Status of biosimilar regulation in Europe
Testing the bioequivalence of biosimilars differs from that of standard generics. Bioequivalence testing procedures for biosimilars are to be performed against the originator product as a control (reference) and include preclinical and clinical testing .
Status of Biosimilar Regulation in US
Basic facts about biosimilars.
List of agencies
- Indian Council for Medical Research (ICMR)
- Central Drugs Standard Control Organisation (CDSCO)
- Department of Biotechnology (DBT)
- Genetic Engineering Approval Committee (GEAC)
- Recombinant DNA advisory Committee (RDAC)
- Review Committee on Genetic Manipulation (RCGM)
- Institutional Biosafety Committee (IBSC)
- National Centre for Biological Sciences
- National Control Laboratory for Biologicals
Biosimilars: how similar or dissimilar are they?
The primary importance of the manufacturing process was highlighted when a slight change in the production process of an originator recombinant erythropoietin resulted in patients developing pure red cell aplasia.
The challenge of biosimilars.The purpose of this report was to review issues associated with the introduction of alternative versions of biosimilars used in the oncology setting.Data were obtained by searches of MEDLINE, PubMed, references from relevant English-language articles, and guidelines from the European Medicines Agency.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.
Biosimilars should provide cost savings and greater accessibility to biopharmaceuticals. A thorough knowledge surrounding biosimilars will ensure the appropriate use of biopharmaceuticals.Pharmacovigilance
Due to the limited clinical database at the time of approval of a biosimilar, vigorous pharmacovigilance is required. EMA guidelines require pharmacovigilance programmes to monitor the safety of biosimilar products post-approval.Substitution
For small molecule generics the issue of substitution is easy, since they are considered identical to the originator molecule. This, however, is not the case for biosimilars, which are large complex molecules prone to heterogeneity.In the US, the BPCI Act gives FDA the authority to designate a biosimilar as interchangeable with its reference product. This means that the biosimilar may be substituted for the originator product by the pharmacist without reference to the prescribing physician. This is not the case, however, in the EU, where decisions on interchangeability are not made by EMA, but at a national level.
Global concerns regarding product safety and quality
Statistical assessment of biosimilar products.
A way forward for India
Biosimilar therapeutics-what do we need to consider?
Biosimilars: policy, clinical, and regulatory considerations.
An abbreviated regulatory pathway for the approval of biosimilars, and a process for safely demonstrating the therapeutic interchangeability of these proteins, has the potential to provide meaningful cost savings. This economic advantage to patients can translate into important public health benefits. But to date, no formal regulatory process exists in the United States for bringing these drugs to market. In addition, the current tools for fully characterizing biopharmaceuticals are not--in certain cases--well developed, especially for proteins that have complex structures or are heavily glycosylated. In addition, using "similar" but not completely "identical" proteins interchangeably raises concerns about potentiating immunogenicity. The bottom line is that demonstrating therapeutic equivalence and interchangeability for biosimilars is not a straightforward matter--it cannot be based on the same criteria as for conventional small-molecule drugs. The science, while obtainable, is more complex. For example, it is assumed that showing that a biosimilar protein can be safely used interchangeably with an innovator protein would require, at the least, some limited clinical data and interchangeability studies. Notwithstanding the more complex scientific and clinical issues particular to protein products, most believe that a process for enabling the approval of safe and effective biosimilar proteins is not only possible, but an important public health goal. The European Union system for biosimilars may provide a model for anticipating and resolving the scientific and policy issues related to biosimilars in the U.S.
The legal and regulatory status of biosimilars remains to be resolved in the United States as policymakers address the scientific and policy issues surrounding product manufacturing, patent terms, and clinical use.
Biosimilars: it's not as simple as cost alone.
Recommendations regarding technical standards for follow-on biologics: comparability, similarity, interchangeability.
Legislative initiatives in Europe, Canada and the US for market authorization of follow-on biologics.