Limitations of the Safe Harbor Defense: Lessons from Amgen v. Hospira
On August 27, 2018, the United States District Court for the District of Delaware denied Hospira, Inc.’s (“Hospira”) motion for judgment as a matter of law and found substantial evidence supported an earlier jury verdict that certain batches of drug product manufactured by Hospira failed to qualify for the safe harbor created by 35 U.S.C. § 271(e)(1). In its decision, the court cited, inter alia, Hospira’s communications describing batches for use as “commercial inventory” and evidence demonstrating that testing performed with certain batches was not required for U.S. Food and Drug Administration (“FDA”) approval as supporting the jury’s verdict.
I. Overview of Section 271(e)(1) “Safe Harbor”
Section 271(e)(1) creates an exception to patent infringement for activities related to obtaining approval for drug products from the FDA. Under this safe harbor, manufacturers are able to engage in otherwise-infringing activities provided that such infringing activities are “solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary products.”
II. Hospira’s Safe Harbor Defense Denied at Summary Judgment, Trial, and Post‑Trial Stages of the Litigation
The Amgen v. Hospira action involves Plaintiffs Amgen, Inc. and Amgen Manufacturing, Limited’s (collectively, “Amgen”) U.S. Patent Nos. 5,856,298 (“the ‘298 patent”) and 5,756,349 (“the ‘349 patent”); both of which cover EPOGEN®, Amgen’s EPO product. In December 2014, Hospira submitted Biologics License Application (“BLA”) No. 125-545 to the FDA, seeking approval for a biosimilar version of EPOGEN®.
Following a five-day trial in September 2017, a jury found only seven of the 21 lots of EPO as entitled to protection under the safe harbor.
In its post-trial motion, Hospira alleged that no reasonable juror could find that the safe harbor defense did not apply to all 21 of its EPO lots because “each batch was used for . . . biosimilarity testing, updating product specifications, process validation, stability testing, or continued process validation.”
III. Considerations Following
Amgen v. Hospira
The history and ultimate outcome of the Amgen v. Hospira district court litigation illustrate potential challenges for biosimilar manufacturers asserting safe harbor defenses under 35 U.S.C. § 271(e)(1), and opportunities for patent owners to successfully overcome such arguments. Although Hospira had argued batches it produced prior to FDA approval were entitled to the defense, the court first found there was a sufficient factual dispute to warrant a jury decision on the issue, and then held that substantial support existed to uphold the jury’s finding of infringement. The court’s decision on Hospira’s motion for judgment as a matter of law affirming the jury’s verdict suggests batches may not be entitled to this defense merely because some amount of product from each batch is used for regulatory testing.
Biosimilar makers should note that additional factors may influence the fact finder as to whether the safe harbor defense applies. As one example, the fact finder may consider whether batches are used for testing required for FDA approval as opposed to post-approval testing, such as release testing. The fact finder may also consider whether batch testing is described in the BLA. The Amgen v. Hospira litigation also made clear that how batches are described in communications with the FDA and in company documents can be instructive. Accordingly, biosimilar makers may want to carefully consider what will constitute a commercial batch and may want to avoid labeling batches as commercial when those batches will also be used for testing as required by the FDA. By doing so, biosimilar makers may avoid giving their opponent additional ammunition by which to attack a safe harbor defense. Conversely, patent owners should be vigilant to identify any facts such as these that would support a challenge to a Section 271(e)(1) safe harbor defense.
In sum, it remains to be seen whether the Amgen v. Hospira litigation is the beginning of a trend toward significantly narrowing the safe harbor defense. Until the answer to that question becomes clear, biosimilar makers may wish to consider a conservative approach toward manufacturing batches that are not necessary to obtain regulatory approval. To the extent that the purpose of a particular batch is unclear, biosimilar makers may wish to avoid building an internal record that takes a position that may prove unhelpful to a safe harbor defense in later litigation. The Amgen v. Hospira decision may be appealed to the Federal Circuit, providing further clarity on these issues.