Table of Contentsmrinstitute.org/Form SOP MRIN EC 2019/Guideline for PI... · 2019-02-13 · or...

Mochtar Riady Institute

for Nanotechnology

Ethics Committee (MRIN EC)

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Table of Contents 1 The Importance of Ethics …………………………………………………………………………………… 2 2 Who has to submit an Ethics Application?.................................................................................... 2 3 Procedure for Protocol Submission for Initial Review and Resubmission…………….. 3 4 Procedure for Submission for Protocol Amendment………………………………………….. 5 5 Procedure for Continuing Review……………………………………………………………………… 6 6 Serious Adverse Event and Unexpected Adverse Drug Reaction 7 7 Final Report of Study………………………………………………………………………………………… 8 8 Study Termination……………………………………………………………………………………………. 8 9 Type of Review…………………………………………………………………………………………………. 8 10 Length of Review……………………………………………………………………………………………… 10 11 References ………………………………………………………………………………………………………. 10 12 Appendices………………………………………………………………………………………………………. 10 12.1 Application Form for Initial Review…………………………………………………………… 11 12.2 Summary Sheet of Study Protocol……………………………………………………………… 13 12.3 Protocol Submission Form for the Use and Care of Animal/animal Tissue in

Research / Teaching / Testing ………………………………………………………………… 15

12.4 Protocol Amendment Submission Form …………………………………………………... 25 12.5 Continuing Review Application Form ……………………………………………………… 27 12.6 Serious Adverse Event Report Form………………………………………………………… 29 12.7 Unexpected Adverse Event Summary Report……………………………………………. 31 12.8 Study Report Form………………………………………………………………………………….. 32 12.9 Study Termination Application ……………………………………………………………….. 34 12.10 Response to Animal Welfare Violation Report ………………………………………. 35 12.11 Flow Chart of Application Submission Process………………………………………… 38 12.12 Glossary………………………………………………………………………………………………… 39 12.13 List of Abbreviation………………………………………………………………………………… 40


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1. The Importance of Ethics

Research involving animals should be based on a fundamental moral commitment to

the animal concerned. The research should also result in advancing animal welfare,

knowledge and understanding. It is a universal requirement mandated by all research

bodies that all institutions should establish an Ethics Committee to monitor research

activities.

2. Who has to submit an Ethics Application?

Anyone employed in Mochtar Riady Institute for Nanotechnology (MRIN), Faculty of

Medicine, Faculty of Nursing, Department of Biology Universitas Pelita Harapan (UPH)

or Siloam Hospitals who intends to undertake a research or teaching project involving

any form of animal studies has an ethical responsibility toward the subjects of that

project. This includes research carried out on MRIN premises or conducted elsewhere.

The MRIN Ethics Committee is the body that reviews and approves such projects to

ensure that the ethical responsibilities are appropriately addressed in the project. Their

review is based on details provided by the completion of an ethics application for

research involving animals.

The following guideline is prepared to assist Researcher/ Principal Investigator (PI) to

outline the submission requirements for full or expedited review of new protocols and

modification to an approved protocol. As an ethics conduct has to be maintained

throughout a study, this guideline describes procedure for additional report mechanism

after a protocol is approved.


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3. Procedure for Protocol Submission for Initial Review and Resubmission

New protocol should be submitted for Initial Review by the MRIN EC to obtain ethics

approval. Care and use of laboratory animals for research /testing/teaching /breeding

purposes requires ethics approval by MRIN EC prior to implementation.

The Procedure for Protocol Submission for Initial Review or Resubmission is as follows:

1. Complete two (2) copies of Application Form for Initial Review (Annex 1, Form

AF/AS/01-010/2019/01.0).

2. Complete two (2) copies of Summary Sheet of Study Protocol (Annex 2, Form

AF/AS/02-010/2019/01.0).

3. Complete two (2) copies of Protocol Submission for the Use and care (Annex 3,

Form AF/AS/03-010/2019/01.0) to include attachments : CV of PI , Approval

from animal expert, approval from occupational health and safety officer,

research proposal approved by authorized supervisor, etc (see Annex 3)

4. Research Proposal should contain:

Title

Table of Content

Summary of Research

Background

Research Problem

Aim /Objective. consist of General aim and specific aim

Benefit or Outcome of Research

Hypothesis

Materials and Methods including

a. Theoretical and Conceptual Frame Work

b. Time and Place

c. Study design

d. Sample Number, Sample calculation

e. Inclusion , Exclusion Criteria, With drawal Criteria


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f. Definition of Operation

g. Instruments and Process of Data Collection

h. Management and Data Analysis

i. Method of Analysis, etc

Detailed Budget

Timeline

References

5. All documents are to be submitted in both formats, hard and soft copy (pdf file)

with the signatures. The soft copy with the signature of the PI must be emailed

to MRIN EC Secretariat ([email protected]).

6. MRIN EC Secretariat will verify the completeness of submitted documents. The

MRIN EC will only consider complete documents for ethical review.

7. If necessary, MRIN EC may invite the Principal Investigator (PI) to give

clarification on issues that can arise during review process.

8. When the review process has been concluded, MRIN EC Secretariat will notify the

PI about MRIN EC’s Decision, if the approval is granted, requires major or minor

modification, or rejected.

