Life Sciences Legal Insights

Testing and Characterizing Biosimilarity: Will The Hatch-Waxman Safe Harbor Apply?

By: Michael Shuster

Two recent conflicting Federal Circuit cases (Classen and Momenta) interpreting the Hatch-Waxman safe harbor provision (35 USC 271(e)(1)) have stirred debate in the biosimilars community.  While the new biosimilars pathway (the Biologics Price Competition and Innovation Act) is different from Hatch-Waxman of course, and its interpretation by FDA is still evolving, the controversy emanating from the recent cases is drawing concern.

The Biologics Price Competition and Innovation Act ("BPCIA") has not yet led to an approved biosimilar, but one may not be far off. The FDA has conducted meetings with potential biosimilar sponsors and INDs (investigational new drug applications) for biosimilars have been filed. FDA's draft guidelines set forth detailed standard for 'biosimilarity' which must be met by the follow-on product.

The recent Momenta v. Amphastar case has led some in the biosimilars community to ask how an experimental safe harbor might work in the biological drug context, where we would likely see far more complex and sophisticated (and thus likely patented) compliance testing than what is typically found in the small molecule context.

If the Momenta case gets extrapolated to the biosimilars context, then the hard (and likely expensive) work of the first biosimilar candidate to figure out a method of testing and characterizing his large molecule will be used, legally and without compensation,  by other follow-on candidates in order to test their own candidate molecules. On the other hand, if the reasoning in Momenta is rejected by the Supreme Court (assuming they grant certiorari, which appears increasingly likely) then whichever biosimilar candidate can come up with (and patent) an effective means of characterizing large molecules for purposes of establishing biosimilarity sufficient to meet FDA's standards will likely become the de facto exclusive biosimilar competitor, as other competitors will be unable to satisfactorily characterize the biosimilarity of their candidate products without violating the patent.

Kevin Noonan, in the exceptional Patent Docs blog, has a comprehensive post on Judge Rader's dissent in Momenta. Judge Rader's various opinions on the topic of Hatch-Waxman safe harbor portend the problem of free-riding - "trespass" in the Judge's words - by competitor follow-on candidates, severely distorting incentives in the process.

We'll be looking for the Supreme Court to resolve the tension between Momenta and Classen and perhaps provide some guidance that can in turn be relied upon by the FDA.

Generic Drug Testing “Safe Harbor” Expanded by Recent Court Decision to Include Post-approval Activities Under Hatch-Waxman

By: Michael Shuster

The August 2012 decision in Momenta Pharmaceuticals v. Amphastar Pharmaceuticals, Inc. has expanded the “safe harbor” provisions of Hatch-Waxman, with serious implications for the pharma and biotech industries.

Hatch-Waxman contains a "safe harbor" provision for the use of patented inventions "reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs.” 35 U.S.C. § 271(e)(1)

Generally understood as a provision permitting companies to test or experiment with patented inventions prior to an FDA submission - such as a generic drug maker prior to submission of an ANDA - the provision's scope has expanded over the years.

The biochemical facts of the Momenta v. Amphastar case are involved, but it boils down to a conflict between two generic producers of the anti-coagulant drug enoxaparin (brand name: Lovenox). Momenta, which had received FDA approval for its ANDA on enoxaparin in July 2010 owns a patented method for ensuring enoxaparin's bioequivalence to Lovenox. Amphastar's ANDA was approved by FDA in September of 2011. Momenta alleged that Amphastar was in ongoing violation of the Momenta patents in determining the bioequivalence of its own version of enoxaparin. Without establishing bioequivalence, generics cannot be legally marketed.

Momenta was granted a preliminary injunction, but the Court of Appeals for the Federal Circuit vacated, reasoning that Amphastar's batch testing of its enoxaparin for purposes of establishing bioequivalence fell under the Hatch-Waxman safe harbor. The majority found that Amphastar's ongoing testing was part of a system of required record keeping for FDA, and thus brought the testing within Hatch-Waxman safe harbor.

A strong dissent from Chief Judge Rader suggests that we have not heard the end of this case. Perhaps further appeal and an en banc hearing may be in store. 

Biotech M&A Surges in Advance of Patent Expirations

By: Michael Shuster

We've known for some time that the pharma patent cliff was driving M&A, and now we have additional empirical evidence. Biotech M&A is at a 5 year high, according to Reuters.  The volume of biotech M&A is more than $25 billion so far this year, with particular strength in oncology and immunology.

It serves as a good reminder to life science companies to have their patents in good shape and be up-to-date on the latest in confidentiality agreements for when suitors come knocking.

Are Biosimilar Names Key to Biosimilar Fates?

By: Michael Shuster

"People's fates are simplified by their names" goes the quote from the Bulgarian novelist and playwright Elias Canetti. Whether this is indeed true for people is debatable but for biological drugs names are apparently critical, or so we can gather from recent warring between branded and generic industry organizations. Last week industry organizations BIO and PhARMA issued a rare joint letter to FDA commissioner Margaret Hamburg strongly supporting the use of unique names for all biosimilar products, whether deemed fully 'interchangeable' or merely biosimilar. The Generic Pharmaceutical Industry, understandably, disagreed, in its own letter to Commissioner Hamburg.

The naming situation with biological drugs is more complicated than for small molecule drugs because even interchangeable biologics are not identical in the strict chemical sense that small molecule drugs are identical.

Thus there can only be one trastuzumab ("herceptin"), and a biosimilar version, even an interchangeable one under the law, could, at best, be called "biosimilar trastuzumab" - but BIO would prefer FDA require such a biologic to have an entirely new name. For the generics industry, the marketing burden of educating doctors (and patients) that a drug with an entirely new name is actually biosimilar herceptin would be formidable.

It will be up to FDA to decide on the naming rules, and the rest will be up to fate (or marketing genius).

Supreme Court Allows Generic Manufacturers to Challenge Use Codes

By: David Tellekson, Ewa Davison

On April 17, 2012, the U.S. Supreme Court issued a unanimous decision in Caraco Pharmaceutical Laboratories, Ltd. v. Novo Nordisk A/S, holding that a generic drug manufacturer may file a counterclaim to force correction of an overbroad use code that encompasses unclaimed methods of using the drug at issue. In interpreting the text of 21 U.S.C. § 355(j)(5)(C)(ii)(I), the Court gave substantial weight to ensuring that the Food and Drug Administration fulfills its statutory duty to approve non-infringing generics in accord with Congressional intent. Brand manufacturers are advised to review active use codes to ensure that they reasonably reflect the scope of any claimed methods of use.

Learn more about the Court’s ruling in Caraco Pharmaceutical Laboratories v. Novo Nordisk.

PDUFA Working Its Way Through Capitol Hill

By: Jake Handy

The Prescription Drug User Fee Act (PDUFA) re-authorization wrangling is underway on Capitol Hill. Today the House of Representatives takes up its version of the FDA bill the Senate passed last week. On May 24th the Senate version of the PDUFA bill passed on a 96-1 vote. The current PDUFA will expire on October 1st and debates in the House could, potentially, take all summer. However, legislators and industry observers have expressed hope for a final bill to be presented to the President for signature in early July. We'll be closely following the progress of the reconciliation of the House and Senate bills.

Estimates vary but the present PDUFA will likely bring in around 6.4 billion dollars to FDA over its active period. Since PDUFA fees account for the majority of the FDA's drug review budget, the core PDUFA legislative mandate has broad bi-partisan support. While PDUFA itself is fairly non-controversial, the various amendments that were attached at the beginning of the week led to intense debate. Many of those proposed amendments - such as energy drink registration and Canadian drug importation - were dropped from the final version of the Senate bill.