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7 Anthrax Vaccine Manufacture
Pages 180-197

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From page 180...
... Among the issues that the committee was charged with addressing is "validation of the manufacturing process focusing on, but not limited to, discrepancies identified by the Food and Drug Administration in February 1998." This chapter provides some background to clarify this portion of the charge, including a description of the role of the FDA in regulating the manufacture and marketing of vaccines, the history of the manufacturing process, and problems particular to the currently licensed anthrax vaccine. The committee's findings regarding the manufacture of the anthrax vaccine are also presented.
From page 181...
... The committee requested from BioPort copies of the Form FDA 483s (Form FDA 483is a list of observations provided by an FDA investigator at the conclusion of an inspection) from FDA inspections conducted since 1998, as well as BioPort's responses to these inspection reports.
From page 182...
... , as specified in the Code of Federal Regu~tions.i To ascertain compliance, FDA conducts periodic GMP surveillance inspections. In the case of vaccines, the inspections are carried out by a team of experts in GMPs and experts in the product in question, an approach adopted in 1999 under the Team Biologics program.
From page 183...
... to produce protective antigen that was precipitated and concentrated with aluminum potassium sulfate (alum)
From page 184...
... Jan. 31, 2002 FDA approval of BLA supplement for the filling operations and labeling change.
From page 185...
... after 6 months. No significant local reactions were reported after the first dose, but 0.6
From page 186...
... (Safety and efficacy data from the five annual progress reports submitted as part of the IND application are presented elsewhere in this report.) Additional data indicating that the vaccine protected guinea pigs from challenge were also submitted (Pittman, 1969~.
From page 187...
... 51002~. 187 The advisory report includes recommendations classifying products into one of three categories: · Category I designates those biological products determined by the pane!
From page 188...
... In the prelicensing phase of research, physicochemical, immunological, and molecular biological test methods were all used to provide evidence of the identity, purity, and genetic stability of the protein product (Parkman and Hardegree, 1999~. Protein characterization techniques included sodium dodecy!
From page 189...
... to estimate levels of protective antigen. Detailed characterization of vaccine constituents was not routine in the 1960s.
From page 190...
... FDA conducted an inspection of the MDPH anthrax vaccine manufacturing facility in January 1993, which was followed in July 1993 by FDA approval of amendments to the license application for new equipment and
From page 191...
... Meanwhile, FDA inspections of MDPH product lines other than AVA in 1993 and 1995 resulted in findings of significant deviations from GMP and an official warning letter. During a follow-up inspection of MBPI conducted in November 1996 that did not include the facilities for manufacture of AVA, FDA documented many deviations from the Food, Drug, and Cosmetic Act, FDA regulations, and current GMPs for the manufacture of blood-derived products and bacterial vaccines other than AVA (Elengold, 2000, 2001; Zoon, 1997~.
From page 192...
... MBPI's response to the NOIR letter was a Strategic Plan for Compliance, provided to FDA in April 1997. Periodic updates to the strategic plan that reported on MBPI's progress were also provided to FDA (Michigan Biologic Products Institute, 1997-1998~.
From page 193...
... The inspection report (FDA, 2001a) noted seven observations that needed attention, many of which BioPort successfully addressed during the inspection (FDA, 2001b)
From page 194...
... Furthermore, the committee took into consideration the recent and increasing BioPort and Department of Defense investments in facility renovations and process improvements, including the major action of shutting down the inadequate filling operations and transferal of those operations, with CBER approval, to a contractor meeting GMP standards. Finally, the committee noted the evident availability of technical support and assistance from CBER and Department of Defense research and development resources and the results that have been achieved in the form of progress in correcting the deficiencies noted in the Form FDA 483, as reported by BioPort and confirmed by FDA at the committee's meeting of July 10 and 11,2001.
From page 195...
... The manufacturing facility licensed to produce AVA has been the subject of numerous specific citations regarding the manufacturing process and equipment on FDA inspection reports. The manufacturer also responded, however, and worked toward full compliance with FDA requirements and lot release.
From page 196...
... 1998a. Form FDA 483 issued to Michigan Biologic Products Institute.
From page 197...
... IV. Factors influencing elaboration of the protective antigen of Bacillus antI7racis in chemically defined media.


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