9. In case a minor or major revision is required, after revision the PI has to resubmit

all forms again to MRIN EC for a re-review. Changes made in any of the documents

must be typed/ written in bold letters, and indicated in the cover letter when the

documents are resubmitted.

10. Please include table of revision as following for the resubmission

MRIN EC Recommendation Revision from PI Remark/Page No.

11. The decision on the resubmission will be communicated to the PI once MRIN EC

has finished conducting the re-review.

mailto:[email protected]


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4. Procedure for Submission for Protocol Amendment

During the course of the study, investigators can amend the protocol/project proposal

from time to time. The PI should submit the amendments to the MRIN EC for either

“expedited” or full review by submitting 3 (three) copies of the Protocol Amendment

Submission Form (AF/AS/01-013/2019/01.0), including the letter from the referring

institution and 1 copy of the revised protocol/project proposal

All documents are to be submitted in both formats, hard and soft copy (pdf file) with the

signatures. The soft copy with the signature of the PI must be emailed to MRIN EC

Secretariat ([email protected]).

Criteria for “expedited” review may include:

administrative revisions, such as correction of typos

addition or deletion of non-procedural items, such as the addition of study

personnel names, laboratories, etc

non-significant risk research activity

Modification /amendment of protocol with major modification with regards to

the expedited review on initial submission

Research activity involving the species of rodent or lower orde with project

classification B or C

Those that involve collection of biological specimens for research purposes by

non-invasive means (e.g. collection of body fluids or excreta non-invasively,

collection of hair or nail clippings in a non-disfiguring or non-threatening

manner).

Collection of data for research purposes through non-invasive procedures (not

involving general anesthesia or sedation) routinely employed in clinical practice

and using medical devices which have been already approved for use. Examples

of such procedures include collection of data through acoustic testing, tests using

the Doppler principle, non-invasive blood pressure and other routine clinical

measurements, exercise tolerance etc. However procedures involving the use of

x-rays or microwaves are NOT recommended for expedited review.



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Changes in protocol, which increase risk to study animals are subject to full review by

the MRIN EC. Examples are changes in study design, which may include but are not

limited to:

significant decrease or increase in dosage amount additional treatments or the

deletion of treatments that may increase pain category.

changes in the species of animal

change in method of dosage formulation, such as, oral changed to intravenous

increasing the biohazards level on the protocol

significant change in the number of subjects (increasing the number of

nonhuman primates, dogs or cats, or increasing the number of small animal more

than 10% is significant)

significant decrease or increase in dosage amount

MRIN EC Secretariat will notify the PI if the protocol amendment is approved or not. In

case the MRIN EC votes to require modifications to any of the documents, or the

protocol amendment, the Secretariat sends a written request about the specific changes

to the PI asking him or her to make the necessary changes and resubmit the documents

to MRIN EC.

5. Procedure for Continuing Review

The purpose of a continuing review is to monitor the progress of the entire study to

ensure continuous protection of the rights and welfare of research animals. Depending

upon the degree of risk to the animals, the nature of the studies, and duration of the

study, the MRIN EC may choose to review or monitor the protocols more frequently.

MRIN EC Secretariat will inform the ‘Study team’ in advance regarding the due date for

the continuing review by post, e-mail or by other appropriate means. The PI is required

to fill up and submit 3 copies of the Continuing Review Application Form (AF/AS/01-

014/2019/01.0) and 1 copy of the latest project proposal approved by the MRIN EC.


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The MRIN EC will conduct a review of the study and the Secretariat will inform the PI

after a decision has been reached no later than 7 working days after the review has

taken place.

All documents are to be submitted in both formats, hard and soft copy (pdf file) with the

signatures. The soft copy with the signature of the PI must be emailed to MRIN EC

Secretariat ([email protected]).

Elements for Progress Report including:

1. Is this still an active protocol ?

2. Has the number of animals being used in this protocol changed ?

3. Has the type of animal being used for this protocol changed ?

4. Have the procedures being used for this protocol changed ?

5. Have the personnel working on this protocol changed ?

6. Have there been any adverse effects of problems observed in this project and how have they been managed or will be managed ?

7. In what room(s) are the animal housed ?

8. Provide a brief summary of results to date ?

9. Have you published of any work /accomplishment ?

10. Please list any Amendments that have been submitted since the date indicated on the Letter of Initial Ethics Approval

6. Serious Adverse Event and Unexpected Adverse Drug Reaction

Unanticipated risks are sometimes discovered during the course of studies.

Information that may impact on the risk/benefit ratio should be promptly reported to

and reviewed by the MRIN EC to ensure adequate protection of the welfare of the study

animals.

The unanticipated risks may as well include any event that in the investigator’s opinion

may adversely affect the welfare or safety of animals in the study.

The investigators must report the SAE within 5 (five) working days after the incident

occurred and unexpected events should be included in the continuing review report

submitted to MRIN EC. Investigators should use Forms Serious Adverse Event Report

(AF/AS/01-019/2019/01.0) or Unexpected Adverse Event Summary Report

(AF/AS/02-019/2017/01.0) to inform the MRIN EC about the event.



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Categories of incidence for Serious Adverse Event (SAE) and Unexpected Adverse Drug

Reaction (ADR) are listed in Table 1.

Table 1. Criteria for SAE and Unexpected ADR

Serious Adverse Event (SAE)

The adverse event is SERIOUS and should be reported when the animal outcome is:

Death - Report if the animals's death is suspected as being a direct outcome of the adverse event.

