Rules for Clinical Research Organisation

6058 GI/202 4 (1) रजिस्ट्री सं. डी.एल.- 33004/99 REGD. No . D. L. -33004/99 EXTRAORDINARY PART II —Section 3 —Sub-section ( i) PUBLISHED BY AUTHORITY No. 539] NEW D ELHI, THURSDAY , SEPTEMBER 19, 2024/BHADRA 28, 1946 CG-DL-E-23092024-257393 - 5. --------------------------------------- रुपये रसीि या चालान या लेनिेन आईडी ----------------------------------------- तारीख : जडजिटल हस्ट्तािर तारीख :----------------- मुहर " MINISTRY OF HEALTH AND FAMILY WELFARE (Department of Health and Family Welfare) NOTIFICATION New Delhi, the 19th September, 202 4 G.S.R. 581(E).— Whereas a draft of certain rules further to amend the New Drugs and Clinical Trials Rules, 2019, was published, as required under sections 12 and 33 of the Drugs and Cosmetics Act, 1940 (23 of 1940) vide notification of the Government of India in the Ministry of Health and Family Welfare (Department of Health and Family Welfare) number G.S.R. 364 (E), dated the 11th May, 2023, in the Gazette of India, Extraordinary, Part II, section 3, sub -section (i), inviting objections and suggestions from persons likely to be affected thereby, before the expiry of a period of fifteen days from the date on which the copies of the Official Gazette containing the said notification were made available to the public; And whereas, copies of the said Official Gazette were made available to the public on the 11th May, 2023; And whereas, objections and suggestions received from the public on the said rules have been considered by the Central Government; Now, therefore, in exercise of the powers conferred by sections 12 and 33 of the Drugs and Cosmetics Act, 1940 (23 of 1940), the Central Government, after consultation with the Drugs Technical Advisory Board, hereby makes the following rules further to amend the New Drugs and Clinical Trials Rules, 2019, namely: - 1. (1) These rules may be called the New Drugs and Clinical Trials (Amendment) Rules, 2024 . (2) They shall come into force on and from the 1st day of April, 2025. 2. In the New Drugs and Clinical Trials Rules, 2019 (h ereinafter referred to as the principal rules), in rule 2, in sub-rule (1), after clause (i), the following clause shall be inserted, namely: - ‘(ia) “Clinical Research Organisation” means the sponsor or a body, commercial or academic or of other category, owned by an individual or an organisation having status of legal entity by whatsoever name called, to which the sponsor may, delegate or transfer in writing, some or all of the tasks, duties or obligations regarding clinical trial or bioavailability or bioequivalence study;'. 3. In the principal rules, after Chapter V, the following Chapter shall be inserted, namely: - “CHAPTER VA CLINICAL RESEARCH ORGANISATION 38A. Registration of Clinical Research Organisation. - Without prejudice to anything contained in any other provisions of these rules, no Clinical Research Organisation shall conduct any clinical trial or bioavailability or bioequivalence study of new drug or investigational new drug in human subjects without registration granted by the Central Licencing Authority under these rules. 38B. Application for Registration of Clinical Research Organisation. - (1) The Clinical Research Organisation shall make an application in Form CT -07B to the Central Licencing Authority for the purpose of registration for conducting clinical trial or bioavailability or bioequivalence study. Provided that any bioavailability or bioequivalence study centre already registered under rule 44, shall be deemed to be registered under this Chapter for the purposes of bioavailability or bioequivalence study. (2) The application for registration shall be accompanied by a fee as specified in the Sixth Schedule alongwith such documents and other information as specified in the Ninth Schedule. 38C. Grant of registration to Clinical Research Organisation. - (1) The Central Licencing Authority may, after scrutiny of the information and requirements furnished with the application under rule 38B and such further enquiry, if any, as may be considered necessary, – (i) if satisfied, that the requirements of these rules have been complied with, grant registration to the applicant in Form CT -07C within a period of forty -five working days from the date of receipt of the application; or (ii) if not satisfied, reject the application, for reasons to be recorded in writing, within a period of forty -five working days reckoned from the date of the receipt of the application ; or (iii) If satisfied, that any deficiency in the application is required to be rectified, it shall inform the applicant of the deficiency not later than forty -five working days from the date of receipt of the application, to rectify the deficiencies within such period as may be specified by it: Provided that where the applicant rectifies the deficiency within the period so specified, the Central Licencing Authority, shall if satisfied, grant registration to the applicant or if not satisfied, reject the application within a period of ninety days reckoned from date of the receipt of the rectification. (2) In case of rejection of application under sub -rule (1), the applicant may request the Central Licencing Authority to reconsider the application within a period of sixty days from the date of rejection of the application on payment of fee as specified in the Sixth Schedule and submission of required information and documents. (3) Any applicant aggrieved by the decision of the Central Licencing Authority under sub -rule (1) or sub -rule (2), may file an appeal within forty -five days from the date of such decision, before the Central Government and Government may, after such enquiry and after giving an opportunity of being heard to the appellant, dispose of the appeal within a period of sixty days from the date of receipt of the appeal. 