Section 505New Drugs

Of the different chapters and sections covered in the FDCA, it is Section 505 of Chapter V for New Drugs which sets the overall foundation or basis for having pharmaceutical manufacturers or sponsors submit information to FDA before a product is allowed to market. Section 505 establishes that before the introduction of any new product into interstate commerce, an application needs to be filed with FDA for approval. Under Sections 505(b)(1), 505(b)(2), and 505(j), three types of drug applications are described. It is noted that Sections 505(b)(2) and 505(j) are the result of the Drug Price Competition and Patent Term Restoration Act of 1984. Together, these two sections replaced FDA's paper NDA policy that permitted an applicant to rely on studies published in the scientific literature to demonstrate safety and effectiveness of duplicates of certain post-19622 innovator or pioneer drug products.

For an NDA that is covered under 505(b)(1), the application contains full reports of clinical investigations of safety and effectiveness that are conducted by or for the applicant. For an NDA covered under 505(b)(2), one or more of the safety and effectiveness investigations used to support the application's approval are not conducted by or for the applicant and the applicant has not obtained a right of reference or use from the person by or for whom the investigations are conducted. Section 505(b)(2) allows for the approval of products other than generic products (see below) and it permits the use of literature or an Agency finding of safety and/or effectiveness of a FDA-approved drug to support the approval of a product.

In addition to safety and efficacy information. Section 505 also indicates that 505(b)(1) and (2) applications need to provide(i) a list of the articles used as components for the drug, (ii) a statement of the composition of the drug, (iii) a description of the methods used in, and the facilities and controls used for the manufacture, processing, and packing of the drug, (iv) samples of the drug and the articles used as components if requested, and (v) samples of the proposed labeling.

The third type of application is a 505(j) application that is also known as an abbreviated new drug application (ANDA). The 505(j) application is for duplicates of already approved products, or generic products, and although it is beyond the scope of this chapter, it is noted that such an application is to contain, among other things, information to show that the product for approval is the same in active ingredient, dosage form, strength, route of administration, labeling and performance characteristics (i.e., is bioequivalent) as that of a previously approved product (i.e., the reference listed drug or RLD), that is, unless a suitability petition is filed and accepted, for example, for a different active ingredient in a combination drug product, or a different dosage form, strength or route of administration than the RLD.

If a generic product is found to be bioequivalent to the RLD and it is approved, it will then be included in the FDA reference text entitled,

Approved Drug Products with Therapeutic Equivalence Evaluations which is often referred to as the "Orange Book"3 [http://www.fda.gov/cder/orange/ default.htm] [2]. In this book, a generic product that is bioequivalent to the RLD will be assigned a code of "A" which means that it can be substituted for the RLD product or any other generic product that is approved and coded A.

Via Section 505(i), the bases for dealing with new pharmaceuticals that are under investigation or development prior to filing an NDA are addressed (i.e., investigational new drug (IND) applications). This section indicates that regulations should be promulgated to address the investigational situation for new drugs. It further indicates that a clinical investigation for a new drug may begin 30 days after the applicant has submitted information about the drug and the intended clinical investigation. The information to be provided should include a description of the design of the clinical investigation plus information to allow an assessment of safety that is to include "adequate information on the chemistry and manufacturing of the drug, controls available for the drug and primary data tabulations from animal studies or human studies." A clinical investigation may be prevented from being initiated during the 30-day window of time (i.e., a "clinical hold") if insufficient information is provided to allow for assessment of safety considerations, or there are real safety concerns based on the information that is provided. Following the initial IND clinical investigation, the FDA allows subsequent IND clinical investigations to not be restricted to the 30-day requirement before a study can be started. However, a clinical hold can be imposed on any IND investigation before it is started or after it is initiated if there are justified safety concerns.

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