Life-Threatening - Report if the animal was at substantial risk of dying at the time of the adverse event or it is suspected that the use or continued use of the product would result in the patient's death.

Examples: Gastrointestinal hemorrhage; bone marrow suppression; etc

Disability- Report if the adverse event resulted in a significant, persistent, or permanent change, impairment, damage or disruption in the animal's body function/structure, physical activities or quality of life.

Examples: Cerebrovascular accident due to drug-induced hypercoagulability; toxicity; peripheral neuropathy.

Requires Intervention to Prevent Permanent Impairment or Damage – Report if suspect that the use of a medical product may result in a condition which required medical or surgical intervention to preclude permanent impairment or damage to animal.

Examples: Burns from radiation equipment requiring drug therapy; breakage of a screw requiring replacement of hardware to prevent malunion of a fractured long bone.

Unexpected Adverse Drug Reaction (ADR)

Unexpected Adverse Drug Reaction is an adverse reaction, the nature or severity of which is not consistent with the information sheets or the applicable product information (e.g., investigator’s


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brochure for the unapproved investigational product or package insert / summary of product characteristics for an approved product.

7. Final Report of Study

Once the study has been completed, the Principal Investigator is required to fill up and

submit 3 copies of the Study Report Form (AF/AS/01-015/2019/01.0), and one copy of

the latest project proposal/protocol. All the amendments approved by the MRIN EC

should be attached to the latest approved protocol. Report is written in letter format.

Each Board member will review the Final Report, and if appropriate to the discussions,

MRIN EC may call for consensus on whether to request further information or to take

other action with the investigator.

All documents are to be submitted in both formats, hard and soft copy (pdf file)

with the signatures. The soft copy with the signature of the PI must be emailed to

MRIN EC Secretariat ([email protected]).

8. Study Termination

Protocols are usually terminated at the recommendation of the MRIN EC, Scientific

Director, or other authorized bodies before the scheduled end of the study, when the

safety or welfare of the animal subject is doubtful or at risk. Upon notification from

MRIN EC Secretariat the Principal Investigator is then required to prepare and submit

Study Termination Application (AF/AS/01-018/2019/01.0) to MRIN EC. Once the

review has been completed, MRIN Secretariat will inform the PI of MRIN EC’s decision

on the study termination.

9. Type of review

The protocol submission will be determined as Exempted, Expedited or Full Board by

the Chairperson/Vice chairperson/Secretary of EC.



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10. Length of Review

PI will receive notification from Secretariat within 1-4weeks after the submission of

completed document for expedited and exempted and 7 working days after the full

board meeting.

11. References

1. World Medical Association (WMA), Declaration of Helsinki, 2008

2. WMA Statement on Animal Use in Biomedical Research, 2016

3. Council for International Organization of Medical Science (CIOMS) -International

Council for Laboratory Animal Science (ICLAS). International Guiding Principles

for Biomedical Research involving animals, 2012

4. Office of Laboratory Animal Welfare (OLAW). Institutional Animal Care and Use

Committee Guidebook, 2002

5. National Research Council. The Guide for the Care and Use of Laboratory

Animals. , 8th edition, 2010

6. Federation of Animals Science Societiest. Guide for the Care and Use for

Agricultural Animals, 3th edition, 2010.

7. American Veterinary Medical Association (AVMA). Guidelines for the Euthanasia

of Animals: 2013 edition

8. Javier Guillén. Laboratory Animals : Regulations and Recommendations for the

Care and Use of Animals in Research. 2nd Edition, 2016

9. National Research Council. Occupational Health and Safety in the Care and Use of

Research Animal, 1997

10. Law of the Republic of Indonesia No. 18, 2009, Chapter VI, Veterinary Public

Health and Animal Welfare; Part 2, Animal Welfare; Articles 66 – 67 (UU RI NO.

18 Tahun 2009 Bab VI . Kesehatan Masyarakat Veteriner. Bagian kedua :

Kesejahteraan Hewan Pasal 66 – 67)

11. Law of the Republic of Indonesia No. 18, 2009, Chapter VII, Veterinary

Authority; Articles 74 (UU RI NO. 18 Tahun 2009 Bab VII – Otoritas Veteriner,

Pasal 74)


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12. Government of Republic of Indonesia’s Regulation no. 95, 2012 . Veterinary

Public Health and Animal Welfare. (Peraturan Pemerintah RI No. 95 tahun 2012.

Kesehatan Masyarakat Veteriner dan Kesejahteraan Hewan)

13. The National Guidelines on Health Research Ethics. Health Research Ethics

Commitee. Republic of Indonesia : The Ministry of Health, 2011 (Pedoman

Nasional Etik Penelitian Kesehatan, Komisi Nasional Etik Penelitian Kesehatan.

2011).

14. Standard Operating Procedures Mochtar Riady Institute for Nanotechnology

Ethics Committee (MRIN EC), 2019

12. Appendices

12.1. Application Form for Initial Review (AF/AS/01-010/2019/01.0)

APPLICATION FORM for INITIAL REVIEW

Protocol Title:

Protocol number:

STUDY TYPE: (Mark “ “ whichever apply to the study)

Research Testing Teaching Pilot Study

Others : …..

CHARACTERISTICS of ANIMALS : Age : ............ Sex : .................. Body Weight : .................

