Cliniox Site Management SOP

Site Name KLES Dr.
Prabhakar Kore Hospital and MRC, Belagavi_I0
Authorized by vice chancellor of KLE University-KAHER, Nehru Nagar,

Beragavi
soP-03/2019
KLE Site Management office-SOp
VERSION and DATE: 03 and September -2019
Validity 30-Sep-201 9 to 29-Sep -2021
DRAFTED BY:
Revana S Devarinti Assistant Coordinator-SMO
sE'P 201
REVIEWED and APPROVED BY:
Prof.(Dr)M. S.Ganachari Member Seuetary of KLE-

SMO 3 0 sEP ?0
Name Title Signature Date
KLE-Site Management office of KLE Academv qnrr

of Hisher
KLE Academy of Higher Education and Research
Site Management Office

KLES Prabhakar Kore Hospital Medical Research Center, Belgaum
Standard Operating Procedures- Version-3.0 (SOPs)
Sl.No Contents Page No
1. SOP for Principal investigator 01-07
2. SOP for obtaining ICF process 08-11
3. SOP for Clinical research coordinators 12-17
4. SOP for check in and check out of the subjects 18-20
5. SOP for dosing at subject monitoring restrictions 21-23
6. SOP for Handling of Biological samples at site 24-28
7. SOP for Handling and reporting of AE/SAE 29-38
8. SOP for instructions for filling of screening form and CRFs 39-45
9. SOP for Investigational product management 46-53
10. SOP for Screening and enrollment of Subjects 54-62
11. SOP for Audio-Video recording of ICF process 63-69
12. SOP for Archival of study Documents 70-80
13. Site Protocol --
14. Routine Hospital flow chart --

Title 001: Standard operating procedure for Principal investigator
Sl. No Contents Page No
1. Objectives 02
2. Prior to Intimation of the study 02
Make sure that the facilities are sufficient to allow the study to be
3. undertaken efficiently. 03
Arrange archiving of trial documents according to GCP and regulatory

4. 03
requirements. It is important to check
If the IEC and others approve the trial, sign the final copy of the
protocol and confirm in writing that he/she has read and understood,
and will adhere to, the protocol, study procedures and ICH Good
5. 03
Clinical Practice, will collaborate with the monitor, and accords with
Sponsoring agencies on publications policy.
6. During the Study 04
7. After Completion of the study 07
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KLE SITE MANAGEMENT OFFICE- SOP VERSION-3.0 ,
Note: When a trial is sponsored by another agency/pharmaceutical company, the Investigator may
also be requested to follow their procedures in order to comply with company obligations.
Agreement between all parties will be discussed before initiating the trial.
Aims: To define Investigators’ responsibilities and to provide instruction, when performing

clinical study (ies) facilitated by KLES Dr. Prabhakar Kore Hospital & MRC, Belagavi
I. Objectives:
i. To provide the Investigator with general instruction to ensure that he/she understands and
accepts the obligations incurred in undertaking the study.
ii. To ensure that the study is planned, set up, conducted, documented and reported according to the
protocol, related site SOPs, Recent IEC SOPs, ICMR Guidelines, ICH GCP and applicable local
regulatory requirements.
iii. To ensure that the rights, safety, and wellbeing of study subjects/Participants are properly
protected.
iv. To ensure that data are generated, collected and documented with accuracy, consistency and
integrity.
v. To ensure that the Investigator is acquainted with the study procedures, verification procedure,
audits and inspection procedures.
vi. To responsible for the third-party staff (Site management organization employees), whoever
working in the respective clinical trials.
Co-investigators:
Co-investigators are authorized healthcare professionals who work alongside the PI at a trial site,
e.g. other Consultants in the department, Post Graduate Medical students). The co-investigator
may conduct all or part of the PI’s duties, and must be available to act up as PI if the PI is
unavailable for any length of time (e.g. annual leave) or in an emergency situation that could affect
the safe conduct or oversight of the trial.
Note: PI/Co-I not affiliated to the KAHER (KLE University), those cannot be delegated in the
clinical trial team.
II. Prior to initiation of the study:
The Investigator should:
i. Be interested in the scientific aspects of the study and ensure that the study is responsive to the
needs of public health within the country of the population in which it will be conducted.
ii. Ensure the confidentiality of the product, the protocol and trial procedures by giving a
confidentiality agreement in writing to CRO/sponsoring agencies.
iii. Have sufficient time free from other obligations to prepare and conduct the trial.
iv. Clinical trials are time consuming and the Investigator should ensure that sufficient time can be
dedicated to the study, including for informing and supervising study staff.
v. Review Investigator’s Brochure and any up-to-date information on the investigational product.
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vi. The Investigator must be familiar with the product, including pre-clinical toxicology,
pharmacology, pharmacokinetics and up-to-date clinical data.
vii. Review and discuss investigators' SOPs and protocol with the Clinical Monitor
viii. The Investigator should clearly define: Factors that may alter the feasibility and acceptability of
the trial. An adequate recruitment rate for the trial by providing retrospective data on numbers
of patients who would have satisfied the proposed entrance criteria during proceeding time
periods.
ix. Make sure that the procedures stated in the study protocol are applicable in his/her center and
fully understood. The Investigator should ask the Clinical Monitor to clarify any points of
possible misunderstanding.
x. Make sure that there are sufficient medical, paramedical and clerical staffs to support the study
and deal with foreseeable emergencies.
III. Make sure that the facilities are sufficient to allow the study to be undertaken efficiently.
Ensure:
 Confidentiality and safety conditions for trial subjects.
 Adequate equipment/facilities for subject follow-up, examination and care.
 Adequate facilities for Investigational Medicinal Products storage
 Adequate facilities for laboratory assay of the Subjects blood parameters investigations.
 Adequate facilities for retention of trial documents, ensuring confidentiality of all information
about trial subjects and information supplied by KLEs Prabhakar Kore Hospital Medical
research Centre, Belagavi /sponsoring agencies.
 Make sure that the IPD trial subject should be in house in the Private Wards
IV. Arrange archiving of trial documents according to GCP and regulatory requirements. It is
important to check.
 The duration of retention of patient records with the Institution's archive. In case the
Institution's archive does not ensure retention of documents for the period of time requested by
sponsor.
 The Investigator must arrange for the retention of the subjects’ source documents/records for
the period requested by sponsor and regulatory requirements.
V. If the IEC and others approve the trial, sign the final copy of the protocol and confirm in
writing that he/she has read and understood, and will adhere to, the protocol, study
procedures and ICH Good Clinical Practice, will collaborate with the monitor, and accords
with Sponsoring agencies on publications policy.
Submit requested documents to the Site Management Office of KAHER, including:
 Signed agreement to comply with this SOP
 Approved protocol, signed and dated.
 Approved informed consent form and other subject information, advertisement (local language
and English translation).
 Investigator’s and co-investigator’s curriculum vitae (CVs).
 Recent ICH-GCP training certificate
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 Authorized Staff Form

 Product exportation/importation authorization.
 Laboratory certification/recent list of normal laboratory ranges, dated and signed by lab
head/Investigator.
 Lab Accreditation certificate
 Final Clinical trial agreement
 Signed agreement that the product will not be used before the site Initiation Visit has been
made and authorization obtained from the SMO Clinical Research Coordinator (if applicable).
 Ethics Committee accreditations
 Visit of archival facilities (situated at G-0 at KLES Dr. Prabhakar Kore Hospital and MRC,
Belagavi
VI. During the Study:
The trial can be initiated (begin screening and/or enrolment of trial subjects) only after the
Clinical Monitor has satisfactorily conducted a Trial Initiation Monitoring Visit and the SMO
Clinical Coordinator has given written authorization.
i. Delegation of duties: PI can delegate the CRC/Sub-I/Phlebotomist when the study is ongoing at
site. PI should provide a comprehensive list of study staff members and the duties that have been
delegated to them by the PI. It is applicable for both observational and interventional clinical trial
studies at KLES Dr.PK Hospital and MRC, Belagavi.
ii. Completion of the delegation log:
The Clinical trial delegation log provides documented evidence of the appropriate delegation of
the PI’s responsibilities. The delegation log must state clearly the name of the person, their role
and the activities they are delegated by the PI as well as being signed and dated by the PI prior to
the activity being undertaken by the individual. All key personnel must be on the delegation log.
The PI may delegate activities to a named person in a large department such as pharmacy, and
the relevant trials pharmacist would then take responsibility for the conduct of that activity by
the department. The dates of entries must be in chronological order and the PI must NOT pre-
sign logs (for members of the research team to add names and tasks at a later date).
iii. Investigator’s File, Including Storage and Retention:
On initiation of the study, the Investigator must prepare a file containing all the documents
related to the trial. During the study, the Investigator is responsible for updating the File and
regularly adding trial-related documents.
The Investigator should keep the File in a locked cabinet, in a secure area accessible only to the
Investigator and authorized study staff. The Investigator File and associated source documents
should be retained for the time agreed with /sponsors. Patient identification codes should be kept
for at least 15 years after completion of the trial.
iv. Written approval from sponsors and site administrations, PI must be obtained prior to
destroying records.
 Lab kits
 IPs
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 Study Documents (after completion of 15 years)

Lab kits and IPs as per sponsor requirements, during the study
v. The Investigator's File contains:
Administrative and Regulatory Documents
 Composition of IEC of KAHER, Belagavi
 IEC Accreditation details
 Lab head CV and MRC
 Local regulatory requirements.
 IEC and other authorities’ written approval for all documents (protocol, informed consent(s)
and any written information including advertisements for recruitment of study subjects).
 Protocol initial submission letter and initial IEC of KAHER Decision letter.
 Correspondence with the Ethics Committee and the Authorities, including: Protocol
submission. Amendment submission, if any.
 SAE Initial, Follow Up and Final reports and SAE review report by IEC of KAHER.
 Protocol modification notification, if any.
 Interim report/written summaries of the trial, if applicable.
 Final Report/written summaries of the trial, if applicable.
 Product importation authorization.
 Correspondence about product importation.
 For studies under IND, a copy of the completed and signed Form FDA 1572 and FDA 3455
 Investigator’s and Co/Sub-investigators’ C.V.s.
 New Investigator and Sub-investigators’ C.V.s along with recent ICH-GCP certificate.
 Authorized Staff Form (ASF).
vi. Investigators/sub-Investigators qualifications and agreements
 The investigator(s) should be qualified by education, training, and experience to assume
responsibility for the proper conduct of the trial, should meet all the qualifications specified
by the applicable regulatory requirement(s), and should provide evidence of such
qualifications through up-to-date curriculum vitae and/or other relevant documentation
requested by the sponsor, the IEC, and/or the regulatory authority (ies).
 The investigator should be thoroughly familiar with the appropriate use of the investigational
product(s), as described in the protocol, in the current Investigator’s Brochure, in the product
information and in other information sources provided by the sponsor.
 The investigator should be aware of, and should comply with, GCP and New Drugs and
Clinical Trial Rules, 2019
 The investigator/institution should permit monitoring and auditing by the sponsor, and
inspection by the appropriate regulatory authority (ies).
 The investigator should maintain a list of appropriately qualified persons to whom the
investigator has delegated significant trial-related duties.
 PI should Signed confidentiality agreement
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 PI should Signed agreement stating that products will not be used before the Trial Initiation.
 Monitoring Visit has been made and approval from the SMO Clinical Coordinator obtained.
 Sub investigator should be affiliated to KLES Dr. Prabhakar Kore Hospital and MRC,
Belagavi and KLE’s JN Medical College staff.
vii. Correspondence and Monitoring
 Correspondence with sponsoring agencies (including the telephone call, E-mail etc). Notes of
meetings with sponsoring agencies.
 Summary list of site visits (copy).
 Site Initiation visit Report (copy).
 Notification by Investigator to/Sponsor of serious adverse event and related reports.
 Documentation of serious adverse event reporting by/Sponsor to other investigators.
 Investigator interim report/summaries of the trial for /sponsoring agencies, if applicable.
 Investigator final report/summary of the trial for/sponsoring agencies, if applicable.
 Sponsoring agencies should inform through Mail/Telephonically Prior to Visit for site
monitoring.
 Copies of the Investigator's interim report/written summaries of the trial to the IEC of
KAHER and authorities.
 Monitoring visit of IEC members at site: PI/CRC should arrange/ready for the all study
related documents for Monitoring. IEC secretariat will informed via mail/letter about the IEC
monitoring visit. IEC members will select randomly which have approved and ongoing
studies at site.
 To ensure to submit the SIV and SMV report to IEC of KAHER, Belagavi
viii. Compliance with study protocol
 The investigator/institution should conduct the trial in compliance with the protocol agreed by
the sponsor and, if required, by the regulatory authority (ies) and which were given
approval/favorable opinion by the IEC of KAHER. The investigator and the sponsor should
sign the protocol, or an alternative contract, to confirm agreement.
 The investigator should not implement any deviation from, or changes in the protocol without
agreement by the sponsor and prior review and documented approval/favorable opinion from
the IEC of KAHER of an amendment, except where necessary to eliminate an immediate
hazard(s) to trial subjects, or when the change(s) involves only logistical or administrative
aspects of the trial (e.g., change in monitor(s), change of telephone number(s)).
 The investigator, or person designated by the investigator, should document and explain any
deviation from the approved protocol.
 The investigator may implement a deviation from, or a change of, the protocol to eliminate an
immediate hazard(s) to trial subjects without prior IEC of KAHER approval/favorable
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opinion. As soon as possible, the implemented deviation or change, the reasons for it, and, if
appropriate, the proposed protocol amendment(s) should be submitted:
a) To the IEC for review and approval/favorable opinion,

b) To the sponsor for agreement and, if required,
c) To the regulatory authority (ies)
xi. Adequate sources:
 The investigator should be able to demonstrate (e.g., based on retrospective data) a

potential for recruiting the required number of suitable subjects within the agreed
recruitment period.
 The investigator should have sufficient time to conduct and complete the trial within the
agreed trial period.
 The investigator should have available an adequate number of qualified staff and adequate
facilities for the foreseen duration of the trial to conduct the trial properly and safely
manner.
VII. After Completion of the study:
 The CRA has to confirm the close out visit in writing to the Investigator/study site. The
letter will detail all persons expected to attend, and all administrative documents, IMP, and
regulatory documents required for review at this visit. The CRA will confirm recruitment
status at the end or premature end of the trial. If the site is closed prior to the end of the
trial, a reason for early closure should be clearly documented.
 The CRA will ensure that all Serious Adverse Events (SAE’s) have been reported by the
Investigator to the Sponsor and that the investigator is aware of any future reporting
requirements and follow up on any ongoing SAEs. If applicable, a line listing of all
SAEs/SUSARs that have occurred at the site should be filed in the TMF. If closing the lead
site in a multi-center trial, a line listing for all the SAEs/SUSARs at each site should be
filed in the TMF.
 The CRA will ensure that all outstanding data queries are resolved at the time of the close
out visit.
 All outstanding issues from previous monitoring visits will be resolved or appropriately
documented.
 The CRA will verify that final drug accountability is complete
 If applicable, the CRA will ensure that Sponsor authorization for IMP destruction has been
obtained and that the destruction or return of unused or partially used IMP is appropriately
commented and documented in the Pharmacy file.
 PI along with the study CRA review the all study related documents in study close out visit.
After completion of the study, all the study documents should be archived. (Please Refer:
title: 0012 SOP for archival study documents)
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Title: 002- SOP for Obtaining Informed Consent Form
Sl. No Contents Page No
Policy
1. 09
2. Objectives 09
3. Scope 09
4. Definition 09
5. Procedure 09
6. Applicable rules and regulations 11
KLE SITE MANAGEMENT OFFIC-SOP VERSION-3.0 Page 8

I. Policy:
The ethical conduct of clinical investigations is based on the voluntary consent of the subject,
who has been appropriately informed about a study’s risks and benefits, and is designed to
protect the rights, safety and wellbeing of human subjects. It is the responsibility of the
investigator to ensure compliance with all ethical standards, guidelines and federal and state
regulations have been met through the language of the informed consent document, and that
informed consent itself has been properly obtained from the subject or the subject’s legal
representative.
II. Objective:
This SOP gives the procedure for obtain informed consent from all trial subjects.
III. Scope:
Applicable for all Clinical trials at the site
IV. Definition-
Informed Consent: A process by which a subject voluntarily confirms his or her willingness
to participate in a particular trial, after having been informed of all aspects of the study that
are relevant to the subject's decision to participate. Informed consent is documented by
means of a written, signed and dated informed consent form.
V. PROCEDURE:
1) All the clinical trial related ICFs should be obtained in the respective Principal
investigator OPD.
2) Procedure for Obtaining Informed Consent from Volunteers for participation in study
3) The Subject Information sheet and the Informed Consent form will be given to the subject
on the day of Screening.
4) The Study Coordinator/designated person will issue a copy of Institutional Ethics
Committee of KAHER approved ‘Subject Information Sheet and Informed Consent Form’
(SIS/ICF) to the subject in the language best understood by him/her.
5) Investigator/designated person will give study related information from the Institutional
Ethics Committee of KAHER approved ‘Subject Information Sheet and Informed Consent
Form’ to the volunteer.
6) Investigator/designated person will inform and explain the subject about the purpose of
the study, the study procedure, the risk and discomforts associated with the study
procedure and restrictions, the adverse effects of study drug, housing period, total blood
loss, duration of the study, the remuneration, number of volunteers to be included in study,
voluntary participation, withdrawal from the study, identity confidentiality etc, from the
IEC/ approved ‘SIS/ICF’. The name of the subject to whom the SIS/ICF is issued and sign
and date of the person counseling the subject will be documented in the source document.
7) Investigator/ designated person will take the Informed Consent in one to one manner, the
Investigator/ designated person will answer to all personal queries of the subject or their
Legal Acceptable Representative (LAR) or Guardian during this session.

8) Investigator/designated person will inform that the eligible and interested subject or the
volunteer’s Legally Acceptable Representative (LAR) will have to sign the SIS/ICF’ and
if the subject is unable to read and if the Legally Acceptable Representative (LAR) is
unable to read then an impartial witness who is independent of the study will be present
during the entire informed consent discussion and will explain the contents of the SIS/ICF
to the subject or the volunteer’s legally acceptable representative in the best language
understood to the volunteer.
9) Each subject will be given sufficient time and opportunity to enquire about the study drug
or the study procedure or consult his/her family physician to decide for his/her
participation in the study.
10) The Investigator(s), Sponsor or the staff will not coerce or unduly influence the potential
volunteer/subject to participate or to continue to participate in the study.
11) Investigator/Physician/ designated person will ensure that the subject as understood all the
aspects of the study including the purpose of the study, the study procedure, the risk and
discomforts associated with the study procedure and restrictions, the adverse effects of
study drug, housing period, total blood loss, duration of the study, the remuneration,
number of volunteers to be included in study, voluntary participation, withdrawal from the
study, identity confidentiality etc, from the Institutional Ethics Committee Of KAHER
approved ‘SIS/ICF’ and is participating in the study willingly.
12) Investigator/designated person will document the name of the subject to whom the
SIS/ICF is issued and the name of Investigator/designated person counseling the
volunteer, in the source document.
13) The volunteer/volunteer’s legally acceptable representative (LAR) will write all the details
like his/her name, address, date of birth, qualification, occupation, annual income of the
volunteer, name of nominee(s), relation of the nominee with the subject, address of the
nominee, and sign the ICF (declaration) with date.
14) In case of the volunteer/legally acceptable representative is unable to read/write then the
subject will give the left thumb impression at the appropriate place and the impartial
witness will write volunteer’s name and date below the thumb impression and all the
respective details as mentioned above in the ICF, with the consent of the volunteer. The
impartial witness will write his/her name, address and contact details, sign and date the
declaration for witnessing the entire process of obtaining the informed consent of the
volunteer.
15) The impartial witness by signing the consent form attest that the information in the
consent form and any other written information is accurately explained and is apparently
understood by the subject of the volunteer’s legally representative or the guardian, and
that the informed consent was freely given by the subject or the volunteer’s legal
representative.
16) The Investigator/Co-Investigator will sign and date and will put his/her name in the ICF.
17) Site coordinator will give photo copy of signed consent to Subjects/Legally Acceptable
Representative.
18) The researcher has an obligation to convey details of how confidentiality will be
maintained to the participant.

19) After the completion of consent process the study designee record the all protocol related
information in sources documents.
20) If the patient is literate and unable to write in ICF then LAR can write the details on behalf
of the patient and no LAR signature is required to authenticate the same. But reflection f
the movement should be recorded in ICF process.
VI. Applicable rules and regulations:

FDA 21 CFR 50.20—General Requirements for Informed Consents
National Ethical Guidelines for Biomedical and Health Research Involving Human
Participants-2017
HHS 45 CFR 46.116—General Requirements for Informed Consent
New Drugs and Clinical Trial Rules, 2019

Title: 003-SOP for Roles and Responsibilities of Clinical Research Coordinators
Sl. No Contents Page no
1. Purpose 13
2. Scope 13
3. Responsibilities 13
4. Procedure 15
5. Applicable Staff 16
KLE-Site management Office-SOP Versio-3.0 Page 12

1. Purpose
This SOP defines the procedure and recommendation of training of study team members and
adequate handover to CRC/study team member, to ensure that the patient safety, protocol
compliance, data integrity and overall quality assurance at the investigational site is protected
and integrated as per the applicable regulations and guidelines.
Study team members must understand the responsibilities of the trials conducted at site and be
appropriately qualified by education, training and/or experience to perform his or her research-
related task(s).
The purpose of a handover is to ensure continuity of operations when the study team member,
usually responsible, is not available due to temporary or permanent absence. A handover can
be supported by a discussion to explain the status of the tasks, a summary of the work status in
an email/ memorandum or, a more detailed file.
2. Scope:
This SOP will apply to all study research coordinator at site management office in KLEs
Dr.Prabhakar Kore Hospital and MRC, Belagavi.
3. Responsibilities:
i. Study start up activities like Feasibility/Synopsis and Clinical disclosure agreements.

ii. Reviews and develops a familiarity with the study protocol (e.g. study procedures and
timelines, inclusion/exclusion criteria, confidentiality).
iii. Document date of training and signatures of study personnel trained on study specific
training log.
iv. Collect documents needed to initiate the study and submit to the sponsor (e.g. forms 1572,
CVs, etc.)
v. Conduct or participates in the informed consent process, including interactions with the IEC
and discussions with research participates, including answering any questions related to the
study.
vi. Obtain appropriate signatures and dates on forms in appropriate places. Assures that
amended consent forms are appropriately implemented and signed/Dated.
vii. Screen subjects for eligibility using protocol specific inclusion and exclusion criteria,
documenting each potential subject eligibility or exclusion. Creates and utilizes Eligibility
Checklist to inclusion/exclusion criteria.
viii. Coordinate participant tests and procedures, including scheduling and registration of
subjects with hospital Outpatient/ in patient departments at site (e.g. radiology for CT scan).
ix. Collect data as required by the protocol. Assure timely completion of Case Report Forms
x. Maintain study timelines per the event schedule (e.g. subject visits, procedures and data
entry are completed within the allotted time window per study protocol).
xi. Maintains adequate inventory of study supplies. If handling investigational drugs/devices,
follows the sponsor protocol and/or UCSF Policy on Investigational Drug/Device
Accountability.
xii. Complete study documentation and maintains study files in accordance with sponsor
requirements and University policies and procedures including, but not limited to, consent
forms, source documentation, narrative notes if applicable, case report forms, and
investigational material accountability forms.
xiii. Maintain effective communication with sponsor, research participants, IEC of KAHER and
PI during the course of the study.
xiv. Work with the PI to manage the day-to-day activities of the study including problem
solving, communication and protocol management.
xv. Report all findings and correspondence from external or internal study monitoring and
audits to the research manager and department Chair in a timely manner.
xvi. Assist the PI in reporting of research-related incidents, including protocol deviations or
potential violations, as well as findings and correspondence from external or internal study
monitoring and audits to the IEC of KAHER, Belagavi in a timely manner.
xvii. Assist the Principal Investigator in submission of accurate and timely closeout documents to
applicable Federal agencies, University entities, and the sponsoring agency in accordance
with Federal regulations and Hospital/University policies and procedures.
xviii. Study Handover: If any study team member is planning for leave or to resign, he/she must
ensure that the proper handover is given to concern person identified by the PI, the identified
person should be briefed in time before the person goes on leave to allow for any follow up
questions.
xix. Prior to leaving the study, the existing study team member should complete the
following:
 Training on protocol and procedures
 Information regarding study subjects, study documents and all study related activities
 Outstanding data entry and/or data queries
 Training to complete source documents
 Explanation on the objectives & priorities
 Notification to the sponsor of the study team changes
 Notification to the active subjects of the study team changes if the research team contact
information will change for the subjects.
 Provide a list of study-specific contacts (e.g., sponsor, monitor, vendors involved etc)
 Provide a list of outstanding issues
 The leaving person has to make sure that the documentations concerned for the tasks is up
to date and easily available, and if needed, revise it when preparing the hand over.
If there is a change in PI, the following documents need to be revised and completed;
 Inform Sponsor and IEC of KAHER regarding the change in PI in the Study team.
 Consider revising the protocol and informed consent form, as appropriate. Also consider
notifying current subjects; correspondence sent to all subjects must be approved by the
IEC, if applicable.
 Update the Form FDA 1572 or the Investigator Agreements, Investigator Undertaking and
other required forms
 Update the Duty Delegation log
 Ensure that the new PI has completed the SOP required training and study-specific
training

 Written hand over should be given in order to ensure the continuity of work. The format
can be a briefing note, a check list, or a schedule prepared to give all information.
When the study member returns from leave a hand over should be prepared to give updates on
the status of the tasks.
The existing and new study team member should document the study handover in a note to file
or other documentation in the TMF. The note should contain some of the items above and the
date of the handover. The new study team member should obtain documented study-specific
training and any required approvals prior to being added to the duty delegation log.
4. Procedure:
Appointment Procedure:
The site clinical research coordinators have been appointed through respective site
management organisations. Before assigning the CRC to KLEs Dr.PK Hospital, the
Organisation has to intimate the site personnel via mail or letter for communication with proper
appointment letter and period of agreement (If applicable).
Study Team Training:
1. On appointment, all study team members will be given an appropriate study depending on
the job specification to possess the right experience and qualifications and further training
may be provided to bring them up to the required level for specific tasks. Duty delegation /
job responsibility document will be given to every Clinical research Coordinator/team
member.
2. The Medical Director and department of clinical research recommend that all Investigators,
CRC and other study team members must undergo training which will enable them to
understand their responsibilities, applicable regulations, guidelines and research studies and
training should be documented in the training log.
3. Each Investigator, CRC and study team members will review and learn the site's SOPs. It is
recommended that SOP training must be included in the orientation of new clinical research
personnel. All applicable clinical research personnel should be knowledgeable of new or
revised SOPs.
4. Good Clinical Practice (GCP) is a universal standard in clinical research that must be
followed in every research protocol. GCP training and education are recommended for
research team members, especially the Investigator and CRC. However, any member of the
research team with a significant role in the conduct of a research study must be
knowledgeable in GCP. All members of the clinical research team should GCP trained and
certified.
5. If scheduled, the PI and CRC will attend the Investigator Meeting (organized by Sponsor)
and complete all required training for a study. If PI is unable to attend the meeting, PI can
recommend other study team member(s) to attend the IM. PI should be informed regarding
the study contents discussed in IM.

6. Before study initiation the Sponsor/CRO will organize SIV meeting at site to train all study
team members and all study team members should attend the meeting for thorough
understanding of the study.
7. In the study start up activities like feasibility/study synopsis CRC should intimate to the site
personnel.
8. The PI and study team member(s) should be prepared to demonstrate all training received.
CVs, GCP and other training certificates should be updated as required. It is recommended
that an assessment of the employee’s knowledge of the regulations and guidelines can be
conducted upon recruiting and on a regular basis. It is recommended that an assessment of
any additional protocol-specific skill requirements be conducted prior to activation of each
new study
9. Study team members should attend the course to acquire training or to update themselves.
10. PI can also train the study team and should maintain the training record.
11. It is recommended that the PI and study team must maintain the Site SOP training Record.
12. Entry in to Study drug store at site: The access will be given only blinded/unblinded
pharmacist and who are delegated (Delegation log) in clinical study for the IP management.
The entry access will be restricted.
5. Applicable Staff:
This SOP applies to all the existing personals of the clinical research team and any new
member appointed who may be responsible for training and study handover as mentioned in
this SOP( as per the delegation log).
These include the following:
 Investigator
 Research Team (listed in the delegation log)
 Clinical Research Coordinator
Staff responsible for Implementation:

 The department and Investigator will ensure that the research team involved in the conduct
of the study will comply with this site SOP.
 The department and PI will ensure that at the time of implementation of the SOP, which
the research team at the site management office (clinical research unit) in KLES
Dr.Prabhakar Kore Hospital and MRC, Belagavi are trained and in the event that an SOP
is modified, provide training regarding the change(s) and ensure their compliance with the
changes.

 It is the responsibility of each individual who are about to go on short / long term absences
or leave their current position / the Agency/third party employees to prepare a hand over
file.

Title: 004- SOP for Check in and check out of the subject
Sl.No CONTENTS Page No
Objective
1. 19
Scope
2. 19
19
Procedure For Check In

Procedure For Check Out
3.
KLE SITE MANAGEMENT OFFICE-SOP VERSION-3.0 Page 18

I. OBJECTIVE: This SOP gives the procedure for check-in and check –out of subject, from the
housing area before the start and the completion of the hospitalization period in a PK/PD
studies.
II. SCOPE: This SOP is applicable to all volunteer/subjects participating in a PK/PD studies. All
the PK/PD Should be preplanned and Make sure to avoid dosing schedules on Sundays (on
Sunday Registration counter will be remains closed/Unavailability of the Study Nurses/PIs)
III. PROCEDURE:
1.0 Procedure for Subject Check-In (in the First period of the study):-
1.1 The subjects who have given the written (signed) Informed Consent and have found eligible
for the study in Screening, pre-enrollment checks and are complying with the inclusion and
exclusion criteria’s as mentioned in the study protocol, and who are found negative in breath
alcohol, Urine screen for drug of abuse and urine pregnancy test or any other screening
procedure as mentioned in the study protocol will be checked-in into the private/Semi Private
wards as per direction from the Medical Director of KLES Dr,Prabhakar Kore Hospital and
MRC, Belagavi.
1.2 The Study coordinator/designated person will allot the subject number to each subject in
ascending order (01 onwards) in first period of study or as specified in the respective study
protocol on a first come first basis.
1.3 Study coordinator/designated person/ Subject Custodian will check the subject’s belongings,
clothing and pockets for any prohibited products like gum, medication, cigarettes and tobacco
or sharp instruments.
2.0 Procedure for Check-In For Subsequent Period(s):-
2.1 The PI will perform the medical checks (history from the last visit), vital sign measurement
and well being assessment, Clinical examination or any other investigation requirements as
specified in the study protocol for the subject, before enrolling for subsequent Period of the
study.
2.2 Blood/urine samples will be collected and for testing in the Clinical laboratory as specified in
the study protocol (if applicable).
2.3 PI will review the above reports and will record the status of subject’s fitness in the CRF.
2.4 If the subject is found to be eligible in all the above procedures, then he/she will be checked-
in into the housing area as mentioned in point 1.2.
2.5 The subject who is found to be unfit in any of the above parameters will be withdrawn from
the study and will be checked-out as per the procedure mentioned in point 3.0. If the subjects
have not reported to the study center for subsequent period or if the subject withdrew his/her
consent from the study then the details of his/her withdrawal will be documented in the
format for ‘Subject Dropout/Withdrawal /Termination Form’ of the CRF.
3.0 Procedure for Check-Out
3.1 Subject will be checked out after completion of the study /after completion of the housing
period of each study period or due to withdrawal/termination of subjects from the study.

3.2 In case subject is discharged after completion of the housing period of each study period or
due to withdrawal/termination of the subjects from the study then the details will be recorded
in the format ‘Discharge summary’ of the CRF of the respective subject.
3.3 The Physician/designated person will measure the vital signs and assess the well being of
subject and will perform the Clinical examination before discharge from the Clinical facility.
3.4 The Subject Custodian/designated person will return the subjects belongings from the locker;
will ensure that all the items provided by clinical facility are returned by the subject and also
ensure that the subjects are informed about the schedule date and time of subsequent period
or ambulatory sample (if applicable). The details of the check-out activity will be recorded in
the form in the CRF.
3.5 After completion of the study the Physician/designated person will perform the post study
safety evaluation as mentioned in the study protocol.
3.6 Physician/designated person will measure the vital sign, assess the well being of subject, take
the 12 lead ECG, perform the Clinical examination and will record details in the ‘Post study
evaluation form’ of the CRF of the respective subject.
3.7 Physician and/or Clinical Investigator/Co-Investigator will check the ECG report of
respective subject and will put the appropriate comment on the same after interpretation.
3.8 As per the requirements of the protocol, the blood and /or urine samples for Post-study
Clinical laboratory investigations will be collected and sent to the Clinical laboratory.
3.9 The subject will be advised to contact the responsible person of the study center if any health-
related problem arises after discharge from the study center. The details of the telephonic
communication will be recorded in the ‘Telephonic communication and Subject follow-up
form of the CRF.
3.10 After receipt of Post-study Clinical laboratory investigation reports from the laboratory, it
will be checked and reviewed by the Physician/designated person and the details of
observation will be recorded in the Post study evaluation form of the CRF of the respective
subject. The Physician/designated person will review the Post study Clinical laboratory report
values with the base line (Screening report) values and determine its significance to judge if
any Adverse Event has occurred/or any follow-up is required to resolve the same.
3.11 If any significant abnormal results are found then the subject will be followed up to resolve
the same and to ensure subject safety. The details will be recorded as adverse event in the
CRF of the respective subject.

Title: 005- SOP for dosing the subject and monitoring restrictions
S.No Contents Page no
22
OBJECTIVE
1.
22
SCOPE
2.
PROCEDURE:
 Monitoring Restriction
3.  Dosing the subject 22
KLE-Site Management Office-SOP Version-3.0 Page 21

I) OBJECTIVE
This SOP gives the procedure for dosing the subjects and Monitoring Restrictions in
compliance to the study Protocol for the Clinical study.
II) SCOPE
The SOP is applicable to PK/PD studies at the site
III) PROCEDURE:
1.0 Monitoring Restriction
1.1 The Subject Custodian/designated person will be responsible for monitoring the compliance
of diet, water, or any other restriction to be followed by the subjects in compliance to the
Study protocol during the hospitalization period of the PK/PD study.
1.2 The Subject Custodian/designated person will monitor these restrictions and will record the
details of the pre-dose and post-dose restriction compliance, in the Format for ‘Dosing and
Restriction monitoring Record’ of the CRF of the respective subject. Any deviation will be
documented in the CRF and will be justified appropriately.
2.0 Dosing the subject
2.1 The dosing activity during the hospitalization period for Pharmacokinetic studies will be
performed under the supervision of the Principal Investigator/ Co-Investigator.
2.2 The Principal Investigator /Co-Investigator will assign the responsibility of dosing to the
trained staff.
2.3 Staff responsible for dosing will ensure that gloves, dosing fluid (as per Protocol), flash
light, tongue depressor, scissors (if applicable) and format ‘Dosing and Restriction
monitoring Record’ for the subjects is kept ready on the dosing station well before scheduled
time of dosing.
2.4 The dose for each subject will be administered in a staggered manner to maintain subsequent
blood collection schedule.
2.5 The designated person will arrange the container containing the dispensed IP as per the
subject number in the dosing station before initiation of dosing activity.
2.6 The Subject Custodian will call subject by subject number for dosing prior to the scheduled
time of dosing.
2.7 The Designated person will give IP container of the respective subject to the respective staff
dosing the subject in the dosing station.
2.8 Staff responsible for dosing activity will verify the subject number and photo on ID card and
the subject number on the label on the dispensed IP container before dosing.
2.9 Staff responsible for dosing will assess the well being of the subject verbally before dosing,
and will also briefly explain the procedure to be followed for dosing and the restriction to be
followed thereafter.
2.10 Staff responsible for dosing activity will administer the IP directly in mouth of subject along
with water/dosing fluid or as per the procedure mentioned in the respective study protocol at
the scheduled dosing time for the respective subject.

2.11 Staff responsible for dosing activity will remove the duplicate label from the dispensed IP
container and stick it on the ‘Dosing and Restriction monitoring Record’ of the CRF of the
respective subject.
2.12 Staff responsible for dosing activity will store the empty IP container/syringe/ dosing
cup/glass/tongue depressor used for the subject.
2.13 Staff responsible for dosing activity will record the actual time of dosing and dosing details in
the ‘Dosing and Restriction monitoring Record’ of the CRF of the respective subject and will
sign and date it.
2.14 The Clinical Investigator/Co-Investigator will verify the dosing activity and the compliance
of the restrictions and will sign and date this record.
2.15 The Designated person will collect unused IP(s) (due to subject dropout/terminated before
dosing) and will take it to the IP storage room and will record in the IP accountability Record
as per the respective SOP.
2.16 In case of formulation where there is any specific requirement for administration/application
of the IP the procedure for dosing/dose administration will be followed as per respective
Study Protocol/Pack Insert/on the IP container.

Title 006: SOP for Handling of biological samples
Sl.No Contents Page no
OBJECTIVE
1. 25
SCOPE
2. 25
PROCEDURE:
 Procedure for blood sample collection
 Precaution to be taken for Photo sensitive and
3. Temperature Sensitive Drug Product 25
 Transfer of samples from the Clinical Facility to the
Bio-analytical Facility.

I. OBJECTIVE:
This SOP defines the procedure for collection and processing of blood samples,
separation of plasma/serum from blood samples, storage and transfer of
plasma/serum/whole blood samples.
II. SCOPE: This SOP is applicable to PK/PD with/and Phase I, II, III and IV studies.
III. PRECAUTIONS:
1. Proper care should be taken while handling the blood sample/plasma/serum during
transfer to avoid spillage. (appoint the trained Phlebotomist from Sponsor/Hospital if
Applicable)
2. Correctness of the vaccutainer type and capacity and to be used for the collection as
per the study protocol should be checked.
IV. PROCEDURE:
A. Procedure for Blood Sample Collection
1. The Phlebotomist/Nursing Staff/designated person will arrange the labeled
vacutainer/centrifuge tubes in the racks in each blood sample collection station as per
the sampling time point.
2. The Phlebotomist/Nursing staff/designated person will ensure the availability of the
required medical accessories like labeled vacutainers/centrifuge tubes with appropriate
anticoagulant as mentioned in the study protocol, syringes, cotton, tourniquet,
vacutainer/centrifuge tube stands, needles, gloves and blood sample collection
formats, or any other requirement(s) as specified in the study protocol, on the sample
collection table before the start of the blood sample collection activity.
3. The Phlebotomist/Nursing staff/ designated person of standby collection station will
check the pre-labeled vacutainers/centrifuge tubes and will arrange them in sequence
on the rack for each sample collection station and will enter the details in ‘Pre-Sample
Collection Vacutainer/Tube Check format’
4. Intravenous cannula will be inserted in the fore arm of the subject for collection of the
blood samples for Pharmacokinetic study.
5. The Subject custodian will call the subject(s) by their subject number in sequence and
will direct them to the respective sample collection station, at least 2 minutes before
the scheduled blood sample collection time.
6. Bed-side blood sample collection will be done as per requirement or if stated in the
study protocol.
7. The Phlebotomist/Nursing staff/designated person will verify the
vaccutainer/centrifuge tube label for the study code, sampling time and the subject
number and will also verify the identity of the subject by checking photograph and
subject number on the Identity card and the subject number on the wrist band, before
the start of each blood sample collection.
8. The sample collection timings will be staggered as per the dosing time of each subject.
Phlebotomist/Nursing staff/designated person will record the schedule time of each
sample time point mentioned in the ‘Blood Sample Collection Details’ of the CRF for
each subject.

9. The Phlebotomist/Nursing staff/ designated person will discard the initial saline mixed
blood (approximately 0.3 mL or volume as per Study specific protocol) from the
intravenous canula using a 2 mL syringe before collecting the blood sample.
10. The Phlebotomist/Nursing staff/ designated person will secure the disposable (10
mL/5 mL/2 mL) syringe to the intravenous cannula, will open the three-way stop-cock
and will collect the blood sample on the scheduled time within two minutes (or as
mentioned in the study protocol The volume of the blood sample to be collected will
be as per the Study Protocol. After collection of blood samples, the vacutainer/tube
with samples will be shaken mildly for mixing with the anticoagulant in the
vaccutainer/tube.
11. After collecting the blood sample, the 3-way stop cock will be closed and the blood
sample will be transferred into the respective vacutainer/centrifuge tubes of the
subject.
12. At the time of transfer of blood samples the Phlebotomist/Nursing staff/ designated
person will ensure that the samples are transferred into the correct
vacutainer/centrifuge tubes of the respective subject.
13. After each sample, 1 mL isotonic saline solution will be injected into the 3-way stop
cock to avoid blockage of cannula. The 3-way stop cock will be kept closed till the
next scheduled sample collection of the subject.
14. The Phlebotomist/Nursing staff/ designated person will record the actual time of each
sampling time point for each subject and will sign and date in the format for ‘Blood
Sample Collection Details’ of the CRF.
15. In case of cannula blockage observed during the sample collection, the blood sample
will be collected by direct vein puncture using a syringe with needle, thereafter the
subject can be recanulate, if required. Any deviation in the sample collection time of
more than two minutes (or as mentioned in the study protocol) and the reason for the
same (canula block/canula replaced/direct prick/poor blood flow) will be recorded in
the ‘Blood Sample Collection Details’ of the CRF of respective subject.
16. The Phlebotomist/Nursing staff/designated person will transfer the vacutainer
/centrifuge tubes with blood samples at each sampling time from each sampling
station(s) to the sample processing area.
17. The Technician/designated person will receive the vacutainer/centrifuge tubes with
blood samples and check for the time point, receiving time, total number of samples
received, and record the details in ‘Centrifugation and Separation of Biological
Samples Record’.
18. In case of requirement of whole blood or serum, the sample will be processed as
specified in the respective Study Protocol.
19. The Technician/designated person will place the vacutainer/centrifuge tubes in the
centrifuge machine.
20. The Technician/designated person will set the speed (RPM), time and temperature (as
mentioned in the study protocol) of centrifuge machine and will operate the centrifuge
machine as per the Standard operating procedure for Centrifuge machine. The details
of the set parameters and the centrifugation start and end time will be recorded in
‘Centrifugation and Separation of Biological Samples Record’.

21. After completion of the centrifugation, the Technician/designated person will remove
the vacutainer/centrifuge tubes carefully (without disturbing the contents) from the
centrifuge machine and will arrange it in vacutainer/centrifuge tube stand.
22. The Technician/designated person will arrange the pre labeled vials of respective
sampling hour sequentially in the rack/tray.
23. The Technician/designated person will harvest the plasma/serum from each
centrifuged vacutainer/centrifuge tube using micro pipette with disposal tips without
disturbing the sediment layer and will transfer the harvested plasma/serum to
respective subject’s pre labeled vials into two aliquots as ‘Replicate’ (1 mL) and
‘Analytical’ (remaining quantity) sample. Or as specified in the Study Protocol, and
will cap the vials.
24. The Technician/designated person will record the observation [like hemolysed samples
(H), missing sample (M), subject not reported (N)], or any other observation as remark
in the ‘Centrifugation and Separation of Biological Samples Record’.
25. The Technician/designated person will pack these vials with plasma/serum samples of
each sampling time point into labeled zip-lock bags (each for Analytical and Replicate
samples) of all the subjects, and store in the deep freezer maintained at suitable storage
temperature as specified in Study Protocol.
26. The Technician/designated person will record details of samples stored in the deep-
freezer.
B. Precaution to be taken for Photo sensitive and Temperature Sensitive Drug
Product.
1. For study of Photosensitive molecules, appropriate measures will be taken (like use of
sodium vapor lamp/covering the glass windows with dark paper) to avoid exposure to
light while performing all the procedures done in sample collection and processing
area.
2. The Technician/designated person will use pre labeled amber colored vials for storage
of Plasma/Serum samples of light sensitive drug product.
3. For temperature sensitive drug products, the following measures will be taken or will
follow the measures/procedures mentioned in the respective Study Protocol.
4. The blood sample will be collected into pre-chilled vacutainer /centrifugation tube.
This vacutainer/centrifugation tube with blood samples will be placed in ice water bath
till it is centrifuged. After centrifugation at the set parameters the plasma/serum will be
harvested using micropipettes with disposable tips into pre-labeled vials as
‘Analytical’ and ‘Replicate’ sample, these vials containing the harvested plasma/serum
will be placed into deep-freezer maintained at a temperature specified in the Study
Protocol.
5. The Phlebotomist/Nursing staff/designated person will record the sample time point
deviation in the ‘Deviation Reporting Form’. The responsible Physician/designated
person will also give the details of sample time point deviation, missing samples and
the delay in sample time for ambulatory samples to the Statistical Department for
considering in the statistical analysis.
C. Transfer of samples from the Clinical Facility to the Bio-analytical Facility.
1. Study Coordinator/designated person will take the authorization from Clinical
investigator/designated person for transfer of biological samples to the bio-analytical

facility and will get the name and address of the bio-analytical facility where the sample
has to be transferred.
2. Study Coordinator/designated person or the Contract Courier person (who will be
shipping the samples) will arrange insulated boxes with appropriate coolant before
initiation of the transfer activity.
3. Study Coordinator/designated person or the Contract Courier person will place the
temperature monitoring device to record the temperature during the transfer of
biological samples.
4. Study Coordinator/designated person will identify and remove the biological sample
boxes/polybags from the deep-freezer and will record the retrieval of samples in
respective format.
5. Study Coordinator/designated person will transfer these labeled samples
boxes/polybags as per the specified requirements, into the insulated box with sufficient
coolant to maintain the storage condition of the biological sample during transportation
and will seal the box (es).
6. Study Coordinator/designated person will record the details of samples to be transferred
in the format for ‘Transfer of Biological Samples from Clinical facility to Bio-analytical
Facility’.
7. Study Coordinator/designated person or the Contract Courier service person will paste
appropriate labels {e.g. warning label as “Biological Samples”, “Handle with Care”,
“Light Sensitive samples” (if any)} and will also paste label mentioning the complete
address of the bio-analytical facility where samples are to be transferred, on the box. If
Applicable.
8. Study Coordinator/designated person will handover the samples/insulated box(es), the
format for ‘Transfer of Biological Samples from Clinical facility to Bio-analytical
Facility’ and the covering letter with the details of the samples, to Contract Courier
service person or the person shipping the samples (in case the samples are hand
delivered).
9. The Contract Courier service person will sign the transfer format as ‘Received by’ and
will write the time of receipt. The Contract Courier person will also fill the details in the
shipment tracking form, and submit a copy of it to the Study Coordinator/designated
person.
10. In case the samples are hand delivered the person receiving the sample at bio-analytical
facility will verify details of the sample from the covering letter and/or from the transfer
format and sign as ‘Received by’ write the time of receipt on the format and will
acknowledge the receipt of the samples.
11. A copy of this transfer format will be maintained in the Study File at the Clinical site.
12. The person receiving the sample at bio-analytical facility/Contract Courier service
person will remove the temperature monitoring device and the print of the temperature
record during transportation will be maintained along with the Sample transfer format.
13. If it is genetic samples (Please submit the Material transfer agreement and Data
Transfer Agreement to the Institution/IEC.

Tittle: 007-SOP for Handling and reporting of AE and SAE
No Contents Page no
1. Objective 30
Scope
2. 30
3. Precautions 30
4. Definitions 30
5. Procedure 31
32
5.1 Handling of Adverse Events
33
5.2 Reporting of Adverse Events
System of Pre-Screening for submission of reports of

44
5.3 SAE to CDSCO
46
6. References
KLE-SITE MANAGEMENT OFFICE-SOP VERSION-3.0 Page 29

I. OBJECTIVE:
This SOP gives the procedure for handling and reporting the Adverse Events and Serious
Adverse Events encountered during the clinical studies at KLES Dr. Prabhakar Kore Hospital &
MRC, Belagavi
II. SCOPE:
Applicable to all Clinical studies.
III. PRECAUTION: Nil
IV. DEFINITION:
a. Definitions:
Serious Adverse Event: Any untoward medical occurrence that at any dose results in death, is
life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization,
results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Serious Adverse Event or Serious Adverse Drug Reaction: An AE or ADR that is associated
with death, inpatient hospitalization (in case the study was being conducted on out-patients),
prolongation of hospitalization (in case the study was being conducted on in-patients), persistent
or significant disability or incapacity, a congenital anomaly or birth defect, or is otherwise life
threatening.
 Adverse Event: An AE is any untoward medical occurrence in a patient or clinical
investigation of subject administered a pharmaceutical product and that does not
necessarily have a causal relationship with this treatment. An AE can therefore be any
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or
disease temporally associated with the use of a medicinal (investigational) product,
whether or not related to the medicinal (investigational) product.
 Unexpected Adverse Event: Any adverse event occurring in one or more subjects
such that, the nature, severity or frequency of which is not consistent with either:
a) The known or foreseeable risk of adverse event associated with the procedures involved in
the clinical study that are described in (a) the protocol-related documents, such as the IEC-
approved Study protocol, any applicable investigator brochure, and the current IEC-
approved informed consent document and (b) other relevant sources of information, such as
product labeling and package inserts; or
b) The expected natural progression of any underlying disease, disorder, or condition of the
subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile
for the adverse event (if applicable).
1) Relatedness/ Causality assessment of Adverse Event to an Investigational Drug:

Relatedness/ Causality assessment of Adverse Events will be as per the WHO-UMC
causality assessment system as mentioned.

WHO-UMC Causality Categories
Causality term Assessment criteria*

• Event or laboratory test abnormality, with plausible time
Certain relationship to drug intake
• Cannot be explained by disease or other drugs
• Response to withdrawal plausible (pharmacologically,
pathologically)
• Event definitive pharmacologically or phenomenologically (i.e. an
objective and specific medical disorder or a recognized
pharmacological phenomenon)
• Rechallenge satisfactory, if necessary
• Event or laboratory test abnormality, with reasonable time
Probable/ relationship to drug intake
Likely • Unlikely to be attributed to disease or other drugs
• Response to withdrawal clinically reasonable
• Rechallenge not required
• Event or laboratory test abnormality, with reasonable time

Possible relationship to drug intake
• Could also be explained by disease or other drugs
• Information on drug withdrawal may be lacking or unclear
• Event or laboratory test abnormality, with a time to drug intake that

Unlikely makes a relationship improbable (but not impossible)
• Disease or other drugs provide plausible explanations
• Event or laboratory test abnormality
Conditional/ • More data for proper assessment needed, or
Unclassified • Additional data under examination
• Report suggesting an adverse reaction
Un • Cannot be judged because information is insufficient or
assessable/ contradictory
Unclassifiab • Data cannot be supplemented or verified
le points should be reasonably complied with
*All
2) Severity: The degree of an adverse event is divided into mild, moderate, or severe.
 Mild: Minimal interference in day-to-day activities, Special treatment may not be required
to treat adverse event, Symptoms are transient.
 Moderate: Discomforting event, interference in day-to day activities, therapeutic measures
are required to treat adverse event.
 Severe: (As mentioned in the ‘Definitions’ section above) Severe discomfort, Day-to day
activities are impossible, major therapeutic intervention is required to treat adverse event.
V) PROCEDURE:
1.0 Handling of Adverse Event
a. The Clinical Investigator/Medical Officer will explain the expected adverse events
identified in the Study Protocol/product literature or package insert in the study meeting
held prior to the conduction of the Clinical study.
b. The designated person will monitor the subject(s) for any untoward or unfavorable and
unintended sign (including abnormal Clinical laboratory finding), symptom during the

Visits and study housing. The designated person will also consider any Adverse Event
occurring after discharge of the subject from the clinical facility (during washout period,
during the anticipated duration of action of the drug(s) or also thereafter at the discretion
of the Clinical Investigator).
c. On occurrence of an Adverse Event the designated person will examine the subject and
will give assurance or provide appropriate medical care to ensure well being of the subject
in accordance with currently acceptable clinical standards and guidelines.
d. The designated person will further ask the subject about the adverse event in detail to
ascertain the severity and/or circumstances contiguous to the adverse event, including any
medication taken (if any) after discharge from the study center, so that the event can be
judged clinically.
e. Whenever required, the designated person will also inquire about the progress of the
adverse events to the subject telephonically. The subject is also requested to report the
Adverse Event at any time to the designated person.
f. The designated person will review the post study clinical laboratory report (pathological
report) for any out of range values, these values will be compared with the baseline reports
values to determine its significance for evaluation of any Adverse event. If any clinically
significant observation(s) are found in the Clinical laboratory reports then it will recorded
in the Adverse Event Form of the CRF, attached as Annexure-01, and the designated
person will inform the subject about the evaluation and will request him/her to report to
the Study center for follow up.
g. The designated person will record the follow ups in the ‘Telephonic Communication and
Subject Follow-up Form’ of the CRF, attached as Annexure-02
h. The decision for any further diagnostic test(s) or specialist consultation is required for the
management of the adverse event, will be done on the discretion of the Clinical
Investigator/Co-Investigator.
i. The designated person will monitor the subject or follow up with the subject till the
resolution of the Adverse Event.
j. designated person will record the Adverse Event, time of occurrence, time/date of
resolution, the assessment of causality, severity, expectedness/unexpectedness and course
of treatment or action (if appropriate), in the ‘Adverse Event Form’ of the CRF of the
respective subject.
k. If in the judgment of the Clinical Investigator/Co-Investigator the continuation of the
subject proves harmful to him/her, then will take the decision to terminate the subject from
the study. The termination details will be recorded in the ‘Subject Drop-
Out/Withdrawal/Termination Form’ of the CRF of the respective subject. Handling of
Serious Adverse Event (SAE).
l. In case of occurrence of any Serious Adverse Event, Clinical Investigator/Co-
Investigator/Medical Officer will give preliminary treatment (if required) to the subject in
the Emergency Care Unit (ECU) of Hospital. As per the ‘Standard Operating Procedure
for ECU maintenance and handling Emergency Situation’ and then will shift the subject to
the emergency facility (if required).
m. The subject will be monitored till the resolution of the Serious Adverse Event or on the
discretion of the Clinical Investigator/Co-Investigator.
n. The Medical Officer will record the Serious Adverse Event, time of occurrence, time/date
of resolution, the assessment of causality, severity, expectedness/unexpectedness and
course of treatment or action (if appropriate), in the ‘Serious Adverse Event Form’ of the
CRF of the respective subject, The Medical Officer will keep all the relevant medical
record including the hospital record along with the CRF of the respective subject.

o. The Medical Officer will also record details in the ‘Logbook for Serious Adverse Event
details.
p. Clinical Investigator/Co-Investigator will review the details recorded in respective
subject’s CRF and in ‘Logbook for Serious Adverse Event Details’.
q. The termination of the subject from the study due to a Serious Adverse Event will be
documented in the ‘Subject Drop-Out/Withdrawal/Termination Form’ of the CRF of the
respective subject.
2.0 Reporting of Adverse event:
Reporting of the adverse event by the Investigator:
 Unanticipated problems involving risks to subjects should be reported promptly.
 Summary of the adverse events and any unanticipated problems involving risks to the
subjects should be reported at continuing review.
 Any information about risks associated with the clinical study, should be reported at
continuing review.
 A single occurrence of a serious, unexpected event that is uncommon and strongly
associated with drug exposure (e.g agranulocytosis, hepatic injury)
 A single occurrence, or more often a small number of occurrences, of a serious,
unexpected event that is not commonly associated with drug exposure, but uncommon in
the study population.
 Multiple occurrence of an AE that, based on an aggregate analysis, is determined to be an
unanticipated problem. There should be a determination that series of AEs represents a
signal that the AEs were not just isolated occurrence and involve risk to human subjects. A
summary and analyses supporting the determination should accompany the report.
 An AE that is described or addressed in the investigator’s brochure, protocol, or informed
consent documents, but occurs at a specificity or severity that is inconsistent with prior
observations.
 A Serious Adverse Event that is described or addressed in the investigator’s brochure,
protocol, or informed consent documents, but for which the rate of occurrence in the study
represents a clinically significant increase in the expected rate of occurrence.
 Any other AE or safety finding that would cause the sponsor to modify the investigator’s
brochure, study protocol, or informed consent documents or would prompt other action by
the IEC to ensure protection of human subjects.
 An AE observed during the conduct of a study should be considered an unanticipated
problem involving risk to human subjects, and reported to the IEC, only if it were
unexpected, serious, and would have implication for the conduct of the study (e.g.
requiring a significant, and usually safety-related, change in the protocol such as revising
inclusion/exclusion criteria or including a new monitoring requirement, informed consent,
or Investigator’s brochure). An individual AE occurrence ordinarily does not meet these
criteria because, as an isolated event, its implications for the study cannot be understood.
Many types of AEs generally require an evaluation of their relevance and significance to
the study, including an aggregate analysis of other occurrence of the same (or similar)
events, before they can be determined to be an unanticipated problem involving risk to
human subjects.
2.1 Reporting of the adverse event by the Investigator to Sponsor:
There is no severity or expectation threshold to trigger the investigator’s responsibility to
report to the sponsor adverse events related to the drug. The sponsor however is required to
report only serious, unexpected and related adverse event experiences to the Regulatory.

 Adverse events that could be reasonably regarded as caused by or probably caused by the
drug, to be reported promptly unless the event is alarming, in which case, to be reported
immediately;
 Serious adverse events, to be reported immediately unless the protocol or other document
indicates otherwise. It is essential to specify clearly in the protocol and the adverse event
reporting section of the protocol, what is and is not expected as well as what is and is not
regarded as serious.
 The time lines for notifying of SAE both death and other than death events by the
Investigator to Sponsor as per 122 DAC of New Drugs and Clinical Trial Rules.2019 is
within 24 hours of identifying the event
2.2. Reporting of the serious adverse event by the Sponsor to the Regulatory authorities:
Reporting requirements for the Sponsors to the Regulatory include time frames as follows:
 Adverse experiences that are associated with the use of the drug and that are both Serious
and Unexpected, Unexpected fatal or life-threatening experience associated with use of
the drug, to be reported within 24 hours of the occurrence;
 Any adverse experience with a licensed product that is serious and unexpected, whether
domestic or export, to be reported by the license holder within 24 hours of the occurrence,
by the licensed manufacturer.
 The time lines for reporting of SAE-death and other than death events by the Sponsor
(after due analysis) to the Licensing authority (DCGI) as per 122 DAC of New Drugs and
Clinical Trial Rules.2019 is within 10 days of occurrence of SAE and reporting of death
to chairman of the expert committee –at CDSCO office within 10 calendar days of
occurrence of SAE.
 As per 122 DAC of New Drugs and Clinical Trial Rules,2019 the Sponsor/representative
shall pay the compensation in case of clinical study related injury or death within 30 days
of receiving the order from licensing authority (DCGI). For SAE other than death, the
study subject will get the compensation and in case of death, the nominee of the subject
will get the compensation.
 In post marketing studies, sponsors must not only report under MedWatch (The FDA’s
safety information and adverse event reporting program, which provides information
about safety issues and provides an online gateway for reporting adverse events)
requirements but also be consistent with reporting obligations for IND research that
require reporting serious consequence or adverse effects of an already approved and
legally marketed drug.
2.3. PI Reporting of the serious adverse event to the IEC of KAHER
 It is the responsibility of The Principal Investigator should submit within 24 hours SAE
report or the unexpected adverse event report to the Sponsor, IEC, DCGI by hard copy/
by email.
 The report of SAE of due analysis shall be forwarded by the Investigator to IEC, DCGI,
sponsor and Head of the institution within 14 calendar days of occurrence SAE.
 The report should be accompanied by detailed narrative of the SAE and New Drugs and
Clinical Trial Rules.2019
 It should be submitted as per checklist detailed by Licensing Authority.
 IEC will perform Causality Assessment with reasoning for Relatedness/Un-relatedness
and will communicate to DCGI within 30 days of Occurrence of SAE (as per CDSC
Rules)
 PI also communicate the SAE initial report to the Medical director of the Institution

2.4. Reporting of the adverse event by the Sponsor to other Investigators:

Sponsors are required to report to other investigator in a multisite trial. The requirements are
similar to those for sponsors reporting to the Regulatory. The reporting obligations include
the following:
 Adverse events those are serious, unexpected, and associated with the drug, to be reported
promptly.
 Any new observations discovered by or reported to the sponsor about the drug (other than
the other safety information) as the investigation processed.
 The Ethic Committee shall forward its report of death and/or any other SAE after due
analysis on SAE with its opinion on the financial compensation (if any) to be paid by the
Sponsor to DCGI office, and the report of death to the Chairperson of expert committee –
at CDSCO office within 30 calendar days.
2.5. Reporting of the Serious Adverse Event (SAE) by the Investigator to DCGI/CDSCO:
a) All SAEs occurring in clinical studies should be reported as per the details provided in
New Drugs and Clinical Trial Rules.2019 within the applicable timeline to,
The Drugs Controller General (India)
Directorate General of Health Services Central Drugs Standard Control Organization
(CDSCO) FDA, Bhawan, Kotla Road, New Delhi – 110 002
b) Pharmaceutical company/the Sponsor/CRO (Investigator in investigator-initiated studies)
is responsible for reporting SAEs within the applicable timelines.
c) Every report (both initial as well as follow-up reports) should be submitted along with a
covering letter.
d) Covering letter should be prepared using the template as guide, and printed on the
company/CRO’s letter head, attached is the template of covering letter.
e) Instructions are provided in the template as highlighted text in “Italics”. Delete all
instructions from the final letter.
f) All the sections of the covering letter should be completed. When some information is not
available at the time of report e.g. causality assessment by medical monitor of
Sponsor/CRO, compensation provided for study related injury or death, the same has to be
provided as a follow-up report.
g) Covering letter of every report arising from the clinical trials (CT) has to capture, (at
stipulated box provided in the template) as per the format.
i. DCGI CT file number
ii. Complete address of Sponsor and CRO (if any) including phone & e-mail address
iii. Phase of clinical trial
iv. Category of clinical trial as per the codes mentioned below. Mark the appropriate Code
from this list provided in the covering letter using below details.
v. Protocol or Study No./Code/ID and the study title.
vi. Adverse event term/diagnosis (Whenever possible provide a ‘preferred’ term)
vii. A brief narrative of the event, not exceeding 10 lines. A detailed narrative may be
enclosed, if available.
Code SAEs occurring in clinical trial

CT-1-IND New Drug - Investigational New Drug (IND) study (where IND is filed in
India and is an NCE)
CT-2-Reg New Drug –Local Clinical Trial– For product approval in India
CT-3-GCT New Drug –Global CTs
CT-4rDNA Biological –Recombinant products (Global CTs, India IND and study for
product approval)

CT-5-Vac Biological –Vaccines (Global CTs, India IND and study for product
approval)
CT-6-Oth Biological – Others (e.g. stem cell studies)
CT-7-Dev Device study (Global CTs, India IND and study for product approval)
CT-8-Oth Others
viii. Unexpected SAEs have to be submitted to the office as per Schedule Y of Drugs and
Cosmetics Rules, 1945.
ix. Causality assessment by investigator and the medical monitor of Sponsor /CRO.
x. The assessment report should clearly mention whether the SAE occurred is related or not
related (Situations like unlikely, possibly, suspected, doubtful etc should not be used).
xi. Whether the outcome is fatal
xii. Details of compensations provided for injury or death. In case no compensation has been
paid, reason for the same should be submitted. It is pertinent to mention that in case of study
related injury or death, complete medical care as well as compensation for the injury or death
should be provided.
xiii. Mention whether it is “initial” or “follow-up” report. For follow-ups, clearly mention the
follow-up report number e.g. Follow-up #01, Follow-up #02, etc. In case of follow-up
reports, mention the date of submission of initial (first) report, as narrative.
xiv. Forms should be completed in legible English, illegible forms, incomplete with respect to
critical information and improperly scanned / fax copies would be rejected by DCGI office.
xv. Relevant supportive documents may be enclosed
NOTE: Submission of same SAE in different forms/ format, in different occasions has to be
avoided (e.g. submitting CIOMS forms and then later submitting the same event details as
per New Drugs and Clinical Trial Rules, 2019
3.0. System of pre-screening for submission of reports of SAEs to CDSCO

i. In order to streamline the submission of reports of SAEs a pre-screening of reports of SAE
submitted to CDSCO, this SAE includes death occurring during the clinical study to arrive at
the cause of death/injury to the subject, as the case may be and to determine the quantum of
compensation, if any to be paid by the Sponsor or his representative whosoever have obtained
permission from CDSCO in a time bound manner.
ii. As per this procedure, each SAE including death will be examined by the CDSCO and
decision regarding causality of death and quantum of compensation (if any) will be taken by
CDSCO in a time bound manner as per the procedure specified in the New Drugs and
Clinical Trial Rules, 2019
iii. As per this New Drugs and CT rules 2019, the investigator shall report all serious and
unexpected adverse events to CDSCO, the Sponsor or his representative whosoever had
obtained permission from the CDSCO for conduct of the clinical study and the Ethics
committee within 24 hours of their occurrence.
iv. In case of serious adverse event of death, the reports shall be examined by an Independent
expert committee constituted by DCG(I) to determine if the cause of death is due to following
reasons, which are considered as clinical study related death and gives recommendation to
CDSCO. In case of clinical study related death, the committee shall also recommend the
quantum of compensation to be paid by the sponsor or his representative, to CDSCO.
a) Adverse effect of Investigational product (s)
b) Violation of the approved protocol, scientific misconduct or negligence by the Sponsor
or his representative or the investigator;
c) Failure of investigational product to provide intend therapeutic effect;
d) Use of placebo in a placebo –controlled study

e) Adverse effects due to concomitant medication excluding standard care, necessitated

as part of approved protocol;
f) For injury to a child in-utero because of the participation of parent in clinical study.
g) Any clinical study procedures involved in the study.
v. CDSCO shall consider the recommendations of the expert committee and shall determine
the cause of the death and also the quantum of compensation in case of clinical studies
related death within three months of receiving the report of SAE of death.
vi. In cases of serious adverse event other than death, CDSCO shall determine the cause of
injury, if any, due to any of the reasons mentioned above as in the case of death, which is
considered as clinical study related injury.
Note: CDSCO has option to constitute as independent Expert Committee, wherever
considered necessary, to examine such serious adverse event. In case of clinical study
related injury, CDSCO shall also determine the quantum of compensation within three (3)
months of receiving of the SAE)
vii. In case of clinical study related injury or death, the Sponsor or his representative
concerned shall pay the compensation as per the order of CDSCO within thirty (30) days
of the receipt of such order.
viii. As per this procedure the preliminary scrutiny of the SAE reports will be done by CDSCO
Officer (s) based on laid down checklist attached as Annexure -06. During the preliminary
examination, the CDSCO Officer(s) will scrutinize the SAE report to ensure that it
contains all the required administrative as well as technical information in proper manner
as per the checklist. CDSCO will only accept the SAE reports for further examination, if it
is submitted in accordance with the format and the checklist.
ix. Once the report of SAE is accepted by the CDSCO, the information in the report will be
reviewed by CDSCO as per the specified procedures:
a) The Sponsor or his representative conducting clinical studies in India will have to
prepare the SAE reports for submission to CDSCO as per New Drugs and CT rules,
2019
b) The SAE reports must be submitted with proper binding, indexing and page number.
a) The reports of SAEs of death should be prepared and submitted in red cover.
b) The reports of SAE of injury other than death should be prepared and submitted in blue
cover.
c) The SAE report other than that mentioned at (i) & (ii) above is to be prepared and
submitted in white cover.
c) Clear and unequivocal information should be provided in the SAE report.
d) Text and tables should be prepared using margins that allow the document to be printed
clearly without losing any information and the left-hand margin should be sufficiently
large so that information is not obscured by the methods of binding. The documents
printed on both sides of a page, can be submitted. However care should be taken that the
information is not obscured when the page is placed in a binder.
e) While submitting reply to a query, the applicant should always enclose with the reply, a
copy of query letter issued by CDSCO.

VI) RFERENCES:
1. Standards and Operational Guidance for Ethics Review of Health-Related Research with
Human Participants-2011
2. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human
Subjects 2013
3. National Ethical guidelines for Biomedical and health research involving research
participants Guidelines-ICMR-2017
4. New Drugs and Clinical Trial Rules, 2019

Title: 008- Instruction for filling of screening form and CRF
Sl.No Contents Page no
1. Objectives 40
2. Scope 40
3. Procedures 40
Screening form & CRF Filling guidelines

4. 41
KLE Site Management Office-SOP Version-3.0 Page 39

I. OBJECTIVE: This SOP gives the procedure for recording of the Screening & Case
Report Form in the all the clinical studies
II. SCOPE: This SOP is applicable to all the clinical studies at site
III. PROCEDURE:
1.0 The approved Screening Form and Case Report Form will be used for recording the
clinical studies
2.0 Investigator/ designated person will fill the Screening Form/CRF as per the details
mentioned in the IEC approved Study Protocol and Screening Form /CRF.
3.0 General Instruction for Filling the Screening Form/CRF
1. Filling of the Screening/CRF will be done by black ballpoint pen.
2. The date should be written in the format of DD/MM/YY, e.g. for 27th Feb 2017 - 27/02/17.
3. The time should be written in the format of 24 hours by HH:MM, e.g. for 3 hours 15
minutes P.M. – 15:15.
4. Hand-write all data on all pages of the CRFs. Do not type data onto the forms.
5. Do not use any type of correction fluid (white-out), pencil, or erasable pen on the CRFs.
6. Open boxes are for entry of numerical or alphabetical (in block letters) data. The boxes
should be completely filled-up.
7. Closed boxes are for tick mark (inside the box) purpose only. Many items have a box or
series of boxes for recording a response. Mark the box clearly with an only. Do not shade
in the box or mark it with a slash or other character.
8. If data is written on the form incorrectly and the error is noticed, draw a single line
through the incorrect entry, place the correct answer near the box, and sign and date the
correction. If errors are identified again, find the appropriate space and do the same
correction method.
9. Blank items on data forms are considered missing data and will therefore result in a query
unless they are blank due to skip pattern requirements. To avoid a query on items where
the answer to an item is unknown or is not available, or where the participant refuses to
answer an item.
 In case of unknown, write “UNK”, then initial and date the item.
 In case of answer not available, write “N/A”, then initial and date the item.
 DO NOT enter a line through items that are blank due to skip patterns.
10. The assigned staff must review each completed form for completeness and legibility. This
could include the clinician or coordinator completing the forms and the Data Management
Coordinator (DMC). The following list can be used as a review checklist.
 Review all completed CRFs before being sent to Sponsor/CRO.
 Make sure all items are answered, unless skipped according to the instructions on the
form. If a question cannot be answered, write “UNK” for unknown or “N/A” for Not
Available, then initial and date the item.
 Make sure only one response box per item is marked, unless instructed otherwise.
 Make sure all written entries are clear enough to be legible for data entry.
 Check for common errors. The largest percentages of avoidable queries are associated with:
 missing dates
 Transposed or incorrectly transcribed patient screening or enrolment IDs.

 Invalid site numbers
 missed skipped pattern
VI. Screening form & CRF Filling guidelines

Header (Applicable to all the Pages)
1. Screening ID/Enrollment ID will be as first two boxes will be Centre No. (Allotted by
the CRO) and the rest three box will be the Sequence no.
2. Record Date of visit in DD/MM/YY Format.
3. Record date Patient Initials i.e. first letter of First, Middle & Last name
Footer
1. Sign and Date in ‘Done by’ box.
2. Sign and Date in ‘checked by’ box after checking the entire page for correctness and
completeness.
Informed Consent form:
1. Record date when subject/ LAR/witness signs the Informed Consent.
Demography:
1. Record Date of birth in DD/MM/YYYY format. Year should be provided at minimum.
2. Check gender as either ‘Male’ or ‘Female’
3. Age will be recorded as completed years.
4. Record the Body Weight in kilograms in the box provided.
5. Record height in meters.
6. Calculate and record BMI.
7. Tick the smoking and tobacco Chewing Habit of the subject as Mild, Moderate & Severe.
8. Tick alcohol consumption details.
9. Orally take the history of any drug abuse and tick the appropriate box.
10. Considering DSM-IV tick the appropriate ‘YES’ or ‘NO’ box for presence of significant
alcoholism and Drug dependency.
11. Put Remarks if any in given space.
Diagnosis and Type of Epilepsy
1. Tick the appropriate box for Mode of diagnosis of epilepsy and add if any comments are
there.
2. Tick the appropriate box depending upon Type of Partial (Focal/localized) Epilepsy and
3. Add if any comments are there.
4. Tick the YES and NO box depending upon Diagnosis of Refractory Partial Epilepsy.
Medical History:
1. Check ‘YES’ or ‘NO’ depending upon the presence of any relevant Medical/ Surgical
History.
2. If YES, please record appropriate body system number from corresponding code
provided on the CRF page. E.g. record 07 for Neurological system and give the details of
state if the condition is currently/potentially active. Use a separate line for each
condition.
3. Record clinical condition in the condition column. Preferably provide diagnosis rather
than symptom.
4. Record Start and End dates of the recorded condition.\

Previous and concomitant medications
1. Record all the details of the Prior and concomitant Medications on the Previous and
concomitant medications page.
2. If Yes, Record Medication Name (Generic/Brand name)
3. Record ‘Start’ and ‘End’ dates for the medication. Check ongoing, if the medication is
still being consumed and leave End date blank.
4. Record the value of Dose and Unit of the medication in the space provided. E.g. for unit,
record the unit as mg, ml, etc. Record ‘NA’ for Dose & Unit where data is not available
or not applicable.
5. Record Route of drug administration and frequency of drug.
Physical examination
In Physical Check table, check all the given system and tick the appropriate
corresponding box and if any abnormality is found, specify the same in given adjacent
space.
Systemic examination
During systemic examination, check all the given system in the table during subject
examination and tick the appropriate box, and if any abnormality is found then specify the
same in given adjacent space.
Vital sign measurements and wellbeing
Vital Signs to be performed at Screening & other scheduled visits.
1. Record the Pulse Rate value in bpm (beats per minute) in the box provided.
2. Record the Systolic and Diastolic Blood Pressure value in the box provided.
3. Record Respiratory rate value in /min in the box provided.
4. Record axillary Temperature in oF in the box provided
Sample collection
1. In this section record the date and quantity of blood sample collected for Pathological
examination during screening.
2. Designated Person who has done the above activity will sign and date in ‘Collected by’
box.
Hematology, Urine Analysis, Biochemistry, Serology and Serum Pregnancy Test
After receiving the Pathological report
1. Record results of the analysis in the values column.
2. Check ‘Normal’ or ‘Clinically Significant’ or ‘Clinically Non significant’ values in the
check box depending upon the value, if the value is out of acceptable range or not.
3. Specify any relevant information in the comment section, if necessary.
4. Check ‘reactive’ or ‘non reactive’ box depending upon the result of serological
examination and specify any relevant information in the comment section, if necessary.
5. Check ‘Positive’ or ‘negative’ box depending upon the result of serum pregnancy test. If
result is Positive, exclude the subject from study.
12-Lead ECG and Chest X-Ray
1. Fill the date of ECG and X-RAY done in space provided for date in DD/MM/YY format.
2. Check ‘Normal’ or ‘Abnormal’ box depending upon the report.
3. If abnormality is found the put the comments in the space provided.

Any Additional Laboratory Test / Procedure
1. In this section If Investigator feels any additional investigation is needed other than
protocol specific then record the name of test/procedure.
2. Add Values or observations in the space and write if any comments.
Inclusion Criteria:
1. Check ‘Yes’, ‘No’ or ‘N/A’ boxes as appropriate for every criterion.
Note: For Subject to be eligible for the study, all respective criteria for inclusion should be
either ‘Yes’ and/or ‘N/A’.
Exclusion Criteria:
1. Check ‘Yes’, ‘No’ or ‘N/A’ boxes as appropriate for every criterion.
Note: For Subject to be eligible for the study, all respective criteria for exclusion should
be either ‘No’ and/or ‘N/A’.
End Of Visit Checklist:
1. Tick ‘Yes’ Or ‘No’ depending upon completion of the screening procedure and if any
procedure is not done mention the same and reason in space for comment.
2. Tick ‘Yes’ Or ‘No’ as per the eligibility of the subject for the Inclusion /Exclusion
criteria status. If any answer is ‘NO’ then specify the reason in the comment box.
Onset of Clinical Up-Titration/Down titer and Issuance Record
1. Mention the dosage of Felbamate in the mg
2. Put the total number of Felbamate tablet(s) dispensed to the subject.
3. Tick one box of qd or bd or od depending upon the frequency prescribed to consume
felbamate tablet to the subject.
4. Tick the name of prescribed medication concomitantly used by the subject.
5. Mention Dosage frequency and route of the concomitant medication prescribed along
with Felbamate to the subject.
6. Tick ‘YES’ or ‘NO’ depending upon the dosing instruction is explained or not explained
to the subject.
7. Tick ‘YES’ or ‘NO’ depending whether the patient Dairy card has been issued or not
issued to the subject.
8. Tick ‘YES’ or ‘NO’ depending upon the Patient dairy card filling instruction is explained
or not explained to the subject.
9. Put the date on which the patient is asked to visit the centre and then tick YES if you have
conveyed the next visit date to subject.
Follow-up for laboratory investigations, Safety & Concomitant medications

1. Tick YES or NO depending upon if investigator doubts about any laboratory values and if
he wants to repeat that particular investigation and if response of investigator is YES then
he has to fill the form
2. Tick YES or NO depending upon if subject has consumed any medication other than apart
from Felbamate and Levetiracetam, Valproic acid, Gabapentin or Pregabalin and response
is YES then filling the form
3. Tick YES or NO after inquiring the subject about whether he/she suffered any adverse
event.
4. Tick YES or No depending on whether the subject has suffered any Serious Adverse
Event.

Checking for Dosing Compliance

1. Fill the details for quantity of Felbamate tablet and concomitant medication issued, any
dose missed and quantity returned. And tick YES or NO depending upon the dosing
compliance.
2. Tick YES or NO depending upon the Investigator’s discretion whether the patient can
continue the study or not.
Randomization
1. Put the date of Informed consent Taken
2. Fill Screening ID
3. Put the Date of Randomization
4. Fill the Enrollment ID which will consist of centre code and Randomization ID.
5. Tick either Test or Reference arm depending upon the randomization obtain
telephonically from the CRO during period I and tick reverse arm for Period II.
6. Put Sign and Date who has conducted this activity.
7. Put Sign & Date who has checked this activity.
Clinical stabilization and issuance record
1. Tick Test or Reference box as per randomization.
2. Mention the Quantity of Felbamate Issued and then Tick ‘YES’ or ‘NO’ depending upon
the Patient stabilized on dose (mg) & frequency.
3. Fill the details like Quantity issued frequency of dose dosage and route of concomitant
medication
Check In & Out Procedure
1. Tick ‘YES’ or ‘NO’ depending upon patient satisfies inclusion and exclusion criteria.
2. Tick ‘YES’ or ‘NO’ depending upon patient fit for check-in.
3. Tick ‘YES’ or ‘NO’ after issuance of ID to subject.
4. Tick ‘YES’ or ‘NO’ after checking body and belongings of the subject.
5. Tick ‘YES’ or ‘NO’ depending upon issuance of personal kit to subject.
6. Record subject’s Check-in time in 24 Hours format.
In House Dosing
1. Fill Pre determined Schedule Time by in 24 Hrs Format
2. Tick ‘YES’ or ‘NO’ after properly checking ID no of the subject.
3. Tick either ‘YES’ Or ‘NO’ depending upon the instruction is conveyed to the subject or
not.
4. Tick Test or Reference depending upon the subject’s randomization arm
5. Tick either YES or NO after ensuring that subject has drank 240 ml of water for dosing.
6. Tick YES or NO depending upon checking the mouth of subject.
7. Record the time of actual dosing in 24 Hr format.
8. Put Remark about if any deviation occurs or any spillage is there etc.
Meal Record
1. Record predetermined Schedule time for meal in 24 Hr Format.
2. Record the time as Start time when subject Start Eating the meal in 24 Hr Format.
3. Record the time as ‘END’ time when subject finishes the meal in 24 Hr Format.
4. Put comment for any unscheduled event happens.

Pre-Dose Blood Sample

1. Record the time of 5ml Blood sample collection which will be prior to morning dosing.
2. Designated Person who collected the blood sample will Put Sign and date in done by
column
Pharmacokinetic Blood Sampling
1. Below will be applicable for All PK sampling point
2. Record predetermined Schedule time for blood collection in 24 Hr format.
3. Record Actual time for blood collection in 24 Hr format.
4. Designated Person who collected the blood sample will Put Sign and date in collected by
column
Removal or Replacement of Cannula
1. Record The time of recannullation if cannulla is removed or change and specify the
reason in comment space and
2. Designated Person who has carried out the activity will Put Sign and date in done by
column
Pre-dose Compliance
1. Tick Yes or NO depending upon the whether patient has maintained fasting for 8 hours
prior to dosing
2. Tick Yes or NO depending upon restriction for not allowing to drink water
Post dose Compliance
1. Tick Yes or NO depending upon Drinking water not permitted 1.00 hr post-dose
2. Tick Yes or NO depending upon Posture restricted for 2.00 hrs post-dose.
3. Tick Yes or NO depending upon Maintenance of fasting for 4.00 hrs post-dose
Is Patient to Needs to be Further Down-Titrated for Felbamate Dose Study?
1. If Patient needs further down titration then Investigator has to fill Annexure F form
2. If Response is NO fill the study completion status.
Study Completion Status

1. Tick YES or NO depending upon whether the patient completed the study.
2. And if response is NO complete the questionnaire of Part A by ticking the reason for
withdrawal & then complete the part B by mentioning the date of when subject was out of
the study.
Investigator’s Declaration
1. Investigator will Sign and Date in checked by box after checking the entire Screening
form and CRF for its correctness and completeness.

Title: 009- SOP for Investigational Medicinal Product Management
Sl.No. Contents Page Nos
1. Goals of Investigational Product (IP) Management 46
2. Communications 46
3. Roles and Responsibilities 46
4. Pharmacy 47
5. Source of IP 50
6. Participants consultation and counselling 50
7. IP Shipment and Receipt 51
8. IP Storage 51
9. IP Repackaging and Relabelling (if applicable) 52
10. IP Dispensing and Accountability 52
11. IP Return and Destruction 53
12. References 53
KLE SITE MANAGEMENT OFFICE- SOP VERSION-3.0 , 45

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Introduction: the KLE Research Pharma [Clinical Trial IMPs] is constituted by KLE
College of Pharmacy/Registrar respectively under Drugs and Cosmetic Act, 1940 at KLE
Research Pharma, , 02nd Floor, site management office, KLES Dr.PK Hospital and MRC.
1. GOALS OF INVESTIGATIONAL PRODUCT (IP) MANAGEMENT
1.1. The goals of IP management for this clinical trial include the following:
a) To ensure protection of the subject and traceability;
b) To enable identification of the product and the trial;
c) To facilitate proper use and storage of the product;
d) To ensure the reliability and robustness of data generated in the trial.
e) To ensure to maintain the Temperature of IMPs
2. Communications:
a) Periodic GCP/Protocol Training will be conducted for the site Research pharmacists
by the Sponsors/CROs/Site
b) The purposes of these GCP/Protocol training are to keep abreast of new information
and protocol changes, to follow up on action items, to problem solve, to coordinate
and collaborate on activities, to build relationships, and to review the results of
pharmacy audits.
c) Pharmacists also communicate via email, fax and telephone as needed.
d) Electronically transmitted documents will be password protected.
e) Pharmacists will conduct cross-site visits as appropriate.
3. ROLES AND RESPONSIBILITIES:
 ROLES AND RESPONSIBILITIES OF SITE
3.a.1. The following Pharmacist will be responsible for IP management:
a) IP Shipment and receipt
b) IP Storage
c) IP Repackaging and Relabelling
d) IP Dispensing and Accountability
e) IP Return and Destruction
3.a.2. The roles and responsibilities of the Pharmacist / study staff involved in IP
management for this clinical trial will be documented in a Signed Signature Sheet.
Study staff/Pharmacist will be trained on IP management procedures.
3.a.2.1. Training will be documented and maintained in the Investigator Site Files.
 ROLES AND RESPONSIBILITIES OF SPONSOR
a) This clinical trial will be monitored by the Sponsor monitor.
(For sites involved in IP repackaging and relabelling, describe that there will be two
separate monitors:

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a) The blinded monitor will be responsible for monitoring all aspects of the clinical
trial except IP management. [to be intimated to site pharmacist prior to one week
of the Monitoring]
b) The unblinded monitor will be responsible for monitoring the IP management of
this clinical trial). [to be intimated to site pharmacist prior to one week of the
Monitoring]
4. Pharmacy Procedures:
a) Pharmacy procedures specific to the protocol
 Forms and Labels: Pre-printed medication labels and forms to be used in the study.
 Pharmacist’s Prescription List Provided by the Study Investigators on the Study
Identification Number.
 Additional treatment assignment lists are added as they are Received from
Sponsors/CRO/PI
b) Drug Supply Statement
a. New drug supply statements are added as they are received from
Sponsors/CROs/WHO
c) Prescriber Information
a. Copy of the signed FDA form 1572 or Investigator of Record Agreement and a
Prescribers List and Signature Log (names and signatures of providers authorized
to prescribe)
d) Shipments
a. Completed order forms and packing slips for each shipment stapled together and
filed after the drug shipment has been received, verified and entered on drug
accountability/logs records.
e) Return Records
a. Records of all medications returned to Sponsors/CROs/WHO
f) Correspondence
a. Letters and memos to and from Sponsors/CROs/PIs and other study-specific
correspondence
g) IMP/Devices Request Procedure: Flow Chart
IMP/Devices Request Procedure: Flow Chart
Received from the courier personnel from the sponsors By Blinded/Unblended/site

personnel
Checking the Present temperature of the IMPs (If applicable)
Temp. Registration (Any excursion/deviations)

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If No Proceed to next step/if yes Notify to sponsors
Store as per the requirements of sponsors and site SOP [Location and label]
Stored by the bin card system [Bin Card implies a document which records the quantity
of material received by, issued to and remained in stores]
Request for IMP/Indent or Prescription by the study designee/Principal Investigator

through annexure [ Prescription Form]
Dispensing by the registered research pharmacist
Received by the CRC/Study Designee
Return of used trips/vials/bottles Return of unused IMPs/devices
Sponsors will be intimated about the same if they have facility to destruct the study
Drugs Used/Unused
Destruction of used/unused IMPs at site level
Letter would be written to head of the institution/Clinical services administrators by the

Principal Investigator for permission to destruct- (it will take 15-20 days to complete the
Process) if sponsors have provision can send the Used and Unused IMPs/Kits.
 Request letter contains – No of IPs, quantity, batch no and date of Expiry
Destruction certificate from the Hospital administrators will be generated a copy of

certificate to be maintained

Page
Annexure: 01- Prescription Form
-----------------------------------------------------------------------------------------------------------
-------
PRCICRIPTION FORM-Only for clinical trial purpose
Clinical trial Prescription- Dispensary KLES Dr.Prabhakar Kore Hospital and

MRC, Belagavi
KLE Research Pharma, CTS No: 5434, 2nd SOP version 3.0 Page no 01 of 01
Floor, SMO office, Room No: 04
Protocol No:
Hospital/Site Code:
CTRI No:
Subject Initial Prescriber/PI name
IWRS/IVRS number Contact No
Visit No CRC Name
Visit Date Randomization no
Rx..
Date/Time Quantity Drug Route Dose Checked by Received

by
Study designee/PI signature and date
Chief Pharmacist sign Pharmacist sig

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5. SOURCE OF IP
5.1. Table 1 summarizes the name(s), manufacturer(s), source(s) and recommended storage
temperature(s) of the IP(s) used in this clinical trial.
Research Office Use: {individual study}
IMPs Dispense tracker
Protocol No:
PI Name:
Blinded/Unblinded study:
Sponsored by:
Manufactured by:
Sl.No No. of IMPs Recommended No of Dispensed/Date Balance

Requested/date storage IMPs
condition received
1.
2.
3.
4.
6. Participant Consultation and Counselling: if Applicable

At the KLE site, the pharmacist is responsible for ensuring that all participants are adequately
counselled when they receive their first supply of study medication with information on
proper use and storage of each medication and possible side effects and adherence. The
pharmacist provides written materials that explain proper use and storage of each medication,
the possible side effects and contact information for the study team at the site. This
counselling can be done by the pharmacist or by someone delegated by the pharmacist and
will be documented. At the KLE Hospital, the study nurse is responsible for medication and
compliance counselling at the entry visit. After the initial counselling, the pharmacists will
continue to serve as a resource at the KLEs D.PK Hospital and MRC will be available to the
participant and the study nurse to provide further counselling and consultation as needed. The
pharmacists at the site dispense medications to the patient and provide counselling at each
study visit. The pharmacist will notify the study nurses/CRC if there is a problem with
adherence based on estimated measurements/accurate counts of returned medication

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7. IP SHIPMENT AND RECEIPT:

7.1. The Blinded CRC / Unblinded CRC / Study Pharmacist should file <receipts of purchase
/ IP Shipping Documentation> and the GMP certificate / Certificate of Analysis (COA) /
Product Insert of the IP in the Pharmacy Binder. If possible SMPC.
7.1.1. The Blinded CRC / Unblinded CRC / Study Pharmacist should ensure that the contents
of the <receipts of purchase / IP Shipping Documentation are in compliance with Section
4.6.3 of ICH E6 Guideline for Good Clinical Practice.
7.2. The Blinded CRC / Unblinded CRC / Study Pharmacist should verify the inventory of the
IP and update the IP Inventory Log(s). The IP Inventory Log(s) will be filed in the
Pharmacy Binder.
7.2.1. The Blinded CRC / Unblinded CRC / Study Pharmacist should ensure that the contents
of IP Inventory Log(s) are in compliance with Section 4.6.3 of ICH E6 Guideline for
Good Clinical Practice.
8. IP STORAGE:
8.1. The Blinded CRC / Unblinded CRC / Study Pharmacist should monitor the storage
temperature of the IP on daily twice.
8.1.1. IP Storage Temperature Logs will be maintained in the Pharmacy Binder.
8.2. In the event of excursions from the recommended storage temperature of the IP as
referenced in Table 1, the Blinded CRC / Unblinded CRC / Study Pharmacist should
complete the IP Storage Temperature Excursion Report and notify the Principal
Investigator and/or Sponsor for appropriate action to be taken.
8.3. The IP affected by the temperature excursion should be quarantined until a decision has
been made by the Principal Investigator and/or Sponsor to use or destroy the IP.
8.4. All relevant documentation and correspondences pertaining to temperature excursions
should be filed in the Pharmacy Binder.
8.5. Power Loss: Refrigerators and Freezers at KLEs Dr.PK Hospital and MRC connected to
an emergency generator backup power system. At the KLE Hospital the system is
activated automatically if the main power is interrupted. The generators are being set up
to come on automatically within 22 seconds
8.6. Temperature Monitoring: At KLE Hospital refrigerator and freezer temperatures are
checked daily when the pharmacy is open and recorded on a manual/electronic
temperature log. In addition the room, refrigerator and freezer temperatures are
monitored by a constant temperature monitoring, data logging, and alarm system. If the
temperature varies outside the defined range, an alarm will go off in the hospital room.
This room is manned 24 hours a day, seven days a week. Checked two times daily when
the pharmacy is open and recorded on temperature logs. A 24-hour recording device that
records the temperature on a paper chart monitors each KLE site Management office
[KLE-Research Pharma]
8.7. If the temperature varies out of range an audible alarm will sound and the system will
automatically and immediately call to the site research pharmacist/study designee. If an

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alarm is activated, pharmacy personnel will take action to either correct the malfunction
or move product to an area of appropriate temperature.
9. IP REPACKAGING AND RELABELLING (if applicable)
9.1. IP repacking and relabelling of IMPs, the Study Team Should Be Notified to Site
Ethics Committee.
9.2. The unblinded study team should perform IP repackaging and relabelling in accordance
with the protocol and Good Manufacturing Practice (GMP) guidelines.
9.3. The unblinded study team should apply the following GMP principles during IP
repackaging and relabelling:
9.3.1. IP repackaging and relabelling should be performed by delegated and trained
unblended study staff.
9.3.2. IP repackaging and relabelling should be witnessed by an unblinded study staff.
9.3.3. Line clearance should be observed during IP repackaging and relabelling whereby
one IP will be repackaged and relabelled at a time.
9.3.4. Label reconciliation should be performed and documented on the IP Repackaging

and Relabelling Form.
9.3.5. The IP Repackaging and Relabelling will be documented on the IP Repackaging
and Relabelling Form.
9.3.6. The IP Inventory Logs for the IP(s) will be updated accordingly.
9.4. The unblinded study team will perform IP repackaging and relabelling <prior to study
initiation / at each subject visit/ etc.>.
9.5. The unblinded study team will assign a dummy batch number and dummy expiry date for
the repackaged and relabelled IP and document it on the relevant IP Repackaging and
Relabelling Form.
9.5.1. For example, the dummy batch number will be set as ‘YYYYMMDD’ in accordance
with the date of IP repackaging, and the dummy expiry date will be set as the earlier
expiry date of the IP.
9.6. The unblinded study team should ensure that all documentation pertaining to IP
shipment, receipt, inventory, storage, repackaging and relabelling, transfer, return and
destruction should be filed in the Pharmacy Binder with access secure and limited to the
unblinded study team.
10. IP DISPENSING AND ACCOUNTABILITY
a. The Blinded CRC / Unblinded CRC / Study Pharmacist should dispense the IP to the
subject with prescription from the PI/study designee.
b. The Blinded CRC / Unblinded CRC / Study Pharmacist should advise the subject on the
proper use of the IP in accordance with the protocol.
c. The Blinded CRC / Unblinded CRC / Study Pharmacist should advise the subject to return
all used and unused to the site at the next study visit for determination of compliance.
d. The Blinded CRC / Unblinded CRC / Study Pharmacist should train the subject how to fill
subject dairy on daily basis.
e. The <Blinded CRC / Unblinded CRC / Study Pharmacist should update the IP Dispensing
and Accountability Logs and file it in the Investigator Site File / Subject CRF.

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f. The Blinded CRC / Unblinded CRC / Study Pharmacist should ensure that the contents of
the IP Dispensing and Accountability Logs are in compliance with Section 4.6.3 of ICH
E6 Guideline for Good Clinical Practice.
11. IP RETURN AND DESTRUCTION
a) The Blinded CRC / Unblinded CRC / Study Pharmacist should collect the used and
unused IP from the subject at the next study visit.
b) The Blinded CRC / Unblinded CRC / Study Pharmacist should document the returns in
the IP Dispensing and Accountability Logs.
c) The Blinded CRC / Unblinded CRC / Study Pharmacist should return the used and unused
IP to the Sponsor for destruction / send the used and unused IP for destruction in
accordance with institution policy.
d) The Blinded CRC / Unblinded CRC / Study Pharmacist should send the used and unused
IP for destruction once a final IP Accountability has been performed by the monitor; all
discrepancies have been investigated, satisfactorily explained and reconciliation
accepted; and written approval has been sought from the Sponsor / Principal Investigator.
e) The Blinded CRC / Unblinded CRC / Study Pharmacist> should ensure that IP Return and
/ or Destruction is documented on the IP Return and Destruction Forms. The IP Return
and Destruction Forms will be filed in the Pharmacy Binder.
f) The Blinded CRC / Unblinded CRC / Study Pharmacist should ensure that the contents of
the IP Return and Destruction Forms are in compliance with Section 4.6.3 of ICH E6
Guideline for Good Clinical Practice.
Note: If the sponsor/CRO request for on-site destruction of the IP, the delegated member
should:
 Obtain a copy of the site’s SOP of Waste Management from Clinical services
administrators for IP destruction/disposition, provide a copy to the monitor, and file a
copy in the TMF.
 Obtain written confirmation from the CRA/Monitor identifying the specific IP that can
be destroyed.
 Obtain appropriate paperwork concerning destruction of the drug that is required in the
site’s Waste Management SOPs and place a copy in the TMF.
 Provide the CRA/Monitor with written proof of IP destruction at site.
 Complete the Drug Return/Destruction Form or similar form provided by the
sponsor/CRO.
 Provide a signed copy of the form to the CRA/Monitor and retain the original in the
TMF.
12. REFERENCES
12.1. Health Products (Clinical Trials) Regulations
12.2. Medicines (Clinical Trials) Regulations
12.3. ICH E6 Guideline for Good Clinical Practice
14.4. New Drugs and Clinical Trial Rules, 2019

Page
Title: 010- for screening and enrollment of subjects
Sl. No Page No
Contents
OBJECTIVE
1. 55
2. Scope 55
3. Procedure 55
AF-I/SMO/SOP-010/V3.0
4. 58
AF-II/SMO/SOP-010/V3.0
5. 62
KLE-Site Management Office-SOP Versio-3.0 Page 54

I) OBJECTIVE: This SOP gives the procedure for screening and enrollment of subject in the all
clinical trials at KLES Dr.PK Hospital and MRC, Belagavi
II) SCOPE : This SOP is applicable for all clinical studies conducted in the facility.
III) PROCEDURE :
1) It is important that the principal investigator resolves all questions from his/her staff concerning
the interpretation of Exclusion/Inclusion criteria.
2) The investigator should be able to dedicate time to the recruitment of each subject is likely to
be longer than the time required for normal consultation.
3) The Clinical Investigator/Co-investigator will inform the subject (s) by word of mouth about
the recruitment of subject s for the study.
4) The Clinical Investigator/Co-investigator will schedule the screening dates and will inform the
subject (s).
5) The Study Coordinator/designated person will issue the IEC of KAHER approved ‘Inform
Consent Form’ to the subject s who have come for the screening procedure.
6) The Designated person will give the information of the screening and the study related activity
to the subjects.
7) Clinical Investigator/Co-investigator/Medical Officer will request the interested subjects and
the subject’s Legally Acceptable Representative’s (LAR) to sign the IEC of KAHER approved
‘Informed Consent Form” in the language best understood by them.
8) If the subject / Legally Acceptable Representative’s (LAR) is unable to read, then an impartial
witness present during the presentation of the screening and study related activities will explain
the contents of the Informed Consent Form in the best language understood by the subject.
After the subject consent for participation in the study the subject and /or the LAR will sign
/put thumb impression on the consent form and then the witness will sign and date the
‘Informed Consent Form’ as per ‘Standard Operating Procedure for Obtaining Informed
Consent from Subject’.
9) In case the subject requires more than the allotted time to inquire about the details of the study
/drug product/or to consult his family Physician to decide about the participation in the Clinical
trials, then the Investigator shall permit him/her to leave the study center and will ask him to
return if he/she is willing to participate in the particular study.
10) The subject who is found eligible for participation in the study will be given a unique
Screening identification number for identification of subject.
11) The responsible Person will measure the height, weight, and calculate the BMI of subject as per
the BMI chart (Refer APPENDIX 1). The details of the demographic data will be recorded in
the Screening Form of the CRF designed for the study.
12) Investigator/designated person will take the medical history, will conduct the physical
examination (General and Systemic examination) and the vital measurement and record the
details in the ‘Screening Form’ of the CRF.

13) Technician/designated person will take the 12 lead ECG of the subjects. The
Technician/designated person will sign and date the ECG print and will attach the same to the
respective subject’s ‘Screening form’ of the CRF.
14) Investigator/designated person will review the ECG of respective subject and will put the
appropriate comment on the same after interpretation.
15) During the entire process of screening if the subject is found to be ineligible at any point of
time, then the subject will not be considered for further screening procedure and will be
excluded at that stage.
16) If the ECG of the subject is within normal limits then he/she will be sent for collection of blood
and urine samples for Clinical Laboratory Investigations.
17) The Laboratory Technician (pathology)/Phlebotomist/Nursing staff will request the subject to
collect the urine sample and will collect the blood sample after verifying the screening
identification number of the subject from the ‘Screening form’, and on the labeled
container/vial/vacationers used for collection of the respective sample and will make
appropriate entry of the collection in the ‘Test Requisition form’ and the ‘Screening form’. The
biological samples will be then transferred to the Clinical Pathological Laboratory.
18) In case the Clinical Laboratory Investigation has to be done in an outsourced facility then the
Study Coordinator/designated person will give the details of subject ’s identification (screening
identification number, initial, gender and age) and other required test information(s) to the
respective Clinical laboratory person in the ‘Test requisition form’.
19) After receiving Clinical Laboratory Investigation reports the Investigator/ designated person
will review the reports and if any significant observations then it will be recorded in the clinical
investigation details of the ‘Screening form’ of the respective subject. The Clinical Laboratory
Investigation report will be attached to the ‘Screening form’ of the CRF of the respective
subject.
20) The Investigator/designated person will review the complete screening record forms for the
health status of the subject.
21) The X-ray has to be done for the subjects who are found fit in all the above procedures to avoid
unnecessary exposure to radiation hazard.
22) The Investigator/designated person will record the observations reported by the radiologist in
the ‘Screening Form’. The X-ray film will be kept along with the screening documents and the
report will be attached to the respective subject’s ‘Screening form’.
23) Study coordinator will compile the screening documents in following sequence:
a) Screening Consent Form
b) Screening form (including the Demographic profile, medical history of subject s, Vital Sign
and physical examination form, ECG and Clinical Investigation details form)
c) Clinical Laboratory Report(s), X-Ray reports
d) Other Investigation Report (if any)
1.0 Study Coordinator/designated person shall inform the eligibility of the subject to the subject
or the LAR of the subject.

2.0 Laboratory Technician (pathology)/Phlebotomist/Nursing staff will request the subject to

collect urine in labeled container and will perform the ‘Urine Screen for Drugs of abuse’ test
for Urine Screen for Drug of Abuse and Serum Pregnancy test (for female subjects). The
results will be recorded in the respective Pre-Enrollment Day Activity format of the subject. If
the Test is found to be negative then the subject will be sent for further procedures.
3.0 If any additional test has to perform on this pre-enrollment day, then it will be performed as
per the requirements specified in the Study protocol.
4.0 The Clinical laboratory Investigation report obtained from the in house/ outsourced laboratory
will be reviewed by the Investigator/designated person and the comments/discrepancy will be
noted and recorded in the ‘Pre-enrollment day activity’ format of the respective subject . The
Clinical Laboratory Investigation reports will be attached to this format.
5.0 After enrollment of the subject in the study the Study coordinator/designated person will issue
Subject identification number/Subject number (ID card) and will be checked-in to the clinical
facility.
6.0 The Study coordinator/responsible person will prepare the list of subjects enrolled in the
format for ‘Screening and Enrollment Log’ (Refer APPENDIX 2).
7.0 Randomization Procedures and Unblinding
 The Investigator must follow the randomization procedures, if any In the case of a
randomized, Controlled, double-blinded trial, the code is usually prepared in the form of
numbered envelopes, each containing the identification of the corresponding treatment in
order to enable the Investigator to open the code when needed, without identifying other
patients’ treatment
 Ensure that the code is broken only in accordance with the Protocol and mainly for medical
reason(s).
 Premature unblinding must be reported to the Clinical Monitor immediately and should be
documented in the File. The reason for premature unblinding of the investigational product
should be given, e.g. due to a serious adverse event.
 At the end of the trial, the Investigator must return all the unbroken codes to the Clinical
Monitor to prove that the study was blinded throughout

AF-I/SMO/SOP-010/V2.0




AF-II/SMO/SOP-010/V2.0
SCREENING AND ENROLLMENT LOG (if applicable)
Protocol No.:
Investigator Centre No.:
Screening Screening Date Subject Enrolled Patient ID allocated Screening Signatur

No. (DD/MM/YY) Initial Yes/No (if enrolled) Failure Reason e & Date

Title: 011-SOP for Audio-Video Recording of ICF Process
Sl.No. Contents Page no
Principle of Privacy and Confidentiality

1. 68
Procedure of Audio-Visual Recording

2. 68
Quality of Audio-Visual Recording

3. 69
Storage & Archival of Audio-Visual Recordings

4. 69

In the drugs and cosmetics rules, 1945, in schedule, (Gazette notification New Delhi the 31 st
July, 2015
 An A-V recording of the informed consent process in cases of vulnerable subjects in clinical
trials of New chemical entity or new molecular Entity including procedure of providing
information to the subject and his understanding on such consent, should maintained by the
Principal Investigator.
 In case of anti-HIV and anti-leprosy drugs, only audio recording of the informed consent
process of individual subject and his understanding on such consent should maintained by
Principal Investigator and team
Note: The A-V consenting procedure should be done in the respective PIs OPD / in some
cases it will be done at site management office.
I. Principle of Privacy and Confidentiality
1. During the audio-visual recording of informed consent process, the identity and records of the
trial subjects are as far as possible kept confidential; and that no details about identity of said
subjects, which would result in the disclosure of their identity, are disclosed without valid
scientific and legal reasons which may be essential for the purposes of therapeutics or other
interventions, without the specific consent in writing of the subject concerned, or someone
authorized on their behalf, and after ensuring that the said subject does not suffer from any
form of hardship, discrimination or stigmatization as a consequence of having participated in
the trial.
2. The Investigator must safeguard the confidentiality of trial data, which might lead to the
identification of the individual subjects. Data of individual subjects can be disclosed only in a
court of law under the orders of the presiding judge or in some cases may be required to
communicate to Drug regulatory/ Health authority.
3. In order to maintain the confidentiality, the videographer should be engaged as part of the
study team. Prior to initiation of the study, the Investigator should define and allocate the
activities of audio-video recording of informed consent process to the respective identified
person as videographer. The Investigator shall maintain the details of the person to whom he
has delegated the duties of audio video recording.
II. Procedure of Audio-Visual Recording
1. At the beginning of the video recording process, the Investigator will identify the protocol, the
subject/LAR/IW and the language understood by the subject/LAR/IW. If the Investigator does
not know the language of the subject/LAR/IW a member of the study team who understands
the language, would become the interpreter.
2. In order to identify the subject/LAR/IW his/her photo ID may be documented. The video
camera for the audio-visual recording should be of adequate capability to simultaneously
capture the facial details of subject, LAR/Impartial Witness (if any), Investigator/authorized
person present during the consent process. The audio-visual recording should be conducted in a
room conducive to recording of disturbance-free audio and video of the consent process.

