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Nda and Anda
Nda and Anda
Agenda
PRE-DISCOVERY
250
IND SUBMITTED
NDA SUBMITTED
PHASE 1
PHASE 2
PHASE 3
3 6 YEARS
0.5 2 YEARS
INDEFINITE
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?
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.
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
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-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.
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.