Investigational new drug application

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Investigational new drug application

  1. 1.  03/22/15 1 Investigational New Drug Application (INDA) www.PharmInfopedia.com
  2. 2.   INTRODUCTION  REGULATORY ASPECT  TYPE OF IND  REQUIERMENT IND  CONTENT OF IND  IND AMENDMENT  ANNUAL REPORT OF IND  CONCLUSION 03/22/15 2 WHAT I WILL TELL www.PharmInfopedia.com
  3. 3.  What is INDA 03/22/15 3 General introductionGeneral introduction this data and information is generated andthis data and information is generated and gathered from three broad areas:gathered from three broad areas: Animal P’cology & Toxicology studiesAnimal P’cology & Toxicology studies Manufacturing informationManufacturing information Clinical Protocols & InvestigatorClinical Protocols & Investigator InformationInformation www.PharmInfopedia.com
  4. 4.   The regulations in 21 CFR 312 cover procedures and requirements for Investigational New Drug Applications (INDs)  These regulations define the roles and responsibilities of FDA reviewers, IND sponsors, and clinical investigators 03/22/15 4 Regulation www.PharmInfopedia.com
  5. 5.  Sponsor  A sponsor is an individual, company, institution, or organization that takes responsibility for and initiates a clinical study (21 CFR 312.3(b), 312.50) 03/22/15 5 Definitions www.PharmInfopedia.com
  6. 6.  A sponsor is responsible for:  Selecting qualified investigators  Ensuring study monitoring  Maintaining an effective IND, and  Ensuring AE risk information is provided to the FDA and investigators 03/22/15 6 Sponsor www.PharmInfopedia.com
  7. 7.  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-investigators (21 CFR 312(b), 312.60) 03/22/15 7 Definitions www.PharmInfopedia.com
  8. 8.  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 (21 CFR 312(b)) 03/22/15 9 Definitions www.PharmInfopedia.com
  9. 9.  03/22/15 10 IND Requirements www.PharmInfopedia.com
  10. 10.  1. Commercial IND 2. Emergency use IND 3. Treatment IND 03/22/15 13 TYPE OF IND www.PharmInfopedia.com
  11. 11.  To focus FDA’s attention during early phase of clinical research on assuring the safety of human test subjects.  To provide sponsors with a greater measure of flexibility in conducting Phase 1 trials.  To facilitate consultation between FDA & sponsors, especially after there is an indication that the new drug is safe and efficacious in humans. 03/22/15 14 Objective www.PharmInfopedia.com
  12. 12.  Cover Sheet (Form FDA 1571)  Table of Contents  Introductory Statement & General investigational plan  Investigator’s Brochure  Protocols  Chemistry, Manufacturing & Control Information  Previous Human Experience with the Investigational Drug  Additional Information 03/22/15 15 IND Content Requirements 21 CFR 312.23 www.PharmInfopedia.com
  13. 13.   The form is provided for basic information like name of drug, submission date, sponsor identification, phase of proposed clinical investigation, sponsor commitments, identification of clinical monitor and safety evaluator, information regarding transfer of responsibilities to a contract research organization. 03/22/15 16 Cover Sheet (form FDA 1571) www.PharmInfopedia.com
  14. 14.  Drug Name® IND table of contents Item title volume/page Introductory statement & general investigational plan… (i) Introductory statement…. (ii) summary of previous human experience with drug……. (iii) If the drug has been withdrawn from Investigation/Marketing…… 03/22/15 17 Table of Contents www.PharmInfopedia.com
  15. 15.  03/22/15 18 iv)iv) General Investigational Plan…..General Investigational Plan….. 5 Investigator’s Brochure…….5 Investigator’s Brochure……. 6 Protocol……..6 Protocol…….. 7 Chemistry, Manufacturing & Control7 Chemistry, Manufacturing & Control Information…Information… (a) Drug substance…………(a) Drug substance………… (b) Drug Product…………….(b) Drug Product……………. (c) Placebo (if applicable)…(c) Placebo (if applicable)… (d) Labeling…………………….(d) Labeling……………………. (e) Environmental Analysis ….(e) Environmental Analysis …. 8 Pharmacology & Toxicology8 Pharmacology & Toxicology Information…….Information……. www.PharmInfopedia.com
  16. 16.  9)Previous Human Experience with the Investigational Drug……. (i) Summary of Previous Human Experience…. (ii) If the drug is a combination of drug previously investigated/marketed……. (iii) If the drug has been marketed outside the United States…… 10 Additional Information (as applicable for radioactive drugs or drugs with dependence or abuse potential)…. 03/22/15 19www.PharmInfopedia.com
  17. 17.  It consists of four subsections: 1st subsection: (introductory statement)  Name of drug  P’cological Class  Structural formula  Route of administration  Broad objectives  Planned duration of the proposed clinical investigation03/22/15 20 Introductory Statement & General Investigational Plan: www.PharmInfopedia.com
  18. 18.  2nd subsection:  Brief summary of any previous human experience with the drug, including investigational or marketing experience in other countries 3rd subsection:  It is a statement as to whether or not the drug has been withdrawn from investigation or marketing in any country for any reason of safety or efficacy 03/22/15 21www.PharmInfopedia.com
  19. 19.  4th subsection:  Brief description of overall investigational plan for drug during the following year like: Indications to be studied, kinds of clinical trials to be conducted in first year 03/22/15 22www.PharmInfopedia.com
