SOP

Standard Operating Procedures

This Document was prepared by

Khadiga Gaafar

Professor of Endocrinology

Faculty of Science, Cairo University

A. Assurances

The IACUC will oversee the research proposals submitted for approval to the committee and assures that these practices will conform to the principles of international research ethics as found in the Guide. Part of this assurance includes the establishment of an appropriated constituted Institutional Animal Care and Use Committee (IACUC) which shall have the responsibility to review and monitor research involving experimental animals.

B. Constitution of the IACUC

The IACUC will be constituted to ensure a) competent review of the ethical aspects of the research and b) independence from influences that could affect the performance of unbiased reviews.

1. Chairperson

a. Appointment:

The chairperson will be appointed directly by the Dean of the Faculty of Science, Cairo University. Neither the Chairperson of the Department nor any other high-ranking official should be involved in the committee to ensure independence of the IACUC from institutional influence.

b. Qualifications of the chair:

The chairperson shall have the following qualifications:

i. A professor on the academic staff of the Zoology Department, Faculty of Science, Cairo University

ii. Reasonable experience in performing research,

iii. Aware of IACUC procedures and had training in research ethics

iv. Reasonable communication skills and leadership characteristics.

v. Committed to the welfare of animals in research

c. Term of appointment: The chairperson shall serve for a period of three-years and could be renewed for a second term. The chairperson shall not serve for more than two consecutive three-year terms.

d. Vice-Chairperson: The chairperson will choose a vice-chairperson to help him or her in carrying out his or her responsibilities. The vice-chair will carry out the chairperson duties in his/her absence upon written permission from the chairperson.

2. Members of the IACUCs

a. Members: Members of the IACUCs will reflect a multidisciplinary and multisectorial composition, including relevant scientific expertise (i.e., appropriate to the types of protocols that will be reviewed), balanced age and gender distribution, a mix of junior and senior staff members, a mix of scientific and non-scientific persons including non-affiliated lay representatives (e.g., lawyer, journalist) to reflect the different viewpoints of the community.

b. Numbers: The number of persons in the IACUC should be kept fairly small, between 7-11 members. It is generally accepted that a minimum of five persons is required to compose a quorum. There is no specific recommendation for a widely acceptable maximum number of persons, but it should be kept in mind that too large an IACUC will make it difficult in reaching consensus. Hence, 11-15 is the maximum recommended number.

c. Composition:

Chairperson
Representative from the Faculty of Science Board, Cairo University, and/or a

Representative from the Quality Assurance Unit of Faculty of Science, Cairo University

Faculty member(s), practicing scientists experienced in research involving animals.
Non-affiliated member(s) representing general community interests. This member has equal status (e.g., voting) to every other committee member and is provided the opportunity to participate in all aspects of IACUC functions.
Member(s) representing different educational or research institutions knowledgeable in research ethics.
A veterinarian with knowledge of the IACUC procedure.
A secretary member

d. Qualifications: members will include the following:

i. Holding at least a college degree

ii. Have an interest in research issues and research ethics

iii. be reputable and trustworthy

iv. be willing to volunteer their time and effort

v. be willing to sign a confidentiality agreement regarding meeting

deliberations, applications, information on research subjects and other related matters

vi. The non-affiliated community representative is exempted from having a

College degree to ensure proper representation of a large sector of the community who might not have such qualification.

e. Conditions of Appointment: Each member shall:

i. agree to meet all education and training requirements

ii. Sign a confidentiality agreement regarding meeting deliberations,

applications, and information on research subjects.

f. Appointment Process

Initial Constitution of the IACUC

An initial group of members shall be selected directly by the Chairperson, who initiated the establishment of the IACUC. The Chairperson will then seek the approval of the Dean of the Faculty of Science, Cairo University and its Board

Subsequent appointment of members:

The Chairperson will identify, interview, and then choose members and review with them the nature and demands of serving on the IACUC. If the member is willing to serve, then the chairperson shall seek approval from the Dean.

Conflicts of interest should be avoided when appointments are made, but if unavoidable, there should be transparency and management of the conflict of interest with regard to such interests on a case by case basis.

g. Terms of Appointment

i. Duration: Each member shall be appointed for a cycle of 3 years.
ii. Renewal: There will be no bar on the members serving for more than one term but it is desirable to have around one third fresh members At the end of each cycle of appointment, members wishing to stay on should make a written request to the Chairperson. Subsequent renewal will depend on prior quality of work and attendance performance and be determined by a consensus of the full committee.
iii. Resignation: Members wishing to terminate their appointment prior to the 3 year cycle shall send a written letter of resignation to the Chairperson 2 months in advance in order to have enough time to appoint another member. The Chairperson then will replace the member.
iv. Disqualification: Members may be asked to leave the IACUC if any of the following occurs:

1) Failure to attend three consecutive meetings without permission or more

than half of the meetings.

2) Negligence in reviewing protocols.

3) Breach of confidentiality agreement.

4) Termination shall be decided by a majority vote of the full IACUC

5) Authority to replace the member shall be with the Chairperson.

h. Orientation and training of IACUC members:

Initial Education: Following appointment the new member will go through the IACUC orientation, which consists of an introductory lecture followed by an informational session on practical matters with the IACUC chair. Subsequent education may take one of the following types:

i. Previously held workshop (of at least two days duration) in research ethics

ii. Completion of a training website in research ethics.

Continuing education: The IACUC should set standards for continuing education of its members every three years (e.g., regularly scheduled review of published articles in research ethics, attendance at workshops, etc.)

i. Conflicts of Interest

The IACUC member should be not participate in the IACUC review or approval of an activity in which that member has a conflicting interest, (e.g. is personally involved in the activity) except to provide information requested by the IACUC

Examples of such conflicts of interest could include: a member of the IACUC who serves as an investigator on research under consideration by that IACUC; or a member who holds a significant financial interest in a sponsor or product under study.

If the investigator submitting a protocol believes that an IACUC member has a potential conflict, the investigator may request that the member be excluded. The Chair (or in his/her absence, the Vice-Chair) will present the declared conflict and the Committee will determine whether a conflict exists. Should an IACUC member declare involvement in any way in a research protocol under review by the IACUC, or state a conflict of interest with the research protocol, then the member(s):

 May remain in the meeting room to provide information requested by the IACUC;

 Leave the meeting room for discussion and voting; and

 Are not counted towards quorum.

3. Independent Consultants

The IACUC may, at the discretion of the chair or its members, invite individuals with competence in special areas to assist in the review of issues that require expertise beyond or in addition to that available on the IACUC. These individuals may not vote with the IACUC. Consultants are not included in determining or establishing a quorum at the meetings. IACUC meeting minutes reflect the presence of consultants.

E. IACUC Research Review Evaluations Procedures, Criteria and Actions

The IACUC is charged with the responsibility for reviewing and monitoring animal research conducted under the mandate of Universities and research institution. Therefore, the first question with respect to IACUC review of a project is a determination of whether the project fits the definition of research.

a. Is it research? Research is defined as “a systematic investigation, including development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. Thus, a key aspect of research is that there be a systematic design in advance, generally utilizing a scientific approach or protocol, for the defined purpose of contributing to generalizable knowledge. Research can encompass a wide variety of activities, including: experiments, observational studies, surveys, tests, and recordings.

b. Does it involve experimental animal? An experimental animal is defined as “a living animal on which an investigator conducts research.”

Intervention includes physical procedures, manipulations of the animals or manipulations of the animal’s environment for research purposes.

1. Meeting Frequency

The IACUC will meet at regular time intervals in accordance to the needs of the workloads, but generally the IACUC should meet at least once a month on a regularly scheduled day. For example, every two weeks, every month, etc. In certain circumstances, IACUCs can meet on an “as needed” basis.

Scheduled meetings may be cancelled by the chair due to a) insufficient number of applications requiring review at a convened meeting, b) inability to secure a quorum for attendance, or c) other reasons as may arise that make a scheduled meeting unnecessary or otherwise inappropriate.

The Member Secretary will be responsible for organizing the meetings, maintaining the records and communicating with all concerned. He/she will prepare the minutes of the meetings and get them approved by the Chairperson before communicating to the PI. Before finalizing a project, the IACUC Chairperson should call for a preliminary meeting with the project leaders or guides and request them to detail the projects. After finalizing the project proposal, the IACUC protocols dealing with small animals should be posted one month prior to the IACUC meeting.

2. Quorum Requirements

a. The number required to compose a meeting will be half of the members

with a minimum of five.

No quorum will consist entirely of members of one profession (e.g., medicine)
A protocol is approved only if a quorum is present, and if more than 50% of the quorum votes in favor of protocol approval.

