Biosimilars

Accelerating Biologic and Biosimilar Drug Development: Ready-to-Use, Cell-Based Assays for Potency and Lot-Release Testing

With the drug industry’s expanding emphasis on biologics, the need for robust cell-based assays has grown at all stages of development. Requirements for efficacy, quality, and potency testing often demand a complex set of bioassays and/or cell-based assays for new therapeutics or biosimilars. Developers of the latter have found this need for cell-based assays to be particularly challenging. Commercially available, ready-to-use cell-based assays provide a robust functional response from specific therapeutic targets. They can significantly shorten assay development time while…

Primary and Higher-Order Structural Characterization Strategy for Biosimilarity Assessment

The development pathway of a biosimilar is unlike that of a novel biotherapeutic. Many regulatory authorities reference a stepwise approach to establishing biosimilarity. Analytical requirements are greatly increased before a product enters clinical testing. Enhanced analytical efforts entail physical, chemical, and biological characterization of a biosimilar product compared with an originator reference product. Strategies at this early stage must include intensive characterization of multiple batches to determine variability of quality attributes. Here I address some issues involved in meeting regulatory…

Special Report on Assays, Test Methods, and Comparability The CMC Strategy Forum Series, Part 4, Biosimilar Products: Scientific Principles, Challenges, and Opportunities

The Chemistry, Manufacturing, and Controls (CMC) Strategy Forum held on 22 January 2012 in San Francisco, CA, focused on selected scientific and regulatory aspects in the development of biosimilar products. Such products are an increasingly important area of interest for both the biopharmaceutical industry and its regulatory agencies. Biosimilars are highly complex, so scientists have been unable to demonstrate identity to a level typically possible for small molecules. Consequently, specific scientific and regulatory approaches are required to ensure the high…

Special Report: A World of Difference — Biosimilars and Biobetters Offer Unique Benefits — and Risks

by John Otrompke, with Cheryl Scott and S. Anne Montgomery When the United States Food and Drug Administration (FDA) approved the country’s first ever biosimilar on 6 March 2015, it had been a long time coming. After all, the European Union had approved the first biosimilar in 2006, and a number of others have followed in Europe since then. Still, the approval of biosimilar filgrastim, a recombinant colony-stimulating factor used to offset the complications of chemotherapy, was a welcome step…

Rapid Development and Scale-Up of Biosimilar Trastuzumab: A Case Study of Integrated Cell Line and Process Development

Compared with that for new drugs, biosimilar development faces significantly condensed timelines from cell line to first-in-human (FIH) trials. A biosimilar development program needs to accelerate quickly toward preclinical and phase 1 studies; phase 2 studies typically are not required because dose response and other patient-treatment concepts are already established by the original, comparator medicine. Phase 3 studies typically are limited to fewer patients, which ultimately shortens overall timelines and costs. The key challenge remains: demonstrating comparability and high similarity…

The US Biosimilars Future Is Hard to Predict: Global Health Policy, Innovation, Prices, and Profits Are All at Stake

Enthusiasm in the United States over opportunities for biosimilars has waned since such products were first launched in Europe. The hesitation stems from confusion and uncertainty surrounding regulations. Manufacturers and suppliers are looking for guidance from the US Food and Drug Administration (FDA), which has promised guidelines that are still in process after five years. Even naming protocols for biosimilars are clogging the works. And in the absence of coherent FDA guidelines, many US states are haphazardly implementing laws concerning…

Guidance Is Lacking in the European Biosimilar Regulatory Framework: Considering the Dynamic of Quality Profiles in Development

Biopharmaceutical medicinal products (biologics) had an estimated global commercial market size of US$100 billion in 2013. Because they are more complex than small molecules — and defined by the uniqueness of their manufacturing processes — the generics approval process is not applicable for biologics. Article 10(4) of European Medicines Agency (EMA) directive 2001/83/EC was amended in 2004 in response to the industry’s desire for market access by launching a “similar” biologic abbreviated approval pathway. Leading the subsequent process, the EMA…

Due Diligence of Early Stage Technologies: Achieving Rapid Product Development with Low R&D Costs

Increased understanding of human diseases at molecular and cellular levels is leading to development of novel life-science technologies. Such advancements typically pertain to discovery and manufacturing of novel human therapeutics, new modes of drug delivery, and novel diagnostic technologies. The majority of those technologies are developed by early stage biopharmaceutical companies that have a greater appetite for risk than do larger companies. Early stage biopharmaceutical companies, however, have limited capital raised through personal sources, angel investors, venture capital, or government…

Higher-Order Structure Comparability: Case Studies of Biosimilar Monoclonal Antibodies

Great successes for monoclonal antibody (MAb)–based biologics over the past decade have provided many valuable options for patients combating some of the most serious diseases in the world, including cancer and autoimmune diseases. MAbs and antibody–drug conjugates (ADCs) are among the fastest growing biologic segments in development, with hundreds of candidates currently under clinical study. Meanwhile, society is facing the challenge of increasingly higher costs in healthcare including the cost of pharmaceuticals. With an aging population in many parts of…

Biosimilars Awaken CROs

Biosimilars are revolutionizing the bioprocessing industry. Over the years, company CEOs have pushed different models, expanding and closing down huge amounts of internal manufacturing, research and development, and quality control facilities. Sometimes services were pushed to Asia, only to get brought back a few years afterward when a new CEO was appointed. Mergers and acquisitions further complicated those ideas. Consequently, many biopharmaceutical companies now have “gaps” in their drug development service provisions. Filling those gaps will fall on contract research…