SITE GEN-001 01_SOP on Site Activities

8/14/2019 SITE GEN-001 01_SOP on Site Activities

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STANDARD OPERATING PROCEDURE: Dr XXXXX Site

Title: Standard operating procedure of site activities

SOP No.: GEN-01 Version No.: 01 Effective Date: dd-mmm-yyyy

Author:

__________________________________________________Name

__________________________________________________ ____________________Signature Date

Authorised by:

__________________________________________________Name

__________________________________________________Title

__________________________________________________ ____________________Signature Date

PURPOSE

This SOP describes the process to ensure that all activities performed at Dr. ABC XYZ siteunder Clinical Trials are performed in a consistent manner.

SCOPE

This SOP applies to all the site members of Dr. ABC XYZ site.

DEFINITIONS/ABBREVIATIONS

Adverse Event (AE)Any untoward medical occurrence in a patient or clinical investigation subject administered apharmaceutical product and which does not necessarily have a causal relationship with thistreatment. An adverse event (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 (see the ICH Guideline for Clinical Safety Data Management:Definitions and Standards for Expedited Reporting).

GEN-001.01 Page 1 of 17Confidential


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Applicable Regulatory Requirement(s)Any law(s) and regulation(s) addressing the conduct of clinical trials of investigationalproducts.

Approval (in relation to Institutional Review Boards)The affirmative decision of the SITE EC/IRB that the clinical trial has been reviewed and maybe conducted at the institution site within the constraints set forth by the SITE EC/IRB, theinstitution, Good Clinical Practice (GCP), and the applicable regulatory requirements.

AuditA systematic and independent examination of trial related activities and documents to

determine whether the evaluated trial related activities were conducted, and the data wererecorded, analyzed and accurately reported according to the protocol, sponsor's standardoperating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatoryrequirement(s).

Blinding/MaskingA procedure in which one or more parties to the trial are kept unaware of the treatmentassignment(s). Single-blinding usually refers to the subject(s) being unaware, and double-blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, dataanalyst(s) being unaware of the treatment assignment(s).

Case Report Form (CRF)

A printed, optical, or electronic document designed to record all of the protocol requiredinformation to be reported to the sponsor on each trial subject.

Clinical Trial/StudyAny investigation in human subjects intended to discover or verify the clinical,pharmacological and/or other pharmacodynamic effects of an investigational product(s),and/or to identify any adverse reactions to an investigational product(s), and/or to studyabsorption, distribution, metabolism, and excretion of an investigational product(s) with theobject of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study aresynonymous.

Clinical Trial/Study ReportA written description of a trial/study of any therapeutic, prophylactic, or diagnostic agentconducted in human subjects, in which the clinical and statistical description, presentations,and analyses are fully integrated into a single report (see the ICH Guideline for Structureand Content of Clinical Study Reports).

Compliance (in relation to trials)Adherence to all the trial-related requirements, Good Clinical Practice (GCP) requirements,and the applicable regulatory requirements.

ConfidentialityPrevention of disclosure, to other than authorized individuals, of a sponsor's proprietary

information or of a subject's identity.



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ContractA written, dated, and signed agreement between two or more involved parties that sets outany arrangements on delegation and distribution of tasks and obligations and, if appropriate,on financial matters. The protocol may serve as the basis of a contract.

Direct AccessPermission to examine, analyze, verify, and reproduce any records and reports that areimportant to evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatoryauthorities, sponsor's monitors and auditors) with direct access should take all reasonableprecautions within the constraints of the applicable regulatory requirement(s) to maintain theconfidentiality of subjects' identities and sponsors proprietary information.

DocumentationAll records, in any form (including, but not limited to, written, electronic, magnetic, andoptical records, and scans, x-rays, and electrocardiograms) that describe or record themethods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken.

Essential DocumentsDocuments which individually and collectively permit evaluation of the conduct of a studyand the quality of the data produced (see 7. Essential Documents for the Conduct of aClinical Trial).

Good Clinical Practice (GCP)

A standard for the design, conduct, performance, monitoring, auditing, recording, analyses,and reporting of clinical trials that provides assurance that the data and reported results arecredible and accurate, and that the rights, integrity, and confidentiality of trial subjects areprotected.

