The Letter - issued by the Center for Biologics Evaluation and Research division of the US Food and Drug Administration (FDA) - followed an inspection at Instituto Bioclon’s biomanufacturing facility in Mexico City, which produces the first FDA approved anti-venom for the treatment of bark scorpion stings.
The Letter cited a number of violations in current Good Manufacturing Practice (cGMP), including: failures to ensure procedures to prevent microbiological contamination of the sterile drug were followed, issues in controlling the temperature of media fill vials, inadequate growth promotion testing of media, and failure to establish time limits for the sterile filtration and aseptic filling of Anascorp.
The firm was also pulled up on its failing to ensure staff involved with manufacturing processes had adequate “education, training or experience, or any combination thereof,” which led to problems with sterility testing records for Anascorp.
“Additionally, significant deviations in the manufacture of your intermediates were observed during the inspection,” the letter stated.
However, Bioclon has already commenced addressing these issues, according to Rare Disease Therapeutics (RDT), a Tennessee-based biopharma firm specialising in orphan drug products who is in partnership with Bioclon for the exclusive rights to sales, marketing and distribution of their anti-venoms in the US.
“The Warning Letter was a result of an inspection in January and a programme of remediation was immediately begun,” Jude McNally, VP Medical Science Liaison at RDT told Biopharma-Reporter.com. “We expect this to be resolved very quickly and are completely confident a re-inspection will successfully lead to a close-out letter.”
Furthermore he did not anticipate a shortage of Anascorp due to both the remediation effort and the low demand for the drug, used by only about 250 patients a year in America’s South-West.
Not all scorpion stings are dangerous, but stings from the Centruroides sculpturatus (bark scorpion) which is native to Arizona can be deadly, McNally said, and therefore RDT partnered Bioclon to bring the anti-venom to the US.
The facility in Mexico City manufactures Anascorp in a similar way to other biologics he explained, by exposing host animals to the antigen over a period of time such that they develop high titres of AD2 antibodies against the venom.
“Plasma is obtained from the host animal which contains the desired antibodies,” he continued, adding: “There are purification and separation steps and pepsin digestion to yield F(ab’)2 antibody fragments.”
RDT and Bioclon have also collaborated to produce an anti-venom against pit-vipers, under review from the FDA, and a treatment against bites from the black widow spider – currently undergoing Phase III trials.