CMC Forums

Cell Lines Are the Foundation: A Methodical Approach to Derisking Outsourced Development and Improving Manufacturability of Novel Biologics

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The most important choice for bringing a novel biologic into clinical development could be the cell line for expressing it. Somewhat determined by that, development of the initial manufacturing process comes in a close second. After an investigational new drug (IND) application, early clinical studies use materials made from the cell line and manufacturing process that were selected at the start of a clinical candidate’s life cycle. The objective for most sponsor companies is to get IND-enabling material produced in…

April 20, 2023

Risk-Based Biologics: CMC Flexibilities in the EU Regulatory System

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Pharmaceutical companies and regulatory agencies strive to foster scientific excellence in drug development and evaluation so that members of the public can access the high-quality medicines that they need. Recent European Medicines Agency (EMA) approvals for COVID-19 vaccines highlight those organizational accomplishments and showcase the application of risk-based chemistry, manufacturing, and controls (CMC) flexibilities that are embedded within the European Union (EU) regulatory system. Many of the CMC flexibilities outlined herein were established for PRIME (priority medicine), a scheme that…

March 21, 2023

DNA to IND in 13 Months: A CMC Strategy for Bispecifics

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Multichain protein biotherapeutics such as bispecific molecules have been developed to treat cancer, neurological and ophthalmic disorders, and autoimmune and inflammatory diseases. Early successes now are driving greater numbers of such molecules toward clinical evaluation and commercial approval. However, the complexity of bispecific development and manufacture calls for innovative tools and technologies to facilitate the clinical journeys of such products and prevent costly setbacks for their sponsors. In its commitment to fostering novel biomolecular formats, Lonza has designed a chemistry,…

November 16, 2022

20 Years of Chemistry, Manufacturing, and Controls Strategy. A Conversation About the CASSS CMC Forum Series

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Formerly known as the California Separation Science Society, the CASSS organization has maintained a close relationship with BioProcess International since its inaugural year. In particular, the CMC Strategy Forum series began the same year that BPI’s original staff joined Informa to develop a new international trade publication covering biopharmaceutical development and manufacturing. Beginning with our February 2004 issue, BPI has been proud to publish dozens of reports from this influential series of meetings over the years. Their success around the…

August 19, 2022

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

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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…

May 20, 2022

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

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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…

November 30, 2021

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

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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…

October 28, 2021

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

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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…

April 16, 2021

Automation of Potency Assays: A Strategic Journey

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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…

March 9, 2021

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

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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:…

March 9, 2021