Independent Ethics Committee (IEC)An independent body (a review board or a committee, institutional, regional, national, orsupranational), constituted of medical professionals and non-medical members, whoseresponsibility it is to ensure the protection of the rights, safety and well-being of humansubjects involved in a trial and to provide public assurance of that protection, by, amongother things, reviewing and approving / providing favourable opinion on, the trial protocol, thesuitability of the investigator(s), facilities, and the methods and material to be used inobtaining and documenting informed consent of the trial subjects.The legal status, composition, function, operations and regulatory requirements pertaining toIndependent Ethics Committees may differ among countries, but should allow theIndependent Ethics Committee to act in agreement with GCP as described in this guideline.

Informed ConsentA process by which a subject voluntarily confirms his or her willingness to participate in aparticular trial, after having been informed of all aspects of the trial that are relevant to thesubject's decision to participate. Informed consent is documented by means of a written,signed and dated informed consent form.

InspectionThe act by a regulatory authority (ies) of conducting an official review of documents,facilities, records, and any other resources that are deemed by the authority (ies) to berelated to the clinical trial and that may be located at the site of the trial, at the sponsor's



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and/or contract research organizations (CROs) facilities, or at other establishments deemedappropriate by the regulatory authority(ies).

Institution (medical)Any public or private entity or agency or medical or dental facility where clinical trials areconducted.

Institutional Review Board (SITE EC)An independent body constituted of medical, scientific, and non-scientific members, whoseresponsibility is to ensure the protection of the rights, safety and well-being of humansubjects involved in a trial by, among other things, reviewing, approving, and providing

continuing review of trial protocol and amendments and of the methods and material to beused in obtaining and documenting informed consent of the trial subjects.

Investigational Product (IP)A pharmaceutical form of an active ingredient or placebo being tested or used as a referencein a clinical trial, including a product with a marketing authorization when used or assembled(formulated or packaged) in a way different from the approved form, or when used for anunapproved indication, or when used to gain further information about an approved use.

InvestigatorA person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted bya team of individuals at a trial site, the investigator is the responsible leader of the team and

may be called the principal investigator.

Investigator's BrochureA compilation of the clinical and nonclinical data on the investigational product(s) which isrelevant to the study of the investigational product(s) in human subjects (see 7.Investigators Brochure).

MonitoringThe act of overseeing the progress of a clinical trial, and of ensuring that it is conducted,recorded, and reported in accordance with the protocol, Standard Operating Procedures(SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).

Monitoring ReportA written report from the monitor to the sponsor after each site visit and/or other trial-relatedcommunication according to the sponsors SOPs.

Multicentre TrialA clinical trial conducted according to a single protocol but at more than one site, andtherefore, carried out by more than one investigator.

Nonclinical StudyBiomedical studies not performed on human subjects.

ProtocolA document that describes the objective(s), design, methodology, statistical considerations,and organization of a trial. The protocol usually also gives the background and rationale for



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the trial, but these could be provided in other protocol referenced documents. Throughoutthe ICH GCP Guideline the term protocol refers to protocol and protocol amendments.

Protocol AmendmentA written description of a change(s) to or formal clarification of a protocol.

Quality Assurance (QA)All those planned and systematic actions that are established to ensure that the trial isperformed and the data are generated, documented (recorded), and reported in compliancewith Good Clinical Practice (GCP) and the applicable regulatory requirement(s).

Quality Control (QC)The operational techniques and activities undertaken within the quality assurance system toverify that the requirements for quality of the trial-related activities have been fulfilled.

RandomizationThe process of assigning trial subjects to treatment or control groups using an element ofchance to determine the assignments in order to reduce bias.

Regulatory AuthoritiesBodies having the power to regulate. In the ICH GCP guideline the expression RegulatoryAuthorities includes the authorities that review submitted clinical data and those that conductinspections (see 1.29). These bodies are sometimes referred to as competent authorities.

Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR)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

(see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards forExpedited Reporting).

Source DataAll information in original records and certified copies of original records of clinical findings,observations, or other activities in a clinical trial necessary for the reconstruction andevaluation of the trial. Source data are contained in source documents (original records orcertified copies).

Source DocumentsOriginal documents, data, and records (e.g., hospital records, clinical and office charts,laboratory notes, memoranda, subjects' diaries or evaluation checklists, pharmacydispensing records, recorded data from automated instruments, copies or transcriptionscertified after verification as being accurate copies, microfiches, photographic negatives,microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at thelaboratories and at medico-technical departments involved in the clinical trial).



