Pharmaceutical products manufacturing site

Evidence of compliance with an acceptable standcird of GMP should be supplied for each finished product manufacturing site and packaging site specified in an application, except for related products used externally. This requirement includes manufacturers of intermediate products and sterilisers of the finished product. For bulk active pharmaceutical ingredients, evidence should be supplied to show that the material is manufactured consistently and produced with acceptable quality-... 

All formulations for administration to humans must be prepared in compliance with good manufacturing practice (GMP) and the certificates of analysis must be provided. The European Clinical Trials Directive requires that details of the formulations be provided to, and approved by, regulatory authorities and a qualified person at the investigator site(s). In principle, the Directive has been in force throughout the EU since May 2004 though it has been implemented at various times in different member states. The Directive applies to healthy volimteer as weU as patient studies. The requirements for pharmaceutical products for administration to humans are summarised in Box 4.6. 

Manufacturing sites within Australia must comply with the Australian Code of GMP for Medicinal Products - August 2002, which is based entirely on the international standard Guide to Good Manufacturing Practices for Medicinal Products, Version PHl/97 (Rev.3) 15 January 2002, published by the Pharmaceutical Inspection Cooperation Scheme (PIC/S). The ICH GMP Guide for Active Pharmaceutical Ingredients has also been adopted. 

Many large pharmaceutical companies have established pharmaceutical manufacturing sites in tax havens like Ireland, Puerto Rico, and Singapore. However, the decisions regarding the production programs and the procurement of, for example, PFCs are taken at the companies headquarters. In many cases, these overseas locations are important destinations for the goods supplied under contracts concluded with the headquarters. 

Components are received and are quarantined in ABC Pharmaceutical Industries stores until all testing and certificate of analysis requirements are reviewed and have met the acceptance criteria set forth in manufacturing site standard operating procedures. When all acceptance criteria have been met, the components are released by Quality Control and are ready to be issued for production using the procedures specified in manufacturing site standard operating procedures. 

The use of appropriate DOE can be an invaluable tool to optimize use of resources at all stages of product development, and to shorten the development time from for-mulation/process screening to optimization. When the formulation and manufacturing processes of a pharmaceutical product are designed and optimized by a scientific and systematic approach, the scale-up, technology transfer between manufacturing sites, and process validation can be more efficient because of the robustness of the formulation and manufacturing process. 

In the pharmaceutical industry, production processes are traditionally based on batch-type procedures, whereas continuous processing has fewer applications. An important factor contributing to the limited introduction of continuous production is that it is especially suited for very-high-volume production capacities, whereas batch manufacturing allows more flexibility when smaller volumes of different products have to be manufactured (the most common situation for a pharmaceutical production site). 

Profile This privately held company was founded in 1972. It is a full-service drug synthesis and chemical services company that performs a variety of laboratory, process scale-up, and manufacturing tasks including development of processes and synthesis routes for new medicinal products, validating bulk pharmaceutical processes, and authoring Drug Master Files. The company also has a pilot plant/small volume manufacturing site in North Andover, Massachusetts. 

The long-term goal of these recommendations is the design and implementation of a uniform and harmonized system that will ensure procurement of pharmaceutical products of defined quality for supply to patients, based on a mutually recognized process of prequalification of products and manufacturers by means of product dossier evaluation and inspection of manufacturing sites. Such a process, as defined in the Glossary and described in Module II, will hereafter be referred to as prequalification. 

In principle, products should meet at least the recommendations made by WHO in Marketing authorization of pharmaceutical products with special reference to multisource (generic) products - a manual for drug regulatory authorities (6). Manufacturing sites should comply with at least WHO GMP (5). 

If two or more pharmaceutical products appear to be similar according to these criteria, the choice between them should be made after a carefiil evaluation of their relative efficacy, safety, quality, cost, lead time and availability from prequalified manufacturing sites. When comparing costs of pharmaceu-... 

Different strengths of a multisource formulation, when the pharmaceutical products are manufactured by the same manufacturer at the same manufacturing site, where ... 

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