investigational new drug application
DESCRIPTION
Find more related content at www.Pharminfopedia.comTRANSCRIPT
04/12/23 1
Investigational New Drug
Application (INDA)
www.PharmInfopedia.com
INTRODUCTION REGULATORY ASPECT TYPE OF IND REQUIERMENT IND CONTENT OF IND IND AMENDMENT ANNUAL REPORT OF IND CONCLUSION
04/12/23 2
WHAT I WILL TELL
www.PharmInfopedia.com
What is INDA
04/12/23 3
General introductionGeneral introduction
this data and information is generated this data and information is generated and gathered from three broad areas:and gathered from three broad areas:
Animal P’cology & Toxicology studiesAnimal P’cology & Toxicology studiesManufacturing informationManufacturing informationClinical Protocols & Investigator Clinical Protocols & Investigator InformationInformation
www.PharmInfopedia.com
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
04/12/23 4
Regulation
www.PharmInfopedia.com
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)
04/12/23 5
Definitions
www.PharmInfopedia.com
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
04/12/23 6
Sponsor
www.PharmInfopedia.com
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)
04/12/23 7
Definitions
www.PharmInfopedia.com
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))
04/12/23 9
Definitions
www.PharmInfopedia.com
04/12/23 10
IND Requirements
www.PharmInfopedia.com
1. Commercial IND2. Emergency use IND 3. Treatment IND
04/12/23 13
TYPE OF IND
www.PharmInfopedia.com
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.
04/12/23 14
Objective
www.PharmInfopedia.com
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
04/12/23 15
IND Content Requirements21 CFR 312.23
www.PharmInfopedia.com
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.
04/12/23 16
Cover Sheet (form FDA 1571)
www.PharmInfopedia.com
Drug Name®
IND table of contentsItem 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……
04/12/23 17
Table of Contents
www.PharmInfopedia.com
04/12/23 18
iv) iv) General Investigational Plan…..General Investigational Plan…..5 Investigator’s Brochure…….5 Investigator’s Brochure…….6 Protocol……..6 Protocol……..7 Chemistry, Manufacturing & 7 Chemistry, Manufacturing & Control Information…Control 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 & Toxicology 8 Pharmacology & Toxicology Information…….Information…….
www.PharmInfopedia.com
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)….
04/12/23 19www.PharmInfopedia.com
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
investigation04/12/23 20
Introductory Statement & General Investigational Plan:
www.PharmInfopedia.com
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
04/12/23 21www.PharmInfopedia.com
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
04/12/23 22www.PharmInfopedia.com
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 appropriate
04/12/23 23
Investigator’s Brochure (IB)
www.PharmInfopedia.com
Drug Name®Investigator's Brochure
Table of contentsPage Introduction……………………..Chemistry………………………. Physical Properties…… How Supplied……………. Pharmacology…………………. Specific Effect Studies… General Studies………….
04/12/23 24www.PharmInfopedia.com
Toxicology……………………….. Acute Toxicity……………. Multidose Toxicity………. Special Toxicity Studies………Reproductive Studies…… Mutagenicity Studies…….Pharmacokinetics……………… Preclinical……………………. Clinical………………………….Clinical Trial………………………. Phase 1………………………… Phase 2/3… ………………….
04/12/23 25www.PharmInfopedia.com
Safety/Efficacy Overview Safety………………………….. Efficacy………………………..Possible Risks and Side Effects…References………………………….
04/12/23 26www.PharmInfopedia.com
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.
04/12/23 28
5 Protocols
www.PharmInfopedia.com
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
04/12/23 29www.PharmInfopedia.com
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 hold
04/12/23 30
CMC Information
www.PharmInfopedia.com
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
04/12/23 32
Other IND Items
www.PharmInfopedia.com
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
implementation04/12/23 33
IND Protocol Amendments
www.PharmInfopedia.com
21 CFR 312.31
Information amendments advise the FDA of: New tox, CMC or other technical information Notice of discontinuance of a clinical study
04/12/23 34
IND Information Amendments
www.PharmInfopedia.com
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.
04/12/23 35
IND Safety Reports:
www.PharmInfopedia.com
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 information
04/12/23 36
Annual Reports
www.PharmInfopedia.com
CMC change information Revised/updated investigator brochure with
revisions described Foreign marketing experience Outstanding business with the FDA
04/12/23 37
Annual Reports (cont’d)
www.PharmInfopedia.com
It is option of a sponsor to withdraw an IND at
any time without prejudice.On withdrawn, sponsor must notify the FDA.
04/12/23 43
Withdrawal of an IND
www.PharmInfopedia.com
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
04/12/23 44
Conclusions
www.PharmInfopedia.com
1.www.fda.gov/cder/about/history/time1.htm2.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.htm5.www.fda.gov/cder/handbook/ndabox.htm6.www.fda.gov
04/12/23 46
List of references
www.PharmInfopedia.com
04/12/23 47www.PharmInfopedia.com