CMC Forums

CMC Strategies for Expedited Program Development — Regulatory Perspectives: Session 1 of a CMC Strategy Forum

In response to increasing demands for expedited availability of biotherapeutics around the world — and with the ultimate goal of patient benefit — health authorities have developed accelerated regulatory pathways to reduce development timelines to product licensure. Because of the complexity and unique nature of each program and product modality, some solutions must be worked out case by case between sponsors and regulatory agencies. On 13 October 2020, CASSS–Sharing Science Solutions presented a virtual session overviewing currently available regulatory pathways…

eBook: Creating CMC Strategies for Pandemics and Beyond — Perspectives on the Impact of the COVID-19 Pandemic

The COVID-19 novel coronavirus pandemic has highlighted the biopharmaceutical industry’s need to create and implement chemistry, manufacturing, and controls (CMC) strategies that can expedite drug development during times of crisis. This bold topic was the premise of the 2021 CASSS Well-Characterized Biotechnology Products (WCBP) forum titled “Special Edition: Creating CMC Strategies for Pandemics and Beyond.” Held virtually on 25–28 January and 1–4 February 2021, the eight-day event addressed manifold considerations for SARS-CoV-2 virus prevention, diagnosis, and treatment. Five hundred attendees…

Implementation of Established Conditions: Learnings from a “Sharing Science Solutions” Workshop

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline Q12 (1) (step 4 sign-off in November 2019) is in the process of being implemented in a number of regulatory regions. The document provides additional frameworks for pharmaceutical life-cycle management. It is intended to support globally harmonized regulatory tools such as established conditions (ECs) and product life cycle management (PLCM) documents to facilitate postapproval changes to chemistry, manufacturing, and controls (CMC). Although a harmonized framework…

Emerging Strategies for Drug-Product Comparability and Process Validation: Part 2 — Validation, Legacy Products, and Lifecycle Management

This two-day CASSS CMC Strategy Forum explored many technical, practical, and regulatory facets of biological drug-product (DP) analytics, process validation, and comparability. Part 1 of this report summarized the discussions on drug-product analytics and comparability in BPI’s March 2021 issue (1). Here we report on day two presentations and discussions on validation, legacy products, and lifecycle management. Session Three: Drug-Product Validation The morning session focused on principles of process validation with examples of challenges specific to drug products. New Risk-Based…

Automation of Potency Assays: A Strategic Journey

Cell-based potency testing provides quantitative data concerning a drug’s biological activity. Thus, it plays an essential role in biopharmaceutical quality control (QC), good manufacturing practice (GMP) product release, comparability determination, and stability testing for both drug products and drug substances. Potency is a critical quality attribute (CQA) often scrutinized by regulators and reviewers. Test methods are specific to a drug’s mechanism of action (MoA) and should be validated to internationally harmonized regulatory standards (1). The options preclude applying a simple…

Emerging Strategies for Drug Product Comparability and Process Validation: Part 1 — Analytical Tools and Drug Product Comparability

Process validation is a key part of the development and manufacture of all approved drug products, but its completion can be a daunting task. At a two-day CASSS CMC Strategy Forum held in July 2016 in Gaithersburg, MD, speakers and attendees addressed the many technical, practical, and regulatory facets of drug product process validation and comparability. In part 1 of this report, we summarize the key discussion points of the first day, which focused on analytics and comparability. Session One:…

Next-Generation Biotechnology Product Development, Manufacturing, and Control Strategies, Part 2: Process Modeling and Analytics

Part 1 of this article focused on the first two sessions of a CASSS chemistry, manufacturing, and controls (CMC) forum entitled “Next-Generation Biotechnology Product Development, Manufacturing, and Control Strategies,” which took place on 16–17 July 2018 in Gaithersburg, MD. Those sessions focused on upstream and downstream process technologies and strategies (1). Part 2 highlights the final two conference sessions on process modeling, control, and analytics. Process Modeling and Control The third conference session was “Modeling and Control Strategies.” Advancements in…

Next-Generation Biotechnology Product Development, Manufacturing, and Control Strategies, Part 1: Upstream and Downstream Strategies

Future biomanufacturing must address industry drivers, including the need for decreasing cost of goods (CoG), increasing market globalization, shortening development time for pipeline products, reducing risk to patient supply, and improving product quality. A CASSS chemistry, manufacturing, and controls (CMC) forum entitled “Next-Generation Biotechnology Product Development, Manufacturing, and Control Strategies” took place on 16–17 July 2018 in Gaithersburg, MD, to address those opportunities. Advanced technologies include single-use bioreactors, alternating tangential-flow (ATF) systems used during fermentation, modular and closed process equipment,…

Development of Patient-Focused Commercial Specifications: Understanding Clinical Relevance and Criticality of Quality Attributes

The CASSS chemistry, manufacturing, and controls (CMC) Strategy Forum on 23 January 2019 in Washington, DC, was entitled, “The Development of Patient-Focused Commercial Specifications Through Understanding of Clinical Relevance and Criticality of Quality Attributes.” This forum covered the definition, identification, control, and management of patient-focused attributes throughout the life cycle (from discovery through approval) of biological products, including vaccines. Participants investigated how to differentiate through the product development life cycle which attributes are “clinically meaningful” from those applied for manufacturing…

Trends in Chemistry, Manufacturing, and Controls: Next-Generation Technologies and Product Modalities

New technologies bring new regulatory challenges. The biopharmaceutical industry must be cautious in its implementation of new scientific ideas and technology platforms — no matter how promising those might be. Regulators will look skeptically on any claim that isn’t backed up by good data, and with no solid history of successful use to build on, a company must have all the answers itself. How do compliance professionals anticipate what kinds of questions reviewers will ask when the time comes —…