Biologics and biosimilars: role in modern pharmacotherapy and importance of pharmacovigilance

Biologics are highly sensitive large molecules with complex structure, difficult to characterize and reproduce, derived from living cells; used for treatment, diagnosis or prevention of disease. Examples are therapeutic hormones, vaccines, monoclonal antibodies etc. Biologicals are beneficial in the management of several health conditions which were once upon a time difficult to manage like cancer, multiple sclerosis, Alzheimer’s disease, rheumatoid arthritis, diabetes etc. Biosimilars are proteins that are similar to innovator biologics but not the same as they differ slightly in structure however with no clinically significant difference. Biosimilars are not the exact replicas of originator biologic and are therefore not generics. Biosimilars for their approval are not required to undergo intense clinical trials as innovator biologic but are required to produce data that demonstrates its similarity to an original biologic in terms of clinical efficacy and safety. However, manufactures of both the biologics and biosimilars are required to submit pharmacovigilance and risk management plans as part of their application. Marketing authorization for biosimilars was for the first time framed by EMA along with the guidelines for developing them. As biologics and biosimilars are derived proteins they have immunogenic potential and risk of adverse events which cautions their use. Pharmacovigilance is needed to ensure that adverse events are quickly detected, reported and attributed to the correct product and manufacturer. Regulations are implemented to improve identification and traceability of biologics. Automatic substitution should not be permitted for biologicals.

Biosimilars in Oncology: From Development to Clinical Practice

Biologics play an integral role in the treatment of cancer not only for their therapeutic effects and ability to improve outcomes, but also as supportive care agents. Biologics are more complex to manufacture and take longer to bring to market. Because biologics are considerably more costly than small-molecule drugs, their use has placed an increasing economic demand on healthcare systems worldwide. Biosimilars are designed to be highly similar to existing branded biologics, but because biologics cannot be exactly copied, biosimilars should not be referred to as generic, exact versions of the innovator biologic. Biosimilars have the potential to increase access and provide lower cost options for cancer care as patent protection for some of the most widely used biologics begins to expire. Regulatory requirements for biosimilars are evolving, as are global harmonization and/or standardization strategies that can facilitate their robust clinical development. This review highlights critical factors involved with the integration of biosimilars into oncology treatment paradigms and practices. Clinicians will likely seek out practice guidelines and position statements from established scientific societies to help evaluate key information regarding biosimilars, such as efficacy, safety, comparability, and interchangeability with the reference biologic. Automatic substitution, nomenclature, extrapolation of clinical data from one indication to another, as well as parameters for ongoing pharmacovigilance are evolving considerations. Education of physicians and other healthcare providers, payers, and patients about biosimilars may facilitate informed decision making, promote acceptance of biosimilars into clinical practice, increase accessibility, and expedite associated health and economic benefits

Biosimilar agents in oncology/haematology: from approval to practice

The regulation of biosimilars is a process that is still developing. In Europe, guidance regarding the approval and use of biosimilars has evolved with the products under consideration. It is now more than 3 years since the first biosimilar agents in oncology support, erythropoiesis-stimulating agents, were approved in the EU. More recently, biosimilar granulocyte colony-stimulating factors have received marketing approval in Europe. This review considers general issues surrounding the introduction of biosimilars and highlights current specific issues pertinent to their use in clinical practice in oncology. Information on marketing approval, extrapolation, labelling, substitution, immunogenicity and traceability of each biosimilar product is important, especially in oncology where patients are treated in repeated therapy courses, often with complicated protocols, and where biosimilars are not used as a unique therapy for replacement of e.g. growth hormone or insulin. While future developments in the regulation of biosimilars will need to address multiple issues, in the interim physicians should remain aware of the inherent differences between biosimilar and innovator products

Biologics Price Competition and Innovation Act: Striking a Delicate Balance Between Innovation and Accessibility

