FDA faults Celltrion plant that makes Pfizer's Remicade copy, Inflectra

A Celltrion plant in South Korea that produces Pfizer's biosimilar of Remicade has been written up by the FDA in a Form 483.

Pfizer is leaning heavily on Celltrion for biosimilar development and manufacturing, but its South Korean partner has stumbled with an FDA inspection that uncovered issues at its plant in Incheon.

The FDA found shortcomings in a variety of areas during a May inspection, but its 10-page, 12-observation Form 483 focused (PDF) to a large degree on Celltrion’s slow response to investigating 140 customer complaints of issues tied to vial stoppers. Those were complaints over vials of the Remicade biosimilar that Pfizer has sold for several years in Europe as Remsima and launched last year in the U.S. as Inflectra. 

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The FDA also faulted Celltrion’s methods for preventing contamination of the sterile products and for not promptly investigating reports of particulate in some vials.

In an email this week, a Celltrion spokesperson called the Form 483 routine and said the company has responded to the agency with an action plan. It said it was “confident” that no drug batches released in the U.S. or Europe had been affected by the problems noted during the FDA inspection.

Celltrion pointed out that the 140 complaints noted in the Form 483 were over vials of Inflectra in Europe, and “were not received by the FDA for Inflectra being marketed in the US.” It said the European Medicines Agency has reviewed and approved the fixes it has put in place to address the vial stopper concerns.

That wasn’t the case when the FDA made its visit to the facility and discovered that Celltrion has received the 140 complaints between Q4 2015 and the May inspection. At the time, the agency said, “Adequate corrective and preventive actions have not yet been implemented to address already released product, eliminate the root causes for on-going manufacturing” issues and ensure that faulty vials can be detected and removed prior to the release of batches.

The exact nature of the vial stopper issue was not clear, because the publicly released Form 483 is heavily redacted.

There other issues as well. The FDA also faulted the plant management for not quickly investigating reports of particulate in vials, noting in one case that it took three weeks to open investigation after receiving a report of particulate that was eventually determined to be fibers.

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The FDA concerns come at a pivotal time for Pfizer, which in the fall launched Inflectra in hopes of winning some of the $4.5 billion in sales the Johnson & Johnson drug enjoys in the U.S. It reported global sales of $78 million in Q2, most of that in Europe. It sold about $17 million worth of the drug in the U.S. But Pfizer now faces competition from Samsung and marketing partner Merck & Co., which in July released their Remicade copycat at a 35% discount to the J&J drug.

Inflectra originally came out at 15% discount to Remicade but Pfizer has cut the price as the market has changed. A Pfizer spokesman said in an email today that its average selling price (ASP), currently is $753.40 per 100mg vial, a 35% differential compared to Remicade’s wholesale acquisition cost and the same as Merk's Renflexis list price. He said starting Oct. 1, Pfizer will drop the ASP to $737.91 per 100mg vial. 

RELATED: Targeting a $5B brand, Samsung and Merck launch Remicade biosim at 35% discount

In a note to investors when the Form 483 came to light, Bernstein analyst Ronny Gal indicated it was an unexpected gift to Merck, which he surmises the company will exploit in its marketing against the Pfizer drug.

J&J also is not surrendering Remicade market share easily. It has been fighting biosimilar attacks in court while cutting special Remicade pricing deals with payers. Gal told clients J&J has exclusive contracts in nearly half the market, bundled products together for large hospitals and offered deeper discounts to large independent infusion centers. Those efforts were reflected in its Q2 results with Remicade sales off only 5%.

RELATED: FDA advances two more Herceptin biosims—this time from Amgen and Teva—as Roche braces for impact

Meanwhile, Celltrion hopes to get more biosimilars approved for the U.S. market, which would come out of its plants in South Korea. Those include a copy of Roche’s Herceptin, on which it has partnered with Teva. The FDA recently accepted their application for that drug, as well as for one from Amgen and Allergan.