Washington Editor

WASHINGTON - Flu vaccine manufacturing problems have arisen at Sanofi Pasteur Inc., and the FDA is investigating the matter even as proposed legislation is being pushed to bolster the agency's safety monitoring efforts.

The FDA sent a warning letter to the company after determining that its response to a prior laundry list of concerns was inadequate. The situation stems from sterility failures for monovalent concentrates of Fluzone, Sanofi Pasteur's flu vaccine, as well as good manufacturing practices for finished products. Fluzone is produced in Swiftwater, Pa., and the 11 lots were manufactured between February and April.

That represents "a small proportion" of lots, said Karen Midthun, the deputy director of the agency's Center for Biologics Evaluation and Research (CBER). Adding that the company has been "fully cooperative" in working to address the FDA's concerns, she noted in a conference call that Sanofi Pasteur rejected the failed monovalent lots and did not use them in any further processing. The sterility issue "did not affect any final vaccine product," Midthun said.

Also of note, the FDA said that the manufacturing deficiencies are not expected to significantly affect the product's availability for the coming flu season. Government health officials have estimated that 100 million flu vaccine doses will be available this year from all licensed manufacturers.

No new sterility problems have occurred since early April, which Midthun called "a good sign." Between April 18 and 26, the FDA inspected Sanofi Pasteur's site, which also is being used to produce a vaccine for the H5N1 strain of avian flu. Midthun said the agency does not believe the matter would impact that product's production.

However, she cautioned that because a root cause of the sterility problem has yet to be identified, "we don't know for sure if the problem has been corrected."

Sanofi Pasteur, a unit of Lyon, France-based Sanofi-Aventis Group, first contacted the FDA on March 31. The agency, which issued the warning letter on Friday, is continuing discussions with the company as it works to correct the problem.

The news is at least slightly reminiscent of Chiron Corp.'s flu vaccine miscues of two years ago, when overseas manufacturing problems forced the Emeryville, Calif.-based company to renege on deliveries of its Fluvirin product. Sterility issues at the facility in Liverpool, UK, led the FDA to shutter that manufacturing plant for a period. However, Mary Malarky, the director of CBER's Office of Compliance and Biologic Quality, said the Fluzone issue is "not at all like" the Chiron situation. (See BioWorld Today, Oct. 6, 2004.)

More Safety Wanted At FDA

Lawmakers have made recent pushes to add another level of safety oversight for the FDA through two bills introduced last year. Their efforts gained new attention last week as the agency celebrated its centennial anniversary.

Reps. John Tierney (D-Mass.) and Jim Ramstad (R-Minn.) held a press conference on the Food and Drug Administration Safety Act (H.R. 4429), their proposal to establish an independent office at the agency for post-approval drug monitoring. The measure would transfer the FDA's existing office of drug safety into the Center for Postmarket Drug Evaluation and Research (CPDER) and establish new authority for post-approval review. The director of CPDER would report directly to the FDA commissioner.

The legislation and its Senate companion (S. 930), also introduced last year by Sens. Chris Dodd (D-Conn.) and Chuck Grassley (R-Iowa), have received fairly wide backing from several consumer advocacy groups. However, only six senators and the lower chamber's bipartisan sponsors have signed their names in support of the measure.

A separate proposal to expand post-approval drug oversight at the FDA has been floated by Rep. Maurice Hinchey (D-N.Y.) as part of a sweeping overhaul. First introduced last year, the FDA Improvement Act (H.R. 2090) would create the Center for Post-Market Drug Safety & Effectiveness as an independent office at the agency, and more notably, would end the user fee system that funds a portion of the FDA's budget. Critics, including Hinchey, have charged that the agency is too cozy with the drug industry as a result of the Prescription Drug User Fee Act (PDUFA). It does not have wide support, though, with only 13 co-sponsors on board to date.

The FDA's proposed $1.9 billion budget for the coming fiscal year includes $402 million in industry user fees. (See BioWorld Today, Feb. 7, 2006.)

With those proposed bills in the background, it is said that Sens. Mike Enzi (R-Wyo.) and Edward Kennedy (D-Mass.) are jointly developing their own FDA-related legislation, with a focus on drug safety.