6.11
A. Provide details of the manufacturing process for the device in the form of a list of resources and activities that transform inputs into the desired output. The manufacturing process should include the appropriate manufacturing methods and procedures, manufacturing environment or conditions and the facilities and controls used for the manufacturing, processing, packaging, labeling and storage of the device. A manufacturing process flow chart should be submitted. B. Sufficient details must be provided to enable a person generally familiar with quality systems to judge the appropriateness of the controls in place. If multiple facilities are involved in the manufacture of the device, the physical address of the manufacturing site and manufacturing activities for each facility should be provided. The sites where design and manufacturing activities are performed shall be identified. For example:
(i) if the manufacturing process of a product consists of a number of subassembly processes, the manufacturing sites where each of these subassembly processes are carried out must be identified, and the relationship between these processes must be shown; or
(ii) If multiple sites manufacture the same product, each of these sites must be identified. C. The sites (including contract manufacturers) where design and manufacturing activities are performed shall be identified. Quality Management System certificates are to be provided for the design and manufacturing sites (including contract manufacturers as Annexes to the submission). D. For those multiple facilities involved in the manufacture of medical devices, the applicable information (e.g. quality assurance certificates issued by an accredited third-party inspection body) for each facility must be submitted. Firms that manufacture or process the medical device under contract to the manufacturer may elect to submit all or a portion of the manufacturing information applicable to their facility directly to the Regulatory Authority in the form of a master file E. The manufacturer should inform these contractors of the need to supply detailed information on the medical device. However, it is not the intent of this section to capture information relating to the supply of sub-components (i.e. unfinished medical devices) that contributes to the manufacture of the finished medical device itself. F. Details of the sterilization method and processing should be included, if the device is sold sterile or is to be sterilized, process validation data should include sterility test data, reference to a standardized test method, and attestation or evidence of successful validation under real-life conditions under which the product is to be sterilized. Bioburden determination, culture media used, time and temperature of incubation, controls, number of samples examined and frequency of testing should also be presented. A Sterility Assurance Level (SAL) of 10-6 is generally required G. If a biological indicator was used, its placement needs to be described and rationalized (e.g., most difficult to sterilize location). If a group of devices are to be sterilized together, the worst- case scenario or most difficult to sterilize product should be validated. Attestation of validation may be used. The manufacturer should also demonstrate that they have a process in place to monitor bioburden levels on a regular basis to confirm that the sterilization method remains valid. H. Alternatively, a method of parametric release may be proposed and validated. If a process challenge device was used to assess the sterilization process it must be shown to have comparative resistance or a greater challenge to sterilization than the biological indicators placed inside the product/packaging. I. If the product is to be re-sterilized by the end-user, a description of the recommended sterilization process for the end-user should be provided, and evidence of validation provided. Validation should be for sterility and also to confirm that the process does not compromise integrity or performance of the product. The recommended, validated sterilization method should be stated in the device labeling information.