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1. Drug Discovery Process

2. NDA-New Drug Application

3. ANDA-Abbreviated New Drug Application

Drug Development Process
Drug Discovery Preclinical Clinical Trials FDA Review Scale-Up to Mfg.

~ 5,000 – 10,000 250 5




1 2 3



20–100 100–500 1,000–5,000

0.5 – 2
(Brand Name Drug) (Generic Drug)
NDA Requirements ANDA Requirements
1. Animal Studies 1-3. Bioequivalence
2. Clinical Studies
3. Bioavailability Studies
4. Chemistry 4. Chemistry
5. Manufacturing 5. Manufacturing
6. Controls 6. Controls
7. Labeling 7. Labeling
8. Testing 8. Testing


 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?
 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 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
 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 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
 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.
 The ANDA is intended to streamline the review
process for genetic versions of approved drug
 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.
 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.
 An ANDA contains data that, when submitted to the
FDA’s 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 ( Orange Book ).
 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 patient’s bloodstream in the same amount of
time as that of the innovator drug.
Annual Reports

 TheFDA 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
A Para I filing is made when the innovator has not
made the required patent information in the Orange
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.
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.
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.