IND Enabling Studies by Kashikant Yadav

Presentation on Investigational New Drug (IND) enabling studies

1. IND Enabling Studies PRESENTED TO : DR. NAGARATHNA P.K.M. Ass prof ., KCP Department Of Pharmacology BY : Kashikant Yadav M pharm (Pharmacology)

2. Submission application to FDA requesting permission to initiate the study of New drug product. Pharmaceutical company obtains permission to clinical trial before a marketing application for the drug has been approved IND Enabling Studies

3. FDA reviews the IND application for safety to assure that research subjects will not be subjected to unreasonable risk Product is reasonably safe for initial use in humans If the compound exhibits pharmacological activity that justifies commercial development

4. Pharmaceuticals may move across state lines during two stages of human use • Research prior to “approval” – Requires research permit: e.g., Investigational New Drug Exemption (IND) • Marketing after “approval” – Requires marketing permit: e.g., New Drug Application (NDA)

5. Applicant (Drug Sponsor): who assumes responsibility for the marketing of a new drug IND application provides FDA with data necessary to decide : New drug proposed Clinical trial pose a reasonable risk to human subjects participating in the study Who can apply for IND????

6. The IND application allows the company to initiate & conduct the clinical studies of their new drug Product. • The safety of the Clinical trial Subjects is always the primary concern of FDA .

7. Primary goal of the Sponsor should be to demonstrate to the FDA that the - new drug - proposed trial - entire clinical development plan described in the IND is designed to minimize the risk to the trial subjects.

8. New chemical entity not approved for the indication Being administered at the new dosage level combination with anther drug All clinical studies where the new drug is administered to human subjects When do We need an IND?

9. Non clinical studies Approved drug and the study is within its approved indication for use When We Don’t Need An IND

10. COMMERCIAL IND : goal is to obtain marketing approval for a new product. NON-COMMERCIAL IND : It includes INVESTIGATOR IND : In this case ,the physician is both the sponsor and investigator CATEGORIES OF IND

11. EMERGENCY IND : FDA authorize immediate dispensing of a non-approved drug in a life threatening situation when no standard acceptable therapy is available . TREATMENT IND : FDA will permit investigational drug to be used to treat a serious or life threatening disease or if there is no comparable alternative drug available.

12. The content & format of IND application

13. 312.20 REQUIREMENTS OF AN IND • A sponsor shall submit an IND to FDA who intends to conduct a clinical investigation. • Investigation is not supposed to begin without prior written authorization of FDA SUBPART B INVESTIGATIONAL NEW DRUG APPLICATION

14. • Phase 1 - ADME (20- 80) healthy subjects • Phase 2 – effectiveness in particular indication (several hundred patients) • Phase 3 – safety and effectiveness ( 100- 1000) subjects. 312.21 PHASES OF INVESTIGATION

15. To assure safety and rights of the subject. • To assure the scientific quality of investigation will yield data capable of meeting statutory standards for marketing approval • Focus should be on general investigational plan & protocol which should be supported by additional information including animal toxicological studies 312.22 GENERAL PRINCILPLE OF IND

16. 1. Cover sheet (FORM FDA 1571) 2. Table of contents 3. Introductory statement and a general investigational plan 4. Investigators brochure 5. Protocols 6. Chemistry , manufacturing and control information 7. Pharmacology and Toxicology information 8. Previous human experience with the investigational drug 9. Other relevant information like no of IND submissions 10. Protocol amendments, any changes in the protocol     312.23 IND CONTENT & FORMAT Of An IND Application

17. Name of the sponsor Date of submission Address Telephone number Name(s) of Drug IND Number Indication Phase of clinical investigation to be conducted list no.of all investigational new drug application Serial no. Contents of application Cover sheet

18. Description of clinical studies planned for the experimental drug Purpose of the study Indication to be studied Types of trials to be initiated Number of study subjects Risks involved GENERAL INVESTIGATIONAL PLAN

19. Structural formula of drug Summary of pharmacological , toxicological , pharmacokinetic effects in animals Safety and efficacy Purpose of study Dose / dose frequency Monitoring procedures Investigators brochure(IB)

20. - It describes – the objective of the study - the trial design - how subjects would be selected - how the trail is to be conducted. Protocols

21. Determines the adequacy of methods used to manufacture and assay investigational compound Safety concerns Describe drug substances Method of preparation Reagent and solvents Acceptable limits and analytical methods to ensure quality and purity of drug. Chemistry , manufacturing and control information

22. non-clinical safety data that sponsor generated to prove that the IP is safe for clinical study . the amount & type of data depends on class of new drug duration of proposed clinical trial, patient population that will be exposed during the trial Pharmacology and Toxicology information

23. Pk studies Pd studies observed adverse event profile Previous human experience with the investigational drug

24. purpose of this section is to facilitate the availability of promising new drugs to desperately ill patients In the case of an immediately life-threatening disease , a drug may be made available for treatment use under this section earlier than Phase 3, but ordinarily not earlier than Phase 2. Treatment use of an investigational new drug

25. The “treatment use” of a drug includes the use of a drug for diagnostic purposes. If a protocol for an investigational drug meets the criteria of this section, the protocol is to be submitted as a treatment protocol

26. A treatment protocol is required to contain the following: • The intended use of the drug. • An explanation of the rationale for use of the drug, • A brief description of the criteria for patient selection, The method of administration of the drug and the dosages . • A description of clinical procedures, laboratory tests, or other measures . Submissions for treatment use

27. Once the IND is stamped as received , it is sent to CDER for review. • It is further categorically divided into different sections – Medical Chemistry Pharmacology / Toxicology Statistics FDA’s IND REVIEW PROCESS

28. Safety Review Clinical Hold Decision Notify Sponsor Sponsor Notified of Deficiencies Study Ongoing • Once CDER's 30-day initial review period expires, clinical studies can be initiated, unless a clinical hold has been placed.

29. 1.Helps in the result of successful preclinical development program. 2.IND is also the vehicle through which a sponsor advice the next stage of drug development i.e. clinical trial . 3. The preclinical study, helps the sponsor’s primary goal to determine that the product is reasonably safe for initial use in human . 4.It is important in the commercial development of compounds if it exhibit pharmacological activity . 5.It is important in assuring the marketing of a new drug and responsibility for compliance of sponsor. Importance of IND

30. 6. It is important for the company to initiate and conduct the clinical studies of their new product. 7. It secure the safety and effectiveness of the clinical trial subjects. 8.IND can be alternative in a life threatening situation when no standard acceptable therapy is available. 9.It gives the indication of new drugs. 10. Pharmacology and toxicology information of new drugs.