Senate Bill Could Eliminate Potential Access Barrier for Biosimilars

May 13, 2016

The Senate companion to last year’s 21st Century Cures Act could help biosimilars bypass a potential roadblock to patient access. The bill would exempt biologics from the U.S. Food, Drug and Cosmetic Act’s requirement to meet specifications from the United States Pharmacopeia (USP) compendium. Otherwise, applying the compendium requirements to biologics and biosimilars might cause the drugs unintentionally to be labeled “adulterated” or “misbranded,” unnecessarily delaying access for patients.

Why Monographs Matter

USP’s compendium, known as the United States Pharmacopeia and National Formulary, is the country’s official compilation of information on approved drugs. Issued by USP, the compendium includes comprehensive descriptions of active pharmaceutical ingredients and drug products. Known as “monographs,” these descriptions act as public standards used by the Food and Drug Administration (FDA) to gauge drug quality, purity and content.

The compendium also plays a role in drug naming. The name used in the USP monograph appears on the drug’s label and, if a drug bears a name other than the one recorded in the USP, it can be considered “mislabeled” under federal law.

Similarly, if a drug’s construction varies from the description in USP’s monograph, the medication can be deemed “adulterated.” Either result can lead to the drug being pulled from the market and out of consumers’ hands.

The Naming Debate Revisited

By exempting biologics from compendium standards, the Senate bill might protect regulatory progress on the issue of naming. In draft guidance, the FDA has acknowledged the value of distinct names for clarity and pharmacovigilance with biological drugs. Consistent with the World Health Organization’s approach, the agency proposes using suffixes to distinguish one biologic or biosimilar from another.

Physicians and patient advocates have also aligned on the issue. They argue that distinct names will alert physicians to slight variations between products, dispel confusion about which indications correspond to which biologic medications, and aid the cause of pharmacovigilance. Distinct names allow physicians and regulators to quickly, accurately trace adverse events back to their origin.

The USP, however, prefers the “well established” approach used for traditional drugs and their generic counterparts, whereby generics carry the same non-proprietary name as their reference product.

A Power Struggle over Naming

Opposing stances belie a deeper difference of opinion about which body – the FDA or the USP – has the final word on drug names. According to the USP, the non-proprietary name selected by the Food and Drug Administration is interim until the USP creates the drug’s monograph. The FDA sees things differently, as explained in a March 2015 article from The Pink Sheet (“The Curious Case of FDA, Zarxio’s Name and the USP Monograph”).

As the article explains, the issue came to a head during the 2015 approval process for the first U.S. biosimilar. The FDA determined that the innovator filgrastim’s monograph did not apply to Sandoz’s biosimilar and issued the drug the placeholder name “filgrastim-sndz.” The USP, however, contended that the FDA’s name “would not be considered final by law.” Though the USP is a nonprofit, not a government entity, its authority on drug quality is recognized by federal statute.

Exempting biologics from adherence to the compendium could reduce confusion and potential delays in access stemming from a disagreement between the FDA and the USP. It could also reduce the likelihood that a drug bearing its FDA-given name might be considered “mislabeled” for not bearing the name selected by the USP.

Quality & Adulteration

The issue of drug quality and adulteration present yet another challenge for biological drugs under the USP system. Biologics’ complexity makes them much harder than traditional drugs to reduce to a list of properties and processes, as a reflection paper from the International Federation of Pharmaceutical Manufacturers and the European Biosimilars Group explains. Biologics can be “well characterized” but not “fully characterized.”   Thus, establishing a monograph for a biological drug – and potentially using that monograph as the standard for gauging follow-on biosimilars’ quality and purity – presents unique challenges.

For example, a biosimilar deemed acceptable solely because it complies with the reference product’s monograph could still pose immunogenicity problems for patients. Conversely, a product considered “adulterated” because it does not mirror USP’s specifications on a molecular level might in fact produce patient results comparable or even better than those of its reference product.

Thus, the reflection paper suggests, USP and other pharmacopeia organizations should develop a broader approach for biologics. They might consider not just end product testing but also manufacturing process as well as clinical and pre-clinical studies. Rather than looking for molecular equivalency, as with traditional drugs, the process should consider the totality of evidence provided by a biosimilar.

Senate Action

The Senate’s FDA and NIH Workforce Authorities Modernization Act recognizes the patient access challenges that might stem from applying traditional standards requirements to innovative medicines.  Though the USP argues the measure will “undermine medical quality,” the Senate Health, Education, Labor and Pensions Committee explains that it will “preven[t] delays” in the biosimilar approval process.

Regardless of the bill’s fate, biosimilars must still receive FDA approval for safety and efficacy before becoming available to patients.

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