Basically, there are two types of drug products: (1) new drug products (NDA) and (2) generic drug products (ANDA). New drug product development is required to go through through a tedious process, which is divided into three phases. When there is only "one" phase for the generic product development. However, it doesn't mean that ANDA is earlier than NDA. The formulation and process developement for ANDA product can be MUCH MORE difficult to develop, if the formulator is developing a bio- equivalent and non-infringing products (paragraph iv). A summary for how drug product development is outlined as below: NEW DRUG PRODUCT (NDA) After a drug company identifies a potential drug candidate, it files an Investigational New Drug Application (IND). If the IND is approved by the FDA, the drug company can begin the first phase of development. The IND consists of three phases: Phase 1, Phase 2 and Phase 3. In Phase 1, the company first designs a "vehicle" to the drug candidate and conducts clinical trials using healthy subjects to determine this "drug product's" basic properties, such as ithe extent of drug absorption, drug absorption rate and its safety profile in humans. Typically, this stage lasts for one to two years. At the beginning of Phase 2, the drug company conducts a long-term, small-scale toxicology study (e.g. nine months) for the drug product using animal subjects. If the drug company demonstrates that its product is safe to use. The company will initial a long-term, small-scale clinical study to assess the product's efficacy and safety in hamans. Drug company also determines the optimal dosage levels in this stage. At the end of Phase 2, the drug company will meets with FDA agents to discuss the development process, test results and the protocols for Phase III. Phase 3 is usually the most extensive and most expensive part of the drug product development. Large-scale testings for safety and efficacy are conducted in multiple centers. The testings may take years to complete. It usually involves a few hundred to a few thousand patients. The information obtained will be used to decide if the drug satisfies its "benefit- risk relationship". Once Phase III is complete, the drug company files an New Drug Application (NDA). The NDA describes the manufacturing process and composition of the drug product, it also provides evidence of its safety and effectiveness to FDA. If the FDA usually takes one to two years to review and approve the NDA. During the NDA stage, the FDA consults advisory committees made of experts to abain advices on drug safety, effectiveness and labeling. Once FDA approves the drug product, the company can market the drug product with FDA regulated labeling. GENERIC DRUG PRODUCT (ANDA) Regulatory Affairs A generic drug product is identical, or bioequivalent to a brand-name drug product in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use. Although generic drugs are chemically identical to their branded counterparts, they are typically sold at substantial discounts from the branded price. It is because generic manufacturers donÂ’t have the investment costs of the developer of a new drug. New drug is developed under patent protection. The patent protects the investment including research, development, marketing, and promotion by giving the company the sole right to sell the drug while it is in effect. As patents near expiration, manufacturers can apply to the FDA to sell generic versions for the original drug product. Because those manufacturers don' have the same development costs, they can sell their product at substantial discounts. Drug companies must submit an abbreviated new drug application (ANDA) for approval to market a generic drug product. The Drug Price Competition and Patent Term Restoration Act of 1984, more commonly known as the Hatch-Waxman Act, made ANDAs possible by creating a compromise in the drug industry. Generic drug companies gained greater access to the market for prescription drugs, and innovator companies gained restoration of patent life of their products lost during FDA's approval process. Under the Hatch-Waxman Act, a company can also seek approval from FDA to market a generic drug product before the expiration of a patent relating to the brand name drug upon which the generic is based. The first company to submit an Abbreviated New Drug Application (ANDA) with the FDA has the exclusive right to market the generic drug for 180 days. Generic Drug Product Development Process Generic drug product development typically begins by identifying potential market opportunities. Factors such as market size, patent expiration date(s), market exclusivity, source of raw materials can affect the whole generic drug product development process. Once the generic drug manufacturer select a candidate, the generic drug manufacturer begins the development process. The ANDA sponsor's first task is to identify a reliable source of the active pharmaceutical ingredient (API or the drug) that can meet established standards of identity, strength, quality, and purity. Then the ANDA sponsor will select the inactive ingredients for the formulation based on compatibility and patents on the innovator's formulation. After the ANDA sponsor developed the prototype formulation, he will conduct small-scale bio-equivalence studies (6-8 subjects)to test the product performance. The ANDA sponsor manufactures the test products under current good manufacturing practice (cGMP). cGMP represents the minimum regulatory standards that address every aspect of drug development, testing, materials, equipment, manufacturing, record keeping, documentation practices, facilities, and personnel. If the data for the small-scale study is promising, the ANDA sponsor manufactures a full bio-batch (100,000 units) for full bioequivalence studies (> 24 subjects). For controlled release products and certain types of products, the ANDA sponsor also needs to run food effect bioequivalence study. After the product demonstrates for being bio-equivalent to the innovator product and it is stable under accelerated conditions (elevated temperature and humidity) for 3 months, the ANDA sponsor can file an ANDA to the Office of Generic Drugs (OGD) for the product. And, the generic applicant must: 1) certify in its ANDA that the patent in question is invalid or is not infringed by the generic product (known as "paragraph IV certification"); and 2) notify the patent holder of the submission of the ANDA. As that certification is later sent to the brand company - which, by filing a patent infringement suit against us, automatically prevents the FDA's approval of our product for up to 30 months. ANDA sponsor must then defend itself against the inevitable patent litigation that will be initiated by the brand company. The total duration from development to marketing of a product is typical from 4 to 7 years. Though the generic drug product development process is tedious, the profit can be huge. ARTICLE INDEX CREAM LOTION PREPARATION | PRODUCTS UNDER DEVELOPMENT ALL RIGHTS RESERVED 2006 zhion. |
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