NDA and ANDA

Agenda

1. Drug Discovery Process

2. NDA-New Drug Application

3. ANDA-Abbreviated New Drug Application

Drug Development Process

INDEFINITE

Drug Discovery Preclinical Clinical Trials FDA Review Scale-Up to Mfg. Post-MarketingSurveillance

ONE FDA-APPROVED

DRUG

0.5 2 YEARS6 7 YEARS3 6 YEARS

NUMBER OF VOLUNTEERS

PHASE 1

PHASE 2

PHASE 3

5250~ 5,000 10,000

COMPOUNDS

PRE-

DIS

CO

VER

Y

20100 100500 1,0005,000

IND

SU

BMIT

TED

ND

A SU

BMIT

TED

4NDA vs. ANDA

(Brand Name Drug) NDA Requirements 1. Animal Studies2. Clinical Studies3. Bioavailability Studies 4. Chemistry5. Manufacturing 6. Controls7. Labeling8. Testing

(Generic Drug)

ANDA Requirements1-3. Bioequivalence

4. Chemistry5. Manufacturing6. Controls7. Labeling8. Testing

NDA-IS THE DRUG IS SAFE?

Is the drug safe? If used in the manner prescribed in the proposed label.

Is there clear and compelling evidence that the drug will do no harm or that any side effects are insignificant when compared with the potential benefits?

Note that the question is not composite and asked across all patients: A drug that cures 70% of the population but kills the remaining 30% to whom it is administered is not acceptable.

For any and every individual patient, is there a strong reason to believe that the drug is fundamentally safe?

NDA-IS THE DRUG IS EFFECTIVE?

Is the drug effective?

The relative safety is balanced in a cost/benefit analysis: Unless there is a demonstrable, clear benefit t, no drug is sufficiently desirable to deserve approval.

The FDA does not approve placebos whose only benefit is subconscious. Compelling evidence of effectiveness, ideally tied to sound theory, is required.

If there is sound evidence of safety, well - designed and well conducted studies of effectiveness, and conformity to the logistical requirements, the NDA should be approved with a minimum of difficulty.

NDA Filing Checklist Form 1571 completed Cover letter Name and address of sponsor Name, address, title, telephone, and e - mail of contact person Generic and trade name of drug or drug product FDA Code Number (assigned at time of preconference) Form 3674 Certification of Compliance with Requirements of Clinical-Trails.gov Data Bank completed Three copies of application in indexed binders Pagination: All pages included and properly numbered Headings: Section headings confirming to submission subparagraphs, with initial Table of Contents Integrated references: All referenced articles included in final

section, internally referenced in text

NDA Filing Checklist

Bibliography: Complete standard format bibliography listing all referenced articles

Container closure and packaging system information provided

Microbiological analysis provided Human Pharmacokinetics and Bioavailability

information provided Complete CMC (Chemistry, Manufacturing and

Control Director) Information provided, including evidence of purity, stability, toxicology testing, and integrity of API, placebo, and final product.

Analysis of all cited published studies and of all cited FDA findings, summarizing relevance and results

NDA Filing Checklist

Complete study protocol of BE/BA study and for any additional studies conducted by applicant.

Raw data for all applicant - conducted studies Drug Master File (DMF) completed, including

information on facilities, processes, and articles used in manufacturing, processing, packaging, and storage

Analysis of all applicant - conducted studies Investigators Brochure for all applicant - conducted

studies included with detailed information for investigators and Institutional Review Board records

NDA-CONTENT: Overview NDA provides sufficient information to permit

determination of whether the drug is safe and effective in its proposed use and whether the benefits of the drug outweigh the risks.

NDA provides sufficient information to permit determination of whether the drug s proposed labeling (package insert) is appropriate and what it should contain.

NDA provides sufficient information to permit determination of whether the methods used in manufacturing the drug and the controls used to maintain the drug s quality are adequate to preserve the drug s identity, strength, quality, and purity.

