IND IND (Investigational New Drug Application)

&& NDA NDA (New Drug

Application)

Presented by:Swati Sarin

DRUG DEVELOPMENT

Development of a new therapeutic drug is a complex, lengthy and expensive process

costs nearly 900 million dollars and an average of 15 years.

THE TWO TRANSLATIONAL THE TWO TRANSLATIONAL BLOCKSBLOCKS

Basic Biomedical Research

Clinical Science

and Knowledge

Goal: Improved

Health

Translation from basic science to

human studies

Translation ofnew knowledge

into clinical practice

DRUG DEVELOPMENT PROCESS

IND (Investigational IND (Investigational New Drug New Drug

Application)Application)

IND (Investigational New Drug Application)

FDA's role in the development of a new drug begins when the drug's sponsor has screened the new molecule for pharmacological activity and acute toxicity potential in animals, wants to test its diagnostic or therapeutic potential in humans

The molecule changes in legal status under the Federal Food, Drug, and Cosmetic Act and becomes a new drug subject to specific requirements of the drug regulatory system

Drug is to be the subjected to an approved marketing application before it is transported or distributed across state lines

IND- notice of claimed investigational exemption for a new drug must be filed with regulatory body

TYPES OF INDTYPES OF IND Investigator IND

o Submitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed.

o Physician might submit a research IND to propose studying an unapproved drug, or an approved product for a new indication or in a new patient population

Emergency Use IND o  Allows FDA to authorize use of an experimental drug in

an emergency situation o Does not allow time for submission of an IND in

accordance with  21CFR , Sec. 312.23 or Sec. 312.34

Treatment IND o 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

CLASSIFICATION OF INDCLASSIFICATION OF INDCommercial

oPermits sponsor to collect data on clinical safety and effectiveness needed for application for marketing in the form of NDA

Research (non-commercial)

oPermits the sponsor to use drug in research to obtain advanced scientific knowledge of new drug

oNo plan to market the product

CONTENT OF INDCONTENT OF INDIn three broad areas: Animal Pharmacology and Toxicology Studies –

o An assessment as to whether the product is reasonably safe for initial testing in humans

o Any previous experience with the drug in humans Manufacturing Information

o composition, manufacturer, stability, and controls used for manufacturing the drug

Clinical Protocols and Investigator Information o Commitments to obtain informed consent from the research

subjects, to obtain review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations.

Once the IND is submitted, the sponsor must wait 30 days 30 days before initiating any clinical trials.  During this time, FDA  has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk

FORMAT OF INDFORMAT OF INDA. Cover sheet (Form FDA-1571)o Name, address, telephone of sponsoro Identification of phaseso Commitment not to begin CT until IND approvalo Commitment by IRB- Form 56o Commitment for conducting CT- accordance with regulationso Name, title – Monitoro Name, title – person(s) for reviewingo Name, Address of CRO, if anyo Signature of sponsor

B. Table of contentsC. Introductory statement & general investigational

planD. Investigators brochureE. Study protocolF. Investigator facilities & IRB dataG. Chemistry manufacturing & control dataH. Pharmacology & toxicology dataI. Previous human experience

RESOURCES FOR IND RESOURCES FOR IND APPLICATIONSAPPLICATIONS

• Pre-Investigational New Drug Application (IND) Consultation Program

o 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 INDso 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

GUIDANCE DOCUMENTSGUIDANCE DOCUMENTS For the complete list of CDER guidance, For the complete list of CDER guidance,

please see the please see the Guidance IndexGuidance Index Safety Reporting Requirements for INDs and BE/BA Studies CGMP for Phase 1 Investigational Drugs Exploratory IND Studies Content and Format of Investigational New Drug Applications (INDs)

for Phase 1 Studies of Drugs, Including Well Characterized, Therapeutic, Biotechnology-Derived Products

Q & A - Content and Format of INDs for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-Derived Products

Bioavailability and Bioequivalence Studies for Orally Administered Drug Products

IND Exemptions for Studies of Lawfully Marketed Drug or Biological Products for the Treatment of Cancer

Guideline for Drug Master FilesA Drug Master File (DMF) is a submission to the Food and Drug

Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs.

Required Specifications for FDA's IND, NDA, and ANDA Drug Master File Binders

Immunotoxicology Evaluation of Investigational New Drugs

LAWS,REGULATIONS, LAWS,REGULATIONS, POLICIES, PROCEDURESPOLICIES, PROCEDURES

The Federal Food, Drug, and Cosmetic Act is the basic food and drug law of the U.S The law is intended to assure consumers that foods are pure and wholesome, safe to eat, and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are safe and made from appropriate ingredients; and that all labeling and packaging is truthful, informative, and not deceptive.

LAWS,REGULATIONS, LAWS,REGULATIONS, POLICIES, PROCEDURES POLICIES, PROCEDURES Cont…..Cont….. Code Of Federal Regulations (CFR)

o The final regulations published in the Federal Register (daily published record of proposed rules, final rules, meeting notices, etc.) are collected in the CFR. 

o The CFR is divided into 50 titles that represent broad areas subject to Federal regulations. 

o The FDA's portion of the CFR interprets the The Federal Food, Drug, and Cosmetic Act and related statutes.  Section 21 of the CFR contains most regulations pertaining to food and drugs.  

