After several delays the FDA has finally released its draft guidance that says a biosimilar’s label does not have to be identical to that of its reference product, adding that differences may be appropriate to inform safe and effective use of the product. FDA also says it may be appropriate to include information about reference product uses not approved for the biosimilar for safety reasons, and additionally calls for a “biosimilarity statement” as part of the prescribing information highlights. FDA did not resolve how interchangeable products should be labeled, but the agency said it is considering the types of information that would support a demonstration that a biosimilar is interchangeable with a reference product. FDA indicating that labeling recommendations will be included in a future guidance.
Comments to the draft guidance are due June 3. They can be submitted to http://www.regulations.gov using Docket Number FDA-2016-D-0643.
The Guidance
FDA’s general principle is outlined in the guidance, recommending that, “in the biosimilar product labeling, applicants incorporate relevant data and information from the reference product labeling, with appropriate product-specific modifications.” As a general matter, FDA believes the product should not include a description of these data because a clinical study supporting the licensure of the biosimilar product generally would not be designed to independently demonstrate the safety and efficacy of the product. However, labeling must meet the content and format requirements of the physician labeling rule and the pregnancy and lactation rule, regardless of the format of the reference product label.
The guidance outlines that relevant data and information from the reference product labeling that should be incorporated into the biosimilar product labeling depends on “whether the applicant is seeking approval for all conditions of use or fewer than all conditions of use of the reference product for the biosimilar product.” FDA says that it anticipates “similar” text in biosimilar product labeling that is based on the reference product labeling, although it need not be identical and should reflect currently available information necessary for the safe and effective use of the biosimilar.
Furthermore, FDA outlines that the labeling for the biosimilar product should be “specific to the conditions of use sought for the biosimilar product and should be consistent with language previously approved for the reference product for those conditions of use.” FDA explains circumstances where there may be a biosimilar licensed for fewer indications than the reference product. Additionally, FDA discusses inclusion of initial U.S. approval of the biosimilar and a biosimilarity statement which the FDA recommends including “on the line immediately beneath the initial U.S. approval date in highlights, that the product is biosimilar to the reference product.”
The FDA also notes that in biosimilar product labeling, “the approach to product identification depends on the context of the information being presented.” FDA recommends that the biosimilar product name be used in the labeling text that is “specific to that biosimilar product or refers solely to the biosimilar product.” FDA further recommends that if the product has a proprietary name, “the proprietary name be used in these instances.” If “a proprietary name is not available for the biosimilar product, the biosimilar product’s proper name should be used”. FDA outlines examples in the guidance, including when to use the biosimilar product name, the reference product name, core name, and more than one product name.
The guidance discusses FDA-approved patient labeling, including updated safety information and additional conditions of use. FDA also explains its thinking on the submission of initial and revised labeling. Regarding interchangeable biologics, FDA is still considering the issue and will make recommendations on the labeling of interchangeable products in future guidance.
Reaction
According to a report, industry may not be too pleased with the guidance. Although Regulatory Focus quoted Duncan Emerton, senior director at FirstWord Pharma, as saying the guidance does not have any major surprises as it aligns with the way FDA labeled the first approved biosimilar in the US, Zarxio. Emerton says he’s spoken to lots of physicians “and the general consensus has been a need for full disclosure (i.e. include all the relevant data for the biosimilar whenever possible).”
The details of the guidance are important, but it is also important that the document was released in the first place. “The big news about the draft guidance is that they got it out, and this alone will end some uncertainty for both the biosimilar applicant and the originator of the biologic, also known as the reference product sponsor,” Siegmund Gutman, chair of Proskauer’s life sciences patent practice told Bloomberg BNA.
Bloomberg BNA also reported that the Generic Pharmaceutical Association and its Biosimilars Council released a statement that it was a pleased with the guidance that “provides manufacturers with additional clarity needed to manufacture and distribute more affordable versions of biologic medicines for patients.”
Meanwhile, Patients for Biologics Safety and Access and the American College of Rheumatology released statements indicating that the clinical trial data for the biosimilar should be included in the labeling and that the label should specify whether the supporting clinical data for each indication are derived from studies of the biosimilar or the reference biologic.
The guidance comes as an IMS Institute for Healthcare Informatics report highlights that the use of biosimilar drugs could save more than $100 billion in the United States and five European markets by 2020. The report reviewed markets in Britain, France, Germany, Italy, Spain, and the United States. It included eight commonly used brand-name medications that are scheduled to lose patent protection within the next five years and the projected savings that would result if corresponding biosimilars were introduced into the market. The report estimated that the United States and five European markets would save a combined $110 billion. However, the report noted the savings could not be realized unless health care providers are properly educated about biosimilars and drug makers adopt “smart market access strategies” to spur the drugs’ use.