Development of extracellular vesicle-based medicinal products: A position paper of the group "Extracellular Vesicle translatiOn to clinicaL perspectiVEs - EVOLVE France".

Extracellular vesicles (EV) are emergent therapeutic effectors that have reached clinical trial investigation. To translate EV-based therapeutic to clinic, the challenge is to demonstrate quality, safety, and efficacy, as required for any medicinal product. EV research translation into medicinal products is an exciting and challenging perspective.

Controlled Human Infection Studies: Proposals for guidance on how to design, develop and produce a challenge strain.

There is an increasing need to establish quality principles for designing, developing and manufacturing challenge agents as currently these agents are classified differently by various jurisdictions. Indeed, considerations for challenge agent manufacturing vary between countries due to differences in regulatory oversight, the categorization of the challenge agent and incorporation into medicinal/vaccine development processes. To this end, a whitepaper on the guidance has been produced and disseminated for consultation to researchers, regulatory experts and regulatory or advisory bodies.

Acceptability of oral liquid pharmaceutical products in older adults: palatability and swallowability issues.

Background: In institutional care, oral liquid pharmaceutical products are widely prescribed for older patients, especially for those with swallowing disorders. As medicines acceptability is a key factor for compliance in the older population, this study investigated the acceptability of oral liquid pharmaceutical products in this targeted population.

Methods: An observational, multicenter, prospective study was conducted in eight geriatric hospitals and eight nursing homes in France.

Report of the international conference on manufacturing and testing of pluripotent stem cells.

Sessions included an overview of past cell therapy (CT) conferences sponsored by the International Alliance for Biological Standardization (IABS). The sessions highlighted challenges in the field of human pluripotent stem cells (hPSCs) and also addressed specific points on manufacturing, bioanalytics and comparability, tumorigenicity testing, storage, and shipping. Panel discussions complemented the presentations.

[Regulatory science in public health: What are we talking about?].

This article sheds light on a concept little known to public health actors in France: regulatory science, used to describe the range of scientific activities used to produce the knowledge mobilized to support, develop or adapt public policy decisions. The objective is to understand how the expression appeared in the mid-1980s and was formalized into a sociological concept by the American writer Sheila Jasanoff in 1990, and has gradually imposed itself in American, Japanese and European regulatory agencies as a new scientific discipline. The article examines the evolution of the concept and the various approaches proposed to define regulatory science.

A Decision Support Tool Facilitating Medicine Design for Optimal Acceptability in The Older Population.

Purpose: Medicine acceptability, which is of the utmost importance for vulnerable patients' adherence, is driven by both user and product characteristics. Herein, a novel multivariate approach integrating the many aspects of acceptability is used to discriminate positively and negatively accepted medicines in the older population.

Methods: An observational study was carried out in eight hospitals and eight nursing homes to collect a large set of real-life data on medicines uses in older patients (≥65 years).

Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitors for Severe Ischemic Left Ventricular Dysfunction.

Background: In addition to scalability, human embryonic stem cells (hESCs) have the unique advantage of allowing their directed differentiation toward lineage-specific cells.

Objectives: This study tested the feasibility of leveraging the properties of hESCs to generate clinical-grade cardiovascular progenitor cells and assessed their safety in patients with severe ischemic left ventricular dysfunction.

Methods: Six patients (median age 66.

Scientific considerations for the regulatory evaluation of cell therapy products.

Cell therapy involves the administration of a viable somatic cell preparation to a patient for the treatment of a disease or traumatic damage. Because cell therapies are complex and very different from traditional biological products, they present significant challenges for regulatory authorities, manufacturers, developers, health care providers, and patients involved in their application. Like other emerging areas of biomedical research and development, there are many issues where regulatory views and decisions among countries and regions may differ due to minimal scientific evidence to support safety and efficacy, and lack of experience with these novel treatments.

Overview of the Regulatory Oversight Implemented by the French Regulatory Authorities for the Clinical Investigation of Gene Therapy and Cell Therapy Products.

Advanced therapy medicinal products, a new class of products with promising therapeutic effects, have been classified as medicinal products and as such should be developed according to a well-structured development plan, to establish their quality, safety and efficacy profile and conclude, at the time of the marketing authorisation evaluation, on a positive risk/benefit balance for patients. An important part of this development plan is achieved through clinical trials, which have also to be approved according to a well-established regulatory process, prior any initiation. This chapter is dedicated to describe the regulatory pathway to be followed in France, before initiating any clinical trial with those investigational advanced therapy medicinal products.

