This article compares the pertinent aspects of the US Food and Drug Administration's 2009 draft guidance for industry on process
validation (1) and the 2007 ASTM E2500-7 standard guide on the specification, design, and verification of pharmaceutical and
biopharmaceutical manufacturing systems and equipment (2). There are several inconsistencies between the two documents in
terms of terminology and expectations for equipment and system qualification. In addition, the timing of both documents gives
the impression that previously understood qualification documentation practices are being abandoned for newer terminology
and proposed practices.
During the past few years, there seems to have been a directed effort to eliminate the concept of and need for installation
qualification (IQ) and operational qualification (OQ). Industry developed these techniques to address FDA's validation requirement.
The purpose of IQ and OQ was to verify that equipment and systems were able to perform as intended.
Today, many companies still follow the premise of IQ and OQ, but the introduction of other terms has downsized the importance
of these activities. In particular, the term commissioning has been introduced into industry's vernacular to define traditional IQ and OQ tests, among other tests. Today, IQ and OQ
have been reduced to lists indicating that commissioning tests have been properly completed and leveraged.
The present situation
With the introduction of the ASTM standard and FDA draft guidance, industry needs to adjust its understanding of the word
qualification for systems and equipment once again. For example, both documents deemphasize IQ and OQ. The ASTM standard does not mention
the word qualification and the draft guidance does not specifically mention the terms IQ or OQ in its discussions on equipment and system qualification.
(The draft guidance does call for performance and process qualification [PQ] as part of overall process validation.)
It can be argued that the two documents address two different but related subjects within the scope of validation. The ASTM
standard, for example, is geared toward the acceptance of equipment and systems before performance qualification, and the
FDA draft guidance emphasizes PQ.
Role of quality assurance
Traditionally, quality assurance (QA) was carried out by an independent reviewer and approver. The QA department had no direct
role in the design or manufacturing process of the drug product and had an independent reporting structure from engineering
and manufacturing. With the onset of commissioning, the role of QA in the overall qualification scheme came into question.
Nowhere in industry guidelines was it stated that QA should review and approve commissioning tests or related documentation.
QA review was strictly for critical systems and equipment.
The FDA draft guidance on process validation gives more responsibility to the quality unit (QU) than does the ASTM standard.
The QU is supposed to approve the qualification plan as well as PQ protocols and reports. The FDA draft guidance document
notes that the QU should approve individual equipment and system qualifications, as well as the qualification plan and summarizing
The ASTM standard does not formally mention the QU other than suggesting that the QU approve the verification plan and verification
review documents, and decide on vendor documents as they apply to criticality. The QU does not participate in the review or
approval of the verification documents but only the final review documents.
In addition, the QA group has typically been responsible for ensuring that vendors and suppliers are up to date and compliant
with current good manufacturing practice (CGMP). The ASTM standard does not give this responsibility to QA but FDA, in other
documentation, does give QA the responsibility for overall vendor certification.
What is more intriguing is that, based on industry committee meetings involving regulatory bodies, FDA and even the European
Union agree with the concepts of commissioning and the deemphasis of IQ and OQ. FDA not only participated in the drafting
of the documents, but also tacitly approved them. As a result, most of industry instituted the new methodologies.
Even though FDA has not abandoned the concept of qualification, the agency states in the draft guidance that verification
is to be achieved through qualification. In the ASTM standard, the word qualification is replaced by verification. It seems that verification, however, is one step removed from qualification; these words are not necessarily interchangeable.