Biosimilar products have come about as a way to make biopharmaceuticals that are otherwise too costly available to a broader market. Like generic small-molecule drugs, they build on the success of licensed products. And although regulatory pathways allow biosimilar developers to bypass certain expensive testing, they are not generic drugs. Technical challenges remain a part of their development. This Featured Report contains an overview of those challenges and articles that dive into technologies that can help, regulatory hurdles that remain, and a look at the countries that are leading the way globally.
Tackling the Technical and Regulatory Challenges in 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. Now the market is wide open. Early adopters may have a head start, but the real winners will be those who can address and overcome the technical difficulties. Here, BPI’s senior technical editor highlights some technical and regulatory challenges facing those companies seeking to lead the way.
Advancements in Characterizing Therapeutic Protein Higher-Order Structure
Mike Bogan and Henry Benner
Historically, a protein three-dimensional structures have been determined with methodologies developed by the X-ray crystallography community. But their techniques capture only a single protein structure. Structural variations are not revealed. Less-precise but faster techniques can provide only an indirect measurement of protein structure. The authors describe a technology that measures ion shape both directly and rapidly.
Evolving Bioassay Strategies for Therapeutic Antibodies:
Essential Information for Proving Biosimilarity
Regulators require biocomparability testing for follow-on biologics and biosimilars, including accelerated stress condition testing and confirmation of successful production scale-up in addition to the usual bioactivity testing. Developers need a suitable bioassay in the earliest stages of development — and likely more than one assay for products that have more than one function. These assays need to be reliable, reproducible, and precise. Not surprising, surrogate approaches are favored over the time-consuming, tedious, and sometimes highly variable mechanism of action (MoA) assays. This article briefly examines both classical immunological MoA pathway assays (ADCP , CDC, ADCC) and those for therapeutic antibodies designed to block or inhibit immune-checkpoint receptors as an example for target-specific assays.
The Clinical Side of Biosimilar Development
Developing a biosimilar can be a challenging task, with many regulatory hurdles on the road to gaining marketing authorization. A well-developed regulatory strategy in the early phases of development (taking into account the different aspects of the product) is crucial to avoiding problems in later stages. This article summarizes recent highlights the main early phase regulatory challenges, including the need for a solid CMC dossier, selection of optimal countries for the phase 1 studies, interactions with health authorities, and planning for marketing applications with the various regulatory bodies.
Biosimilar Markets and Regulation: Which Countries Are Going All In?
Ronald A. Rader
Regulatory aspects of biosimilar development are different around the world. Ron Rader wraps up this featured report by looking at the global perspective, with a special focus on nomenclature. He describes going “all-in” from many perspectives, including product development and manufacturing, product testing, applications and product approvals, imports/exports and markets, and governmental involvement.