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SponsorAn individual, company, institution, or organization which takes responsibility for theinitiation, management, and/or financing of a clinical trial.

Standard Operating Procedures (SOPs)Detailed, written instructions to achieve uniformity of the performance of a specific function.

SubinvestigatorAny individual member of the clinical trial team designated and supervised by theinvestigator at a trial site to perform critical trial-related procedures and/or to make important

trial-related decisions (e.g., associates, residents, research fellows). See also Investigator.

Subject/Trial SubjectAn individual who participates in a clinical trial, either as a recipient of the investigationalproduct(s) or as a control.

Subject Identification CodeA unique identifier assigned by the investigator to each trial subject to protect the subject'sidentity and used in lieu of the subject's name when the investigator reports adverse eventsand/or other trial related data.

Trial Site

The location(s) where trial-related activities are actually conducted.

Unexpected Adverse Drug ReactionAn adverse reaction, the nature or severity of which is not consistent with the applicableproduct information (e.g., Investigator's Brochure for an unapproved investigational productor package insert/summary of product characteristics for an approved product) (see the ICHGuideline for Clinical Safety Data Management: Definitions and Standards for ExpeditedReporting).

Vulnerable SubjectsIndividuals whose willingness to volunteer in a clinical trial may be unduly influenced by theexpectation, whether justified or not, of benefits associated with participation, or of aretaliatory response from senior members of a hierarchy in case of refusal to participate.Examples are members of a group with a hierarchical structure, such as medical, pharmacy,dental, and nursing students, subordinate hospital and laboratory personnel, employees ofthe pharmaceutical industry, members of the armed forces, and persons kept in detention.Other vulnerable subjects include patients with incurable diseases, persons in nursinghomes, unemployed or impoverished persons, patients in emergency situations, ethnicminority groups, homeless persons, nomads, refugees, minors, and those incapable ofgiving consent.

Well-being (of the trial subjects)The physical and mental integrity of the subjects participating in a clinical trial.



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RELATED SOPs AND OTHER DOCUMENTS

ICH GCPIndian GCPSchedule Y of Drug & Cosmetic Act 1940

PROCEDURES

1. Role & Responsibilities

Step Action

1.1Responsibility and accountability for clinical trials will be allocated among membersof the Dr. ABC XYZ site team. This includes the administrative accountability as wellas general responsibilities of the site team and of individual team members forfulfilling regulatory and clinical requirements.

1.2Responsibilities of the Investigator at Dr. ABC XYZ site:Investigator will conduct the trial in compliance with the protocol, ICH GCP &applicable regulatory requirements.The responsibilities of Investigator will include but not limited to:

1. The safety and welfare of participants in the trial.

2. Reading and understanding all the information in the investigators brochure,the informed consent, and the protocol

3. Informing all participants, including participants used as controls, that theinvestigational agents are being used for investigational purposes andfollowing all requirements relating to obtaining informed consent.

4. Preparing and submitting protocol documents for initial SITE EC review and

approval.

5. Conducting study activities only after SITE EC approval and in accordance with

the approved protocol, and assuring that SITE EC requirements are met.6. Reporting adverse events to the Sponsor within agreed timelines.

7. Implementing modifications in approved research only after consultation with

sponsor followed by review and approval of the modification by the SITE EC,except where necessary to eliminate apparent immediate hazards toparticipants.

8. Appropriate control, inventory, distribution, storage, record keeping anddestruction or return of all clinical supplies including the Investigational



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Product9. Prompt reporting of all the Serious Adverse Events to site EC.10. Providing progress reports to the Site EC as per site EC SOP.12. Assuring the disclosure of financial interest and arrangements to the sponsor

and the Site EC, and if required by the site EC, to participants, by any memberof the research team that may present a conflict with the interests of participantsin the study.

13. While retaining knowledge of and overall authority for the conduct of all researchstudies, supervise members of the research team qualified by appropriateeducation and experience to accept responsibility for study-related activities notdirectly performed by the PI. Assuring that delegation of responsibilities is

appropriate and is documented and that individuals recruited as members of theresearch team are appropriately licensed and trained.

14. Maintaining adequate and accurate records and making records available forinspection to external and internal monitors, Auditors & Inspectors.

