The Emergence of Biosimilar - Research Paper Example

? The Emergence of Biosimilars Biosimilar drugs offer inexpensive alternatives to medication therapy. However, many factors must be considered regarding the safety of the patient, the efficacy of the biosimilar, and the general impact on society. This article discusses the therapeutic value of biosimilars, the biochemistry of the drugs, and the potential for biosimilars to effectively treat disease. It is hoped that discussion of biosimilars will provide new avenues for molecular structure research and potential for discovery of affordable treatments for human disease. The Emergence of Biosimilars Opportunities for pharmaceutical companies to develop, produce, and market biosimilars or follow-on biologicals have been provided by expiration of patents covering biopharmaceuticals. Although it is the hope that their introduction may lower the cost of such expensive medicinal products, there have been concerns over the introduction and manufacturing considerations, immunogenicity, degree of similarity of these complex drugs, and regulatory approaches to biosimilars around the world. In addition, of concern are arguments and techniques employed by pharmaceutical companies to advance or discredit biosimilars, as well as issues with post-marketing surveillance programs and their limitations. The issues associated with introduction of biosimilar medicines across a range of pharmacological indications are controversial, as well as differences between biopharmaceutical products not subjected to regulatory approval and regulatory approved medicines. There are rapid changes in licensing of biosimilars and regulatory approval. Non-transparent promotion of biosimilar products gives clinicians a need to be wary. Hopefully, widespread availability of biopharmaceutical products will be provided by biosimilar medicines (Roger, 2010). More than 150 biopharmaceutical products have been marketed across the globe since the formation of the first biotechnology company almost three decades ago. The development of' biosimilars is increasing as the oldest of these biotechnology-derived products are now at the end of their patent lives. Biosimilars differ from generic drugs in aspects like size and complexity of the active substance, and the nature of the manufacturing process, although the active substance of a biosimilar medicine is similar. The manufacture of a biopharmaceutical involves several isolation and purification steps, and the product is complex. In terms of safety and efficacy of the product, even minor changes in production can have serious implications, and these procedures are proprietary to the manufacturer of the originator product. Existing and future regulation should prevent inappropriate and automatic substitution of a biosimilar for a reference biopharmaceutical product, and biosimilars should not be brought to market using the same procedure applied to generics (Misra A, 2010). Living systems or organisms are used to produce biological products, medicines, and therapeutic agents. Because of their expensive cost, access to these life-saving biological products is limited. In the next few years, patents on the early biological products will soon expire. This will allow other biotech/biopharmaceutical companies to manufacture the generic versions of the biological products, which are referred to as biosimilar medicinal products by the European Medicine Agency of the European Union, or as follow-on biological products by the U.S. Food and Drug Administration. Increase in patients' access to the much-needed biological pharmaceuticals by competition of cost-effective follow-on biological products with equivalent efficacy and safety can cut down the costs. Evaluation of equivalence (similarity) between the biosimilar products and their corresponding innovator product is a great challenge for both the scientific community and regulatory agencies due to the complexity and heterogeneity of the molecular structure, complicated manufacturing process, different analytical methods, and possibility of severe immunogenicity reactions, unlike for the conventional pharmaceuticals of small molecules. A review of current criteria for evaluation of bioequivalence for the traditional chemical generic products and an overview of the current regulatory requirements for approval of biosimilar products is needed. A detailed description of the differences between the biosimilar and chemical generic products with respect to size and structure, immunogenicity, product quality attributed, and manufacturing processes, statistical considerations including design criteria, fundamental biosimilar assumptions, and statistical methods are warranted. There is also possibility of using genomic data in evaluation of biosimilar products (Chow and Liu, 2010). The legal, regulatory, and scientific framework for approval of the new class of medicine in biosimilars has been pioneered by the European Medicines Agency. Biosimilars expected to be similar, but not identical, to the innovator biologics they seek to copy has been one of the foundational principles of the European framework. Chemical medicines, generics, which are based on the expectation that the innovator and generic drug substance are identical, contrasts with the legal, regulatory, and scientific framework for biosimilars. The approval, rejection, and withdrawal of biosimilar marketing applications, and the clinical data being made public, is utilized by the European biosimilar regulatory pathway (Fox, 2010). For vaccines, biosimilarity is a significant issue, and licensing of follow-on products of similar design could be facilitated. However, the molecular composition of a vaccine’s active substances can rarely be defined precisely. The definitions and guideline criteria developed for similar versions of biotherapeutics may be too restrictive for vaccines. Furthermore, an essential, rather than undesirable, characteristic