The subject matter expert

The role of the SME is emphasized in the ASTM standard. This is a role that has been described in other industry articles and documents but the consequences are not well defined. First and foremost, who are the SMEs? How do we pick them or justify them? Are SMEs to be consultants or a separate group with a different reporting structure within a company, since it is also stated that for certain functions, they are to be independent?

The FDA draft guidance makes no mention of subject matter experts but does speak of an integrated team using expertise from a variety of disciplines and the use of a statistician for continual process monitoring.

In compliance with another FDA initiative for the pharmaceutical industry, the ASTM standard discusses quality by design (QbD). The current FDA validation guidance makes no mention of the subject but does discuss design of experiment (DOE). It is not clear if DOE is the same as QbD. For QbD, the ASTM standard does emphasize critical aspects, assurance of fit, and GEP. The FDA guidance indicates that risk-analysis tools are to be used with DOE.

On another note, and in addition to the term quality by design, the ASTM standard discusses design review (DR). Design reviews are to incorporate risk assessments. They are to be performed by the SME. Nowhere is it apparent that the quality unit is to play a part in the review or approval of the DR. The relationship between the DR and the FDA DOE is also not explained in either document.

Plans

The FDA has always stressed the need for plans. Among the plans were those for compliance, remediation, and qualification. The plans have always been implemented as a means of expressing to the regulatory bodies the intent of the validation exercise and to logically, deterministically, and intelligently convey that the qualification process is under control and that the desired end result of regulatory compliance would be achieved.

With these two documents, we have a number of plans introduced. Words such as verification plan, project plan, and qualification plan are mentioned. The later two items in the previous sentence can be found in the FDA validation guideline. Neither document mentions the validation master plan (VMP), which was introduced by the industry to satisfy the need for a plan in qualification and validation and to control the cost and schedule of the qualification and validation activities. The question that emerges is what is the role of the VMP, or has it, too, been discarded? In today's pharmaceutical and medical-device industries, an entire hierarchy of plans has arisen around the VMP. Every site has endeavored to have an overall site-validation plan with the individual project and process validation plans referring to it. The site-validation plan is different from the site file, which is a European requirement. Though one would infer that verification plans and project plans are just a substitution of words, the word validation is missing in the definitions of the plans in both of these documents.

Change management

Change management is emphasized in both documents. In each document, changes during design and through the process are to be identified and evaluated. Among the differences between the documents is that the FDA guidance indicates that the project plan is to address how the evaluation of change is to take place.

Change management at one time was to be official once the production process was operational. Change control during design and validation was not handled exactly the same way. Typically once documents in design and validation were reviewed and approved by QA, official change management would then be in play. We have a situation where it is not clear what the extent of change management is to be during design and installation. Both documents stress the need for it, and most importantly the need for change management once the process in placed into operation. What is also missing from both of these documents is the mention or implementation of a corrective and preventative action (CAPA) system for which change control is very closely linked. More importantly is change management as practiced prior to manufacturing operations (i.e., engineering change management) the same and with the same stipulations as QA-supervised change management that is used during commercial manufacturing.