Current Regulatory Requirements For Conducting Clinical Trials In India For IND/New Drug (Version 2.0) - PDF
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This document provides an overview of the Indian drug regulatory system, including the introduction of CDSCO. It details the learning objectives, covering topics such as the introduction to CDSCO, its hierarchy, and the responsibilities of central and state governments.
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CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (Version 2.0) OVERVIEW OF INDIAN DRUG RE REGULATORY SYSTEM (CDSCO/SLA) LEARNING OBJECTIVES The The faculty...
CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (Version 2.0) OVERVIEW OF INDIAN DRUG RE REGULATORY SYSTEM (CDSCO/SLA) LEARNING OBJECTIVES The The faculty faculty will will W HAT cover cover WILLthe the following WE following LEARN IN in in this this LECTURE lecture: lecture: 1? Introduction to CDSCO and its different offices, laboratories Hierarchy at CDSCO State Licensing Authority Responsibilities of Central Government and State Government Achievements of CDSCO Other Ministries/Department involved Regulatory gaps/challenges/initiatives CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) INTRODUCTION § Indian drug regulatory system regulates drugs, cosmetics and medical devices through Drugs and Cosmetics Act, 1940, and Rules thereunder 1945. § It is exercised at two levels (i. e. at Central level and State level). § The subject (health) ‘drug’ falls under concurrent list in the Constitution of India. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) INTRODUCTION § At central level, the regulatory agency is Central Drugs Standard Control Organization (CDSCO), which is attached office to the Directorate General of Health Services (DGHS) under the Ministry of Health and Family Welfare (MoH&FW), Government of India (GOI). § At every state level, it is State Licensing Authority (SLA). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CDSCO § CDSCO is the central drug regulatory authority, headed by Drugs Controller General (India) [DCG(I)], under the Ministry of Health & Family Welfare, Government of India. § It is the National Regulatory Authority (NRA) of India. § CDSCO headquarter is situated at the FDA Bhawan, Kotla Road, New Delhi. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CDSCO § CDSCO is mainly responsible for the approval of clinical trials, new drugs, medical devices, biopharmaceuticals including vaccines, biosimilars, stem cell products, etc. § CDSCO has thirteen (zonal and sub-zonal) offices across the country which are also involved in the monitoring of clinical trials. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) HIERARCHY HIERARCHY CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CDSCO OFFICES & LABORATORIES CDSCO OFFICES & LABORATORIES ZONAL OFFICES (SIX) Ghaziabad, Mumbai, Chennai, Kolkata, Ahmedabad, Hyderabad. SUB ZONAL OFFICES (SEVEN) Chandigarh, Bangalore, Goa, Jammu, Guwahati, Indore, Varanasi. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CDSCO OFFICES & LABORATORIES CENTRAL DRUGS LABORATORIES (EIGHT) Kolkata, Mumbai, Chennai, Hyderabad, Chandigarh, Guwahati, Kasuali, NIB Noida. PORT OFFICES (THIRTEEN) For import and export. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) VARIOUS DIVISIONS AT CDSCO, NEW DELHI VARIOUS DIVISIONS AT CDSCO, HQ, New Delhi New drugs Biologicals Medical Cosmetics devices & IVD IND New Registration SND Biological CI GCT Biosimilar CPE FDC GCT NMD BA/BE Import/ Import Import Registration TL TL TL SAE AEFI EC Abbreviations: IVD = in vitro Diagnostics; IND = Investigational New Drug; SND = Subsequent New Drug; GCT= Global Clinical Trial; FDC = Fixed Dose Combination; BA/BE = Bioavailability/Bioequivalence; TL = Test License; SAE = Serious Adverse Event; EC = Ethics Committee; AEFI = Adverse Events Following Immunization; CI = Clinical Investigation; CPE = Clinical Performance Evaluation; NMD = New Medical Device CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CDSCO ORGANOGRAM Drugs Controller General (India) ZONAL SUB ZONAL PORT OFFICE LABORATORY HEAD QUARTER OFFICE (6) OFFICE (6) (13) (8) § New drugs Enforcement § GMP audits § Import § Testing of drugs § Clinical trials GMP audits § Coordination § Export § Validation of § Imports Drawing drug § with states test protocols § Biologicals samples § sampling § Medical devices QMS audit § Quality Assurance Clinical trial § Pharmacovigilance audit § Legal etc. Abbreviations: GMP = Good Manufacturing Practice; QMS = Quality Management System CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) STATE LICENSING AUTHORITY (SLA) SLA State licensing authority (SLA) is known by various names such as FDA, DCA, Drug license authority, DCO, DCA ,etc. Every state/union territory of the country has established its own licensing authority to regulate drug/cosmetics in their state. The SLA is headed by Commissioner or Drug Controlling Authority and supported by Joint Commissioner/Assistant Commissioner/Deputy Drug Controller/Assistant Drug Controller /Drugs Inspector etc. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) OTHER MINISTRIES DEPARTMENTS INVOLVED OTHER MINISTRIES/DEPARTMENTS INVOLVED Related ministries and other department involved are: Ministry of Chemicals & Fertilizers National Pharmaceutical Pricing Authority (NPPA) Genetic Engineering Appraisal Committee (GEAC) Indian Council of Medical Research (ICMR) Department of Biotechnology - Review Committee on Genetic Manipulation (DBT - RCGM) Department of Science & Technology (DST) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) VARIOUS MINISTERIES/DEPARTMENTS INVOLVED Ministry of Ministry of Health Ministry of State Licensing Chemicals & Fertilizers Environment & Forest Authority Directorate General of Genetic Department of Health Services Engineering Manufacturing, Pharmaceuticals (DGHS) Genetic Appraisal Engineering sales & inspections Approval Committee Committee (GEAC) Central Drugs Standard Control Department of National Biotechnology (DBT) Pharmaceutical Organisation (CDSCO) Pricing Authority (NPPA) Review Committee of Gene Manipulation (RCGM) Pricing regulations CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG ( VERSION 2.0) REGULATORY FUNCTIONS REGULATORY FUNCTIONS CENTRAL