Biosimilars, Biostatisticians, and the New EEU

There are very few days during which the worlds of drugs and medical devices are entirely quiescent, thanks to very active American courts and international regulatory churn. There is some good news in all this, but how good is it?

If you’re in the biosimilars business, the latest news is quite good, indeed.

SCOTUS rules for Sandoz

The U.S. Supreme Court ruled on June 12 that makers of biosimilars do not have to wait six months after the issuance of a biologics license application to begin marketing that product, a development that could bring some less costly biotech drugs to market more quickly and possibly take a bite out of spending on these agents.

In a 9-0 vote, the Court ruled in favor of Sandoz in Sandoz v. Amgen, a case that made a stop at the Court of Appeals for the Federal Circuit, where the outcome was quite different. Sandoz had argued that the terms of the Biologics Price Competition and Innovation Act of 2009 had essentially worked to add half a year of exclusivity to the 12 years already granted by the statute, and by some accounts, Sandoz’s Zarxio is about 15 percent less expensive than Amgen’s Neupogen, a drug for chemotherapy-induced neutropenia.

The news might not change the field dramatically in the near term, given that the FDA has approved only about half a dozen biosimilars to date, but one possible candidate for a quick entry to market is an oncology biosimilar for Avastin, which will undergo an FDA advisory committee review in mid-July. In an ironic twist, Amgen teamed up with Allergan to produce this biosimilar.

Expert witness refuted in Zoloft lawsuit

Pfizer scored a victory in the running lawsuit pertaining to the company’s flagship antidepressant Zoloft, but what may have been the most interesting part of this story is that a court rejected expert testimony relating to allegations that the selective serotonin reuptake inhibitor (SSRI) causes congenital heart defects.

The decision may have brought to a close an effort by more than 300 litigants, which absorbed a second consecutive negative outcome in the U.S. Court of Appeals for the Third Circuit. Both the appeals court and a district court decreed that the expert witness, Nicholas Jewell, a biostatistician at the University of California at Berkeley, had failed to plausibly link the drug to the birth defects. Among the problems with Jewell’s presentation is that he had rejected meta-analyses he had previously cited in a separate lawsuit pertaining to another SSRI.

Whether the plaintiffs will take this lawsuit any further is difficult to forecast, but a footnote on page 10 of the Appeals Court decision remarked that the plaintiffs’ attorneys had conceded that they are “unable to establish general causation” if the courts jettisoned Jewell’s testimony. Summary judgment was granted in favor of Pfizer.

This is not the only multi-district litigation keeping attorneys at Pfizer busy, however. A very active set of lawsuits dealing with proton pump inhibitors and purportedly associated kidney damage would seem to implicate the OTC version of Nexium, marketing rights for which Pfizer picked up five years ago in a deal with AstraZeneca. The U.S. Judicial Panel on Multidistrict Litigation (JPML) declined in January to consolidate these lawsuits, but another motion for consolidation has been filed by attorneys with Seeger Weiss of New York.

Regulations, regulatory agreements on the move

Efforts to ramp up medical device regulatory schemes in outside-U.S. jurisdictions are nothing new, but device makers can add Malaysia and the Eurasian Economic Union (EEU) to the list of national and international entities diving into deeper regulatory waters. The news for device makers is somewhat mixed, but greater clarity alone is sometimes enough to overcome other considerations.

First, Malaysia’s Medical Device Authority has declared that adverse events associated with medical devices will have to be reported to the agency within 30 days. This apparently applies to all devices that are on the Malaysian market, regardless of where the adverse event took place. Any fatalities have to be reported within 10 days, and device makers have a mere 48 hours to advise the agency of any problems that might carry a public health consideration.

The EEU continues to work toward a single market for drugs and devices, a move which if successful would capture the markets of Russia and four other nations for a total 2015 population of nearly 184 million. There are reports that Tehran is interested in a free trade agreement with the EEU, although there is no indication that Iran would take part this new med tech regulatory bloc despite the deepening geopolitical ties with Moscow. Serbia is likewise said to be interested in doing business with the EEU, but it’s not clear whether Belgrade has full-blown membership in mind, either, although the protracted and difficult negotiations for entry into the European Union might strike some as suggestive.

To date, the EEU regulatory regime lacks several critical documents, such as a framework for quality management systems. Registration requirements for this international regulatory system would be phased in over the next four years, however, giving industry a little breathing room for offerings already available in this market.

Breathing Room but Hefty Fines: NIH’s Final Rule for Study Registration

The National Institutes of Health has finalized the rule for registration of drug and device trials at clinicaltrials.gov, one of the most commercially important documents the agency has published in decades. While the NIH did relent on a couple of points essential to industry, it appears that the requirements will be retroactive, thus exposing device makers to a fine of $10,000 per day per violation for any studies that are not up to date regardless of when those studies first appeared at the clinical studies website.

The NIH notice of proposed rulemaking (NPRM) came to light in 2014, and the docket for this proposal drew more than 900 comments, some of which was reflective of a considerable amount of consternation by those in the life science industries. Among the concerns expressed by industry early on was that the draft rule would have forced the disclosure of confidential information that could compromise a drug or device maker’s competitive position. However, industry was not the only target of the rule. By some accounts, most of the failures to register a study are accounted for by researchers working on studies not sponsored by industry. In any case, members of the NIH team said in an article in the New England Journal of Medicine that only about 10% of the studies registered at clinicaltrials.gov include results data from the registered study.

