Request to Modify Animal Use Protocol (AUP)
General Instructions:
NOTE: Adding/Removing Personnel from an AUP is a separate form.
NOTE:
Procedure – a method described in an Animal Use Protocol
Protocol – the entire Animal Use Protocol document with all of the methods, justifications,
assurances, etc.
In other words, Procedures are part of a (Animal Use) Protocol.
Modifications need to be “stand-alone” documents. Therefore, if specific
information is requested, please provide that information even if the
information is in the original Animal Use Protocol (AUP). Otherwise, the
modification will need to be returned and cannot be approved until such
information is supplied.
Because of the vast number of different types of modifications that are submitted, the
modification form is designed to use “modules”. Depending on the type of modification,
different modules will need to be completed.
The reason for developing a Request to Modify Form is to provide proper instructions to
the Principal Investigator (PI) so they can submit complete, and compliant, modifications.
Background
NOTE: Adding/Removing Personnel from an AUP is a separate form and is considered a
minor change unless the change involves the PI.
Protocol Number: This is the assigned IACUC number.
Date Original AUP Submitted to IACUC: Please provide the month and year of submission of
the AUP to be modified. This aids the reviewer and administrative staff to find the original
AUP.
Protocol Title: Provide the title of the original AUP. Do not give a separate title to the
modification.
Principal Investigator: This is the principal investigator (PI) on the AUP that is to be modified.
The PI must be a full-time Jefferson Faculty Member.
Department: Department name in which the PI has a primary appointment
Species: Use the common name for the species; not the Linnean Binomial name (Greek or latin
form name). For example, use Rat instead of Rattus norvegicus. Modifications may not be
used to change the species, or to add new species, on the original AUP. There can only be 1
species per AUP and all its associated modifications.
Age, Gender: self-explanatory
Veterinary Consultation: If animals in class D or E are USDA covered species (USDA
Animal), the attending veterinarian must be consulted before submission of this form.
This is a new USDA guideline. Provide the date for this consultation in the box using the
month/day/year format.
USDA Definition of “Animal”
“Animal: any live or dead dog, cat, nonhuman primate, guinea pig, hamster, rabbit, or
any other warm blooded animal, which is being used, or is intended for use for research,
teaching, testing, experimentation or exhibition purposes, or as a pet. This term
excludes: birds, rats of genus Rattus and mice of the genus Mus bred for use in research
and horses not used for research purposes and other farm animals, such as, but not
limited to livestock or poultry, used or intended for use as food or fiber, or livestock or
poultry used or intended for use for improving animal nutrition, breeding, management, or
production efficiency, or for improving the quality of food or fiber. With respect to a dog,
the term means all dogs, including those used for hunting, security, or breeding
purposes.” Taken from: Animal Care Resource Guide, Research Facility Inspection
Guide, “Definitions” 2.1.2; 4/01.
Protocol Modification Policy
Summary: Modifications in excess of 3 major modifications in the 3 year approval period of an
AUP will require a revised AUP. The 3 year renewal cycle is reset upon approval of the revised
AUP. For further information, consult the Protocol Modification Policy or contact the IACUC
Office.
Examples of Minor and Major Modifications (Lists are not all inclusive).
Minor Modification
a) add new, similar, strains of the same animal species
b) add new compounds in the same class (i.e. substitute one antibiotic for another antibiotic).
However, if the new compound is in a different chemical/functional grouping, or if a
hazardous compound replaces a non-hazardous compound, this change may be considered
as a major modification.
c) add new cell lines
d) add more organs for tissue harvest
Major Modification
a) any addition or significant change to a procedure involving pain/distress, or with the potential to
cause pain/distress, especially if anesthetics/analgesics are to be discontinued. Note: A
change in anesthetic agent may not be considered a significant change, but stopping the use
of post-operative analgesia is a significant change that needs a strong justification.
b) addition of, or change in, procedures involving hazardous materials or procedures (depends on
the hazard and the nature of the change)
c) change of PI
d) change involving exception to, or modification of, an Animal Care and Use policy or Standard
Operating Procedure (SOP) (depending on the change and policy)
e) significant change in the purpose of the AUP (i.e. addressing a new scientific question) – Note
that this type of change may require a new or revised AUP.
The determination of whether a change is minor, major, or warrants a new or revised AUP is
made by the IACUC. It is recommended to consult the IACUC Regulatory Officers or the
IACUC Chair for guidance on what are major or minor changes, however, the final decision
rests with the entire IACUC.
Changes to an Animal Use Protocol that increase the pain/distress classification (see AUP
Section 7) are usually major changes or may require a new or revised AUP.
Change in the species (i.e. converting an AUP for mice to rats) cannot be made by a modification
and will require a new or revised AUP.
1. Describe how this modification relates to the original question or purpose of
the Animal Use Protocol (AUP)
It is usually a good idea to state the original question, hypothesis to be tested, or purpose of
the approved AUP. Then, indicate how the modification will provide information addressing
the original intent of the AUP.