The Biologics Price Competition and Innovation Act of 2009 (BPCIA, also known as the Biosimilar Act) was signed into law in 2010 by President Barack Obama as part of the healthcare reform bill. The central mission of the BPCIA is two-fold: (1) providing sufficient incentives for continuous innovations in biologic therapies (i.e., promoting innovation); and (2) lowering the price of biologic therapies (i.e., promoting accessibility). To promote innovation, the BPCIA provides twelve-year Food and Drug Administration (FDA) exclusivity to innovator biologics. This twelve-year FDA exclusivity prevents generic biologics, also known as follow-on biologics (FOBs), from being approved. To promote accessibility, the BPCIA provides an abbreviated pathway for FOBs—the abbreviated biologic license application (ABLA). The ABLA allows FOB manufacturers to cut short the time and the expensive cost of clinical testing by referring to innovator biologics’ clinical data to establish safety and efficacy. The goal of this Note is to discuss the advantages and drawbacks of the mechanisms established in the BPCIA and to suggest modifications to strike a better balance between innovation and accessibility. Part I of this Note introduces the legal and scientific background of the BPCIA and Hatch-Waxman Act in order to engage in further analyses. Part II of this Note analyzes the competing interests of innovation and accessibility and suggests a novel six-year data exclusivity and a six-to-twelve-year market exclusivity regulatory scheme. This Note concludes that the current design of the BPCIA tips too favorably toward innovation and compromises accessibility. The suggested six-year data exclusivity and six-to-twelve-year market exclusivity regulatory scheme potentially strike a better balance between innovation and accessibility

Emergence of the Biosimilar Sector and Opportunities of Developing Country Suppliers

As biologic products begin to come off-patent, a market is emerging for biosimilars (also known as biogenerics or follow-on biologics). Firms from emerging countries such as India and China have dominated the production of active ingredients in pharmaceutical industries all over the world and are now developing capabilities in biosimilar production. This emergence of a new market dynamic is disruptive to current key players as it has potential challenge their current dominant hold over the market, while for firms from developing countries it creates a sea of opportunities. This rise of biosimilars and capabilities for cheap production in developing country firms has potential to transform patient care in developing countries as well as advanced countries. This paper reviews study data collected at Innogen and the most recent literature to understand how the sector for biosimilars is evolving and the opportunities and challenges faced by emerging suppliers. The aim of the paper is to identify the gaps in the current literature and opportunities for further study in this area

Biosimilar medicines in dermatology: key aspects

Article reproduced (or made available) with permission of Practical Dermatology®, www.practicaldermatology.com.En el artículo se recoge la aplicación de los medicamentos biosimilares biotecnológicos) en patologías dermatológicas

Is Interchangeability Possible? Understanding and Evaluating the Evidence Base-Implications for Quality and Safety

Geno Merli, a board-certified specialist in internal medicine and physical medicine and rehabilitation, is Director of the Jefferson Center for Vascular Disease at Jefferson Medical College and Senior Vice President and Chief Medical Officer at Thomas Jefferson University Hospital. Dr. Merli received his medical degree from Jefferson Medical College and completed his residency in rehabilitation medicine and internal medicine at Thomas Jefferson University Hospital. Dr. Merli is a nationally recognized expert in the areas of prophylaxis for and management of deep-vein thrombosis and pulmonary embolism (DVT/PE), as well as for the medical consultation of surgical patients. His research interests have focused on prophylaxis for DVT/PE and the management of DVT in acute spinal cord injury, total joint replacement, trauma, and high-risk cancer patients. Former editor-in-chief of Internal Medicine, Dr. Merli currently serves on the editorial board of Patient Care, Journal of the Society of Hospital Medicine, and The Hospitalist. He is also a reviewer for the Archives of Internal Medicine, Annals of Internal Medicine, Chest, Journal of Thrombosis and Thrombolysis, Journal of Thrombosis and Hemostasis and JAMA. He is co-editor of the book Medical Management of the Surgical Patient and co-chairs for a national course on the perioperative care of the surgical patient with medical problems. Dr. Merli is a fellow of the American College of Physicians and a member of American Venous Forum, the Society of Hospital Medicine, American Medical Association, Society of Vascular Medicine and Biology, and the International Society of Thrombosis and Hemostasis