Biosimilars

Introduction: Tackling the Technical and Regulatory Challenges of Biosimilar Development

In a just a few years, the biopharmaceutical industry has gone from questioning the feasibility of “follow-on biologics” (around the time of BPI’s first issues) to fearing them (when we published our first supplement on the topic in 2013) to the acceptance and strategizing of today. Perhaps because of its more socialized medicine, Europe led the way in biosimilar regulation and approved its first such product nearly 10 years before the first US biosimilar launch in 2015. In between came…

Advancements in Characterizing Therapeutic Protein Higher-Order Structure

Electrospray-ionization mass spectrometry (ESI-MS) is a well-established tool for biotherapeutic analysis. It draws intact proteins or peptide ions into the vacuum of a mass spectrometer, where the ion mass is measured. Electrospray ion-mobility mass spectrometry (ESI-IMS) introduces ions into a low-pressure gas, where the effects of aerodynamic drag reveal their shape. This technique is just emerging as a valuable tool for characterizing intact proteins, even though for a decade it’s been the basis of a commercially available medical diagnostic test…

Biosimilar Markets and Regulation: Which Countries Are Going All In?

The pipeline of follow-on (biosimilar and biobetter) products in development for the US, EU, and other major markets is very healthy. It includes nearly 800 biosimilars, about three-quarters of which are presumed to be targeted for major markets, and about 500 biobetters in development. Nearly 1,200 follow-on biopharmaceutical products in the development pipeline are intended to compete with more than 100 currently marketed biopharmaceuticals. This is not just an opportunity in the Western world; biosimilars development is expanding globally. But…

The Clinical Side of Biosimilar Development

Biosimilars have become common on pharmacy shelves in Europe. The first biosimilar product — Sandoz’s Omnitrope version of Lilly’s Humatrope (somatropin) — was approved by the European Medicines Agency (EMA) in 2006. In the decade that followed, more than 20 biosimilars have gained regulatory approval in Europe. The first biosimilar monoclonal antibodies (MAbs) — comparators to Janssen’s Remicade (infliximab) — were approved in 2013. The pace of approvals in the United States has been much slower. The US Food and…

Evolving Bioassay Strategies for Therapeutic Antibodies: Essential Information for Proving Biosimilarity

The modern age of biologics began 35 years ago with the approval of Lilly’s Humulin product — a biosynthetic form of human insulin derived from recombinant DNA and microbial cell culture (1). Today, about a quarter (27%) of the drugs approved yearly by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are biopharmaceuticals: primarily monoclonal antibodies (MAbs), but also vaccines, blood products, and (recently), advanced therapies based on genes and cells. A decade ago, the average…

Outsourcing Biosimilar Development

As the debate continues over the high cost of pharmaceutical treatment options, the development of biosimilars continues to play a dominant role in that discussion and will be an important part of the solution. Biosimilar companies are working at a feverish pace to develop the next generation of follow-on products. Outsourcing to a growing group of contract development and manufacturing organizations (CDMOs) is a key strategy for savvy developers to accelerate their products’ launch. Finding the right CDMO isn’t an…

Biosimilar Therapeutic Monoclonal Antibodies: Gaps in Science Limit Development of an Industry Standard for Their Regulatory Approval, Part 2

Last month, Part 1 of this discussion briefly described the regulatory landscape for developing biosimilar therapeutic monoclonal antibodies (TMAbs). We identified certain specific structural components of TMAb drug substances that warrant particular attention because alterations to them are likely to affect therapeutic safety and effectiveness. Now we conclude by considering whether studies of reference materials can further the development of analytical industry standards to ensure comparability of putative biosimilar TMAbs with innovator TMAbs. We suggest that the time is right…

Biosimilar Therapeutic Monoclonal Antibodies: Gaps in Science Limit Development of an Industry Standard for Their Regulatory Approval, Part 1

Biosimilars are biologically derived pharmaceuticals intended to have clinical similarity to a legally marketed innovator product when that product’s patent or market exclusivity has expired. By contrast with generic small-molecule drugs, clinical performance of a biologic pharmaceutical is a function of its structural complexity and higher-order structure (HOS). Biomanufacturing controls of such complex products cannot fully ensure chemical similarity between an innovator product and putative biosimilar because minor differences in chemical modifications and HOS can significantly alter a product’s safety…

Outsourcing Trends in Biosimilars Development: A Discussion with Niall Dinwoodie (Charles River Laboratories)

No discussion about the future of the biopharmaceutical industry would be complete without assessing the impact of biosimilars. But such discussions no longer focus on whether biosimilars will enter the market, but rather when and how much market share will they take. The rapid progression of biosimilar candidates in company pipelines and the strong biosimilars research conducted by international organizations are strong indications that if your company is not already working within the biosimilars market, it may already be too…

Enhanced Biosimilar Product Characterization: A Case Study Using Raman Spectroscopy Combined with Dynamic Light Scattering

Biophysical characterization has drawn great attention from the biopharmaceutical industry and regulatory agencies across the globe, especially for use in biosimilar drug product development. Currently available biophysical characterization tools can help in screening and optimizing better (more stable) formulations for such products. However, most tools cannot be used for head-to-head comparison of the biophysical properties of an optimized biosimilar formulation with those of an innovator product at higher concentrations. We developed and optimized a formulation for monoclonal antibody MAb B…