The 15th WCBP CMC Strategy Forum, “Raw Material Control Strategies for Bioprocesses,” met on Sunday, 11 January 2009 in San Francisco, CA. This forum considered the design and implementation of control strategies for complex raw materials used in bioprocessing. Discussion focused on key approaches and application of risk assessment tools that can be used to identify and assist in mitigating potential safety and efficacy concerns that can affect the quality of biological products.

To fully explore the topic, the forum first focused on recognizing and assessing potential risks associated with raw materials (RMs) and then applied those rationales to actual case studies with audience participation. The morning session began with an introduction to the topic followed by five presentations. Areas of discussion included how expectations for raw material control are evolving within changing regulatory and business paradigms including quality by design (QbD), counterfeiting, complex supply chains, and sourcing changes.

PRODUCT FOCUS: ALL BIOLOGICS
PROCESS FOCUS: UPSTREAM AND DOWNSTREAM PROCESS DEVELOPMENT
WHO SHOULD READ: PRODUCT AND PROCESS DEVELOPMENT SCIENTISTS, ANALYTICAL, MANUFACTURING, QA/QC
KEYWORDS: INSULIN, PROTEIN A, QUALITY BY DESIGN, RISK MANAGEMENT
LEVEL: INTERMEDIATE

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Presenters discussed risk assessment and mitigation strategies along with supplier risk management plans.

During the afternoon, two case studies were presented, and forum participants were polled for their assessment of the level of risk pertaining to different scenarios. For the first time, the forum used an electronic audience response system, which made it possible to tally participant responses to a variety of questions and to compare and evaluate those responses in real time. (Responses are detailed in the “Audience Participation” box.)

After an introduction to the topic of raw materials by organizers John Dougherty (Eli Lilly) and Mark Schenerman (MedImmune), a series of presentations filled the morning schedule. They highlighted different aspects and issues involved in raw materials for use in biologic applications. Ruth Cordoba-Rodriguez of the FDA's Center for Drug Evaluation and Research (CDER in Bethesda, MD) spoke on “Raw Materials in the Manufacture of Biotechnology Products: Regulatory Considerations.” A vendor perspective was presented by Kathy Carroll and Denise DeTommaso of SAFC Biosciences (Lenexa, KS) in “Raw Material: A Supplier's Perspective.” “Implementing Risk Assessment Tools for Identifying Critical Raw Material Attributes” was presented by Gregory Beck of Eli Lilly (Indianapolis, IN) and followed by Eric Berg of Amgen (Thousand Oaks, CA) with “Supplier Lifecycle Management: Ensuring Raw Material Authenticity and Quality.” Finally, Arifa Khan from the FDA's Center for Biologics Evaluation and Research (CBER, Bethesda, MD) presented “CBER's Perspective on Regulating Raw Materials in Biologics.” The presenters were then joined by Keith Webber, CDER, as panel members, with Mark Schenerman facilitating subsequent discussion and development of a risk-assessment tool for raw materials.





BPI EXTRA: CASE STUDY AUDIENCE PARTICIPATION
For the first time, the forum used an electronic audience response system, which made it possible to tally participant responses to a variety of questions and compare and evaluate those responses in real time. Questions were posed by the panel and displayed on screen. Participants had several seconds to respond to each using hand-held voting devices provided by Meridia Audience Response (www.meridiaars.com). Find the case study questions and responses online at www.bioprocessintl.com/bpiextra. Regulatory Considerations

The presenters pointed out the lack of a consistent definition of raw materials in regulations pertaining to the pharmaceutical industry. In its Q7 guideline, the International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) defines raw materials as “starting materials, reagents, and solvents intended for use in the production of intermediates or APIs.” However, the term as defined by different speakers could cover a wide range of materials including the following:

• starting or source materials (cell lines, viral or bacterial stocks, media components, chemicals, tissues, serum, water)

• in-process materials (resins, buffers, filters, column housings, tubing, reagents)

• excipients

• packaging components, both primary and secondary (syringes, vials, stoppers, plungers, crimps, boxes, trays, and labels)

• device/delivery components (pen/injector components, IV bags, filters).