|
E XHIBIT
10.30
CONFIDENTIAL TREATMENT
REQUESTED
Redacted Portions are
indicated by [****]
MANUFACTURING, MARKETING
AND SALES AGREEMENT
THIS MANUFACTURING,
MARKETING AND SALES AGREEMENT (this “ Agreement
”) is made effective as of the 1 st day of January, 2008 (the “
Effective Date ”), by and among BioMarin
Pharmaceutical Inc., a Delaware corporation having its principal
place of business at 105 Digital Drive, Novato, California 94949
(“ BioMarin ”); Genzyme Corporation, a
Massachusetts corporation having its principal place of business at
500 Kendall Square, Cambridge, Massachusetts 02142 (“
Genzyme ”) and BioMarin/Genzyme LLC, a Delaware
limited liability company having its principal place of business at
500 Kendall Street, Cambridge, Massachusetts 02142 (“
BioMarin/Genzyme LLC ”).
R
ECITALS
A. BioMarin, Genzyme and
BioMarin/Genzyme LLC are parties to a Collaboration Agreement dated
as of September 4, 1998 (the “ Original Collaboration
Agreement ”) pursuant to which BioMarin and Genzyme
through BioMarin/Genzyme LLC develop, manufacture, market and sell
Aldurazyme (as defined herein).
B. The Parties no longer
desire to develop, manufacture, market and sell Aldurazyme through
a joint venture and instead have agreed that: (1) BioMarin
will manufacture Aldurazyme and sell finished product to Genzyme;
(2) Genzyme will label and commercially distribute, market and
sell Aldurazyme globally; (3) each of Genzyme and BioMarin may
conduct its own research and development of Aldurazyme and other
Collaboration Products (as defined herein) in accordance with the
terms of this Agreement and the Amended and Restated Collaboration
Agreement (as defined herein); and (4) BioMarin/Genzyme LLC
will maintain and provide intellectual property licenses and
sublicenses to BioMarin and Genzyme so that they may fulfill their
respective obligations under this Agreement, the Amended and
Restated Collaboration Agreement and the Fill Agreement (as defined
herein).
C. BioMarin and Genzyme have
amended and restated the Original Collaboration Agreement so that
hereafter BioMarin/Genzyme LLC will no longer engage in commercial
activities and will solely (1) hold the intellectual property
relating to Aldurazyme and license all such intellectual property
on the terms set forth herein to BioMarin and Genzyme on the terms
set forth in the Amended and Restated Collaboration Agreement (as
defined below) and (2) and engage in research and development
activities that are mutually selected and funded by BioMarin and
Genzyme.
D. To effect the foregoing,
the Parties are also entering into (1) a separate Fill
Agreement of even date herewith pursuant to which Genzyme will
continue to provide fill services for Aldurazyme to BioMarin (the
“ Fill Agreement ”); (2) the aforementioned
amendment and restatement of the Original Collaboration Agreement
of even date herewith (the “ Amended and Restated
Collaboration Agreement ”); and (3) a Members
Agreement of even date herewith pursuant to which certain current
assets and liabilities of BioMarin/Genzyme LLC and its subsidiaries
will be distributed to its Members (the “ Members
Agreement ”).
A
GREEMENT
NOW, THEREFORE, in
consideration of the mutual promises set forth in this Agreement
and other good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the Parties hereto
hereby agree as follows:
| 1.1 |
“ Adverse Experience ” shall mean any
undesirable physical, psychological or behavioral effect
experienced by a human Patient or subject that is associated with
the use of Aldurazyme, whether or not considered product-related,
including an adverse experience occurring: in the course of the use
of Aldurazyme in professional practice; from an overdose of
Aldurazyme (whether accidental or intentional); from the abuse of
Aldurazyme; from the withdrawal of Aldurazyme; or from any
failure of Aldurazyme’s expected pharmacological
action. |
| 1.2 |
“ Affiliate ” shall mean any corporation,
limited liability company, firm, partnership, limited liability
partnership or other entity, whether de jure or de facto, which, at
the time in question, is directly or indirectly owned by or
controlled by, or under common control with, BioMarin or Genzyme,
as the case may be. For the purposes of this definition, a Party
shall be deemed to have “ control ” if such
Party: (a) owns, directly or indirectly, fifty percent
(50%) or more (or such lesser percentage which is the maximum
allowed to be owned by a foreign corporation in a particular
jurisdiction) of (i) the voting stock or shareholders’
equity of a corporation, (ii) the partnership interests in a
partnership, (iii) the membership interests in a limited
liability company, or (iv) in the case of any other entity,
the right to receive fifty percent (50%) or more of either the
profits or the assets upon dissolution; or (b) possesses,
directly or indirectly, the power to direct or cause the direction
of the management and policies of the corporation or other entity
or the power to elect more than fifty percent (50%) of the
members of the governing body of the corporation, limited liability
company or other entity. |
| 1.3 |
“ Agreement ” shall have the meaning set
forth in the introductory paragraph hereof. |
| 1.4 |
“ Aldurazyme ” shall mean
alpha-L-iduronidase meeting the Specifications. |
| 1.5 |
“ alpha-L-iduronidase ” shall mean
recombinant human alpha-L-iduronidase. |
| 1.6 |
“Amended and Restated Collaboration
Agreement” shall have the meaning set forth in the
recitals. |
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| 1.7 |
“ Annual Net Sales ” shall have the meaning
set forth in Section 6.1(a) . |
| 1.8 |
“ Batch ” or “ Lot ”
shall mean each separate and distinct quantity of Aldurazyme
processed under continuous conditions and designated by BioMarin
with a batch or lot number. |
| 1.9 |
“ BioMarin Companies ” shall mean BioMarin
and BioMarin Genetics. |
| 1.10 |
“ BioMarin Genetics ” shall mean BioMarin
Genetics, Inc., a Delaware corporation and wholly-owned subsidiary
of BioMarin. |
| 1.11 |
“ BLA ” shall mean a Biologics License
Application or similar application as approved by the FDA on
April 30, 2003, that provides for marketing approval for
Aldurazyme in the United States, as the same may be updated or
amended from time to time. |
| 1.12 |
“ cGMP Regulations ” means the applicable
current Good Manufacturing Practices as promulgated under ICH
Q7A-Good Manufacturing Practice Guidance for Active Pharmaceutical
Ingredients, U.S. Federal Food, Drug and Cosmetic Act at 21 CFR and
the EEC Guide to Good Manufacturing Practices for Medical Products
(Vol. IV — rules governing medical products in the European
Community 1989) in the most recent version. |
| 1.13 |
“ Certificate of Analysis ” or “
COA ” shall mean a document in the form attached as
Exhibit B executed by BioMarin to certify that a Batch or
Lot of Aldurazyme meets the Specifications. |
| 1.14 |
“ Certificate of Compliance ” or “
COC ” shall mean a document certifying a Batch or Lot
of Aldurazyme meets Genzyme’s product release criteria and
was produced in compliance with cGMP requirements. |
| 1.15 |
“ Collaboration Product ” shall mean
Aldurazyme and any other pharmaceutical compositions of
alpha-L-iduronidase, including without limitation any and all
improvements, derivatives, analogs, combination products, delivery
systems and dosage forms related thereto. |
| 1.16 |
“ commercially reasonable and diligent efforts
” will mean that level of effort which, consistent with the
exercise of prudent scientific and business judgment, is applied by
the Party in question to its other therapeutic products at a
similar stage of development and with similar commercial
potential. |
| 1.17 |
“ Control ” shall mean possession of the
ability to grant a license or sublicense as provided for herein
without violating the terms of an agreement with a Third
Party. |
| 1.18 |
“ Effective Date ” shall mean
January 1, 2008. |
| 1.19 |
“ EMEA ” shall mean the European Agency for
the Evaluation of Medical Products or any successor
agency. |
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| 1.20 |
“ European Commission ” shall mean that body
of the European Union that grants Marketing Application
Approvals. |
| 1.21 |
“ FDA ” shall mean the United States Food
and Drug Administration, or any successor agency. |
| 1.22 |
“ Field ” shall mean any and all therapeutic
applications of alpha-L-iduronidase for MPS I and other
alpha-L-iduronidase deficiencies. Notwithstanding the foregoing,
the Field shall not include Gene Therapy for MPS I or other
alpha-L-iduronidase deficiencies. For purposes of this Agreement,
“ Gene Therapy ” shall mean treatment or
prevention of MPS I or other alpha-L-iduronidase deficiencies by
means of ex vivo or in vivo introduction (via viral
or nonviral gene transfer systems) of nucleotide sequences
(including without limitation, DNA, RNA and complementary and
reverse complementary nucleotide sequences thereto, whether coding
or non-coding). |
| 1.23 |
“Fill Agreement” shall have the meaning set
forth in the recitals. |
| 1.24 |
“ GAAP ” shall mean the then-current United
States generally accepted accounting principles, consistently
applied. |
| 1.25 |
“ Insolvency Event” shall mean, with respect
to a Party, that the Party (i) applies for or consents to the
appointment of a receiver, trustee, liquidator or custodian for
itself or of all or a substantial part of its property;
(ii) becomes unable, or admits in writing its inability, to
pay its debts generally as they mature; (iii) makes a general
assignment for the benefit of its or any of its creditors;
(iv) is dissolved or liquidated in full or in part;
(v) commences a voluntary case or other proceeding seeking
liquidation, reorganization or other relief with respect to itself
or its debts under any bankruptcy, insolvency or other similar law
now or hereafter in effect or consents to any such relief or to the
appointment of or taking possession of its property by any official
in an involuntary case or other proceeding commenced against it; or
(vi) takes any action for the purpose of effecting any of the
foregoing; or (vii) the Party has commenced against it
proceedings for the appointment of a receiver, trustee, liquidator
or custodian, or an involuntary case or other proceedings seeking
liquidation, reorganization or other relief under any bankruptcy,
insolvency or other similar law now or hereafter in effect and such
proceeding is not dismissed or discharged within sixty
(60) calendar days of commencement. |
| 1.26 |
“ Labeling Materials ” shall have the
meaning set forth in Section 3.1 . |
| 1.27 |
“ MAA ” shall mean the Marketing Application
as approved by the EMEA on June 10, 2003 that provides for
marketing approval for Aldurazyme in the European Union, as the
same may be updated or amended from time to time. |
| 1.28 |
“
Manufacturing Know-How ” shall mean all information,
techniques, inventions, discoveries, improvements, practices,
methods, knowledge, skill, experience and other technology, whether
or not patentable or copyrightable, and any copyrights based
thereon, relating to or necessary or useful for the production,
purification, packaging,
|
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storage and transportation
of Collaboration Products, including without limitation
specifications, acceptance criteria, manufacturing batch records,
standard operating procedures, engineering plans, installation,
operation and process qualification protocols for equipment,
validation records, master files submitted to the FDA, process
validation reports, environmental monitoring processes, test data
including pharmacological, toxicological and clinical test data,
cost data and employee training materials.
|
| 1.29 |
“ Marketing Application ” shall mean a
marketing authorization application filed by or under authority of
Genzyme with the requisite health regulatory authority of any
country requesting approval for commercialization of Aldurazyme for
a particular indication in such country, including as applicable,
the MAA. |
| 1.30 |
“ Marketing Application Approval ” shall
mean, with respect to each country approval of the Marketing
Application filed in such country by the health regulatory
authority in such country, including as applicable, the
MAA. |
| 1.31 |
“ Marketing Costs ” with respect to
Aldurazyme shall mean the sales and marketing costs and expenses
incurred by Genzyme with respect to work performed by Genzyme and
its Affiliates and subcontractors in connection with the
performance of and in accordance with the marketing plan for
Aldurazyme, including without limitation, sales and marketing costs
related to performing market research, advertising, producing
promotional literature, sponsoring seminars and symposia, sales
training meetings and seminars, originating sales, providing
reimbursement and other patient support services, recruitment costs
and salaries and associated expenses for sales and marketing
personnel and support staff, and distribution fees. |
| 1.32 |
“ Master Batch Record ” shall mean a written
description of the procedure to be followed by BioMarin in
processing of a Batch of Aldurazyme, which description shall
include, but not be limited to, a complete list of all active and
inactive ingredients, components, weights and measures and
procedures used in processing the Aldurazyme within the meaning of
21 CFR part 211.186, or its successor as in effect from
time to time. |
| 1.33 |
“Members Agreement” shall have the meaning
set forth in the recitals. |
| 1.34 |
“ MPS-I ” shall mean mucopolysaccharidosis
I. |
| 1.35 |
“ Multiple Products Sale ” shall mean a sale
of Aldurazyme by Genzyme or its Affiliates to an independent Third
Party customer that is associated, by contract or course of
dealing, with the use or sale or one or more other products or
services [ ****]. In determining the consideration received for
Aldurazyme, the following shall be excluded: (i) Aldurazyme
from the quantities provided to Genzyme pursuant to
Section 6.1(d)(i) , and (ii) transfers of
Aldurazyme that are excluded from the definition of Net Sales under
Section 1.36 below. |
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| 1.36 |
“ Net Sales ” with respect to Aldurazyme
shall mean the gross invoiced sales price of Aldurazyme billed to
independent Third Party customers, including without limitation
Third Party distributors, in fully legitimate, arms length
transactions, less : (a) credits or allowances
granted upon billing corrections, (b) credits or allowances
granted upon returns or rejections, provided that such Aldurazyme
shall be deemed to be unsold and treated in accordance with
Section 6.7 ; (c) freight, shipping and insurance
costs (incurred in transporting Aldurazyme to such customers to the
extent separately billed); (d) quantity, cash and other trade
discounts [****], credits or allowances actually allowed and taken;
(e) customs duties, surcharges and taxes and other
governmental charges incurred in connection with the production,
sale, transportation, delivery, use, exportation or importation of
Aldurazyme in final form; (f) amounts incurred resulting from
governmental mandated rebate or discount programs; and
(g) Third Party rebates and charge backs, hospital buying
group/group purchasing organization administration fees or managed
care organization rebates; all in accordance with standard
allocation procedures, allowance methodologies and accounting
requirements consistently applied, which procedures, methodologies
and requirements are in accordance with GAAP. “ Net
Sales ” with respect to Aldurazyme sold in Multiple
Products Sales shall be calculated by Genzyme in good faith and
shall equal a fair and equitable allocation of all consideration
received by Genzyme in connection with a Multiple Products Sale,
considering the nature and economic value of each component of the
Multiple Products Sale. The transfer of Aldurazyme by Genzyme or
one of its Affiliates to another Affiliate of Genzyme in
furtherance of a sale to a Third Party shall not be considered a
sale; in such cases, Net Sales shall be determined based on the
invoiced sales price by the Affiliate to its customer, less the
deductions allowed under this Section 1.36 . “
Net Sales ” shall not include transfers of Aldurazyme
for use for clinical purposes, in compassionate or expanded access
programs, or in programs for patients paying a nominal price for
Aldurazyme. |
| 1.37 |
“ Operating Agreement ” shall mean that
certain Operating Agreement of BioMarin/Genzyme LLC dated as of
September 4, 1998 entered into by and among the BioMarin
Companies and Genzyme. |
| 1.38 |
“ Order ” shall mean a firm purchase order
originated by Genzyme and sent to BioMarin which sets forth, at a
minimum, the quantities of Aldurazyme ordered, the delivery dates
and other material information as set forth in Section
3.3. |
| 1.39 |
“ Original Collaboration Agreement ” shall
have the meaning set forth in the recitals. |
| 1.40 |
“ Party ” shall mean BioMarin, Genzyme or
BioMarin/Genzyme LLC, as applicable, and “ Parties
” shall mean BioMarin, Genzyme and BioMarin/Genzyme LLC,
collectively. |
| 1.41 |
“ Patent Rights ” shall mean all US and
foreign patents and patent applications (including continuations,
continuations-in-part, divisionals, reissues, re-examinations,
renewals, supplemental protection certificates and extensions)
which are or become owned or controlled by a Party or to which such
Party has, now or in the future, the right to grant licenses and
other rights, which generically or specifically claim Collaboration
Products, a process for manufacturing Collaboration Products, an
intermediate used in such process or a use of a Collaboration
Product. |
-6-
| 1.42 |
“ Patient ” shall mean any person who is the
actual recipient of Aldurazyme for clinical or medical
purposes. |
| 1.43 |
“ Percentage Interest ” shall have the
meaning set forth in the Operating Agreement. |
| 1.44 |
“ Post-Marketing Studies ” shall mean any
clinical trial using Aldurazyme performed by Genzyme or its
Affiliates required by regulatory authorities as a condition to the
issuance, continuation, or maintenance of a Marketing Application
Approval. Post-Marketing Studies shall not include
registries. |
| 1.45 |
“ Regulatory Approvals ” shall mean all
approvals from regulatory authorities in any country required
lawfully to manufacture and market Aldurazyme in any such country,
including without limitation approval of any BLA, any establishment
license application filed with the FDA to obtain approval of the
facilities and equipment to be used to manufacture Aldurazyme, any
Marketing Application Approval and any product pricing approvals
where applicable. |
| 1.46 |
“ Regulatory Scheme ” shall mean the U.S.
Food, Drug and Cosmetics Act and the regulations, interpretations
and guidelines promulgated thereunder by the FDA or the regulatory
scheme applicable to Aldurazyme in any country other than the
United States, as such statutes, regulations, interpretations and
guidelines or regulatory schemes may be amended from time to
time. |
| 1.47 |
“ Related Agreements ” shall mean the
Amended and Restated Collaboration Agreement, the Members
Agreement, the Fill Agreement and the Operating
Agreement. |
| 1.48 |
“Serious Adverse Experience” shall mean any
Adverse Experience associated with the use of any of Aldurazyme
that results in one or more of the following outcomes: death; a
life-threatening experience; required or prolonged inpatient
hospitalization; persistent or significant disability or
incapacity; a congenital anomaly or defect; or the occurrence of an
important medical event that may jeopardize the health of a Patient
or subject, and may require medical or surgical intervention to
prevent one of the outcomes listed above. |
| 1.49 |
“ SOP” shall mean standard operating
procedure. |
| 1.50 |
“ Specifications ” shall mean the written
specifications for Aldurazyme set forth in Exhibit A hereto;
provided that such specifications shall at all times comply
with the relevant Regulatory Scheme in the country of sale and in
the country of use. The Specifications with respect to any
particular country shall automatically be amended upon receipt of
required Regulatory Approvals from the regulatory authorities in
such country for any changes thereto. Copies of the then-current
Specifications shall be maintained by both BioMarin and Genzyme and
shall become a part of this Agreement as if incorporated
herein. |
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| 1.51 |
“ Taxes ” shall have the meaning set forth
in Section 6.5 . |
| 1.52 |
“ Technology ” shall mean inventions, trade
secrets, copyrights, know-how, data and other intellectual property
of any kind (including without limitation any proprietary
biological or other materials, compounds or reagents, but not
including Patent Rights). |
| 1.53 |
“Technical Agreement” shall have the meaning
set forth in Section 3.18 . |
| 1.54 |
“Territory” shall mean the
world. |
| 1.55 |
“ Third Party ” shall mean any entity other
than BioMarin/Genzyme LLC, BioMarin or Genzyme and their respective
Affiliates. |
| 1.56 |
“ Third Party Licenses ” shall mean those
licenses between BioMarin/Genzyme LLC and Third Parties set forth
on Schedule 1.56 . If after the Effective Date any Party
enters into an agreement to license or acquire rights from a Third
Party with respect to subject matter to be utilized in connection
with Aldurazyme in accordance with Section 3.1.4 of the
Amended and Restated Collaboration Agreement, such agreements shall
also be included in the definition of Third Party Licenses for
purposes of this Agreement. |
| 2. |
E XCLUSIVE R ELATIONSHIP
. |
| 2.1 |
Non-Compete . Except as otherwise expressly provided
herein or in the Amended and Restated Collaboration Agreement and
the Fill Agreement, during the term of this Agreement, neither
BioMarin/Genzyme LLC, Genzyme nor BioMarin, nor any of their
respective Affiliates, shall independently, or with or through a
Third Party, conduct research or development activities regarding,
or engage in the manufacture, marketing, sale or distribution of,
Collaboration Products in the Field and in the
Territory. |
| 3.1 |
Manufacturing . Subject to the terms and conditions of
this Article 3 , during the term of this Agreement,
BioMarin shall supply Genzyme with filled (but not labeled)
Aldurazyme, and Genzyme shall exclusively purchase its requirements
from BioMarin except as provided herein. The Aldurazyme supplied to
Genzyme (i) shall conform in all respects to the
Specifications, (ii) will be manufactured under cGMP using the
process licensed or approved by regulatory authorities,
(iii) shall have a remaining shelf life at the time of
delivery to Genzyme of at least [****] of the total expiry of the
product and (iv) shall not have experienced any manufacturing
process deviations that would require notice to any regulatory
authorities unless, prior to delivery to Genzyme, such regulatory
authorities have been notified and have approved the deviations.
