Life science manufacturing giants Baxter Healthcare and Amgen were each sent Warning Letters by the US Food and Drug Administration (FDA) in January 2014 chiding them for medical device manufacturing problems at their respective facilities.
The Amgen letter refers to a June 2013 inspection of the company's Thousand Oaks, CA facility where it makes three products:
- Prolia with prefilled syringe and manual needle guard
- Enbrel lyophilized vial and diluent with vial adapter
- Enbrel prefilled syringe with "Sureclick 1.5" auto injector
FDA's inspection determined that the medical device components of the three combination devices had been manufactured under deficient good manufacturing practices (GMPs), leaving them adulterated under Section 501(h) of the Federal Food, Drug and Cosmetic Act (FD&C Act).
Specifically, the company was alleged to have failed to "establish and maintain design validation procedures," which are used to ensure that the devices meet user needs through testing in actual or simulated use conditions. While the company indicated to FDA that it would remedy this situation, FDA noted that its response was deficient in that it "did not describe the actions [the company] will take to ensure that established procedures will be followed in the future." Regulators also questioned whether the proposed studies-assumed to be simulation studies-would adequately convey actual use conditions.
The Warning Letter also alleged that Amgen had failed to document, validate and verify design changes prior to their implementation. One noted change to Enbrel's vial adapter had "resulted in a significant increase in product complaints" observed by the company. Amgen has since stopped using the adapter, it told FDA, but the agency said it had not seen evidence the company would refrain from similar activities in the future.
Finally, the letter claims the company "failed to evaluate and select potential suppliers, contractors, and consultants on the basis of their ability to meet specified requirements, including quality requirements." In at least one case, the company was unable to certify that a contractor had been properly evaluated.
A second and more extensive letter to Baxter Healthcare was sent after a July and August 2013 inspection of the company's Round lake, IL facility where it manufacturers the following three devices:
- HomeChoice Automated Peritoneal Dialysis (APD) Systems
- HomeChoice Pro Automated Peritoneal Dialysis (APD) Systems
- IPUMP syringe-style intravenous, epidural or subcutaneous delivery infusion pump
All three are Class II (moderate risk) medical devices and, according to FDA, adulterated under the FD&C Act due to GMP deficiencies found during its inspection.
The agency's letter to Baxter appears to be more serious than the one sent to Amgen in that it cites five instances in which current deficiencies had been noted in a previous Warning Letter to the company.
For example, the company was alleged to have improperly invested device failure reports by conducting less-than-thorough assessments. Some reports were "either incomplete or lacking of conclusions and corrective actions of the reviews," FDA wrote. Three other observations were also repeats:
- Baxter's alleged failure to "adequately establish procedures for corrective and preventive actions"
- Failure to establish and maintain corrective and preventive action procedures that include requirements for ensuring the corrective and preventive action is effective
- Failure to adequately establish procedures to ensure equipment is routinely calibrated, inspected, checked and maintained
All observations had previously been made in 2012, FDA said.
Two additional observations noted failure to adequately establish design validation procedures or valid statistical techniques to verify product capabilities and characteristics.
Both companies were given FDA's customary warning that they had 15 days in which to respond to FDA, after which time the agency may initiate regulatory actions if insufficient corrective actions have been taken.