Site Gen-001 01_sop On Site Activities

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 site under 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 a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. 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 17 Confidential

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

Applicable Regulatory Requirement(s) Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products. Approval (in relation to Institutional Review Boards) The affirmative decision of the SITE EC/IRB that the clinical trial has been reviewed and may be conducted at the institution site within the constraints set forth by the SITE EC/IRB, the institution, Good Clinical Practice (GCP), and the applicable regulatory requirements. Audit A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor's standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s). Blinding/Masking A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s). Single-blinding usually refers to the subject(s) being unaware, and doubleblinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(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 required information to be reported to the sponsor on each trial subject. Clinical Trial/Study Any 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 study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study are synonymous. Clinical Trial/Study Report A written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted 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 Structure and 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. Confidentiality Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of a subject's identity.

GEN-001.01

Page 2 of 17 Confidential

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

Contract A written, dated, and signed agreement between two or more involved parties that sets out any 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 Access Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsor's monitors and auditors) with direct access should take all reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of subjects' identities and sponsor’s proprietary information. Documentation All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records, and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken. Essential Documents Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced (see 7. Essential Documents for the Conduct of a Clinical 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 are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected. Independent Ethics Committee (IEC) An independent body (a review board or a committee, institutional, regional, national, or supranational), constituted of medical professionals and non-medical members, whose responsibility it is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial and to provide public assurance of that protection, by, among other things, reviewing and approving / providing favourable opinion on, the trial protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial subjects. The legal status, composition, function, operations and regulatory requirements pertaining to Independent Ethics Committees may differ among countries, but should allow the Independent Ethics Committee to act in agreement with GCP as described in this guideline. 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 trial 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. Inspection The 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 be related to the clinical trial and that may be located at the site of the trial, at the sponsor's GEN-001.01

Page 3 of 17 Confidential

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

and/or contract research organization’s (CRO’s) facilities, or at other establishments deemed appropriate by the regulatory authority(ies). Institution (medical) Any public or private entity or agency or medical or dental facility where clinical trials are conducted. Institutional Review Board (SITE EC) An independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human subjects 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 be used 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 reference in 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 an unapproved indication, or when used to gain further information about an approved use. Investigator A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a 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 Brochure A compilation of the clinical and nonclinical data on the investigational product(s) which is relevant to the study of the investigational product(s) in human subjects (see 7. Investigator’s Brochure). Monitoring The 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 Report A written report from the monitor to the sponsor after each site visit and/or other trial-related communication according to the sponsor’s SOPs. Multicentre Trial A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator. Nonclinical Study Biomedical studies not performed on human subjects. Protocol A 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 GEN-001.01

Page 4 of 17 Confidential

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

the trial, but these could be provided in other protocol referenced documents. Throughout the ICH GCP Guideline the term protocol refers to protocol and protocol amendments. Protocol Amendment A 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 is performed and the data are generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and the applicable regulatory requirement(s). Quality Control (QC) The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled. Randomization The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias. Regulatory Authorities Bodies having the power to regulate. In the ICH GCP guideline the expression Regulatory Authorities includes the authorities that review submitted clinical data and those that conduct inspections (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 for Expedited Reporting). Source Data All 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 and evaluation of the trial. Source data are contained in source documents (original records or certified copies). Source Documents Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, 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, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories and at medico-technical departments involved in the clinical trial). GEN-001.01

Page 5 of 17 Confidential

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

Sponsor An individual, company, institution, or organization which takes responsibility for the initiation, 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. Subinvestigator Any individual member of the clinical trial team designated and supervised by the investigator 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 Subject An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control. Subject Identification Code A unique identifier assigned by the investigator to each trial subject to protect the subject's identity and used in lieu of the subject's name when the investigator reports adverse events and/or other trial related data. Trial Site The location(s) where trial-related activities are actually conducted. Unexpected Adverse Drug Reaction An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). Vulnerable Subjects Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory 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 of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent. Well-being (of the trial subjects) The physical and mental integrity of the subjects participating in a clinical trial.