3.Functions of IACUC

IACUC should provide independent, competent and timely review of the ethics of proposed studies before the commencement of a study and regularly monitor the ongoing studies. IACUC will review and approve all research proposals involving animal experiments up to physiological level only with a view to assure quality maintenance and welfare of animals used in laboratory studies while conducting biomedical and behavioral research and testing of products. IACUC will review the proposals before start of the study as well as monitor the research throughout the study and after completion of the study through six monthly reports, final report and visit of the laboratory in the animal house where the experiments are conducted. The committee will also ensure compliance with all regulatory requirements, applicable guidelines and laws.

IACUC will also:

Monitor and inspect the housing of animals of breeders/establishments and ensure that it is as per specified standards.
Grant permission for conducting experiments on animals. Regulate experiments on animals as per stipulated conditions and standards.
Ensure that animals which in course of the experiments are so injured that their recovery would involve serious sufferings are euthanized as per specified norms.
Ensure that experiments on animals are avoided whenever it is possible to do so and propagate the principles of 3Rs (Reduce, Refine & Replace the use of animals in experiments).
Ensure that experiments on larger animals are avoided when it is possible to achieve the same results by experiments upon small laboratory animals like guinea-pigs, rabbits, frogs, rats, mice and pottery.
Ensure that required records are maintained with respect to experiments performed on animals.
Ensure that as far as possible experiments are not performed merely for the purpose of acquiring manual skill.
Ensure that animals intended for the performance of experiments are properly looked after both before and after experiments.

4. Submission of Applications for New Studies

a. Persons Submitting: An application for review of the ethics of a proposed research project shall be submitted by the principal investigator (PI) of the research.

The date of meeting will be intimated to the PI who should be available to offer clarifications if necessary.

The decision of IACUC will be communicated in writing. If revision is to be made, the revised document in required number of copies should be submitted within a stipulated period of time as specified in the communication.

b. Materials Submitted: All research proposals should be submitted with the following documents:

1. A signed and dated application form (developed by the IACUC)

2. Names of the PI and Co-investigators with designation.

3. Name of any other Institute/Hospital/Field area where research will be conducted.

4. Endorsement of the Head of the Department.

5. Protocol of the proposed research. Time plan for the study

6. Proposal should be submitted with all relevant annexure like proforma and product brochure for new drug/device.

CVs for the principal and co-investigators

8. Agreement to submit six monthly progress report and final report at the end of study.

9. The PI should provide the details of other ongoing research projects related to the Animal studies (Title of the project, Date of starting and duration, source and amount of funding).

10. Signed investigator assurance agreement to comply with ethical principles and legal requirements set out in relevant laws and guidelines.

If the application is incomplete or otherwise not fully prepared for review, it is returned to the investigator or a request is made for necessary changes or to provide additional information.

c. Deadlines

i. Submission: The deadline for submission will be at least 15 days prior to the meeting at which the protocol will be reviewed by the IACUC.

ii. Investigator notification: investigators will be notified of an IACUC decision within 72 hours after a decision has been reached.

4. Review of Applications of New Studies

The IACUC will use a primary & secondary reviewer system in which two members will be assigned to lead the review and present the protocol for discussion at the convened meeting. All IACUC members will be provided with detailed materials describing the research so that each member will be able to discuss the protocol at the meeting.

a. Member review:

A member will be selected to be the primary reviewer of the protocol and will be responsible for:
1. Completing the primary reviewer form
2. Presenting the protocol for discussion at the meeting

All members shall receive protocols for review at least 1 week prior to the review meeting
All members are required to review all submitted materials and be prepared to discuss all protocols at the convened meeting.

b. IACUC Evaluation Criteria: The IACUC will assess the following review criteria:

1. Scientific design and conduct of the study.

2. Approval of scientific review committee and regulatory agencies.

3. Assessment of predictable risks/harms to the animals. The IACUC will identify all environmental risks. Possibility of alternative approaches of experimental animals

4. Protocol and proforma of the study.

5. Plans for data analysis and reporting.

6. Adherence to all regulatory requirements and applicable guidelines.

7. Competence of investigators, research and supporting staff.

8. Facilities and infrastructure in the animal house.

c. Expedited Review

Certain minimal risk protocols may receive expedited review by the chairperson. All expedited decisions shall be communicated to the next convened meeting of the IACUC. The IACUC shall establish criteria by which protocols can be reviewed by such an expedited procedure.

5. Voting and Decision making

a. All members who attended the meeting while the protocol was discussed will participate in the voting unless a member has a conflict of interest. Those members physically present for the vote should be recorded as either voting for, against, or abstaining. Members who are excused from the vote (e.g. due to conflict of interest) should physically leave the room, would not be counted in the aforementioned tally, and should be identified by name in the minutes.

b. Decisions should be made at meetings where a quorum is present.

c. Decisions should be arrived at through consensus, where possible. In cases where a consensus appears unlikely or when discussions become prolonged, the chairperson shall call for a vote. In such instances, a majority vote will be sufficient to arrive at a decision. In case of a tie, the decision favored by the chairperson shall be determinate.

d. When an IACUC member has a conflict of interest that requires him/her to excuse himself/herself from discussion of and voting on a particular protocol, that member should leave the meeting room for the duration of the discussion and vote, except as requested to address questions raised by other members. If the member’s conflict of interest causes a loss of quorum, the vote should be postponed to another meeting. For this reason, IACUC members should notify the chair prior to the meeting if they have a conflict of interest related to a specific protocol slated for review at the meeting, and every effort should be made to ensure transparency of the decision

e. Types of decisions allowed:

Approval of research: In the case of an approval with no changes, the research may proceed once the PI receives written documentation of IACUC approval.

Approval with minor changes: The IACUC may determine that a study may be approved with stipulated minor changes or clarifications.

For minor changes, the Chair or a voting IACUC member(s) designated by the Chair must ensure that the investigator makes the appropriate changes to the research protocol. Such changes must be clearly delineated at the convened meeting so that subsequent review requires simple verification of concurrence. The research may proceed after the required changes are verified and the designated reviewer approves the protocol.

Deferral: The term “deferral” is used to describe the situation in which the IACUC determines that substantive changes must be made before approval may be granted. The investigator’s response, including any amended materials, must be reviewed by the convened IACUC.

Disapproved: The project, as proposed, is disapproved and may not go forward. Disapproval usually indicates that a proposal requires major changes not likely to be feasible without a complete reassessment of the protocol by the investigator and/or sponsor.

Suspension and termination of research study by IACUC: The chair of the IACUC or the convened IACUC may suspend a study at any time if it is determined that the study requires further review or evaluation. This determination may be made due to an adverse event, noncompliance or other environmental issues. Once a study has been suspended, the convened IACUC should review the study and either require changes to the protocol, allow the study to restart, or terminate the study. Though the chair may suspend a study, only the convened IACUC can make the decision to terminate a study.

f. Appeal of IACUC decisions: Investigators may appeal the REC’s decisions. At the discretion of the chair, the investigator may make such an appeal in writing to the REC. At the REC’s discretion, the investigator may be invited to the REC meeting at which his or her appeal will be considered.

g. Each protocol will be assigned a risk level (minimal risk, greater than minimal risk, or too risky (in the latter case, the protocol will be disapproved) and the follow-up intervals will be determined according to the level of risk of the protocol. In general, duration of approval will be a maximum of one year.

f. IACUC Meeting Minutes should be in sufficient detail to show the following:

Attendance at the meetings:

· date and time meeting starts and ends

· names of members present

· names of members absent

· names of alternates attending in lieu of specified absent members

· names of consultants present

· names of investigators present

· names of guests present

Actions taken by the IACUC

· Actions taken by the IACUC at a convened meeting as well as the vote on these actions including the number of members voting for, against, and abstaining, and (if applicable) notation that any members with a conflict of interest (identified by name) were excused and were absent for the discussion and vote;

· The basis for requiring changes in or disapproving research

· For each protocol in which changes are stipulated by the IACUC, a determination of whether the changes represent minor modifications that do not require verification by the convened IACUC, or whether they are significant, requiring convened IACUC review; and,

· A written summary of the discussion of controversial issues and their resolution.

IACUC findings and determinations

The following are required findings and determinations, and must be noted in the minutes

· Determination of the level of risk for human subjects in the research study (no citation required).

· Justification for the usage of animal model;

· Justification for number of animals used

· Special protections warranted in specific research projects for Species of animals under protection and at the risk of extinction

The secretary of the IACUC will be responsible for taking the minutes of the meeting. At each meeting, one member of the committee will take notes and review the minutes to ensure accuracy and completeness.

