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Implementation of Patient Centric Specifications from an Industry & Regulator Perspective

ISPE PQLI® Patient Centric Specification Working Group
Patient Centric Specifications from an Industry & Regulator Perspective

Over the past twenty years, an evolution of pharmaceutical development has resulted in new approaches to ensuring product quality and patient safety. The science and risk-based concepts outlined in ICH Q8-Q12 encourage a more holistic approach to the product control strategy. Under this paradigm, product quality should not be ensured by the quality specification, rather it should be confirmed. Over-reliance on batch history for setting specification limits at the time of registration may result in limits that are too tight if manufacturing experience at the time of registration is minimal and batch data ranges are very narrow. Push back from regulators could force pharmaceutical manufacturers to Introduce additional purification steps that would lead to products meeting the tighter limits with concurrent loss in product yield. In turn, this may also result in unnecessary product rejection and/or increased manufacturing costs. Conversely, over-reliance on batch history might discourage companies to consistently manufacture material of the highest quality for clinical batches, to later enable a justification for wider limits for the registration specifications. Finally, this reliance on batch data could conflict with the current regulatory environment to expedite clinical studies through the Breakthrough therapy designation or Prime pathways.

The ISPE Patient Centric Specification working group’s objectives are to enable an approach to specification setting that places the focus on ensuring patient safety and efficacy. The approach to the quality specifications for a new drug substance and drug product should be reconsidered to more appropriately comprise QbD concepts. In place of the past reliance on batch history to derive limits, specification limits should consider such things as upstream and downstream controls, impact to other critical quality attributes, impact to the downstream critical process parameters, and most importantly, impact to patient safety and efficacy. In addition, a risk assessment would be completed to evaluate the robustness of the relevant chemistry, manufacturing, and associated controls. Process consistency can be monitored under the pharmaceutical quality system and patient centric specifications can be implemented.

An upcoming webinar, Patient Centric Specifications from an Industry and Regulatory Perspective, will bring regulatory and industry representatives together to discuss their perspectives on implementation of patient centric specifications (also known as “clinically relevant specifications” or “patient centric quality standards”). The rationale for patient centric or clinically relevant specifications are articulated in two quotes from FDA Pharmaceutical Quality Oversight: One Quality Voice.

Clinically relevant specifications can be defined as a set of criteria and acceptance ranges to which drug products should conform in order to deliver the therapeutic benefit indicated in the label.

Clinically relevant specifications increase flexibility within the pharmaceutical manufacturing sector while maintaining quality by establishing acceptance criteria based on clinical relevance, instead of process capability or manufacturing process control.

Several recent publications from industry have focused on the establishment of patient centric specifications, most notably: (1) J. Bercu, et al. “Establishing Patient Centric Specifications for Drug Substance and Drug Product Impurities,” Journal of Pharmaceutical Innovation, Volume 14, Pages 76–89 (2019) and (2) Margaret N. Ruesch, et al. “Strategies for Setting Patient-Centric Commercial Specifications for Biotherapeutic Products,” Journal of Pharmaceutical Sciences, Volume 110, Issue 2, Pages 771-784, (2021).

The webinar will focus on the regulatory experience and expectations for a company to establish patient centric specifications. The session will include brief presentations from industry and regulators and will be followed by an extended panel discussion.

Learning Objectives/Takeaways

  1. Hear from industry representatives about their perspectives on implementation of patient centric specifications.
  2. Hear from regulatory representatives about their perspectives on implementation of patient centric specifications.
  3. Conduct a panel discussion with industry and agency representatives to clarify points of agreement and areas where further discussion is required, focusing on “how does ICH Q6A/B facilitate or impede the implementation of patient centric specifications?”

Whether you’re from development, operations/manufacturing, regulatory, or quality organizations, this topic is relevant to your work to bring new drugs to the patient. Development history and associated resources can be considered to create appropriate patient-centric specifications. These discussions will help facilitate the evolution to this revised approach.

Patient Centric Specifications from an Industry and Regulatory Perspective
Tuesday, 30 November, 1100-1330 ET