The draft guidance has a broad scope from API production through to finished dosage forms and therefore must be applicable
in various situations. The validation methodology outlined provides substantial flexibility to the industry, avoiding details
that might fit well in one instance but be wholly inappropriate in another. Objectively speaking, the guidance's lack of definitions
can be viewed both positively and negatively. Firms with extensive knowledge of their processes will appreciate that FDA believes
that they should be abe to validate their own processes without having to accommodate arbitrary precepts. On the other hand,
firms lacking the requisite process knowledge would likely have preferred substantially more detail with regard to regulatory
expectations for process validation. The draft describes FDA's process-validation expectations from a "what to" rather than
a "how to" perspective. That approach is wholly consistent with the 21 CFR Part 211 current good manufacturing practices (CGMPs), where firms are given great latitude with respect to the methods used
to realize the compliance requirements (5).
The document properly places process equipment in a secondary role. Equipment qualification is certainly expected, but only
as a means to support the process and not as the focus of the effort or an end in itself. Providing clarity in this regard
is an important step forward and is consistent with FDA's risk-based compliance objective, the recent American Society for
Testing and Materials effort at refocusing equipment qualification activities, and industry publications that cite the need
for focus on critical end-product quality concerns (6–8).
In summary, the usefulness of the draft guidance for validating pharmaceutical production processes and products is unquestionable.
The life-cycle model will result in development and validation exercises that provide relevant and meaningful information.
The link between the process parameters that influence the critical quality attributes will serve the industry well. The use
of statistical methods will add a rigor to the validation efforts that has been sorely lacking.
Applying the guidance outside the process or product focus
Perhaps the only question that need be asked is how easily the draft guidance can be applied to processes and systems that
are less clearly related to end-product quality attributes, or where the development model described might be substantially
different. The most important of these systems and processes commonly used in the pharmaceutical industry include:
- Critical process utilities (e.g., water systems and compressed gases)
- Classified and controlled environments (e.g., ISO 5–8 rooms and cold boxes)
- Computerized systems (e.g., process control and manufacturing resource planning)
- Inspection of product attributes (e.g., visible particle and labeling)
- Cleaning and preparation procedures (e.g., product-contact parts and surfaces)
- Sterilization processes (e.g., steam, dry heat, and radiation)
- Aseptic processing (e.g., filling and compounding)
- Manual procedures (e.g., gowning and sanitization).
The ease with which the guidance can be applied varies substantially with the particular process, and each general category
is best considered individually.