Manufacturing Agreement - MedImmune Inc. and Dr. Karl Thomae GmbH
MANUFACTURING - AGREEMENT
This Agreement is made as of November 27, 1997, by and between
MEDIMMUNE INC.,
whose registered office is at 35 West Watkins Mill Road, Gaithersburg,
Maryland 20878 U.S.A.
(hereinafter referred to as "MEDIMMUNE")
and
DR. KARL THOMAE GMBH,
whose registered office is at Birkendorfer Strabe 65, 88397 Biberach an der
Riss, Federal Republic of Germany
(hereinafter referred to as "THOMAE").
WITNESSETH
WHEREAS the parties have - among others - concluded a Contract Research and
Development Agreement regarding the research and development of a method to
produce MEDI-493 in a commercial scale; and
WHEREAS MEDIMMUNE has all rights to the Product and is the owner of the
Process and
WHEREAS MEDIMMUNE wishes THOMAE to act as its agent to manufacture Product
for MEDIMMUNE, and THOMAE accepts, to manufacture Product as agent for
MEDIMMUNE for commercial use, manufactured in accordance with the Process.
NOW THEREFORE, the parties hereto agree as follows:
1. DEFINITIONS
In this Agreement the following terms shall have the meanings indicated:
1.1 "MEDIMMUNE" means MedImmune Inc. as laid down first above.
1.2 "Contract Research and Development Agreement" means the agreement
on MEDI-493 (the humanized IgG 1 monoclonal antibody specifically
directed against Respiratory Syncytical Virus (RSV)) between the
parties to this Agreement dated November 27, 1997regarding the
development of the Process.
(PAGE 1)
1.3 "Product-price" means THOMAE's prices for manufacturing Product,
Bulk Product, Final Product and/or Finished Product (as the case
may be) to be calculated on the basis of the assumptions set forth
in Appendix 1.
1.4 (CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
1.5 "Product" means any product containing MEDI-493 in Bulk Product or
as Final Product or as Finished Product its sole or combined active
ingredient and produced according to the Process.
1.6 "Bulk Product" means Product which has been purified to a
concentrated form and can be stored in a liquid or frozen form
under appropriate conditions.
1.7 "Final Product" means unlabelled final container containing
lyophilized Product.
1.8 "Finished Product" means Final Product and also labelled and
packaged.
1.9 "Specifications" mean the specifications to be enclosed hereto as
Appendices 3 for Product, Final Product and Finished Product
produced and supplied hereunder by THOMAE. These Appendices will be
agreed upon by the parties after the finalization of the Process.
1.10 "Process" shall be the final Process for manufacturing Product
developed and agreed by the parties according to the Contract
Research and Development Agreement.
1.11 All other terms used herein shall have the same meaning as defined
in the Contract Research and Development Agreement.
2. MANUFACTURING
2.1 (a) Subject to MEDIMMUNE's right to manufacture set forth in
Section 2.1 (b), MEDIMMUNE hereby appoints THOMAE as
MEDIMMUNE's exclusive agent to manufacture Product for
MEDIMMUNE and THOMAE hereby accepts such agreement
(b) Subject to MEDIMMUNE's right to manufacture Bulk Product
and/or Final Product and/or to have a third party to produce
Final Product and/or Finished Product from Bulk Product
produced by MEDIMMUNE, THOMAE will manufacture Product for
MEDIMMUNE
exclusively throughout the world during the full term of
this Agreement and according to the provisions of this
Agreement (incl. Rolling Forecasts and Minimum quantities) and
MEDIMMUNE
(PAGE 2)
will have and cause its licensees to have Product
manufactured by THOMAE throughout the world for the period of
this Agreement.
2.2 Subject to Section 3 below THOMAE undertakes to manufacture for
MEDIMMUNE the quantities of Product ordered by MEDIMMUNE within its
Capacity. All manufacture of Product hereunder will be made in
accordance with the Process and will be delivered in agreed form
suitably packed as specified in the Specifications.
2.3 All quantities of Product will be produced in a production facility
designated by THOMAE which is approved by the FDA and all of the
European Community regulatory authorities for commercial scale
production and deliveries.
