Helping Our Readers to be Proactive
Author: Paul L. Pluta

Past “From the Editor-in-Chief” commentaries have discussed the objectives and approaches of the Journal of Validation Technology (JVT). In brief, we aim to provide readers with useful information based on scientific and technical principles whenever appropriate. We strive for dialogue with our readers to learn our reader’s needs. Dialogue with readers helps us to be relevant, useful, and meet your expectations.

JVT Objective
Our objective in providing information is to support and assist in the variety of situations in which our readers may be involved. These range from significant work events to practical information for individual personal growth. There may be individual lot release events with substantial financial impact, long-term policy decisions, organizational planning, preparation of specific procedures, specific technical topic discussions, specific problem investigations, and so on. Many of these are “reactive” situations (i.e., reacting to some specific occurrence). Many, however, may be “proactive” situations involving considerations at an organizational level, project level, or involving a manufacturing process or equipment change.

Successfull organizations are proactive. Just as in business, validation organizations must be proactive in order to survive. McDonald’s was proactive in transitioning their menu to include a health-conscious clientele. In contrast, companies who experienced recurring toxicity events in the global marketplace due to ethylene glycol contamination obviously were not. We all know of situations in which future problems were suspected or even highly predictable, but there was no proactive effort to prevent the failures.

Successful validation organizations must proactively be aware of evolving requirements to ensure that they are compliant with industry and regulatory expectations. A proactive validation group will work ahead of initiating validation to be sure development work is thorough, sources of variation have been identified, control methods have been developed, and so on to prevent validation failures. Proactive groups will also ensure that adequate preparatory work has been done to be sure that process changes or equipment changes are successful. After successful validation, proactive validation groups will ensure that the validated state is maintained. The aforementioned activities should be conducted and prioritized with consideration for the risk involved.

The 2008 US Food and Drug Administration’s draft validation guidance was issued with validation problems in mind. Certain companies viewed process validation as a singular, distinct, one-time event. Development efforts were not thorough or complete, and validation was initiated prematurely. There was inadequate knowledge and understanding of processes. Variables were not identified nor controlled. If the three-lot validation was successful, subsequent commercial production often had ongoing problems and was not adequately maintained. The process validation draft guidance stresses a coordinated and ongoing organizational approach to process validation throughout the product lifecycle. Development work should be conducted with an objective of successful validation and continuing successful commercial manufacturing—a proactive attitude. This applies to new product manufacturing processes as well as relatively minor process changes on approved products.

JVT Articles
Validation organizations can “set the tone” for a coordinated approach in their companies by a proactive approach to validation. Several articles in this issue of JVT are particularly supportive to such a proactive approach. In “Cleanroom Design, Construction, and Qualification,” Ed White discusses the basics of an aseptic area. Another article demonstrating a proactive approach to validation is “Hand Washing—A Critical Aspect of Personal Hygiene in Pharma,” by Scott Sutton, Ph.D. This topic was actually suggested by a reader who related his concerns about validating various aseptic and “clean” processes when personnel were not adequately performing fundamental tasks, such as hand washing. Training and ongoing refresher training as part of an organizational culture that emphasizes and rewards excellent job performance are key in these situations. In “Understanding Biopharmaceutics Properties for Pharmaceutical Product Development and Manufacturing I: Oral Absorption and the Biopharmaceutics Classification System,” Deliang Zhou and Yihong Qiu discuss fundamental properties of drugs that directly relate to product performance. Validation and manufacturing professionals should be aware of the properties of their products, especially high-risk products and processes. In “Understanding Analytical Error—The Use of Controls and Blind Controls,” Brian K. Nunnally, John McConnell, and Bernard McGarvey discuss approaches to post validation monitoring of analytical data. The approaches discussed in this article are applicable to monitoring of all processes. Process monitoring is another focus of the validation guidance previously not emphasized in process validation. These and many other articles published in JVT have a common theme: Basic understanding of products, processes, and systems in advance of validation and post-validation monitoring to maintain validated performance, all of which being conducted according to risk analysis. The three-stage strategy identified in the FDA process validation draft guidance is also being generally applied in JVT articles to equipment, utilities, computers, cleaning, and other systems.

Successful validation groups are proactive. We encourage the proactive use of the information provided in JVT to improve compliance and prevent problem situations from occurring. Validation groups should work closely with technical development and engineering groups and with the quality unit throughout the product lifecycle. This general approach should also be applied to equipment, facilities, cleaning, and other associated systems. These activities must be conducted under the umbrella of risk analysis. The effort involved in these endeavors will vary with the management and culture, but there is no doubt that this is the direction that should be taken. Validation groups should be proactive to accomplish this end.

ABOUT THE EDITOR-IN-CHIEF
Paul L. Pluta, Ph.D., has extensive pharmaceutical industry and university academic experience and has been involved with the Journal of Validation Technology as a writer and editor for several years. He may be reached at paul.pluta@comcast.net.