Erwinaze (asparaginase Erwinia chrysanthemi) is approved in the US to treat acute lymphoblastic leukemia in patients who have developed an allergy to E. coli derived chemotherapy drugs.
It is marketed by Jazz Pharmaceuticals, but made by Salisbury, UK-based and government-owned biomanufacturer Porton Biopharma Limited (PBL) which was on the receiving end of a US Food and Drug Administration (FDA) warning letter published yesterday.
Among the Agency’s concerns were deficiencies relating to aseptic operations, failures in investigating particulate matter observed in batches of Erwinaze, and problems with PBL’s management of process changes surrounding the working cell banks inadequate.
The process changes “were not approved by FDA before you manufactured, or your customer, Jazz, distributed, Erwinaze,” the Agency said.
“Specifically, working cell banks (b)(4) were used in commercial production prior to approval. These working cell banks were not reviewed and approved by the Agency for their suitability for Erwinaze manufacture, even though the changes in the source material or cell line have a substantial potential to adversely affect the identity, strength, quality, purity or potency of Erwinaze.”
While the FDA criticised PBL, it also noted that the firm was acting as a contract manufacturer for Jazz and as such both firms are “responsible for the quality of drugs released and ultimately administered to patients.”
Remediation
In a statement sent to Biopharma-Reporter, the firm said it is fully committed to working with “the Biologics License Application (BLA) holder, Jazz Pharmaceuticals, to develop a comprehensive Compliance Action Plan to address the concerns raised by the FDA.”
This includes conducting an ongoing end-to-end review of its manufacturing capacity, processes and procedures using third-party industry experts, as well as continuing to “increase the capacity of the Erwinaze manufacturing process, while also developing a longer-term plan for improvements in quality control, including improving the consistency and quality of primary packaging components.”
PBL is currently constructing a 530m2 bioprocessing development and manufacturing facility to support Erwinaze – known as Erwinase outside the US – at its site, set to open this year.
“We are confident that we will fully address the FDA’s concerns,” the firm said.