MEMORANDUM
DATE:
December 10, 1997
TO:
M. Carolyn Hardegree, M.D., Director
Office of Vaccines Research and Review
CBER
THROUGH:
Paul Richman, Ph.D., Chief
Bacterial Vaccines and Allergenic Products Branch
DVRPA
FROM.
Jeanne Novak, Ph.D., Scientific Reviewer
DVRPA
CC:
Karen Goldenthai, M.D., Director
Division of Vaccines Research and Review
SUBJECT:
Anthrax Vaccine, Adsorbed - Dating of Container Product (Michigan Biologic Products Institute - License #0099)
Background
In October of 1996, I was informed that staff members of DBP and the Michigan Field Office had met with Dr. Baylor to discuss deficiencies revealed upon inspection of the MBPI (formerly MDPH) facility.
In the same time frame, it came to the attention of OVRR staff that FIBPI was routinely submitting potency retest data for lots of Anthrax Vaccine Adsorbed to DPQC for extension of dating and release approval. DPQC released numerous lots with a 3 year extension of dating.
I had numerous telephone conversations with Dr. Myers of MBPI in the Fall of 1996 and the Winter of 1997 (dates and records available in the license file). We specifically discussed the issue of redating of Anthrax Vaccine Adsorbed. Dr. Myers stated that redating of Anthrax Vaccine Adsorbed had been done since its initial licensure in 1970. He said that DPQC had been reviewing these requests and approving the extension of dating in three year increments.
I informed Dr. Myers (Fall 1996) that any extension of dating of product must first be reviewed and approved as a Supplement to the product license. This is no longer true- they have the additional option of submitting a protocol as a supplement to be used for extension of dating. He acknowledged this and committed to submitting a supplement to the license regarding extension of dating and that he would submit a supplement in the near future.
NOTE: Dr. Richman has pointed out that the in accordance with 21 CFR 601.12 changes, the sponsor has the additional option of submitting a protocol as a Supplement to be used for the extension of dating.
I contacted Dr. Fitzgerald of DPQC in the Fall of 1996 to investigate the redating issue further. He as unable to provide any details regarding how many lots of Anthrax Vaccine had been redated but acknowledged that extension of dating was occurring for this product.
I contacted DBP staff members, in the Fall of 1996, who had also recently become aware of the redating but they did not have any details regarding how many lots had been given an extension of dating. DBP did confirm that to their knowledge, the license had not been supplemented for extension of dating.
To date, a supplement for extension of dating has not been submitted to CBER. In the Spring/Summer of 1997, I contacted Dr. Myers to check on the status of a Supplement for extension of dating. Dr. Myers said he was accumulating data to compile such a Supplement.
In the Fall of 1997, I contacted Dr. Myers again to check on the status of this submission. He provided some summary information to me by telephone on 10/22/97 (See below). In asked that he submit the information to FDA even if he was not prepared to submit a complete Supplement.
10/22/97 - Dr. Myers left a message that he has an update on the redating of 32 lots of Anthrax Vaccine. Of those, he had stability data on 11 lots at 2-8°C and stability on 5 lots at 25°C and 37°C. Further, 10 lots have been redated twice based on potency testing at 3 and 6 years post-final fill.
On 12/07/97, I sent a facsimile to Dr. Myers requesting summaries of retest data for anthrax Vaccine Adsorbed. On 12/08/97, Dr. Myers provided a 13 page fax regarding this issue.
Summary of Anthrax Vaccine Adsorbed Information Provided 12/08/97
1.
Lot 019 - manufactured--------------Used as the reference lot
in potency assays until 07/12/94.
Lot FAV 009 - manufactured ----------- This lot is serving as the current reference lot.
3.
A summary of release potency tests for --- lots of Anthrax Vaccine Adsorbed manufactured from 1990 through 1997 has been provided. All lots passed. There are no reports of failures (although this needs to be confirmed by manufacturer.)
4.
A total of --- lots of Anthrax Vaccine Adsorbed have been manufactured during the period 06/04/90 through 11/18/97 (4 lots are still ~on test:). Of these lots, 11 have been placed in a stability testing program (date of initiation of stability testing program not provided.
a)
Of the --. lots indicated above (#4), 19 lots have been retested for potency at least once. The dates of manufacture of these--~ lots range from 03/06/91 through 07/12/94. The dates of retest range from 08/09/94 to 07/15/97. All~ lots passed the potency retest.
b)
Of the -~ lots indicated above (#4a), 6 have been retested a second time for potency. The dates of manufacture of these 6 lots range from 03/06/91 through 10/15/91. The dates of retest range from 08/04/97 to 11/11/97. Five of the 6 lots passed the potency retest. One lot is still on test.
Outstanding Issues
1. ----
2. ----
3. ----
Summary available upon request.
4. ----
5.
The sponsor needs to submit complete history of potency testing, including a report of failures, to the license file.
6.
Sponsor has initiated a new stability testing program. To my knowledge, the stability protocols have not been submitted to the FDA for review. I would highly recommend the sponsor submit this information for FDA review and comment. This could be submitted as a Supplement to allow future extensions of dating to be submitted to the Annual Report.
7.
Although I am not a reviewer on Supplement 91-0079, I would recommend that the potency assay in the license file be reviewed. It is not clear if significant changes have occurred since licensure of this product.~ Further, I do not know if appropriate SOPs are in place for retest of ~failures:, potency test calculations, qualification of new reference lots, etc.
8.
Dr. Myers indicated that he would like to date Anthrax Vaccine Adsorbed for an initial ~ years. However, 21 CFR 610.53, currently dictates 2 years in manufacturer's storage (1 to 5°C) and 1 year after leaving manufacturer's storage (2 to 8°C). Follow-up by FDA staff on this issue is needed.