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Linking Pharma Quality to Clinical Relevance Workshop Recap


Clinically Relevant Specifications (CRS) are a set of criteria and acceptance ranges—such as impurities, dissolution, and in vitro release testing—to which drug products should conform to deliver their therapeutic benefits. Questions remain on establishing acceptance criteria based on clinical relevance instead of process capability or manufacturing process control. This workshop nonetheless encouraged participants to incorporate their experiences and propose solutions as we strive to identify potential efficiencies and continuous improvement. The objectives of this workshop, led by Daniel Peng, PhD, Senior Principal Scientist/Director, at Shire, were to identify how to ensure pharmaceutical product quality in the modern world, and what can be done to remove roadblocks. In this rotation of the workshop, the facilitator was Susan Berlam, RPh, Senior Director Regulatory CMC, Pfizer Inc., and colleagues Peng; Shrinivas Murti, PhD, Director, Global Regulatory CMC, Merck & Co Inc.; Sarah Pope Miksinski, PhD, Director, Office of New Drug Products, Director (Acting) Office of Surveillance, FDA/CDER/OPQ; and Paul Seo, PhD, Director (Acting), Division of Biopharmaceutics, FDA/CDER/OPQ/ONDP, led table discussions.

Berlam began by reminding participants that patients and caregivers alike expect medicines “to be available and of high quality, deliver the same performance as defined on the label, and to perform consistently: this is the standard of quality that patients and caregivers expect.” Safeguarding clinical performance and ensuring that all human drugs meet these standards is the primary responsibility of the US FDA Office of Pharmaceutical Quality (OPQ). She then presented the Office of Pharmaceutical Quality's definition of clinically relevant specifications, which state, “These specifications connect quality to safety and efficacy, by establishing acceptance criteria based on clinical relevance rather than process capability or manufacturing process controls.”

Berlam could not have anticipated what happened when she brought up a slide that articulated the problem statement, “How can the various aspects of clinical relevance be successfully incorporated into quality (clinically relevant specifications, communications with clinical disciplines, QTPP, life cycle management)?” The workshop attendees spent the better part of an hour debating the problem statement, and its premise. One question that resonated with all the tables was, “If we are talking about this, does it mean we have a problem with current specifications?” The debate was intellectual in nature yet rooted in the practical experiences of the room. Once over, table discussions ensued. When volunteers presented the results of their conversations, the room once again became very animated. Questions ranged from questioning the definition of clinically relevant specifications, redesigning clinical studies to include variability in product, to whether modeling has clinical relevance.

Get a full conference recap by visiting the official 2017 ISPE/FDA/PQRI Quality Manufacturing Conference website.