Manufacturers Seek Strategies for Life-Cycle Approach to Process Validation

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The US Food and Drug Administration and industry have been working to incorporate process validation as an integral component of drug development and production, and to avoid divergent policies in the US and Europe.

The US Food and Drug Administration and industry have been working to incorporate process validation as an integral component of drug development and production, and to avoid divergent policies in the US and Europe. A good deal of progress has been made in this area, but manufacturers continue to feel uncertain about the details in revising existing systems and updating long-held practices to fit new approaches, as seen in the discussion at the PDA/FDA Process Validation Workshop in Bethesda, Md., May 20-21. Participants assessed FDA’s Process Validation guidance, which was published in January 2011, and the corresponding PDA technical report on “A Lifecycle Approach to Process Validation” (TR 60) issued in January 2013 [available at].

The aim is to help manufacturers who are wrestling with and working to implement the FDA guidance, explained Harold Baseman, chief operating office of ValSource and co-chair of the PDA process validation interest group. The workshop program followed FDA’s three stages for process validation, starting with process design and moving through process qualification to achieve continued process validation to provide ongoing assurance that a production process remains in a state of control.

Workshop attendees discussed the importance of gaining extensive knowledge about a process early in design and development stages to ensure that the system is well controlled. Patrick Swan, deputy director of the Division of Monoclonal Antibodies, Office of Biotechnology Products (OBP) in the Center for Drug Evaluation and Research (CDER), highlighted the value of tapping prior knowledge to support process validation activities, noting that this may expedite product development for lifesaving breakthrough therapies.
Process qualification involves identifying and interpreting information from process design functions to establish testing and acceptance criteria. Methods for equipment and facility assessment are important, as are sound process qualification sampling plans.

The lifecycle approach also involves linking process validation activities to a manufacturer’s Quality Risk Management system. While manufacturers and regulators are looking to shift away from assessing a set number of batches, questions remain about how much data is needed to show that something is or is not in control, Baseman explained.

Similar efforts by the European Medicines Agency (EMA) to update policies on these issues were discussed, with an emphasis on the importance of achieving similar approaches to validation requirements. Concerns were raised that EMA doesn’t consider process development part of process validation, that different terms are emerging, and that divergent regulatory approaches may cause confusion. Manufacturers filing applications in some 150 countries emphasized the importance of common formats and systems.


OBP deputy director Jeffrey Baker explained that FDA and EMA officials discuss these and other issues at “cluster meetings,” held to address topics such as biosimilar evaluation, good manufacturing practices and differences in review policies. Regulatory authorities at these sessions don’t consider specific companies or applications, Baker noted, but address general policy approaches, with an eye to gaining alignment on regulatory guidance.

Baker and others suggested that questions about data collection and regulatory requirements can be addressed by focusing on the science, which is key to appropriate terminology, data formats and determining what information is needed to assure product quality.

Yet, legacy products raise challenges, as manufacturers have to determine what would be involved in updating process validation data to support manufacturing changes or address safety issues.

One benefit of revised process validation policy that reduces the volume of unnecessary testing is to streamline the development and approval of important, life-saving therapies. Future FDA guidance on its regulatory approach to “breakthrough” therapies should explain further how the agency will address manufacturing and quality assurance issues for such products, Baker noted. But he pointed out that companies request the breakthrough designation and thus should be able to explain how they will supply a quality product efficiently and quickly for sick patients.