Act II, Scene II: A Rose By Any Other Name Would Smell as Sweet? “No!” Says GPhA in Citizen Petition to FDA on Biosimilar Naming
September 19, 2013By Kurt R. Karst –
The titles – and sometimes even the content – of some of our posts are inspired by the things we experience (or have experienced) in our regular, non-attorney lives. For years now we’ve weaved together with food and drug law topics such seemingly disparate things as movies (A Few Good Men and Fletch – see our posts here and here), television (Star Trek and Monty Python and the Holy Grail – see here and here), and even Frau Rommelfanger’s seventh grade German class (see here). We hope these (clever) mash-ups grab readers’ attention and keep you interested in things that can, at times, seem boring or hypertechnical, or that may not be in your bailiwick, but that matter nevertheless.
Although one of our posts from way back in 2007 shortly after we started this blog was inspired by the Bard of Avon, William Shakespeare, and the famous line he penned in Hamlet – “To be, or not to be” (see here) – we’ve never dragged the Bard’s Romeo and Juliet into food and drug law. As you can see, now we have. And it’s a nice fit with a Citizen Petition (Docket No. FDA-2013-P-1153) the Generic Pharmaceutical Association (“GPhA”) recently submitted to FDA on biosimilar naming. If Act I of what will likely be a long-running and many-act play on biosimilars concluded with the March 23, 2010 enactment of the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), then Act II has been all about topics related to, but that are not specifically covered by, the BPCIA. Act II, Scene I is about the continuing state-by-state battle over biosimilar substitution laws (see our scorecard here). Act II, Scene II is about the battle over whether biosimilar versions of their brand-name reference product counterparts should each be assigned a distinct nonproprietary name specific to the manufacturer. (Act III, which is only in early development, may be based on the April 2012 Citizen Petition – Docket No. FDA-2012-P-0317 – submitted by Abbott Laboratories requesting that FDA not accept for filing, file, approve, or even discuss with any company any application or any investigational new drug application for any biosimilar that cites as its reference product any product for which the BLA was submitted to FDA prior to the date on which the BPCIA was enacted (see our previous post here)).
In Act II, Scene II of Romeo and Juliet – the famous balcony scene – Juliet argues that the names of things don't matter, and all that matters is what things are:
'Tis but thy name that is my enemy;
Thou art thyself, though not a Montague.
What's Montague? it is nor hand, nor foot,
Nor arm, nor face, nor any other part
Belonging to a man. O, be some other name!
What's in a name? that which we call a rose
By any other name would smell as sweet;
So Romeo would, were he not Romeo call'd,
Retain that dear perfection which he owes
Without that title. Romeo, doff thy name,
And for that name which is no part of thee
Take all myself.
While it might be true that names don’t matter when it comes to matters of love, names do matter in other contexts, like in food and drug law. As such, GPhA respectfully disagrees with the Bard and says that names do matter when it comes to biosimilars!
In its September 17, 2013 Citizen Petition, GPhA requests that FDA implement its International Nonproprietary Name (“INN”) naming policy equally to all biologics, whether that biological product is approved as a biosimilar under Section 351(k) of the Public Health Service Act (“PHS Act”) as added by the BPCIA, or as a brand-name reference product under PHS Act § 351(a). More specifically, GPhA says that “because all biologics approved under the Section 351(k) pathway are ‘highly similar’; and thus, have no clinically meaningful differences from the reference protein product (RPP) [they should] share the same INN name as the RPP, just as comparable originator products produced by a change in a manufacturing process or facility (post-change product) share the same INN as the original RPP (pre-change product).” (Emphasis in original)
The BPCIA, as enacted, does not specifically address biosimilar product naming. Although previous biosimilar legislation did address the issue, such as Representative Henry Waxman’s (D-CA) Access to Life-Saving Medicine Act (H.R. 1038) and Senator Judd Gregg’s (R-NH) Affordable Biologics for Consumers Act (S. 1505) (both from 2007), it was ultimately decided that naming provisions should not be included in the final biosimilars bill. Given this history, GPhA says that “[w]ithout new statutory authority, FDA lacks specific authority to require separate INNs for biosimilars, and existing conventions for biologics should be expected to prevail.”