RESPONSIBILITIES STATE RESPONSIBILITIES § Approval of new drug § License to manufacture, /medical devices sale and distribution § Import of drugs/medical § Monitoring quality of drugs devices/cosmetics and cosmetics § Clinical trials § Investigations and § EC registration prosecutions § SAE evaluation § Enforcement of DMR Act, & § Amendments to D&C Act & DPCO Rules thereunder § Joint inspection etc. § Pharmacovigilance § DTAB/DCC Abbreviations: DTAB = Drugs Technical Advisory Board; DCC = Drugs Consultative Committee; DMR = Drugs and Magic Remedies; DPCO = Drugs Price Control Order CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CDSCO ACHIEVEMENTS ACHIEVEMENTS 344 Irrational Fixed Dose Combinations (FDCs) prohibited under D & C Act. (matter is subjudiced in court of law). Various measures taken for ease of doing business: Ø E-Governance system introduced (SUGAM Portal). Ø GSR 227 (E) “New Drug & Clinical Trial Rules, 2019” has been published (w.e.f. 19/03/2019). Ø Medical Devices Rules, 2017 published (w.e.f. 01/01/2018). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ACHIEVEMENTS ü Nation wide drug survey conducted and around 47000 drugs samples tested in different Government labs. ü Pharmacovigilance, haemovigillance, materiovigilance programme started. ü Testing of cosmetics on animals prohibited. ü Timelines prescribed for processing of applications. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ACHIEVEMENTS ü 24X7 clearance of consignments at ports offices. ü The CDSCO was declared by WHO as a functional National Regulatory Authority (NRA) against stringent international indicators. ü Public Relation Office (PRO) as a single window system for grievance redressal started. ü Intelligence cell constituted at CDSCO, HQ. This cell conducted several raids. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) GAPS/CHALLENGES GAPS/CHALLENGES Shortage of manpower Space constraints Technical, administration. CDSCO, HQ, New Delhi, other locations. Inadequate drug testing facilities/ laboratories To notify all medical devices Chemical, biological, medical available in market. device, cosmetics. Enforcement Additional work added in last few years Complete monitoring of clinical trials (site inspections). Registration of all Ethics Committees in India. Responsibility of DCGI in causality assessment and decision on amount of compensation in case of trial related deaths. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SUMMARY In Lecture 1 (L1), we briefly learned about: CDSCO structure including hierarchy, zonal, sub zonal offices, laboratories. Various departments at CDSCO, HQ, New Delhi. Responsibilities of the state and centre. Achievements by CDSCO. Regulatory gaps/challenges faced by CDSCO. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RECAP State true or false: CDSCO is responsible for approval of new drugs and clinical trials in India. True § NRA Fill in the blanks: § CDSCO is headed by ________________________. Drugs Controller General (India) [DCG(I)] CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG Version 2.0 DISCLAIMER The information within this presentation is based on the presenter’s expertise and experience and represents the views of the presenter for the purpose of training. END OF LECTURE L1- OVERVIEW OF INDIAN DRUG REGULATORY SYSTEM THANK YOU. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (Version 2.0) OVERVIEW OF DRUGS & COSMETICS ACT, 1940 AND RULES THEREUNDER 1945 LEARNING OBJECTIVES WHAT WILL WE LEARN IN LECTURE 2? Overview of Drugs and Cosmetics Act, 1940 & Rules thereunder 1945. Chapters and schedules of the D & C Act. Various schedules to the Rules. Note: Act means Drugs and Cosmetics Act, 1940 CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) OUTLINE § Drug falls under the concurrent list of the Indian Constitution. § The Act is a Central Act, enforced by both Central and State Government. § Extended to whole of India. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) The Drugs & Cosmetics Act was passed on 10th April 1940, with the main objective to regulate: q Import q Manufacture q Distribution q Sale of drugs and cosmetics Regulate import of drugs and cosmetics in India, so that no sub- standard, spurious or misbranded drugs enter into India (by issuing Import License & Registration Certificate). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) § Prohibits manufacture of sub-standard or spurious or misbranded drug in India. § Provides control over the sale & distribution of drugs by restricting it to approved pharmacist. § Provides for the control over the manufacture of Ayurvedic, Siddha, and Unani medicines. § Provides for the control over manufacture, sale & distribution of Homeopathic drugs. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) § Provision for regular inspection of licensed premises by Drugs Inspector. § Control over the standards of drugs and cosmetics by drawing samples & analysing them by testing at approved laboratories. § Prescribes the manner and requirement of labelling & packing of the various classes of drugs & cosmetics. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS OF THE ACT CHAPTERS OF THE ACT PART I Five Chapters I to V (including chapter IV A) which includes 38 different sections and many sub sections. Chapter I: Introductory Chapter II: The Drug Technical Advisory Board, The Central Drugs Laboratory and the Drugs Consultative Committee Chapter III: Import of drugs and cosmetics Chapter IV: Manufacture, sale and distribution of drugs and cosmetics Chapter IV A: Provisions relating to Ayurveda, Siddha and Unani Drugs Chapter V: Miscellaneous CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS OF THE ACT PART II Drugs and Cosmetics Rules, 1945. These Rules are divided in XIX parts. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG VERSION 2.0 SCHEDULES SCHEDULES There are two schedules in the Act. First Schedule: Lists of Ayurveda, Siddha and Unani books. Second schedule: Standards to be complied with by imported drugs and drugs manufactured for sales and distribution. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ADMINISTRATION OF THE ACT & RULES ADMINISTRATION OF THE ACT & RULES ADVISORY Drugs Technical Advisory Board (DTAB) Drugs Consultative Committee (DCC) ANALYTICAL Central Drugs Laboratory (CDL) Government Analysts EXECUTIVES Licensing Authorities Controlling Authorities Drugs Inspectors Government Analysts CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) IMPORT, MANUFACTURE & SALE OF DRUGS IMPORT OF DRUGS § Certain classes of drugs are prohibited to import under Act. § Import of drug require Licence: q Specified in Schedule-C/C1 q Specified in Schedule-X q Imported for Test/Analysis q Imported for personal use/for patient q Any new drugs § Drugs exempted from provisions of import. § Offences and penalties. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) MANUFACTURE § Certain drugs are prohibited to manufacture. § Drug require manufacture Licence: q Manufacture of other than in Schedule-C/C1 q Manufacture of those in Schedule-C/C1 q Manufacture of Schedule-X drugs q Loan license q Repackaging license q Offences and penalties CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG VERSION 2.0 SALE OF DRUGS § Certain classes of drugs are prohibited to be sold. § Retail/Wholesale of biological (C/C1). § Retail/Wholesale of other than those specified in C/C1 and X. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SCHEDULES TO THE RULES SCHEDULES TO THE RULES TYPE CONTENT “A” Proforma for forms (Application, issue, renewal etc.). “B” Rates of fee for test or analysis by CDL or Govt. analyst. “C” List of Biological and special products (injectable) applicable to special provisions. “C1” List of Biological and special products (nonparenteral) applicable to special provisions. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SCHEDULES TO THE RULES TYPE CONTENT “D” List of drugs that are exempted from provisions of import. “E1” List of poisonous substances under the Ayurvedic, Siddha and Unani systems. “F” Provisions applicable to blood bank. “F1” Special provision applicable to biological and special products, e.g.. Bacterial and viral vaccines, sera from living animals, bacterial origin diagnostic agents. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SCHEDULES TO THE RULES TYPE CONTENT “F2” Standards for surgical dressings. “F3” Standards for umbilical tapes. “FF” Standards for ophthalmic preparations. “G” List of substances required to be used under medical supervision and labelled accordingly. “H” List of substances (prescription) that should be sold by retail only on prescriptions of R.M.P. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SCHEDULES TO THE RULES TYPE CONTENT “J” List of diseases and ailments that drug should not claim to cure. “K” List of drugs that are exempted from certain provisions regarding manufacture. “M” Requirements of manufacturing premises, GMP requirements of factory premises, plants and equipment. “M1” Requirements of factory premises for manufacture of Homeopathic medicines. “M2” Requirements of factory premises for manufacture of cosmetics. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SCHEDULES TO THE RULES TYPE CONTENT “M3” Requirements of factory premises for manufacture of medical devices. “N” List of equipment to run a Pharmacy. “O” Standards for disinfectant fluids. “P” Life period (expiry) of drugs. “Q” Coal tar colors permitted to be used in cosmetics. “R” Standards for medical devices. “S” Standards for cosmetics. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SCHEDULES TO THE RULES TYPE CONTENT “T” Requirements (GMP) of factory premises for Ayurvedic, Siddha, Unani drugs. “U” Manufacturing and analytical records of drugs. “U1” Manufacturing and analytical records of cosmetics. “V” Standards for patent or proprietary medicines. “W” List of drugs marketed under generic names – Omitted. “X” List of narcotic drugs and psychotropic substances. “Y” Requirement and guidelines on clinical trials for import and manufacture of new drugs. (Not applicable for drugs to be used in human beings) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) NEW RULES TO THE ACT 1. Medical device Rules, 2017 2. New Drugs and Clinical Trials Rules, 2019 3. New cosmetic Rules (Draft) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) MEDICAL DEVICE RULES, 2017 MEDICAL DEVICES RULES, 2017 § Ministry of Health & Family Welfare, GoI, has published the Medical Devices Rules, 2017 vide G.S.R. 78(E) dated 31.01.2017 which is effective from 01.01.2018. § To harmonise with the international regulatory practices. § To provide comprehensive legislation for the regulation. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SALIENT FEATURES § Definitions § Chapters § Schedules § Forms/Fees CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SUMMARY In Lecture 2 (L2), we briefly learnt about: D & C Act and Rules, its main objectives. Schedules to the Act. Import, manufacture and sale of drugs require licence and those prohibited in India. All the schedules to the Rules. Brief about the MD Rules, 2017. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RECAP Under which schedules to the rules are the standards of surgical dressings covered? F2 State true or false DTAB is Drug Training Advisory Board. False. DTAB is Drugs Technical Advisory Board. How many schedule(s) are in the D & C Act, 1940? Two (First Schedule and Second Schedule). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (Version 2.0) DISCLAIMER The information within this presentation is based on the presenter’s expertise and experience and represents the views of the presenter for the purpose of training. END OF LECTURE L2 - OVERVIEW OF DRUGS & COSMETICS ACT AND RULES THEREUNDER. THANK YOU. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (Version 2.0) VERVIEW OF NEW DRUGS & CLINICAL TRIALS RULES, 2019 LEARNING OBJECTIVES WHAT WILL WE LEARN IN LECTURE 3? Draft and final notification. Overview of New Drugs and Clinical Trials (NDCT) Rules, 2019 with respect to number of Chapters, Schedules, Rules etc. Different Chapters and their key content. Different Schedules and their content. The applicable Rules. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) INTRODUCTION ▪ Draft of the New Drugs and Clinical Trials Rules, 2018 was published, vide notification number G.S.R. 104 (E), dated 1st February, 2018, by the Central Government, after consultation with the Drugs Technical Advisory Board (DTAB). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) INTRODUCTION ▪ Thereafter, in exercise of the powers conferred by section 12 and section 33 of the Drugs and Cosmetics Act, 1940 (23 of 1940), the Central Government, after consultation with the DTAB, has published the rules vide G.S.R. 227(E) - New Drugs and Clinical Trials Rules, 2019 which is effective from 19.03.2019. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) These Rules have come in to force from the date of publication in the Official Gazette, i.e. from 19th March 2019 except Chapter for IV which shall come in to force after one hundred and eighty days. The said Rules contains 13 chapters and 8 schedules.They shall apply to all new drugs, investigational new drugs for human use, clinical trial, bioequivalence study, bioavailability study and Ethics Committee. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) New Drugs and Clinical Trials Rules (NDCT), 2019 comprises of: ❑ Chapters - 13 ❑ Rules - 107 ❑ Schedules - 8 ❑ Forms - 27 CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents I PRELIMINARY Rules applicable: from Rule1-2 Short title commencement and applicability. Definitions: Academic clinical trial, Act, API, AE, SAE, bioavailability, bioequivalence, BA/BE study centre, biomedical and health research, CL A, SLA, clinical trial, clinical trial protocol, clinical trial site, efficacy, effectiveness, ethics committee, CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents I PRELIMINARY Good Clinical Practices Guidelines, global clinical trial, investigational new drug, investigational product, investigator, medical management, new chemical entity, new drug, orphan drug, pharmaceutical formulation, pharmacovigilance, phytopharmaceutical drug, placebo, post-trial access, registered pharmacist, schedule, similar biologic, sponsor, trial subject. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents II AUTHORITIES Rules applicable: from Rule 3-5 AND OFFICERS Central Licencing Authority, delegation of powers of Central Licencing Authority, controlling officer. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents III ETHICS COMMITTEE Rules applicable: from Rule 6-14 FOR CLINICAL TRIAL, Requirement, constitution, BIOAVAILABILITY AND registration, renewal, functions, BIOEQUIVALENCE proceedings of the ethics committee. STUDY CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents IV ETHICS COMMITTEE Rules applicable: from Rule 15-18 FOR BIOMEDICAL Constitution, registration of ethics AND HEALTH committee for biomedical and health RESEARCH research. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents V CLINICAL TRIAL, Rules applicable: from Rule 19-30 BIOAVAILABILITY AND Part A clinical trial. BIOEQUIVALENCE STUDY Part B bioavailability and OF NEW DRUGS AND bioequivalence (BA & BE) study. INVESTIGATIONAL NEW DRUGS CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents VI COMPENSATION Rules applicable: from Rule 31-38 Compensation in case of injury or death in clinical trial or BA or BE study of new drug or investigational new drug. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents VII BIOAVAILABILITY AND Rules applicable: from Rule 39-43 BIOEQUIVALENCE STUDY Registration, application, inspection CENTRE of bioavailability (BA) and bioequivalence (BE) study center. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents VIII MANUFACTURE OF NEW Rules applicable: from Rule 52-66 DRUGS/INVESTIGATIONAL Application for permission, license, NEW DRUGS FOR CLINICAL validity, conditions. TRIAL, BIOAVAILABILITY OR BIOEQUIVALENCE STUDY OR FOR EXAMINATION, TEST AND ANALYSIS CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents IX IMPORT OF NEW DRUGS Rules applicable: from Rule 67-73 AND INVESTIGATIONAL Application, license, validity, NEW DRUGS FOR CLINICAL conditions. TRIAL OR BIOAVAILABILITY OR BIOEQUIVALANCE STUDY OR FOR EXAMINATION, TEST AND ANALYSIS CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents X IMPORT OR Rules applicable: from Rule 74- 85 MANUFACTURE OF NEW Application for permission, license, DRUG FOR SALE OR validity, conditions. FOR DISTRIBUTION CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents XI IMPORT OR MANUFACTURE Rules applicable: from Rule 86-96 OF UNAPPROVED NEW Application for permission, license, DRUG FOR TREATMENT OF validity, conditions. PATIENTS IN GOVERNMENT HOSPITAL AND GOVERNMENT MEDICAL INSTITUTION CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents XII AMENDMENTS OF DRUGS Rules applicable: from Rule 97 AND COSMETICS RULES, 122DAA. Non-application of certain 1945 (NON APPLICABILITY rules for new drugs and OF SCHEDULE Y & PART X investigational new drugs for human A) use. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CHAPTERS Chapter Key contents XIII MISCELLANEOUS Rules applicable: from Rule 98-107 Pre-submission and post submission meeting, constitution of expert committee, mode of payment of fees, debarment of applicant. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SCHEDULE S. No. Schedule Key content I FIRST General principles and practices for clinical SCHEDULE trial. (Rules 19 and 31) II SECOND Requirements and guidelines for permission SCHEDULE to import or manufacture of new drug for sale (Rules 21, 75, 80 or to undertake clinical trial. and 97) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SCHEDULE S. No. Schedule Key content III THIRD SCHEDULE Conduct of clinical trial. (Rules 8, 10, 11, 25, 35, 42 and 49) IV FOURTH Requirements and guidelines for conduct of SCHEDULE bioavailability and bioequivalence study of (Rules 33, 45, 48, new drugs or investigational new drugs. 49 and 52) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SCHEDULE S. No. Schedule Key content V FIFTH SCHEDULE Post market assessment. (Rules 77 and 82) VI SIXTH SCHEDULE Fee payable for licence, permission and (Rules 21, 22, 33, registration certificate. 34, 45, 47, 52, 53, 60, 67, 68, 75, 76, 80, 81, 86, 91, 97 and 98) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SCHEDULE S. No. Schedule Key content VII SEVENTH Formulae to determine the quantum of SCHEDULE compensation in the cases of clinical trial (Rules 39, 40, and related injury or death. 42) VIII EIGHTH Various forms (CT-01 to CT-27). SCHEDULE (Rules 8, 10 and 17) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SUMMARY In Lecture 3 (L3), we briefly learnt about: Overview of NDCT Rules, 2019. Different Chapters (from Chapter I-XIII). Various definition covered under this rule. Rules applicable to different Chapters. Schedules. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RECAP How many Chapters are there in the NDCT Rules 2019? 13 chapters. In which schedule of NDCT Rules, the forms for application are given? Eighth schedule. In which chapter post-submission meeting and pre- submission meeting are mentioned? Chapter XIII (Miscellaneous). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (Version 2.0) DISCLAIMER The information within this presentation is based on the presenter’s expertise and experience and represents the views of the presenter for the purpose of training. END OF LECTURE L3- OVERVIEW OF NEW DRUGS & CLINICAL TRIALS RULES 2019. THANK YOU. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (Version 2.0) PRE-CLINICAL DATA REQUIREMENTS LEARNING OBJECTIVES The The faculty faculty will cover thethe following in this lecture: Wwill cover following in this HAT WILL WE LEARN IN LECTURE 4? lecture: Why pre-clinical toxicity studies are required? Regulatory authorities involved. Different types of animal toxicity tests. Different types of animal pharmacological studies. Animals used, species used, number of animals required for each test. Route of administration, dose, duration of study. Retention of record. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) PURPOSE OF STUDY PURPOSE § Toxicological studies are very important for development of new drugs and for extension of therapeutic potential of existing molecule. § Toxicity studies are mostly used to examine the specific adverse events or specific end points such as cancer, cardiotoxicity and skin/eye irritation. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) PURPOSE § Toxicity testing also helps to calculate No Observed Adverse Effect Level (NOAEL) dose and helpful for clinical trial. § As per CDSCO regulations, it is essential to screen new molecules for pharmacological activity and toxicity potential in animals (NDCT Rules 2019, Second Schedule Para 2 & 3). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) PURPOSE § Preclinical studies are conducted to define pharmacological and toxicological effects not only prior to initiation of human studies, but throughout the clinical development. § Both in vitro and in vivo can contribute to this characterization CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) REGULATIONS IN INDIA REGULATORY AUTHORITIES IN INDIA New Drug and Clinical Trials Rules, 2019 (Second Schedule) under D & C Act, 1940 and Rules thereunder 1945. Institute Animal Ethics Committee (IAEC). Committee for Purpose of Control & Supervision of Experiments in Animals (CPCSEA). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) REGULATORY AUTHORITIES IN INDIA Department of Biotechnology, Ministry of Science & Technology Review Committee for Gene Manipulation (RCGM). § Second Schedule of NDCT Rules, 2019. § Requirements and guidelines for permission to import or manufacture of new drugs for sale or to undertake clinical trial in India. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) REGULATORY REQUIREMENTS Applicant is required to give data in accordance with Table-1, Table-2, Table-3 and Table-4, as per this Schedule: Animal toxicology data. Animal pharmacology data. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) TYPES OF STUDIES TYPES OF STUDIES TYPES OF TOXICITY STUDIES : 1. Animal toxicology study: §Systemic toxicity studies §Repeated-dose systemic toxicity studies §Dose-ranging study CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) TYPES OF STUDIES q Male fertility study q Female reproduction and developmental toxicity study ü Female fertility study ü Teratogenicity study ü Perinatal study CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) TYPES OF STUDIES q Local toxicity § Dermal toxicity study § Photo-allergy or dermal photo toxicity § Vaginal toxicity test § Rectal tolerance test § Parenteral drugs § Ocular toxicity studies § Inhalation toxicity study CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) TYPES OF STUDIES q Allergenicity or hypersensitivity Guinea pig maximization test Local lymph node assay q Genotoxicity q Carcinogenicity CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) TYPES OF STUDIES 2. Animal pharmacology q Specific pharmacological actions q General pharmacological actions § Cardiovascular system § Respiratory system CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) TYPES OF STUDIES q Follow-up and supplemental safety pharmacology studies q Follow-up safety pharmacology studies § CVS, CNS, respiratory system studies q Supplemental safety pharmacology studies § Urinary, Autonomic Nervous System (ANS), gastrointestinal and other organ system CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON-CLINICAL TOXICITY STUDIES) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) General principle: Toxicity studies should comply with norms of Good Laboratory Practice (GLP) standards. Toxicokinetic studies (generation of pharmacokinetic data either as integral component of the conduct of non-clinical toxicity studies or in specially designed study) should be conducted to assess systemic exposure achieved in animals and its relationship to dose level and time course of toxicity study. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) Systemic toxicity studies. Single dose toxicity studies: ü 2 rodent species (mice and rats). ü Same route as intended for humans. ü At least one more route (unless it is intravenous). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) q Minimum Lethal Dose (MLD) and Maximum Tolerated Dose (MTD) should be established. If possible, the target organ of toxicity should also be determined. q The dose causing severe toxic manifestations or death should be defined in the case of cytotoxic anticancer agents. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) Repeated-dose systemic toxicity studies: At least two mammalian species, one should be a non-rodent. Dose-ranging studies 14, 28, 90 or 180-day toxicity studies. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) qDose administered 7 days a week by the route intended for clinical use. qThe highest dose should produce observable toxicity; the lowest dose should not cause observable toxicity. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) q The parameters include behavioral, physiological, biochemical and microscopic observations. q In the case of cytotoxic anticancer agents, dosing and study design should be in accordance with the proposed clinical schedule in terms of days of exposure and number of cycles. Two rodent species may be tested for initiating Phase I trials. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) Male fertility study: qOne rodent species (preferably rat). qDose selection from the results of the previous 14 or 28-day toxicity study in the rat. qThree dose groups, the highest one showing minimal toxicity in systemic studies, and a control group should be taken. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) q6 adult male animals/group. qTest substance for minimum 28 days and maximum 70 days before they are paired with female animals of proven fertility in a ratio of 1:2 for mating. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) Female reproduction and developmental toxicity studies: For all drugs proposed to be studied or used in women of child bearing age. Segment I, II and III studies are to be performed in albino mice or rats, and segment II study should include albino rabbits also as a second test species. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) q Local toxicity: When the new drug is proposed to be used by some special route (other than oral) in humans to determine local effects in a suitable species. Note: (i) Dermal toxicity study: Rabbit and rat. Non- animal alternative tests can be used as given in OECD Guidelines. [OECD=Organisation for Economic Co-operation and Development] CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) (ii) Photo-allergy or dermal photo-toxicity: Armstrong/ Harber test in guinea pig. (iii) Vaginal toxicity test: In rabbit or dog. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) (iv) Rectal tolerance test: Performed in rabbits or dogs. (v) Parenteral drugs: For products meant for intravenous or intramuscular or subcutaneous or intradermal injection, the sites of injection in systemic toxicity studies should be specially examined (grossly and microscopically). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) (vi) Ocular toxicity studies for products meant for ocular instillation, in two species. (vii) Inhalation toxicity studies in one rodent and one non-rodent species. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) q Genotoxicity: IVIV test. To detect genetic damage directly or indirectly. q Genotoxic compounds, in the absence of other data, shall be presumed to be trans-species carcinogens, implying a hazard to humans. Such compounds need not be subjected to long-term carcinogenicity studies. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) q However, if such a drug is intended to be administered for chronic illnesses or otherwise over a long period of time, a chronic toxicity study (up to one year) may be necessary to detect early tumorigenic effects. Note: Ames’ Test (S. typhimurium or E. coli should be used). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) q Carcinogenicity: In rodent species (preferably rat). Mouse may be employed. At least 3 dose level. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) For all drugs that are expected to be clinically used for more than six months as well as for drugs used frequently in an intermittent manner in the treatment of chronic or recurrent conditions. If there is concern about their carcinogenic potential. or where SAR suggests carcinogenic risk. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) or when there is evidence of pre-neoplastic lesions in repeated dose toxicity studies or when long-term tissue retention of parent compound or metabolites results in local tissue reactions or other pathophysiological responses. For pharmaceuticals developed to treat certain serious diseases, Central Licencing Authority (CLA) may allow carcinogenicity testing to be conducted after marketing permission has been granted. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) Animal toxicity requirement for clinical trials and marketing of new drug is given. Example: For oral, parenteral or transdermal, single dose or several dosages in one day, up to one week for Phase I, II & III long term toxicity studies should be conducted in two species for two weeks. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL TOXICOLOGY (NON CLINICAL TOXICITY STUDIES) qSpecial toxicity studies: Like male fertility studies for Phase III in male volunteer or patient. § Number of animals required for repeated-dose toxicity studies given for (14-28 days study) and (84–182 days study). § Laboratory parameters like hematological, coagulation parameter, urine analysis parameter etc. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL PHARMACOLOGY ANIMAL PHARMACOLOGY GENERAL PRINCIPLES q Specific and general pharmacological studies should be conducted to support use of therapeutics in humans. q In the early stages of drug development enough information may not be available to rationally select study design for safety assessment. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL PHARMACOLOGY q In such a situation, a general approach to safety pharmacology studies can be applied. Specific pharmacological actions: Specific pharmacological actions are those which demonstrate the therapeutic potential for humans. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL PHARMACOLOGY General pharmacological actions: Need to be conducted to investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure within the therapeutic range and above. § Cardiovascular system: Effects of the investigational drug should be studied on blood pressure, heart rate, and the electrocardiogram etc. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL PHARMACOLOGY § Respiratory System: Effects of the investigational drug on respiratory rate and other functions. Follow-up and supplemental safety pharmacology studies: Additional supplemental and follow-up safety pharmacology studies may need to be conducted as appropriate. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) ANIMAL PHARMACOLOGY Follow-up safety pharmacology studies: § Effect on CVS, CNS, respiratory system should be studied. Supplemental safety pharmacology studies: § Effect on urinary, ANS, gastrointestinal and other organ system should be studied. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) IMPORTANT TO KNOW Notes: 1) Animal toxicity data generated in other countries may be accepted and may not be asked to be repeated or duplicated in India on a case to case basis depending upon the quality of data and the credentials of the laboratory where such data has been generated. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) IMPORTANT TO KNOW 2) Requirements for fixed dose combinations are given in clause 4 of this Schedule. 3) Retention Period: For a minimum of five years after marketing of the drug. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SUMMARY In Lecture 4 (L4), we briefly learned about: Why pre-clinical toxicity studies are required? Regulatory authorities involved. Different types of animal toxicity tests. Different types of animal pharmacological studies. Animals used, species used, number of animals required for each test. Route of administration, dose, duration of study. Retention of record. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RECAP Are pre-clinical toxicity studies are included in the Second Schedule of NDCT Rules, 2019? Yes, under the ‘New Drugs & Clinical Trials (NDCT) Rules, 2019’ Fill in the blank: All the records and documents belonging to pre-clinical studies should be preserved for minimum of _________. Five years, after marketing of the drug. Carcinogenicity study should be carried out in which species? Rodent species (preferably rat). CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG Version 2.0 DISCLAIMER The information within this presentation is based on the presenter’s expertise and experience and represents the views of the presenter for the purpose of training. END OF LECTURE L4 - PRECLINICAL DATA REQUIREMENTS THANK YOU. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (Version 2.0) RULES GOVERNING CLINICAL TRIALS LEARNING OBJECTIVES The The faculty faculty will cover thethe following in this lecture: Wwill cover following in this HAT WILL WE LEARN IN LECTURE 5? lecture: § Be able to know what is clinical trial as per rule. § Rules under which application for clinical trials can be made. § Rules for post trial access. § Rules for deemed approval, timelines for approval. § Rules with respect to BA/BE. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) DEFINITION OF CLINICAL TRIAL Clinical Trial (Rule (2 (J) ): In relation to a new drug or investigational new drug means any systematic study of such new drug or investigational new drug in human subjects to generate data for discovering or verifying its - (i) clinical or; (ii) pharmacological including pharmacodynamics, pharmacokinetics or; (iii) adverse effects, with the objective of determining the safety, efficacy or tolerance of such new drug or investigational new drug CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) LEGAL PROVISIONS FOR REGULATION OF CLINICAL TRIALS RULE 21 Application for permission to conduct clinical trial of a new drug or investigational new drug - Any person or institution or organization which intend to conduct CT shall make application to CLA in Form CT-04. - Application shall be accompanied with the information and documents as specified in the Second Schedule and fee as specified in Sixth Schedule. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 22 Grant of permission to conduct clinical trial. CLA may after scrutiny of the application (Form CT- 04) along with information and document furnished by the applicant may grant permission to conduct CT for new drug or IND in Form CT-06. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 23 Permission to conduct clinical trial of a new drug or investigational new drug as part of discovery, research and manufacture in India. Not withstanding anything contained in this Rules, where any person or institution or organization make an application under Rule 21 to conduct CT of new drug or IND should fulfil the following conditions namely: The drug is discovered in India, or R&D of the drug are being done in India and also the drug is proposed to be manufacture and marketed in India CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 23 cont.… Such applications shall be disposed within a period of 30 working days from the date of receipt of the application by the said authority. The applicant who has taken the deem approval as per above shall before initiating that CT, inform the CLA in Form CT-4A and CLA shall on the basis of the said information keep a official record in the Form CT-4A. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 24 Permission to conduct clinical trial of a new drug already approved outside India. new drug which is already approved and marketed in a country, as specified under rule 101, the application, shall be disposed of within a period of ninety working days. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 25 Conditions of permission for conduct of clinical trial § CT at each site shall be initiated only after approval from CLA. § CT site where there is no EC of its own may initiate the CT after obtaining approval of protocol from EC of another trial site under the provision given at Rule-7. § The approval granted by the EC should be forwarded to CLA within 15 working day. § CT shall be registered with the CTRI. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 25 cont.… § CT shall be conducted in accordance with the requirement of GCP guidelines. § Six monthly status report shall be submitted to the CLA § Any SAE after due analysis may be forwarded to the CLA, Chairperson of EC and Institute within 14 days of its occurrence. § In case of injury complete management and compensation shall be provided. § Premises of the sponsor including and CT site shall be open for inspection. § CLA may, impose any other. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 26 Validity period of permission to initiate a clinical trial: period of two years from the date of its issue. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 27 Post-trial access of investigational new drug or new drug; the post trials access shall be provided by the sponsor free of cost. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 28 ACADEMIC CLINICAL TRIAL - No permission for conducting Academic CT shall be required for any dug from CLA where: § The CT in respect of permitted drug formulation is intended solely for academic research for new indication, new route of administration, new dose/new dosage form and CT must be approved by EC. § Observations generated from such CT are not required to be submitted to the CLA. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 28 cont.… § The observation of such CT are not used for any promotional purposes. - Academic trial shall be conducted in accordance with the approved CT protocol by EC and principles specified in National Ethical Guidelines for Biomedical and Health Research by ICMR. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 29 Inspection of premises relating to clinical trial shall allow any officer authorised by the Central Licencing Authority, who may, if considered necessary, be accompanied by an officer authorised by the State Licencing Authority, to enter the premises and clinical trial site with or without prior notice to inspect, search or seize, any record, etc. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 30 Suspension or cancellation of permission to conduct clinical trial. Non compliance of stipulated conditions may lead to suspension or cancellation of permission to conduct clinical trial. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 31 Bioavailability or bioequivalence study of new drug or investigational new drug. Every person associated with the conduct of BA/BE study of a new drug or IND shall follow the general principle and practices as specified in the First Schedule. No BA/BE study of new drug or IND shall be conducted without permission of CLA and approval by EC. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 32 Oversight of bioavailability or bioequivalence study centre. The work of every BA/BE study center shall be overseen by EC before initiation and throughout the duration of the conduct of the study. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 33 Application for permission to conduct bioavailability or bioequivalence study. § By making an application in Form CT-05. § Fees as per Sixth Schedule and other information and documents as specified in table 2 of Fourth Schedule. § No fee for conducting BA/BE by central and state government funded institution. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 34 Grant of permission to conduct bioavailability or bioequivalence study. CLA if satisfied may grant permission in Form CT-07, if not satisfied may reject. Some deficiencies in the applications may be rectified within the stipulated period of 90 working days. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 34 cont.… - In case of rejection, applicant may request CLA to reconsider their application within a period of 60 working days from the date of rejection. - May also file appeal within 45 working days and such case may be dispose of within a period of 60 working days. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 35 Conditions of permission for conduct of bioavailability or bioequivalence study. The permission granted by CLA under Rule 34 shall be subject to following conditions: § BA/BE study at each site shall be initiated after approval of protocol and other document by registered EC at the site. § When there is no EC at that site the study may be initiated after obtaining approval from registered EC within the radius of 50 kilometer within the same city. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 35 cont.… § Approval granted by EC shall be informed to the CLA within a period of 15 working days. § BA/BE study of new drug/IND shall be conducted only at the study center registered with CLA. § Before enrolling 1st subject for the study for IND protocol shall be registered in CTRI. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 36 Validity period of permission to conduct bioavailability or bioequivalence study. 1. Valid for a period of one year from the date of its issue, unless suspended or cancelled by the Central Licencing Authority. 2. The said authority may, on the request of the applicant made in writing, extend the period of permission granted for a further period of one year. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 37 Inspection of premises relating to bioavailability or bioequivalence study. shall allow any officer authorised by the Central Licencing Authority, with or without prior notice to inspect, search or seize, any record, statistical result, document, etc. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 38 Suspension or cancellation of permission to conduct bioavailability or bioequivalence study. Any person or Institution to whom the permission has been granted under Rule 34 in Form CT-07 fails to comply with any provision of the act and these Rules. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RULE 101 The Central Licensing Authority, with the approval of the Central Government, may specify, by an order, the name of the countries, from time to time, for considering waiver of local clinical trial for approval of new drugs under Chapter X and for grant of permission for conduct of clinical trial under Chapter V. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) SUMMARY In lecture 5 (L5), we briefly learnt about: Clinical trials, BA/BE, Academic clinical trials (CT). Rules regarding Application/permission. Rules regarding deemed approval, time lines Rules for the condition of license, inspection, cancellation of permission, etc. CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) RECAP Under which rule, permission to conduct clinical trial of a new drug already approved outside India is mentioned? Rule 24 What Rule does Rule 36 address? Validity period of permission to conduct bioavailability or bioequivalence study. Clinical trials shall be registered with the CTRI is addressed under which rule? Rule 25 and 35 CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG (VERSION 2.0) CURRENT REGULATORY REQUIREMENTS FOR CONDUCTING CLINICAL TRIALS IN INDIA FOR IND/NEW DRUG Version 2.0 DISCLAIMER The information within this presentation is based on the presenter’s expertise and experience and represents the views of the presenter for the purpose of training. END OF LECTURE L5: RULES GOVERNING CLINICAL TRIALS THANK YOU
