Biosimilar Name and Shame: Senators Call Out FDA Guidance Efforts

Republicans express deep concern about agency’s biosimilar naming and labeling process.

Congressional dissatisfaction with FDA’s approach to guidance development reached a boiling point April 30, with eight Republican senators stating that finalizing biosimilar guidance may have in fact have made the agency’s policy position less certain.

The letter follows a series of correspondence and hearings in which senators questioned how FDA was offering advice to sponsors in the absence of final guidance in areas ranging from medical devices to biomarkers.

The need for final guidance on biosimilars was even the subject of legislative debate when the approval pathway was being created, and while the 2010 law that governs biosimilars doesn’t mandate guidance be finalized before the agency can take action on applications, Republican legislators and sponsors of innovator sponsors have been pressing for it ever since (Also see "Biosimilar Approval Is New Focus In Senate Critique Of FDA Guidance Policy" - Pink Sheet, 10 Mar, 2015.).

So when FDA issued some final biosimilar guidances on April 28, it might have expected a nod or a clap from its congressional overseers. Instead, it got an angry letter.

“Although we are encouraged that FDA recently finalized three draft guidance documents, FDA did not finalize these documents until after reviewing and approving the first biosimilar application, and much of FDA’s guidance still is not final – to the extent it has been issued at all,” noted the letter, which was signed by HELP Committee Chair Lamar Alexander ,R-Tenn., as well as Sens. Michael Enzi, R-Wyo.; Richard Burr, R-N.C.; Johnny Isakson, R-Ga.; Mark Kirk, R-Ill.; Orrin Hatch, R-Utah; Pat Roberts, R-Kan.; and Bill Cassidy, R-La.

“This is problematic because draft guidance documents do not provide adequate notice to the public about FDA’s approval process because they do not necessarily represent FDA’s current thinking on the topics addressed and do not bind FDA staff in any way,” the letter states.

Drafts Are Bad, But So Are Changes From Them

FDA’s difficult position on guidances is underscored by one section of the letter where the senators question a change that FDA made in the final version from the draft version of the guidance on scientific considerations in demonstrating biosimilarity.

FDA “deleted, without explanation, all discussion of what the labeling should say about a product’s interchangeability status” – senators’ letter

“In February 2012, FDA issued draft guidance in which it advised that the ‘[l]abeling of a proposed product should include all the information necessary for a health professional to make prescribing decisions, including a clear statement advising that … [t]his product (has or has not) been determined to be interchangeable with the reference product,’” the letter states.

“But the first approved labeling for a biosimilar product – which was approved as biosimilar to, but not interchangeable with, its reference product – contains no statement regarding the product’s interchangeability status. Indeed, the label does not even include the word ‘biosimilar,’ which could further increase consumer confusion about how this product relates to the reference biologic,” the senators argue (Also see "Biosimilar Labeling Dissected: Sandoz’s Zarxio Uses Amgen’s Neupogen Text" - Pink Sheet, 6 Mar, 2015.).

“And, earlier this week, FDA issued a final version of the 2012 guidance document in which it deleted, without explanation, all discussion of what the labeling should say about a product’s interchangeability status. Given FDA’s earlier statement in draft guidance that information regarding interchangeability status is ‘necessary’ for health professionals to make prescribing decisions, we are concerned that FDA has made its policy on this issue more uncertain, even while approving the first biosimilar product.”

The letter’s argument puts the agency in a pretty tight spot: draft guidances aren’t good because sponsors don’t know if they represent the agency’s opinions, the senators say, but changes in guidances when finalized might not be good either because they create uncertainly.

What’s A ‘Placeholder’ Name, Anyway?

Another specific concern raised by the senators relates to FDA’s decision to approve the first U.S. biosimilar – Sandoz Inc.’s Zarxio, referencing Amgen Inc.’s Neupogen (filgrastim) – with a placeholder name: filgrastim-sndz (Also see "Zarxio’s Placeholder Name Hints FDA Wants Generic Feel To Biosimilar Market" - Pink Sheet, 6 Mar, 2015.).

“Because FDA still has not announced a policy on nonproprietary names for biosimilar products, FDA approved the product with a ‘placeholder’ nonproprietary name that may not be ‘reflective of the agency’s decision on a comprehensive naming policy for biosimilar and other biological products,’” the letter states.

