Wyeth DT Vaccine Seized By FDA; Manufacturing Upgrades Under Way

Wyeth-Ayerst has been working on process improvements at its Marietta, Penn. plant for six months, the company said following a June 15 seizure action filed by FDA against products produced at the facility.

The seizure action targeted four injectable products: the dyptheria-tetanus vaccine, the sedative Phenergan (promethazine) and the antihistamines diphenyhdramine and dimenhydrinate.

Production of all four products was halted at the Marietta plant last December, Wyeth said. At that time, Wyeth also suspended production of the protein enzyme Wydase (hyaluronidase) and the snake bite treatment Antivenin (micrucus fluzius).

Wyeth's flu vaccine Flushield is also affected by the shutdown, since it is filled at the Marietta facility. However, Wyeth said it anticipates no supply problems for the influenza vaccine related to the shutdown.

Since halting production, the Marietta facility has been undergoing manufacturing process improvements, the company said.

The company said it is in discussions with the agency and is trying to schedule a meeting following the seizure. FDA seizure actions are typically the prelude to a GMP consent decree.

FDA seized the product from a Wyeth warehouse in Vonore, Tenn. on June 15. The seizure action was filed in Knoxville federal court, citing good manufacturing practices violations that rendered the products "adulterated while held for sale after shipment in interstate commerce."

The seizure followed an FDA inspection of the Marietta plant between November and February. Wyeth received a 483 inspection report on Feb. 17.

The inspection began at a time when Wyeth's senior management was concentrating on other issues. American Home Products announced an agreement to merge with Warner-Lambert on Nov. 4 and then spent the next two months fighting to save the deal following Pfizer's hostile takeover bid for Warner-Lambert.

Wyeth has conducted at least one recall following the inspection. The company initiated a Class II recall of 95,786 vials of meperidine injection manufactured in Marietta on March 13. The recall was due to lack of assurance of sterility (¹ ).

FDA's concerns about sterility problems in Marietta were presumably heightened by prior warnings to the company about conditions at other facilities.

Last year FDA issued a warning letter to Wyeth citing sterility failures for products manufactured at the company's West Chester, Penn. facility.

One of the findings in the Sept. 28 letter specifically addressed meperidine. "Post inspectional correspondence from your firm states that exceeded action levels were associated with environmental sampling conducted prior to filling the meperidine HCl," the letter states.

FDA noted that Wyeth's disinfection procedures and its adherence to them were not sufficient to prevent failures, and therefore, "call into question the assurance of sterility for an epinephrine injection lot and a meperidine injection lot" (² (Also see "Wyeth Cited For Not Identifying Cause of Discoloration of Epinephrine Units" - Pink Sheet, 18 Oct, 1999.)).

Wyeth has also experienced supply difficulties with the trivalent flu vaccine Flushield in the past.

In September 1998 Wyeth reported delays in production of the vaccine due to manufacturing difficulties. CDC said that Wyeth was in the midst of a manufacturing process change when the antigens for the 1998 season were determined and thus fell behind in manufacturing the new antigens (³ (Also see "Flu Vaccine To Be Fully Available By Mid-November, One Month Late" - Pink Sheet, 12 Oct, 1998.)).

The GMP action occurs at a time when Wyeth is facing a separate investigation of its compliance with FDA's adverse event reporting rules. In May, AHP disclosed that the Maryland U.S. Attorney is investigating Wyeth-Ayerst's "adverse events reporting system and the reporting of adverse events related to Redux and Pondimin."

AHP "is in the process of responding to the subpoena and continues to believe that its conduct with respect to the diet drugs has at all times been lawful and appropriate" (⁴ (Also see "American Home Products" - Pink Sheet, 22 May, 2000.)).