Representatives of the US Food and Drug Administration and Industry*
*Authors of this report include:
Moheb Nasr (FDA), Gerald Migliaccio (Pfizer), Barbara Allen ( Eli Lilly and Company), Robert Baum (Pfizer), Ronald Branning
(Genetech), Chi-wan Chen (FDA), Joseph Famulare (FDA), Richard Friedman (FDA), Musa Ghannam (Schering-Plough), Frank Holcombe
(FDA), Nirdosh Jagota (Wyeth), Christopher Joneckis (FDA), Zena Kaufman (Abbott Laboratories), Steven Kozlowski (FDA), LaiMing
Lee (FDA), Anthony Lubiniecki (Centocor), Mary Malarkey (FDA), Christine Moore (FDA), Elaine Morefield (FDA), Gene Murano
(Genentech), Richard Norgard (Pfizer), Helen Winkle (FDA), and Janet Woodcock (FDA).
All correspondence should be addressed to Dr. Moheb Nasr, FDA, Office of New Drug Quality Assessment, 10903 New Hampshire
Ave., Bldg 21, Rm #2630, Silver Spring, MD 20993-0002.
Progress and updates* on FDA's pharmaceutical quality initiatives
A Q&A with workshop participants by Angie Drakulich
Q: "Regulatory flexibility" continues to be a hot topic, especially with regard to design space. Companies want to know what
type of flexibility they may actually see if they submit quality-by-design (QbD) based documents. Will there be any near-term
clarification of such flexibility from the US Food and Drug Administration?
A: The types of "regulatory flexibility," better known as "flexible regulatory approaches," are described in the International
Conference on Harmonization's Q8 Guideline, Section 2. They include: risk-based regulatory decisions (reviews and inspections);
manufacturing process improvements, within the approved design space described in the dossier, without further regulatory
review; reduction of postapproval submissions; and real-time quality control, leading to a reduction of end-product release
testing. FDA developed and implemented a few regulatory pathways of the agreed-upon flexible regulatory approaches, including,
if appropriate, movement within design space, reduction of postapproval submissions without prior approval or changes-being-effected
supplements, real-time release, etc.—Answered by Dr. Moheb Nasr, director of the Office of New Drug Quality Assessment, Center for Drug Evaluation and Research,
Q: With regard to design space and other QbD-based documents, many of these are considered "living" documents that will continuously
change and be updated. How will these constant changes impact the inspection process, postapprovals, etc.?
A: According to ICH Q8, movement within the design space is not considered a change. Thus, verifying and updating the design
space can be accomplished under the applicant's quality system. But, redefining or expanding the design space postapproval
will require a supplement. It is possible that the design space management can be captured as part of the CMC Postapproval
Management Plan (PMP), formerly known as 'regulatory agreement' '....FDA is considering...the issuance of a guidance to implement
a PMP. The PMP policy, when implemented, would be on a voluntary basis. However, if a PMP is submitted by the applicant and
reviewed and approved by FDA, it will be binding on the applicant and FDA.—Answered by Dr. Nasr
Q: One of the primary action items proposed during the 2007 Pharmaceutical Quality Initiatives Workshop was the publication
of a process validation guidance in 2008 to focus on what process validation would look like under QbD. What is the status
of this guidance? Will industry see a draft in 2008? And will manufacturers be allowed the typical comment period?
A: Yes to all questions posed. The draft guidance will be in line with the ICH Q10 document on pharmaceutical quality systems
which is currently at Step 3, the public comment period.—Answered by Joe Famulare, deputy director of CDER's Office of Compliance