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Drug manufacturing woes grow

FDA inspections raise issues that delay approvals

by Ann M. Thayer
January 9, 2017 | A version of this story appeared in Volume 95, Issue 2

Several companies are trying to overcome manufacturing roadblocks that stopped their new drugs from being approved by FDA in 2016. In responses to their applications, FDA cited problems found during preapproval plant inspections. Most problems were in Western facilities and centered on formulation, rather than active ingredient production.

Only two companies—AstraZeneca and Opko Health—responded to the problems in time to refile in 2016. And Opko got an approval after its manufacturing partner, Catalent, fixed problems at its St. Petersburg, Fla., extended-release capsule plant. Ocular Therapeutix expects to refile this quarter, while Roche’s review is delayed until late March.

Meanwhile, Sanofi and Regeneron Pharmaceuticals face a major setback for the potential blockbuster drug sarilumab, a monoclonal antibody targeting the interleukin-6 receptor. If approved, it will compete in the rheumatoid arthritis field against Abbvie’s Humira, the industry’s top-selling drug.

During an October earnings call, Sanofi CEO Olivier Brandicourt said the company was working quickly to address deficiencies at a fill-and-finish facility in Le Trait, France. He said the issues should be resolved ­before the expected March review date for an even bigger potential blockbuster, the new ­dermatitis treatment dupliumab.

After analyzing the warning letter, Leerink stock analyst Geoffrey C. Porges was less optimistic, given the scope of the problems. “It is possible that the FDA has deliberately ‘gone overboard’ in the granularity of the issues they have cited for remediation, with the intention of sending a sharp wake-up call to Sanofi,” he told clients.

The preapproval manufacturing issues cited in FDA’s responses are noteworthy because the agency’s focus is usually on safety and efficacy concerns, chemistry and manufacturing controls, or bioequivalence deficiencies, points out Arlene Ocampo of Lachman Consultants on the firm’s website.

It’s unclear whether the rise is the result of heightened vigilance by FDA. But in the past two years, FDA has been developing a more integrated review and inspection process through its Office of Pharmaceutical Quality, including a new inspection protocol project. And furthering its quality initiative, the agency published guidance in November on how companies can submit quality metrics data.


Manufacturing problems delayed new drug applications in 2016.

Opko HealthRayaldeeMarch
Soon to be refiled  
Ocular TherapeutixDextenzaJuly
Not yet refiled  
Portola PharmaceuticalsAndexXaAugust
Valeant ­PharmaceuticalsLatanoprostene bunodJuly

Source: Companies



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