Report of the international conference on regulatory endeavors towards the sound development of human cell therapy products.

The regulation of human cell therapy products is a key factor in their development and use to treat human diseases. In that regard, there is a recognized need for a global effort to develop a set of common principles that may serve to facilitate a convergence of regulatory approaches to ensure the smooth and efficient evaluation of products. This conference, with experts from regulatory agencies, industry, and academia, contributed to the process of developing such a document.

Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report.

Aims: Comparative studies suggest that stem cells committed to a cardiac lineage are more effective for improving heart function than those featuring an extra-cardiac phenotype. We have therefore developed a population of human embryonic stem cell (ESC)-derived cardiac progenitor cells.

Methods And Results: Undifferentiated human ESCs (I6 line) were amplified and cardiac-committed by exposure to bone morphogenetic protein-2 and a fibroblast growth factor receptor inhibitor.

Biosimilars: from technical to pharmacoeconomic considerations. 30th Rencontres Nationales de Pharmacologie et Recherche clinique pour l'Innovation et l'Evaluation des Technologies de Santé. Tables rondes.

A biosimilar is a biological medicinal product claimed to be similar to a reference biological medicinal product. Its development plan includes studies comparing it with the reference product in order to confirm its similarity in terms of quality, preclinical safety, clinical efficacy, and clinical safety, including immunogenicity. Biosimilars differ from generics both in their molecular complexity and in the specific requirements that apply to them.

Guidelines for translational research in heart failure.

Heart failure (HF) remains a major cause of death and hospitalization worldwide. Despite medical advances, the prognosis of HF remains poor and new therapeutic approaches are urgently needed. The development of new therapies for HF is hindered by inappropriate or incomplete preclinical studies.

Manufacturing, characterization and control of cell-based medicinal products: challenging paradigms toward commercial use.

During the past decade, a large number of cell-based medicinal products have been tested in clinical trials for the treatment of various diseases and tissue defects. However, licensed products and those approaching marketing authorization are still few. One major area of challenge is the manufacturing and quality development of these complex products, for which significant manipulation of cells might be required.

Biosimilars: from Technical to Pharmacoeconomic Considerations.

A biosimilar is a biological medicinal product claimed to be similar to a reference biological medicinal product. Its development plan includes studies comparing it with the reference product in order to confirm its similarity in terms of quality, preclinical safety, clinical efficacy, and clinical safety, including immunogenicity. Biosimilars differ from generics both in their molecular complexity and in the specific requirements that apply to them.

Demonstration of biosimilarity, extrapolation of indications and other challenges related to biosimilars in Europe.

The regulatory framework for biosimilars was established across Europe in 2005 based on the concept of biosimilarity. This legislation secures the manufacturing, evaluation, and market authorization (MA) of high-quality safe and efficacious biopharmaceuticals that are highly similar to their reference medicinal product (biosimilars). Demonstration of biosimilarity is documented by full-scale comparability exercises between the biosimilar and the reference product at quality, preclinical, and clinical level.

Summary of knowledge gaps related to quality and efficacy of current influenza vaccines.

Influenza viruses are a public health threat, as they are pathogenic, highly transmissible and prone to genetic changes. For decades vaccination strategies have been based on trivalent inactivated vaccines, which are regulated by specific guidelines. The progress in scientific knowledge and the lessons learned from the A(H1N1)2009 pandemic have highlighted further the need to improve current guidelines, including the immunogenicity criteria set by the CHMP in 1997, and to promote the discussion on the shortcomings encountered, e.

Towards a clinical use of human embryonic stem cell-derived cardiac progenitors: a translational experience.

Aim: There is now compelling evidence that cells committed to a cardiac lineage are most effective for improving the function of infarcted hearts. This has been confirmed by our pre-clinical studies entailing transplantation of human embryonic stem cell (hESC)-derived cardiac progenitors in rat and non-human primate models of myocardial infarction. These data have paved the way for a translational programme aimed at a phase I clinical trial.

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.

Biosimilars and the European experience: implications for the United States.

Biologics are medicines derived from a biological source. Their high prices and rapid uptake have raised hopes that with the gradual expiration of patents on the first generations of biologics, the advent of lower-cost follow-on products known as biosimilars will help "bend the cost curve." Although biosimilars have been available since 2006 within the European Union and are expected to save $15-$44 billion by 2020, the Food and Drug Administration (FDA) has yet to finalize the necessary regulatory processes for their approval in the United States.

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.