By Curtis Rooney
Pharmaceutical ‘clones’ have the potential to increase patient access to
life-saving medications and reduce costs for the entire healthcare system
March 6, 2015, will go down as the day in healthcare supply chain history that government forces unleashed pharmaceutical clones – biosimilars – on the market. This might sound more dramatic than it probably is (especially when you imagine James Earl Jones doing the voiceover) if you consider that Europe has allowed biosimilars on the market for some time. But the U.S. Food & Drug Administration’s recent approval of Sandoz’s Zarxio (which treats low white-blood-cell counts) – the first biosimilar in the United States – signals the start of something new, important and potentially competitive with reference biologic products. In addition, three other companies have publicly announced they have biosimilar applications under FDA review.
Shortly after FDA’s action, the Centers for Medicare and Medicaid Services (CMS) released its own guidance on biosimilars:
- Similar to other new products, Part D plan sponsors are allowed to add coverage of biosimilars at any time as a formulary enhancement.
- Generally, CMS will consider formulary changes in which the reference product is removed and replaced with the biosimilar product as a non-maintenance change. Therefore, CMS will evaluate these changes on a case-by-case basis.
- However, CMS does not consider reference and biosimilar products to be different drugs; therefore, they will not be considered two drugs for the purposes of satisfying USP formulary requirements.
- Because biosimilars are not considered a generic drug, they will be subject to the higher maximum copayments for Low-Income-Subsidy-eligible beneficiaries and non-LIS beneficiaries in the catastrophic coverage period.
- Biosimilars are not considered “applicable drugs” for the purposes of the Coverage Gap Discount Program; therefore they will not be discounted or otherwise subject to the Discount Program requirements.
- CMS noted that additional guidance may be issued for “interchangeable” biosimilars at a later date.
- Biosimilar products fall within the definition of single-source drugs for purposes of the Medicaid Drug Rebate (MDR) program.
- States may consider total rebates for biosimilar products, as well as the total rebates for the reference product, in determination of Preferred Drug Lists (PDLs).
- States are encouraged to educate physicians and pharmacists on how to prescribe and dispense biosimilars, depending on each state’s requirements.
- States are encouraged to use their existing Drug Utilization Review (DUR) programs and P&T committees to education physicians and pharmacists on the appropriate prescribing and dispensing of biosimilars.
FDA approval process
Even more recently, the FDA released three guidance documents regarding biosimilars. On April 29, the agency essentially gave the green light to drug makers who are developing copycat versions of branded biological drugs under an abbreviated pathway established by the Affordable Care Act. The FDA guidance follows after the public comments period completed on February 2012.
It is now known, for example, that the FDA will not always require a comparative clinical trial for biosimilar approval, because the guidance provides an example of when a trial would not be needed even though some of the comments received by the FDA had urged that at least one clinical study evaluating safety and effectiveness be required for any biosimilar approval.
The guidance comes in three parts. The first two describe the scientific and quality considerations for demonstrating “biosimilarity” to a reference drug. The third document contains questions and answers on the biosimilar pathway and suggestions for biosimilar development. The FDA, for example, will allow an approach for extrapolating data from one indication of a biosimilar to additional indications of the brand biologic, which makes it easier for a biosimilar to obtain all of the branded drug’s approved uses. The agency also provides new information for companies looking to develop biosimilars for approval in the United States and abroad without duplicating all prior work, including offering enhanced alignment with the European Medicines Agency.
Following this guidance, the Senate Health, Education, Labor and Pensions (HELP) Republican members, led by Chairman Lamar Alexander (R-Tenn.), sent a letter to the FDA urging the agency to immediately finalize all guidance regarding the approval of biosimilar drugs. The Senators raised concerns that the agency has “not provided sufficient guidance on important issues relating to the review and approval of license applications for biosimilar products,” such as:
- Production of patent information
The letter also criticized FDA for not having a policy in place for nonproprietary names for biosimilar products, but rather relying on a “placeholder” nonproprietary name that provides little clarity.
Where does HSCA stand?
The Healthcare Supply Chain Association (HSCA) and its members strongly believe that biosimilars have the potential to increase patient access to life-saving medications and to reduce costs for the entire healthcare system. One recent study projected savings of $250 billion over ten years. HSCA and its members are working with FDA to help ensure a pathway to market for biosimilars that prioritizes patient safety and encourages development and uptake of these less-costly therapies.
HSCA believes that these medicines should share the same International Nonproprietary Name (INN) as their reference biologic. This is sound public policy and based on the fact that biosimilars are, by definition, highly similar and have no clinically meaningful differences that would require a unique name. If biosimilars are not allowed to share the INN of their reference biologic, it could jeopardize patient safety, inhibit market competition, and slow the uptake of biosimilars, which could result in billions of dollars in lost potential cost savings.
Multiple nonproprietary names may increase confusion among patients and providers and hamper the clinical decision-making of physicians. Requiring unique names would run counter to existing international naming standards for generic pharmaceuticals. Shared INNs are already being used safely and effectively in highly regulated countries in the European Union, Canada, Australia and Japan. Since 2006, in Europe there have been no issues with traceability of biosimilars that use the same INN in their products. The manufacturer name, National Drug Code (NDC), and lot number guarantee full traceability.
HSCA agrees that the FDA should issue clear, robust guidance on interchangeability. The ability to safely substitute FDA-approved biosimilars for innovator biologics will be critical to realizing the full cost-savings and access potential of biosimilars. FDA should issue clear guidance on the requirements to obtain an “interchangeable” designation. Manufacturers should be allowed to use data collected from Europe to gain FDA approval for interchangeability in the U.S.
HSCA also maintains that states should stand out of the way and support a pathway for the expedient and safe implementation of biosimilars as soon these drugs are approved.
Biosimilars have the potential to create a whole new world. That world has just begun in the United States. Let’s hope that unleashing these clones will not only allow for the successful attack of those patients struck by disease, but also the budget deficits of the healthcare providers administering their care.
Curtis Rooney is president of the Healthcare Supply Chain Association, www.supplychainassociation.org.
What are biosimilars?
Many of today’s important medications are biological products. Biological products are made from living organisms. The material they are made from can come from many sources, including humans, animals and microorganisms such as bacteria or yeast. Biological products are manufactured through biotechnology, derived from natural sources or, in some cases, produced synthetically.
Biological products are among the medications used to treat conditions such as rheumatoid arthritis, anemia, low white blood cell counts, inflammatory bowel disease, skin conditions such as psoriasis and various forms of cancer.
Most biological products are more complex in structure and have larger molecules or mixtures of molecules than conventional drugs (also called small-molecule drugs). Conventional drugs are made of pure chemical substances and their structures can be identified. Most biologics, however, are complex mixtures that are more difficult to identify or characterize.
There are two new types of biological products – biosimilar and interchangeable. Biosimilars are a type of biological product that are licensed (approved) by FDA because they are highly similar to an already FDA-approved biological product, known as the biological reference product (reference product), and have been shown to have no clinically meaningful differences from the reference product. An interchangeable biological product, in addition to meeting the biosimilarity standard, is expected to produce the same clinical result as the reference product in any given patient.
Biosimilars are not the same as generic drugs. Generic drugs are copies of brand-name drugs, have the same active ingredient, and are the same as those brand name drugs in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use. That means the brand-name and the generic are bioequivalent. Biosimilars are highly similar to the reference product they were compared to, but have allowable differences because they are made from living organisms. Biosimilars also have no clinically meaningful differences in terms of safety, purity, and potency from the reference product.
Source: U.S. Food and Drug Administration, www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm241718.htm