Celltrion, an Incheon, Korea-based life-sciences company, has received a Warning Letter (dated January 26, 2018) from the US Food and Drug Administration (FDA) for good manufacturing practice (GMP) violations for finished pharmaceuticals. The Warning Letter was in response to an inspection the FDA carried out from May 22 to June 2, 2017 at the company’s drug-manufacturing facility in Incheon, South Korea.

The Warning Letter raised issues related to certain manufacturing processes at the facility. The FDA cited the firm for failing to establish and follow appropriate written procedures to prevent microbiological contamination of drug products purporting to be sterile and that include validation of all aseptic and sterilization processes. Specifically, the FDA identified multiple poor aseptic practices during the set-up and filling of certain batches. The FDA also noted deficiencies for smoke studies for restricted access barrier system (RABS) filling and loading areas. The agency also noted multiple deficiencies related to the validation of the company’s aseptic processes, including media-fill deficiencies.

The FDA also cited the firm for failing to thoroughly investigate discrepancies or failure of a batch or any of its components in meeting specifications. The FDA noted that from October 2015 to May 2017, the company received approximately 140 complaints relating to a certain product in vials with a substantial number of these complaints for US batches. The FDA said that the defect “can significantly affect” multiple quality attributes of the product over its shelf life. The FDA said that the company investigated recurring complaints without resolution for more than two years. The FDA said that the company failed to thoroughly investigate visible particle issues in a finished drug product.

“We are making progress addressing these concerns, and we are committed to working with the agency to fully resolve all outstanding issues with highest priority,” said the company in a January 30, 2018 statement.  Upon review of the agency’s feedback outlined in the letter, the company said it will provide a full response to the FDA within the next 15 days [from January 26, 2018].

In its Warning Letter, the FDA outlined several requirements for the company to do, which included: (1) specify a plan to assure appropriate aseptic practices and cleanroom behavior during production; (2) provide a thorough risk assessment that evaluates how poor aseptic technique and cleanroom behavior such as that observed during the inspection may have affected quality and sterility of the company’s drugs; (3) provide a corrective action and preventive action (CAPA) plan to fully remediate any contamination hazards to sterile product contact surfaces during set-up, including improved equipment design and procedures and provide a CAPA plan with timelines to address the findings of the contamination hazards risk assessment; (4) provide a standard operating procedure (SOP) that requires routine sterilization of the company’s RABS and specifies maximum use time; and (5) provide a comprehensive identification of all contamination hazards with respect to the company’s aseptic processes, equipment, and facilities.

The company said the Warning Letter does not affect Celltrion’s ability to manufacture and supply Inflectra (infliximab-dyyb) products, a biosimilar to Johnson & Johnson’s Remicade (infliximab), from the site in Incheon, South Korea. The company does not currently anticipate any impact on the supply of Inflectra based on the Warning Letter. Inflectra is manufactured by Celltrion for Pfizer through its subsidiary, Hospira, which Pfizer acquired in September 2015 for $17 billion. In 2009, Hospira and Celltrion formed a pact for developing biosimilars, including Inflectra. Pfizer holds exclusive commercialization rights to Inflectra in the US and certain other jdurisictions. The FDA approved Inflectra from Hospira and Celltrion in April 2016.

Source: Celltrion and FDA