BioMarin shall ensure that Genzyme has a complete and accurate copy
of the Master Batch Record (as it may be modified from time to time
pursuant to this Agreement). BioMarin and Genzyme shall be
responsible for release testing as provided in the Technical
Agreement; provided , however , that BioMarin agrees
to complete all release testing for which is responsible under the
Technical Agreement and provide the testing and release
documentation to Genzyme within [****] of delivery of each such
Lot. Genzyme shall prepare all Aldurazyme in final packaged form,
including, without limitation, all product labeling and other
package inserts and materials required by applicable regulatory
agencies (collectively, “ Labeling Materials
”). |
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| |
3.2.1 |
Initial Forecast and Initial Shipments . Prior to the
Effective Date, Genzyme will provide to BioMarin a written initial
forecast of sales and estimates of forthcoming orders of Aldurazyme
from BioMarin that will cover the fifteen (15) month period
commencing on the Effective Date. On the Effective Date, BioMarin
will deliver sufficient vials of Aldurazyme to Genzyme such that
Genzyme will hold at least [****] of filled Aldurazyme. Thereafter,
BioMarin will promptly deliver all additional quantities of filled
Aldurazyme as soon as each Lot is available for delivery in
accordance with the delivery schedule specified in the initial
forecast through September 30, 2008. |
| |
3.2.2
|
Rolling Forecasts .
Beginning on March 17, 2008, Genzyme will provide to BioMarin
a rolling written fifteen (15) month forecast of sales
and estimates of forthcoming orders of Aldurazyme from BioMarin
that will cover the period commencing at the beginning of the third
(3 rd ) following calendar quarter. For example, assuming that
this Agreement is effective as of January 1, 2008, the
forecast delivered by March 17, 2008 would cover the period of
October 1, 2008 through December 31, 2009. Genzyme shall
update such rolling fifteen-month forecast every calendar quarter
(such that each forecast shall cover fifteen (15) months on a
rolling basis), and such updates shall be provided not later than
fifteen (15) days prior to the commencement of each
quarterly period during the term hereof. The first
three (3) months of each such forecast (i.e.
October 1, 2008 through December 31, 2008 in the above
example) shall constitute a binding commitment to order the
quantity of Aldurazyme forecast for such period (the “
Firm Period ”). Projections for months four
(4) through fifteen (15) (i.e., January 1, 2009
through December 31, 2009 in the above example) shall
constitute Genzyme’s reasonable best estimates of future
orders, but shall not be binding on Genzyme. To the extent that any
new quarterly forecast calls for BioMarin to provide vials of
Aldurazyme in quantities that exceed the average quarterly volume
sold by Genzyme for the previous [****] period by more than [****],
BioMarin shall not be required to provide such increased quantity
of Aldurazyme without its consent; provided , however
, that BioMarin will use its commercially reasonable and diligent
efforts to supply the entire quantity of Aldurazyme ordered by
Genzyme during such period. Additionally, BioMarin shall not be
obligated to supply vials of Aldurazyme in quantities that exceed
[****] of Genzyme’s estimate for vials of Aldurazyme for the
relevant twelve-month non-binding period (based on the lowest
non-binding forecast for each respective calendar quarter);
provided , however , that BioMarin will use its
commercially reasonable and diligent efforts to supply the entire
quantity of Aldurazyme ordered by Genzyme during such period,
provided further, that BioMarin shall be under no obligation to
alter its scheduled manufacturing of other products.
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| 3.3 |
Orders . Genzyme shall submit to BioMarin an Order with
each rolling fifteen-month forecast covering the Firm Period
reflected in each such forecast. Each Order shall specify the
quantity ordered, the required delivery date ( provided that
such delivery date is not earlier than [****] days after the
date of such Order), and any special instructions or invoicing
information. For example, the forecast delivered by March 17,
2008 shall state a required delivery date no earlier than [****],
2008 for the Order covering the Firm Period (i.e., the quarterly
period running from October 1, 2008 through December 31,
2008) reflected in such forecast. With respect to the quantity
ordered, Genzyme shall indicate in the Order the number of vials of
Aldurazyme (specifying the number of vials of Aldurazyme meeting
each different Specification) to be used for each of the following
categories, based on Genzyme’s good faith estimates at such
time: (a) commercial sales, (b) compassionate use or
expanded access programs, (c) Post-Marketing Studies (other
than Post-Marketing Studies conducted under the Amended &
Restated Collaboration Agreement), and (d) acceptance and
in-country testing, final Lot release and regulatory requirements.
Each Order issued shall be governed by the terms of this Agreement.
BioMarin shall accept and fill all properly placed Orders that are
consistent with the rolling forecasts and the limitations set forth
in Section 3.2 . BioMarin shall notify Genzyme
(i) within [****] business days of the date of the Order with
respect to all Orders that conform to this Agreement of its
acceptance of such Order and (ii) within [****] business days
of the date of the Order with respect to all Orders that BioMarin
questions, in good faith, the consistency of such Order with the
rolling forecasts or the limitations set forth in
Section 3.2 , whether or not it is accepting such
Order. Any terms or conditions of any such Order that conflict or
are inconsistent with the terms of the Agreement are hereby
rejected. Genzyme agrees to use its commercially reasonable and
diligent efforts to manage the purchase and delivery cycle so that
Genzyme or its Affiliates is at all times after October 1,
2008 holding at least [****] of filled inventory of Aldurazyme,
with the exact amount being held in inventory to be determined
based on anticipated demand as determined by Genzyme in good
faith. |
| 3.4 |
Safety
Stock . Except as provided below, BioMarin agrees to use its
commercially reasonable and diligent efforts to hold at least
[****] inventory of Aldurazyme at all times after October 1,
2008, with the exact amount being held in inventory to be
determined based on anticipated demand as reflected in
Genzyme’s rolling forecasts. In addition, in the event that
there is a proposed change in the facilities used to manufacture
Aldurazyme pursuant to Section 3.10 below or a proposed
modification of the Specifications or the processes used to
manufacture Aldurazyme pursuant to Section 3.11 ,
BioMarin shall (i) hold ready for immediate transfer to
Genzyme sufficient additional inventory of filled Aldurazyme
(“ Change Control Safety Stock ”) to reasonably
ensure uninterrupted supply of such Aldurazyme in each country in
the Territory in which Aldurazyme is distributed, marketed and sold
until the necessary Regulatory Approvals for such change or
modification are obtained in such country; and (ii) ensure
that all such Change Control Safety Stock shall at all times be
manufactured and produced using the facilities, Specifications or
processes approved by
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the appropriate government
or regulatory authorities in each country in the Territory as
appropriate to enable sale of such Change Control Safety Stock in
such country until the necessary Regulatory Approvals for such
change or modification are obtained in such country.
