DCGI issues detailed check-list to ensure quality of informed consent by trial subjects

DCGI issues detailed check-list to ensure quality of informed consent by trial subjects

August 22, 2012, 0800 IST – Source : Pharmabiz News

With a view to further streamline the ‘informed consent’ aspect in the clinical trials, the Drugs Controller General of India (DCGI) has issued detailed format and exhaustive check-lists to ensure the quality of informed consent being taken from the trial subjects.

For the first time, the Central Drugs Standard Control Organization (CDSCO) has prescribed the “essential elements” of informed consent documents used for enrolling subjects to a drug trial. The sponsors were asked to ensure that all subjects, before signing up for the trials, are given detailed information based on these essential elements.

“In all trials, a freely given, informed, written consent is required to be obtained from each study subject. The investigator must provide information about the study verbally as well as using patient information sheet, in a language that is non-technical and understandable by the study subject. The subject’s consent must be obtained in writing using an informed consent form. Both the patient information sheet as well as the informed consent form should have been approved by the ethics committee and furnished to the Licensing Authority. Any changes in the informed consent documents should be approved by the ethics committee and submitted to the licensing authority before changes are implemented,” said the notice by the DCGI.

The essential elements are designed to ensure that subjects are aware of their rights (e.g. for compensation etc.) and clearly understand that they are agreeing to participate in a research of their free will even though alternate treatment options may be available.

Specifically, the CDCSO has outlined 14 essential elements that will have to be incorporated into informed consent documents. These include: a statement that the study involves research and explanation of the purpose of the research; expected duration of the subject’s participation; a description of the procedures to be followed, including all invasive procedures; a description of any reasonably foreseeable risks or discomforts to the subject; a description of any benefits to the subject (if no benefits are expected, the subjected should be made aware of this); information on appropriate alternative procedures or therapies available to the subject; a statement describing the extent to which confidentiality about the subject’s records would be maintained; information on the trial’s treatment schedule and the possibility of random assignment of each treatment (in case of randomised trials); information on compensation and/or treatments available to the subject in the event of a trial-related injury; information on whom to contact for trial-related queries and rights of a subject, especially in case of a trial-related injury; information on the payment, if any, to the subject for participating in the trial; and a statement that participation is voluntary and that the subject can withdraw at any time while clarifying that withdrawal from the trial will not involve any penalty or less of benefits to which the subject is otherwise entitled.

In addition, the CDSCO put six additional elements that may be required for informed consent documents depending on the trial. These include, among other things, a statement that the subject will be notified if significant new findings are highlighted during the course of the research which may affect the subject’s willingness to continue participating in the study.

 

CDSCO notifies draft rules on inspection of clinical trial sites

CDSCO notifies draft rules on inspection of clinical trial sites
August 09, 2012, 0800 IST – Source Pharmabiz News

In a move to further streamline the clinical trials in the country, the Central Drugs Standard Control Organisation (CDSCO) has finalized and issued draft rules regarding the inspection of premises of clinical trial sites by the regulatory officials with or without prior notice.

“The premises of sponsor/clinical research organization and clinical trials shall be open to inspection by the officer of the CDSCO, who may be accompanied by an officer of the concerned state drug control authority to verify compliance to the requirements of Schedule Y, good clinical practices and other applicable regulation,” according to the notification seeking to change the Drugs and Cosmetics Act (D&C Act).

“The sponsor/CRO, investigators shall allow CDSCO officer who may be accompanied by an officer of the concerned State Drug Control Authority to enter, with or without prior notice, any premises of sponsor/CRO and clinical trial site to inspect, search, seize any record, data, document, books, investigational drugs etc. related to clinical trials and provide adequate replies to any queries raised by the inspecting authority in relation to the conduct of the trial,” the document said.

The rules, already approved by the DTAB, will be the third amendment to the Drugs and Cosmetics Rules, 2012 and will be implemented after final notification, the notification said, while seeking inputs and suggestions from the stakeholders.

