FDA

What is more intriguing is that FDA and even the European Union (EU) agree with these concepts of commissioning and the de-emphasizing of IQ and OQ—but not their elimination. This conclusion has been reached following FDA's participation in the very industry committees that have written these concepts into industry guidelines. FDA not only participated, but reviewed the documents from these committees and also tacitly approved them as well. Tacit approval was achieved by not making any statement pro or con with regard to the implementation of these practices over time. Most of the industry moved ahead and instituted the new methodologies.

The present situation

The other document that also has been introduced for our use is FDA's Draft Guidance for Industry: Process Validation: General Principles and Practices (3). Both of these documents have been made public over the past year. Granted, we have known about their development for some time now.

Both documents have been tacitly approved by FDA. The agency reviewed and participated in the development of the ASTM standard, which is an issued document that can be purchased from the ASTM website. The FDA guidance is still in draft form but will certainly be issued as official guidance once FDA addresses the comments and finalizes the guidance document.

The most striking aspect of the documents is that they both deemphasize IQ and OQ. Neither document mentions these activities as installation qualification and operational qualification. The ASTM standard does not even mention the word qualification. The FDA draft guidance discusses qualification, but does not specifically mention the terms IQ or OQ. The draft guidance does expect performance and process qualification as an aspect of the overall process validation. Process validation is the sum total of all qualification activities performed.

It can be argued that the two documents address two different but related subjects within the scope of validation. The ASTM standard is geared to the acceptance of equipment and systems prior to performance qualification. The FDA guidance document emphasizes PQ but does have a major section devoted to the same subject matter as the ASTM standard.

GEP, risk assessment, and subject matter experts

The ASTM standard emphasizes verification, GEP, risk assessment, and subject matter experts (SMEs). Though the standard discusses documented verification and SME review, it is not clear what that documented evidence will look like. Certainly, QA or the quality unit is not being held responsible for review or approval of this verification activity. Criticality aspects of equipment and systems is reserved for QA review. Risk assessment is emphasized in the standard but it is not clear how that is to be achieved. Other than mentioning that the extent of verification and level of detail of documentation should be based on risk, not much else is said.

The FDA draft guidance also mentions risk assessment. It only references ICH Q9 in a footnote, but it does reference FDA's 21st Century Risk-Based Approach document (4, 5). The ASTM standard also references this FDA program. Though each document emphasizes risk and risk assessment, neither one indicates how it is to be achieved. The FDA guideline talks about risk in the sense of "control of variation and to combine conditions that pose a high risk of failure." The ASTM standard, however, requires that risk management be used throughout every aspect of the process and with every decision.

As stated above, the FDA draft guidance emphasizes qualification and only speaks to verification in the sense that it is to be achieved through qualification and continued process verification after process validation is completed.

The draft guide does not mention GEP, but interestingly it does mention commissioning and the "need to reduce redundant information gathering." It appears FDA through this draft document has finally given recognition to the practice of commissioning by mentioning it in the document.