation Policy (Revised)

  • The policy section describes NEW requirements for acclimation periods based on the intended use of the animal. These requirements are effective immediately. Acclimation requirements now include:
    • All laboratory animals intended for use in survival requiring a combined anesthesia and anesthetic recovery period longer than 15 minutes must be acclimated in a Yale animal facility for at least 2 days prior to initiating the anesthetic procedure.
    • Acclimation should occur in a single facility. If internal relocation by vehicle transport is necessary, at least 2 days must be provided for acclimation to the new setting.
  • NEW recommendations include:
    • Investigators should be aware that stress-related physiological alterations resulting from transport and relocation activities occur in animals without acclimation. Therefore a 2-day holding period is also recommended for animals undergoing non-survival or euthanasia only procedures.
  • A more descriptive section on wild-caught animals was added, including a list of several documents that will be used as guidance by the IACUC for wild animals in both field and laboratory studies.

Analgesia Policy (Revised)

NOTE: This policy includes several major changes that investigators need to be aware of due to the impact it will have on their protocols and studies. These new requirements will not be retroactive. However, they are required for any new modifications to procedures that involve analgesia as well as protocol renewals. Please contact your protocol liaison for more specific information.

Changes to this policy include:

  • The policy section now describes specific considerations investigators should make regarding an animal’s environmental and physiological derangement and the impact this may have on the research data. This section also describes justifications that must be made to withhold analgesia.
  • Some of the policy requirements have changed. Those include:
    • Delivering analgesic drugs in the drinking water is prohibited due to the inability to control the amount of water consumed and ensure therapeutic levels have been achieved.
    • The use of multimodal analgesia is required.  
  • The policy includes several NEW tables illustrating recommended multimodal regimens.
    • Section 4401.6 lists surgical procedures commonly performed in laboratory animals which have been grouped based upon the “range” of expected post-operative pain.
      • Minimal to Mild
      • Mild to Moderate
      • Moderate to Severe
    • Below the table is a detailed description of each group’s recommended analgesia regimens.
    • A second table shows multimodal options permitted for pre-emptive and post-operative analgesia based on the above ranges. These options will be chosen based off the investigator’s preference (i.e. which drugs are preferred).
  • Section 4401.8 lists common drugs and dosages for several species. NOTE: many doses and routes of administration have changed. Investigators will also notice this change when choosing specific drugs in MAPS.
    • Sustained Release analgesics are no longer listed in this policy or in MAPS, as they are no longer available.

IACUC Standard Procedure Updates

These are pre-approved documents that will eventually become implemented into MAPS so that investigators may select from a library and attach it to the protocol. Being that they are pre-approved, there won’t be a need for investigators to re-write that procedure nor for the IACUC to re-review that procedure. These are only the first two documents that will be added to the library, while more are being consistently drafted.

Blood Collection in Mice and Blood Collection in Rats (New)

These Standard Procedures describe acceptable methods of blood collection for each species. Both documents include the following:

  • The approximate volume that may be collected depending on route.
  • A section describing procedure preparation.
  • Depending on route and comfort level of person performing the procedure, a chart describing recommended types of anesthesia including dose.
  • The actual blood collection procedures, separated by route (retro-orbital, saphenous vein, etc.) that are appropriate for that species.
  • A description of the acceptable collection volumes based on weight.

MAPS Updates

Policy Hyperlinks

The IACUC policy hyperlinks embedded within the MAPS application have been corrected.   All policy hyperlinks will direct the user to its associated policy, procedure, guideline or instruction page.  The MAPS application currently contains hyperlinks to several policies, including (but not limited to) Analgesia, Anesthesia, Surgery, Euthanasia, and Experimental Agents.

Consistent Dropdowns

The MAPS application includes species-specific dropdown values for Euthanasia, Anesthesia and Analgesia.   The dropdowns previously contained multiple species within a single dropdown, as well as species labelling issues.  This release will now consistently display a single species entry within all dropdowns. 

PQF View Rights

An enhancement has been made to the Protocol Workspace to allow the Administrative Contact and all Edit Study Staff Users to be able to view all PQFs that have been submitted for the protocol.

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Census Disclaimer

A statement has been added to the protocol to inform researchers that all animals counts included in the protocol are associated to the new research protocol.  All existing animals from a previous protocols have already been justified as part of that submission.

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Numbers justified above will be used in new experiments.  Animals remaining in the facility (at the 3-year renewal of the protocol) have previously been justified, approved, and counted and it is understood that these animals will complete experiments until their endpoint.  Reminder: all procedures that are part of these continuing experiments must also be described in this version of the protocol.

Training Numbers

MAPS now has a feature that allows Investigators to add animal training numbers if relevant to the protocol.   

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Special Instructions

Special Instructions (SI) have been moved from within the experimental group to its own page within the main study of the application.  This will rectify the previous need to enter a duplicate SI multiple times when associated with more than one experimental groups.  For example, experimental groups A, C, and D all utilize the same high fat diet (HFD), so the SI for HFD had to previously be entered three times, once for each experiment.  Now the SI for HFD will only need to be entered once and can apply to any of the experimental groups.

Analgesics

The updated list of available analgesics to choose from within MAPS reflects the recent changes made to the Analgesia policy.  Please reference the Policy & Standard Procedure article, which is included in this edition of The Beacon.

Administrative Rights to Edit a Protocol

In preparation of this fall’s AAALAC site visit, certain units within OARS, namely the Protocol Liaisons and Regulatory Specialists, now have the access and ability to make some administrative edits to already-approved protocols, e.g. adding/editing animal housing and use locations.  This will help reduce the number of modifications that would normally need to be submitted by a PI to make these changes.

The Protocol Approval Unit (PAU) has the ability now to make simple changes to a Personnel Qualification Form during the review process.  The goal here is to reduce the amount of time to approval.

AALAS Learning Library

The launch of the American Association for laboratory Animal Science (AALAS) Learning Library (ALL) occurred in February 2018 to provide more standard and efficient training opportunities for the research community. The mandatory course Regulatory Training for Animal Care and Use is now linked to the ALL Working with the IACUC 2018. Registering for the course has not changed, the course is still accessed via the Training and Certification website.  As an important reminder, you may experience a delay in the course being reflected in your TMS record. There is a download required by TMS which can take 24-48 hours. (This is stated on the training page in the upper right-hand corner)

Thank you to the initial users for your patience with the programming issues that are now corrected.

 If you have questions or concerns please contact the OARS Training Manager, Layne Ochman at layne.ochman@yale.edu.

Don’t see your completed enrollment in your TMS file?

Depending upon the course you have taken, it may be 24-48 hours for recently completed courses to appear in your TMS record. Please wait until this time period expires before contacting tmsadmin@yale.edu regarding your missing enrollment.

Welcome, Jinah!

Jinah Han, Ph.D., joined OARS as a Research Support Specialist on January 2, 2018.  Jinah has over ten years of experience in biomedical research, including six years as a postdoctoral researcher and lab manager at Yale.  She has studied adult stem cells, hippocampal neurogenesis, and cardiovascular diseases utilizing various animal models.  Jinah’s research experience is expected to bring a researcher’s perspective to the office, as well as help facilitate communication within the research community.  She is now conducting comparative reviews, start-up meetings, and lab assessments for various departments.