SPECIAL RESOURCE REQUIREMENTS (check all that apply):

Intensive Care Isolation Unit Surgery

Special Housing Controlled substances (Narcotics/Psychotropics)

Others, specify : ………….. .

IONIZING RADIATION USE (X-rays, radioisotopes, etc):

None Study requirements


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PROCEDURE USE: Invasive Non-invasive

MULTI-SITE COLLABORATION: Yes No

FINANCIAL DISCLOSURE: Yes No

INSTITUTE RESEARCH CONTACT Name:……………………………………………………………………………………

Address: ………………………………………………………………………………… Telephone:…………………………………………

Fax:………………………………………………… E-mail:……………………………………………...

PARTICIPATING INVESTIGATORS (add extra pages if necessary):

First / Last Name Institution Telephone / Fax No.

E-mail

1.

2.

3.

4.

5. CONTACT PERSON: Name:……………………………………………………………………………………. Institute/ Address:…………………………………………………………………….. ……………………………………………………………………………………………. Telephone:……………………………………………………………………………… Fax:………………………………………………………………………………………. E-mail:…………………………………………………………………………………… SIGNATURE:

__________________ Date: ………………..

Principal Investigators

TYPE OF INITIAL REVIEW:* ASSIGNED REVIEWERS:*

☐ Exempted from Review

☐ Expedited Review

☐ Full Board Review

1.

2.

3.


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SIGNATURE: Date:…………………

*to be filled by Chairperson/Vice chairperson/Secretary

12.2. Summary Sheet of Study Protocol

(AF/AS/02-010/2019/01.0)

SUMMARY SHEET OF STUDY PROTOCOL

Title of the Protocol*

Principal Investigator (Name, Institution)*

Sponsor

Abstract*


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Aims*

Anticipated Outcome*

Mode of Intervention to the Animals*

Methodology (Synopsis of Study Design)*

Analysis method*

Timeline*

* indicates required field. Describe in details (What , Where, When, How)


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Principal Investigator Signature _____________________________________ ___________________ Name Date 12.3. Protocol Submission Form (AF/AS/03-010/2019/01.0)

PROTOCOL SUBMISSION FORM FOR THE USE AND CARE OF ANIMAL/

ANIMAL TISSUE IN RESEARCH/ TEACHING/ TESTING To be filled by Principal Investigator

Please fill out the form completely and return to the Secretariat of MRIN Ethics Committee (MRIN-EC), Jalan Boulevard Jendral Sudirman 1688, Tangerang 15810, Tel. +62 21 54210123, Fax. +62 21 54210110, Email: [email protected] Protocol registration no.:

(To be filled by the Secretariat of MRIN EC) A. General Information

1 Principal Investigator: (Title, Name, Institution)

2 Title of Research (include the species of animals to be used):

3 Type of Research Non-cooperation National collaboration International collaboration (Attach ethical approval from corresponding country)

Involvement of foreign researcher (Attach approval from the State Ministry for Science and Technology)


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4 Description of the Study in brief: Mark whatever applied to the study. Used of tissue sample Used of blood sample Used of genetic materials Multi center study Screening Others : …................

5 Type of Proposal New Protocol Continued Protocol If continued or modified, please state previous ECL No

6 Institution

7 Funding Resources

8 Total of Research Funding

Rp

9 Research Location

10 Period of Research Start................................ End................................

11 Has this protocol been submitted to other Ethics Committee before

Yes; accepted rejected No

B. ANIMAL STUDY

12 Has this research protocol been discussed with animal research expert/ attending/ consulting veterinarian? Yes No

13 If yes, are there recommendations on proposed research protocol? Yes No (Attach recommendation if applicable)


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14 Purpose of this project Research Antibody Production

Teaching/ Training Breeding Animal/Veterinary Other, please specify: Care or Health

Surveillance 15 Information on Research Animal Data:

Animal Species :

Strain : Age : Body Weight :

Gender :

Quantity : Animal Origin:

16 Animal Housing ( ) Individual ( ) Pair ( ) Group Provide justification for social animals to be housed individually

17 Information on Project

a. Lay Summary Please describe the objective of study, and the experimental approaches to be used that easily understood by non-scientists.

b. Background This should include a brief statement of the requirement or need for the information being sought. Lengthy explanations are not required. Typically, the "literature or the experience that led to the proposal will be briefly reviewed", and a description of the general approach should be provided. Unnecessary duplication of effort should be strictly avoided.

c. How long will the animal be held for the project? Study Duration: .........(.............) month(s) (.....................-........................)

..........(.............) year(s) (......................-.......................)

d. Objectives In non technical terms, state the objective of this protocol


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e. Hypothesis State the hypothesis to be accepted or rejected

g. Literature search

You should provide the name of two or more data bases (e.g. pubmed, AWIC, Science Direct, etc) search for alternatives to animals, alternatives to painfull procedures and unnecessary duplication of experiments Databases searched

Date of search Years covered Key Words Number of hints

Result of search :

h. Project Description and Procedures Please describe all procedures carried out on each animal species/ tissue, including experimental design and methods in detail

18 Ethical Consideration

a. Species Justification Please describe the characteristic of this animal model that makes it the most appropriate for the study (e.g. size, previous data, unique physiological characteristics, supported by reference if possible, or based on experience). And, please explain if there is no alternative model, other than the use of animal described above for this research.

b. Animal Number Justification Please, explain how the number of animals were determined and explain statistical methods used, if applicable.