|
| 3.5 |
Shipping of Aldurazyme . BioMarin will deliver
Aldurazyme sold to Genzyme [****] by such means of transportation
as shall be reasonably determined by BioMarin from time to time.
BioMarin shall use its commercially reasonable and diligent efforts
to ship Aldurazyme so that it will arrive at Genzyme’s
facility on or within [****] business days of the date specified in
the relevant Order. To the extent BioMarin incurs any shipping
charges, premiums for freight insurance, customs duties or other
import or export fees, or other transportation costs in connection
with shipments of Aldurazyme to Genzyme, BioMarin will be solely
responsible for such amounts. Included with each shipment or
provided separately but concurrently with such shipment shall be
the Certificate of Analysis for the drug product, Certificate(s) of
Analysis for each Lot of drug substance or intermediate that went
into the drug product, and a certificate of cGMP compliance in a
form reasonably agreed to by BioMarin and Genzyme. All other
obligations of BioMarin relating to the documents to be provided in
connection with each shipment of Aldurazyme shall be governed by
the Technical Agreement. |
| 3.6 |
Compliance with Laws. BioMarin shall comply with all
applicable laws, rules and regulations applicable to the
manufacture, storage, handling and shipment of
Aldurazyme. |
| 3.7 |
Direct Shipment to Customers . BioMarin shall not be
required to ship Aldurazyme directly to a customer of Genzyme
unless Genzyme first seeks and obtains BioMarin’s prior
written approval for such a shipment. BioMarin shall not ship
Aldurazyme to any Third Party (other than bulk material to vendors
for the sole purpose of filling Aldurazyme on behalf of BioMarin),
without Genzyme’s prior written authorization. |
| 3.8 |
Risk of Loss . [****] |
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| |
(g) |
Genzyme shall not be obligated under any circumstances to
accept delivery of any Lot of Aldurazyme unless it meets the
Specifications and Regulatory Approvals for the relevant country in
the Territory (as determined through the mechanism set forth in
this Section 3.9 ) and the applicable warranties set
forth herein. Genzyme shall be entitled to return to BioMarin any
Aldurazyme which the Parties reasonably agree cannot or should not
be sold due to a change in the Specifications or Regulatory
Approvals, and BioMarin shall promptly replace, at no additional
expense to Genzyme, such Aldurazyme with new Aldurazyme that does
conform with the approved Specifications and Regulatory Approvals
for the relevant country in the Territory. |
| 3.10 |
Suppliers . Without limiting BioMarin’s
responsibility under this Agreement, BioMarin shall have the right
at any time to satisfy its supply obligations to Genzyme hereunder,
either in whole or in part, through arrangements with Third Parties
engaged to perform services or supply facilities or goods in
connection with the manufacture, testing, and/or packaging of
Aldurazyme. BioMarin shall ensure that all such facilities comply
with applicable regulations and will give Genzyme written notice at
least [****] days in advance of any such arrangement to determine
whether such arrangement would require changes to a Marketing
Application Approval application filed in any country and, if so,
whether prior approval of any such changes is required by the
regulatory authority in such country. To the extent that a change
is required, after receipt of all necessary data from BioMarin,
Genzyme shall, at BioMarin’s expense, use its commercially
reasonable and diligent efforts to prepare and make such filings
and, if required, seek approval for such change in such countries
that Genzyme has responsibility for pursuant to
Section 5.1.2(a) ; and BioMarin shall, at its own
expense, use its commercially reasonable and diligent efforts to
make such filings and, if required, seek approval for such change
in the United States. BioMarin shall be required to continue to
supply drug product using materials or testing from previously
approved suppliers for each country in the Territory until such
Regulatory Approvals are received in such country and to clearly
mark which Lots use the new suppliers or testing laboratories at
the time of shipment. |
| 3.11 |
Changes to Aldurazyme . |
| |
(a) |
BioMarin may, at its election and in its sole discretion,
modify the Specifications of or processes used to manufacture
Aldurazyme at any time, subject to (i) BioMarin generating
such data, including without limitation development, comparability,
stability and validation data, as may be necessary to obtain
Regulatory Approvals for such changes and (ii) such Regulatory
Approvals being obtained; provided , however , that
to the extent that any such modification would require clinical
trials with MPS-I patients in order to obtain the necessary
Regulatory Approvals for such modification, BioMarin may not
implement such modification without the prior written consent of
Genzyme, which consent shall not be unreasonably withheld, delayed
or conditioned. BioMarin will give Genzyme written notice of any
such change at least [****] days prior to its implementation,
together with a proposed amendment to Exhibit A
reflecting and identifying such change. Exhibit A shall not
be amended to reflect any such change unless and until any
necessary amendments to any Marketing Applications and Regulatory
Approvals to implement such changes are approved by the appropriate
regulatory authorities. |
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| |
(c) |
Additionally, Genzyme may be required, as a result of
negotiations with or directions from a regulatory authority of a
country in the Territory, to propose changes in the Specifications
as a condition to marketing or continuing to market Aldurazyme in
that country. BioMarin shall use its commercially reasonable and
diligent efforts to accommodate such changes to the Specifications
for such country; provided that BioMarin may decide not
accommodate any such change to the extent that it would require a
change to the manufacturing process, if (i) historical data
does not support such proposed Specification changes,
(ii) such change would increase BioMarin’s cost of goods
sold, or (iii) such change would jeopardize BioMarin’s
