2
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Basic Facts about Biosimilars

      Kidney and Blood Pressure Research

      S. Karger AG

      Epoetin, Biosimilars, Biotechnological medicines, Biologics, follow-on, Immunogenicity

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Biotechnological drugs have become an essential part of modern pharmacotherapy and are expected to reach a 50% share in the pharmaceutical market in the next few years. The expiry of patent protection for many original biotechnological medicines has led to the development of what are called biosimilars or follow-on biologics. Biosimilars attempt to copy the original technology leading to the production of innovative biotechnological medicines to obtain a product which is similar to the original one. The first two biosimilars have recently been approved in the European Union and one application was rejected. Many more biosimilars will likely see approval in the near future. Our experience with biosimilars has been very limited to date and long-term safety data including immunogenicity are not available. Although biosimilars will likely lower the cost of modern therapies there are issues which have to be discussed at this stage among physicians regarding in particular the differences between biosimilars and generics of the classical chemical drugs, need for appropriate regulations as well as identification of potential problems with biosimilars. Other specific problems which will also be addressed in this review are safety of biosimilars, pharmacovigilance, automatic substitution, naming and labeling/prescription rules.

          Related collections

          Most cited references 9

          • Record: found
          • Abstract: found
          • Article: not found

          Biosimilars: how similar or dissimilar are they?

           D Roger (2006)
          The imminent expiry of patents on biological medicinal products, such as epoetin alfa in 2006, has significant implications for nephrology in Australia. The purpose of this review is to examine the differences between biosimilars (similar biological medicinal products) and generic low molecular weight (chemical) drugs. The approach that regulatory agencies, including the European Medicines Agency (EMEA) and the Therapeutic Goods Administration (TGA), are taking towards biosimilars is also discussed. Biosimilars differ from generic chemical drugs in many important ways, including the size and complexity of the active substance, the nature of the starting materials (cell banks, tissues and other biological products), and the complexity of the manufacturing processes. Therefore, it has been acknowledged by the EMEA that established legal and regulatory principles of 'essential similarity' that are applied to standard chemical generics cannot be readily applied to biosimilars. One of the key areas of concern with the introduction of biosimilars into the field of nephrology will be guaranteeing the safety and efficacy of biosimilars. New manufacturers will need to ensure that their biopharmaceutical has a similar efficacy and safety profile to the innovator product through more extensive clinical trials than the limited testing done for generic versions of low molecular weight chemical medicines.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Comparative testing and pharmacovigilance of biosimilars.

            Unlike traditional generic pharmaceuticals, biosimilars (also called 'follow-on biopharmaceuticals' in the USA) aim to copy a complex recombinant, three-dimensional protein structure with high molecular weight. Small changes in the manufacturing process can alter the product's effect and safety. According to the guidelines of the European Agency for the Evaluation of Medicinal products (EMEA), extensive comparability testing will be required to demonstrate that the biosimilar has a comparable profile in terms of quality, safety and efficacy as the reference product. Various analytical assays are available to compare physicochemical and biological properties between production batches of a potentially similar biopharmaceutical (comparability) and in comparison with a reference product (similarity). It is important to recognize the limits of existing assays so that the results can be accurately interpreted for market authorization. This article examines the quality and limits of such analytical methods. The analytical tests to demonstrate comparability and similarity of a biosimilar product to a reference drug with respect to protein content, activity, physiochemical integrity, stability, impurities and additives, as well as immunogenicity are discussed. Although several assays are available, reliable tests for safety and efficacy still require development. Furthermore, international standards are missing and materials and methods differ from laboratories making the comparison of results very difficult. Clinical trials and post-authorization pharmacovigilance are essential to guarantee the product's safety and efficacy over time. Pharmacovigilance, as part of a comprehensive risk management programme, will need to include regular testing for consistent manufacturing of the drug.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Biosimilar epoetins: an analysis based on recently implemented European medicines evaluation agency guidelines on comparability of biopharmaceutical proteins.

              Patents of innovator biopharmaceutical products, such as epoetin, are expiring, and biosimilar versions of these products may soon enter European and American markets. Copies of these products, termed biosimilars or follow-on biologics, are not truly equivalent and cannot gain market approval through the procedure typically applied to generic drugs. We evaluated literature reports of both analytic and clinical studies conducted with biosimilar epoetin products currently marketed outside the United States and Europe in light of recently implemented European Medicines Evaluation Agency guidelines. The analytic studies reported that products differed widely in composition, did not always meet self-declared specifications, and exhibited batch-to-batch variation. Although several clinical studies demonstrated correction of anemia with biosimilar epoetins by using an open-label or placebo-controlled study design, only 4 of 22 studies were competitor controlled. Most of the studies were small (median 41 patients, range 18-1079 patients) and of short duration (median 12 wks, range 6 wks-1 yr). Clinical experience with epoetin shows that the dosage required to achieve similar hemoglobin levels varies among patients, making it impossible to demonstrate bioequivalence without a comparator. The analytic reports did not demonstrate comparability of biosimilar epoetin products with innovator epoetin alfa, and the clinical studies were not rigorous enough to show equivalent safety and efficacy of a biopharmaceutical product. The variation between products illustrates the challenge in replicating and consistently producing biopharmaceutical proteins. Immunogenic reactions with epoetin indicate that large, long-term studies are needed to adequately monitor safety.
                Bookmark

                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2007
                September 2007
                04 July 2007
                : 30
                : 5
                : 267-272
                Affiliations
                Department of Nephrology, Hypertension and Kidney Transplantation, Medical University of Łódź, Łódź, Poland
                Article
                105133 Kidney Blood Press Res 2007;30:267–272
                10.1159/000105133
                17622764
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, References: 23, Pages: 6
                Categories
                Review

                Comments

                Comment on this article