Food and Drug Administration

Center for Drug Evaluation and Research

Advisory Committee Conference Room, Room 1092

5630 Fishers Lane, Rockville, MD

The meeting was held in the CDER Advisors and Consultants Conference Room. Prior to the meeting, the members, consultants and guests had reviewed the background information from the FDA. There were approximately 30 persons in attendance. The meeting started at 8 a.m. both days and ended at approximately 5 p.m. on May 6^th and at 1:30 p.m. on May 7^th

PCAC Members Present: Randy Juhl, Ph.D., Chair, Lloyd Allen, Jr., Ph.D., Carmen Catizone, M.S., R.Ph., Elizabeth McBurney. M.D., William Rodriquez, M.D., Sarah Sellers, Pharm.D., Garnet Peck. Ph.D., William Rusho, R.Ph., Lawrence Trissel, F.A.S.H.P., Joan LaFollette, R.Ph.(Industry Representative, non-voting), Rose-Ellen Hope, R.Ph. (Consumer Representatiave), David Liebman, D.P.A., R.Ph.(Industry Representative, non-voting), Judith Martin Riffee, R.Ph., Tony Welder, R.Ph.

PCAC Members Absent: Christopher Rhodes, Ph.D.

Consultant to the Committee: Kenneth Giddes, B.A., M.B.A. (Patient Representative – voting on hydrazine only)

Guests to the Committee: Sid Gilman, M.D., Janice Dutcher, M.D. (both non-voting)

FDA Participants: Jane Axelrad, J.D., Lana Ogram, M.S., James Vidra, Ph.D., Paul Brown, Ph.D., Martin Okun, M.D., Joel Hathaway, Ph.D., John Feeney, M.D., Wiley Chambers, M.D., Norman Stockbridge, M.D., Saul Malozowski, M.D..

E. William Rosenberg, M.D. (American Academy of Dermatology), Christopher T. Bever, Jr., M.D., Ron Cohen, M.D., Andrew Blight, M.D. (Acorda Therapeutics), Sharon Hamm, Pharm.D., (Elan Corporation), Donald Sanders, M.D. (Duke University), David Jacobus, M.D. (Jacobus Pharmaceutical Company, Inc.), Charles L. Loprinzi (Mayo Clinic), Mary McCabe (National Cancer Institute).

Open Public Hearing Speakers : 5/6/99:Larry Sasich, Pharm.D. (Public Citizen Research Group), Thomas Mick Countee, Jr., (Executive Director of the National Spinal

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Cord Injury Association), Gina Ford (Executive Director of the International Academy of Compounding Pharmacists), Craig Basch, M.D., (Paralyzed Veterans of America), Jackie Havner (multiple schlerosis patient). 5/7/99: Rosemary Jacobs (argyria patient), John Brandon (Central Add-Mixture Pharmacy Services)

FDA sought to obtain comment from the Committee regarding whether the following bulk substances, which are neither approved drugs, nor the subject of a USP/NF monograph, should appear on the Bulk Drug Substances (BDS) List: dinitrochlorobenzene (DNCB), diphenylcyclopropanone, squaric acid dibutyl ester, peruvian balsam, 4-aminopyridine, 3,4-diaminopyridine, mild silver protein, monosodium aspartate, cyclandelate, betahistine dihydrochloride, pentylenetetrazole, chloramine-T and hydrazine sulfate.

Since the uses of peruvian balsam, pentylenetetrazole, or chloramine-T appeared to be quite limited or restricted to a very few limited sites, there was no consideration of these agents for inclusion on the BDS List.

The following is a summary of the Committee’s votes for the remaining products recommending either for or against inclusion on the BDS List:

Squaric acid dibutyl ester (6-5 vote for inclusion)

Monosodium aspartate (11-0 vote for)

Cyclandelate (8-3 vote for)

Betahistine (11-0 vote for)

DNCB (11-0 vote against inclusion)

Diphenylcyclopropanone (6-5 vote against)

4-aminopyridine (9-2 vote against)

3,4-diaminopyridine (7-4 vote against)

Mild silver protein (11-0 vote against)

Hydrazine (12-0 vote against – includes vote of the patient representative attending for this bulk)

Of note, a representative of the American Academy of Dermatology presented the Academy’s position that they hoped that at least one of the three bulk substances nominated would appear on the BDS List (squaric acid dibutyl ester was indeed recommended for inclusion on the BDS List). Much of the Committee’s debate focused around issues of allowing a bulk product to continue to be compounded versus having the bulk made available under more regulated expanded access means (e.g., open-label IND

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programs). Thus, although both 4-aminopyridine and 3,4-diaminopyridine were rejected for inclusion on the BDS List, firms that hold INDs for these products (Acorda for 4-aminopyridine and Jacobus for 3,4-diaminopyridine) promised to pursue expanded access programs via the IND route. Issues of assurances of sterility raised during debate for monosodium aspartate were felt to apply not just to this bulk but to the general compounding of sterile products by pharmacists. FDA’s review of the data for mild silver protein and hydrazine concluded that there was little evidence of efficacy for these products. This factor coupled with the potential danger of a patient not seeking more proven therapies in lieu of trying either of these two products were reasons given for the recommendation of rejection of these two bulks for inclusion on the BDS List.

A verbatim transcript of this meeting will be available on the FDA’s Docket’s Management Branch Website approximately 30 days after the meeting. The address is: HTTP:/www.fda.gov/ohrms/dockets/ac/acmenu.htm.

I certify that I attended the May 6 and 7, 1999, meeting of the Pharmacy Compounding Advisory Committee and that these minutes accurately reflect what transpired.

_____________________ ___________ ________________ ______

Jayne Peterson, R.Ph., J.D. Date Randy Juhl, Ph.D. Date

Executive Secretary, PCAC Chair-PCAC