Exhibit 10.6
CONFIDENTIAL
TREATMENT
AMENDMENT NO. 2
to the
MANUFACTURING AND SUPPLY
AGREEMENT
entered into as of September 30, 2001
by and between
ACS Dobfar, SpA and Cubist
Pharmaceuticals, Inc.
This AMENDMENT NO. 2 (“
Amendment No. 2 ”), to that certain
Manufacturing and Supply Agreement (the “ Agreement
”) entered into as of September 30, 2001, is made this 12
th day of February, 2003, by and between ACS Dobfar,
SpA, an Italian corporation (“ ACSD ”) and
Cubist Pharmaceuticals, Inc., a Delaware corporation (“
Cubist ”). Unless otherwise defined herein,
capitalized terms used but not defined herein shall have the
meaning set forth in the Agreement, and the Agreement shall be
amended to incorporate any additional definitions provided for in
this Amendment No. 1, including definitions in the preamble and
recitals hereto.
WHEREAS , Cubist and ACSD desire to amend the Agreement
as set forth in this Amendment No. 1;
NOW, THEREFORE
, in consideration of the foregoing
and the mutual promises made herein, and for other good and
valuable consideration, the receipt and sufficiency of which are
hereby acknowledged, the parties hereto agree to amend the
Agreement as follows:
1.
Amendment of Section
2.1. The
Agreement is hereby amended by deleting Section 2.1 thereof in its
entirety and replacing it with the following Section
2.1:
2.1
Facility Construction and
Timetable
(a) By [*] (the Facility
Completion Target Date ), ACSD will construct, equip, test and
qualify (IQ/OQ/PQ) and make operational the Facility in accordance
with current Good Manufacturing Practices. ACSD’s obligations
hereunder include, but are not limited to:
(i)
construction of building(s)
necessary to perform the Process in a dedicated
Facility;
(ii)
provision of [*] for production of
commercial batches of Product;
(iii)
the [*] of all required [*] for the
manufacturing and warehousing of Product and validation of Process:
and
(iv)
[*] to manufacture
Product.
Subject to adjustment in accordance
with Section 2.2, ACSD will complete all activities and to meet all
dates set forth in this Agreement. ACSD agrees that the following
events (the “Targets”) shall occur by [*]: (i)
ACSD shall produce [*] full commercial consistency batches for FDA
registration of the Facility; (ii) all data and reports
related thereto shall be completed and ready for submission to the
FDA; (iii) ACSD shall commence validation processes; and (iv) ACSD
will be prepared in all respects for a site inspection by the
FDA. The target date for FDA approval of the NDA
Manufacturing Supplement for the ACSD facility (the Facility
Approval Target Date ) is [*]. In addition, ACSD shall (i)
complete IQ/OQ/PQ and validation of the fermentation process by
[*]; and (ii) complete
* CONFIDENTIAL TREATMENT REQUESTED: MATERIAL HAS
BEEN OMITTED AND FILED WITH THE COMMISSION
theconsistency batches, the
IQ/OQ/PQ, and the [*] validation batches for the purification
process by [*]. ACSD agrees that time is of the essence
in completing the tasks set forth in this Section 2.1 in order to
comply with ACSD’s obligation to supply Product in [*].
In connection with ACSD completing all activities required to meet
the aforementioned dates, Cubist shall remit to ACSD [*]of [*] on
each of (i) the date of execution by both parties of this Amendment
No. 2 (the “February Payment”); (ii)May 1, 2003
(the “May Payment”); and (iii) August 1, 2003 (the
“August Payment”).
(b) By March 1, 2003, ACSD and
Cubist shall mutually agree upon a schedule for all tasks required
to meet the Targets set forth in section 2.1(a) above (the
“Schedule”). In the event that, in Cubist’s sole
discretion, Cubist determines that the Schedule will not enable
[*], the May and August Payments shall not be payable to ACSD and
ACSD shall promptly refund to Cubist the February
Payment.
2.
Amendment of Section
3.2. The
Agreement is hereby amended by deleting Section 3.2 thereof in its
entirety and replacing it with the following Section
3.2:
3.2
Process Validation
ACSD will develop and complete a
validation process at the Facility in accordance with
Exhibit D herein, and at ACSD expense. [*] and limits
for the process must span the [*]and limits developed and
documented during the manufacture of consistency batches at [*]. No
Process changes will be made during the period beginning on [*] and
ending on the [*]. All post-validation process changes must be
approved by Cubist in writing. Cubist will provide [*] and [*]as
such reports become available. ACSD will provide Cubist with a
[*]for the Facility and Process.
3.
Amendment of Section
3.3. The
Agreement is hereby amended by deleting Section 3.3 thereof in its
entirety and replacing it with the following Section
3.3:
3.3
Process
Improvements
Following the [*] of the date of the
Facility Approval, ACSD may continue operating [*] Process
improvements with the prior written approval of Cubist. No Process
improvements will be made during the period beginning on [*] and
ending on the [*]. [*]for the purpose of improving
ACSD’s margins will be entirely at ACSD’s expense. ACSD
will reimburse Cubist for any additional Cubist expenses [*]. All
[*] related to the [*] will be implemented only after [*]. The
authorization will be obtained in writing following a successful
and complete cGMP change control process outlined in the approved
standard operating procedures (SOPs) of both ACSD and
Cubist.
4.
Amendment of Section
3 .
The Agreement is hereby amended by
adding the following Section 3.5 immediately following the end of
Section 3.4 of the Agreement
* CONFIDENTIAL TREATMENT REQUESTED: MATERIAL HAS
BEEN OMITTED AND FILED WITH THE COMMISSION
2
3.5
Q.A.
Director
In order to ensure and maintain
consistent quality assurance with respect to the Product and the
process, on or before April 1, 2003 ACSD shall have hired, with the
approval of Cubist (which approval shall not be unreasonably
withheld), a full-time Quality Assurance Director and shall
en
