Manufacturers - 1
The processing authority's evaluation report should contain sufficient information to document that the deviant process is commercially sterile, meets the requirements for the minimal thermal process, or is unsafe. In all cases the report should list the critical factors considered in the evaluation.
Although there are situations in which FDA may need to know the actual maximum or minimum values for the critical factors considered, and the heating factors to determine if a proper evaluation has been made, there are legitimate reasons for not including this information in an evaluation report to the processor. An example, is a case where a deviation evaluation report listed the fill weight used in the evaluation of a deviant process that happened to be greater than the maximum fill weight listed in the scheduled process. When a FDA investigator found fill weight in excess of the scheduled process at this firm, the firm's manager told the investigator that this fill weight was an authorized process, based on the previously referenced process deviation evaluation report. The initial report should have reminded the firm that their filed process fill weight value was the scheduled fill weight, and deviations from this weight should be used to identify a process deviation.
If the processing authority evaluates a deviant process as unsafe they should inform the firm of their options (reprocess in accordance with a process established by qualified individuals, or destroy) and remind them the FDA must be notified if any product has been distributed.
The processing authority must keep complete records covering all aspects of the establishment of a scheduled process, including associated incubation tests (21CFR 113.83), and all records covering deviation evaluation procedures used and the results (21CFR 113.89). The sections of the regulations dealing with venting or retort come-up (21CFR 113.40) require data or documentary proof demonstrating adequate temperature distribution, be kept on file.
When requested by FDA in writing, a processor must provide FDA with any information concerning processes and procedures which is deemed necessary... to determine the adequacy of the process (108.35(c)(3)(ii)). In many instances, the information requested, such as heating factors, heat penetration data, conditions of the heat penetration tests, minimum public health sterilizing value, etc., will be in the possession of the processing authority. FDA realizes that processing authorities do not generally like to provide this information to the processor. When processing authorities are not employees of the processor, FDA does not request this information directly. If a processing authority does not wish to provide the requested data and information to the processor, the FDA investigator should obtain a written release from the processor to permit FDA to acquire the data and information directly from their processing authority. FDA is required by law to protect the confidentiality of this information.
An example of an inadequate 'record of evaluation procedures used and the results', as required by 21 CFR 113.89, is a firm in which the only records supplied by the processing authority (which happened to be the firms corporate headquarters) to the processor was a statement that two deviations resulted in questionable processes, and the lot should be held 90 days; 100 percent examined; and any swells found should be submitted for further testing.
CFSAN notified the processing authority its' deviation evaluation report did not constitute a proper 'record of evaluation procedures used and the results', and the firms hold, sort and ship method of process deviation evaluation, was, by itself, not acceptable.
While CFSAN accepted the firm's policy of not providing its processing plants with all the data and information generated during the process evaluation, it found the processing authority's written communication to the plant lacking because it did not state that the deviations had been evaluated (in this case computer calculations and evaluations by their technical personnel), or indicate whether the product was commercially sterile, meets the requirement for the minimal thermal process, or is unsafe.
INSPECTIONAL CONSIDERATIONS: Investigators should not routinely ask for process establishment data (the data used to establish the scheduled process), or records of the evaluation procedures used for evaluating deviant processes. During an inspection you will routinely ask (by use of a FDA 482b) for written documentation from a processing authority which delineates the recommended scheduled process and the venting/come-up procedure. You may also request evaluation reports for deviant processes, which FDA is entitled to under the regulations.
If you have any doubts about the adequacy of the firms scheduled processes or procedures, or deviation evaluation, or if you question the qualifications of the processing authority, after discussing the matter with you supervisor, or LACF monitor, contact HFS-617.
If the firm is using someone other than a