The rules, to be incorporated in Part X-A after Rule 122 DAB, in detail lays down mandatory procedures for getting permissions, approval of the ethics committee, registration with Clinical Trials Registry-India, reporting of injuries and death, and procedures for submitting replies if notices were issued by the CDSCO on the lapses.

If any company fails to comply with any of the conditions, the licensing authority, may after giving an opportunity, will take proceed to take actions, as required. The can be warning letter on the deficiency found during the inspection, recommendation for rejecting the study, suspension or cancellation of the trial permission and restriction of the investigator/CRO from conducting studies, the draft rules said.

Registration of Ethics Committees becomes mandatory for clinical trials

Registration of Ethics Committees becomes mandatory for clinical trials

August 07, 2012, 0800 IST – Source : Pharmabiz.com

Registration of Ethics Committees attached with the Clinical Trial Organisations (CROs) for conducting clinical trials has been made mandatory in the country by the Drugs Controller General of India (DCGI).

A draft notification, issued by the Central Drugs Standard Control Organisation (CDSCO), said, “No ethics committee shall review and accord its approval to a clinical trial protocol without prior registration of the committee with the licensing authority as defined in clause (b) of rule 21”.

Earlier in October last year, the Drugs Technical Advisory Board (DTAB), the highest decision-making body under the Union health ministry on technical matters, had taken the decision to make registration of Ethics Committees mandatory in the country for clinical trials. The DTAB’s decision came in the wake of widespread complaints that the Ethics Committees at most of the clinical trial sites are not independent and also not active with no monitoring of the trials by the authorities.

So far, only the registration of clinical trials with the drugs controller general of India (DCGI) is mandatory in the country. Independent ethics committees are constituted by the individual companies and its registration is not mandatory. For starting any clinical trial, the approval of the ethics committee is crucial as without which the DCGI will not provide his sanction for beginning the study in the country.

As per the notification, an application for registration of ethics committee shall be made to the licensing authority in accordance with the requirements prescribed in Schedule Y-I. The licensing authority after being satisfied that the requirements of the rules have been complied with and the conditions of the registration will be observed, may grant registration subject to the condition stated therein.

The ethics committee will review and accord its approval to a clinical trial as per Schedule Y, the Good Clinical Practice Guidelines for Clinical Trials in India and other applicable regulatory requirements for safeguarding rights, safety and well being of the trial subjects.

The ethics committee shall allow inspectors/officials of CDSCO to enter the premises of the committee to inspect any record, data, document etc. related to clinical trial and provide adequate replies to any queries raised by the inspecting authority in relation to the conduct of clinical trial. The registration, unless it is sooner suspended or cancelled, shall be valid for a period of five years from the date of issue.

If the licensing authority is not satisfied, he shall reject the application and shall inform the applicant of the reasons for such rejection and the conditions which must be satisfied before the registration can be granted. If the ethics committee fails to comply with any of the conditions of registration, the licensing authority may after giving an opportunity to show cause why such an order should not be passed, by an order in writing stating the reasons therefore, suspended or cancel the registration of the ethics committee for such period considered necessary.

The ethics committee whose registration has been suspended or cancelled by the licensing authority may within ninety days of the receipt of the copy of the order by him prefer an appeal to the central Government and the central Government may, after giving an opportunity of being heard, confirm, reverse or modify such order, the draft notification said.

CDSCO team recommends health ministry to cancel registration of one unit in China

CDSCO team recommends health ministry to cancel registration of one unit in China
June 26, 2012, 0800 IST – Source : Pharmabiz News

The three-member team of the Central Drugs Standard Control Organization (CDSCO), which had audited four manufacturing units in China in February this year, had recommended to the union health ministry to cancel the registration of at least one of these units as it was not found in proper condition.

The three-member delegation, consisting of Dr S Eshwar Reddy, assistant drug controller, CDSCO New Delhi; B Kumar, assistant drugs controller, CDSCO sub-zonal office (Chandigarh) and Dr C Sokhey, senior scientist at National Institute of Biologicals (Noida), inspected a total of four manufacturing units in China, during their visit to China from February 11 to 22 this year. They had inspected three API units and one diagnostics unit.

