Updated: FDA Form 483 for Celltrion Site Manufacturing Remicade Biosimilar

Regulatory NewsRegulatory News
| 06 September 2017 | By Zachary Brennan 

The US Food and Drug Administration (FDA) on Wednesday released a Form 483 sent to Korea’s Celltrion with 12 observations, which an industry analyst believes could be the reason why the commercialization of Celltrion and Pfizer’s Inflectra (infliximab-dyyb), a biosimilar to Remicade, has not gone as well as planned in the US, though Pfizer says the limited uptake has more to do with Johnson and Johnson's exclusionary contracts.

The Form 483 for the Incheon, Korea-based manufacturing site, following an inspection last May and June, includes several repeat observations, including the site’s failure "to demonstrate that your manufacturing process can reproducibly manufacture drug substance meeting its predetermined quality attributes."

Celltrion told Focus in a comment that it "is confident that no drug product batches have been released to either the US or EU market that may have impacted by any potential quality maintenance process listed in the form 483, and we do not anticipate any disruption to the supply of our products in the future which may be caused by the observations listed in the FDA form 483."

The company also said the critical issue from the 483 is related to vial stoppers and that FDA "is aware of 140 complaints (presumably from physicians) about the stopper. Per Pfizer, these complaints are from a European source."

FDA inspectors also found that the source of particles detected in a visual inspection "has not been identified," and there was mold on some of the facility’s walls.

In a note to investors, Bernstein biotech analyst Ronny Gal said some of the problems "should be solvable" though the observations suggest Celltrion "ran into a solid inspector who picks on stuff like how they label equipment and validating the cleaning supply for washing the walls (as well as more material stuff like computer record)… However, the inspector did not suggest that (i) Celltrion has intentionally hid stuff from FDA, although there some 'unofficial' documentation and testing which FDA hates; (ii) bad product is released or could be released, (iii) there are ‘structural’ problems with the facility or culture (e.g. poor airflow/ fundamental misunderstanding of requirements)."

For the first quarter of 2017, Pfizer reported Inflectra and Remsima, which is the name of the Remicade biosimilar in the EU, sales as $78 million, which is more than double what the company reported in the same quarter in 2016, but also shows the company has not yet nabbed a large share of the market from the brand name product.

Gal noted recently that the Inflectra's "very modest market inroads" may also be due to an effective strategy from Johnson & Johnson.

A Pfizer spokesman told Focus: "Inflectra uptake in the US is being limited due to exclusionary contracting of originator companies with insurers and providers. In the commercial insurance space our lower-priced Inflectra has not received access at parity to Remicade and remains in a disadvantaged position despite recent price increases taken by J&J. This is in contrast to Medicare, where biosimilar coverage has been strong."  

Although as prices come down with more Remicade biosimilar competition, the share of biosimilars may continue to increase.

Pfizer noted Inflectra’s list price (Wholesale Acquisition Cost (WAC)) is $946.28 per 100mg vial which is 19% lower than the current wholesale acquisition cost (WAC) for Remicade. The list price is not inclusive of price discounts, rebates and other factors. And beginning 1 October, Inflectra’s Average Selling Price (ASP) will be $737.91 per 100mg vial vs. Remicade’s ASP of $822.96.

Form 483

Updated with comment from Pfizer and updated prices for Inflectra, and updated on 9/25 with comment from Celltrion.


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