The European Medicines Agency is seeking information on an implant sold by a Medtronic unit after inspectors determined that a U.S.-based supplier of an active substance for the product had deviated from good manufacturing practices.
Specifically, the EMA’s Committee for Medicinal Products for Human Use is asking Medtronic BioPharma, which is based in the Netherlands, how the findings from an April inspection of an Integra LifeSciences facility in Plainsboro, N.J., affect the risk-benefit balance of InductOs. The implant is used to treat patients with spinal disc problems and leg fractures.
The implant kit includes a powder that contains dibotermin alfa, a solvent, as well as an absorbable collagen sponge, an excipient.
During the inspection, investigators from the Netherlands and Spain found that the Intergra facility didn’t have adequate measures in place to prevent particle contamination of the sponges, which remain in the body until they are degraded. The investigators recommended that importation of InductOs into the EU be halted and Integra’s GMP certificate withdrawn.
The action could lead to a shortage of the product in the EU starting in October, the EMA says.
The findings follow a January 2014 inspection of the Integra facility that turned up numerous GMP violations, with the main concerns being particulate contamination and sterility assurance. The company created a corrective action plan that was rejected. Integra sent a new plan the following month that was accepted, resulting in the receipt of a restricted GMP certificate that was valid until January 2015.
In the wake of the most recent inspection, Integra submitted a follow-up corrective action plan that was received in June and subsequently rejected due to a lack of clarity on the nature and extent of the contaminants. “Metal fragments, salt residues, hairs and PVC fibers are identified, but for none of these the most likely source has been established,” according to a statement of noncompliance with GMP. No new GMP certificate was issued.
To assess whether a change to InductOs’ marketing authorization is needed, CHMP is reviewing the inspection findings on the product’s overall risks and benefits. The committee has asked Medtronic for a timeline of steps it intends to take to ensure the manufacturing of ACS will be GMP-compliant again, including specific measures Integra already has undertaken.
In addition, the Committee wants information on the number of batches available in the EU and vulnerable subpopulations treated with the product that should receive priority treatment.
A Medtronic spokeswoman tells IDDM that the company takes the findings seriously, adding that the EMA has said that there is no current indication of risk to patients and no product recall.
She says that the EMA has informed healthcare professionals that they should use InductOs per the instructions and that any product they currently have or will receive may be used.
“Medtronic BioPharma is working closely with Integra LifeSciences in an advisory capacity to develop an action plan to remediate the quality issues in a timely manner,” the spokeswoman tells IDDM. “At this time, there is no impact to any regions outside the EU or Switzerland.”
— Elizabeth Hollis