 21CFR Part 312 Investigational New Drug Application

21CFR Part 314INDA and NDA Applications for FDA Approval to Market a New Drug (New Drug Approval)

21CFR Part 316 Orphan Drugs

21CFR Part 58 Good Lab Practice for Nonclinical Laboratory [Animal] Studies

21CFR Part 50 Protection of Human Subjects

21CFR Part 56 Institutional Review Boards

21CFR Part 201 Drug Labeling

21CFR Part 54 Financial Disclosure by Clinical Investigators

LAWS,REGULATIONS, LAWS,REGULATIONS, POLICIES, PROCEDURES POLICIES, PROCEDURES Cont…..Cont…..CDER's Manual of Policies and

Procedures (MaPPs)MaPPS are approved instructions

for internal practices and procedures followed by CDER staff to help standardize the new drug review process and other activities.

IND REVIEW PROCESSIND REVIEW PROCESS

Guidance for preparation of INDGuidance for preparation of IND

Reference to document:

http://www.fda.gov/cder/regulatory/applications/

ind_page_1.htm

NDA (NEW DRUG NDA (NEW DRUG APPLICATION)APPLICATION)

NDA NDA (New Drug (New Drug Application)Application)

The vehicle through which drug sponsors formally propose that the regulatory body approve a new pharmaceutical for sale and marketing.

Form 44

The data gathered during the animal studies and human clinical trials of an Investigational new product become part of the NDA.

GOAL OF NDAGOAL OF NDAProvide enough information to permit FDA

reviewers to establish the following:

Safety & effectiveness of drug?

Benefits overweigh risks?

Is the drug’s proposed labelling (package insert) appropriate, and what should it contain?

Are the methods used in manufacturing (Good Manufacturing Practice, GMP) the drug and the controls used to maintain the drug’s quality adequate to preserve the drug’s identity, strength, quality, and purity?

Risk Benefit

NDA CONTENTSNDA CONTENTS1. Introduction

o Brief description of the drug and the therapeutic class to which it belongs

2. Chemical and pharmaceutical information

3. Animal Pharmacology

4. Animal Toxicology

5. Human/Clinical Pharmacology phase I

6. Therapeutic exploratory trials (Phase II)

7. Therapeutic confirmatory trials (Phase III)

8. Special Studieso Geriatrics, pediatrics, pregnant or nursing women

9. Regulatory status in other countries

10. Prescribing information

11. Samples and Testing Protocol/s

Once the application is submitted, the FDA has 60 days to conduct a preliminary review which will assess whether the NDA is "sufficiently complete to permit a substantive sufficiently complete to permit a substantive review”review”

If everything is found to be acceptable, the FDA will decide if the NDA will get a standard or accelerated review and communicate the acceptance of the application and their review choice in another communication known as the 74-day letter74-day letter

A standard review implies an FDA decision within about 10 months 10 months

CONTENTS OF ANDACONTENTS OF ANDA Data for a drug already approved in the Data for a drug already approved in the

countrycountry

1. Introduction2. Chemical and pharmaceutical

information3. Marketing information4. Special studies conducted with

approval of Licensing Authority

REQUIREMENTS FOR SIMILAR REQUIREMENTS FOR SIMILAR PRODUCTSPRODUCTS

GENERIC DRUGS Drug product that is comparable to any innovator

drug product in dosage form, strength, route of administration, quality, performance characteristics and intended use but is produced & distributed without patent application.

This drug have already been approved via an NDA submitted by another maker are approved via an Abbreviated New Drug Application (ANDA), which does not require all of the clinical trials normally required for a new drug in an NDAo No need for preclinical and clinical datao Bioequivalenceo Chemistry, microbiology, manufacturing

REQUIREMENTS FOR SIMILAR REQUIREMENTS FOR SIMILAR PRODUCTS Cont….PRODUCTS Cont….

BIOLOGICS

Biologics such as vaccines and many recombinant proteins used in medical treatments are generally approved by FDA via a Biologic License Application (BLA), rather than an NDA.

Manufacture of biologics is considered to differ fundamentally from that of less complex chemicals, requiring a somewhat different approval process.

REQUIREMENTS FOR SIMILAR REQUIREMENTS FOR SIMILAR PRODUCTS Cont….PRODUCTS Cont….

MEDICAL DEVICES

Medical devices are approved by a variety of methods depending on the class of the device

Class I: Devices that do not require premarket approval

Eg; Dental flossEg; Dental floss A Pre-market Application (PMA) largely equivalent to

an NDA is required for class III devices.These tend to be devices that are permanently implanted into a human body or may be necessary to sustain life.

Eg; artificial heartEg; artificial heart 510(k) approval that shows the device is equal to or

better than a predicate device already on the market is required for class II devices.

Eg;Eg;Diagnostic tests, cardiac catheters, and Diagnostic tests, cardiac catheters, and amalgam alloys used to fill cavities, hearing aidsamalgam alloys used to fill cavities, hearing aids

REQUIREMENTS FOR SIMILAR REQUIREMENTS FOR SIMILAR PRODUCTS Cont….PRODUCTS Cont….

Drugs for life threatening/serious disease/relevance to India

Clinical and toxicological data may be abbreviated, deferred or omitted as per the licensing authority

NDA REVIEW PROCESSNDA REVIEW PROCESS

REFERENCESREFERENCES

http://www.hhs.govhttp://www.fda.gov/

regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact

Gupta S. K; Basic principles of clinical research and methodology.

QUESTIONS???QUESTIONS???

THANK YOUTHANK YOU