Regulatory Evaluation of Biosimilars: Refinement of Principles Based on the Scientific Evidence and Clinical Experience.

The World Health Organization (WHO) guidelines on evaluation of similar biotherapeutic products (SBPs; also called biosimilars) were adopted by the WHO Expert Committee on Biological Standardization (ECBS) in 2009. In 2019, the ECBS considered that a more tailored and potentially reduced clinical data package may be acceptable in cases where this was clearly supported by the available scientific evidence. The goal of this publication is to review the current clinical experience and scientific evidence and to provide an expert perspective for updating the WHO guidelines to provide more flexibility and clarity.

Safety, Immunogenicity and Interchangeability of Biosimilar Monoclonal Antibodies and Fusion Proteins: A Regulatory Perspective.

Background: Biosimilars have been used for 15 years in the European Union (EU), and have been shown to reduce costs and increase access to important biological medicines. In spite of their considerable exposure and excellent safety record, many prescribers still have doubts on the safety and interchangeability of biosimilars, especially monoclonal antibodies (mAbs) and fusion proteins.

Objectives: The aim of this study was to analyse the short- and long-term safety and interchangeability data of biosimilar mAbs and fusion proteins to provide unbiased information to prescribers and policy makers.

Is There Any Research Evidence Beyond Surveys and Opinion Polls on Automatic Substitution of Biological Medicines? A Systematic Review.

Background: Biosimilars are expected to decrease growing health care expenditures. Given that uptake of biosimilars has been modest, automatic substitution has been suggested to increase their use, but the practice is not yet allowed or implemented in many jurisdictions.

Methods: A systematic review was performed by searching databases Scopus, Medline (Ovid), CINAHL, and Web of Science.

Medication safety risks to be managed in national implementation of automatic substitution of biological medicines: a qualitative study.

Objectives: To explore relevant Finnish stakeholders' perceptions on the automatic substitution of biological medicines with particular focus on medication safety and issues that need to be considered to create an appropriate model for automatic biological product substitution.

Design: Qualitative interview study.

Methods: Data were collected in semistructured individual (n=17), pair (n=7) and group (n=8) interviews (32 interviews, 62 participants) in 2018.

Compatibility of immunogenicity guidance by the EMA and the US FDA.

The guidelines for immunogenicity studies by the European Medicines Agency and the US FDA are based on different legislations and regulatory philosophies. In spite of the different background, the main guidelines are compatible on the scientific level, especially for new innovative therapeutic protein products. The importance of sensitive and drug-tolerant antidrug antibody assays and multidisciplinary approach to development and assessment are highlighted by both agencies.

2018 White Paper on Recent Issues in Bioanalysis: focus on immunogenicity assays by hybrid LBA/LCMS and regulatory feedback (Part 2 - PK, PD & ADA assays by hybrid LBA/LCMS & regulatory agencies' inputs on bioanalysis, biomarkers and immunogenicity).

The 2018 12 Workshop on Recent Issues in Bioanalysis took place in Philadelphia, PA, USA on April 9-13, 2018 with an attendance of over 900 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event - a full immersion week of bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule bioanalysis involving LCMS, hybrid LBA/LCMS and LBA/cell-based assays approaches.

New study designs in clinical drug development.

Clinical development of a novel drug has traditionally been seen as a series of four phases, each having its own objectives in establishing the efficacy and safety of the drug. Increasingly individualized medicine and the changing mechanisms of drug action are also changing the designs of clinical drug testing. The borders of development phases become blurred and the traditional large, controlled multicenter studies may in part be replaced by individual and risk-based approaches.

2017 White Paper on recent issues in bioanalysis: a global perspective on immunogenicity guidelines & biomarker assay performance (Part 3 - LBA: immunogenicity, biomarkers and PK assays).

The 2017 11th Workshop on Recent Issues in Bioanalysis took place in Los Angeles/Universal City, California, on 3-7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event - a full immersion week of bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule analysis involving LC-MS, hybrid ligand-binding assay (LBA)/LC-MS and LBA approaches.

2017 White Paper: rise of hybrid LBA/LCMS immunogenicity assays (Part 2: hybrid LBA/LCMS biotherapeutics, biomarkers & immunogenicity assays and regulatory agencies' inputs).

The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place in Los Angeles/Universal City, California on 3-7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - a full immersion week of bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecule analysis involving LCMS, hybrid ligand binding assay (LBA)/LCMS and LBA approaches.

Interchangeability of Biosimilars: A European Perspective.

Many of the best-selling 'blockbuster' biological medicinal products are, or will soon be, facing competition from similar biological medicinal products (biosimilars) in the EU. Biosimilarity is based on the comparability concept, which has been used successfully for several decades to ensure close similarity of a biological product before and after a manufacturing change. Over the last 10 years, experience with biosimilars has shown that even complex biotechnology-derived proteins can be copied successfully.

Biosimilar regulation in the EU.

In the EU, the EMA has been working with biosimilars since 1998. This experience is crystallized in the extensive set of guidelines, which range from basic principles to details of clinical trials. While the guidance may appear complicated, it has enabled the development of biosimilars, of which 21 have managed to get marketing authorization.

Biosimilars: the science of extrapolation.

Despite the establishment of a specific approval pathway, the issuance of detailed scientific guidelines for the development of similar biological medicinal products (so-called "biosimilars") and the approval of several biosimilars in the European Union, acceptance of biosimilars in the medical community continues to be low. This is especially true in therapeutic indications for which no specific clinical trials with the biosimilar have been performed and that have been licensed based on extrapolation of efficacy and safety data from other indications. This article addresses the concerns frequently raised in the medical community about the use of biosimilars in such extrapolated indications and explains the underlying scientific and regulatory decision making including some real-life examples from recently licensed biosimilars.

Differences in product information of biopharmaceuticals in the EU and the USA: implications for product development.

The Summary of Product Characteristics (SPC) approved by the European Medicines Agency (EMEA) and the Package Insert (PI) approved by the Food and Drug Administration (FDA) were examined for 32 biopharmaceutical products. The aim was to identify differences in the product information since such information may have an impact on the planning of global clinical development programmes. The EU SPC contained more detailed instructions to the prescriber, including the positioning of the product with regard to the stage of the disease and to other therapies.