To the extent that MEDIMMUNE requests that THOMAE secure regulatory
approval of the manufactured Product in other countries, then
THOMAE shall seek such regulatory approval of its production
facility unless such approval would require change in the
production facility. MEDIMMUNE shall pay any additional costs for
such approval. If changes are required by the respective authority
and if THOMAE does not agree to make such changes at MEDIMMUNE's
expense, then MEDIMMUNE shall have the right to seek a third party
manufacturer for the respective country(ies).
THOMAE shall take reasonable efforts to secure approval of THOMAE's
manufacturing facility by the FDA and the respective European
regulatory authority and THOMAE's obligations under Section 2.1
above are subject to such approval as the case may be.
2.4 Rolling Forecasts
Beginning as of March 10th, 1998 and by the 10th of the last month
of each quarter MEDIMMUNE will provide THOMAE with a 3 (three)
years Product forecast planning horizon for Final Product and
Finished Product or an update thereof . The planning horizon shall
start the first day of the fourth month after the first forecast
which shall be July 1st 1998 or an update thereof.
The rolling forecasts are to be broken down to single months.
The forecast for the first year (months 1-12) are firm orders and
cannot be changed.
The forecast for the second year (months 13-24) is a partly binding
forecast which means that the forecast can fully be changed within
this period as follows:
the forecast be increased within the Capacity, but is limited to
the following restrictions when decreased:
months 13-15 the forecast can be reduced by
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
months 16-18 the forecast can be reduced by
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
(PAGE 3)
months 19-21 the forecast can be reduced by
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
months 21-24 the forecast can be reduced by
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
The forecast for the third year (months 25-36) is a non-binding
forecast.
The rolling forecasts (including firm orders) for Final Product and
Finished Product are laid down in Appendix 2.
2.5 THOMAE shall use reasonable efforts to manufacture and deliver to
MEDIMMUNE all quantities of the Product beyond the binding
forecasts at MEDIMMUNE's request within its Capacity.
2.6 THOMAE shall make deliveries by the 10th day of the month for which
a firm order is made.
2.7 Minimum quantities
Provided that the Product is approved in the USA, beginning January
1st 1999, the minimum quantity of Product to be ordered for
manufacture on behalf of MEDIMMUNE each calendar year is
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED).
If the quantity falls below the minimum quantity of (CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED) annually, THOMAE will charge
MEDIMMUNE an annual surcharge according to Article 5.2.
2.8 Exclusivity/Competition
During the term of this Agreement, THOMAE agrees that it will not
manufacture Product for a third party nor shall THOMAE assist any
third party with respect to development or manufacture of a
monoclonal antibody against RSV, except where THOMAE is granted
marketing rights to such a monoclonal antibody.
3. QUALITY / WARRANTY / LIABILITY / INDEMNIFICATION
3.1 Warranty/Limitation
THOMAE warrants that the Product to be manufactured by THOMAE here
under corresponds to the Specifications and shall be produced
according to current GMP standard and in accordance with all
applicable laws, rules and regulations in the country where
produced.
The Product shall be delivered free and clear of liens and claims
which affect title.
THOMAE makes no other warranty of any kind, express or implied.
(PAGE 4)
3.2 Tests of the Product and agreed upon Audits
MEDIMMUNE shall have the right to carry out agreed upon customary
tests of the Product and agreed upon audits at reasonable times, of
the premises and facilities where THOMAE performs work under this
Agreement, and of the premises where it stores raw materials,
auxiliary materials, intermediates, packing materials for the
Product and the Product itself. The agreed upon tests of the
Product shall be included in Appendix 3 hereto.
3.3 Defective Product (including loss and inaccurate quantity)
Claims on account of quantity, quality, loss or damages to the
Product shall be made by MEDIMMUNE in writing within 90 (ninety)
days following receipt thereof, and THOMAE's liability for damages
for such claims shall in no event exceed the manufacturing price or
replacement of goods for the particular shipment with respect to
which such claims are made. No Product will be returned to THOMAE
without THOMAE's written permission.