2. Modification Description
Note:
Procedure – a method described in an Animal Use Protocol
Protocol – the entire Animal Use Protocol (AUP) document with all of the methods,
justifications, assurances, etc.
In other words, Procedures are part of a (Animal Use) Protocol.
A) All modifications must be “stand alone” documents. It is not acceptable to say that a
procedure from one AUP is now added to another AUP without describing the procedure. It
is also not acceptable to cite published sources in lieu of a protocol description. For example,
it is not acceptable to write “We are adding the surgical procedure described in Jefferson, et
al., J. of Anat., vol 10, pg 70-80, 1999” and not describe the surgical procedure. It is
permissible to cite journal articles to justify why the modification is needed, or to indicate from
where the modification is derived, but not as a sole description of the procedure.
B) Describe the modification to the AUP indicating how the original procedure is modified;
however provide a complete procedure incorporating the modification. In other words, rewrite
the entire procedure (Not the entire Animal Use Protocol form) incorporating the modified
steps. It is recommended to underline, or mark in some way, the modified portions of the
procedure.
Example: A surgical technique changes but the pre-operative preparation and closing
methods remain the same, then it is permissible to write something like “The preoperative preparation is as described in the AUP. The surgery is now performed by…
(describe surgery including the modification). The closure of the surgical incision and
post-operative monitoring will be performed as described in the AUP.”
C) Describe why this modification or addition is necessary. This description does not need to be
lengthy.
Examples:
“A recommendation made by the study section reviewing our grant suggested computerized
tomography (CT) scans or ultrasound imaging should be conducted to monitor tumor
regression instead of using euthanasia/dissection/histology at various time points. This
change will also result in a reduction of the number of animals required for the study.”
“We have decided to switch from ketamine/xylazine anesthesia to isoflurane as isoflurane is
adequate for this procedure, it is easy to use, is supplied by the LAS, and its use does
not require us to maintain drug-use records as for ketamine.”
D) If adding a procedure, indicate when that procedure is performed relative to the other
procedures of the AUP. Note, this information is for addition of a procedure, not for a
modification to a procedure. If a procedure is being modified, it is assumed that procedure is
still used at the same point in the Animal Use Protocol. If this modification replaces a
procedure on the AUP, clearly indicate which procedure is being replaced. When a
modification is accepted, it is not permissible to revert to the original, unmodified version
unless IACUC approval is granted. However, you can provide this option in the
modification description.
Example, “We wish to try a surgical modification to improve post-procedure survivability. If no
increase in post-procedure survivability is obtained, we will revert to the original surgical
procedure.”
When a modification is accepted it is now part of the AUP. Yes, you need to modify a
modification to revert to the original, unmodified, procedure, unless you provided for that
option. THEREFORE, MAKE SURE ANY MODIFICATIONS ARE WARRANTED or provide
the option to revert back to the original procedure!
E) If adding new animal strain(s), briefly describe the phenotype of the strain addressing any
pain/distress issues associated with the phenotype. If pain or distress issues are associated
with the phenotype, describe the use of analgesics or justify why analgesics cannot be used.
Additionally, an Updated Search for Alternatives must be provided if the phenotype involves
pain/distress.
Example 1: “The Tju-null mice are indistinguishable from Tju heterozygous or wild-type
mice.”
Example 2: “The Mtu knock-out mice develop severe intestinal erosions shortly after birth
and perish within two weeks after birth. Analgesics will compromise the inflammatory
response, which is an essential component of this study, and cannot be used. To minimize
pain and distress, the Mtu knock-out mouse strain will be maintained by mating Mtu
heterozygous mice to wild-type mice. Heterozygotes will be mated together only for
production of Mtu knock-out mice for experimental purposes.”
Note: This example would require an Updated Search for Alternatives as the Mtu knock-out
phenotype is probably painful and/or distressful.
Describe the breeding strategy if appropriate. This means that if the animals are to be bred
and maintained on this protocol, then the breeding strategy and number of animals involved
in the breeding strategy needs to be described and justified, either in this section or in the
Animal Number Justification section. IMPORTANT NOTE: If the modification involves adding
a strain to an “experimental” AUP and a breeding protocol is cited as the source of those
animals, the breeding protocol will also need to be modified to accommodate the new strain
and to account for any increase in animal numbers due to breeding of the new strain, etc. If
there is no increase in Animal Numbers on the associated breeding protocol, then state why
there is no increase in Animal Numbers on the breeding protocol.
F) Consider if the endpoints of the experiment will change because of this modification and justify
any change in the endpoints. Often these justifications are straightforward and due to the
time required to perform the modification. These justifications for the change in endpoint do
not require literature searches (Updated Search for Alternatives) unless there is a
pain/distress issue. Essentially, this response is to inform the IACUC that the endpoint must
change and why it must change.