  20. 20.   Sponsor must provide to all clinical investigators, not required for sponsor investigators (21 CFR 312.55). It must include:  Brief product description  Pharm/tox summaries  Previous human experience  Description of anticipated risk and any special monitoring needs  Updates as appropriate03/22/15 23 Investigator’s Brochure (IB) www.PharmInfopedia.com
  21. 21.  Drug Name® Investigator's Brochure Table of contents Page Introduction…………………….. Chemistry………………………. Physical Properties…… How Supplied……………. Pharmacology…………………. Specific Effect Studies… General Studies…………. 03/22/15 24www.PharmInfopedia.com
  22. 22.  Toxicology……………………….. Acute Toxicity……………. Multidose Toxicity………. Special Toxicity Studies……… Reproductive Studies…… Mutagenicity Studies……. Pharmacokinetics……………… Preclinical……………………. Clinical…………………………. Clinical Trial………………………. Phase 1………………………… Phase 2/3… …………………. 03/22/15 25www.PharmInfopedia.com
  23. 23.  Safety/Efficacy Overview Safety………………………….. Efficacy……………………….. Possible Risks and Side Effects… References…………………………. 03/22/15 26www.PharmInfopedia.com
  24. 24.   Phase 1 protocol provides an outline of investigation by specifying information such as estimated number of test subjects, inclusion/exclusion criteria and dosing plan  Phase 2 and Phase 3 protocols are detailed, describing all aspects of the studies, such that any deviation in a design if required, it can be established in the protocol from the beginning. 03/22/15 28 5 Protocols www.PharmInfopedia.com
  25. 25.  All the protocols are required to contain the following elements:  Statement of the objectives and purpose of the study  Patient inclusion/exclusion criteria  Estimate of number of patients to be studied  Description of study design  Dosing information including planned maximum dosage and duration of individual patient exposure to the Drug  Description of the observations and measurements planned to fulfill the study objectives 03/22/15 29www.PharmInfopedia.com
  26. 26.   Emphasis in Phase I is on identification and control of raw materials and new drug substance, including information on any placebo as well  Even for Phase I, need enough information to assess safety  Extent of expected information increases as drug development proceeds  Throughout product development, good documentation of all manufacturing and testing steps is essential  Deficiencies in CMC information can result in clinical hold03/22/15 30 CMC Information www.PharmInfopedia.com
  27. 27.   Previous human experience needs to be included (if applicable)  Additional information such as pre-IND meeting minutes or critical references should be included as well  Serial numbering of pages of an IND is required (21 CFR 312.23(11)(e)) as this facilitates reference if the FDA has questions 03/22/15 32 Other IND Items www.PharmInfopedia.com
  28. 28.  21 CFR 312.30  A new protocol  Safety or design related changes to an existing protocol  New investigator (notification is required within 30 days of being added)  These should be submitted to the FDA prior to implementation  IRB approval is needed prior to implementation03/22/15 33 IND Protocol Amendments www.PharmInfopedia.com
  29. 29.  21 CFR 312.31 Information amendments advise the FDA of:  New tox, CMC or other technical information  Notice of discontinuance of a clinical study 03/22/15 34 IND Information Amendments www.PharmInfopedia.com
  30. 30.   If a sponsor notify any unexpected fatal / life threatening experience associated with the use of the drug requires to notify the FDA by telephone no later than 3 working days after receipt of the information, followed by a written report within 10 days. 03/22/15 35 IND Safety Reports: www.PharmInfopedia.com
  31. 31.  21 CFR 312.33  To be submitted within 60 days of the anniversary of “in effect” date  Include enrollment, demographic and conduct status information for each study  Adverse event summaries (safety reports, deaths, dropouts)  Drug action information  Preclinical study status information03/22/15 36 Annual Reports www.PharmInfopedia.com
  32. 32.   CMC change information  Revised/updated investigator brochure with revisions described  Foreign marketing experience  Outstanding business with the FDA 03/22/15 37 Annual Reports (cont’d) www.PharmInfopedia.com
  33. 33.  It is option of a sponsor to withdraw an IND at any time without prejudice. On withdrawn, sponsor must notify the FDA. 03/22/15 43 Withdrawal of an IND www.PharmInfopedia.com
  34. 34.  Two major outcomes from the IND discussion are:  30 days after an IND is submitted to the FDA, if the sponsor has not heard anything from the FDA it can be assumed that the drug is not on a clinical hold and clinical trials may be started  The Investigator’s Brochure, which will be used during that important first clinical study and in every clinical study thereafter, acts as the approved labeling for the drug while it is under an IND 03/22/15 44 Conclusions www.PharmInfopedia.com
  35. 35.  1.www.fda.gov/cder/about/history/time1.htm 2.Remington the science and practice of pharmacy, 20th edition, Lippincott,Williams & Wilkins, page no: 930-943 3. New Drug Approval Process: second Edition, Revised and Expanded, edited by Richard A. Guarino page no: 39-64, 243-263 4.www.fda.gov/cder/handbook/indbox.htm 5.www.fda.gov/cder/handbook/ndabox.htm 6.www.fda.gov 03/22/15 46 List of references www.PharmInfopedia.com
  36. 36.  03/22/15 47www.PharmInfopedia.com

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