19 Animal Use Procedures

a. Anesthesia a.1. Will any of the animal procedures in this protocol be conducted under anesthesia? ( ) No (Please continue to b) ( ) Yes Please complete the table below. Please include anesthetic, pre-anesthetic, sedation, or tranquilizing agent/ compound which will be used.

Drug (active compound) Dose (mg/ kg BW)* Route (IM/IP/SC/ID/PO)

* - For small animal dose can be given in mg/ 100gram.


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- Unit in ml/ kg BW or other volume unit/ BW unit is not acceptable. With exception, if only the concentration of the compound is explained. IU/ BW or Unit/ BW can be used for compound such as hormone or other compound generally known to use this unit. a.2. What is the frequency of anesthetic procedures in each animal? a.3. What is the estimated duration of each anesthetic procedure? a.4. Please explain how the animal will be monitored during anesthetic procedure, and how often

b. Pain and Distress b.1. Will any of the procedures, minimal 1, known potentially, cause more than momentary pain and/ or distress? ( ) No (Please continue to c) ( ) Yes, Type of procedure: b.2. Please explain how the animal will be monitored? b.3. Will analgesic agent/ pain relief be given prior/ during/ after this particular procedure. ( ) No Please explain, and also state if analgesic agent is contraindicated for the study result. ( ) Yes Please complete the table below.

Drug Dose (mg/ kg BW)*

Route Frequency and duration

c. Administration of drug/ reagents/ vaccine/ cells/ agents/ substances, etc Please explain any drugs or any agents or substances (other than anesthesia, pre-anesthetic, sedation, tranquilizing, and analgesia agents) that will be used in this study (including for experimental purpose or therapeutic, like antibiotic for post surgical, if any).

Drug Dose (mg/ kg BW)*

Route Route

c.1. Is there any agents/ drugs known to be contraindicated/ cause to invalidate the data if administered to the study animal? (Including drug/ agent used for veterinary care purpose.)


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( )No (Please continue to d) ( )Yes Please listed. c.2. Is there any non-pharmaceutical-grade chemicals and other subtances to be used on the animals? ( )No (Please continue to d) ( )Yes The use of a non-pharmaceutical-grade chemicals or substances should be described and justified.

d. Survival Surgery d.1. Does this experiment involve surgery/ surgical procedures? ( ) No (Please continue to e) ( ) Yes, Please specify: ( ) Terminal (Non survival) (Please continue to e) ( ) Survival (Please complete the table below) d.2.

Experimental group (number of animal)

Number of major survival surgery per animal *

Number of minor survival surgery per animal **

Type of surgery

e. Adjuvatants and Antibody Production e.1. Will adjuvant or antibody production be part of this project? ( ) No (Please continue to f) ( )Yes

e.2. How will you monitor the animal and what category will be used to terminate the animal from the production?

f. Behavioral Testing f.1. Will behavioral testing be done in this project? ( )No (Please continue to g ( ) Yes f.2. Will training the animal be required prior to data collecting? ( ) No ( ) Yes f.3. Will food or water deprivation method be conducted? ( ) No (Please continue to g) ( ) Yes Please explain the method of deprivation, amount given, and the monitoring of the animal.

g. Hazardous Agents Radioactive, chemicals and biological agents


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g.1.Will hazardous agents be used in this project? Or will any of the experimental procedures pose any health risk to staff or other animals? ( ) No (Please continue to h) ( ) Yes Please state specific dose, whether to be used on live animal or tissue, effect on animals, danger to humans, monitoring, precaution to protect personnel. Name the agents: _______________________________________________ Chemical Formula (if applicable): _______________________________ Carcinogen: ( )Yes ( ) No Infectious agent: ( )Yes ( ) No Toxic chemical: ( ) Yes ( ) No Other: please explain ____________________ g.2. Which Biosafety level of this procedure/ agent will apply? Please explain. (Please, refer to Reference) g.3. Where is the procedure involving hazardous agents will be conducted? g.4. Please explain the restrictions, if any, to handle or discard this substance and animal waste. g.5. Will Radioisotopes be used in live animals? ( ) No (Please continue to h) ( ) Yes (Please explain the half-life time).

h. Blood sampling h.1.Will blood collection procedure be required in this experiment? ( ) No (Please continue to i) ( ) Yes (Please complete the table below)

Experimental Group

Route Volume (ml, or ml/kg BW)

Frequency

i. Food and Fluid Regulation i.1.Will special diet be given for animal in this project? ( ) No ( ) Yes (Please explain) i.2.Will food or water deprivation method be conducted? ( ) No (Please continue to j) ( ) Yes Please explain the method of deprivation, amount given, and the monitoring of the animal.


