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Biosimilar Medical Products: What a Physician Needs to Know S Kalra, B Kalra, N Pandey

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Biosimilar Medical Products: What a Physician Needs to Know S Kalra, B Kalra, N Pandey The Internet Journal of Family Practice ISPUB.COM Volume 8 Number 2 Biosimilar medical products: What a physician needs to know S Kalra, B Kalra, N Pandey Citation S Kalra, B Kalra, N Pandey. Biosimilar medical products: What a physician needs to know. The Internet Journal of Family Practice. 2009 Volume 8 Number 2. Abstract The first generation of approved biopharmaceuticals was developed a few decades ago. Drugs such as insulin, growth hormone, erythroprotein and cytokines were manufactured using recombinant DNA (rDNA) technology or hybridoma methods. They have improved the lives of countless patients of diabetes, short stature, anaemia, cancer, multiple sclerosis and hepatitis.1 Patents for many of these first- generation biotechnology products have, or are soon going to, expire. In many parts of world , strict patent laws are not in force. This has led to the development of various ‘copies” of these molecules by drug manufacturers. These products are known as biosimilars. INTRODUCTION biological medicinal product or biological medicine, whose The first generation of approved biopharmaceuticals was active substance is made by or derived from, a living 3 developed a few decades ago. Drugs such as insulin, growth organism . hormone, erythroprotein and cytokines were manufactured Example of biopharmaceuticals include hormones such as using recombinant DNA (rDNA) technology or hybridoma insulin , glucagon growth hormone , thyrotropin, human methods. They have improved the lives of countless patients chorionic gonadotropin , follicle – stimulating hormone , of diabetes, short stature, anaemia, cancer, multiple sclerosis luteinising hormone and erythroprotein, cytokines such as and hepatitis.1 interferon – alfa, interleukin and granulocyte colony Patents for many of these first- generation biotechnology stimulating – factor (filgrastim), clotting factors VII, VIII products have, or are soon going to, expire. In many parts of and IX, monoclonal antibodies like bevacizumab, cetocxmab world , strict patent laws are not in force. This has led to the , abciximab, rituximab infliximab, and teplizumab vaccines development of various ‘copies” of these molecules by drug such as those against hepatitis B and human papilloma virus manufacturers. These products are known as biosimilars. , enzyme like glucocerbrosidase, DNase , thrombolytics and urate oxidase , ovel synthetic proteins , pegylated proteins , DEFINITIONS and covalently attached metal chelators , radioactive iodine A clear understanding of the various terms used in this field and other products . is necessary before one can reach an informed opinion on the A biosimilar , also known as a similar biological medicinal matter. product , follow -on biologic , or biogeneric is a medicine A generic drug, or generic medicine, is one that is similar to that is similar to a biological medicine that has already been a medicine which has already been authorized. (the authorized (the biological reference medicine). Their active ‘reference medicine’). It contains the same quantity of active substance are similar , substances are similar , yet not substances (s) is used at the same dose to treat the same identical3. disease , is as safe and as effective as the reference medicine Biosimilars are submitted for separate marketing approval . A generic product has to demonstrate identical chemical after expiry of patent protection of the innovator product. composition and similar pharmacokinetic properties to the 2 reference product . Biosimilars are different from generic drugs. Conventional generics are considered to be therapeutically equivalent to A biopharmaceutical is a biological medicinal product or 1 of 4 Biosimilar medical products: What a physician needs to know the reference medicine once pharmaceutical equivalence (i.e. equivalence and limited toxicology studies need to be done identical active substances) and bioequivalence (i.e for a biosimilar . Clinical studies may be limited to first one comparable pharmacokinetics) have been established. They indication , in a sensitive patient population . It is stated by do not require clinical efficacy and safety studies before the Committee for Human Medicinal Product5 (CHMP) that approval. Biopharmaceuticals are made up of a collection of while the active substance in the biosimilar should be similar large protein isoforms, rather than a single molecular entity to the one in the reference product , it is not expected that the unlike convention generics, As the manufacturing process is quality will be identical. An innovator molecule has to proprietary information it is unlikely that to biosimilars can demonstrate