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
3.4 Indemnification by MEDIMMUNE
In accordance with all applicable law MEDIMMUNE shall be
responsible for, and hold THOMAE harmless from any damage, loss,
cost or expense relating to third party claims or suits arising
from the packaging, use, marketing or sale of the Product by
MEDIMMUNE, or its licensees or other authorized persons or
entities, other than those which arise out of a breach of warranty
by THOMAE and those which arise out of gross negligence or willful
misconduct of THOMAE or its officers, employees or agents, and
provided that upon receipt of notice by THOMAE of any claims or
suits relating to such use or sale of the Product, THOMAE shall
notify MEDIMMUNE thereof without delay and shall permit MEDIMMUNE
to handle such claims or suits at the cost and discretion of
MEDIMMUNE including but not limited to defense, settlement and
compromise thereof.
3.5 Infringement of intellectual property rights
With respect to the Process MEDIMMUNE shall be responsible for and
hold THOMAE harmless from any third party claim of infringement of
its intellectual property rights from a third party based upon
THOMAE's contractual activities hereunder.
3.6 Limitation of Warranty / Liability
Except as provided in Article 3.1 above THOMAE makes no warranty of
any kind, express or implied.
Except for willful misconduct THOMAE shall not be liable for any
lost profits or any special, incidental or consequential damages.
(PAGE 5)
3.7 Delivery/Risk of Loss
THOMAE shall deliver or arrange for the delivery of the Product
manufactured for MEDIMMUNE to a carrier designated by MEDIMMUNE on
the basis of EXW THOMAE's plant in Biberach, in accordance with
Incoterms 1990 as published by the International Chamber of
Commerce.
Title to Product manufactured hereunder shall remain with
MEDIMMUNE and risk of loss of Product shall remain with THOMAE
until delivery to the carrier as set forth in the next sentence.
THOMAE's liability as to risk of loss or damage during
transportation thereof shall cease upon delivery of the Product in
good condition to the carrier at THOMAE's plant in Biberach
designated by MEDIMMUNE.
3.8 Indemnification by THOMAE
THOMAE shall indemnify, defend and hold MEDIMMUNE and its officers,
employees and agents harmless from and against all third party
losses, damages, costs and expenses (including, without limitation,
reasonable attorneys` fees), including injury to persons or damage
to property, resulting from any breach of the warranties made by
THOMAE under this Agreement or which arise out of and are proved to
be directly associated with the gross negligence or willful
misconduct of THOMAE or its officers, employees or agents in
carrying the obligations under this Agreement and provided that
upon receipt of notice by MEDIMMUNE of any claims or suits relating
to such use or sale of the Product, MEDIMMUNE shall notify THOMAE
thereof without delay and shall permit THOMAE to handle such claims
or suits at the cost and discretion of THOMAE including but not
limited to defense, settlement and compromise thereof.
3.9 Superiority
No provision which may purport to impose different conditions upon
MEDIMMUNE or THOMAE, nor any other modification of this Agreement,
will be of any force and effect, unless in writing and signed by
both parties claimed to be bound thereby. In the event of any
inconsistencies the terms of this Agreement shall govern.
4. SUPPORT REGARDING POST LICENSING ISSUES
THOMAE is willing to support MEDIMMUNE with regard to post
licensing issues (e. g. possible registration-issues in the various
countries) on commercial conditions to be agreed upon.
5. PRICE AND PAYMENT
(PAGE 6)
5.1 Product-price
The Product-price for manufacturing the Product shall be calculated
according to the scheme laid down in Appendix 1. The basic
assumptions of that scheme as titer, yield, and production scale
will be reassessed after scale-up of the Process to the commercial
scale and then be valid for this Agreement.
5.2 (CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
5.3 Payment Conditions
The Product-price for Product delivered to MEDIMMUNE or according
to MEDIMMUNE's instructions shall be payable by MEDIMMUNE within
30 (thirty) days after receipt of Product by the respective party
in DEM (Deutsche Mark) by wire transfer to an account to be
nominated by THOMAE.
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
5.4 Currency
"Deutsche Mark" or "DEM" means the lawful currency for the time
being of Germany or, in case of the implementation of the European
Monetary Union, the Euro on the basis of the official conversion
rate.
