04 February1997 (believe this should be 1998)

INFORMATION PAPER

Purpose: To provide LTG John Cusick information on the quality/integrity of DOD anthrax vaccine stockpile that would support waiving of the DOD directed supplemental testing to meet developing contingency use requirements.

Facts:

A. Anthrax Vaccine Quality/Integrity -

(1) All lots, up to and including FAV039, have been released by the FDA, Center for Biologics Evaluation and Research, for use as licensed product. Lots FAV037-FAV039 were released by the FDA 20 October 1997, subsequent to the FDA inspection of MBP127 November 1996, and the issuance of the FDA's letter dated I 1 March 1997 documenting 23 deficiencies at the facility. The FDA has not required any product produced at MBPI to be recalled, nor have they requested MBPI to cease production of any product.

(2) The FDA 11 March letter instructed MBPI to "(conduct) a review of all observations listed on the Form FDA 493 issued 27 November 1996, to determine whether or not product quality has been affected, including addressing the need for possible recall of product if deemed necessary." MBPI completed a review with respect to potential effect on product quality and the necessity of initiating a recall and reported their findings to the FDA in their 09 April 1997 Thirty-Day Response to the FDA letter of11 March 1997. MBPI's conclusions were that there is no concrete evidence that the Form FDA 483 observations have adversely affected product quality. In addition, no
reason was discovered to initiate a recall of any M-BPI manufactured products. Furthermore, MBPI volunteered to thoroughly review within 90 days documentation to ensure purity, potency, efficacy, and safety of the product. This was accomplished and submitted to the FDA and supported the initial finding that ail product quality and integrity is intact and usable as licensed product.

(3) In July 1997 an independent records review of batch production records at MBPI was performed by Mitretek Systems, Inc. at the request of the Joint Program Office for Biological Defense. The review was based on evaluation of the scientific and administrative records, and concluded that MBPI did what was required during production and did it correctly. Mitretek found no reason to retest AVA stockpile lots FAV008 to FAV025 and FAV0027 through FAV039. Based upon Mitretek's experts' opinions, lots up to FAV035 meet the requirements of applicable FDA regulations regarding sterility, purity, safety and potency. At the time of the review lots FAV036 and FAV039 had not yet been initially tested for potency.

B. Supplemental testing -

(1) Supplemental testing is DOD directed and based primarily on non-technical, non-regulatory issues. The testing was not directed by the FDA and the FDA has not requested the manufacturer to perform any additional testing.

(2) The DOD supplemental testing plan is loosely associated (compliant) with the U.S. Code of Federal Regulations (CFR) as it applies to FDA licensed products in that the testing is designed solely for DOD to be able to demonstrate they have gone one step further to show product integrity. It is not correct to infer that supplemental testing is consistent with the 21 CFR. Furthermore, strict regulatory consistency would require testing doses from each lot that were obtained doting the early, mid- and late part of the manufacturing process. This can not be do. Be, however, since the manufacturing process for each lot has already been completed and the doses in each lot can not now be associated with a particular stage of the process. (It is important to note that at the time each of the lots were produced testing that strictly conformed to the CFR requirements was done, and the results were then submitted as part of the lot release criteria to the FDA. Review of the data by the FDA subsequently resulted in the lots being approved for use as licensed product). Cost constraints, testing capacity at MBPI and the use ora significant portion of the anthrax vaccine stockpile required development of a plan that would provide an additional, albeit limited, level of testing of product quality.

(3) Supplemental testing involving short term tests (chemical, general safety, sterility) were started during the 5 to 20 January 1998 period for all AVA lots and are scheduled for completion by April 1998.

(4) The potency testing component of the supplemental testing is the rate limiting factor since the tests are required to be done in Biological Level-3 (high containment) facilities and involve using guinea pigs. Both the BL-3 space and animal holding facility constraints at MBPI impact on the supplemental potency testing. All AVA lots are scheduled.

C) Conclusions:

Prepared by:

Dr. Mike Gilbreath

JPO-BD

(703) 681-9610

Approved by:

BG John C. Doesburg

Joint Program Manager

For Biological Defense