Multiple Sclerosis Centers of Excellence
MSCoE Approach to Generic and Biosimilar Disease Modifying Therapies
Rebecca Spain, MD, MSPH -- Portland, OR
Mitchell Wallin, MD, MPH and Heidi Maloni, PhD, APRN, BC-ANP, MSCN -- Washington, DC
Kathy Tortorice, PharmD, BCPS -- VA Pharmacy Benefits Management
The field of MS is seeing an explosion of FDA approvals for MS disease-modifying therapies (DMT). Some of these approvals are for generic medications and biosimilar medications raising questions among MS providers regarding their place in the treatment armamentarium. This article defines generic and biosimilar medications, their approval process, and their expected place in the VA Formulary.
Generics
A generic medication is a chemically identical copy of an original branded medication, also termed the “innovator” or “reference” drug. In order for a generic drug to be given an AB rating by the FDA, several criteria must be met. First, it must contain the same active ingredient as the brand or innovator product. It must be identical in strength and dosage form. It must have adequate labeling, and it must be manufactured in compliance with good manufacturing process (GMP). The fundamental feature and perhaps the most important feature for clinicians is that the generic product be considered bioequivalent to the brand product. Statistics are used to determine bioequivalence, meaning whether the rate and extent of absorption vary significantly from the brand product. A ratio of the area under the concentration time curve (AUC) of the brand product to the generic product and the 90% confidence interval of that ratio must fall between 80% to 125%. This may appear to be a subtle difference, but in reality, current bioequivalence standards in criteria are far more rigorous than in previous years. The FDA states that using this approach, “there is no more than a 5% chance that a generic product is not truly equivalent to the reference product” (1).
The legal framework to encourage production of generic medications stems from the congressionally approved 1984 Drug Price Competition and Patent Term Restoration (Hatch-Waxman) Act. This act provided protection for drug innovators by extending patents while also providing incentives for generic production by preventing copyright lawsuits and requiring only quality assurance studies. Glatiramer acetate, dimethyl fumarate, teriflunomide and fingolimod are examples of DMT that have approved AB rated generic formulations.
Biosimilars
Biologics comprise many of the other MS DMT. Biologics are made from living organisms and as such, their structures are generally more complex and development more complicated. Biosimilars are defined as having a structure highly similar to and without clinically meaningful differences from another biologic agent. They have same route of administration, strength, dosage, and same potential side effects. Biosimilars are not developed in living organisms, instead they are produced in manufacturer-dependent cell lines. The safety and efficacy of biosimilars compared to branded products is seen from their long history in Europe, where the European Medicines Agency (EMA), the European equivalent of the FDA, approved the first biosimilar in 2006. Since then, over 30 biosimilars have been approved for a variety of indications, and Europe has seen no unexpected or unusual adverse reactions. The European experience shows that biosimilars can be used as safely and effectively for their approved indications as other biological medicines. The FDA’s strict review standards for biologics and biosimilars should lead to similarly positive results in the United States.
The 2009 Biologics Price Competition and Innovation Act established the regulatory framework for an abbreviated FDA approval process for biosimilars. Key requirements for FDA approval of biosimilars are: animal studies including toxicity, a clinical (human) study to demonstrate safety, purity, and potency in one or more indications for which the reference product is licensed, expectation of same clinical result as the reference product, and no increased risk or decreased efficacy caused by switch of the reference to biosimilar product (2). Importantly, a biosimilar only requires evidence of clinical efficacy in one of the reference product’s indications, with the other indications approved for the biosimilar by a process of extrapolation.
The goal of the generic and biosimilar FDA approval processes is to provide non-branded therapeutic products that will, in turn, lower medication costs and improve their access globally due to traditional market forces. Cost containment is particularly relevant in MS as prices continue to rise exponentially (3). Because the biosimilar sponsor is able to rely on the safety and efficacy work completed by the reference product’s sponsor, and focus on a comparative assessment, product development costs should be lower, approval times should be faster, and more products should be brought to market.
The MS Centers of Excellence (MSCoE) recognize both the promise and concerns surrounding AB rated generics and biosimilars. Fortunately the US Food and Drug Administration has some of the highest global standards for approval of both generic and biosimilar medications. Driving down costs and increasing access to effective MS therapies are key to maintaining independence and increasing quality of life among Veterans living with MS. VHA policy is to dispense generically equivalent drugs when they are available. The VA Pharmacy Benefits Management Service (VA PBM) carefully reviews all medications, including innovators, generics and biosimilars, to insure they will provide safe, effective and high quality, value-based care for patients. Together with VA PBM, the MSCoE supports the use of VA approved generic and biosimilar DMT for our Veterans with MS.
References
(1) US FDA: Approved Drug Products with Therapeutic Equivalence Evaluations
(2) US FDA: Biosimilars
(3) Hartung DM, Bourdette DN, Ahmed SM, Whitham RH. The cost of MS drugs in the US and the pharmaceutical industry. Too big to fail? Neurology. 2015 May;84(21):2185-92.
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