THIS DOCUMENT LISTS OBSERVATIONS MADE BY THE FDA REPRESENTATIVE(S) DURING THE INSPECTION OF YOUR FACILITY. THEY ARE INSPECTIONAL OBSERVATIONS, AND DO NOT REPRESENT A FINAL AGENCY DETERMINATION REGARDING YOUR COMPLIANCE. IF YOU HAVE AN OBJECTION REGARDING AN OBSERVATION, OR HAVE IMPLEMENTED, OR PLAN TO IMPLEMENT, CORRECTIVE ACTION IN RESPONSE TO AN OBSERVATION, YOU MAY DISCUSS THE OBJECTION OR ACTION WITH THE FDA REPRESENTATIVE(S) DURING THE INSPECTION OR SUBMIT THIS INFORMATION TO FDA AT THE ADDRESS ABOVE. IF YOU HAVE ANY QUESTIONS, PLEASE CONTACT FDA AT THE PHONE NUMBER AND ADDRESS ABOVE.

DURING AN INSPECTION OF YOUR FIRM (WE) OBSERVED:

3. SOP M198, Sterility Investigation Report (Version 06), was not followed during the Fluvirin Sterility Failure investigations in that, the SOP required a Non-Conformance Report (NCR) be initiated in accordance with the NCR SOP. This was not done for the nine filled vial lots that were contaminated with Serratia spp. Regarding filled vials, the first failure occurred on 8 July 2004. The 9^th failure occurred 2 August 2004. There is no documentation to show that root cause, immediate corrective action, or product impact was addressed at the time of each failure (as per the firm’s SOP). One NCR (dated 28 September 2004) was generated to cover all nine sterility failures as well as monovalent blend failures and serves only to refer to the final Fluvirin Sterility Failure Investigation dated 9 October 2004.
4. No documentation of rationale in the Fluvirin Sterility Investigation #R/0198/10/04 dated October 9^th 2004 indicating that all three (3) monoblend batches of the Fluvirin trivalent strains with sterility failures are the B/Jiangsu strain.
5. The investigation of the root cause analyses, corrective/preventive actions, conclusions and recommendations did not include B/Jiangsu bulk batch [ Redacted ]. The first of the three (3) monoblend batches implicated in the nine (9) Fluvirin final filled vials sterility failures with bioburden level of 67cfu (specification of [ Redacted ] cfu/ml) but failed sterility at the bulk stage (isolate: Serratia marcesens). (Was referenced in the Investigation Report)
6. The investigation did not specifically state that high bioburden levels were noted in the Fluvirin B/Jiangsu strain at the [ Redacted ]/Pre filtration step in [ Redacted ] (83%) of [ Redacted ] monoblend batches manufactured for year 2004 campaign with 170-39,000,000cfu/ml bioburden levels per batch (alert level [ Redacted ]cfu/ml). This is higher bioburden than noted for any of the other two Fluvirin monoblend strains.
7. No documentation in the investigation report of the effect of keeping the monoblend/trivalent formulations at [ Redacted ] for up to [ Redacted ] during processing was considered. Fluvirin finished Fluvirin vials are labeled for shipment at 2-8°C and Fluvirin monoblend/trivalent bulks are stored at temperature of [ Redacted ]°C.

EMPLOYEE(S) NAME AND TITLE (Print or Type)
Omotunde O. Osunsanmi, CSO
Paula A. Trost, CSO
John D. Finkbohner, Ph.D. Supv. Chemist
David S. Cho, Ph.D., Microbiologist
Mark A. Elengold,Deputy Director Oper., CBER

The observations of objectional conditions and practices listed on the front of this form are reported:

1. Pursuant to Section 704(b) of the Federal Food, Drug and Cosmetic Act, or
2. To assist firms inspected in complying with the Acts and regulations enforced by the Food and Drug Administration.

"Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his judgment, indicate that any food, drug, device, or cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under unsanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary."