The regulatory landscape of biosimilars: WHO efforts and progress made from 2009 to 2019 (original) (raw)
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Global regulatory landscape of biosimilars: emerging and established market perspectives
Biosimilars, 2015
Biological product development for launch in multiple geographies with varied regulatory expectations would require a planned and focused strategy, involving the selection of the appropriate reference product, defining the extent of process and product characterization and design of nonclinical and clinical studies. The development for established markets like the European Union and the United States, which have precedence in regulatory pathways, may face very different challenges compared to emerging markets, many of which are still in the nascent stages of regulatory guidelines. A clear and concise understanding of the regulatory framework of each region and awareness of the limitations of health care policies, with an added knowledge of the local factors that influence the biosimilar market, would be desirable for a good business strategy. Herein it is attempted to outline the stages of regional guideline implementation in the various global locations and compare the variability in regulatory requirement between them. The factors that could potentially impact biosimilars business in these regions are also outlined. Finally, the prevailing competition between manufacturers of innovative and biosimilar drugs, which could influence the availability of lifesaving off-patent drugs for critical diseases and the advent of more effective, alternate, or next-generation molecules, is also briefly described.
Generics and Biosimilars Initiative Journal, 2016
Introduction: Biological drugs are improving therapeutic options for many diseases, but access to these therapies is being held back by costs. Biosimilars off er a lower-cost alternative to the corresponding original therapeutic protein, the reference product, with a comparable quality, safety and effi cacy. Despite these apparent advantages, arriving at the best solution for patients will need improved communication between regulators and caregivers. Methods: Representatives from medical societies (European and national) which had issued or published a position paper on biosimilars met with regulators and related experts to discuss recent revisions of the regulatory assessment principles of biosimilars, review the current positions of societies on biosimilars, and improve dialogue between medical societies and regulators on biologicals, notably biosimilars. Results: The positions of the European regulators and medical societies are slowly converging. While many questions were answered, productive discussions identifi ed areas of disagreement and uncertainties. The results of these discussions will inform debate and decision-making in the participants' organizations and home countries. Conclusions: The picture of biosimilars is becoming clearer, and stakeholders are beginning to understand better the basis of biosimilar development, on one hand, and the reasons for concerns, on the other hand. Diff erent stakeholders-patients, doctors, pharmacists, payers-need diff erent information. Above all, this must be a collaborative exercise.
Biosimilars: An Approach to some Current Worldwide Regulation Frameworks
Current Clinical Pharmacology, 2019
Developing new biologics has led to regulations and norms aimed at guaranteeing their safety, quality and effectiveness, in terms of marketing, prescription, use, interchangeability and switching. Biologics are of great importance in treating patients suffering from rheumatic, autoimmune, inflammatory and neoplastic diseases. The expiry/lapse of reference biologics or originators' patents has meant that developing biosimilars involves accompanying legal requirements for their approval in countries worldwide. This paper has thus approached the situation of biosimilar regulation worldwide, the pertinent technical concepts and regulatory differences in some countries of interest.
Biosimilars: Regulatory Status and Implications across the World
Journal of Pharmacovigilance, 2016
Recently, the expiry (or near expiration) of patents of these biological drugs prompted the pharmaceutical industries and governing bodies to replace them with non-innovator similar biologic drugs. These products are a new class of drugs intended to be comparable in both safety and efficacy measures to the reference drug and are generally referred as biosimilars. The major purpose of this replacement is to reduce the costs of production and time of approval for market entry. Biosimilars are also known as similar biological products, followup biologics, second entry biological, subsequent entry biologics, biogenerics, multisource products and off-patent biotech products [5]. Generally, the term biosimilar refers to a product which is biologically and functionally similar to the reference product, also called originator. By this definition, these drugs can be seen as comparable, but not identical to the reference product. These products cannot be deemed as a generic version of their originators, as they are not chemically derived single (small) molecular pharmaceutical entities, which are identical to the original drugs both in pharmaceutical equivalence (identical active substances) and bioequivalence (comparable pharmacokinetics
Biosimilars in Developed Economies: Overview, Status, and Regulatory Considerations
Regulatory Toxicology and Pharmacology, 2019
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Biosimilars: A Multidisciplinary Perspective
Clinical Therapeutics, 2016
A biosimilar is an officially regulated and approved copy of an originator biologic therapy. Improved affordability and consequent wider patient access compared with biologics are a significant appeal of biosimilars. Regulatory guidelines for biosimilar development and approval are rigorous and undergoing constant refinement. The process of licensing approval for all biosimilars requires demonstration of comparability in quality, efficacy, and safety between the biosimilar and reference (originator) product, which is undertaken in a stepwise procedure of nonclinical and clinical evaluation. The approval of 420 biosimilars in Europe in several drug classes, including the first monoclonal antibody biosimilar, bears testimony to the increasing regulatory acceptance of these agents. In contrast, the clinical application of biosimilars remains underrecognized by physicians across therapy areas. Therefore, this article aims to provide a comprehensive review of the biosimilar development process and to provide multidisciplinary guidance on the potential therapeutic utility of biosimilars in clinical practice. Specifically, experts discuss clinical developments in the introduction of biosimilars across the disciplines of gastroenterology, nephrology, oncology, and rheumatology, and from a payer perspective, and also highlight a common need for ongoing pharmacovigilance, robust head-to-head clinical studies, and real-world data to establish the long-term risk-benefit profile of biosimilars. In conclusion, significant potential exists for biosimilars to revolutionize biologic therapy by widening patient access across therapy areas.