15. The PI may delegate responsibility to individual members of the research team;however, the PI cannot delegate accountability for the ethical conduct of thestudy. The PI must sign the form that delegates responsibilities to each memberof the research team. Each individuals name must be initialed and dated. Theform must be updated, initialed and dated, each time there is a personnelchange.

1.3Responsibilities of the Clinical Research Coordinator :The responsibilities will be delegated to the position with the level of qualification,

training and experience appropriate to the task and in accordance with therequirements of the trial:1. Developing organizational aids and checklists to facilitate patient recruitment

and the collection of complete and accurate study data.2. Maintaining the regulatory and study files for each research project.3. Communicating with the SITE EC as appropriate.4. Assuring proper handling of the investigational product.5. Reporting adverse events to the SITE EC and sponsor, as appropriate.6. Meeting with sponsor representatives to discuss planned and ongoing studies.7. Overseeing study closure and reporting of results.8. Participating in quality assurance activities of the sponsor & regulatory

inspections.9. Supervising other clinical research personnel, as appropriate.10. Participating as appropriate in the training of individuals recruited as members

of the research team.11. Managing the business aspects of studies, including developing and negotiating

study budgets and facilitating the contract review process to assure thatprovisions on publication, intellectual property, indemnification, recordsretention, and data ownership are appropriately negotiated with the sponsor.

12. Design appropriate recruitment strategies and track study enrollment.



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13. Accurate and timely data entry & corrections.14 Proper handling & processing of collected samples.

Further to above listed responsibilities medically qualified personnel will also beresponsible for the following activities.1. All procedures requiring medical expertise.2. Screening and enrolling subjects in studies and managing their participation

according to ethical, regulatory, and protocol-specific requirements.3. Obtaining informed consent from trial subjects before performing any study

related procedures. Performing all the study related procedures as per the

protocol.

2. Distributing, Storing & Inventory of Investigational Drugs

Step Action

2.1Principal Investigator- The Principal Investigator is responsible and accountable forthe distribution, storage, and inventory of the investigational drug involved in theapproved clinical study. The PI may delegate responsibility for the investigationaldrug to another qualified researcher involved in the study, but may not delegateaccountability.

2.2 Upon receipt of the study drug, the shipment will be inventoried, verifying that thereceipt date, lot number, drug type, batch number and quantity on the packing slips isthe same as what was actually received;

2.3Promptly bring any discrepancies to the attention of the Sponsor/supplier of the drug.

2.4Retain a copy of the shipping inventory, packing slips and document inventory in thestudy files;

2.5The drug will be stored in a secure environment according to requirements listed inthe protocol or the investigators brochure.

2.6The temperature of the storage area will be recorded daily, or an alarm systemmaintained so research personnel will be notified if the temperature exceeds the

parameters specified for the agent. Access to the storage area will be limited toessential research personnel.

2.7The expiration date of the drug will be noted, and the drug will be returned, disposedof, or destroyed in accordance with the approved protocol when the drug expires.

2.8The site team member designated by the PI to distribute the drug to the participantmust ensure that the participant understands when and how to take the medication.When the protocol requires the participant to record the day, times, and methods oftaking the study drug, the site team member must make sure the participantunderstands how to fulfill the responsibility.

2.9Each time the study drug is distributed to a participant at the study site, it will beappropriately recorded. Documentation will include at least the following: Name of individual distributing the agent,

Participants study ID and/or initials Amount distributed (and lot number, if appropriate), Date of distribution (and time, if appropriate)



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2.10Drug accountability documentation will be completed on arrival of supplies, each timedrugs are distributed, and when drugs are returned to the sponsor or destroyed.

2.11Compliance by the participant with the procedures described in the protocol will beverified. Discrepancies between amounts of the drug or agent used by participantsand amounts returned and the reasons underlying any discrepancies will bedocumented. If the participant has not taken the drug or agent as required by theprotocol, the PI should determine whether the participant will remain in the study orbe withdrawn.

2.12When all participants have completed the study medication, the records will bechecked for accuracy and will be signed and dated.

2.13

During the course of the study, partial doses, used containers and tubing should be

disposed of in the manner described in the protocol, and, if they are biohazards, inaccordance with the institutions biohazard policies.

2.14At the conclusion of the study, the study drug should be inventoried and prepared tobe returned to the sponsor or to be destroyed in accordance with the requirements ofthe sponsor or the manufacturer or the state board of pharmacy. All documentationregarding receipt, storage, dispensing, and return of used containers must becomplete and accurate.

