Question22: What are general responsibilities of the sponsor in clinical trials according to ICH GCP?
Following are the key responsibilities of the sponsor in in clinical trial according to ICH GCP.
Data Management and Record Keeping:
The sponsor should utilize appropriately qualified individuals to supervise the overall conduct of the trial, to handle the data, to verify the data, to conduct the statistical analyses, and to prepare the trial reports.
When using electronic trial data handling and/or remote electronic trial data systems, the sponsor should:
a. Ensure and document that the electronic data processing system(s) conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistent intended performance (i.e., validation).
b. Maintains SOPs for using these systems.
c. Ensure that the systems are designed to permit data changes in such a way that the data changes are documented and that there is no deletion of entered data (i.e., maintain an audit trail, data trail, edit trail).
d. Maintain a security system that prevents unauthorized access to the data.
e. Maintain a list of the individuals who are authorized to make data changes.
f. Maintain adequate backup of the data.
g. Safeguard the blinding, if any (e.g., maintain the blinding during data entry and processing).
The sponsor-specific essential 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 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period however if required by the applicable regulatory requirement(s) or if needed by the sponsor.
The sponsor should inform the investigator(s)/institution(s) in writing of the need for record retention and should notify the investigator(s)/institution(s) in writing when the trial related records are no longer needed.
The sponsor is responsible for selecting the investigator(s)/institution(s). Each investigator should be qualified by training and experience and should have adequate resources to properly conduct the trial for which the investigator is selected. If organization of a coordinating committee and/or selection of coordinating investigator(s) are to be utilized in multicentre trials, their organization and/or selection are the sponsor’s responsibility.
Before entering an agreement with an investigator/institution to conduct a trial, the sponsor should provide the investigator(s)/institution(s) with the protocol and an up-to-date Investigator’s Brochure, and should provide sufficient time for the investigator/institution to review the protocol and the information provided.
The sponsor should obtain the investigator’s/institution’s agreement:
a. to conduct the trial in compliance with GCP, with the applicable regulatory requirement(s) , and with the protocol agreed to by the sponsor and given approval/favourable opinion by the institutional review board/independent ethics committee (IRB/IEC);
b. to comply with procedures for data recording/reporting;
c. to permit monitoring, auditing and inspection and
d. to retain the trial related essential documents until the sponsor informs the investigator/institution these documents are no longer needed .
Allocation of Duties and Functions
Prior to initiating a trial, the sponsor should define, establish, and allocate all trial-related duties and functions.
Compensation to Subjects and Investigators
If required by the applicable regulatory requirement(s), the sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator/the institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence.
The sponsor’s policies and procedures should address the costs of treatment of trial subjects in the event of trial-related injuries in accordance with the applicable regulatory requirement(s).
When trial subjects receive compensation, the method and manner of compensation should comply with applicable regulatory requirement(s).
The financial aspects of the trial should be documented in an agreement between the sponsor and the investigator/institution.
Notification/ Authority(ies)Submission to Regulatory
Before initiating the clinical trial(s), the sponsor (or the sponsor and the investigator, if required by the applicable regulatory requirement(s)) should submit any required application(s) to the appropriate authority(ies) for review, acceptance, and/or permission (as required by the applicable regulatory requirement(s))to begin the trial(s). Any notification/submission should be dated and contain sufficient information to identify the protocol.
Confirmation of Review by IRB/IEC
The sponsor should obtain from the investigator/institution:
a. The name and address of the investigator’s/institution’s IRB/IEC.
b. A statement obtained from the IRB/IEC that it is organized and operates according to GCP and the applicable laws and regulations.
c. Documented IRB/IEC approval/favourable opinion and, if requested by the sponsor, a current copy of protocol, written informed consent form(s) and any other written information to be provided to subjects, subject recruiting procedures, and documents related to payments and compensation available to the subjects, and any other documents that the IRB/IEC may have requested.
Information on Investigational Product(s)
When planning trials, the sponsor should ensure that sufficient safety and efficacy data from nonclinical studies and/or clinical trials are available to support human exposure by the route, at the dosages, for the duration, and in the trial population to be studied.
Manufacturing, Packaging, Labelling, and Coding Investigational Product(s)
The sponsor should ensure that the investigational product(s) (including active comparator(s) and placebo, if applicable) is characterized as appropriate to the stage of development of the product(s), is manufactured in accordance with any applicable
GMP, and is coded and labelled in a manner that protects the blinding, if applicable. In addition, the labelling should comply with applicable regulatory requirement(s).
