Regulatory agencies are making a concerted effort to develop a more sophisticated understanding of where the real quality risks lie that could impact patients and to focus their CMC and GMP regulatory processes more squarely on those risks.
The first story in the IPQ’s Monthly Update for June delves into the rather elegant risk-ranking process that FDA’s generics office has recently implemented to determine which ANDAs, and which aspects of those ANDAs, warrant the most reviewer energy.
Central to the IPQ coverage is an explanation of the development, intent and methodology of the new risk-based approach – and the GDUFA and QbD forces that propelled it – by the OGD official leading the initiative. His analysis is key in understanding the significant impact it will have in streamlining the ANDA review process. The new drug staff was engaged in developing the risk principles and algorithms involved, and they will be incorporated into the CMC review process for innovator products as well.
IPQ’s coverage during June also included an update on other facets of the OGD effort to clarify and streamline the ANDA review process under GDUFA. The second story in this issue includes insights from OGD experts on: ● what is emerging from the ANDA guidance pipeline and the impact of industry input ● common mistakes in submissions ● the increase in controlled correspondences, and ● how to avoid rejections related to DMF deficiencies.
The June Monthly Update next focuses on a key factor in the ability to improve formulations and deliver better products to patients – namely the availability of new and modified excipients that reflect the current scientific understanding and are designed for purpose. The story highlights the increasing pressure coming from industry to establish a regulatory pathway that would make new excipient development and use a more realistic possibility. We explore the problems and quality risks created by the current paradigm and how an independent review pathway is an important factor in addressing them.
While GDUFA and QbD are important drivers in changing the way FDA is assessing and managing manufacturing risk on the CMC review side, and do have implications for inspections as well, FDASIA is the biggest driver for risk-based changes in the GMP regulatory arena. FDASIA gives FDA new tools to manage the risks of an increasingly complex and internationalized supply chain. The act also calls for proactively communicating with FDA about manufacturing risks that could play out in drug shortages or facilitate regulatory surveillance, and has heightened the dialogue on proactive GMP communications in general – when they should be used and the characteristics that make them effective.
The fourth story in IPQ’s June coverage provides insights on this proactive communication process from FDA compliance and enforcement veterans, now serving industry, who have a lot of valuable experience to share.
The final story in the Monthly Update for June has strong relevance to the current discussions between industry and FDA on which metrics would have the most value in the agency’s QA surveillance toolbox. The story takes readers inside Amgen’s eight-year continuous improvement journey to upgrade its nonconformance investigation and follow-up process so that the root causes are found and addressed – the paramount concern of regulators in overseeing quality systems.
Amgen’s journey sheds strong light on which metrics more clearly reflect the process improvements that matter to product quality and offers a roadmap for others to follow in strengthening their QA capabilities. It is a compelling story that warrants top management attention – marked by dramatic declines in the number of errors per lot, distribution cycle times, and scrap.
The in-depth stories in the issue are accompanied by two dozen “updates in brief.” IPQ’s briefs include links to related IPQ coverage and to the documents referenced, and are intended to keep subscribers informed on all of the significant developments in drug and biologics quality regulation worldwide as they are occurring.
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