Standardizing Quality Submissions and Assessments: PQ/CMC and KASA

Over the last two years, there were several ongoing updates and developments in global regulatory CMC (chemistry, manufacturing, and controls) guidelines. Here are some key highlights:

• ICH Q12: The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is working on the development of the Q12 guideline, which aims to establish a framework for the management of post-approval CMC changes for pharmaceutical products. The guideline is intended to promote innovation and continuous improvement in pharmaceutical manufacturing and supply chain management.
• USP General Chapter <665>: The United States Pharmacopeia (USP) is working on the development of a new general chapter on plastic packaging systems and their interaction with drug products. The chapter is intended to provide guidance on the selection and testing of plastic packaging systems to ensure their compatibility with drug products and their manufacturing processes.
• EU Annex 1: The European Medicines Agency (EMA) is revising its Annex 1 guideline on the manufacture of sterile medicinal products. The revised guideline is expected to include new requirements for the control of particulate and microbiological contamination in cleanrooms and other controlled environments.
• FDA Quality Metrics Program: The US Food and Drug Administration (FDA) is continuing to implement its Quality Metrics Program, which aims to encourage the use of objective, data-driven metrics to assess the quality and consistency of pharmaceutical manufacturing processes. The program is intended to support continuous improvement in pharmaceutical manufacturing and supply chain management.

It’s worth noting that the regulatory landscape is constantly evolving, and new developments in CMC guidelines may have emerged since my knowledge cutoff date. It’s important for pharmaceutical companies and other stakeholders to stay up to date on the latest regulatory requirements and guidelines to ensure compliance and maintain the safety and efficacy of their products.

ICH Q13 and Beyond

There are several proposed CMC regulatory guidance that were under development or recently issued. Here are some key highlights:

• ICH Q13: This draft guideline was proposed by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) in 2019 and aims to provide guidance on the use of continuous manufacturing (CM) for drug substances and drug products. The guideline is intended to encourage the implementation of CM in pharmaceutical manufacturing and provide a harmonized framework for the regulatory assessment of CM applications.
• EU MDR and IVDR: The European Union’s Medical Devices Regulation (MDR) and In Vitro Diagnostic Devices Regulation (IVDR) were both scheduled to go into effect in May 2020 and May 2022, respectively, but the implementation dates have been delayed due to the COVID-19 pandemic. The regulations aim to strengthen the oversight of medical devices and in vitro diagnostic devices and will require manufacturers to provide more detailed information on the manufacturing and quality control of these products.
• USP General Chapter <1083>: This new general chapter was proposed by the United States Pharmacopeia (USP) in 2020 and aims to provide guidance on the development and validation of analytical methods for drug substances and drug products. The proposed chapter includes information on method development and optimization, method validation, and method transfer.
• FDA draft guidance on comparability: This draft guidance was issued by the US Food and Drug Administration (FDA) in 2019 and aims to provide guidance on the assessment of comparability for biotechnology products. The guidance outlines the regulatory requirements for demonstrating the comparability of a biotechnology product before and after manufacturing changes and provides a framework for the development of a comparability protocol.

It’s important to note that these proposed guidelines are in draft, and stakeholders should refer to the most recent versions for up-to-date information.

Whats Next

The FDA is working on a project to identify and prioritize pharmaceutical quality/chemistry, manufacturing, and controls (PQ/CMC) information that would benefit from a structured submission approach. The goal is to establish electronic standards for submitting PQ/CMC data, and specific objectives of the project include developing structured data standards and a data exchange standard for submitting the structured PQ/CMC data to the FDA. The submission of structured data in a standardized format is intended to increase the efficiency of FDA’s review of PQ/CMC data contained in the Module 3 of eCTD submissions for various drug applications. The draft standardized data elements and terminologies were created by an Agency workgroup comprised of Subject Matter Experts from different centers within the FDA for consistency of product quality data across FDA centers.