The retroactive nature of the mandate suggests the FDA will be on the look-out for violations of the final rule by drug and device makers. There does seem to be a split on the question of Section 522 post-market surveillance studies, however. The NIH flowchart regarding clinical trial compliance under the Food and Drug Administration Amendments Act of 2007 – the law that gave rise to the NIH rule – suggests that Section 522 studies are only required to register at the NIH site if those studies are of devices in pediatric populations

Nonetheless, any laggardly performance in these non-pediatric Section 522 studies might show up on the FDA radar screen if the agency starts hearing from the public, or from Capitol Hill, about clinical trial compliance generally.

Makers of combination drug-device products were none too happy to see that the NIH draft had stated that trials of combination products would be treated as pharmaceutical agents for the purposes of trial registration. The NIH heard from a number of entities that the final rule ought to reflect the designation applied to the product by the FDA’s Office of Combination Products, which itself has come under a barrage of criticism of late. The final NIH rule conceded the point

On the point of disclosure of trade information, the NIH opted to give sponsors of clinical studies of unapproved drugs and devices a year after the study’s primary completion date to register the results of the study, although sponsors can avail themselves of an additional two years if they certify that they intend to continue development of the product in question. Disclosure of dead-end studies would be required upon the sponsor’s notification of abandonment of the study.

As for timelines, the NIH said the final rule goes into effect on Jan. 18, 2017, and that compliance will turn into enforcement three months later, on April 18, 2017. That leaves sponsors less than six months to determine which of their studies are subject to the final rule and get those studies’ data updated. After all, $10,000 per violation per day can add up quickly.

Nadcap-like Program Holds Promise for Recall Reduction and Enhanced Quality Assurance for Medtech Industry

Courtney A. Stevens, Esq. | Senior Attorney, Medmarc Loss Control

The Performance Research Insitute (PRI), the not-for-profit organization responsible for spearheading the Nadcap program in the aerospace industry, is now turning its focus on medtech and hoping to have the same dramatic results in quality improvement and supply chain management there that is attributed to it for aerospace.

Despite the multitude of standards and regulations that medical device and component part manufacturers are subject to, and indeed the corresponding barrage of audits to which they are subjected, leaders in the medical device industry working with PRI identified a real gap left by all—critical processes. That is, the specific, crucial processes manufacturers use to create their products—heat treating, welding, sterilization, plastics molding, printed circuit board assemblies, cable and wire harness, etc.—are not the focus of quality management system audits. Suppliers can pass all audits imposed on them by the FDA and their OEM-customers without ever having the integrity of their critical manufacturing processes assessed by subject matter experts. PRI’s MedAccred program endeavors to change that, and has already been adopted by some of the largest medical device OEMs (original equipment manufacturer) in the industry, including Johnson & Johnson, Stryker, and Philips Healthcare.

This article, Bringing Nadcap to the Medical Industry, discusses the prospects for the program in greater detail.

FDA Pushes Back the Date for Issuing Generic Drug Labeling Rule to April 2017

Jordan Lipp, Esq. | Partner, Davis Graham & Stubb

On Thursday, the FDA again pushed back the date it expected to issue its final rule on generic drug labeling.  The final rule is now expected in April 2017.  The highly controversial proposed rule, as discussed in more depth in earlier posts, would permit generic drug manufacturers to unilaterally change their labels under the changes-being-effected (“CBE”) process.  Besides likely creating a bureaucratic headache and allowing generic and brand-name labels to differ (potentially in violation of the Hatch-Waxman Act), the proposed rule would also threaten to undermine the generic drug preemption decisions by the U.S. Supreme Court.  The proposed rule has generated significant political heat for these reasons, and the date for the final rule has already been pushed back several times.  Although the FDA did not state a reason for pushing back the announcement of its final rule again, the new date of April 2017 is, of course, after the next election.  Whether the final rule will ever be issued, and what it may look like, are open questions.  In any event, the wait continues.

 

What Scalia’s Passing Means to Life Sciences Companies

Courtney A. Stevens | Senior Attorney, Loss Control | Medmarc Insurance Group

The recent passing of Justice Antonin Scalia, the Court’s longest-serving justice, means more than just political scuttlebutt over who will get to appoint his replacement. For life sciences companies, it means the loss of a real ally in matters of tort liability and a powerful force in intellectual property.

Preemption

Scalia authored the 8-1 majority opinion in Riegel v. Medtronic, 552 U.S. 312 (2008), a pivotal decision in preemption jurisprudence that held that the Medical Device Amendments to the Food, Drug and Cosmetic Act (FDCA) preempted state-law claims relating to the safety and effectiveness of pre-market approval (PMA) devices. This effectively shields makers of PMA devices from products liability claims.

In Wyeth v. Levine, 555 U.S. 555 (2009), which undermined preemption in holding that FDA approval of a medication does not preempt state law failure-to-warn claims, Scalia joined the dissent (authored by Justice Samuel Alito). The dissent argued that this holding was inconsistent with their previously-adopted “conflict preemption” analysis.

Continue reading “What Scalia’s Passing Means to Life Sciences Companies”

Industry Victorious in Landmark Off-Label Promotion Ruling

Courtney A. Stevens, Esq. | Senior Attorney, Medmarc Loss Control

In what industry insiders are calling a “landmark decision,” on Friday, August 7, the Second Circuit granted for Amarin Pharmaceuticals’ motion for a preliminary injunction in an off-label promotion case, ruling that certain truthful, non-misleading statements about off-label uses are constitutionally protected under the First Amendment.

In reaching his decision, Judge Paul Engelmayor relied on the same court’s 2012 decision in U.S. v. Caronia, which overturned the conviction of a pharmaceutical sales representative for his off-label promotion comprised of truthful speech. Continue reading “Industry Victorious in Landmark Off-Label Promotion Ruling”