According to sources, the CDSCO team has submitted its detailed report to the health ministry in which it has recommended to cancel one unit as they have found several anomalies in the unit. However, the official refused to reveal further details.

This is the second time that the Union health ministry has sent its team to China for auditing and inspection of manufacturing units there. As part of its efforts to ensure that only quality products are sourced by Indian companies from abroad, the health ministry had earlier last year started the process of auditing and inspection of manufacturing plants outside India. The first delegation was sent to China in May last year in which the delegation had inspected five manufacturing units there. Though the delegation was to inspect six units, one unit did not allow the delegation to inspect their unit.

The introduction of auditing and inspection of foreign manufacturing facilities by the Indian drug regulators was a long awaited practice, especially in the wake of the fact that even though the government had made registration of imports of drugs and pharmaceuticals into India made mandatory way back in 2003, it failed to bring the desired results as the inflow of inferior raw materials into the country refused to subside.

It was under this background that the ministry earlier last year decided to introduce the practice of inspection of foreign manufacturing facilities.

During the second delegation, the inspections were carried out in China only and the plans to inspect manufacturing plants in Italy has again been deferred. Earlier, the ministry had elaborate plans to start the new practice with one country each in Europe and Asia — Italy in Europe and China in Asia.

 

CDSCO issues guidelines to make activities of zonal, sub-zonal & port offices uniform, transparent

August 09, 2011, 0800 IST – Source : Pharmabiz News

Aiming to make the activities of the subordinate offices working under DCGI uniform, transparent and also to be implemented in rational ways, the Central Drugs Standard Control Organization (CDSCO) has issued guidelines for zonal, sub-zonal and port offices in the country.

These guidelines are intended for the guidance of departmental offices only. It sets out the nature of work that the zonal, sub-zonal and port offices of the CDSCO generally carry out and the guidelines about the policy that should be followed in disposing of the work and duties.

As per the 483-pages long guidelines, the broad functions, activities and duties of the zonal and sub-zonal offices include: to participate in the joint inspection for issuance/revalidation of CoPPs as per WHO certification scheme after receiving the application from the manufacturing firm; to participate in the joint inspection for grant/renewal of blood bank license; to participate in the joint inspection for grant/renewal of license for vaccine/ Sera manufacturing units for both human as well as veterinary; and also to participate in the joint inspection for grant/renewal of license for LVP manufacturing units.

Their functions also include: to participate in the joint inspection for grant/renewal of license for notified Medical Devices and Critical Diagnostics manufacturing units; to participate in the joint inspection for grant/renewal of license for bio-tech and bio-similar products manufacturing units; to participate in the inspection of clinical trial facilities and BA/BE centres as directed by the DCGI from time to time; and to carry out surprise check/raid jointly/independently on the basis of complaint received under whistle blower scheme and also from other sources.

As the zonal/sub-zonal offices deal with various applications, the DCGI has specified the targeted time lines and subsequent actions for disposal of the applications received in the office of zonal/sub-zonal offices.

For grant or renewal of blood bank license, targeted time line should be 21 working days from the date of submission of the application for scrutiny of the documents. In case some deficiencies are observed in the documents, notice of compliance should be forwarded to the applicants within this time frame otherwise tentative inspection date should be proposed to the State Licensing Authority with a copy endorsed to the applicant. On conformation of the date, inspection to be carried out and the application shall be disposed of. For grant or renewal of vaccine manufacturing licenses, targeted time line should be 30 working days, and for grant or renewal of medical devices manufacturing licenses, targeted time line should be 21 working days.

Likewise, for approval of institution for carrying out test on drugs, cosmetics and raw materials as prescribed under Rule 150F of Drugs and also for grant or renewal of LVP manufacturing licenses, targeted time line should be 21 working days.

For grant or renewal of bio-tech/bio-similar products manufacturing licenses and for approval BA/BE studies and clinical trial site, targeted time line should be 30 working days. For grant or revalidation of CoPPs, the targeted time line should be 28 working days and for the issuance of CoPPs for additional products, the targeted time line should be 21 working days.