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j. Paralytic Agents Will paralytic agent/ neuromuscular or similar blocking agent administration to the animal be used in this study? ( ) No (Please continue to k) ( ) Yes Please explain the necessity to use this agent, dose, frequency, and method to monitoring the depth of anesthesia. No use of paralytic agents without anesthesia is allowed unless scientifically justified by the PI and approved by the IACUC.

k. Euthanasia k.1.Will any animal in the study undergo euthanasia? ( ) No (Please continue to l) ( ) Yes k.2.Please describe the method of euthanasia (refer to AVMA Guidelines on Euthanasia).

l. Study End Point Will death of animal be used as an end point of study, instead of euthanasia? ( ) No Please specify what is the projected end point or termination of the study for the animals? Is euthanasia, or recovery expected; and what is the specific plan for determining when the animal experimentation phase will be stopped? Explain the plan for the disposition of surviving animals. ( ) Yes Please provide justification, explain the method and frequency of monitoring to ensure that unnecessary pain or distress is prevented.

m Prolonged Restraint Will animal undergo prolonged restraint (more than 12 consecutive hours)? ( ) No (Please continue to n) ( ) Yes Please explain the method of restraint (e.g. primate chairs, restraint boards, metabolism cages, e.tc.), frequency, and the duration. Also describe habituation procedures for the prolonged restraint.

n. Tumor Transplantation or Induction n.1.Will tumor development be expected to grow from any animal in this study? ( ) No (Please continue to o) ( ) Yes Please explain the type, site, functional deficit, method and frequency of monitoring? Also, please specify the end point use to terminate the animal from the study.


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o. Toxicity Testing o.1.Will toxicity testing be conducted with any animals in this study? ( ) No (Please continue to p) ( ) Yes Please explain the type of toxicity testing, the method and frequency to monitor the animal, and specify the end point to terminate the animal from the study.

p. Collection of Tissue Please identify the tissue will be collected from this study, and method (euthanasia (postmortem), surgery/ biopsy with or without opening body cavity).

Adverse Effect/Humane Endpoint

If you expect any adverse effects (including pain and distress) of your procedures or stimuli on the animals (e.g. weight loss, fever, poor appearance, neurological deficits or behavioral abnormalities), please describe in the space below. Describe the conditions, complications and criteria (e.g. 20% weight loss, maximum tumor size, vocalizing, and lack of grooming) that would lead to euthanasia of an animal before the expected completion of the experiment. Note : if any unanticipated adverse effects not described below do occur during the course of the study, a complete description of those effects and any action taken in response to them must be submitted to the IACUC as an amendment to this protocol.

Project Classification( *)

A B C D E

(*)

A : Research on Invertebrates or Plants, Bacteria, Amoebas

B : Vertebrates being bred, conditioned, or held for use in teaching, testing,

experiment/research but not yet used for search purposes.

C : Research on Vertebrates involving no pain or distress beyond that expected on a momentary nature such as would occur with an injection, a deep palpation, grooming activities, etc.

D : Research on Vertebrate where Stress and Physical Suffering is Inevitable.

E : Procedures That Can Cause Physical Suffering Above Acceptable Threshold, but alleviation of pain or distress are contraindicated for some justifiable reason such as; would confound the experimental results if drugs relieving pain were administered. Detailed justification for putting animals into this category is required.

Category E Justification: C: Research on Vertebrates involving no pain or distress beyond that expected on a momentary nature such as would occur with an injection, a deep palpation, grooming activities, etc

D : Research on Vertebrates where stress and physical suffering is inevitable. Where in anesthesia or analgesia will be administered to avoid or alleviate pain or distress.


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General anesthesia given for surgical preparations, or the use of analgesia or anti-inflammatory would be examples for this category.

E : Research on Vertebrates involving procedures that can cause physical suffering above acceptable threshold, but alleviation of pain or distress are contraindicated for some justifiable reason such as; would confound the experimental results if drugs relieving pain were administered. Detailed justification for putting animals into this category is required.

Category E Justification:

20 Document Requirements for Protocol Completeness (Tick () box when appropriate 20.1 One copy Cover letter from referring institute 20.2 One copy Proposal approved by advisor or institutional head (Attach

approval from authorized parties. Outline of research proposal should refer to guideline for PI Item 3.3f.

20.3 Two copies Application form for initial review 20.4 Two copies Medical ethics submission form for animal research 20.5 Two copies Proposal summary with following attachments: 20.5.1 List of Research Team with Corresponding Expertise and job

description of the team 20.5.3 Personal Information of Principal Investigator (Including Research

Experience and Job Description) 20.5.4 Approval from Attending /Consulting Veterinarian

20.5.5 Approval from Occupational Health & Safety Officer 20.5.6 Memorandum of Understanding between Researcher, Sponsor and

Research Institution (For Research Cooperation) 20.5.7 Budgeting Details 20.5.8 Time line 20.5.9 Others (e.g. Workflow)

21 Assurances

As the Principal Investigator on this protocol, I will provide the following assurances: Animal Use: The animals authorized for use in this protocol will be used only for the study and in the manner described herein, and any deviation from this protocol will be requested and approved by the MRIN EC Duplication of Effort: I have made a reasonable, good faith effort to ensure that this protocol is not an unnecessary duplication of previous experiments. Statistical Assurance: I can assure you that I have consulted with an individual who is qualified to evaluate the statistical design or strategy of this proposal, and that the “minimum number of animals needed for scientific validity are used”. Biohazard/Safety: I have taken into consideration and I have made the proper arrangements regarding all applicable rules and regulations concerning radiation protection, biosafety, recombinant issues, etc., in the preparation of this protocol.


