The FDA has savaged U.K.-based Porton Biopharma (PBL) in a warning letter for repeated contamination of batches of Erwinaze, a blood cancer drug for children that it manufactures for Jazz Pharmaceuticals. The lifesaving med went into short supply last year because of repeated problems at the sterile manufacturing site.
The FDA said Porton, even after earlier citations from the FDA, had not thoroughly investigated why batches of Erwinaze had been contaminated with visible contaminants, including metal, cardboard and some of a “proteinaceous nature.” Further, the FDA said Porton had used new cell banks in the sterile manufacture of Erwinaze without first getting the FDA’s approval.
The fact that “persistent contamination hazards and drug quality issues" had not been resolved, even after a sit-down meeting with the FDA and ongoing discussions, illustrates weak management oversight at the facility, the FDA letter said.
In an emailed statement PBL said it has hired "experts" to asset it and has implemented "measures to deal with the immediate manufacturing capacity constraints." The company also said it is also building a new facility. "We are making important progress and are committed to working with the BLA holder and the FDA to resolve all issues. We are confident that we will fully address the FDA’s concerns."
Jazz said in an emailed statement that it understands the concerns outlined by the FDA in the warning letter and is "working in full collaboration with PBL and the FDA to do everything possible to avoid disruption of patient care while we accelerate resolution of the manufacturing deviations."
According to the warning letter, the FDA first pointed out problems in Porton’s aseptic manufacturing during an inspection in January 2015. Porton offered up solutions and even met with the FDA in November of that year.
But when inspectors returned in March 2016, they found more problems. The FDA said that the CMO had reported visible metal particles in 237 units in one batch of Erwinaze, which Porton decided must have come from the bottle stoppers provided by a supplier. But Porton didn’t work with its supplier and figure out how to fix the problem until the failure was pointed out in the follow-up inspection, the FDA said.
The fact that cardboard fibers were found in another batch and the proteinaceous particulate in another, “call into question your ability to prevent contamination,” the agency told the company.
The agency also cited the facility for using new cell banks without first getting approval for the change from the FDA, “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.”Erwinaze was developed by Eusa Pharma and approved in 2011 as a treatment for a small subset of patients with acute lymphoblastic leukemia, mostly children, who have allergic reactions to the traditional therapy which is made from E. coli. Jazz got the drug in 2012 with the $700 million buyout of Eusa.
In November, Ireland-based Jazz began warning (PDF) healthcare providers that because of the ongoing contamination problems at Porton, it would soon be out of Erwinaze and it would be weeks before it would be available again. The shortage left some parents desperate, worried their children would not survive the shortage.
Last month, Jazz sent a new letter (PDF) to providers saying that that latest batch of the drug also had visible particulate in some vials. It said it had pulled what it believe were all of the affected vials off the market but to make sure that patients were not injected with potentially harmful particulate, doctors should inject the drug intramuscularly and not intravenously.
Porton is building a new facility to manufacture Erwinaze and other sterile drugs.
Editor's Note: The story was updated with a comment from Porton.