2.15A copy of all accountability documents will be maintained in the regulatory files.

3. Recruitment of study subjects

Step Action

3.1Recruitment strategies :Participants will be recruited from a variety of sources including clinician referrals,internet postings, newspaper advertisements, television/radio advertisements, fromsupport groups, health fairs, or from local hospitals and clinics. Clinicians will benotified about research studies by letter or by word of mouth.

3.2Recruitment Materials :Materials directed to patients or the general public with the intent of recruiting them toparticipate in clinical research must be submitted to the SITE EC for review andapproval. These include announcements, advertisements, flyers, phone scripts for

screening, oral scripts for consenting participants, newspaper ads, videos, radio andtelevision announcements, bulletin board tear-offs, Internet postings, and posters.

3.3Enrolment ProceduresRecruitment rates will be regularly evaluated during the recruitment period, withreassessment of the strategy when recruitment targets are not being met. When thereis competitive enrolment, recruitment must be continually reassessed to managescreening of participants.

3.4The Clinical Research Coordinator/Nurse will keep records of recruitment and willinform the Dr. ABC XYZ and the monitor of progress in recruiting patients. Everyperson who is considered a potential candidate for the study should be entered in theScreening and Enrolment Log (based on study inclusion and exclusion criteria). Notewhether individuals have enrolled in the study and, if not, document the reason.

3.5 At the screening visit, the potential participant must give informed consent prior to anyscreening procedures. Signed informed consent forms from subjects who terminatedtheir participation in the study during the screening process will be retained.



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3.6After screening and/or randomization, the participants code/ID number will be enteredin the Screening and Enrolment Log. The Enrolment Log can serve as the codedsubject list, which must be archived at the end of the study. If there is no Screeningand Enrolment Log included in the study, a master log must be kept of all subjectsrandomized in the trial, with subject name, address, year of birth, and treatmentallocation or treatment package number.

4. Informed Consent

Step Action

4.1Obtaining Informed Consent

A completed Informed Consent Document will be obtained from every participant whotakes part in a study prior to performing any study-related activities, includingscreening laboratories, vital signs, or questionnaires. On occasion, a separatescreening consent, approved by the SITE EC, may be used to document consent forscreening procedures only.

When a potential protocol candidate will be identified, the investigator or researchcoordinator discusses the study in detail with the potential participant. An explanation

of the study, its risks and benefits, and what would be required of the subject will bediscussed. The subject will be given a copy of the informed consent document to readin a quiet environment without distraction. The subject will be encouraged to take theconsent form home so that he or she may discuss it with family members. Allquestions and concerns will be addressed throughout this process by the consenterand/or PI.

If a person decides to participate, he/she will be asked to sign the informed consentdocument.

Only after all questions and concerns have been addressed and the consenter issatisfied that there is a clear understanding of the trial.

The informed consent document will be signed and dated by the participant or legal

representative along with the coordinator or investigator obtaining consent.The original signed informed consent will be kept in the patients research chart (i.e.,source documents) or in the patients medical record.

The participant will be given a copy of the signed informed consent document.

Documentation of the Informed Consent process will be entered in the subjectssource documents (see Documentation Section below).

4.2Revised Informed Consent Forms & Re-consenting



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If, during the course of the trial, the protocol has been modified in such a way thatchanges are made to the Informed Consent, participants who have already given theirinformed consent may be required by the SITE EC to be re-consented using theupdated form with the changes bolded. All participants currently enrolled in the studymust sign the bolded copy of the updated informed consent form to acknowledge thechanges. The participant may be re-consented at the next patient contact unlessotherwise stated by the SITE EC or study sponsor.

For potential participants who are not yet enrolled in the study, the revised InformedConsent replaces all previous versions for the Informed Consent and is used in itsclean format. Informed Consent is obtained as described above.

4.3 Obtaining Informed consent from participant who can not readIf an investigator wishes to include a subject who is illiterate or cannot read, theinformed consent document will be read to the subject in the presence of an impartialwitness. Whenever possible, accommodations should be made to permit subjects toread the

consent form if possible; e.g., large type for individuals with visual impairments, ratherthan relying on verbal consent routinely.

The information presented to the subject must include all of the required elements ofconsent and should be at least as extensive as found in the written consent form.

An impartial witness will observe and/or take part in the consent process and then signthe consent form.

The person who is illiterate will also sign her/his mark on the signature line. When astudy is expected to include illiterate subjects, the investigator will describe duringinitial review how the consent process is to be carried out and will submit a shortform for approval.

4.4Obtaining consent from children

Where minors (those who are less than 18 years of age) are involved in research,consent of one or both parents must be obtained, as required by the site EC approvedprotocol.

The SITE EC may require the assent of the child. The SITE EC approved protocol willspecify whether assent is required, and when it is required, whether assent may beverbal or must be written and signed the minor. If assent is required, the child should

be given an explanation of the proposed research procedures in a language that isappropriate to the child's age, experience, maturity, and condition. This explanationshould include a discussion of any discomforts and inconveniences the child mayexperience if he or she agrees to participate.

If the parents consent but the child does not wish to participate, then researcher mustrespect the decision & should not take the child in the study.

The SITE EC may require additional protections when minors participate in research,such as requiring that an independent third party or an advocate of the child bepresent during the informed consent process.

Individuals who are mature minors or emancipated minors under the law of thestate may be able to give informed consent. If a participant is a mature minor oremancipated minor, the researcher should contact the SITE EC before allowing the

minor to give informed consent for participating in the study.

4.5Documentation of Informed consent process



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The PI/ medical study coordinator will maintain documentation of the decision todelegate the responsibility for informed consent, including the qualifications of theindividual(s) selected. This will be done via a Delegation of Duties Form which is filedin the regulatory files. This documentation shall be made available forauditing/monitoring.

The original SITE EC approval letter and the stamped copies of the consent form willbe maintained in the regulatory file and copies forwarded to the sponsor. (SeeRegulatory Preparation Section of this Manual)

The site team member obtaining informed consent will note in the source documentsthe following information pertinent to The Informed Consent Process:

1. Name and title of person who explained the study

2. Name and title of person who obtained Informed Consent (if different thanabove)

3. The actual date and clock time Informed Consent was obtained4. Individual(s) present when Informed Consent was obtained5. Name of staff, if any, who witnessed Informed Consent6. Name of individual who signed the Informed Consent document

5. Adverse Event Reporting

Step Action

5.1 The participant will be assessed at each visit, or study assessment, for AEs thatmay have occurred since the previous visit or assessment, insuring that the followingare appropriately investigated:Spontaneous reports of adverse events by subjects

Observations of adverse events by clinical research staff

Reports by family members or medical care providers

events documented in medical records or progress notes that may be AEs

Reports of the death of a participant during the protocol-defined follow-up

period, whether considered treatment-related or not

5.2A toxicity grade will be assigned using the grading scale described in the protocol (ifpresent).

5.3 All appropriate resources will be directed toward insuring the participants safety andwell-being.



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5.4If necessary for the immediate medical care of the participant, the PrincipalInvestigator may elect to break the drug blind after consultation with the sponsor.Therapeutic intervention measures will be taken as outlined in the protocol. Thesubject should have clinical assessments (frequency to be determined by the primaryinvestigator unless dictated by protocol) until the AE has stabilized or resolved.If the adverse event is serious and unexpected, the sponsor should be informed assoon as possible after the occurrence of the event becomes known to study staff andwhen the participant has stabilized (whether the AE is considered drug-related ornot) so that the sponsor can fulfil its reporting obligations to the FDA. The sponsorshould be updated as information on the AE becomes available. If applicable, theform provided by the sponsor should be completed. As much of the following

information as possible should be provided: Protocol name and number

Possible test articles: investigational product, comparator, or placebo

Lot number and expiration date

Study subject number/identification

Demographic data

Nature of the event

Severity of the event (may be clarified in the protocol)

Probable relationship of the AE to the investigational product

Date (and time) of AE onset and resolution, if available

Dose, frequency, and route of administration of the investigational product

Start and stop dates of test article administration

Concomitant medications and therapies

Clinical assessment of the subject at this time

Results of any laboratory and/or diagnostic procedures, treatments, autopsy

findings

Follow-up plan

Outcome

5.5If the AE results in the subjects death an autopsy report or death certificate will beobtained, if required by the protocol.

5.6Source documentation must be completed, as appropriate. The appropriate case

report form must be completed for collection of adverse event information, and copiesof all reports should be maintained in the participants file and the regulatory files

5.7All SAEs should be reported to the SITE EC as per the Site EC SOP.