38D. Validity period and renewal of registration of Clinical Research Organisation. - (1) The registration granted under rule 38C shall remain valid for a period of five years from the date of its grant, unless suspended or cancelled by the Central Licencing Authority. (2) An application for renewal of registration shall be made in Form CT -07B to the Central Licencing Authority along with documents as specified in the Ninth Schedule prior to date of expiry of its registration: Provided that if the application for renewal of registration is received by the Central Licencing Authority prior to the date of expiry, the registration shall continue to be in force until the orders are passed by the Central Licencing Authority on the application. (3) The Central Licencing Authority shall, after scrutiny of information enclosed with the application and such further enquiry, if any, as may be considered necessary, if satisfied, shall renew the registration in Form CT -07C and in case of rejection or rectification of deficiency, if any, the procedure as specified in rule 38C shall apply. 38E. Inspection of Clinical Research Organisation registered with Central Licencing Authority. - The Clinical Research Organisation registered by the Central Licencing Authority under rule 38C, shall allow any officer authorised by the Central Licencing Authority, who may be accompanied by an officer authorised by the State Licencing Authority, to enter the premises of the Clinical Research Organisation with or without prior consent, to inspect, search or seize, any record, document, investigational product and other related material and reply to queries raised by the inspecting authority in relation to functioning of the Organisation. 38F. Suspension or cancellation of registration of Clinical Research Organisation - (1) Where any Clinical Research Organisation fails to comply with any provision of the Act and these rules, the Central Licencing Authority may, after giving an opportunity to show cause and after affording an opportunity of being heard, by an order in writing, take one or more of the following actions, namely: - (a) withdraw show cause notice issued under sub -rule (1); (b) issue warning in writing to the Clinical Research Organisation describing the deficiency or defect observed during inspection or otherwise, which may affect adversely the right or well -being of trial subject or the validity of any study conducted; (c) reject the results of the clinical trial or the bioavailability or bioequivalence study; (d) suspend for such period as considered appropriate or cancel the registration granted under rule 38C; (e) debar the organisation to conduct any clinical trial study or bioavailability or bioequivalence study in future for such period as considered appropriate by the Central Licencing Authority. (2) Any Clinical Research Organisation aggrieved by the order of the Central Licencing Authority under sub -rule (1), may within a period of sixty days from the date of the receipt of the order, make an appeal to the Central Government and the Central Government may, after such enquiry, as deemed necessary and after affording an opportunity of being heard, pass such orders in relation thereto as may be considered appropriate in the facts and circumstances of the case.” 4. In the principal rules, in the Sixth Schedule, ― (i) in the heading, after the figures ‛’34’’, the figures and letters “38B”, “38C” shall be inserted; (ii) in the table, after serial number 4 and entries relating thereto, the following shall be inserted, namely: - “4A 38B Application for registration of Clinical Research Organisation 5,00,000 4B 38C Reconsideration of application for registration of Clinical Research Organisation 1,00,000” 5. In the principal rules, in the Eighth Schedule, after Form CT -07A, the following Forms shall be inserted, namely: - “FORM CT-07B [See rules 38B (1) and 38D (2)] APPLICATION FOR REGISTRATION / RENEWAL OF CLINICAL RESEARCH ORGANISATION I/We, ..................................................................................................................... (name, designation and full postal address of the applicant) of ................................................. hereby apply for grant of registration of my/Our Clinical Research Organisation. The details of the application are as under: 1. Name of the Applicant: 2. Nature and constitution of applicant: (proprietorship, partnership including limited liability partnership, company, society, trust, other to be specified) 3.(i) Applicant's address including telephone number, mobile number, fax number and e - mail id: (ii) Address for correspondence: [corporate or registered office of the Clinical Research Organization ] 4. Details of accreditation, if any, (self -attested copy of certificate to be attached): 5. Fee paid on ----------------------------------------- Rs. --------------------------------------- Receipt or challan or transaction ID ---------------------------------- . 6. I have enclosed the documents as specified in the Table 1 of Ninth Schedule of the New Drugs and Clinical Trials Rules, 2019 . 7. I hereby state and undertake that: (i) I shall comply with the conditions imposed on the registration certificate along with the adherence to other guidelines like Good Clinical Practices guidelines and provisions of the Drugs and Cosmetics Act, 1940, and the New Drugs and Clinical Trials Rules, 2019. (ii) I shall comply with such further requirements, if any, as may be specified by the Government of India, under the Act and the Rules made thereunder. (iii) I shall allow the Central Licencing Authority and/or any person authorised by him in that behalf to enter and inspect the premises and to examine the process/procedure and documents in respect of any clinical trial conducted by us . Place: Digital Signature Date (Name and designation) FORM CT - 07C [See rules 38C and 38D (3)] GRANT OR RENEWAL OF REGISTRATION OF CLINICAL RESEARCH ORGANISATION Registration No. ------------------------- The Central Licencing Authority hereby registers (Name and full address with contact details of the applicant) for conduct of clinical trial or bioavailability or bioequivalence study of new drugs and investigational new drugs under the New Drugs and Clinical Trials Rules, 2019. Place: …………. Central Licencing Authority Date: ................. Stamp” Conditions of registration : The registration granted under rule 38C or renewal granted under rule 38D shall be subject to the conditions specified in rule 25, rule 35 and the requirements specified in the Ninth Schedule including the following conditions: - (i) the organisation shall maintain the facilities and adequately qualified and trained personnel as specified in the Ninth Schedule for performing its functions; (ii) the organisation shall initiate conduct of any clinical trial or bioavailability or bioequivalence study of any new drug or investigational new drug in human subjects after approval of the protocol and other related documents by the Ethics Committee for clinical trial or bioavailability or bioequivalence study, as the case may be, and permission of such study granted by the Central Licencing Authority; (iii) where a clinical trial site or bioavailability or bioequivalence centre does not have its own Ethics Committee, the study at that site or centre may be initiated after obtaining approval of the protocol from another Ethics Committee of another trial site or an independent Ethics Committee for clinical trial or bioavailability or bioequivalence study registered under rule 8: Provided that the approving Ethics Committee shall be responsible for the study at the trial site or centre, as the case may be, and both the approving Ethics Committee and the trial site or the centre are located within the same city or within a radius of fifty kilometer of the trial site or the centre. (iv) the Central Licencing Authority shall be informed about the approval of the Ethics Committee for clinical trial or bioavailability or bioequivalence study; (v) clinical trial of new drug or investigational new drug shall be registered with the Clinical Trial Registry of India before enrolling the first subject for the study; (vi) bioavailability or bioequivalence study of investigational new drug shall be registered with the Clinical Trial Registry of India before enrolling the first subject for the study (vii) study shall be conducted in accordance with the approved protocol and other related documents and as per requirements of Good Clinical Practices Guidelines and provisions of the Act and these rules; (viii) in case of termination of any such study prematurely, the detailed reasons for such termination shall be communicated to the Central Licencing Authority immediately; (ix) any report of serious adverse event occurring during study to the subject of such study shall, after due analysis, be forwarded to Central Licencing Authority within fourteen days of its occurrence in the format as specified in Table 5 of the Third Schedule and in compliance with the procedures as specified in rule 42; (x) in case of an injury to the study subject during study, the complete medical management and compensation in the case of study related injury shall be provided in accordance with the provisions of Chapter VI and details of compensation paid to the trial subject in such cases shall be intimated to the Central Licencing Authority within thirty days of receipt of the order; (xi) in case of death, permanent disability, injury other than death and permanent disability, as the case may be, of a study subject, compensation shall be provided in accordance with the provisions of Chapter VI and details of compensation paid to the trial subject or his legal heir, as the case may be, in such cases shall be intimated to the Central Licencing Authority within thirty days of receipt of the order; (xii) if there is any change in constitution or ownership of the Clinical Research Organisation, the organisation shall intimate about the change in writing to the Central Licencing Authority within thirty days of such change; (xiii) the clinical research organisation shall maintain data, records, and other documents related to the conduct of the clinical trials for a period of five years after completion of such study or for at least two years after the expiration date of the batch of the new drug or investigational new drug studied, whichever is later; (xiv) the Clinical Research Organisation shall allow any officer authorised by the Central Licencing Authority who may be accompanied by an officer authorised by State Licencing Authority to enter the premises with or without prior notice, to inspect any record, statistical observation or results or any documents related to clinical trials and furnish information to the queries raised by such authorised person, in relation to the conduct of the said study; (xv) the Central Licencing Authority may, if considered necessary, impose additional condition, in writing with justification, in respect of specific clinical trials regarding the objective, design, subject population, subject eligibility, assessments, conduct and treatment of such specific study”. 