GEN-001.01

Page 6 of 17 Confidential

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

RELATED SOPs AND OTHER DOCUMENTS ICH GCP Indian GCP Schedule Y of Drug & Cosmetic Act 1940 PROCEDURES

1. Role & Responsibilities Step 1.1

1.2

Action Responsibility and accountability for clinical trials will be allocated among members of the Dr. ABC XYZ site team. This includes the administrative accountability as well as general responsibilities of the site team and of individual team members for fulfilling regulatory and clinical requirements. Responsibilities 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 investigator’s brochure, the informed consent, and the protocol 3. Informing all participants, including participants used as controls, that the investigational agents are being used for investigational purposes and following 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 to participants. 8. Appropriate control, inventory, distribution, storage, record keeping and destruction or return of all clinical supplies including the Investigational

GEN-001.01

Page 7 of 17 Confidential

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

Product Prompt reporting of all the Serious Adverse Events to site EC. Providing progress reports to the Site EC as per site EC SOP. 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 member of the research team that may present a conflict with the interests of participants in the study. 13. While retaining knowledge of and overall authority for the conduct of all research studies, supervise members of the research team qualified by appropriate education and experience to accept responsibility for study-related activities not directly performed by the PI. Assuring that delegation of responsibilities is appropriate and is documented and that individuals recruited as members of the research team are appropriately licensed and trained. 14. Maintaining adequate and accurate records and making records available for inspection 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 the study. The PI must sign the form that delegates responsibilities to each member of the research team. Each individual’s name must be initialed and dated. The form must be updated, initialed and dated, each time there is a personnel change. Responsibilities 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 the requirements 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 that provisions on publication, intellectual property, indemnification, records retention, and data ownership are appropriately negotiated with the sponsor. 12. Design appropriate recruitment strategies and track study enrollment. 9. 10. 12.

1.3

GEN-001.01

Page 8 of 17 Confidential

STANDARD OPERATING PROCEDURE: Dr XXXXX Site

Title: Standard operating procedure of site activities SOP No.: GEN-01

13. 14

Version No.: 01

Effective Date: dd-mmm-yyyy

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

Further to above listed responsibilities medically qualified personnel will also be responsible 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 2.1

2.2 2.3 2.4 2.5 2.6

2.7 2.8

2.9

Action Principal Investigator- The Principal Investigator is responsible and accountable for the distribution, storage, and inventory of the investigational drug involved in the approved clinical study. The PI may delegate responsibility for the investigational drug to another qualified researcher involved in the study, but may not delegate accountability. Upon receipt of the study drug, the shipment will be inventoried, verifying that the receipt date, lot number, drug type, batch number and quantity on the packing slips is the same as what was actually received; Promptly bring any discrepancies to the attention of the Sponsor/supplier of the drug. Retain a copy of the shipping inventory, packing slips and document inventory in the study files; The drug will be stored in a secure environment according to requirements listed in the protocol or the investigator’s brochure. The temperature of the storage area will be recorded daily, or an alarm system maintained so research personnel will be notified if the temperature exceeds the parameters specified for the agent. Access to the storage area will be limited to essential research personnel. The expiration date of the drug will be noted, and the drug will be returned, disposed of, or destroyed in accordance with the approved protocol when the drug expires. The site team member designated by the PI to distribute the drug to the participant must 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 of taking the study drug, the site team member must make sure the participant understands how to fulfill the responsibility. Each time the study drug is distributed to a participant at the study site, it will be appropriately recorded. Documentation will include at least the following: • Name of individual distributing the agent, • Participant’s study ID and/or initials • Amount distributed (and lot number, if appropriate), • Date of distribution (and time, if appropriate)

GEN-001.01

Page 9 of 17 Confidential

STANDARD OPERATING PROCEDURE: Dr XXXXX Site

Title: Standard operating procedure of site activities SOP No.: GEN-01 2.10 2.11

2.12 2.13 2.14

2.15

Version No.: 01

Effective Date: dd-mmm-yyyy

Drug accountability documentation will be completed on arrival of supplies, each time drugs are distributed, and when drugs are returned to the sponsor or destroyed. Compliance by the participant with the procedures described in the protocol will be verified. Discrepancies between amounts of the drug or agent used by participants and amounts returned and the reasons underlying any discrepancies will be documented. If the participant has not taken the drug or agent as required by the protocol, the PI should determine whether the participant will remain in the study or be withdrawn. When all participants have completed the study medication, the records will be checked for accuracy and will be signed and dated. 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, in accordance with the institution’s biohazard policies. At the conclusion of the study, the study drug should be inventoried and prepared to be returned to the sponsor or to be destroyed in accordance with the requirements of the sponsor or the manufacturer or the state board of pharmacy. All documentation regarding receipt, storage, dispensing, and return of used containers must be complete and accurate. A copy of all accountability documents will be maintained in the regulatory files.