Example: Suppose the AUP stated that the animals will be euthanized 2 weeks after some
event (i.e. a procedure, injection, tumor formation, etc.). Suppose you want to add an
imaging procedure to examine the animals and this modification may require additional
time. That change in endpoints must be justified. The justification can be as simple as
“The addition of the imaging procedure will provide information on tumor growth and
development. The original protocol had an endpoint of 2 weeks post tumor induction.
However, often the tumor had not progressed to a relevant size in this time, hence the
addition of the imaging technique. We will change our endpoint from two weeks to when
the tumor reaches 1 cm in diameter as determined by CT scans, or 6 weeks after tumor
induction (if a tumor has not formed by then, it is unlikely to form later), whichever comes
first.”
3. Modules
If a module is not provided in the modification, that omission indicates to the IACUC that
there are no changes whatsoever in the information contained in the corresponding
section of the original AUP. The IACUC cannot predict all modification types, and
therefore cannot predict what additional information (modules) may be required. The
PI is responsible for providing all pertinent information to the IACUC regarding their
modification. It is recommended that the PI review the AUP form to determine if, and
how, the modification will result in a change(s) in the information provided in any
section of the original AUP.
More than one modification type may apply, for example, Addition of Animal Strains may
also involve Increase in Animal Numbers. Answer all questions in the Module even if
that information is also provided on the original AUP.
The table below is to aid you to provide required information and/or assurances to the IACUC.
Often modifications cannot be accepted because some important information has been omitted.
Consult the list of recommended additional modules. If the modification does not change the
information in that section of the original AUP, then there is no need to add that module to this
modification. For addition of, or change to, a procedure that causes, or may cause, pain and/or
distress, an Updated Search for Alternatives is mandatory.
Examples:
1) A PI is modifying a surgical procedure described in the original AUP by changing the
anesthesia. As anesthesia is covered in the Surgery Summary (7_Surgery_Summary), the
PI needs to include that module in the modification. However, if there is no change to the
Animal Monitoring Plan they do not need to fill out module 8_Animal_Monitoring_Plan.
Surgery may cause pain and or distress, even though the switch in anesthesias may not
involve, or change, the pain/distress status, the module,
15_Updated_Search_For_Alternatives is mandatory.
2) A PI is modifying a step in a surgical procedure (for example, adding the use of anticoagulants). If the modification does not result in a change to the Surgery Summary section
of the original AUP, they do not need to fill out module 7_Surgery_Summary. Similarly, there
may also be no change to the Animal Monitoring Plan. However, they will need module
15_Updated_Search_For_Alternatives because the modification is to a procedure that can
cause pain and or distress.
It is the PI’s responsibility to include all pertinent information regarding the modification.
It is recommended that the PI consult the IACUC office, or an IACUC member, if there
is doubt about which modules to include.
For instructions on how to fill out the additional modules, consult the instructions for the
Animal Use Protocol (downloaded with the Animal Use Protocol Form).
Modification Type:
(Addition of, or Change to:)
Recommended Additional Modules
8_Surgery_Summary
Surgery (both survival and non-survival)
- includes changes in anesthesia and/or
analgesia
9_Animal_Monitoring_Plan (if not in original AUP)
16_Updated_Search_For_Alternatives
8_Surgery_Summary
Change non-survival surgery to survival
surgery
9_Animal_Monitoring_Plan (if not in original AUP)
16_Updated_Search_For_Alternatives
Increase in Animal Numbers
5_Justification_Animal_Numbers
9_Animal_Monitoring_Plan
Procedure involving pain/distress
16_Updated_Search_For_Alternatives
Modification Type:
(Addition of, or Change to:)
Recommended Additional Modules
2_Animal_Suppliers
If the phenotype of the added strains involves pain
and/or distress, then also need:
9_Animal_Monitoring_Plan
Animal Strains
16_Updated_Search_For_Alternatives
If breeding is involved or an increase in animal
numbers, then also need:
5_Justification_Animal_Numbers
Addition of experimental groups
5_Justification_Animal_Numbers
Biologicals,
including
cell
lines,
recombinant
viral
vectors,
DNA,
antibodies, protein, cell extracts, etc., in
procedures
13_Use_Non_Pharmaceutical_Materials
11_Hazardous_Materials
Use
of
Hazardous
procedures
Materials
in
May also need:
13_Use_Non_Pharmaceutical_Materials
Use, or change, of Non-Pharmaceutical
Materials or Out-of-Date
Pharmaceuticals
13_Use_Non_Pharmaceutical_Materials
Procedure(s) resulting in the use of
facilities or laboratories not described in
the original protocol
15_Animal_Housing_Procedures_Transport
6_Restraint_Devices
Restraint devices
16_Updated_Search_For_Alternatives
Euthanasia procedures
10_Euthanasia
Regulated materials or procedures
(Adjuvants, neuromuscular blocking
agents, ascites)
Animal Housing or special
husbandry requirements
animal
14_Regulated_Materials_Procedures
16_Updated_Search_For_Alternatives
15_Animal_Housing_Procedures_Transport