CBER Staff Evaluating Current Anthrax Vaccine Adsorbed Contingencies

Robert C. Myers, DVM, Chief

Biologic Froducts Division

Michigan Department of Public Health

I. Consistency of fermentation

The brief flow chart for the production method is presented in Figure 1. From review of early fermentation runs at MDPH (1966-1968) conducted by this method, Table I was constructed. The parameters consistently monitored at that time were opacity, glucose utilization and immunodiffusion. The information provided in Table I is from samples taken under stirring at the conclusion of fermentation. Although not shown, rates of reduction of X transmission and increase in glucose utilization assayed on intermediate samples indicated these rates to be quite uniform. Table II provides information for our entire production history and includes filtrate protein values for those lots for which this information was recorded.

II. Agar immunodiffusion (Ouchterlony) testing

Review of the records has shown interpretation of this work to be complicated by changes in antisera, incomplete records, and no apparent emphasis to utilize this value as a process control parameter beyond the very early days of production. Assays are being conducted now for some of the most recent fermentation runs and results will be forwarded es they become available.

III. Adsorption by aluminum hydroxide

Consistency of adsorption by A1OH has been studied very little either from the standpoint of specific constituents in the filtrate or from the total amount of protein adsorbed from the filtrate. Based on the certificate of analysis for the A1OH (Alhydrogel), the adsorption capacity for the amount of AIOH added is twice that of the protein present in the culture filtrate (the test method of the vendor evaluates binding of human serum albumin.) Limited work here shows the following with three recent lots (Lowry method):

Since this data is limited and the majority of the protein is not adsorbed there is little basis for consistency other than that provided by the potency test results provided in the next section.

IV. Potency test results

Potency test results for the entire production history are presented in Table III. Where two results are listed for a lot, the second result represents testing for extension of dating. It should also be noted that Lot 15 was not released. Overall, potency test results indicate the average reciprocal time to death (AvRTD) to be quite uniform for all vaccine lots tested. It also appears that the reference testing adds little value to the potency test as it is now done.

V. Adverse Reactions

I hope this information will allow us all to begin to deliberate on the serious matters presently before us. We are continuing to review records and are conducting additional 0uchterlony testing. As information of consequence is identified and compiled, we will fax it to you promptly.