Annals of Oncology, 2007
Background: The purpose of this report was to review issues associated with the introduction of alternative versions of biosimilars used in the oncology setting. Design: Data were obtained by searches of MEDLINE, PubMed, references from relevant English-language articles, and guidelines from the European Medicines Agency. Results: When biosimilars are approved in EU, they will be considered 'comparable' to the reference product, but this does not ensure therapeutic equivalence. Inherent differences between biosimilars may produce dissimilarities in clinical efficacy, safety, and immunogenicity. Switching biosimilars should be considered a change in clinical management. Regulatory guidelines have been established for some biosimilar categories but, because of the limited clinical experience with biosimilars at approval, pharmacovigilance programs will be important to establish clinical databases. Guidelines also provide a mechanism for the extrapolation of clinical indications (approved indications for which the biosimilar has not been studied). This may be of concern where differences in biological activity can result in adverse outcomes or when safety is paramount (e.g. stem cell mobilization in healthy donors). These issues should be addressed in biosimilar labeling. Conclusions: Biosimilars should provide cost savings and greater accessibility to biopharmaceuticals. A thorough knowledge surrounding biosimilars will ensure the appropriate use of biopharmaceuticals.
Clinical Therapeutics, 2012
Background: Biosimilars are defined as biologic products that are highly similar to reference products, notwithstanding minor differences in clinically inactive components, with no clinically meaningful differences between the biologic product and the reference product in terms of safety profile, purity, and potency. Due to the high cost of innovator biologics, as well as an increase in the number of these products reaching patent expiry, the development of a process for approving biosimilar products has become a crucial regulatory issue in the United States. Objective: This commentary explores the relationship between structural/biophysical variation and the risk/ benefit profile of biosimilars and reference biologics that have undergone process changes in the context of the most recent biophysical, nonclinical, and clinical data available. Methods: The search strategy used PubMed, EMBASE, and MEDLINE for the retrieval of documents pertaining to biologic manufacturing, comparative analysis of biosimilars and originator biologics, and relevant review articles on biosimilars. For regulatory documents pertaining to the processes of the approval of biosimilars, biologics, and generics, a search for legislative decisions, briefing summaries, concept papers, guidance, and evaluations of approved and rejected applications for biosimilars published by the World Health Organization, US Food and Drug Administration, European Medicines Agency (EMA), and other national regulatory authorities was conducted. Selected articles from key opinion leaders and manufacturers were also reviewed. These searches were conducted to provide a review of historical and contemporary issues in the consideration of the current status of worldwide biosimilar use and regulation. Results: A total of 18 marketing applications covering 9 development programs were surveyed. Of these, 14 applications were approved and 4 were rejected by the EMA. None of the biosimilars were reported to have evidence of significant clinical variation relative to reference compounds in the absence of corresponding differences in biophysical properties. A single biosimilar (Omnitrope ® [somatropin]) was reported to have evidence of significant variation in both biophysical and clinical parameters in premarketing studies. Biophysical variation in the absence of relevant differences in the efficacy and safety profiles compared with the reference brands was noted for 2 biosimilar epoetin products. Conclusions: This commentary provides evidence that current EU guidelines have resulted in the approval of biosimilar therapeutics with comparable efficacy and safety profiles for the recommended indications of their respective reference originator biologics. It is anticipated that these precedents will serve as a starting point in the development of a process for approving biosimilars in the United States and worldwide to provide efficacious and tolerable biotherapeutics with a significant cost advantage for national health care programs and consumers.
Biosimilars: Overview of current legislation and future prospects
While development of generic medicines is easy, development of similar biological medicinal is certainly not. Biologicals are more complex than small molecules there is a spectrum of increasing complexity which in blurs the differentiation between and non biological product. As with any of the drug, some non-clinical testing will be required prior to to move to the clinic. Current requirement focus on the need for intensive in vitro generally with a study in one species, usually the rat. Just as for standard generic medicines there is a requirement for bioequivalence studies to be performed in either volunteers or patients. However EU regulatory guidelines on biosimilars, focus on the need to also demonstrate similar levels of efficacy. In certain circumstances it may be acceptable to substitute confirmatory clinical trials with pharmacodynamic studies, but usually equivalence trials in will be necessary and these are with difficulties. By far the most relevant concern in substituting one biological medicinal product for another is the potential for increased immunogenicity. Thus monitoring safety, and particularly immunogenicity, is the critical part of the any development programme of biosimilars. As the exact data requirement will vary on case by case basis, any manufacturere involved in the development of biosimilars proteins is well advised to seek the third party and ultimately consider scientific advice from the committee for medicinal products for Human use (CHMP).
International Journal of Pharmacy and Pharmaceutical Sciences, 2016
A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product (reference medicinal product). A biosimilar demonstrates similarity to the reference biological product in terms of quality characteristics, biological activity, safety and efficacy based on a comprehensive comparability exercise. EMA (European Medicines Agency) was the first to introduce the guidelines for biosimilar approval, effective from June 2006. Biosimilar guideline was released in 2010 in Brazil and 2012 in India. Recently China published its guideline for biosimilar approval in 2015. This article summarizes the regulatory requirements for approval of biosimilars in India, Europe, Brazil, and China. These countries require comparability exercise of a biosimilar with reference biological product for generating comparative analytical, non-clinical and clinical data (usually one or two phase 1 and phase 3 comparative studies). A case study of infliximab biosimilar approval in India, Brazil and Europe has also been included.