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12.4. Protocol Amendment Submission Form (AF/AS/01-013/2019/01.0)

PROTOCOL AMENDMENT SUBMISSION FORM

PROTOCOL NUMBER: SUBMITTED DATE:

PROTOCOL TITLE:

PRINCIPAL INVESTIGATOR:

INSTITUTE: Telephone:

PARENT PROTOCOL APPROVED DATE: NO. OF AMENDMENT:

Training: I verify that the personnel performing the animal procedures and manipulations described in this protocol are technically competent and have been properly trained to ensure that there is not any unnecessary pain or distress that will be caused as a result of the study procedures or manipulations. Responsibility: I acknowledge the inherent moral administrative obligations associated with the performance of this animal use protocol, and I assure that all individuals associated with this project will demonstrate a concern for the health, comfort, welfare, and well-being of the animals to be used in this research protocol. Additionally, I pledge to conduct this study in the spirit of the fourth “R”, namely, “Responsibility” for implementing animal use alternatives where feasible, and conducting humane and lawful research. _________________________ Principal Investigator

Painful Procedures: I am conducting biomedical experiments which may potentially cause more than momentary or slight pain or distress to animals that WILL BE / WILL NOT BE (circle one) relieved with the use of anesthetics, analgesics and or tranquilizers. I have considered alternatives to such procedures. However, using the methods and sources described in this protocol, I have determined that alternative procedures are not available to accomplish the objectives of this proposed experiment.

Tangerang, Date.............................20...

Principal Investigator

(……………………………….)


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Summary of previous protocol amendment (if any)

Approval amendment no.

Original Protocol Short description of the amendment

Approved

date

B. Describe of the Amendment Requested : …………………………………......

C. Reason of Amendment Requested : ……………………………………………

SIGNATURES:

Date:…………….. Principal Investigator

TYPE OF AMENDMENT REQUESTED: filled by Chairperson/Vice chair person/Secretary

EXPEDITED

FULL BOARD

COMMENTS: (filled by Reviewer) :

SIGNATURES: Date:……………. Protocol Reviewer

DECISION :

Approved

Minor revision

Major revision

Disapproved


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12.5. Continuing Review (AF/AS/01-019/2019/01.0)

PROGRESS REPORT FORM

PROTOCOL No.: Submission date :

PROTOCOL TITLE:

Ethical Approval period :

1. Is this still an active protocol ?

If yes, and this protocol is for instruction, answer questions 2 through 5

If yes, and this protocol is for research, answer question 2 through 5

2. Has the number of animals being used in this protocol changed ? Yes No

If yes, please indicate the changes :

a. Propose number :

b. Actual number :

c. Describe reason for the change :

3. Has the type of animal being used for this protocol changed ? Yes No

Please indicate changes (and reasons for them) below

4. Have the procedures being used for this protocol changed ? Yes No

Please indicate changes (and reasons for them) below

5. Have the personnel working on this protocol changed ? Yes No

If yes, please indicate the name(s) of personnel no longer working on this protocol, the name(s) of new personnel, their duties as related to this protocol and their specific qualifications to perform in this capacity, and the date he/she completed the CITI training.

6. Have there been any adverse effects of problems observed in this project and how have they been managed or will be managed ? Please describe

7. In what room(s) are the animal housed ?

8. Provide a brief summary of results to date ?

APPROVALS Date: …………... Chairperson/Vice chair person, MRIN EC COMPLETION Date: ………….. Secretary, MRIN EC


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9. Have you published of any work /accomplishment ?

No

Yes, please provide a list of your publications

I certify that the above report is a true account of the status of my project and I agree to abide by the guide for the care and use of laboratory animals (8th edition)

Signature of P.I.:

Date:

MRIN EC/KEPK MRIN

Comment/Decision:

(please write the comment below if decision

is minor/major/disapproved)

Approved

Minor revision

Major revision

Disapproved

SIGNATURES:

Date:………………… Protocol Reviewer

APPROVALS

Date:…………………

Chairperson / Vice Chairperson MRIN EC

COMPLETION

Date:…………………

Secretary, MRIN EC


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12.6. Serious Adverse Event Report Form (AF/AS/01-019/2019/01.0)

SERIOUS ADVERSE EVENT REPORT FORM

Principal Investigator:…………………………………….. Application No:

Study Title:………………………………………………………. Protocol No.:

Name of the study medicine/device………………………..…………………

Report Date :………… initial follow-up Onset date:……………

Sponsor:………………………………………………… Date of first use: ………………………..

Subject’s initial/number: Age: Male Female

Subject’s history:

Laboratory findings:

SAE :

Treatment: Outcome: resolved on-going

Seriousness: Death

Life Threatening Hospitalization – initial prolong Disability / Incapacity Other…………………………………

Relation to Drug Device study Not related Possibly Probably Definitely related Unknown

Changes to the protocol recommended?

No Yes , attach proposal

Changes to the informed consent form recommended?

No Yes , attach proposal

Signature of PI : Date:

Reviewed by : ……………………… Date:


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Comment : ………………………………………………. Action : 1) Continue 2) Continue with remark 3) Discontinue /Terminate


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12.7 Serious Adverse Event Report Form (AF/AS/02-019/2019/01.0)

UNEXPECTED ADVERSE EVENT SUMMARY REPORT

Principal Investigator:…………………………………………………………………………. Application No:

Study Title:……………………………………………………………………………………... Protocol No.:

Name of the studied medicine/device………………………..…………………………….. This report covers the period :

Sponsor:………………………………………………………………………………………... From…………………To……………….