proof of non-clinical studies viz, be exactly identical. There are no analytical techniques to pharmacokinetics and toxicology (safety pharmacology establish biopharmaceutical equivalence. ,reproduction toxicology, mutagenecity and carcinogenicity) and clinical studies (efficacy and tolerability for each DIFFERENCE BETWEEN BIOSIMILAR AND indication) before it is approved. GENERICS Bio-pharmaceuticals are derived from or made by a living This data is not required for a biosimilar . Quality studies , organism , and are polypeptides , proteins, glycoproteins, non clinical data such as pharmacodynamics, repeat dose complex, polysaccharides or nucleic acids. They may have toxicity and local tolerance testing, clinical data on complex tertiary and quaternary structures , high molecular pharmacokinetics and pharmacodynamics, as well as a weights and may be subject to post translational pharmacovigilance plan are required by both the innovator modifications like glycosylation or sialylation , which are and biosimilar molecule. The biosimilar has to demonstrate crucial for optimal activity. comparable short term efficacy and tolerability for just one indication before it gets approval for all indication of the Generics on the other hand , have small well defined , stable reference medicine . These rules have made it much easier to molecules with a low molecular weight , which can easily be get approval for biosimilar product. reproduced. ISSUES OF PRACTICAL IMPORTANCE Biopharmaceuticals are produced by biological reaction in PHARMACOVIGILANCE living organism4 , which are characterized by a high degree of inherent variability. The type of the host( yeast , bacteria), Post –Approval safety data is collected by means of growth conditions , isolation procedures, storage and pharmacovigilance programmes. This is of importance transport conditions all affect the final quality of biological because there is limited clinical data, of regulatory short medicine Traditional generics are produced by chemical5,6 term , at approval . Many adverse effects and effects may reactions which are less variable , more easy to control , and become apparent or clear only after a drug is used more more predictable. The chemical structure or efficacy is not extensively , for a longer period of time , in a greater number markedly affected by storage or transport conditions. of patients. Biopharmaceutical drugs are potentially immunogenic , Pharmacovigilance is even more importance for biosimilar unlike conventional drugs. Even slight structural deviations products , because they are of different manufacture from the or impurities can lead to unwanted immune response in the reference products. Both manufacturers and prescriber 6,7 should be aware of the importance of post marketing receiving patient . vigilance , and keep a watchful eye on patients taking Inter manufacturer , and intra – manufacturer , inter – batch biosimilar especially in those patients with a clinical heterogenicity is more obvious in biopharmaceutical indication which has not be evaluated directly. products than in chemical generics. SUBSTITUTION REGULATORY ISSUES Automatic substitution implies dispensing of generic drug The FDA does not have any legal or regulatory pathway in instead of a prescribed innovator brand name , by a place for approval of biosimilars .The EMEA5,6,7 has pharmacist , without knowledge or consent of a physician . extensive rules and regulations. governing the approval of While this may be valid for small – molecule generics , it is biosimilars , which are more stringent than those for generics not advisable for biopharmaceutical products. ,quality , tolerability and efficacy , pharmacodynamic Doctors , pharmacists and patients should be aware of the 2 of 4 Biosimilar medical products: What a physician needs to know fact that biopharmaceutical products can not be substituted CURRENT BIOSIMILARS by biosimilars . The prescribing clinician must be aware , The European Medicine Agency (EMEA) has recently and must consent to , any change in drug dispensing. approved two biosimilar growth hormone preparations , five LABELLING AND NAMING OF BIOSIMILAR erythropoietin products and is considering four filgrastim biosimilars . The regulators are attempting to meet the For accurate pharmacovigilance , it is essential to distinguish demands of the healthcare market while ensuring the quality and identify biosimilars. As multiple drugs have the same and safety of biopharmaceutical drugs, and have rejected a International Non proprietary Name (INN), e.g, insulin 9 biosimilar version of interferon alfa-2a recently . glargine , or erythropoietin , the brand or source should also be specified. CONCLUSION Biosimilars are complex molecules which are different from Labelling should clearly identify the character of the conventional generic drugs . A mere demonstration of molecule , its
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