Parkedale Turns To Consultants After FDA Halts Fluogen Production

Parkedale Pharmaceuticals is drawing on advice from regulatory consultants The Biologics Consulting Group and regulatory legal counsel Arnold and Porter in "evaluating strategies pertaining to Fluogen," the company said.

The company is also evaluating possible management changes, Parkedale said.

FDA ordered the King Pharmaceuticals subsidiary to stop production of Fluogen (influenza virus vaccine, trivalent, types A and B) in a March 10 letter citing deviations from current Good Manufacturing Practice.

The Parkedale plant in Rochester, Mich., formerly owned by Warner-Lambert, was placed under consent decree in 1993 following the discovery of extensive manufacturing problems. King acquired the facility in February 1998 (¹ (Also see "King To Seek Release From Consent Decree on Former Warner-Lambert Plant" - Pink Sheet, 13 Jul, 1998.)).

Under the consent decree, Parkedale must certify that its labs and personnel are in compliance with FDA regulations, and gain FDA authorization to begin distribution of any new products.

While Fluogen production may resume after the company certifies that it has met FDA's conditions, resumption of distribution depends on FDA reinspection of Parkedale's facilities after additional improvements are made.

Parkedale must submit within 30 days an outline of all critical steps, and testing methods used to evaluate those steps in the manufacture of influenza vaccine, King said.

FDA has asked Parkedale to perform microbial retention validation studies of all .45-micron filters using in-process influenza vaccine product.

Parkedale has also been instructed to "immediately revise its potency testing and laboratory investigation procedures so that excessive retesting and re-reading are prohibited," with all lab and quality assurance personnel to be retrained on the revised testing and investigation procedures.

The letter requires the company to "establish bio-burden specifications for in-process products based on historical data and scientific judgement" and to quarantine products that fail to meet the specifications.

"Procedures for investigating bio-burden failures and determining the final disposition of in-process products that fail to meet bio-burden specifications" are also required by the agency.

"Parkedale shall immediately revise and implement the environmental monitoring program for critical and controlled environments to include investigations and specific corrective actions" if action levels are exceeded, the letter states.

In addition, FDA has also set a 120-day deadline for further actions, requiring submissions to the agency on a quarterly basis thereafter.

The measures include validation studies of the purification process, a revision of specifications referenced in batch production records and procedures, and the establishment of a cleaning validation program for all steps in the manufacturing process.

Parkedale must also conduct proper media fills. "All media vials will be incubated and examined; all positive vials will be recorded; production activities will be stimulated; and records of reconciliation will be accurate," the letter states.

After the additional corrective actions, FDA will verify compliance and could issue written notification that Parkedale may resume distribution.

King said it will "pursue all actions reasonably necessary to assure Fluogen's availability during the upcoming flu season commencing September 2000."

Net sales for Fluogen in 1999 were $28.7 mil. "The company generally recognizes revenue from Fluogen during the third and fourth quarters of each calendar year," King said.

In November 1999, Parkedale had submitted a written response to a 483 following FDA's October inspection of the facility.

FDA also told the company that it would address process validation issues related to Aplisol (tuberculin purified protein derivative) in a separate letter.

Aplisol sales in 1999 totaled $9.2 mil., the company said.