It's final. The FDA is sticking with an alphabet soup approach to suffixes for nonproprietary, or proper, names for originator biologics, related biologics and biosimilars. But it's still scratching its head over the naming of interchangeables.
One of a spate of guidances the agency issued Thursday in the waning days of the Obama administration, the final guidance calls for biologic proper names to consist of a meaningless, four-letter, lowercase suffix attached to the core name with a hyphen. The FDA is encouraging the routine use of the suffixes in ordering, prescribing, dispensing, recordkeeping and pharmacovigilance practices.
The agency has already followed the naming scheme for all but one biosimilar it's approved. As the first out of the gate, Sandoz Inc.'s Zarxio was assigned a "placeholder" proper name with a suffix suggestive of its maker filgrastim-sndz. But subsequent biosimilars were given suffixes "devoid of meaning," to use the FDA's phrasing. (See BioWorld Today, March 9, 2015, and April 6, 2016.)
Going forward, sponsors of biologics and biosimilars may propose up to 10 meaningless suffixes, in their order of preference, when they submit an investigational new drug application or a biologic license application (BLA). If a sponsor of a new biologic or biosimilar doesn't propose an acceptable suffix within an appropriate time frame, the FDA may come up with its own suffix, according to the guidance slated for publication in Friday's Federal Register.
Sponsors of biologics already approved will need to submit proposed suffixes in a prior-approval labeling supplement to their BLA. However, the agency has yet to set a timeline for adding suffixes to previously licensed biologics. In the near term, it said it intends to assign suffixes to a limited group of licensed biologics presumably, those with existing or looming biosimilar competition.
The guidance references a 2015 proposed rule to add random suffixes to the proper names for Zarxio; its reference biologic, Amgen Inc.'s Neupogen; and Teva Pharmaceutical Industries Ltd.'s Granix, a Neupogen copycat that followed the 351(a) route instead of waiting for the biosimilar path to open. The rule also suggested suffixes for Johnson & Johnson's Remicade (infliximab) and Amgen's Neulasta (pegfilgrastim) and Epogen (epoetin alfa), all of which were being referenced by biosimilars under review when the rule was proposed. (See BioWorld Today, Aug. 28, 2015.)
The rule has not been finalized, and while a Remicade biosimilar hit the market a few months ago, no Epogen or Neulasta biosimilars have been licensed yet in the U.S. Meanwhile, the FDA has approved Amgen's biosimilar to Humira (adalimumab, Abbvie Inc.) and Sandoz's biosimilar referencing Amgen's Enbrel (etanercept). It also has accepted a BLA for a biosimilar to Roche AG's Herceptin (trastuzumab) and is considering acceptance of one referencing Roche's Avastin (bevacizumab).
MORE TO COME
As the FDA continues to work out the implementation of the new naming scheme for older biologics, it said sponsors may submit prior approval labeling supplements that include proposed suffixes for those products.
The naming scheme also will apply to simple proteins, such as hormones and insulin, that were approved on the small-molecule path. The Biologic Price Competition and Innovation Act, which authorized the biosimilar path, called for those proteins, and their copies, to be regulated as biosimilars by March 23, 2020. That means the FDA will have to retroactively change the proper names for drugs such as Sanofi SA's Lantus (insulin glargine) and Basaglar, a Lantus copy from Boehringer Ingelheim GmbH and Eli Lilly and Co.
The agency said it plans to provide additional guidance on the transition of those drugs, including one on implementing the proper name suffix.
While the FDA intends to apply a similar naming convention to interchangeable biologics, it's still considering the appropriate suffix format for that group of products. One issue is how to differentiate between a biosimilar and an interchangeable referencing the same biologic.
Unlike biosimilars, interchangeables may be automatically substituted when the reference product is prescribed. One possibility would be to give an interchangeable the same proper name suffix and all as the reference biologic. But that could undermine pharmacovigilance, one of the drivers for unique suffixes.
In justifying its biologic naming approach, the FDA said that, in making the proper names distinguishable, suffixes will facilitate tracking of specific products, provide for more accurate drug identification by doctors and patients, and minimize inadvertent substitution of products not deemed to be interchangeable.
By attaching suffixes to both the reference biologic and follow-ons, the FDA also hopes to avoid inaccurate perceptions about the safety and effectiveness of the drugs based on the path they followed to market. Although the label will indicate whether a drug is a biosimilar, the across-the-board naming scheme will not give innovator biologics an advantage over the follow-ons.
SPATE OF GUIDANCE
With one week left before the Obama administration gives way to the Trump administration Jan. 20, FDA personnel are wrapping up numerous guidances, many of which have been in the works for years. The following are among those slated for publication in Friday's Federal Register:
- Multiple Endpoints in Clinical Trials is a draft guidance describing various strategies for grouping and ordering endpoints for analysis and applying statistical methods for managing multiplicity within a study. The draft partially fulfills a commitment the FDA made in the 2007 FDA Amendments Act. Comments on the guidance are due by March 14.
- Emergency Use Authorization of Medical Products and Related Authorities clarifies and finalizes last year's draft guidance discussing the FDA's authorities, granted under the 2013 Pandemic and All-Hazards Preparedness Reauthorization Act, regarding the use of medical countermeasures in emergencies involving chemical, biological, radiological and nuclear agents, including emerging infectious disease threats.
- 180-Day Exclusivity is a draft guidance that answers commonly asked questions about the 180-day generic drug exclusivity. The guidance is intended to improve transparency and facilitate the development, approval and timely marketing of generics. The FDA plans to update the guidance to include additional questions and answers as appropriate. Comments are due by March 14.
- How to Prepare a Pre-Request for Designation (Pre-RFD) is a draft guidance providing recommendations on submitting a pre-request to the Office of Combination Products (OCP) for a designation program. A pre-request is a flexible option that allows sponsors to get a preliminary, nonbinding assessment about which FDA center will have jurisdiction over a proposed combination product. The draft describes the process the agency will follow in reviewing the requests, the general time frames for sponsors to get OCP feedback, and the steps for scheduling teleconferences and meetings in relation to a Pre-RFD. Comments are due by April 13.
In addition to the guidance, the FDA is opening a docket to seek suggestions, recommendations and comments about policy issues that its Combination Product Policy Council may consider. The agency will use the comments to identify and address combination product issues that need to be clarified. Stakeholders may submit their suggestions to the docket on regulations.gov through April 13.
Even though the FDA will be under new leadership this year, its Center for Drug Evaluation and Research this week issued a guidance agenda for 2017. The list of more than 100 guidances includes one on how drug and device manufacturers may communicate with payers and formulary committees. Two biosimilar guidances also are on the list, including a long-promised one on interchangeability.