Market authorisation quality control

Committee For Proprietary Medicinal Products, Xotes to Applicants for Marketing Authorisations on the Production and Quality Control of Monoclonal... 

An Investigational Medicinal Product Dossier (IMPD) is intended to be more comprehensive than an IB, in that it should contain summaries of available quality data in addition to the safety and efficacy information that constitutes the main part of the IB. In total, it should provide information on the chemistry, manufacture, control and stability ofthe medicinal product, together with the results of non-clinical and clinical studies. In order to avoid repetition, the IB can be cross-referenced for non-clinical and clinical results. Ideally, the IMPD should follow the same structure as that which will be used later for the marketing authorisation application. For products with existing marketing authorisations, the Summary of Product Characteristics may replace the IMPD to varying extents (see Chapter 6). 

Once the clinical and safely evaluation studies for a new medicinal product have shown it to be safe, effective and of acceptable quality, the pharmaceutical company will usually want to submit a Marketing Authorisation Application (MAA) or New Drug Application (NDA) to the regulatory authorities. The chemistry, manufacturing and controls (CMC) section will form a major part of the application. For an MAA in Europe, a development pharmaceutics section is required to describe how the product was developed, and to explain the rationale for the selection of the formulation, pack, manufacturing process and specifications. Also required for Europe are expert reports for each of the pharmaceutical, safety and clinical parts of the application. These have to be written by experienced scientists nominated by the pharmaceutical company who have to critically appraise the development programme for the product. The pharmaceutical expert must acknowledge the acceptability of the CMC part of the application. 

Good Manufacturing Practice is that part of Quality Assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorisation or product specification. 

The confidence in the efficacy and safety of a medicine by a consumer (patient), the latter represented by inspection or regulatory agencies, is based partly on the warranty by the producer and further on requirements laid down in pharmacopoeias and other documents such as the marketing authorisation. The correct interpretation of the results of this system, called statistical quality control [2] or SQC is crucial to understand the character of the guarantee, when provided or asked for. In Sect. 20.4.3 the significance of this system will be discussed more in depth. 

After a product has been authorised, the regulatory system operates to keep the quality, safety and efficacy of that product under review and to control the way in which it is manufactured, marketed and distributed. The pharmaceutical legislation in Europe has recently been consolidated and, pursuant to Commission consultation and review, amended. The majority of the amendments are due to come into effect in November 2005. What follows, reflects the state of legislation as at close of 2004. 

Control—The National Control Laboratory is authorised to ensure the quality of medicciments prior to their market introduction and to control the market. 

Few herbal medicinal products are on the market as authorised medicines in the EU, fulfilling the same stringent requirements that count for conventional medicinal products. This is largely due to the limited availability of randomised controlled trials to support the quality, safety and efficacy of herbal medicinal products. More often they are licensed as traditional herbal medicinal products, following an adapted and simplified registration wherein efficacy is made plausible based on available scientific data (well-established use) or long-term historic use in the EU (traditional use). Sufficient data to underpin the safety should be available in all cases and the quality of the herbal... 

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