WHO informal consultation on regulatory evaluation of therapeutic biological medicinal products held at WHO Headquarters, Geneva, 19–20 April 2007 (original) (raw)
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Regulatory challenges with biosimilars: an update from 20 countries
Annals of the New York Academy of Sciences, 2020
The World Health Organization (WHO) issued guidelines for the regulatory evaluation of biosimilars in 2009 and has provided considerable effort toward helping member states implement the evaluation principles in the guidelines into their regulatory practices. Despite this effort, a recent WHO survey (conducted in 2019–2020) has revealed four main remaining challenges: unavailable/insufficient reference products in the country; lack of resources; problems with the quality of some biosimilars (and even more with noninnovator products); and difficulties with the practice of interchangeability and naming of biosimilars. The following have been identified as opportunities/solutions for regulatory authorities to deal with the existing challenges: (1) exchange of information on products with other regulatory authorities and accepting foreign licensed and sourced reference products, hence avoiding conducting unnecessary (duplicate) bridging studies; (2) use of a “reliance” concept and/or jo...
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.
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.
REGULATORY CONSIDERATIONS OF BIOSIMILARS AND CLINICAL DILEMA OF THEIR USE
Biomedical products are complex molecules , produced by living cells. More accurately, they are molecules that are naturally produced in the human body, like hormones or growth factors, monoclonal antibodies, blood products, immunological medicinal products, sera and vaccines, allergens, and advanced technology products such as gene and cell therapy products. Copies of these drugs, known as biosimilars, are comparable but not identical and are not generic version of innovator biological products. Specific regulatory requirements and abbreviated registration process apply in the case of biosimilars, in order to demonstrate efficacy and safety profile and to prove that product is similar to the original biomedical product. Like all medicines, biological medicines work by interacting with the body to produce a therapeutic outcome, but the mechanisms by which they do this may vary from product to product and through indications. Therefore the role of the physicians in treatment of patients with these complex medicinal products is particularly important. Regulatory issues, manufacturing, safety, physicians have part in develop use of biosimilars as much as generic drugs. Even though, the most important factor for market of biosimilar are commercial factor, still, real clinical dilemma of use are present, so it is necessary to have clear regulatory framework and postmar-keting data on the use of biosimilars.
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
The regulatory landscape of biosimilars: WHO efforts and progress made from 2009 to 2019
Biologicals, 2020
The World Health Assembly in 2014 adopted a resolution that mandates both Member States and the WHO Secretariat to facilitate access to biotherapeutic products in a way that ensures their quality, safety and efficacy. The availability of biosimilars is expected to increase access to biotherapeutic products by providing more treatment options triggering competition which would lead to a consistent reduction in the average price of treatment. Since the WHO guidelines for regulatory evaluation of biosimilars were issued in 2009, WHO has provided immense effort towards harmonizing the terminology and the regulatory framework for biosimilars globally. This article describes the progress made and the regulatory landscape changes for biosimilars in 21 countries during the past ten years. Based on the information from regulators and from publicly available data, the following has been identified: 1) WHO guidelines have contributed to setting the regulatory framework for biosimilars in countries and increasing regulatory convergence at global level; 2) terminology used for biosimilars is more consistent than in the past; 3) biosimilars are now approved in all participating countries; and 4) the dominant product class for candidate biosimilars under development is monoclonal antibodies.
Biosimilars in the European market
GaBI Journal, 2013
Introduction and study objectives Biopharmaceutical medicines ('biologicals') are medicinal products made by or derived from living organisms using biotechnology, i.e. rDNA, controlled gene expression or antibody technologies [1, 2]. These medicines, manufactured from a unique line of living cells, tend to have a complex molecular structure that makes it impossible to ensure an identical copy. This contrast with chemical medicines, with molecules that tend to be small in size, have a simple structure and can be manufactured by predictable chemical processes that generate identical copies [3]. Biologicals constitute a fast-growing segment of the pharmaceutical market. In 2000, only one out of the 10 drugs with the largest worldwide sales was a biological product, whereas in 2008 half of these worldwide bestsellers were biological [4]. Biological medicines have made substantial contributions to improving the effectiveness of therapies in many disease areas and they are expected to continue doing so in the future [5]. But these benefi ts come with increasing higher treatment costs, which threaten accessibility and the fi nancial sustainability of health systems. Biological sales in 2010 account for about US$134 billion in Australia, Canada, EU and Japan [4]. The term 'biosimilars' has been used by the European Medicines Agency to describe offi cially approved subsequent versions of innovator biological products made by a different manufacturer after the patent and exclusivity rights have expired [6]. The expiration of patents and other intellectual property rights of biological innovators opened the opportunity for biosimilars to enter the market and increase competition among producers of biologicals. However, the characteristics of biological medicines, particularly the nature of their production process and the need to guarantee patient safety, require a more comprehensive
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).
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.
Biologicals and biosimilars: safety issues in Europe
Expert opinion on biological therapy, 2017
Medicinal products of a biological origin are approved by the EMA at a centralized level. However, there is no harmonization about their use in Europe. The current regulation referring to the safety of biological medicinal products and biosimilars in Europe has been identified. The safety associated with medicinal products of a biological origin is assured by the pharmacovigilance system, which has evolved, but doesn't yet incorporate all of the specific information from this market segment, namely that related to the identification of drugs, and its use - including the prescription and dispensing, given the possibility of interchangeability and substitution. The terminology, information systems and traceability systems aren't entirely appropriate to ensure the safety requirements for therapy with medicinal products of a biological origin. Areas covered: This article aims to identify the prescription and dispensing profiles of reference biological medicines and biosimilars i...