ANDA

The ANDA is intended to streamline the review process for genetic versions of approved drug products.

It was originally designed with two complimentary intents: to reduce the review time and work effort involved

in review of New Drug Applications. to provide a simplified pathway for submission of

applications for generic versions of already approved drugs.

The ANDA has earned a positive track record in both of these areas.

ANDA-CONTENT

An ANDA relies heavily on the previously approved NDA for evidence of efficacy and ultimate safety and concentrates instead on the manufacturing issues related to the specific generic formulation.

Specifically, the ANDA focuses on three areas: Formulation and manufacturing, Container integrity and packaging Stability and expiration.

ANDA-GENIRIC DRUG

An ANDA contains data that, when submitted to the FDAs CDER, Office of Generic Drugs, provide for the review and ultimate approval of a generic drug product.

Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, low-cost alternative to the public.

A generic drug product is one that is comparable to an innovator drug product in dosage form, strength, route of administration, quality, performance characteristics, and intended use.

All approved products, both innovator and generic, are listed in the FDA s Approved Drug Products with Therapeutic Equivalence Evaluations at http://www.fda.gov/cder/ob/default.htm ( Orange Book ).

ANDA-GENIRIC DRUG

Generic drug applications are termed abbreviated because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness.

Instead, generic applicants must scientifically demonstrate that their product is bioequivalent (i.e., performs in the same manner as the innovator drug).

One of the ways scientists demonstrate bioequivalence (BE) is by measuring the time it takes the generic drug to reach the bloodstream in 24 to 36 healthy volunteers.

This gives them the rate of absorption, or bioavailability (BA), of the generic drug, which they can then compare with that of the innovator drug. T

The generic version must deliver the same amount of active ingredients into a patients bloodstream in the same amount of time as that of the innovator drug.

Annual Reports

The FDA requires annual updating reports for investigational new drug applications (INDs), new drug applications (NDAs) and abbreviated new drug applications (ANDA)s.

FDA Inspection NDA & ANDA

Businesses that manufacture FDA-regulated products are not the only ones that can be inspected by the U.S. Food & Drug Administration at any time.

FDA also inspects clinical trial sites (studies in humans) and nonclinical laboratories that conduct animal, plant or microorganism studies used in FDA applications for drugs, biologics, or devices.

ANDA-Filings

A Para I filing is made when the innovator has not made the required patent information in the Orange Book.A Para II filing for the launch of a generic drug is made when the drug is already off patent.A Para III filing is made when the ANDA applicant does not have any plans to sell the generic drug until the original drug is off patent.A Para IV filing is made when the ANDA applicant believes its product or the use of its product does not infringe on the innovator's patents listed in the Orange Book or where the applicant believes such patents are not valid or enforceable.

ANDA-Filings

A Para IV filing is made when the ANDA applicant believes its product or the use of its product does not infringe on the innovator's patents listed in the Orange Book or where the applicant believes such patents are not valid or enforceable. In the case of Para IV filings, patents are validly circumvented. This involves a lot of research to find out the loopholes in the patents. But the gains are also the most in this case. The Hatch Waxman Act 1984 allows 180 days of exclusive marketing rights to the first ANDA filed and approved.

ANDA-Filings

Dr Reddy's Laboratories' Fluxotene (a 40 mg generic version of Pfizer's blockbuster drug Prozac) was cleared by the FDA and it made $10 million per month in the exclusivity period.

NDA and ANDAAgendaDrug Development ProcessNDA vs. ANDANDA-IS THE DRUG IS SAFE?NDA-IS THE DRUG IS EFFECTIVE?NDA Filing ChecklistNDA Filing ChecklistNDA Filing ChecklistNDA-CONTENT: OverviewANDAANDA-CONTENTANDA-GENIRIC DRUGANDA-GENIRIC DRUGAnnual ReportsFDA Inspection NDA & ANDAANDA-FilingsANDA-FilingsANDA-Filings