IND Enabling Studies (IND)

IND- Investigational New Drug

1. IND ENABLING STUDIES Submitted By - Anurag Chourasia M.Pharma

2. Contents Definitions Categories of IND Pre IND meeting Content and Format of IND FDA Form Pre IND Development IND Clinical Development NDA/BLA Marketing Overview of the Regulatory Process

3. Definitions Sponsor A sponsor is an individual, company, institution, or organization that takes responsibility for and initiates a clinical study Investigator An investigator is an individual under whose immediate direction the study drug is administered or dispensed. If a team is involved, the leader is the investigator; other team members are sub-investigator Sponsor-Investigator A sponsor-investigator is an individual who both initiates and conducts a study and under whose immediate direction the study drug is administered or dispensed. This person must follow the requirements pertaining to a sponsor and those pertaining to an investigator

4. 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.

5. Regulatory Process

6. When Do We Need IND An IND is required any time when we want to conduct a clinical trial of an unapproved drug. An IND would be required to conduct a clinical trail if the drug is : -- A new chemical entity , not approved for the indication under investigation in a new dosage form. -- Being administered at a new dosage level. --In combination with another drug and the combination is not approved.

7. Categories of IND 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. 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.

8. Pre IND Meeting A meeting between the sponsor and the FDA frequently is useful in resolving questions and issues raised during the preparation of an IND.  The FDA encourages such meetings to the extent that :  They aid in the solution of scientific problems and  To the extent that the FDA has available resources.  Most issues and questions are usually related to  Design of animal studies needed to initiate the clinical trials.  The scope and design of the initial study in Humans.

9. Content and Format of IND Application The content and format of an initial IND is laid out in 21 CFR(code of federal regulations) part 312 . 1. Cover sheet – 312.23(a)(1) FDA form 1571 2. Table of contents – 313.23(a)(2) 3. Introductory statement and general investigational plan – 312.23(a)(3) 4. Investigators brochure – 312.23(a)(5) 5. Clinical protocol – 312.23(a)(6) 6. Chemistry , manufacturing and control data – 312 7. Pharmacological and toxicological information – 312.23(a)(18) 8. Previous human exposure – 312.23(a)(9) 9. Additional information – 312.23(a)(10) 10. Relevant information – 312. .23(a)(10) 10. Relevant information – 312.23(a) (11)

10. FDA Form 1571 1.Name of the sponsor : He/she is the person who takes responsibility for and initiates a clinical investigation . May be a pharmaceutical company, a private or academic organization, or an individual 2.Date of submission : It is the date when the application is mailed to FDA . 3. Address : It is the address to which written correspondence from FDA should be directed 4. Telephone number : It is the number where the sponsor is usually available during normal working hours. A telephone number must be provided. 5. Name(s) of Drug : List the generic name(s) and trade name, if available. Also, state the dosage form(s)

11. FDA Form 1571 6. IND Number : If an emergency IND number was previously assigned by FDA, or the Form FDA 1571 is being included with an amendment to the original IND, then that IND number should be entered here; otherwise, the space should be left blank. 7. Indication. 8. Phase of clinical investigation to be conducted. 9. list number of all investigational new drug application. 10. Serial number. 11. Contents of application 12.Name and title of the person responsible for monitoring the conduct and progress of clinical investigation 13. Is any part of the clinical study to be conducted by CRO.

12. FDA Form 1571 14. Name of sponsor’s authorized representative 15.Signature 16.Address 17.Telephone no. 18.Date

13. Pre-IND Development The regulatory approval process usually begins with the submission of an Investigational New Drug (IND) application, which contains information that the FDA needs to decide if a drug is safe to study in humans. The information included in the IND application must be generated before clinical studies can occur, sometimes called the Pre-IND or Pre-clinical phase of development. Although the FDA is not required to be involved during the Pre-IND phase, the FDA can guide sponsors in putting together an IND package through the Pre-IND Consultation Program. >> Critical Question: Is the drug safe?

14. IND Clinical Development A series of progressively larger clinical trials are conducted as more information is learned about the safety and potential efficacy of the drug. The trials are typically separated into three phases of development: Phase I: THESE TRIALS include several small trials designed to learn how the drug is broken down by the body and to begin studying the drug’s safety in humans. Phase II: These larger trials look for evidence that the drug is acting as expected and compare different ways of giving the drug in order to find a safe and potentially effective dosing strategy. Phase III: These MUCH larger trials are intended to verify that the drug is safe and prove that the drug is effective. Critical Question: To what extent is it safe? >> Phase 3 >> Phase 2 Phase 1

15. New Drug Application (NDA)/ Biologics License Application (BLA) If the results of the Phase 3 trials show that the drug is safe and effective, then the Sponsor may submit a New Drug Application (NDA) or Biologics License Application (BLA). If the NDA/BLA is approved, then the drug may be sold and used by the public. The FDA and Sponsor agree upon the drug’s label, which provides information to help physicians and their patients decide if they wish to use the drug and provides instructions for how it should be used. Critical Question: To what extent is it safe? >> Phase 3 >> NDA/BLA Application Phase 2

16. Post-Marketing The FDA may require that additional non-clinical studies or clinical trials be completed after the NDA/BLA is approved. For example, an additional clinical study might be conducted to provide information for a group of people who might benefit from the drug but who were not included in previous trials. The FDA continues to receive and review long-term safety information for approved drugs. Identification of new safety issues could require changes to the drug’s label or, in extreme cases, withdrawal of the drug from the market. Phase 3 Phase 2 Phase 1 >> NDA/BLA Application >> More Trials Manufactured >> Manufactured >> Continual oversight

17. OVERVIEW OF THE REGULATORY PROCESS >> Critical Question: Is the drug safe? >> IND Application Critical Question: To what extent is it safe? >> Phase 3 Phase 2 Phase 1 >> NDA/BLA Application >> More Trials >> Manufactured >> Manufactured Continual oversight

18. References http://www.bioscience.org/2013/v5e/af/627/fig1.jpg https://image.slidesharecdn.com/ctp-150215132923-conversion-gate02/95/clinical-trial-phases-8-638.jpg?cb=1424007678 https://www.researchgate.net/publication/260606556/figure/fig3/AS:273652612595733@1442255275238/The-drug-development-process-from-preclinical-development-to-approval-The-focus-of-this.png