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Product Approval
Information - Licensing Action
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448
December 8, 2000
Michael Scaife, Ph.D.
Vice President, Regulatory Affairs
Elan Pharmaceuticals
800 Gateway Boulevard
South San Francisco, CA 94080
Dear Dr. Scaife:
Your Biologics License Application for Botulinum Toxin Type
B, "MYOBLOC", for the treatment of cervical dystonia, is
approved this date. Elan Pharmaceuticals is hereby
authorized to introduce or deliver into interstate
commerce, botulinum toxin type B produced at your Neurobloc
Production Facility, South San Francisco, CA location under
Department of Health and Human Services U.S. License
No. 1579.
MYOBLOC is indicated for the treatment of patients with
cervical dystonia to reduce the severity of abnormal head
position and neck pain associated with cervical dystonia.
In accordance with approved labeling, your product will
bear the tradename MYOBLOC, and will be marketed in 3.5 mL
single use vials containing 2500 U, 5000 U or 10,000 U per
vial.
Under this authorization you are approved to manufacture
MYOBLOC at the Neurobloc Production Facility (NPF) in South
San Francisco, CA. Drug product will be shipped to a
contract filling and packaging facility, [------------, ---
----------], for filling, labeling and packaging. Packaged
MYOBLOC will be distributed by [---------------------------
---------------------------.
The dating period for this product shall be 21 months from
the date of manufacture when stored continuously at 2-8oC.
The concentrated and diluted bulk products may each be
stored for up to 12 months when stored continuously at
2-8oC. The date of manufacture shall be defined as the date
of the last valid potency test on the final container
product. This potency test should be initiated within 30
days of the filling date. Any extension of the dating
period will require the submission of supporting data as a
supplement to your biologics license application for review
and approval. Alternatively, you may submit a stability
protocol to be used in extension of dating as a supplement
to your license application.
You are requested to submit to the Center for Biologics
Evaluation and Research (CBER) samples of future formulated
product together with the protocols showing the results of
all applicable tests. No lots of product shall be
distributed until notification of release is received from
the Director, CBER.
We acknowledge your commitments dated November 7, 2000,
November 17, 2000, November 21, 2000, and December 7, 2000,
for the following postmarketing clinical and manufacturing
studies and data:
- You have agreed to initiate a postmarketing study to
evaluate the safety and immunogenicity of MYOBLOC in
patients with cervical dystonia. You have made the
following commitments for timeframes of conducting the
study and submission of related materials to CBER:
- The study protocol will be finalized and
submitted to CBER for review and comment by
February 2001.
- The study will be initiated by June 2001.
- A total of 500 study subjects will be enrolled.
- Enrollment of study subjects will be completed in
approximately 3.5 years with the last subject to
be entered by December 2004.
- All study subjects will be followed until the
2-year clinical observation period for the last
enrolled patient is completed in December 2006.
- Closure and initiation of analysis of the
database will occur in June 2007, with completion
of database analysis by November 2007.
- The Clinical Study final report will be completed
and submitted to CBER by February 2008.
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- You have agreed to submit a complete testing data
report from fermentation through the diluted bulk
stage, for the next lot of product manufactured after
the concentrated product lot designated D90001 and
submission of the completed report by the end of
December 2000.
- You have agreed to perform stability studies on a lot
of product in final container manufactured from a new
lot of concentrated product (CP) near the end of its
dating period. This lot of CP will be manufactured by
April 2001 and will be held at 2-8oC for 12 months
before compounding the diluted bulk for further
manufacture by April 2002. The diluted bulk will be
stored for a period of no less than 3 months but no
more than 6 months at 2-8oC to simulate the upper limit
of storage in routine manufacturing. Stability
reports for the final container through the 21 month
dating period will be submitted to CBER starting at
the 3 month timepoint and then at 6 month intervals
through July 2004.
- You have agreed to monitor stability using one lot of
MYOBLOC per year for each fill size (2500 U, 5000 U,
and 10,000 U) in accordance with the current stability
protocol.
This information will be placed in your biologics license
application file for this product.
Changes in the manufacturing process, manufacturing
facility, product testing, packaging or labeling for
botulinum toxin type B (MYOBLOC) may require the submission
of a supplement to your biologics license application for
review and approval prior to implementation.
It is required that adverse experience reports be submitted
in accordance with the adverse events reporting
requirements for licensed biological products (21 CFR
600.80) and that distribution reports be submitted as
described (21 CFR 600.81). All adverse experience reports
should be prominently identified according to 21 CFR 600.80
and be submitted to the Center for Biologics Evaluation and
Research, HFM-210, Food and Drug Administration, 1401
Rockville Pike, MD 20852-1448.
It is required that reports of errors and accidents in
manufacture be submitted in accordance the error and
accident reporting for licensed biological products (21 CFR
600.14). All error and accident reports should be promptly
identified according to 21 CFR 600.14 and be submitted to
the Director, Office of Compliance, Center for Biologics
Evaluation and Research, HFM-600, 1401 Rockville Pike,
Rockville, MD 20852-1448.
Please submit final printed labeling at the time of use and
include implementation information on FDA Form 2567.
Please provide a PDF-format electronic copy as well as
original paper copies (ten for circulars and five for other
labels). In addition, you may wish to submit draft copies
of the proposed introductory advertising and promotional
labeling with an FDA Form 2567 or Form 2253 to the Center
for Biologics Evaluation and Research, Advertising and
Promotional Labeling Branch, HFM-602, 1401 Rockville Pike,
Rockville, MD 20852-1448. Final printed advertising and
promotional labeling should be submitted at the time of
initial dissemination, accompanied by a FDA Form 2567 or
Form 2253.
All promotional claims must be consistent with and not
contrary to approved labeling. No comparative promotional
claim or claim of superiority over other similar products
should be made unless data to support such claims are
submitted to and approved by the Center for Biologics
Evaluation and Research.
Please acknowledge receipt of this letter to the Director,
Division of Vaccines and Related Products Applications,
HFM-475, Center for Biologics Evaluation and Research.
Sincerely yours,
--- signature --- |
--- signature --- |
Karen Midthun, M.D.
Director, Office of Vaccines Research and Review
Center for Biologics Evaluation and Research |
Steven A. Masiello
Director
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research |
Last Updated: 1/15/2001
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Date created: September 25, 2003 |
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