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:

1. to result in procedural requirements for environmental monitoring during all aseptic connections and evaluation of possible reductions in the number of aseptic connections.
2. Settling plates were placed on the formulation tank at least 15 minutes after aseptic connections to the tank during the formulation of New Caledonia lot # 764984 observed on June 4, 2003. [ Handwritten text added “Active” with margin note “rwj 6/10/03”] Viable and non-viable monitoring was initiated at least one hour after all connections were made including those to the [ Redacted ] unit which are made in Class [ Redacted ] conditions [ Redacted ].
3. Klebsiella [ Handwritten text added “oxytoca” with strike-out of “oxytaca” with margin note “wj /10/03”] was isolated in the Centrifugation [ Redacted ]batch 762450 and the [ Redacted ]Zonal Concentrate batch #762451 that went into batch #762492. K. [ Handwritten text added “oxytoca” with strike-out of “oxytaca”] was also isolated in the [ Redacted ] filtration sample as well as the sterile-filtered sample. There was no investigation of water monitoring results or environmental monitoring results prior to this batch.
4. From February 28 2002 to July 5, 2002, 14 [ Redacted ] Monovalent Blend Pools failed bioburden testing with a Klebsiella isolate. Closure of the sterility failure investigation of lot# 762635 (refiltered from lot# 762492) on July 9, 2002 did not include reference to nor investigation of the additional failed batches with the same isolate.
5. There was incomplete review and approval justification for retests in sterility OOS test results reviewed for 2001 and 2002.
5. The following deficiencies were noted in product contact equipment compatibility:
   1. There is no filter compatibility and extractable validation studies on filtered Fluvirin monovalent and/or trivalent bulks. In addition, filter compatibility was not considered in the product stability failure investigations. As such, filter compatibility studies has not been eliminated as the reason for loss of potency after the trivalent filtration step that resulted in failures of four out of five Fluvirin lots placed on stability for year 2001/2002 campaign.
   2. The [ Redacted ] Tubing used throughout the Fluvirin manufacture process to transfer centrifuged, formulated and finished product for filling was out of specification of [ Redacted ] mg for USP Non-Volatile Residue with result of 1327 mg per [ Redacted ] test result. No investigation, corrective and preventive action has been conducted and no justification/rationale is provided for lack of investigation.
6. The investigation into the reported Fluvirin potency stability test failures in 2001/2002 and 2002/2003 was incomplete. For example,

EMPLOYEE(S) NAME AND TITLE (Print or Type)
Omotunde O Osunsanmi, CSO
Robert W. Jennings, CSO
Robin Levis, Ph.D. Regulatory Coordinator
Jonathan McInnis, Biologist

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 judgement, indicate that any food, drug, device, 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 insanitary 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."