Finished product pharmaceutical facilities

Pharmaceutical substances form the backbone of modern medicinal therapy. Most traditional pharmaceuticals are low molecular mass organic chemicals (Table 1.1). Although some (e.g. aspirin) were originally isolated from biological sources, most are now manufactured by direct chemical synthesis. Two types of manufacturing companies thus comprise the traditional pharmaceutical sector the chemical synthesis plants, which manufacture the raw chemical ingredients in bulk quantities, and the finished product pharmaceutical facilities, which purchase these raw bulk ingredients, formulate them into final pharmaceutical products, and supply these products to the end-user. 

The cGMPs require manufacturers to have adequately equipped manufacturing facilities, adequately trained personnel, precisely controlled manufacturing processes, appropriate laboratory controls, complete and accurate records and reports, appropriate finished product examination, and so on. Current GMPs are not best practices rather, they establish threshold or minimum standards which must be satisfied in order for a pharmaceutical manufacturing operation to be compliant. 

Facilities validation is a critical process in a pharmaceutical industry and the types of pharmaceutical forms produced must be considered. Facilities that produce different pharmaceutical forms have different specific requirements and different critical parameters based on risk assessment. All facilities must have an adequate flow of people, raw materials, bulk products, and finished products. These flows must be created in order to avoid cross-contamination. Additionally, pressurized rooms and adequate SOPs should be supplied to minimize the risk of cross-contamination. Controlled air temperature and humidity are also required and should be validated to ensure adequate stability of the product. 

The Validation Master Plan (VMP) includes all relevant aspects relating to the production of pharmaceuticals in the production facility at ABC Pharmaceutical. The principles of validation, the organization of qualification and validation, and the design and nomenclature of the documentation and equipment are also described. The VMP covers all facilities used in the production of tablets, liquids, ointments, creams, suppositories, and sterile products the facilities for storing raw materials, interim and finished products, storage, services, and the rooms for staff. 

This was the next step in the focus of the FDA on the safety of the product. Up until this point, contamination (or lack thereof) was defined by the presence (or absence) of foreign impurities not specified in the analytical protocol for the product. This was the case for either the pharmaceutical product or the API that went into the finished product. Although this could be a definitive test for a uniformly distributed contaminant, it would not necessarily find random contamination that occurred in processing or extraneous matter that could enter the system from dirty facilities or poor operating practices. 

In some facilities, there is a need for refrigerated storage of one or more flammable or combustible raw materials, catalysts, intermediate products, or finished goods. These materials may be in solid or liquid form in containers, boxes, drums, or small portable tanks. Depending on quantity of materials to be stored and required temperature, these facilities can range from cold storage warehouses for storage of food products to walk-in freezer rooms for pharmaceutical materials. 

It is a requirement of the Therapeutic Goods Act that all steps in the manufacture of a prescription medicine, including the manufacture of bulk active drugs and finished pharmaceutical products, are performed in manufacturing facilities of acceptable standards. 

It is the responsibility of the manufacturer of drug products to ascertain and certify that each component in the finished drug was produced, delivered, and handled in accordance with GMPs. To meet this obligation, pharmaceutical companies perform regular audits at each of its suppliers facilities, an expensive exercise for both. 

Similar to the production of a finished pharmaceutical, validation of analytical methods must be performed in a suitable facility. Any organization responsible for developing and validating analytical methods must have the quality elements shown in Table 1 to demonstrate suitability and control. 

From the basic chemical industry come raw materials to use in large-scale formulation of the new product. From the vast fermentation vats come antibiotics. In laboratory-like formulation facilities, the mixing, baking, compressing, coating, and other pharmaceutical processes take place, under the watchful eye of quality control inspectors. In the space-age-clean rooms of biological production, virus vaccines are grown, harvested, purified, and endlessly tested. From start to finish, statistical, numerical, procedural, physical, chemical, and analytical control systems attempt to reduce to near-zero the potential error, mixup, distortion, or hazard. 

Since there are fundamental distinctions between the production of bulk active pharmaceutical ingredients and the formulation of finished pharmaceutical products, the strict application of GMP as set forth in the main part of this guide is not always practical or necessary. The present supplementary guidelines outline procedures and practices that manufacturers should employ to ensure that the methods, facilities, and controls used for the production of active pharmaceutical ingredients are operated or managed so that such products have the quality and purity appropriate for their use in finished pharmaceutical products. 

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