PART 1 _ Documentation of drug trials and regulatory filings (1).pptx

No research without action,no action without research.

1. Documentation of drug trials and regulatory filings Dilsar Ilyas Gohil Master in Pharmacy

2. What is Investigational New Drug An Investigational New Drug (IND) is a drug or biological product that has not been approved for general use by the Food and Drug Administration (FDA). It is used in a clinical trial to investigate its safety and efficacy . The term also includes biological products that are used in vitro for diagnostic purposes. After the successful completion of preclinical research, Drug developer or sponsor, must submit an Investigational New Drug (IND) application to respective regulatory authority such as FDA in order to start clinical research.

3. Investigational New drug application (IND) An IND is a submission to the food and drug administration (FDA) requesting permission to initiate a clinical study of a new drug product. The Federal Food , Drug and Cosmetic act requires that drugs have an approved marketing application before they can be shipped in interstate commerce. The IND application allows a company to initiate and conduct clinical studies for their new drug products. The IND application provides the FDA with the data necessary to decide whether the new drug and the proposed clinical trial pose a reasonable risk to the human subjects participating in the study.

4. The IND filing is the formal process by which a sponsor requests approval for testing of a drug in human subjects . In the IND application, following things are must included: Animal study data and toxicity data Manufacturing information Clinical protocols (study plans) for studies to be conducted Data from any prior human research Information about the investigator Any additional data After submitting IND, respective regulatory authority reviewed all the data and if satisfied, they grant the sponsor to begin clinical trial. It will take 30 -60 days after IND submission to get approval for clinical trial from the FDA

5. TYPES OF IND Investigator IND : Submitted by a physician who initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. Physician might submit a research IND to propose studying an unapproved drug, or an approved product for a new indication or in a new patient population. Emergency Use IND Allows FDA to authorize use of an experimental drug in an emergency situation Does not allow time for submission of an IND in accordance with 21CFR , Sec. 312.23 or Sec. 312.34 Treatment IND Submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place

6. CLASSIFICATION OF IND Commercial: Permits sponsor to collect data on clinical safety and effectiveness needed for application for marketing in the form of NDA Research (non-commercial) : Permits the sponsor to use drug in research to obtain advanced scientific knowledge of new drug o No plan to market the product

7. CONTENT OF IND In three broad areas: Animal Pharmacology and Toxicology Studies : An assessment as to whether the product is reasonably safe for initial testing in humans. Any previous experience with the drug in humans Manufacturing Information : composition, manufacturer, stability, and controls used for manufacturing the drug. Clinical Protocols and Investigator Information : Commitments to obtain informed consent from the research subjects, to obtain review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations. Once the IND is submitted, the sponsor must wait 30 days before initiating any clinical trials. During this time, FDA has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk - USFDA

8. C linical trial : A systematic study of any new drug(s) in human subject(s) to generate data for discovering and/or verifying the clinical, pharmacological (including pharmacodynamic and pharmacokinetic), and/or adverse effects with the objective of determining safety and/or efficacy of the new drug.

9. Clinical trials consist of 4 phases Phase I – Study Participants: 20 to 100 healthy volunteers Length of Study: Several months to one year Purpose: Safety and Dose range Phase II – Study Participants: 100 to 300 volunteers with the disease. Length of Study: Up to 2 years Purpose: Safety and Efficacy Phase III- Study Participants: 300 to 3,000 volunteers who have the target disease Length of Study: 1 to 4 years

10. India Japan South Africa Australia Protocol Yes ( English) Yes ( in Japanese) Yes ( English) Yes ( English) ICF informed c onse n t f o r m Yes ( English and other local Languages) Yes ( in Japanese) Yes ( English ) Yes ( English) Investigator Brochure Yes Yes ( in Japanese) Yes Yes Investigator’s CV Yes NO Yes Yes Case Report Form Yes NO Yes Yes

11. India Japan South Africa USFDA Case Report Form Yes NO Yes Yes Study subject c o m pens a ti o n documents Yes NO Yes Yes CMC documents Yes YES Yes Yes GMP certificate of the investigational drug Yes NO Yes Yes Development S a f e ty upd at e Report Yes YES Yes Yes

12. Investigator’s Brochure A copy of the investigator's brochure, containing the following information: A brief description of the drug substance and the formulation, including the structural formula , if known. A summary of the Pharmacological and toxicological effects of the drug in animals and, in humans. A summary of the Pharmacokinetics of the drug in animals and in humans. A summary of information relating to safety and effectiveness in humans obtained from prior clinical studies. A description of possible risks and side effects to be anticipated on the basis of prior experience with the drug under investigation or with related drugs, and of precautions or special monitoring to be done as part of the investigational use of the drug.

13. P R O T OCO L S An objectives and purpose of the study. description of the dosing plan including duration, dose, or method to be used in determining dose The name and address and a statement of the qualifications A protocol contains the following, with the specific elements and detail of the protocol reflecting the above distinctions depending on the phase of study: III. (curriculum vitae or other statement of qualifications) of each investigator, and the name of each sub investigator (e.g., research fellow, resident) IV. The criteria for patient selection and Exclusion and inclusion criteria.

14. E stimate of the number of patients to be studied. description of the design of the study , including the kind of control group to be used, if any, and a description of methods to be used to minimize bias on the part of subjects, investigators, and analysts. The method for determining the dose(s) to be administered, the planned maximum dosage, and the duration of individual patient exposure to the drug. A description of the observations and measurements to be made to fulfill the objectives of the study. A description of clinical procedures, laboratory tests , or other measures to be taken to monitor the effects of the drug in human subjects and to minimize risk.

15. CHEMISTRY, MANUFACTURING, AND CONTROL INFORMATION This section describing the composition, manufacture, and control of the drug substance and the drug product. each phase of the investigation sufficient information is required to be submitted to assure the proper identification, quality, purity, and strength of the investigational drug. Final specifications for the drug substance and drug product are not expected until the end of the investigational process. stability data are required in all phases of the IND to demonstrate that the new drug substance and drug product Drug development proceeds

16. Drug substance A description of the drug substance, including its physical, chemical, or biological characteristics. T h e n a m e a n d a dd r e s s o f it s m a n u f ac t u r e r ; t h e g e n e r a l m e t ho d of preparation of the drug substance. The specification and analytical methods used to assure the identity, strength, quality, and purity of the drug substance. Stability of the drug substance during the toxicological studies and the planned clinical studies

17. Drug product list of all components, which may include reasonable alternatives for inactive compounds. Quantitative composition of the investigational drug product, Brief general description of the manufacturing and packaging procedure as appropriate for the product. Specification and analytical methods used to assure the identity, strength, quality, and purity of the drug product; Stability data A brief general description of the composition, manufacture, and control of any placebo used in a controlled clinical trial. L a b e lin g . A c op y o f a l l l a b e l s a n d l a b e l in g t o b e p ro v i d e d t o e a ch investigator.

18. PH AR M AC O L OG Y A ND T O X I C O LO G Y I N F O R M A TION Adequate information about pharmacological and toxicological studies of the drug involving laboratory animals or in vitro. Pharmacology and drug disposition. A section describing the Pharmacological effects and mechanism(s) of action of the drug in animals, and information on the of the drug. absorption, distribution, metabolism, and excretion Toxicology summary of the toxicological effects of the drug in animals and in vitro. The description is to include the results of acute, subacute, and chronic toxicity tests; special toxicity test related to the drug's particular mode of administration or conditions of use (e.g., inhalation, dermal, or ocular toxicology). Any in vitro studies intended to evaluate drug toxicity . Toxicology study that is intended primarily to support the safety of the proposed clinical investigation.

19. Thank you