Referencing a 2006 policy paper FDA sent to the World Health Organization (“WHO”) in support of WHO naming conventions, GPhA says:
FDA clearly supports the original purpose of the INN (to identify the active ingredient of a product), rejects the use of nonproprietary names to communicate interchangeability, and states that concerns about pharmacovigilance “transcend a naming convention,” explaining that “[i]t would be the FDA's preference that INNs continue to be granted based only on molecular characteristics and pharmacological class of the active ingredient(s). ” In this paper FDA agrees that there should be no change in global policy and rejects distinctive INN designations for biosimilars. . . . While [the] BPCIA was enacted subsequent to this policy position being presented to WHO, nothing in the new statute is incompatible with the 2006 FDA position on biosimilar naming.
Moreover, says GPhA, FDA is obligated to apply its standards equally to all applicants and products:
Requiring unique INNs for biosimilars while allowing sharing of INNs for other biologics in comparable situations would run contrary to this tenet. FDA routinely allows originator biologic products in the same class approved under separate 351(a) or 505(b) applications and using different manufacturing methods implemented by different sponsors to share the same INN. For example, a number of Anti-hemophilic Factor (Recombinant) products, some of the most complex biologics licensed in the US, share the same INN. [(Appendix A to the Petition is an extensive list of products that share INNs.)] Further, FDA has for many years without question authorized originator manufacturers to modify biologics' manufacturing processes and develop biologics that have minor changes and differences that are not clinically meaningful without requiring a change in non-proprietary name. This authorization is contingent on a sponsor submitting data that the post-change product is “comparable” to the pre-change product. If the sponsor demonstrates such comparability FDA deems the (pre- and post-change) products interchangeable for all indications irrespective of the mechanism of action being understood. The standard for both comparability and biosimilarity is “highly similar” quality attributes.
And what about concerns raised by some that distinct biosimilar names are necessary to facilitate accurate attribution of adverse events? GPhA addresses that issue as well and says:
GPhA concurs that any concerns with pharmacovigilance call for tailored solutions capable of fixing the actual problem without creating additional confusion. Unsupported pronouncements of inadequate tracking capabilities for biosimilars with the same INN as their RPPs represents, at best, a hypothetical problem given that no biosimilars have yet been approved in the US and Europe has been successful at tracking biosimilars which share INNs with their RPPs. . . . Currently, a well-established process exists to track product quality problems that does not rely prirnarily on INNs, but instead uses a product's brand name, manufacturer, lot number and NDC to track quality and safety events. GPhA does not believe requiring unique I NNs for biosimilars could remedy the poorly defined concerns and, instead would cause confusion and potential harm to patients by interfering with the present system. In contrast, we fully support vigorous enhancement of track and trace and education of physicians and pharmacists to include NDCs, manufacturer names and other relevant identifiers on all safety reports. This applies equally to all biologics, and must not be used as a wedge to create an anticompetitive barrier to biosimilar development and commercialization.
On the other side of the debate are organizations like the Alliance for Safe Biologic Medicines (“ASBM”). As we previously reported, ASBM has urged FDA to adopt unique non-proprietary names for all biological products licensed under the PHS Act, and in particular biosimilar versions of reference products (even those that are interchangeable).
Other than FDA’s 2006 policy paper, the Agency has remained pretty silent on the biosimilars naming issue. Over the summer, there was a rumor circulating that FDA was in the process of drafting a guidance document on biosimilar naming issues; however, nothing has been confirmed.
In a typical three-act play, the main character encounters a complication in Act II – an obstacle that prevents that character from achieving his or her dramatic need – and reaches his or her lowest point. In Act II of the biosimilars play at hand, we’re not sure yet who – the brand or generic side of the debate – is playing the role of the main character. But whoever that is is sure to be disappointed with the outcome.
Update: