INVESTIGATIONAL NEW DRUG (IND).....

IND

1. INVESTIGATIONAL NEW DRUG (IND) PRESENTED BY – NIDHI BANSAL M.PHARMACY ROLL NO- 2004610003

2. An Investigational New Drug Application is the submission to Food & Drug Administration (FDA) requesting permission to initiate the study of new drug product. In many ways, the investigational new drug application is the result of successful preclinical development program. The IND application allows a company to initiate and conduct clinical studies for their new products. The IND is also a vehicle through which a sponsor advances to the next stage of drug development known as clinical trials. INTRODUCTION

3. During a new drug’s early preclinical development, the sponsor’s primary goal is to determine if the product is reasonably safe for initial use in humans, and if the compound exhibits pharmacological activity that justifies commercial development. When a product is identified as viable candidate for further development, the sponsor then focuses on collecting the data and information necessary to establish that the product will not expose humans to unreasonable risks when used in limited, early – stage clinical studies. .

4. DRUG-DISCOVERY, DEVELOPMENT

5. It takes 12-15years on an average for an experimental drug to travel from the lab to the patients. Only 5 in 5000 compounds that enter the preclinical- testing stage. One of these 5 tested on people is approved. DRUG DISCOVERY, DEVELOPMENT & APPROVAL PROCESS

6. Applicant (Drug Sponsor) An applicant or drug sponsor, is the person or entity whose assumes responsibility for the marketing of the drug, including responsibility for compliance with applicable provisions of the Federal Food, Drug and Cosmetic Act and related regulations. The sponsor is usually an individual , partnership, corporation, government agency, manufacturer or scientific institution. WHO CAN APPLY FOR IND?

7. The IND application provides FDA with data necessary to decide whether the new drug and the proposed clinical trial pose a reasonable risk to human subjects participating in the study. The safety of the clinical trial subject is always a primary concern of FDA. When preparing the IND and throughout the drug development process the 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 trial subjects. .

8. An IND would be required to conduct a clinical trial if the drug is - a new chemical entity not approved for the indication under investigation in the new dosage form. - Being administered at the new dosage level. All clinical studies where the new drug is administered to human subjects, regardless of whether the new drug will be commercially developed, required an IND. WHEN WE NEED AN IND?

9. 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. No plan to market the product. CLASSIFICATION OF IND

10. Investigator IND Application is submitted by a physician, who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. A physician might submit a research IND application to propose studying of; - An unapproved drug, - An approved product for a new indication or - An approved product in a new patient population. TYPES OF IND

11. 2. Emergency Use IND Application allows the FDA to authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND application, in accordance with 21CFR, Sec.312.23 or Sec.312.20. It is also used for patients who do not meet the criteria of an existing study protocol, or if an approved study protocol does not exist. In such a case, FDA may authorize shipment of the drug for an specified use in advance of submission of an IND application. .

12. 3. Treatment IND Application is 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. A drug that is not approved for marketing, may be under clinical investigation for a serious or immediately life-threatening disease condition in patients for whom no comparable or satisfactory alternative drug or other therapy is available. In the case of a serious disease, a drug ordinarily may be made available for treatment use during phase III investigations or after. In case of an immediately life – threatening disease, a drug may be made available for treatment use earlier than phase III, but not earlier than phase II. .

13. Animal pharmacology and toxicology studies : Preclinical data to permit an assessment as to whether the product is reasonably safe for initial testing in humans. Manufacturing information : Information pertaining to the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product. Clinical Protocols and Investigator Information : Detailed protocols for proposed clinical studies to assess whether the initial-phase trials will expose subjects to unnecessary risks. CONTENTS OF IND APPLICATION

14. Once the IND application is submitted, the sponsor must wait for 30 calendar days before initialing any clinical trials. If the sponsor hears nothing from CDER, then on Day 31 after submission of IND application the study may proceed as submitted. The CDER(Center for Drug Evaluation& Research) is a division of the FDA that reviews Application to ensure that the drugs are safe and effective. .

15. Cover sheet (FORM FDA 1571) Table of contents Introductory statement and a general investigational plan Investigators brochure Protocols Chemistry, manufacturing and control information Pharmacology and Toxicology information Previous human experience with the investigational drug Other relevant information like no. of IND submissions Protocol amendments, any changes in the protocol. IND CONTENT AND FORMAT

16. 1. COVER SHEET (FORM FDA-1571) - Name, address. telephone of sponsor Identification of phases Commitment not to begin clinical trials until IND approval Commitment by IRB- Form 56 Commitment for conducting clinical trials – accordance with regulations Name, title – Person responsible for monitoring the conduct Name, title – person for reviewing Signature of sponsor FORMAT OF IND

17. 2 . TABLE OF CONTENTS- Comprehensive listing of contents of IND application broken in volumes and page number. Table of content should include details of sections, appendices, attachments, reports and other reference material. A well drafted table of content will facilitate the task of review and decrease the review time. 3. INTRODUCTORY STATEMENT &GENERAL INVESTIGATIONAL PLAN- A brief 3 to 4 pages notes on- the investigational product (name of the drug, active ingredients, pharmacological class, structural formula, formation of dosage from, route of administration) Sponsor’s Investigational Plan Goal of the section is to – to provide brief description of the drug layout development plan of the drug .

18. 4. INVESTIGATORS BROCHURE- Description of drug substance and formation Pharmacological and toxicological effects of drug in animals. Pharmacokinetics and biological disposition of drug Information related to safety and effectiveness Anticipated risk and effectiveness 5.PROTOCOLS – Describes how the clinical trial would be conducted It describes the objective of the study, the trial design, how subjects would be subjected, how the trial is to be conducted. .

19. 6. CHEMISTRY,MANUFACTURING AND CONTROL INFORMATION Sufficient detail on quality, identity, purity and potency of the drug product. Manufactured in conformance with cGMP. CMC section includes the following- - Introduction CMC - Summary - Information of Placebo, if any - Proposed clinical label - Categorical exclusion of any environmental assessment .

20. 7. PHARMACOLOGY AND TOXICOLOGY INFORMATION- Non- clinical safety data that sponsor generated to prove that the IP is safe for clinical study. The amount and type of data depends on- class of new drug, duration of proposed clinical trial, patient population that will be exposed during the trial. 8.PREVIOUS HUMAN EXPERIENCE WITH THE INVESTIGATIONAL DRUG Integrated summary report of any human studies conducted on the investigational drug. Relevant to the safety of the investigations to be done – Pk studies, Pd studies Observed adverse event profile .

21. 9. OTHER RELEVANT INFORMATION No. of copies to be submitted Additional information- special topics like drug dependence & abuse potential, radioactive drugs and pediatric population. Information specially requested by FDA .

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23. Once the IND is stamped as received, it is sent to the review division with CDER. On arrival at the review division, it is critically evaluated by several reviewers of - Chemistry - Biopharmaceutics - Medical - Statistics - Microbiology - Pharmacology/ Toxicology sections FDA REVIEW OF IND

24. Sponsors should submit an annual report that provides the FDA with a brief update on the progress of all investigations included in the IND. It should contain the following: Individual study information Summary of the study Listing of any significant foreign marketing developments with the drug e.g. approval in another country. INDA ANNUAL REPORTS

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