Investigational New Drug application

Investigational New Drug application

1. Investigational New Drug Studies (IND) By: Omkar Dattatray Janjire Guide: Dr. Vaishali Undale Dr . D .Y. Patil Institute Of Pharmaceutical Sciences & Research Pimpri

2. Contents: Drug development process IND definition Classification of IND Types of IND Format of INDA FORM’S of INDA IND review process

3. Drug Development Process: Drug discovery Preclinical(Animals ) 1)Efficacy 2)Safety 3)4+years Investigational New Drug 1)INDA submission 2)IND approval(30 days) Clinical Trails(Humans) Phase-1: Healthy Volunteers(28-80)(safety) Phase-2: Patient volunteers(100-300)(expanded safety ) Phase-3: Patient volunteers(1000-3000)( safety & efficacy) NDA(2months) 1)NDA application 2)NDA approval Phase-4 Post marketing approval Range:1-3 yrs, avg-18months Range: 2-10 yrs The overall process takes almost 10-15 years for drug to come in market

4. Wha t is Investigational New Drug (IND): An IND is application which allows sponsor to lawfully Use a investigational drug for conducting clinical trials In humans .

5. Importance of INDA: An INDA is required any time to conduct a clinical trail of an unapproved drug An IND would be required to conduct a clinical trail if the drug is a) If a drug is new chemical entity ,which is not approved for certain indications. b) Being administered at a new dosage level. c) In combination with another drug and the combination is not approved. 3. All clinical studies where a new drug is administered to human subject, regardless of whether the drug will be commercially developed, require an INDA.

6. Classification of IND: Commercial: Permits sponsor to collect data on clinical safety and effectives needed for application for marketing in the form of NDA. Non commercial(Research): Permits the sponsor to use drug in research ton obtain advanced scientific knowledge of new drug. NO plan to market the product.

7. Types of IND applications:

8. Three Broad Areas of IND Application: Animal pharmacology and toxicology studies: Preclinical data to permit an assessment as to whether the product is reasonably safe for initial testing in humans. 2. Manufacturing information: Information pertaining to the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product. This information is assessed to ensure that the company can adequately produce and supply consistent batches of the drug. 3 . I nvestigator information: It contains information about qualification of Investigator.

9. Format of INDA: Cover Sheet: Name of Sponsor Sponsor Address Name of Drug Commitment of Sponsor Signature of Sponsor

10. Table Content: Description of the investigational drug All active ingredients Drug's pharmacological classification Structural formula Route of administration Summary of previous human experience Formulation of dosage forms Objective and planned duration of proposed clinical investigation.

11. Investigational plan: Description of clinical studies planned for the experimental drug Purpose of the study Indication to be studied Types of trials to be initiated 1.Number of study subjects 2.Risks involved

12. Investigator Brochure: Structural formula of drug Summary of pharmacological, toxicological, pharmacokinetic effects in animals. Safety and efficacy Purpose of study Dose/dose frequency Monitoring procedures

13. Protocol: A clinical protocol describes how a particular clinical trial is to be conducted. It describes : the objectives of study the trial design how subjects are selected how the trial is to be carried out

14. FORM`S: 1)FORM 1571: Sponsor files the IND application in form 1571 to FDA for review once successful series of preclinical studies are completed.

15. 2) FORM 1572: Along with the IND application the sponsor submits the statement of the investigator (investigator`s undertaking)

16. Once the INDA is submitted the sponsor must wait 30 calendar days before initiating any clinical trails The CDER( Centre For Drug Evaluation & Research) is division of the FDA that reviews INDA to ensure that the drug is safe and effective If the sponsor here nothing from CDER then on 31 day after submission of INDA the study may proceed as submitted

17. The sponsor should not initiate clinical study until 30 days until he receives the FDA approval for IND. The sponsor should not start clinical study when it’s placed on clinical hold. The sponsor shall see that IRB do initial and continue approval of each study proposed in the trial. Conduction of investigation in accordance with all the other applicable regulatory requirements. He should conduct or supervise the investigation. Commitments of sponsor:

18. Sponsor Responsibilities: Select qualified investigators Ensure that the investigation is conducted in accordance with the protocols in the IND Ensure proper monitoring of the investigation Maintain an effective IND Promptly inform FDA and all investigators of significant new adverse events Maintain adequate records, reporting and monitoring of the investigation to include product accountability

19. Resources for IND Applications: The following resources include the legal requirements of an IND application, assistance from CDER to help you meet those requirements, and internal IND review principles, policies and procedures. Pre-IND Consultation Program : Offered by CDER (Center for Drug Evaluation and Research) to foster early communications between sponsors and new drug review divisions in order to provide guidance on the data necessary to warrant IND submission. Guidance Documents for INDS : documents are prepared for FDA review staff and applicants/sponsors to provide guidelines to the processing, content, and evaluation/approval of applications and also to the design, production, manufacturing, and testing of regulated products Laws, Regulations, Policies and Procedures

20. Code Of Federal Regulation( CFR): It’s the codification of the general and permanent rules and regulations published in the Federal Register by the executive departments and agencies of the federal government of the United States. The CFR is divided into 50 titles that represent broad areas subject to Federal regulations. The FDA's portion of the CFR contains most regulations pertaining to food and drugs comes under CFR 21. 21 CFR part 312: IND 21 CFR part 314: INDA & NDA for FDA approval to market new drug.

21. INDA Annual reports 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:

1) Individual study information.
2) Summary of the study. 3) List of changes made in investigators broucher 4) Significant marketing developments like approval, withdrawal or suspension in any particular country.

22. Applicant ( Drug Sponsor) IND (Review by CDER) Medical Chemical Pharmacology/Toxicology Statistical Safety review INDA Review Process:

23. Safety acceptable for study to proceed Clinical hold decision Complete reviews Notify sponsor Reviews complete and acceptable Sponsor notified of deficiencies No deficiencies Study ongoing NO YES YES NO YES YES

24. FDA Review of The INDA: Once the IND is stamped as received ,it is sent to the review division within CDER. On arrival at the review division, it is critically evaluated by several reviewers of ✓Chemistry ✓Biopharmaceutics ✓Medical ✓Statistics ✓Microbiology ✓Pharmacology/toxicology sections

25. Role of Pharmacologist in IND submission & review: This team is staffed by pharmacologists who evaluate the results of animal testing and attempt to relate animal drug effects to potential effects in humans. This section of the application should contain, if known: A description of the pharmacologic effects and mechanism(s) of action of the drug in animals Information on the absorption, distribution, metabolism and excretion (ADME) of the drug.

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