Sandoz and Momenta Pharmaceuticals confirmed last week that Pfizer CentreOne – their contract manufacturing partner for Glatopa, a generic version of Teva’s bestseller Copaxone (glatiramer acetate injection) – received a warning at its McPherson, Kansas site.
And now the US Food and Drug Administration (FDA) has published the February 14 letter highlighting details of significant violations of current good manufacturing practice (cGMP) observed during an inspection last May and June.
Specifically, the facility was criticised for failing to adequately investigate complaints regarding particulate matter found in a number of sterile injectables.
“The presence of visible particulates in sterile injectable products is an indication of a significant loss of control in your manufacturing process and represents a severe risk of harm to patients,” the FDA said.
One example was of a cardboard contaminant found in vials of vancomycin hydrochloride late December 2015, most likely related to the handling of vial stoppers.
“Extrinsic contaminants, such as cardboard, pose a significant risk to patients and indicate that your process for manufacturing sterile injectable products is out of control.”
And while the affected lot was recalled, the Agency said it was more than four months after receiving the initial product complaint and further action was not taken.
Unidentified “brown agglomerates” in an unspecified number of vials of ketorolac tromethamine injection, 30 mg/mL were also inadequately investigated, and the firm failed to provide either a scientific rationale for the conclusions reached in investigations or information on the methodologies used during testing.
Poor aseptic technique
Failures in establishing in-process specifications, establishing scientifically sound and appropriate laboratory controls, and controlling rejected in-process materials under a quarantine system were also highlighted by the FDA.
As was the facility’s poor aseptic technique in manufacturing a lot of hydromorphone:
“The investigator observed the introduction of a bottle of sterile water with a shrink- wrapped plastic tamper-resistant seal into the (b)(4) isolator material transfer chamber,” the FDA said.
“Our inspection documented that at least two, and possibly four, of your operators observed the presence of this sealed bottle in the chamber, despite the explicit prohibition in the SOP. Our investigator identified this issue during production, and you were unable to explain why your operators did not recognize this problem.”
When Pfizer acquired Hospira for $17bn in 2015, the firm said it felt “comfortable that issues raised by regulators either have been, or are being properly and adequately addressed.”
The McPherson site is one of a number of former Hospira sites which have struggled with compliance issues over the past few years, and this was noted by the FDA which cited other warning letters at plants in India, the US, Australia and Italy.
“These repeated failures at multiple sites demonstrate that your company’s oversight and control over the manufacture of drugs is inadequate,” the FDA said.