3. Recruitment of study subjects Step 3.1

3.2

3.3

3.4

3.5

Action Recruitment strategies : Participants will be recruited from a variety of sources including clinician referrals, internet postings, newspaper advertisements, television/radio advertisements, from support groups, health fairs, or from local hospitals and clinics. Clinicians will be notified about research studies by letter or by word of mouth. Recruitment Materials : Materials directed to patients or the general public with the intent of recruiting them to participate in clinical research must be submitted to the SITE EC for review and approval. These include announcements, advertisements, flyers, phone scripts for screening, oral scripts for consenting participants, newspaper ads, videos, radio and television announcements, bulletin board tear-offs, Internet postings, and posters. Enrolment Procedures Recruitment rates will be regularly evaluated during the recruitment period, with reassessment of the strategy when recruitment targets are not being met. When there is competitive enrolment, recruitment must be continually reassessed to manage screening of participants. The Clinical Research Coordinator/Nurse will keep records of recruitment and will inform the Dr. ABC XYZ and the monitor of progress in recruiting patients. Every person who is considered a potential candidate for the study should be entered in the Screening and Enrolment Log (based on study inclusion and exclusion criteria). Note whether individuals have enrolled in the study and, if not, document the reason. At the screening visit, the potential participant must give informed consent prior to any screening procedures. Signed informed consent forms from subjects who terminated their participation in the study during the screening process will be retained.

GEN-001.01

Page 10 of 17 Confidential

STANDARD OPERATING PROCEDURE: Dr XXXXX Site

Title: Standard operating procedure of site activities SOP No.: GEN-01 3.6

Version No.: 01

Effective Date: dd-mmm-yyyy

After screening and/or randomization, the participant’s code/ID number will be entered in the Screening and Enrolment Log. The Enrolment Log can serve as the coded subject list, which must be archived at the end of the study. If there is no Screening and Enrolment Log included in the study, a master log must be kept of all subjects randomized in the trial, with subject name, address, year of birth, and treatment allocation or treatment package number.

4. Informed Consent Step 4.1

4.2

Action Obtaining Informed Consent A completed Informed Consent Document will be obtained from every participant who takes part in a study prior to performing any study-related activities, including screening laboratories, vital signs, or questionnaires. On occasion, a separate screening consent, approved by the SITE EC, may be used to document consent for screening procedures only. When a potential protocol candidate will be identified, the investigator or research coordinator 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 be discussed. The subject will be given a copy of the informed consent document to read in a quiet environment without distraction. The subject will be encouraged to take the consent form home so that he or she may discuss it with family members. All questions and concerns will be addressed throughout this process by the consenter and/or PI. If a person decides to participate, he/she will be asked to sign the informed consent document. Only after all questions and concerns have been addressed and the consenter is satisfied 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 patient’s research chart (i.e., source documents) or in the patient’s 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 subject’s source documents (see Documentation Section below). Revised Informed Consent Forms & Re-consenting

GEN-001.01

Page 11 of 17 Confidential

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

If, during the course of the trial, the protocol has been modified in such a way that changes are made to the Informed Consent, participants who have already given their informed consent may be required by the SITE EC to be re-consented using the updated form with the changes bolded. All participants currently enrolled in the study must sign the bolded copy of the updated informed consent form to acknowledge the changes. The participant may be re-consented at the next patient contact unless otherwise stated by the SITE EC or study sponsor. For potential participants who are not yet enrolled in the study, the revised Informed Consent replaces all previous versions for the Informed Consent and is used in its clean format. Informed Consent is obtained as described above. 4.3

4.4

4.5

Obtaining Informed consent from participant who can not read If an investigator wishes to include a subject who is illiterate or cannot read, the informed consent document will be read to the subject in the presence of an impartial witness. Whenever possible, accommodations should be made to permit subjects to read the consent form if possible; e.g., large type for individuals with visual impairments, rather than relying on verbal consent routinely. The information presented to the subject must include all of the required elements of consent 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 sign the consent form. The person who is illiterate will also sign her/his mark on the signature line. When a study is expected to include illiterate subjects, the investigator will describe during initial review how the consent process is to be carried out and will submit a “short form” for approval. Obtaining 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 approved protocol. The SITE EC may require the assent of the child. The SITE EC approved protocol will specify whether assent is required, and when it is required, whether assent may be verbal 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 is appropriate to the child's age, experience, maturity, and condition. This explanation should include a discussion of any discomforts and inconveniences the child may experience if he or she agrees to participate. If the parents consent but the child does not wish to participate, then researcher must respect 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 be present during the informed consent process. Individuals who are “mature minors” or “emancipated minors” under the law of the state may be able to give informed consent. If a participant is a mature minor or emancipated minor, the researcher should contact the SITE EC before allowing the minor to give informed consent for participating in the study. Documentation of Informed consent process

GEN-001.01

Page 12 of 17 Confidential

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

The PI/ medical study coordinator will maintain documentation of the decision to delegate the responsibility for informed consent, including the qualifications of the individual(s) selected. This will be done via a Delegation of Duties Form which is filed in the regulatory files. This documentation shall be made available for auditing/monitoring. The original SITE EC approval letter and the stamped copies of the consent form will be maintained in the regulatory file and copies forwarded to the sponsor. (See Regulatory Preparation Section of this Manual) The site team member obtaining informed consent will note in the source documents the 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 than above) 3. The actual date and clock time Informed Consent was obtained 4. Individual(s) present when Informed Consent was obtained 5. Name of staff, if any, who witnessed Informed Consent 6. Name of individual who signed the Informed Consent document 5. Adverse Event Reporting Step 5.1

5.2 5.3

Action The participant will be assessed at each visit, or study assessment, for AEs that may have occurred since the previous visit or assessment, insuring that the following are 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 A toxicity grade will be assigned using the grading scale described in the protocol (if present). All appropriate resources will be directed toward insuring the participant’s safety and well-being.

