Drugs

EpiPen Contractor Warned on Drug CGMP, QS Violations

David McFarland

— 2 min read
Share

A 2/20-3/24 FDA inspection at Pfizer’s Meridian Medical Technologies manufacturing facility in Brentwood, MO, which holds a contract to produce EpiPen and EpiPen Jr. for Mylan, found significant violations of current good manufacturing practice (CGMP) requirements for combination products, according to a 9/5 Warning Letter from the agency’s Kansas City District Office. The inspection also found that the firm’s combination products are adulterated due to Quality System Regulation (QS) violations. Specific violations referenced in the letter were: 

  •          failing to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch was already distributed;
  •          failing to establish and follow adequate written procedures describing the handling of all written and oral complaints regarding a drug product;
  •          failing to adequately analyze processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems, employing appropriate statistical methodology where necessary to detect recurring quality problems;
  •          failing to adequately establish and maintain procedures for verifying the device design, confirming that the design output meets the design input requirements, and documenting results of the design verification in the design history file; and
  •          failing to adequately establish and maintain procedures for validating the device design to ensure that devices conform to defined user needs and intended uses, including risk analysis where appropriate.

The letter says that Meridian “failed to thoroughly investigate multiple serious component and product failures for your EpiPen products, including failures associated with patient deaths and severe illness. You also failed to expand the scope of your investigations into these serious and life-threatening failures or take appropriate corrective actions, until FDA’s inspection.”

FDA notes that Meridian and Mylan have a quality agreement regarding the manufacture of EpiPen products. “You are responsible for the quality of combination products you produce as a contract facility, regardless of agreements in place with Mylan Specialty or with any of your suppliers,” the letter says. “You are required to ensure that your combination products are compliant with the CGMP requirements applicable to each manufacturing process that occurs at your facility.”

A 2014 inspection found similar CGMP violations, FDA says. The company proposed specific remediation for the violations in its 12/17/15 response, and “these repeated failures demonstrate that your facility’s oversight and control over the manufacture of these products is inadequate.”

Meridian was told to respond with a list of actions it has taken since the inspection to correct the violations and prevent their recurrence, with a timetable for completion.

Read more