During the videography process, care should also be taken not to include unrelated
persons/patients at the hospital within the field of vision.
III. Quality of Audio-Visual Recording
The Video recording of informed consent may not serve the intended purpose if the quality of
the recording fails to meet a minimum standard required for the purpose. The video recording
should be done using video camera of appropriate resolution and in a room free from any
disturbance to ensure that the image is recognizable and the audio is clearly audible.
IV. Storage & Archival of Audio-Visual Recordings
Audio visual recording of informed consent process and other related documents should be
preserved safely after the completion / termination of the study for at least a period of 03 years
if it is not possible to maintain the same permanently.

Title: 012-SOP for Archival of study documents
Sl.No Contents Page No
1. Purpose 71
2. Introduction 71
3. Scope 71
4. Responsibility 71
5. Definition 72
6. Procedure 73
7. Frequency of Archival 74
8. References 74
9. Annexures 75
76
AF-I/012/SMO/SOP - V3.0 Entry and exit register of archives
77
AF-II/012/SMO/SOP-V3.0 Retrieval Data form
78
AF-III/012/SMO/SOP-V3.0 Destruction Form
79
AF-IV/012/SMO/SOP-V3.0 Archival room visual Audit log
80
AF-V/012/SMO/SOP-V3.0 Document location form

I. PURPOSE:
The purpose of this Standard Operating Procedure (SOP) is to describe the standard procedures
to be followed when archiving essential paper/electronic documents related to clinical
research/trial of sponsored and conducted at KLEs Dr. Prabhakar Kore Hospital and Medical
Research centre, Belagavi.
All trial data must be kept so that the data can be accessed after the trial is finished. This may be
necessary in the event of unexpected side effects after the trial drug has been approved. It is the
responsibility of the Sponsor, and the Principal Investigator/ Institution to keep these records.
II. INTRODUCTION
Archiving is the act of storing and preserving non-active records with an enduring value .the
archivist coordinates and ensures quality storage and easy retrieval of the records.
As specified in GCP, the sponsor as well as the investigator / institution (i.e. investigational site)
should maintain essential trial documents in accordance with applicable regulatory requirements.
Essential study documents should be retained until at least 2 years after the last approval of a
marketing application in an ICH region and until there are no pending or contemplated marketing
applications in an ICH region or at least 5-10 years (total 15 Years) have elapsed since the
formal discontinuation of clinical development of the investigational product. However, these
documents should be retained even longer if required by applicable regulatory requirements or
else agreed with the sponsor.
III. SCOPE:
This SOP Will applies to all Clinical trials conducted at KLE’s Dr.Prabhakar Kore Hospital
&MRC, Nehru Nagar, and Belagavi.
IV. RESPONSIBILITY:
 Archivist or designated personnel are responsible to follow this SOP during archival
retrieval and re-archival of documents / data.
 Relevant department personnel has to follow this SOP while submitting documents for
archival / re-archival and requesting for retrieval of documents / data.
 It is responsibility of the Site Management of KAHER, KLES Dr.Prabhakar Hospital to
conduct periodic audit to assure the implementation of this SOP.
V. DEFINATION
 Archival: The procedure of preserving documents in any media for longer storage, in a safe
environment with controlled access.
 Retrieval: The procedure of getting the documents from the archives for reference,
regulatory requirements etc.
 Re-archival: The procedure of re-archiving the documents after the purpose of retrieval is
completed.
 Clinical Trial - Any investigation in human subjects, other than a non-interventional

trial intended to discover or verify the clinical, pharmacological or other
Pharmacodynamic effects of one or more medicinal product or to identify any adverse

reactions to one or more such products and to study absorption, distribution

metabolism and excretion in one of more such products with the object of ascertaining
the safety or efficacy of those products.
 International Council for Harmonisation (ICH) - Produced a series of guidelines in
1996, E6 being the guideline on Good Clinical Practice, otherwise known as
ICH-GCP. Formerly known as International Conference on Harmonisation.
 Investigator Site File (ISF) - A standard filing system which contains all essential
documents held by Principal investigator(s) conducting a trial. Which individually and
collectively permit the evaluation of the conduct of a trial and the quality of the data
produced.
 Principal Investigator (Pl): A Registered Physician, Dentist who has responsibility for
the conduct of the trial at a host site.
 Essential Documents: Essential documents are those documents that individually and
collectively permit evaluation of the conduct of a trial and the quality of the data produced.
Essential documents include the Trial Master File, source documents and Case Report
Forms (CRFs).
 Trial Master File:The Trial Master File is a file that consists of essential documents, which
enable both the conduct of a clinical trial and the quality of the data produced to be
evaluated. Those documents shall show whether the investigator and the sponsor have
complied with the principles of Good Clinical Practice and with the applicable regulatory
requirements.
 Source Documents: Source documents are original documents, data, and records (e.g.,
hospital records, clinical and office charts, laboratory notes, subjects' diaries or evaluation
checklists, pharmacy dispensing records, recorded data from automated instruments, copies
or transcriptions certified after verification as being accurate copies, microfiches,
photographic negatives, x-rays, subject files, and records kept at the pharmacy, at the
laboratories and at medico-technical departments involved in the clinical trial).
 Case Report Forms (CRFs): A printed, optical or electronic document designed to record
all of the protocol required information on each trial subject.
VI. PROCEDURE:
i. Archival Room Maintenance and Access control
 Access to the archival room shall be controlled and tracked.
 Access to archives is restricted to Archivist and Administration. Entry of other individuals
Third Party employees and external personnel such as Auditors / Clients) into the archival
facility shall be escorted by the archivist during visit. Entry and exit details shall be captured
in the logbook as per Annexure 01 – Entry and Exit of Archives.
 Archival room is provided with the CCTV Camera, fire extinguisher, Heat and smoke
detector.
 The temperature of 23( +/-) 4oC and humidity 30-70% RH shall be maintained in archival
room.
 Pest control activity shall be performed quarterly or as whenever required

 The archivist shall perform quality check of the archives once in 06 months by visual audit
for any signs of deterioration.
 The minimum signs of deterioration for visual evaluation includes the following but not
limited to:
Presence of Paper Mites
Presence of Dust in the storage cabinets
Presence of Rodents / insects Excreta
Presence of any growth of moulds
Presence of any self-deterioration of paper documents / files
 For any deterioration noticed, ensure immediate remedial actions are taken.
ii. Archival period:
 All essential documents relating to clinical study including monitoring documents, projects
files and audit documents shall be archived in accordance with the requirements of the
applicable regulations / guidelines as follows:
o As defined in protocol or/ and as per the contract agreement with the sponsor
o Until at least 2 years after the last approval of a marketing application in a region
where the ICH guidelines applies
o Until there are no pending or contemplating marketing applications in an ICH
region.
 Documents relating to clinical study documents shall be archived for a minimum period of
10 to 15 years (or) in accordance Regulatory guidelines and KLES Dr.Prabhakar Kore
Hospital and MRC which shall be decided by the management team as per requirement.
iii. Location of Archival Documents:
 Archived material shall be stored in a legible condition at KLES Dr.Prabhakar Hospital and
MRC in Ground floor (G+2), opposite of Free X-Ray Department, Belagavi.
 The documents shall be archived in fire proof steel cabinets and shall be identified as I, II,
III…etc.
For example if the documents archived in cabinets –I and shelf – 1, shall be assigned the
archival location as “I1”
 Each cabinet shall have register maintained by the archivist as per Annexure 07 – Format
of archival register
 The register shall contain the details of documents or materials archived in each shelf.
VII. Frequency of archival:

i. Study documents:
 During the conduct of a study, study documents and data can be retained in Archival room
at KLES Dr.Prabhakar Kore Hospital and MRC, Belagavi and stored in the project file and
/or e-directory, or otherwise as specified in the contract/work order with the sponsor.
 Once the trial is completed, project documents shall be returned to the client or archived
according to the terms and conditions as per regulations/site policies.
 Study documents shall be archived after the completion of the study and within 30 days.
The Study completion letter along with study progress to submitted to the IEC of KHAER,
Nehru Nagar, Belagavi.

ii. Non-Study related documents:

Superseded SOPs shall be archived within 10 working days from the date the y become
obsolete.
iii. Archival of paper documents:
 The respective department head/designee is responsible for notifying the archivist in
writing, the intent to archive study documents.
 All records related to the project shall be retained in a manner that shall preserve the
security, integrity and authenticity.
 All study related documents shall be given to archivist in appropriately labelled files by
the concerned department as shown below: AF-I/012/SOP- V3.0
 The contents in the files shall be verified against the index given in the respective files by
the archivist before archival.
 Upon completion of the contracted archival period, the sponsor shall be

informed/intimated in writing. If the archival period is extended by the sponsor
 Archive master copies of the superseded versions or absolute of the SOPs/Work

procedures in the labelled box files
 While archiving do not compile all versions of single SOPs/Work Procedures of different
departments together.
 The details of archive shall be captured in AF-III/012/SOP- V3.0 archival inventory log by
the archivist
iv. Archival of Electronic Documents/data (if applicable)
 Once the study completed at KLES Dr.Prabhakar Kore Hospital and MRC, Belagavi, all
the created electronically or received electronically by KLES Dr.PK Hospital shall be
archived on appropriate electronic media in read only format duplicate copies or as per
procedure specified in the contract with sponsor.
 After that the data shall be deleted from the shared network directories and individual
computers.
 All the electronic documents/data shall be appropriately labelled by the concerned

department as shown as below: Annexure-III

Name of the study document:

Study title/Number:
Name of Principal investigator/Co-I:
Date of creation:
 Appropriate security measures shall be taken to avoid my unauthorised access to the

electronic data.
 If the responsibility of electronic archival is not delegated to KLES Dr.PK Hospital and
MRC, Belagavi, the protocol specific electronic data, along with details of e-Data, shall
be returned to sponsor.
v. Disposition of archived data/documents:
 Under circumstances, shall any archived material be removed/ destroyed by the Clinical
services administrators of KLEs Dr.PK Hospital without intimation from sponsor or any
other specified in the contract with the sponsor.
 Processes for identifying materials that have reached the end of their retention period
 Upon completion of the contracted archival period, the sponsor shall be
informed/intimated in writing. If the archival period is not extended by the sponsor then
the study documents shall be returned to the sponsor and a list of documentation
provided to the sponsor shall be created. A sponsor acknowledgment copy of this shall
be retained.
 If required, disposition of study documents/data shall be out sourced to an external
vendor by KAHER’s Site Management office, KLES Dr.Prabhakar Kore Hospital and
MRC, Belagavi
VIII. References:
1. 21 CFR 312.55-Informing Investigators
2. 21 CFR 312.57- Record Keeping and Record Retention
3. 21 CFR 312.58- Inspection of Sponsor records and Reports
4. 21 CFR 312.62- Investigator Record Keeping and Record retention
5. 21 CFR 312.64- Investigator Reports
6. Appendix V-CDSCO guideline: Essential Documents
7. ICH Guidelines for GCP (E6) Section 4.4- communication with IRB/IEC
8. ICH Guidelines for GCP (E6) Section 4.9- Records and reports
9. ICH Guidelines for GCP (E6) Section 5.22- Clinical Tail/Study Reports

Annexure: I AF-I/012/SMO/SOP- V3.0

Entry and Exist register of Archives:
Sl.No Name of Department/ Purpose Time in Time out Sign and Authoriz
the Sponsor/ date ed by
Person Regulators

AF-II/012/SMO/SOP-V3.0
Retrieval Data Form
.
Sl.No Protocol No Request for & Date Retrieved by/ Returned Date Authorized by
signature and signature

Annexure: III AF-III/012/SOP- V3.0

Destruction Form
Sl.No File/Document Box/Shelf No No.of Boxes Date of destruction Verified by

No

Annexure: IV AF-V/012/SMO/SOP- V3.0

Archival room –Visual Audit log
Archival room visual audit for the quarter of_____________________ (MM/DD/YYYY)
Location of damage/Deterioration and remedial actions taken (if any observed)
Observations:
Visual Audit performed by:
Name
Designation:
Signature:

Annexure: V AF-V/012/SMO/SOP- V3.0
Document location Form

Cabinet ID:
Shelf ID Contents Shelf ID Contents

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Site Name KLES Dr.

Prabhakar Kore Hospital and MRC, Belagavi_I0

Authorized by vice chancellor of KLE University-KAHER, Nehru Nagar,

VERSION and DATE: 03 and September -2019

Validity 30-Sep-201 9 to 29-Sep -2021

Revana S Devarinti Assistant Coordinator-SMO

REVIEWED and APPROVED BY:

Prof.(Dr)M. S.Ganachari Member Seuetary of KLE-

Name Title Signature Date

KLE-Site Management office of KLE Academv qnrr

Site Management Office

Sl.No Contents Page No

1. SOP for Principal investigator 01-07

2. SOP for obtaining ICF process 08-11

3. SOP for Clinical research coordinators 12-17

4. SOP for check in and check out of the subjects 18-20

5. SOP for dosing at subject monitoring restrictions 21-23

6. SOP for Handling of Biological samples at site 24-28

7. SOP for Handling and reporting of AE/SAE 29-38

9. SOP for Investigational product management 46-53

10. SOP for Screening and enrollment of Subjects 54-62

11. SOP for Audio-Video recording of ICF process 63-69

12. SOP for Archival of study Documents 70-80

13. Site Protocol --

14. Routine Hospital flow chart --

Sl. No Contents Page No

2. Prior to Intimation of the study 02

Arrange archiving of trial documents according to GCP and regulatory

6. During the Study 04

7. After Completion of the study 07

Aims: To define Investigators’ responsibilities and to provide instruction, when performing

 Authorized Staff Form

 Study Documents (after completion of 15 years)

viii. Compliance with study protocol

a) To the IEC for review and approval/favorable opinion,

xi. Adequate sources:

 The investigator should be able to demonstrate (e.g., based on retrospective data) a

VII. After Completion of the study:

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6. Applicable rules and regulations 11

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VI. Applicable rules and regulations:

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i. Study start up activities like Feasibility/Synopsis and Clinical disclosure agreements.

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Staff responsible for Implementation:

KLE-Site management Office-SOP Versio-3.0 Page 16

KLE-Site management Office-SOP Versio-3.0 Page 17

Sl.No CONTENTS Page No

Procedure For Check In

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KLE SITE MANAGEMENT OFFICE-SOP VERSION-3.0 Page 20

S.No Contents Page no

KLE-Site Management Office-SOP Version-3.0 Page 21