ability to manufacture Aldurazyme for global demand. BioMarin
recognizes that any such failure to accommodate any changes
required by a regulatory authority in the Territory (or any delay
in accommodating any such changes) may result in the prevention or
suspension of distribution and sales of Aldurazyme in that
country. |
| |
(d) |
Subject to Sections 3.2 and 3.3 , BioMarin shall
continue to supply Genzyme with Aldurazyme for each country in the
Territory conforming to the then-approved Specifications or
manufacturing process for such country as requested by Genzyme
until such time as any change in the Specifications or
manufacturing process, as applicable, is approved by the relevant
regulatory authority(ies) for such country. |
| 3.12 |
Responsibility for Costs . BioMarin shall be solely
responsible for all costs resulting from decisions made by BioMarin
pursuant to Sections 3.10 and 3.11 above, including without
limitation, Genzyme’s fully burdened costs incurred in
accordance with such Sections (including Genzyme’s FTE
costs, filing fees, translation costs, and the costs of any changes
to Labeling Materials resulting from decisions or changes made
pursuant to such Sections) unless the change is
related to (a) updating filings for raw materials, reagents,
replacements for obsolete equipment or other material used in the
manufacture or testing of Aldurazyme that are no longer available
on commercially reasonable terms or (b) updating filings
related to material used in the manufacture, release or testing of
Aldurazyme based on the process and procedures included with then
current Regulatory Approvals (such as validation of quantities of
reference material), in which cases Genzyme shall make such filings
and secure such Regulatory Approvals outside of the United States
at Genzyme’s sole expense and BioMarin shall make such
filings and secure such Regulatory Approvals in the United States
at BioMarin’s sole expense. Genzyme shall provide BioMarin
with quarterly, reasonably detailed invoices for all such costs,
and BioMarin shall reimburse Genzyme for such costs within
forty-five (45) days after receipt thereof. Notwithstanding
any of the above, (i) any changes resulting from the request
or direction of the FDA, EMEA or any other regulatory authority
other than as a direct result of a change proposed or implemented
by BioMarin pursuant to Section 3.10 or 3.11,
(ii) those changes set forth on Schedule 3.12 and
(iii) the
|
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| |
validation of a Third
Party [****] pursuant to Section 3.8 of the Fill
Agreement shall not be deemed to be decisions made by BioMarin
pursuant to Section 3.10 and 3.11 above and Genzyme
shall bear all costs and expenses related to making all filings and
seeking approval for such changes in all countries outside of the
United States while BioMarin shall bear all costs and expenses
related to making all filings and seeking approval for such changes
in the United States; provided , however , that with
respect to the changes set forth in Schedule 3.12 , priority
shall be given to those changes that fall into the categories
described in clauses (a), (b) and (i) above;
provided further that Genzyme’s responsibility under
this Section 3.12 with respect to the cost of making
regulatory filings and securing Regulatory Approvals outside of the
United States (A) for the changes set forth in Schedule
3.12 shall end upon the earlier of (x) completion of such
regulatory activities or (y) such time as the costs incurred
with respect to such regulatory activities equal [****] and
(B) related to the validation of a Third Party pursuant to
clause (iii) above shall be for the first [****] of
such costs (thereafter, BioMarin shall be responsible for the next
[****], of such costs and BioMarin and Genzyme shall share equally
any such costs in excess of [****] (with BioMarin reimbursing
Genzyme for BioMarin’s portion of all such costs within
forty-five (45) days after receipt of reasonably detailed
invoices therefor)).
|
| |
(a) |
In the event that technical, regulatory or other reasons or
events beyond BioMarin’s reasonable control prevent BioMarin
from producing Aldurazyme, BioMarin will use its commercially
reasonable and diligent efforts to secure a Third Party contract
manufacturer in a timely manner. All such contract manufacturing
activities will be at BioMarin’s sole cost and expense and
BioMarin shall have full authority to direct and control the
contract manufacturer and Genzyme, except as provided below, shall
continue to purchase Aldurazyme from BioMarin. Notwithstanding the
foregoing, during the technology transfer to and validation of any
Third Party contract manufacturer, Genzyme may, at its election and
expense, have technical representatives present for such activities
and BioMarin will consider, but will have no obligation to
implement, any suggestions or recommendations made by such
representatives. |
| |
(b) |
In the event
that BioMarin is unable to secure a Third Party contract
manufacturer within [****] days, then BioMarin shall offer Genzyme
the opportunity to produce Aldurazyme. If Genzyme agrees to produce
Aldurazyme, then BioMarin and Genzyme shall promptly negotiate in
good faith commercially reasonable and diligent terms and
conditions for such arrangement; provided , however ,
BioMarin and Genzyme shall negotiate in good faith for payment
amounts and structures to compensate Genzyme for its out of pocket
and internal expenses incurred in the technology transfer and
regulatory process, cost of involvement to allow it to manufacture
Aldurazyme and variable costs associated with the actual production
of Aldurazyme. If BioMarin and Genzyme enter into such arrangement,
then BioMarin will promptly initiate a technology transfer process
during which BioMarin and its
|
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| |
subcontractors, as
appropriate, will provide Genzyme or its designee with all
know-how, data and information necessary or desirable to enable
Genzyme to manufacture or have manufactured Aldurazyme for the
Territory. Additionally, BioMarin will make such employees involved
in the development, manufacture and release of Aldurazyme available
to ensure a complete technology transfer is achieved in a timely
fashion.
