I participated in an ISPE webinar yesterday with FDA’s Grace McNally regarding the agency’s recently released draft guidance, Process Validation: General Principles and Practices. The guidance is meant to serve as a revision to the 1987 Guideline on General Principles of Process Validation.
Applicable to both large- and small-molecule drugs as well as APIs (but not medical devices), the new draft guidance takes FDA’s quality-by-design and life-cycle approaches by the horns and aims to steer industry even farther down this new track of pharmaceutical manufacturing.
The draft guidance, expected to be finalized by the end of 2009, says McNally, breaks down process validation into three stages: process design, process qualification, and continued process verification. This third area focuses on what industry has often referred to as “revalidation,” but FDA is trying to get out of that mindset and no longer use that term. Gone are the days where three batches of qualified product meant it was time to go to market. Rather, “reproducibility” and “periodic evaluation” are critical, said McNally. “The three batches aren’t important…it’s what you’re looking for in those batches that’s important,” she said.
The overall message behind the draft guidance, she explained, is that companies need to have enough data—and the right data—to feel confident about their product and to be able to justify to FDA and patients why their process and end product will be safe and effective time and time again. FDA’s goal is for manufacturers to better link process development to their commercial process so that a true life-cycle approach is carried out (QbD, PAT, and the ICH quality guidelines really come into play here).
Some webinar participants questioned whether the draft guidance applies to legacy products. “There’s no need to go back to five-year-old DOE records or open new studies and processes,” said McNally. But most companies who are concerned about quality are reviewing their products and processes at least once a year and when companies go through this activity, they may want to keep the draft guidance’s third stage in mind, she said.
Other concerns arose from participants regarding potential conflicts with other existing guidelines such as ICH Q7A and the aseptic processing guidance. McNally said that the new draft guidance is not meant to conflict with any current standards, but that any foreseen problems should be submitted to the agency as part of the review-and-comment process.
Of note, said McNally, the comment period is being extended by 30 days from Jan. 20 to Feb. 20, 2009 to allow industry more time to provide feedback. Comments can be submitted electronically at www.regulations.gov.