6. In the principal rules, after the Eighth Schedule, following Schedule shall be inserted, namely: - “NINTH SCHEDULE (See rules 38B, 38C, 38D and 38E) REQUIREMENTS FOR REGISTRATION OF CLINICAL RESEARCH ORGANISATION 1. The applicant shall comply with the following requirements for the purpose of registration of a Clinical Research Organisation, namely: - (i) the Clinical Research Organisation shall be under the charge of a person who is responsible for the overall activities of the organisation and shall have competent persons who are thoroughly familiar with the investigational products, the protocol, written informed consent forms or other information provided to the subjects, the standard operating procedures by the sponsors, good clinical practices guidelines and other rules applicable to the conduct of clinical trial and or bioavailability or bioequivalence study; (ii) the Clinical Research Organisation shall have adequate facilities, resources, qualified and trained staff for handling any oversight of clinical trials and bioavailability or bioequivalence studies and such staff shall be trained regularly to update their skills; (iii) the trial or study related duties and functions transferred to and assumed by the Clinical Research Organisation shall be specified in writing and properly quantified; (iv) the Clinical Research Organisation shall ensure that the trials and bioavailability or bioequivalence studies are adequately monitored and the trial or study related responsibilities transferred to it, partially or fully, by the sponsor are discharged effectively and efficiently; (v) the Clinical Research Organisation shall implement quality assurance and quality control as per standard operating procedures designed for the purpose and such standard operating procedures shall be well documented; (vi) the Clinical Research Organisation shall maintain complete data, documentations and other related records accurately including checking and ensuring that the essential documents required for the conduct of the trial are maintained properly by the investigators; (vii) the Clinical Research Organisation shall ensure that the investigators receive all documents and trial or study related supplies needed to conduct the clinical trial or bioavailability or bioequivalence study properly; (viii) the Clinical Research Organisation shall have education programmes to help its investigators carry out the research studies as per the guidelines and regulations applicable to such trials and studies including imparting trainings as to protocol adherence, good clinical practices guidelines, informed consent process, and investigators responsibilities for good clinical practices compliance; (ix) all records (written documents, electronic, magnetic or optical records, scans, etc.), such as protocols, approvals from the Central Licencing Authority and Ethics committee, investigators particulars, blank consent forms, monitor reports, audit certificates, relevant correspondence, reference pages, completed and the final reports shall be maintained; (x) all documentation and communication shall be dated, filed and preserved safely for a period of five years after completion of such study or for at least two years after the expiration date of the batch of the new drug or investigational new drug studied, whichever is later; (xi) strict confidentiality shall be maintained during access and retrieval procedures; (xii) if there is any change in the constitution or ownership of the Clinical Research Organisation, the organisation shall intimate about the change in writing to the Central Licencing Authority within thirty days of such change. 2. The following particulars and documents shall be required for the purpose of registration of a Clinical Research Organisation, namely: - (i) name and address of the organisation to be registered along with its telephone number, fax number and email address; (ii) name and address of the proprietors or partners or directors; (iii) status of the organisation as legal entity; (iv) a brief profile of the specific activities or services undertaken by the organisation including facilities, resources and infrastructure; (v) an organogram of the organisation including brief Curriculum Vitae of key personnel; (vi) list of Standard Operating Procedures with salient highlights about specific areas to be scrutinised; (vii) details of accreditation or approval of other regulatory agencies, if any, (self -attested copy of certificate); (viii) copy of agreement with third party service providers for site management, translation, biostatistics, data management, laboratory services etc; (ix) an undertaking to declare that, - (a) we shall comply with the conditions imposed on the registration certificate along with the adherence to other guidelines like Good Clinical Practices guidelines and provisions of the Drugs and Cosmetics Act, 1940 (23 of 1940), and the New Drugs and Clinical Trials Rules, 2019; (b) we shall comply with such further requirements, if any, as may be specified by the Government of India, under the Act and the rules made thereunder; (c) we shall allow the Central Licencing Authority or any person authorised by him in that behalf to enter and inspect the premises and to examine the process or procedure and documents in respect of any clinical trial conducted by us. [F. No. X -11014/23/2021 -DR] RAJIV WADHAWAN, Adviser (Cost). Note: The principal rules were published in the Gazette of India vide notification number G.S.R.227(E), dated the 19th March, 2019 and subsequently amended vide notification numbers G.S.R. 605 (E), dated 31st August, 2021, G.S.R. 14 (E), dated 13th January, 2022, G.S.R. 21 (E), dated 18th January, 2022, G.S.R. 778 (E), dated 14th October, 2022 and G.S.R. 175 (E), dated 9th March, 2023. Uploaded by Dte. of Printing at Government of India Press, Ring R oad, Mayapuri, New Delhi -110064 and Published by the Controller of Publications, Delhi -110054.