# Description of Unexpected Adverse Events

Date of Event (D/M/Y)

Date start and end of Tx (D/M/Y)

F or M

Ini-tial

Age (Y)

Serious Yes No

Related to Study Yes No

Concomitant medication

Intervention


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12.8 Final Repot (AF/AS/01-019/2019/01.0)

STUDY REPORT FORM

Protocol No.: Submission date :

Protocol Title : Principal Investigator: Ethical Approval Period :

Phone number: E-mail address : Sponsor’s Name

Address:

Phone : E-mail : Study site(s): Total Number of study animals :

No. of Treatment Group :

Number of animals who received the test articles:

Study materials:

Treatment form:

Study dose(s):


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Duration of the study

Objectives:

Results: (Use extra blank paper, if more space is required.)

Adverse /Unanticipated Events

Did you experience any unanticipated adverse events, complication or incidence

Yes No

If yes, describe the event and how it was handled

Did you receive any complaints about the research ?

Yes No

If yes, describe the complaint and how it was handled

Data Storage

1. Where are your project files being stored ?

2. Have you verified the status of all project files and confirmed they are stored in a safe and secure location ? Data must be kept for At least 3 years after project is completed

Yes No

If No, Please explain

Signature of PI :

Date:

Accepted Accepted with remarks . please state the remarks : ……………………….


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SIGNATURES:


ACCEPTED:

Date: ……………….. Chairperson/Vice chair person MRIN EC COMPLETION:

Date:…………………

Secretary, MRIN EC

12.9. Study Termination Application

(AF/AS/01-018/2019/01.0)

STUDY TERMINATION APPLICATON

PROTOCOL NUMBER:

PROTOCOL TITLE:

PRINCIPAL INVESTIGATOR:

PHONE : E-MAIL:

INSTITUTE:

SPONSOR:

MRIN EC APPROVAL DATE:

DATE OF LAST REPORT:

STARTING DATE:

TERMINATION DATE:

NO. OF ANIMALS APPROVED

NO. OF ACTUAL ANIMAL USED :


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SUMMARY OF RESULTS (include description of number of dead/excluded animal )

ACCRUAL DATA:

P.I.SIGNATURE:

DATE:

SIGNATURES:


APPROVAL:

Date: ……………….. Chairperson / Vice chair person, MRIN EC COMPLETION:

Date:…………………

Secretary, MRIN EC


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12.10. Response to Animal Welfare Violation Report (AF/AS/01-017/2019/01.0)

ANIMAL WELFARE VIOLATION REPORT FORM

1. Nature of concern

Animal use

Animal Health

Animal Husbandry

Housekeeping

Veterinary care

Occupational Health and Safety

Please describe the concern(s) :

2. General Information

Please provide the following information, if available :

Principal Investigator

EC Protocol Number

Species involved

Number of animals involved

Location

Room No.

Date /time of observation

3. Person reporting

Please provide the following information for further clarification and /or notification of the outcome of EC investigation. But you may opt to hide your identity.

Individuals who have made this report in good faith will be protected and the report will treated with strict confidentiality.

Name ( optional )

Telephone ( optional )


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Fax ( optional )

Email ( optional )

Institution ( optional )

Signature (optional)

Date


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12.11. Flow Chart of Application Submission Process


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12.12. Glossary Initial Review The first time review of that protocol made by two or

three individual reviewers (MRIN EC members or non-members) in advance of the full Committee meeting, and comments of the reviewers will be reported to the full Committee meeting.

Stipulation Specify as terms of or condition for an agreement,

contract, etc. state, put forward for a necessary condition.

Expedited review A review process by only two or more designated MRIN EC/KEPK MRIN members who then report the decision to the full Board meeting. An expedited review is a speedy one for minor changes to the approved protocol and for research proposal with minimal risk in nature.

Approved Protocols Protocols that have been approved by the MRIN EC/KEPK MRIN may proceed.

Protocols that have been approved with recommendations by the MRIN EC/KEPK MRIN may not proceed until the conditions set by the MRIN EC/KEPK MRIN in the decision have been met. Protocols should be amended and submitted to the MRIN EC/KEPK MRIN within one month for re-review.

Suspension Termination

Stop until further clarification Permanently stop of the study

Adverse Event Any untoward medical occurrence in a patient or clinical investigation participant administered an investigational product and which does not necessarily have a causal relationship with this treatment. The adverse event can therefore be any unfavorable or unintended sign or experience associated with the use of the investigational product, whether or not related to the product.

Adverse Drug Reaction

In the pre-clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not established all noxious or unintended responses to the product related to any dose should be considered adverse drug reactions. The phrase “responses to a medicinal product” means that a causal relationship between the product and the adverse event


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is at least a reasonable possibility, i.e., the relationship can not be ruled out.

Regarding marketed products, a response to a product which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis or therapy of diseases or for modification of physiological function.

IND Investigational New Drugs means substances with

potential therapeutic actions during the process of scientific studies in human in order to verify their potential effects and safety for human use and to get approval for marketing.

12.13. List of Abbreviation ADR Adverse Drug Reaction EC Ethics Committee IND Investigational New Drugs MRIN Mochtar Riady Institute for Nanotechnology PI Principal Investigator SAE Serious Adverse Event

Table of Contentsmrinstitute.org/Form SOP MRIN EC 2019/Guideline for PI... · 2019-02-13 · or...

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