is immunogenicity. In vaccines, of more relevance is similarity in antigenic composition. Only careful clinical evaluation can determine concealed differences in biosimilarity. Superficial similarity may be revealed by significant differences in performance. For current types of bacterial and viral vaccines, these issues have been reviewed in detail. Limited clinical studies could be acceptable provided that they permit side-by-side comparison with the original product or another suitable reference for truly biosimilar products. The need for improved regulatory tests capable of detecting subtle but biologically significant differences in vaccines is emphasized by the prospect of the development of biosimilar products. The need for guidelines relevant to vaccines is emphasized by an acceptable definition of biosimilarity (Corbel and Cortes Castillo Mde., 2009). Approved for clinical use are many glycoproteins and glycosaminoglycans. Biopharmaceutical reactivity with receptors and circulating half-life, and physicochemical properties and thermal stability, are affected by carbohydrate moieties. One target of drug design for enhancement of efficacy is modification of glycans. However, serious adverse events caused by some carbohydrates have been reported. For the efficient and safe use of glycosylated biopharmaceuticals, it is crucial to maintain the constancy of carbohydrate moieties. In contrast, changes in the manufacturing process are frequently made either during the development or after the approval of new biopharmaceuticals for scientific, safety-related, and economic reasons. Also, different manufacturers have attempted development of biosimilar glycoprotein products. Alteration of glycosylation by pharmaceutical manufacturing processes possibly cause and raise concerns about changes in their quality, safety, and efficacy (Kawasaki et Al., 2009). It is still a matter of debate whether biosimilars are truly interchangeable and comparable with their reference biopharmaceutical products in terms of quality, efficacy and tolerability. Related to the criteria for regulatory approval of biosimilars, there are still controversies. An example of these concerns is illustrated by recombinant human growth hormone (rhGH) biosimilars. Consultations of the websites from the American Food and Drug Administration and the European Medicines Agency (EMA) Regulatory status illustrate the aforementioned concern. In terms of quality, efficacy and tolerability, comparability with an approved reference biopharmaceutical product is needed for a biosimilar to obtain regulatory approval by the EMA. Therefore, non-clinical and clinical efficacy and tolerability studies are required to compare quality. However, to obtain approval of a biosimilar, comparative non-clinical pharmacokinetics, safety pharmacology, reproduction toxicology, mutagenicity and carcinogenicity studies are not mandatory. Also, extrapolation to all other approved indications of the reference product to comparable efficacy and tolerability only needs to be established by one study in a single population during a limited time interval (12 months). Subsequently, long-term efficacy and tolerability in all indications has not been proven, to the same degree as for the reference products, for the currently approved rhGH biosimilars. It remains controversial whether biosimilars have the validity of the current criteria for comparability and interchangeability as their reference products. Systematic monitoring of the efficacy and tolerability and long-term clinical investigations and of rhGH biosimilars in all indications is needed. Also, physicians should be allowed to make a free and informed decision about the type of rhGH to be prescribed in the current medico-economical environment (Declerck et Al., 2010). Alternative versions of biosimilars have been used in the oncology setting. Biosimilars are considered 'comparable' to the reference product when they are approved in EU, but this does not ensure therapeutic equivalence. Dissimilarities in clinical efficacy, safety, and immunogenicity may be produced by inherent differences between biosimilars and their reference products. A change in clinical management should be considered when switching biosimilars. Because of the limited clinical experience with biosimilars, pharmacovigilance programs will be important to establish clinical databases. For approved indications for which the biosimilar has not been studied, guidelines provide a mechanism for the extrapolation of clinical indications. When safety is paramount, as in stem cell mobilization in healthy donors, this may be of concern where differences in biological activity can result in adverse outcomes. In biosimilar labeling, these issues should be addressed (Mellstedt, 2008). In conclusion, careful molecular analysis and clinical study is warranted prior to the approval of a biosimilar to treat a human disease. Factors including immunogenicity, glycosylation, and manufacturing alteration need to be considered when substituting a biosimilar for a government-approved drug. With this in mind, the savings in expense of production of a biosimilar may provide for the treatment of disease, and in turn benefit society by making appropriate health care affordable. It is the hope of biosimilar production to create an array of biologics that will treat a large number of diseases. Careful regulation of biosimilar production will ensure that previously unattainable healthcare will be available for a more expansive population. Biosimilar Reference Omnitrope® http://www.emea.europa.eu/humandocs/PDFs/EPAR/valtropin/H-602-en1.pdf Eprex® 5. http://www.emea.europa.eu/pdfs/human/biosimilar/9452605en.pdf. Valtr- opin® Schellekens, H. (2009). Biosimilar therapeutics—what do we need to consider? NDT Plus 2: i27-i36. Genotropin® http://www.emea.europa.eu/humandocs/PDFs/EPAR/Omnitrope/060706en1.pdf. 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