|
| |
(c) |
In the event that BioMarin and Genzyme enter into an
arrangement pursuant to clause (b) above and BioMarin
is subsequently able to resume production of Aldurazyme, BioMarin
may elect, upon [****] days prior written notice to Genzyme to
reacquire such production responsibilities from Genzyme. If
BioMarin elects to reacquire production responsibilities from
Genzyme, then BioMarin will promptly reimburse Genzyme the total
amount of costs incurred by Genzyme (including, without limitation
any and all capital expenditures) in connection with the technology
transfer process described in clause (b) above,
building or acquiring capacity and resources to manufacture
Aldurazyme, filing for and obtaining all necessary Regulatory
Approvals to produce Aldurazyme, and transferring such
manufacturing responsibility back to BioMarin. Such amounts to be
reimbursed by BioMarin to Genzyme pursuant to the previous sentence
shall be offset by the amount such costs have already been
recovered by Genzyme pursuant to payments made by BioMarin pursuant
to clause (b) above. BioMarin shall reimburse Genzyme
for such amounts within forty-five (45) days after receipt of
reasonably detailed invoices therefor. Upon BioMarin resuming
production responsibilities from Genzyme with respect to
Aldurazyme, the royalty payable by Genzyme to BioMarin shall be
increased to those levels set forth in Section 6.1 for
Aldurazyme produced by BioMarin. |
| |
(d) |
BioMarin will use its commercially reasonable and diligent
efforts to continue to produce Aldurazyme for supply to such
countries in the Territory where Aldurazyme is used or sold until
such time as this Third Party manufacturer or Genzyme, as the case
may be, has been approved in all countries in the Territory. If
BioMarin is not able to do so, then Genzyme will not be held in
breach of any of its obligations due to an inability to supply
Patients and commercialize Aldurazyme in such country resulting
from BioMarin’s failure to supply product that meets the
regulatory requirements in such country. |
| 3.14 |
Certificates of Analysis . BioMarin shall perform, or
cause its contract manufacturer(s) to perform, quality assurance,
control tests, and release on each Lot of Aldurazyme, to the extent
specified in and in compliance with the Technical Agreement, before
delivery and shall prepare, or cause its contract manufacturer(s)
to prepare and deliver, a written report of the results of such
tests (for purposes of Sections 3.14 through 3.17
(inclusive), such contract manufacturer(s) shall be included in the
definition of the term “BioMarin”). Each test report
shall set forth for each Lot delivered the items tested,
specifications and results in a Certificate of Analysis containing
the types of information typical for such reports or required by
the FDA or other applicable regulatory authority. BioMarin shall
maintain such certificates for a period of not less than five
(5) years from the date of manufacture or for such longer
period as required under applicable requirements of the FDA or
other applicable regulatory authority. |
-15-
| 3.15 |
Certificates of Manufacturing Compliance . BioMarin
shall prepare, or cause to be prepared and delivered, and maintain
for a period of not less than five (5) years or for such
longer period as required under applicable requirements of the FDA
or other applicable regulatory authority for each Lot of Aldurazyme
manufactured a certificate of manufacturing compliance containing
the types of information typical for such reports or required by
the FDA or other applicable regulatory authority, which certificate
will certify that the Lot of Aldurazyme was manufactured in
accordance with the Specifications and the cGMP Regulations as the
same may be amended from time to time. |
| 3.16 |
Regulatory Inspections; Reports . BioMarin shall advise
Genzyme immediately if an authorized agent of the FDA or other
regulatory authority visits any of manufacturing facilities used to
produce Aldurazyme, for an inspection with respect to the
Aldurazyme, and of any written or oral inquiries by any such
authority about such facilities or the procedures for the
manufacture, storage or handling of Aldurazyme or the packaging,
labeling, marketing, distribution, promotion, commercialization for
sale and sale of Aldurazyme. BioMarin shall furnish to Genzyme the
report and any and all correspondence issued by or provided to such
agency in connection with such visit or inquiry, to the extent that
such report or correspondence relates to Aldurazyme, within ten
(10) business days after BioMarin’s receipt of such
report or correspondence, as the case may be, and Genzyme shall
have the right to comment on any response by BioMarin to such
inspecting agency. Notwithstanding the prior sentence, BioMarin
shall be under no obligation to accept any comments provided by
Genzyme on any response by BioMarin to such inspecting agency and
all submissions to such agency by BioMarin shall be at its sole and
absolute discretion. |
| 3.17 |
Access to BioMarin Facilities . Genzyme shall have the
right to audit once annually each of those portions of the
manufacturing, finish processing or storage facilities where
Aldurazyme is being manufactured, finished or stored, or any
subcontractor who is manufacturing, finishing or storing Aldurazyme
for BioMarin, at any time during regular business hours and upon
reasonable advance notice to ascertain compliance with the cGMP
Regulations, as the same may be amended from time to time. Subject
to the terms and conditions of Section 8.1 below,
confidential information disclosed to or otherwise gathered by
Genzyme during any such audit or provided by BioMarin shall be
maintained as confidential. |
| 3.18 |
Technical Agreement . Within ninety (90) days after
the Effective Date, the Parties shall execute and deliver a new
Technical Agreement containing customary provisions consistent with
the allocation of responsibilities set forth in this Agreement.
Until a new agreement is executed and delivered, the Parties shall
operate under the existing Technical Agreement. |
| 3.19 |
Hollister-Stier Agreement. BioMarin shall have sole
responsibility for managing the relationship with Hollister-Stier
Laboratories, LLC pursuant to the Supply Agreement
|
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| |
by and between
Hollister-Stier Laboratories, LLC and BioMarin/Genzyme LLC dated as
of November 6, 2006, as it may be amended from time to time
(as amended, the “ Hollister-Stier Agreement ”)
and shall be solely responsible for all amounts payable to
Hollister-Stier and liabilities arising under such Agreement. As
soon as practicable after the Effective Date, BioMarin shall use
its commercially reasonable and diligent efforts to cause the
Hollister-Stier Agreement to be assigned from BioMarin/Genzyme LLC
to BioMarin.
|
| 4.1 |
Exclusive Right to Market, Sell and Distribute . Subject
to the terms and conditions of this Article 4, Genzyme
shall have the exclusive right to distribute, market and sell
Aldurazyme throughout the world, including without limitation all
pricing and reimbursement activities. Genzyme agrees (by itself or
through its Affiliates or Third Parties selected by Genzyme at its
election and in its sole discretion) to use its commercially
reasonable and diligent efforts to establish Aldurazyme in the
markets, fulfill market demand and meet the marketing and
distribution goals for Aldurazyme determined by Genzyme in its good
faith, subject to the receipt of necessary Regulatory Approvals and
subject to BioMarin’s performance of its obligations under
Article 3 . |
| 4.2 |
Compliance With Laws . Genzyme shall comply with
applicable laws, rules and regulations in each country in which
Aldurazyme is licensed, marketed or sold relating to the marketing,
sale and distribution of Aldurazyme. Without limiting the
foregoing, Genzyme shall comply with all U.S. federal and state
laws pertaining to price reporting and, except to the extent such
compliance is BioMarin’s responsibility as the holder of the
BLA and subject to BioMarin’s compliance with its obligations
under Section 5.1.2 , marketing disclosure. |
| 4.3 |
Marketing and Distribution Expenses . |
| |
4.3.1 |
Genzyme shall be solely responsible for payment of all
Marketing Costs. |
| |
4.3.2 |
Beginning on January 1, 2008 and continuing so long as
this Agreement remains in force, Genzyme agrees to
[****]. |
| |
4.3.3 |
Genzyme shall keep complete and accurate books and records of
all Marketing Costs relating to Aldurazyme. BioMarin shall have the
right, at BioMarin’s expense, through a certified independent
public accountant, to have reasonable access upon reasonable
advance notice and during normal business hours to such books and
records for the purpose of verifying the accuracy of such Marketing
Costs; provided , however , that BioMarin shall not
have the right to perform any audit work pursuant to this
Section 4.3.3 unless and until [****]. BioMarin and
Genzyme shall agree in good faith upon reasonable procedures before
BioMarin’s auditors begin the audit work pursuant to this
Section 4.3.3 . The report issued by such auditor shall
be final, binding and conclusive upon each of BioMarin and Genzyme.
Such verifications may be conducted not more than once in each
calendar year. The books and records for any particular calendar
quarter may not be examined under this Section 4.4.3
more than once. |
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| |
4.3.4 |
BioMarin agrees that all information subject to review under
this Section 4.3 (other than information directly
related to Aldurazyme) is Genzyme’s confidential information
and that it shall cause its accounting firm to retain all such
information in confidence (even as to BioMarin) subject to the
confidentiality restrictions of Article 8 hereof.
