Biosimilars: what clinicians should know.

Biosimilar medicinal products (biosimilars) have become a reality in the European Union and will soon be available in the United States. Despite an established legal pathway for biosimilars in the European Union since 2005 and increasing and detailed regulatory guidance on data requirements for their development and licensing, many clinicians, particularly oncologists, are reluctant to consider biosimilars as a treatment option for their patients. Major concerns voiced about biosimilars relate to their pharmaceutical quality, safety (especially immunogenicity), efficacy (particularly in extrapolated indications), and interchangeability with the originator product. In this article, the members and experts of the Working Party on Similar Biologic Medicinal Products of the European Medicines Agency (EMA) address these issues. A clear understanding of the scientific principles of the biosimilar concept and access to unbiased information on licensed biosimilars are important for physicians to make informed and appropriate treatment choices for their patients. This will become even more important with the advent of biosimilar monoclonal antibodies. The issues also highlight the need for improved communication between physicians, learned societies, and regulators.

Cell and Gene Therapies: European View on Challenges in Translation and How to Address Them.

Advanced therapy medicinal products (ATMPs), i.e., cell and gene therapy products, is a rapidly evolving field of therapeutic development. A significant proportion of the products are being developed by academia or small/medium-sized enterprises (SMEs). The many challenges in translation posed by this class of products include aspects covering: manufacturing, non-clinical development plan as relevant to clinical trial, marketing authorization, and reimbursement. In this context, the term translation refers to the relevance of non-clinical data in relation to how it impacts on appropriate and efficient clinical development. In order to successfully overcome these challenges, a clear understanding of the requirements and expectations of all the stakeholders is critical. This article aims to cover the potential challenges related to such translation and suggested approaches to find solutions based on experience and learnings from the perspective of European Union. While commercial challenges have a significant impact on the ATMPs in general, it is considered outside the scope of this article. However, by adopting a strong scientific basis for translation as suggested in this article, it is likely such an approach would help rather than harm successful real world clinical use of ATMPs.

Clinical development of gene therapy needs a tailored approach: a regulatory perspective from the European Union.

Gene therapy is a rapidly evolving field that needs an integrated approach, as acknowledged in the concept article on the revision of the guideline on gene transfer medicinal products. The first gene therapy application for marketing authorization was approved in the International Conference on Harmonisation (ICH) region in 2012, the product being Alipogene tiparvovec. The regulatory process for this product has been commented on extensively, highlighting the challenges posed by such a novel technology. Here, as current or previous members of the Committee for Advanced Therapies, we share our perspectives and views on gene therapy as a treatment modality based on current common understanding and regulatory experience of gene therapy products in the European Union to date. It is our view that a tailored approach is needed for a given gene therapy product in order to achieve successful marketing authorization.

The committee for advanced therapies' of the European Medicines Agency reflection paper on management of clinical risks deriving from insertional mutagenesis.

In the European Union, the Committee for Advanced Therapies of the European Medicines Agency takes the lead in the scientific assessment for marketing authorization applications for advanced therapy medicinal products, which include gene therapy medicinal products, somatic cell therapy medicinal products, and tissue-engineered products. The Committee for Advanced Therapies also takes the lead in defining the scientific framework for the quality, nonclinical and clinical development of such products. This reflection paper represents the Committee's current thinking on management of clinical risks deriving from insertional mutagenesis. A multidisciplinary approach to insertional mutagenesis is provided. This reflection paper has been adopted by the committee in its April 2013 meeting.

Assessing the safety of stem cell therapeutics.

Unprecedented developments in stem cell research herald a new era of hope and expectation for novel therapies. However, they also present a major challenge for regulators since safety assessment criteria, designed for conventional agents, are largely inappropriate for cell-based therapies. This article aims to set out the safety issues pertaining to novel stem cell-derived treatments, to identify knowledge gaps that require further research, and to suggest a roadmap for developing safety assessment criteria. It is essential that regulators, pharmaceutical providers, and safety scientists work together to frame new safety guidelines, based on "acceptable risk," so that patients are adequately protected but the safety "bar" is not set so high that exciting new treatments are lost.

Challenges with advanced therapy medicinal products and how to meet them.

Advanced therapy medicinal products (ATMPs), which include gene therapy medicinal products, somatic cell therapy medicinal products and tissue-engineered products, are at the cutting edge of innovation and offer a major hope for various diseases for which there are limited or no therapeutic options. They have therefore been subject to considerable interest and debate. Following the European regulation on ATMPs, a consolidated regulatory framework for these innovative medicines has recently been established. Central to this framework is the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), comprising a multidisciplinary scientific expert committee, representing all EU member states and European Free Trade Association countries, as well as patient and medical associations. In this article, the CAT discusses some of the typical issues raised by developers of ATMPs, and highlights the opportunities for such companies and research groups to approach the EMA and the CAT as a regulatory advisor during development.