Future Evolution of Biosimilar Development by Application of Current Science and Available Evidence: The Developer’s Perspective

Abstract

Biosimilars have been available in the USA for over a decade, and in Europe for almost two decades. In that time, biosimilars have become established in the treatment landscape for a wide range of diseases, facilitating patient access and affordability of healthcare. However, patients can still struggle to access biological therapies in some markets. There is a need to streamline the process of developing biosimilars without compromising their quality, safety, or efficacy. This opinion piece considers the efficiencies that could be achieved within the biosimilar approval process. In clinical trials for biosimilars, clinical efficacy endpoints have been shown to be less sensitive measures of biosimilarity than biochemical, biophysical, and biological functional assays. Additional clinical efficacy studies comparing potential biosimilars and reference products do not add information that is useful for regulatory purposes. Large clinical studies of biosimilars with immunogenicity endpoints are of limited value, given the quality control processes in place for all biologics, including biosimilars. The expectation for multiple-switch studies for US interchangeability designation should be reconsidered immediately, and the category should be eliminated in the future. As biosimilars are typically approved globally based on a single set of clinical trials, and all subsequent manufacturing changes are already carefully monitored by regulatory authorities, comparative pharmacokinetic testing of EU and US reference products is unnecessary. Manufacturers and regulators could take greater advantage of existing real-world evidence. Streamlining biosimilar development would enable biosimilar development of more and a wider variety of biological drugs, accelerating biosimilar development without impacting patient safety or effectiveness.

Long-Term Real-World Post-approval Safety Data of Multiple Biosimilars from One Marketing-Authorization Holder After More than 18 Years Since Their First Biosimilar Launch

“…At that time none had been withdrawn for safety reasons nor had any biosimilar specific AEs been added to product labels. Based on increased scientific knowledge and cumulative experience with biosimilars to date, recommendations have been made by HAs and other stakeholders for a more streamlined approach in biosimilar clinical development and a reduction in the requirement for clinical data [5,[29][30][31][32]. It may also be possible to streamline post-approval reporting requirements based on data provided over time by the MAH.…”

Biosimilar drug lag and evolution in Malaysia: A retrospective analysis of regulatory approvals

“…The observed lag in biosimilar approval in this study therefore suggests that patients may experience delayed access to new biosimilar treatments that have already been approved on the international market. Thus, to mitigate this possibility in countries, there have been calls for streamlined regulatory approval for biosimilars between countries to improve the availability and access to affordable biological therapies around the world [5,10,33]. However, as earlier mentioned, drug lag comprises submission lag time and regulatory review time.…”

“…Therefore, identifying and addressing any challenges in the biosimilar approval process can help patients have timely access to life-saving biological therapies. This could include streamlining regulatory approval processes or incentivizing companies to submit their biosimilar registration dossiers on time [5,33,37]. For example, reducing uncertainties over patent or other exclusivity issues and providing clarity on regulatory requirements can potentially foster biosimilar submission and entry.…”

“…According to NPRA, the revised guidance was initiated to align with the current version of the WHO biosimilar guideline, which was released in 2022, with the goal of making some of the clinical and nonclinical requirements more consistent with current practices and other guidelines, as well as providing clari cation and exibility [39]. In addition to re ning regulatory requirements and providing more clarity, adequate resource allocation, training, exploring opportunities for mutual recognition of regulatory assessments, and leveraging existing data from stringent regulatory authorities' approvals may be needed to expedite the regulatory process in Malaysia [32,33,40].…”

Impact of Excipient Extraction and Buffer Exchange on Recombinant Monoclonal Antibody Stability

“…Industry manufacturers and regulatory agencies worldwide strive to approval pathways for affordable biologics such as biosimilars. − Biosimilars are biologics that are highly similar to the original product (innovator) in terms of quality, safety, and efficacy. − The requirements for demonstration of the similarity of biological products, from the viewpoints of safety and efficacy, are stringent. The guidelines from the World Health Organization are designed to serve as a framework for the evaluation of biosimilars across the globe .…”