5.8The IND Safety Report should be submitted to the SITE EC within ten (10) days ofreceipt of the report from the sponsor or within 24 hours of the onset of the event orthe sites having been made aware of the event.

5.9If further action is required by the SITE EC, the sponsor should be informed.

5.10A summary of all adverse events (both serious and non-serious) will be reported to theSITE EC as part of continuing review.

6 Source Documentation



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Step Action

6.1 The SITE EC approved protocol describes the information to be obtained from eachparticipant during screening and study visits. This information will be obtained by avariety of means including interviewing, assessment procedures and performance ofstudy-specific diagnostic and laboratory tests. These various processes/proceduresmust be performed according to Professional Standards of Practice, applicableregulatory requirements, and GCP (Good Clinical Practice).

6.2 Original documentation, containing the subjects health information and medical testresults, must be retained in the subjects medical/study record. This information mayinclude the clinical medical report, laboratory results, laboratory notes, copies of

hospital charts, primary physician or other related consultations, communicationbetween study team, subject diaries, questionnaires, check lists, photographs,negatives, drug records, X-rays, EKGs and electronic data. Documentation shouldalso note if a procedure was not performed and should be accompanied by anappropriate explanation e.g. subject refused, subject had to leave before test could beperformed.

6.3 At the start of the study, the collection of source documentation begins once eachparticipant has signed the approved informed consent form. This file will be updated ateach subsequent visit. Documentation, outlining any issues associated with a specificparticipants involvement in the research study, should be updated as necessary ateach subsequent study visit with any new medical conditions or with any past medicalhistory that becomes known to the research team.

6.4 The original study documentation must be completed, signed and dated by theresearcher who obtained the data.

6.5 Source documentation will be completed and filed at the end of study visit. All sourcedocumentation must be in compliance with sponsor/CRO specified recommendations.

6.6 Case Report Forms and source data are maintained separately, but source documentsshould accompany the case report form for sponsor verification.

7 Essential Documents

Step Action

7.1 A regulatory file labelled with sponsor name, investigator name, protocol number andtitle will be prepared for each clinical trial prior to enrolling subjects or collecting anydata.

7.2 The regulatory file will contain the following documents, as they apply to the study.Sponsor should be consulted for the same;

FDA Form 1572 ) listing the PI and sub-investigators and all revisions

Financial Disclosure Forms/ SITE EC Conflict of Interest Forms

CVs for Investigators, and all sub Investigators or other key personnel, signed

and dated. CVs should be updated at least every 2 years, or more often if theSponsor requires

Current licenses of all key study personnel

The current Protocol signed and dated by the PI



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Investigators Brochure (Investigators at all sites must have a copy) and signed

acknowledgement that the PI and sub investigators have read it.

all SITE EC approvals

Informed Consent forms

Documentation of protocol deviations/violations whether SITE EC approved or

not,

Correspondence to and from the SITE EC,

Amendments to the Protocol,

Progress reports submitted to the SITE EC

Final study report (study status reports)

SITE EC approved recruitment materials

Form delegating responsibilities among the members of the research team,

initialed and dated by the PI for each person on the form

Site Signature Log

Subject Identification Log

Site Monitoring Visit Log

Laboratory Reference Ranges

Laboratory Certifications

Drug Inventory Log and Drug Labels

Drug Return/Destruction Log

Serious Adverse Event (SAE) Reports

IND Safety Reports, signed and dated, and a copy of the transmittal memo to

the SITE EC and any SITE EC acknowledgement.

Screening Randomization Log Phone Logs and Correspondence, documents/

submissions/correspondence sent and received during the study to SITE EC,to the sponsor, and to regulatory, licensing, and accrediting agencies, includingcopies of SAE notifications, faxes, emails, newsletters, meeting notes, memosto file

7.3 The regulatory file will be maintained and updated as necessary, addingappropriate documents as they are generated or received. The regulatory fileswill be updated to reflect the following:

Changes in Study Personnel Changes in Study Personnel Responsibilities

Changes in the Financial Arrangements of Study Personnel

Renewal of SITE EC Approvals

Renewal of Investigator and sub Investigator CVs, Lab

Certifications and other required licenses and certifications

All Amendments to the protocol, Investigators Brochure, Informed Consent

and other key documents.

Appendix Listing

None



17/17




REVISION HISTORY

SOPRevision #

Page (s) Description of change(s) SupersededDocument

New SOP N/A
