FDA'S JON CLARK INFORMS ABOUT THE AGENCY'S CURRENT INITIATIVES

   

GMP/GDP – On Demand Online Training

You can book the desired online training from our extensive database at any time. Click below for more information.

   

Stay informed with the GMP Newsletters from ECA

The ECA offers various free of charge GMP newsletters  for which you can subscribe to according to your needs.

At the University of Heidelberg's PAT Conference last October, Dr Jon Clark, Associate Director for Program Policy, Office of Pharmaceutical Science, CDER, of the American Food & Drug Administration (FDA), presented the Agency's ideas about contributing to the improving of drug product quality.

Right at the start he explained why things often take so long at the FDA. At the CMC Review Program of the Office of Pharmaceutical Science, for example, many partners are involved within the FDA at "Chemistry Manufacturing and Controls (CMC)". Partners include: 

  • ONDQA New Drugs
  • OGD Generics
  • OBP Biotech
  • NDMS Microbiology

The goal of the current FDA initiatives was already presented by Janet Woodcock phrased in October 2005: the FDA wants a maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drug products without extensive regulatory oversight. Jon Clark emphasised that this wording has already survived several crises (among others the Heparin case!) and that it is still valid in this form.

The FDA representative encouraged the pharmaceutical industry to borrow successful principles and proceedings from other industrial branches.

QbD Pilot Programme

Clark presented the FDAs Quality by Design (QbD) pilot programme. According to him, the "Question Based Review" (QbR) of the ONDQA Pilot Programme was implemented successfully. It was presented as a success story by the FDA but this project was not perfect. "We need to assure a continuing process of improvements!"

The "Question Based Review" is a general framework for a science and risk-based assessment of product quality. It also utilises the CTD format for approval - or even better, the electronic eCTD format! In the section "Quality Overall Summary (QOS)", the product and process development need to be described. Pharmaceutical manufacturers are encouraged to use quality-by-design concepts to do so. With the help of this concept, firms can substantiate decisions during the development process towards the FDA and discuss the critical parameters of a product or a process. With this QbR approach, the FDA has more clearly defined its expectations towards the industry.

GMP-Basiskurs Packmittel / Verpackung (PM 7) - Live Online Seminar

Recommendation

17. April 2024

GMP-Basiskurs Packmittel / Verpackung (PM 7) - Live Online Seminar

How will the Question based Review (QbR) proceed? For 2009, a first revision is planned which will take into consideration experience of the industry and the reviewer, says Clark.

Quality by Design (QbD) furthermore extends to other sectors. A QbD pilot programme is now starting for biological products. This programme, however, can only be successful through industry participation.

Clark also commented on risk management: "The pharmaceutical industry does not utilise Risk Management as imagined by the FDA. Approaches must be optimised since Risk Management tools can help to further develop QbD."

He also presented the Biotech Lifecycle Programme which he considers to be a difficult concept! The programme comprises a risk-based change control system. The FDA expects the application of multivariate, statistical process controls to be able to predict the result of a product.

Clark used two examples (effect of polymer concentration on dissolution and on-line NIR monitoring to determine blend uniformity) to demonstrate that visualising specifications and limits can be very helpful for assessment. A good chart can easily be understood. With the help of this visualisation, it is easy to show that a definite process is stable.

Formerly, it was assumed that using a statically specified production procedure (validation!) in a pharmaceutical manufacturing process would automatically assure the quality of the final product. But this old paradigm did not take into account that it is not possible to lash the output parameters (the mechanistic properties of the APIs and excipients utilised). The new PAT paradigm considers the variability introduced into the manufacturing process (for example, because of different qualities of the raw material) and instead makes it possible to measure and control the process variables. The goal is to be able to react to the different variations of the raw material with a variable process and thus to assure the manufacture of a drug product that corresponds in all points to the quality requirements.

PAT increases the quality of drug products, partly because of more representative information about the process and more science based release criteria. But Clark also made clear that "PAT is not the answer to every question!"

Life Cycle Management

The FDA speaker also commented on the new concept of "Life Cycle Management". Part of this concept involves changes of processes and analytics, site transfers, outsourcing, transfers and so on. Other important points of Life Cycle Management include:

  • Risk Management
  • Process tracking and trending
  • Knowledge Management
  • Model maintenance and updating

Clark stressed the importance of statistical process control ("this is a good thing") inviting participants to counteract trends in manufacturing processes before they become a problem.

The OBP Programme: Links between Attributes and Processes

Clark furthermore commented on the OBP pilot programme that was made public in June 2008. This programme aims at linking clinically relevant attributes for protein products (regulated by OBP) to manufacturing processes. At the same time, it is a question of utilising QbD in supplements as well as in original applications. Firms that wish to participate in the new OBP pilot programme are obliged to send their requests to "Division of Dockets Management" (FDA-2008-N-0355).

What has all of this to do with PAT? Is PAT merely a sampling issue? Or can it be handled as a validation issue? At this point Jon Clark referred to the new FDA Guideline on Process Validation. At the time of the conference, the industry was still awaiting its publication. But now the FDA has published it: FDA Draft Guidance for Industry - Process Validation: General Principles and Practices, November 2008. Many points mentioned by Clark in his lecture in Heidelberg can be found in this guideline (Product Life Cycle, Risk Management, statistical process control, assessment of trends, etc.). This new FDA validation document also hints at a possible utilisation of PAT.

Excel in the GxP-regulated Environment - Live Online Training

Recommendation

Thursday, 2 May 2024 13.30 - 18.00 h

Excel in the GxP-regulated Environment - Live Online Training

At the end of the conference, the FDA representative had a simple piece of advice for the participants concerning their dealings with the agency: "Say what you do - do what you say!"

Author:
Dr Günter Brendelberger
CONCEPT HEIDELBERG

Go back

To-Top
To-Bottom