The sponsor should determine, for the investigational product(s), acceptable storage temperatures, storage conditions (e.g., protection from light), storage times, reconstitution fluids and procedures, and devices for product infusion, if any. The sponsor should inform all involved parties (e.g., monitors, investigators, pharmacists, storage managers) of these determinations.
The investigational product(s) should be packaged to prevent contamination and unacceptable deterioration during transport and storage.
In blinded trials, the coding system for the investigational product(s) should include a mechanism that permits rapid identification of the product(s) in case of a medical emergency, but does not permit undetectable breaks of the blinding.
If significant formulation changes are made in the investigational or comparator product(s) during the course of clinical development, the results of any additional studies of the formulated product(s) (e.g., stability, dissolution rate, bioavailability) needed to assess whether these changes would significantly alter the pharmacokinetic profile of the product should be available prior to the use of the new formulation in clinical trials.
Supplying and Handling Investigational Product(s)
The sponsor is responsible for supplying the investigator(s)/institution(s) with the investigational product(s).
The sponsor should not supply an investigator/institution with the investigational product(s) until the sponsor obtains all required documentation (e.g., approval/favourable opinion from IRB/IEC and regulatory authority(ies)).
The sponsor should:
a. Ensure timely delivery of investigational product(s) to the investigator(s).
b. Maintain records that document shipment, receipt, disposition, return, and destruction of the investigational product(s).
c. Maintain a system for retrieving investigational products and documenting this retrieval (e.g., for deficient product recall, reclaim after trial completion, expired product reclaim).
d. Maintain a system for the position of unused investigational product(s) and for the documentation of this disposition.
The sponsor should:
a. Take steps to ensure that the investigational product(s) are stable over the period of use.
b. Maintain sufficient quantities of the investigational product(s) used in the trials to reconfirm specifications, should this become necessary, and maintain records of batch sample analyses and characteristics. To the extent stability permits, samples should be retained either until the analyses of the trial data are complete or as required by the applicable regulatory requirement(s), whichever represents the longer retention period.
The sponsor should ensure that it is specified in the protocol or other written agreement that the investigator(s)/institution(s) provide direct access to source data/documents for trial-related monitoring, audits, IRB/IEC review, and regulatory inspection.
The sponsor should promptly notify all concerned investigator(s)/institution(s) and the regulatory authority(ies) of findings that could affect adversely the safety of subjects, impact the conduct of the trial, or alter the IRB/IEC’s approval/favourable opinion to continue the trial.
Selection and Qualifications of Monitors
a. Monitors should be appointed by the sponsor.
b. Monitors should be appropriately trained, and should have the scientific and/or clinical knowledge needed to monitor the trial adequately. A monitor’s qualifications should be documented.
c. Monitors should be thoroughly familiar with the investigational product(s), the protocol, written informed consent form and any other written information to be provided to subjects, the sponsor’s SOPs, GCP, and the applicable regulatory requirement(s).
Extent and Nature of Monitoring
The sponsor should ensure that the trials are adequately monitored. The sponsor should determine the appropriate extent and nature of monitoring. The determination of the extent and nature of monitoring should be based on considerations such as the objective, purpose, design, complexity, blinding, size, and endpoints of the trial. In general there is a need for on-site monitoring, before, during, and after the trial; however in exceptional circumstances the sponsor may determine that central monitoring in conjunction with procedures such as investigators’ training and meetings, and extensive written guidance can assure appropriate conduct of the trial in accordance with GCP
Audits:Sponsor should perform regular audit duringClinical trial.
a. The sponsor should ensure that the auditing of clinical trials/systems is conducted in accordance with the sponsor’s written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports.
b. The sponsor’s audit plan and procedures for a trial audit should be guided by the importance of the trial to submissions to regulatory authorities, the number of subjects in the trial, the type and complexity of the trial, the level of risks to the trial subjects, and any identified problem(s).
c. The observations and findings of the auditor(s) should be documented.
d. To preserve the independence and value of the audit function, the regulatory authority(ies) should not routinely request the audit reports. Regulatory authority(ies) may seek access to an audit report on a case by case basis when evidence of serious GCP non-compliance exists, or in the course of legal proceedings.
e. When required by applicable law or regulation, the sponsor should provide an audit certificate.
Noncompliance with the protocol, SOPs, GCP, and/or applicable regulatory requirement(s) by an investigator/institution, or by member(s) of the sponsor’s staff should lead to prompt action by the sponsor to secure compliance.
If the monitoring and/or auditing identifies serious and/or persistent noncompliance on the part of an investigator/institution, the sponsor should terminate the investigator’s/institution’s participation in the trial. When an investigator’s/institution’s participation is terminated because of noncompliance, the sponsor should notify promptly the regulatory authority(ies).