Full Quality Assurance

Figure 9.9 The principle of applying a full quality assurance (QA) system to minimise product failures and reduce costs.

For all products in Classes Ila, lib and III, and AIMDs, a full quality assurance system, audited periodically by a notified body (Annex II of the MDD), which includes examination and certification by the notified body of the design dossier of each product covered. The manufacturer must keep documentation on the quality system and the design dossier of each product plus other documentation. The quality system obligations include post-marketing and vigilance aspects. Compliance with Annex II may be achieved (this is not mandatory but is invariably adopted voluntarily) by compliance with the EN 29000... 

The EC Declaration of Conformity procedure (full quality assurance Annex IV), or... 

Since 1998, all medical devices marketed in Europe (EEA) must bear the CE mark, which signifies conformity to the essential requirements of the MDD. The MDD harmonized the European requirements along with device certification and the inspection procedures for manufacturers to ensure the highest degree of safety and product quality of the medical devices throughout the EC. Most important was the requirement for a full quality assurance system (Annex II of the MDD, 93/42/EEC), which included design controls for new medical device products. This was in line with the ISO 9000 series of standards established for quality systems by the International Organization for Standardization. 

Ideally, extemporaneous products are prepared from pure drugs (or less suitably from chemicals) but, more frequently, commercial dosage forms intended for adults are manipulated into a suitable form for administration to children. They should be prepared in registered premises (pharmacy, hospital, health centre) under the supervision of a pharmacist and in accordance with a prescription for administration to a particular patient or in anticipation of such a prescription. These manipulations come under the heading of magistral (extemporaneous) preparations. Specials have a similar status but are made in larger volumes by licensed manufacturers (licence issued by the MHRA in the UK), which include suitably licensed hospital units. However, these products are not always subjected to full quality assurance. 

Full quality assurance with design examination and special surveillance of the final assessment... 

Have minimum work experience acceptable to lATF that includes at least three years full-time appropriate practical experience in the automotive or associated industry including two years dedicated to quality assurance activities completed in the last six years... 

A quality assurance component must be integral to the study to verify the accuracy of its measurements and to estimate a precision for each one. This component should include co-located sampling, replicate analysis, station audits, data validation, interlaboratory comparisons and a full set of standard operating procedures. The quality of the data set generated should be discussed and should include the results of validation, analysis of outliers and overall estimates of accuracy and precision. 

The principles of GLP require an independent quality assurance (QA) program to ensure that the study is being conducted in compliance with GLP. The QA personnel cannot overlap with those of the study because of the potential conflict of interest, but they may be part-time staff if the size of the study does not warrant a full-time QA section. The responsibilities of the QA unit are to maintain copies of plans, standard operating procedures, and in particular the master schedule of the study, and to verily, in writing, that these conform to GLP. The QA unit is responsible for inspections and audits, which must be documented and the results made available to the study director and the principal investigator. The QA unit also signs off on the final report. Any problems discovered or corrective action that is recommended by the unit must be documented and followed up. 

Problems more serious than a single OOS result, such as multiple OOS results, product mix-ups, and contamination, require full-scale formal investigations involving QC and quality assurance personnel in addition to laboratory and production workers in order to identify exact nonprocess or process-related errors. 

It is ultimately the sponsor s responsibility to ensure that cGCP is followed in its clinical trials, even though some of the work is contracted out to CROs and other service providers. With regard to analytical laboratories, GCP guidances require that all laboratories have full documentation, data-audit trails, standard procedures, trained staff, archives of samples and data, and routine quality assurance inspections (Prokscha, 2007). If multiple laboratories were to be used, the sponsor would need assurance that GCP requirements were met for every one. In contrast, if a central laboratory is used and all samples are shipped to it, the sponsor only needs to check GCP compliance at that laboratory. 

Quality assurance efforts within this phase will focus on four types of studies conducted for safety evaluation (a) safety studies on regulated products, (b) safety studies that encompass the full scope of laboratory operations, (c) studies that are significant to safety assessment, e.g., carcinogenicity, reproduction, chronic toxicity studies, and (d) studies that encompass operations for several species of animals. 

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