 

CDSCO issues draft guidelines for approval of clinical trials, new drugs

CDSCO issues draft guidelines for approval of clinical trials, new drugs – Source : Pharmabiz News dt : July 26, 2011, 0800 IST

The Central Drugs Standard Control Organisation (CDSCO) has issued draft guidelines on the approval of clinical trials and new drugs with a view to put in place general requirements for approval of different phases of trials and different categories of new drugs, as the requirements usually vary depending on nature of new drugs.

The draft guidelines, published for the comments from the stakeholders, are expected to help industry to submit the required documents in a ‘more realistic manner which in turn will also help reviewer of CDSCO to review such applications in systematic manner.’ The CDSCO has asked the industry to send in comments by August 24, 2011 in this regard, ahead of finalising the guidelines.

The guidance document also has laid down guidelines for different categories of new drugs like investigational new drugs, new drug substances, additional strength, additional indication, modified release form etc. “It is apparent that this structured application with comprehensive and rational contents will help CDSCO to review and take necessary action in a better way and would ease the preparation of electronic submissions, which may happen in the near future at CDSCO,” according to the document.

“These guidelines apply to approval of clinical trial and approval of manufacture/import for marketing of various categories of new drugs in the form of API and finished formulation which are considered as new drug as per Rule 122E of Drugs and Cosmetics Rules. This guideline describes requirements for approval of clinical trials and new drugs and the procedure for review of technical dossiers of such applications by CDSCO under Rule 122 A, 122B, 122DA, 122DAA, 122E and Schedule-Y of Drugs and Cosmetics Rules,” it said.

“This guideline is based on regulatory requirement for drug approval in India as prescribed under Drugs and Cosmetic Act and Rules made there under and its various amendments. For development of any new drug the applicant is required to obtain license in Form-29 from State Licensing Authority based on NOC obtained from CDSCO. Test batches of new drugs for development and generation of data of any new drug should be manufactured only after obtaining the license in Form-29, it added.

CDSCO draft guidance for industry in reporting serious adverse events in clinical trials

May 21, 2011, 0800 IST – Source : Pharmabiz News

As part of further streamlining the clinical trials sector in the country, the CDSCO has framed guidelines for reporting serious adverse events occurring during the time of trials. The move is intended to bring in uniformity in the process as at present different pharmaceutical companies and contract research organisations are using multiple and different formats and procedures to report serious adverse events.

“Though most reports adhere to Appendix XI of Schedule Y, multiple formats and missing information, including improper referencing for submission of follow-up reports have lead to difficulties in segregation and further processing of these reports by the CDSCO. Hence, this guidance document has been developed to achieve uniformity and completeness of data received by this office with respect to SAE reporting in clinical trials,” according to the draft.

The adverse event has been defined as any untoward medical occurrence (including a symptom/disease or an abnormal laboratory finding) during treatment with a pharmaceutical product in a patient or a human volunteer that does not necessarily have a relationship with the treatment being given.

“An adverse event that is associated with death, in-patient hospitalisation (in case the study was being conducted on out-patients), prolongation of hospitalisation (in case the study was being conducted on in-patients), persistent or significant disability or incapacity, a congenital anomaly or birth defect, or is otherwise life threatening,” the draft said.

All SAEs occurring in clinical trials should be reported as per the details provided in Appendix XI of Schedule Y (Annexure I) within the applicable timeline (14 calendar days), to, the Drugs Controller General (India). Pharmaceutical company/the sponsor/CRO (Investigator in investigator-initiated studies) is responsible for reporting SAEs within the applicable timelines, it said.

“As per the regulations (Schedule Y of Drugs & Cosmetics Rules), all Unexpected SAEs (serious adverse events) have to be reported to CDSCO within 14 calendar days. Every report (both initial as well as follow-up reports) should be submitted along with a covering letter. Unexpected SAEs have to be submitted to this office as per Schedule Y of Drugs and Cosmetics Rules, 1945. The assessment report should clearly mention whether the SAE occurred is related or not related (Situations like unlikely, possibly, suspected, doubtful etc. should not be used),” draft said.