Finished Dosage Forms

PhRMA is a trade association of over 100 research-based pharmaceutical companies. For membership a company must manufacture and market finished dosage-form products under its own brand names and must conduct a significant amount of research and development in the United States. 

Good Manufacturing Practice. The GMPs were issued by the U.S. FDA in 1978 to provide minimum quahty standards in the production of pharmaceuticals (qv) for the finished dosage form as well as their ingredients. The standard has been updated periodically. 

GMP) controls and inspection, although where appropriate these requirements should be complied with. Manufacture of the finished dosage form should always be GMP compliant. There are also proposals for GMP compliance for active ingredient manufacture, which have been submitted for comment by the Enterprise Directorate General and under the auspices of the Pharmaceutical Inspection Convention-Pharmaceutical Inspection Co-operation Scheme (PIC-PIC/S) and the ICH process. 

AQ2a Manufacture of the finished dosage form (pages 11-18)... 

CPMP/QWP/2570/98 Concept paper on the development of a CPMP note for guidance on in-use stability testing of non-sterile human medicinal products (November 1998) CPMP/QWP/2934/99 draft Note for guidance on in-use stability testing of human medicinal products (released for comment December 1999) CPMP/QWP/598/99 draft Note for guidance on process validation (released for comment September 1999, also issued under CVMP reference EMEA/CVMP/598/99 draft) CPMP/QWP/486/95 Note for guidance on manufacture of the finished dosage form (reissued April 1996)... 

The Committee for Proprietary Medicinal Products [8] applied the BCS, with certain requirements, to dispense with bioequivalency tests if the active pharmaceutical ingredient is class I and the in vitro dissolution of the finished dosage form is fast [9], An active substance is considered highly soluble if the amount contained in the HDS of an IR product is dissolved in 250 ml of each of three buffers within the range of pH 1-8 at 37°C (e.g., pH 1.0, 4.6, and 6.8). There should be linear and complete absorption, which indicates HP to reduce the possibility of an IR dosage form influencing the bioavailability [8], The similarity of the dissolution profiles of the test and reference products is demonstrated in each of three buffers within the range of pH 1-8 at 37°C (e.g., pH 1.0,4.6, and 6.8). If there is rapid dissolution of the product, where at least 85% of the active substance is dissolved within 15 min, no further comparison of the test and reference is required. Further requirements include that excipients be well established and have no interaction with the pharmacokinetics of the active substance and that the method of manufacture of finished product... 

To modify processing properties for the manufacture of finished dosage forms (tablets, capsules, parenterals, etc.)... 

In API manufacture, whether via chemical synthesis, rDNA technology, or extraction from natural products, there are significant changes (physical and chemical) from the starting materials to the API. In the formulation process, however, the quality and specifications of the API are retained. The addition of excipients to produce the drug product in a finished dosage form does not present physical or chemical changes to the API. 

Manufacturing of drugs, whether the API or finished dosage form, is required to comply with GMP regulations (see Chapter 9). Figure 10.1 shows the implementation of GMP concepts in drug manufacture. 

The finished product is centrifuged and purified via a number of processes, including filtration, fractional distillation, condensation, crystallization, and chromatographic separation techniques. The purified API is tested and then it is ready to be formulated into the finished dosage form, as discussed in Section 10.6. Exhibit 10.5 illustrates some of the typical reagents for API manufacture and Exhibit 10.6 presents selected chemical reactions as examples of the... 

The production of the API and finished dosage form is required to comply with GMP regulations discussed in Chapter 9 and Section 10.2. The quality system, quality control, and validation of equipment and processes have to be developed and adhered to in the manufacturing process. Proper records and documentation are required to be kept in the forms of batch records. 

A finished dosage form is a drug formulated with an API and excipients in a form that is suitable for administering to patients. The following are some of the reasons for preparing finished dosage forms ... 

Purified drug substances are mixed with excipients into finished dosage forms sohds, liquids, parenterals, inhalants, and ointments and creams, then packaged and labeled and shipped for distribution. 

Twenty years ago the vast majority of all drug substanees and finished dosage forms used in the United States were prepared in United States. For various reasons before... 

The FDA s regulations define drug product as a finished dosage form, for example, a tablet, capsule, solution, etc., that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredients. 21 C.F.R. 210.3(4). 

Drug produet means the finished dosage form of a drug approved through an NDA or AND A. 

For each Drug Product for which the company has filed an ANDA containing a paragraph IV certification, state the company s sales" (if any), in units and dollars, by each finished dosage form for each calendar year since, and including, the year the company received FDA approval of such ANDA. 

Although even quality issues are still a problem (poor quality of starting materials including active pharmaceutical ingredients, quality problems with finished dosage forms, spreading of counterfeit medicines) it is likely that new technologies... 

Stability tests on finished dosage forms and products Tests for conformance to pharmacopeial standards Exploratory studies on viruses and cell biology Tests of functionality and/or appropriateness of food additives... 

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