Changing the pharma mindset
How long do you expect before QbD and its related tools and concepts become a natural practice in drug manufacturing?
Many of the approaches of QbD (e.g., continual improvement) are a change to the traditional approach of putting a validated
process in place and not touching it. I think that the pharmaceutical community has already made huge strides in advancing
QbD concepts. Five years ago, practically no one had heard of design space, and formalized quality risk-management was rarely
done. Today, we see a growing number of manufacturers incorporating these concepts in their day-to-day development practice
and manufacturing operation.
One way to break down barriers to QbD implementation is to increase communication between industry and the regulatory authorities.
Do you expect FDA to seek more interaction with firms during the review process or inspection process?
We have already seen a greater level of interaction in many of the QbD applications, both within and outside of the pilot.
As I often mention in my presentations, we encourage companies looking to implement QbD approaches to meet with us prior to
their submission. Even though not all the details of the design space will be available yet, we find that an end-of-Phase-II
meeting [as Mr. Famulare mentioned above] is a good time to start discussing the proposed approaches. Pre-NDA meetings are
a good time to discuss more specifics of the content and format of a QbD application. For legacy products, a meeting can be
requested to discuss proposed QbD approaches in a supplemental application.
Does FDA expect to see more communication and interaction between, for example, research and development (R&D) departments
and quality-control departments?
Yes, these are really important links for successful implementation of a PQS approach within a company to relay not only information
but knowledge from development to manufacturing with quality integrated throughout. This applies whether or not QbD approaches
are used in product development and especially important to transmit commercial manufacturing information back to R&D. This
will also provide for a more robust change-management system within a company to recognize when change can be made to foster
continual improvement or in response to a corrective action/preventive action (CAPA). This is an important tenant of the ICH
Q10 change-management system element.
It is also important for the regulator to have systems to transfer knowledge between review and inspection. The OC is developing
a system of knowledge transfer to facilitate this communication.
There is an informal practice among industry to avoid providing FDA with too much detail out of fear that more information
will lead to more questions, and perhaps more 483s. Can you address how the agency is trying to change this mindset?
A discussion point in the FDA 2004 report on pharmaceutical quality was to focus on important, well-summarized information
in the application, rather than voluminous raw data. I think quality risk-assessment is a good example of the additional important
information in a QbD application. It is a change in mindset for companies to admit that they have risk. Of course, their processes
have always had risk, and reviewers have always looked for the risks. Addressing these risks and their control in a formalized
manner increases transparency and aids in understanding the firm's assurance of product quality.
Is the agency planning to increase its practical workshops or speaking engagements to help clarify the questions that still
exist around QbD concepts and quality systems?
There are [still] questions about the regulatory implications [of ICH Q8, Q9, and Q10] and how to present some of these proposals
to the agency and how investigators may look at these proposals. I believe that conferences, papers, and shared learning on
good case studies will help answer some of these questions and relieve some of these concerns. Those regulators, including
myself, and industry members involved in ICH quality initiatives realize that ICH Q8, Q9, and Q10 are forward-looking and
that help is needed for implementation. Hence, the ICH Implementation Working Group (IWG), led by rappateur John Louis Robert,
is looking to do that through papers and conferences beginning next year. Papers drafted will have input and guidance from
I WG members. Any questions about manufacturing and various approaches to science- and risk-based approaches and CGMP interpretations
can be directed to DMPQ. So far, we have looked at proposals for RTRT, PAT, and approaches to validation involving continuous
manufacturing and verification.
1. ICH, Q8 (R2) Pharmaceutical Development (Geneva, Aug. 2009).
2. ICH, Q9 Quality Risk Management (Geneva, Nov. 2005).
3. ICH, Q10 Pharmaceutical Quality System (Portand, OR, June 2008).