Notwithstanding the prior sentence, Genzyme acknowledges and agrees
that such accounting firm’s obligation to retain all such
information in confidence from BioMarin shall not apply in the
event that BioMarin and Genzyme are involved in a dispute under
Section 13.8 related to this Section 4.3
and such information is necessary for BioMarin’s use in
connection with such dispute; provided , however ,
that BioMarin shall only use such information in connection with
such dispute and such information shall remain subject to the
confidentiality restrictions of Article 8 . |
| 4.4 |
Medical Information . Genzyme shall have sole
responsibility for responding to all requests for medical
information regarding Aldurazyme. If BioMarin receives any such
requests, it shall promptly direct such requests to Genzyme.
Notwithstanding the foregoing, BioMarin may maintain a website or
other informational resources where it may publish general medical
information relating to MPS I, so long as such website complies in
all respects with applicable laws, rules and regulations. This
Section 4.4 shall not prohibit BioMarin from publishing
non-medical information in its investor relations communications,
including on BioMarin’s website, provided that such
publication is consistent with the terms and conditions of
Article 8 . |
| |
4.5.1 |
Genzyme and its Affiliates will be responsible for continuing
all pharmacovigilance activities with respect to Aldurazyme,
including without limitation maintaining Aldurazyme Core Safety
Information. BioMarin shall have the right to audit, at any time
during regular business hours and upon reasonable advance notice to
audit such pharmacovigiliance activities with respect to
Aldurazyme. Such audit rights shall include the right to review,
inspect and/or audit any systems or processes involved or utilized
in such pharmacovigilance activities as well as the right to
review, inspect or audit all information or data necessary to be
filed with any regulatory or governmental authority. |
| |
4.5.2 |
In the event
that the Aldurazyme Labeling Materials must be updated per new Core
Safety Information, after receipt of all necessary information and
data from Genzyme, BioMarin agrees to use its commercially
reasonable and diligent efforts make all necessary regulatory
filings to FDA and obtain approvals in order to ensure the content
of Aldurazyme Labeling Materials in the United States is in-line
with the Core Safety Information. Genzyme shall be responsible for
using its commercially reasonable and diligent efforts
to
|
-18-
| |
make such filings and
obtain such approvals outside of the United States. Each of
BioMarin and Genzyme shall be given the opportunity to attend and
participate in any meetings or discussions that the other Party may
have with any regulatory authorities regarding any submissions or
approvals and shall be provided with an opportunity to review and
comment upon any correspondence, submission or communication that
the other Party may have with any such regulatory authority prior
to such correspondence, submission or communication being made or
submitted to such regulatory authority.
|
| |
4.5.3 |
As of the Effective Date and throughout the term of this
Agreement, Genzyme shall maintain one or more written SOP(s) to
collect Adverse Experience information. The content of any SOP(s)
shall include, but not be limited to, specific instructions
regarding the type of Adverse Experience information collected, the
time frame for collection, provisions for secure transmissions, and
inter-company processes to be used for notification of said
information. In addition to the foregoing, the Parties shall update
the current guidelines and procedures to govern receipt,
processing, assessment and submission of Aldurazyme Adverse
Experience and Serious Adverse Experience reports to the FDA, the
European Commission and other regulatory authorities within sixty
(60) days after the Effective Date. Procedures described
therein shall ensure compliance with all applicable laws and
regulations. The Parties acknowledge that Genzyme’s SOPs as
they exist as of the Effective Date satisfy the requirements of
this Section 5.2.1 for reports to the FDA. |
| |
4.5.4 |
BioMarin shall have responsibility for filing all 15-day alert
reports, 15-day alert follow-up reports and periodic adverse event
reports to the FDA per 21 CFR §600.80. Genzyme or its designee
shall have responsibility for filing such reports outside of United
States, including EMEA and other regulatory authorities according
to the local regulations. |
| 4.6 |
Complaints . Within sixty (60) days after the
Effective Date, Genzyme and BioMarin shall develop a written
protocol for exchanging information on product complaints
concerning Aldurazyme of which either Party becomes aware, so as to
allow each of Genzyme and BioMarin to comply with its regulatory
obligations. At a minimum, such protocol shall provide that the
Party receiving such complaint or information shall promptly, but
in any event not later than twenty-four (24) hours after
receipt, advise the other Party (excluding, for purposes of this
Section, BioMarin/Genzyme LLC) in writing of the details of such
complaint or information, after learning of such information.
Promptly thereafter, Genzyme shall report such incident to the
appropriate regulatory authorities in the countries in which
Aldurazyme is being commercialized, in accordance with the
appropriate laws and regulations of the relevant countries and
authorities; provided , however , that with respect
to reports that are to be made with the FDA, BioMarin shall make
such report using the information prepared by Genzyme. Such
reporting activities shall be coordinated between Genzyme and
BioMarin where time and law permit. The Party initially receiving
the complaint or information shall provide the other Party with all
follow-up information related to such incident generated by the
receiving Party or required by the other Party to satisfy its
regulatory filing obligations. |
-19-
| 4.7 |
Registries; Post-Marketing Studies . |
| |
4.7.1 |
Registries . Genzyme shall have the responsibility for
conducting the MPS-I registry program as it exists on the Effective
Date at Genzyme’s sole expense. In the event that the scope
of the registry program is expanded to implement any Post-Marketing
Studies required by regulatory authorities to be conducted through
or as part of the registry program, such costs above the general
cost of maintaining the registry program as currently conducted
will be funded by BioMarin/Genzyme LLC pursuant to the terms of the
Amended and Restated Collaboration Agreement. |
| |
4.7.2 |
Post-Marketing Studies . With respect to any Post
Marketing Studies required by a jurisdiction where Aldurazyme does
not have Regulatory Approval as of the Effective Date, Genzyme
shall, at its sole expense and in its sole discretion, have the
responsibility for conducting any such Post-Marketing Studies that
are not funded by BioMarin/Genzyme LLC pursuant to the terms of the
Amended and Restated Collaboration Agreement. |
| 4.8 |
Use of Trademarks . Aldurazyme shall be sold under
trademarks determined by Genzyme and owned by or licensed to
Genzyme or BioMarin/Genzyme LLC. |
| 4.9 |
Records . Genzyme shall maintain complete and accurate
records of all movements and transactions involving Aldurazyme by
an appropriate identifier and by customer so that all such
movements and transactions can be traced quickly and effectively.
Genzyme shall maintain such records for a minimum period of five
(5) years after the relevant movement or transaction contained
in such record. The records maintained by Genzyme pursuant to this
Section 4.9 shall be Genzyme’s confidential
information under Article 8 and subject to BioMarin’s
audit rights und |
|
