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August Excipient Community Open Scientific Discussion: Raw Material Variability

  • 1.  August Excipient Community Open Scientific Discussion: Raw Material Variability

    Community Leadership
    Posted 08-16-2024 10:52

    Dear all,

       We are excited to announce that three experienced scientists from Merck will join us in the upcoming Aug AAPS Excipient Community Monthly Scientific Discussion (Aug 22nd 12-1pm US EDT) to explore the impact of raw material attribute variability. Please see the presentation abstract and speaker bio below. Look forward to another great discussion!

    Discussion with authors of a recent J Pharm Sci Perspective article on raw material variability

    J Pharm Sci Perspective article title: A Rational Hierarchy to Capture Raw Material Attribute Variability in the Pharmaceutical Drug Product Development and Manufacturing Lifecycle

    J Pharm Sci Perspective article web link: https://doi.org/10.1016/j.xphs.2023.10.014

    J Pharm Sci Perspective article abstract:

    Assessing the robustness of a drug product formulation and manufacturing process to variations in raw material (RM) properties is an essential aspect of pharmaceutical product development. Motivated by the need to demonstrate understanding of attribute-performance relationships at the time of new product registration and for subsequent process maintenance, we review practices to explore RM variations. We describe limitations that can arise when active ingredients and excipients invariably undergo changes during a drug product lifecycle. Historical approaches, such as Quality-by-Design (QbD) experiments, are useful for initial evaluations but can be inefficient and cumbersome to maintain once commercial manufacturing commences. The relatively miniscule data sets accessible in product development − used to predict response to a hypothetical risk of variation − become less relevant as real-world experience of actual variability in the commercial landscape grows. Based on our observations of development and manufacturing, we instead propose a holistic framework exploiting a hierarchy of RM variability, and challenge this with common failure modes. By explicitly incorporating higher ranking RM variations as perturbations, material-conserving experiments are shown to provide powerful and enduring robustness data. Case studies illustrate how correctly contextualizing such data in formulation and process development can avoid the traps of historical QbD approaches and become valuable for evaluating changes occurring later in the drug product lifecycle.

    Stephen Conway, Ph.D., is currently a director in the Packaging Commercialization & Manufacturing Technology group at Merck & Co, Inc. Previously, he led the Global Technical Operations team at the Cramlington, UK manufacturing site and prior to that led a team in the Merck Center for Materials Science & Engineering (CMSE) supporting pharmaceutical product development. While in the CMSE, Stephen also led a cross-functional team of scientists and engineers executing development, capital project and commercialization activities for Merck's first implementation of Continuous Manufacturing, including participation in external pre-competitive collaborations and numerous Agency engagements.

    Kenny Rosenberg, Ph.D., spent over a decade in the Center for Materials Science & Engineering at Merck & Co., Inc., supporting programs in both late development and the commercialization space. Currently, he is a Principal Scientist in the Product Development group at Neurocrine Biosciences supporting end-to-end development of both small and large molecule programs.

    David Goldfarb, Ph.D., is a Principal Scientist in the Center for Materials Science & Engineering, a physical/materials science laboratory within the Manufacturing Division of Merck & Co., Inc. The group supports late development and commercial products; within the group, he currently leads the group's small molecule commercial products portfolio, having led until recently the development portfolio. Externally, David serves on the USP's Physical Analysis Expert Committee (third term), as co-editor of the Handbook of Pharmaceutical Excipients, and as an Editorial Advisory Board Member of the Journal of Pharmaceutical Sciences.

    Best regards,

    Jiaying on behalf of AAPS Excipient Community LT

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    ------------------------------
    Jiaying Liu
    Associate Principal Scientist
    Merck & Co, Inc - Rahway, NJ
    Rahway NJ
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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  • 2.  RE: August Excipient Community Open Scientific Discussion: Raw Material Variability

    Community Leadership
    Posted 08-28-2024 15:47

    Dear all,

         Last Thursday, we had a great seminar and deep discussion led by David, Kenny and Steve on raw material variability. Many thanks to the speakers to share their slides and paper link. Here also attached the recording of the seminar. I'm sure you all will find it useful. Please feel free to post your feedback or further thoughts or questions by replying to this post. See you again in September!

         Slides and video: see attached

         Paper link: https://doi.org/10.1016/j.xphs.2023.10.014



    ------------------------------
    Jiaying Liu Ph.D.
    Associate Principal Scientist
    Merck & Co, Inc - Rahway, NJ
    Rahway NJ
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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