“It is unclear to us what it means for a nonproprietary name to be a ‘placeholder,’ what authority FDA has to make such a designation, or what treatment a ‘placeholder’ name will receive once FDA formalizes a naming policy. In addition, we are concerned that hospitals, consumers, patients, doctors, and others may be confused by a name that appears temporary or not fully approved.”

No ‘Cure’ For These Problems

The senators’ letter demonstrates the pressure FDA will face in the coming years, regardless of how the biosimilars spat plays out.

Already, the agency was directed to finalize a guidance on abuse-resistant opioid products due to congressional language, and the biomedical reform legislation being developed this session promises even more policy deadlines, even as FDA argues that would distract from its core application review responsibilities (see related story, (Also see "Congressional ‘Cures’ Debate Shifts To FDA Funding" - Pink Sheet, 30 Apr, 2015.)).

The biosimilar letter could also be an effort to discourage FDA from making more approvals without further guidance; many observers had been expecting firms and the agency to press on to new biosimilar frontiers even without more formal policy decisions (Also see "Biosimilar Sponsors May Seek Interchangeability Before FDA Sets Rules" - Pink Sheet, 24 Apr, 2015.).

The letter also contains seven questions that not too subtly challenge many of the basic conclusions upon which FDA has based its biosimilar operations. Some of the questions seem relatively straightforward for the agency to answer (the just-issued guidance agenda should take care of #5) but the sheer breadth of the inquiry – from patient education to application information exchange – puts the agency on notice that whatever it does with biosimilars, Congress will be watching closely.

The full text of the questions to FDA appears below:

We respectfully request that FDA answer the following questions by May 22, 2015:

1. What is a “placeholder” nonproprietary name, and what is FDA’s legal authority to issue and/or to change such a name? How do “placeholder” nonproprietary names differ from other forms of nonproprietary names, including (a) established names under Section 505(e) of the federal Food, Drug, and Cosmetic Act (FDCA); (b) interim established names as recognized under Novartis Pharmaceuticals Corp. v. Leavitt; and (c) proper names under Section 352(a)(1)(B)(i) of the Public Health Service Act (PHSA)?

2. What is the process for changing a “placeholder” nonproprietary name, and what is the estimated economic impact of such a change? In the event a “placeholder” nonproprietary name changes, what steps would FDA and the manufacturer take to avoid potential confusion among patients and public health professionals and to ensure that no misbranded product is sold on the market?

3. What guidelines have FDA staff members been following in reviewing biosimilar applications? Please provide copies of all written guidelines provided to staff regarding such review since February 2012. Has any staff member been instructed either to follow, or not to follow, recommendations in any of the draft guidance documents that FDA has published regarding biosimilarity or interchangeability (including documents that were in draft form at the time of review but have since been finalized)?

4. Under what circumstances does FDA consider it necessary for a biosimilar product to disclose in its labeling that it has or has not been found interchangeable with its reference product (or other products found biosimilar to the same reference product)? Why did FDA (a) withdraw the draft guidance it published on this issue and (b) approve labeling for a biosimilar product that contains no such disclosure?

5. What guidance documents regarding biosimilar or interchangeable products does FDA currently intend to publish, and on what schedule? Please provide: (a) the schedule on which FDA currently intends to finalize or withdraw each draft guidance document that FDA has published on these topics, if FDA has not provided it already; and (b) a list of additional guidance documents that FDA currently intends to publish on these topics, including the anticipated timeframe for publication and whether FDA intends to publish the document in draft or final form.

6. Why has FDA declined to provide guidance regarding whether the information exchange provisions of Section 351(l) of the PHSA are mandatory? If FDA is not providing such guidance because of pending litigation between private parties, please provide FDA’s position on the circumstances under which private litigation precludes FDA from issuing guidance regarding statutes within its jurisdiction.

7. How is FDA communicating with and educating patients regarding biosimilars, including on issues such as biosimilarity, extrapolation, and interchangeability?

We also urge FDA to prioritize the publication of final guidance on the issues identified above, and to improve the transparency of its biosimilar review and approval process going forward.