GEN-001.01

Page 13 of 17 Confidential

STANDARD OPERATING PROCEDURE: Dr XXXXX Site

Title: Standard operating procedure of site activities SOP No.: GEN-01 5.4

5.5 5.6 5.7 5.8 5.9 5.10

Version No.: 01

Effective Date: dd-mmm-yyyy

If necessary for the immediate medical care of the participant, the Principal Investigator may elect to break the drug blind after consultation with the sponsor. Therapeutic intervention measures will be taken as outlined in the protocol. The subject should have clinical assessments (frequency to be determined by the primary investigator unless dictated by protocol) until the AE has stabilized or resolved. If the adverse event is serious and unexpected, the sponsor should be informed as soon as possible after the occurrence of the event becomes known to study staff and when the participant has stabilized (whether the AE is considered drug-related or not) so that the sponsor can fulfil its reporting obligations to the FDA. The sponsor should be updated as information on the AE becomes available. If applicable, the form 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 If the AE results in the subject’s death an autopsy report or death certificate will be obtained, if required by the protocol. Source documentation must be completed, as appropriate. The appropriate case report form must be completed for collection of adverse event information, and copies of all reports should be maintained in the participant’s file and the regulatory files All SAEs should be reported to the SITE EC as per the Site EC SOP. The IND Safety Report should be submitted to the SITE EC within ten (10) days of receipt of the report from the sponsor or within 24 hours of the onset of the event or the site’s having been made aware of the event. If further action is required by the SITE EC, the sponsor should be informed. A summary of all adverse events (both serious and non-serious) will be reported to the SITE EC as part of continuing review.

6 Source Documentation

GEN-001.01

Page 14 of 17 Confidential

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

Step

Action

6.1

The SITE EC approved protocol describes the information to be obtained from each participant during screening and study visits. This information will be obtained by a variety of means including interviewing, assessment procedures and performance of study-specific diagnostic and laboratory tests. These various processes/procedures must be performed according to Professional Standards of Practice, applicable regulatory requirements, and GCP (Good Clinical Practice). Original documentation, containing the subject’s health information and medical test results, must be retained in the subject’s medical/study record. This information may include the clinical medical report, laboratory results, laboratory notes, copies of hospital charts, primary physician or other related consultations, communication between study team, subject diaries, questionnaires, check lists, photographs, negatives, drug records, X-rays, EKGs and electronic data. Documentation should also note if a procedure was not performed and should be accompanied by an appropriate explanation e.g. subject refused, subject had to leave before test could be performed. At the start of the study, the collection of source documentation begins once each participant has signed the approved informed consent form. This file will be updated at each subsequent visit. Documentation, outlining any issues associated with a specific participant’s involvement in the research study, should be updated as necessary at each subsequent study visit with any new medical conditions or with any past medical history that becomes known to the research team. The original study documentation must be completed, signed and dated by the researcher who obtained the data. Source documentation will be completed and filed at the end of study visit. All source documentation must be in compliance with sponsor/CRO specified recommendations. Case Report Forms and source data are maintained separately, but source documents should accompany the case report form for sponsor verification.

6.2

6.3

6.4 6.5 6.6

7 Essential Documents Step

Action

7.1

A regulatory file labelled with sponsor name, investigator name, protocol number and title will be prepared for each clinical trial prior to enrolling subjects or collecting any data. 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. CV’s should be updated at least every 2 years, or more often if the Sponsor requires • Current licenses of all key study personnel • The current Protocol signed and dated by the PI

7.2

GEN-001.01

Page 15 of 17 Confidential

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

•

7.3

Investigator’s 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, including copies of SAE notifications, faxes, emails, newsletters, meeting notes, memos to file The regulatory file will be maintained and updated as necessary, adding appropriate documents as they are generated or received. The regulatory files will 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, Investigator’s Brochure, Informed Consent and other key documents.

Appendix Listing None

GEN-001.01

Page 16 of 17 Confidential

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

REVISION HISTORY SOP Revision # New SOP

Page (s)

Description of change(s)

Superseded Document

N/A

GEN-001.01

Page 17 of 17 Confidential