6. Communication of Decisions

a. A decision of the IACUC shall be communicated to the investigator in writing within three days of the meeting.

b. Each decision shall include:

A clear statement of the decision reached,
Justifications of any disapproval
In cases of deferral approval, a list of the conditions needed for approval and its associated justifications
In cases of a positive decision, a statement of the responsibilities of the investigator (e.g., confirmation of the acceptance of any requirements imposed by the IACUC, submission of progress reports, the need to notify the IACUC in cases of protocol amendments, changes to recruitment materials, and the reporting of any unexpected adverse events or unanticipated problems or termination of the study).
The date and place of the decision
Any advice given by the IACUC
Signature of the chairperson

7. Investigators’ Responsibilities During Conduct of the Study

Deviations from the project is not allowed, without the permission from IACUC.

During the conduct of the study, the investigator shall submit within a specified period of time (to be determined for each category) the following:

Amendments to the protocol
Serious and unexpected adverse events
Safety reports (if applicable)
Reports of any Data and Safety Monitoring Board
Unanticipated problems
Termination of the study
Change of investigators should be done with the approval of IACUC.

The IACUC will determine which of the above can be reviewed by an expedited procedure and which requires full committee review

8. Continuing Review

a. Submission: At the time of continuing review, the investigator shall submit the following information for review:

Number of animals’ change and reasons
Adverse events (Cumulative and type for the previous period since the last review)
Modifications to the protocol
Changes of investigators
Results, if available
IACUC’s should determine which continuing reviews can be reviewed by an expedited process and which continuing protocols require full committee review.

b. Lapsed studies: A lapsed study is one for which the approval period has expired prior to the renewal of approval by the IACUC. If the investigator fails to submit the materials for continuing review prior to the IACUC meeting that needs to review the study before the expiration date, then the lapsed study will be classified as inactive. Once a study has lapsed notification should be sent to the investigator ordering that all study-related measures must immediately cease. If the investigator desires to continue a study that has lapsed for more than one month, then the investigator must submit a new application for re-review by the IACUC, and must wait for IACUC approval before resuming research under the protocol.

9.Record keeping and archiving

All following documents must be stored for a period of five years.

1. Curriculum Vitae (CV) of all members of IACUC.

2. Minutes of all meetings duly signed by the Chairperson. Copy of all correspondence with members, researchers and other regulatory bodies.

3. All study related documents (study projects with enclosed documents) should be archived for minimum of five years after the completion of study. A copy of filled proforma related to the projects shall remain with the PI for minimum of five years.

10.Performance of experiments

1. Experiments shall be performed under supervision of a qualified person trained to handle experimental animals (Veterinary/Medicine/Postgraduate in life sciences/Pharmaceutical sciences/Lab animal science) and under the responsibility of the person performing the experiment.

2. Experiment shall be performed with due care and humanity.

3. Animals intended for the performance of experiments shall be properly looked after both before and after experiments.

4. Personnel using experimental animal(s) shall be responsible for the welfare of animal(s) during their use in experiments.

5. Investigators shall be responsible for the aftercare and rehabilitation of animal(s) after experimentation, and shall not euthanize animal(s) except in situations as defined.

6. The following parameters shall be adopted for application of euthanasia. Namely;

(a) When the animal is paralyzed and is not able to perform its natural functions or it becomes incapable of independent locomotion or it can no longer perceive the environment in an intelligible manner.

(b) If during the course of experimental procedure the animal has been left with a recurring pain wherein the animal exhibits obvious signs of pain and suffering.

(c) Where the non-termination of the life of the experimental animal will be life threatening to human beings or other animals.

7. Rehabilitation treatment of an animal after experimentation shall extend till the point the animal is able to resume a normal existence and will involve providing a lump-sum amount as costs for rehabilitation and care of such animal to cover its entire statistical expected life span.

It is mandatory that the cost of after care and rehabilitation should be met from the contingency of the project.

8. Experiments involving operative procedures shall be performed under anesthesia to be administered by a veterinary surgeon/scientist/technician so trained for the purpose.

9. Animals which in course of experiments under the influence of anesthesia are so injured that their recovery would involve pain or suffering shall be destroyed humanely.

10. Experiments shall not be performed by way of an illustration.

11. Experiments shall not be performed as a public demonstration.

12. No experiment the result of which is already conclusively known shall be repeated without justification.

11 Penalties

If the decisions made by IACUC are not followed the research is discontinued