5.5 Prices Adjustments
(a)The Product-price mentioned in Article 5.1 above (basis
01.09.1997) may be increased by THOMAE effective at the
beginning of a calendar year (for the first time effective
January 1st 2000) by (CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED) per year for increasing costs of labour and raw
material.
(b) In case any cost (in terms of cost of labour, material and/or
regulatory requirements for producing Bulk Product, Final
Product and/or Finished Product increases by more than
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED) in a given calendar
year, which THOMAE must demonstrate, the parties shall agree
upon the direct amount of such increase based on good faith
negotiations to be effective on January 1st of the calendar
year
following the more than (CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED) increase and the price for Product in such calendar
year shall be increased for such amount, provided that the
price increase taken by THOMAE under Article 5.5 (a) shall be
credited toward any corresponding increase under this Article
5.5 (b).
(c)In case of a change of the Process which influences the basic
assumptions the price shall be recalculated according to
Appendix 1.
(PAGE 7)
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
6. CONFIDENTIALITY
6.1 THOMAE shall not disclose MEDIMMUNE Confidential Information to any
person other than its employees or employees of affiliated
companies of the Boehringer Ingelheim group who have a need to know
such information in order to perform their duties in carrying out
the work hereunder and who have an obligation to maintain the
confidentiality thereof as provided herein.
6.2 MEDIMMUNE shall not disclose any THOMAE Confidential Information to
any person other than
(a)its employees or consultants who are bound by similar
obligations of confidentiality and who have a need to know such
information in order to provide direction to THOMAE or evaluate
the results of the work, or
(b)regulatory authorities, for example, the FDA, that require such
information in order to review an IND, BLA or other regulatory
filing. THOMAE will be informed and must agree prior to filing
of any THOMAE Confidential Information to regulatory
authorities. In these cases where THOMAE restricts MEDIMMUNE's
ability to file THOMAE Confidential Information, THOMAE agrees
to provide the Confidential Information directly to the
regulatory authorities and will provide a letter of
authorization for cross-reference to MEDIMMUNE.
(c)persons or entities that manufacture Product for MEDIMMUNE
after termination of this Agreement or during this Agreement as
permitted herein.
6.3 The obligations of confidentiality applicable to MEDIMMUNE
Confidential Information and THOMAE Confidential lnformation shall
not apply to any information that is:
(a)known publicly or becomes known publicly through no fault of
the recipient;
(b) learned by the recipient from a third party entitled to
disclose it;
(c)developed by the recipient independently of information
obtained from the disclosing party;
(d)already known to the recipient before receipt from the
disclosing party, as shown by its prior written records;
(PAGE 8)
(e)required to be disclosed by law, regulation or the order of a
judicial or administrative authority; or
(f)released with the prior written consent of the disclosing
party.
7. LICENSE
7.1 Use of MEDIMMUNE Cell Line and Intellectual Property
(a) MEDIMMUNE and THOMAE hereby acknowledge and agree that
MEDIMMUNE is providing Cell Line, Process and MEDIMMUNE
Confidential Information to THOMAE for use by THOMAE on behalf
of and for the benefit of MEDIMMUNE for the purposes of this
Agreement, that THOMAE will make use therof solely for such
purposes and that MEDIMMUNE hereby consents to such use.
(b) MEDIMMUNE hereby delegates to THOMAE as agent for MEDIMMUNE the
authority to manufacture Product solely on behalf of and for
the benefit of MEDIMMUNE.
7.2 Except as granted under this Agreement, no right or license, either
express or implied, under any patent or proprietary right is
granted hereunder by virtue of the disclosure of MEDIMMUNE
Confidential Information or THOMAE Confidential Information.
8. TERM AND TERMINATION
8.1 (CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
8.2 To the extent permitted by law, if either party shall become
insolvent or shall make assignment for the benefit of creditors, or
proceedings in voluntary bankruptcy shall be instituted on behalf
of or against a party or a receiver or trustee of all, or
substantially all of the property of a party shall be appointed,
the other party shall be entitled to terminate this Agreement by
giving written notice to this effect to the first party whereupon
this Agreement shall so terminate, unless such situation is
rectified within a period of 60 (sixty) days.
8.3 Either party may terminate this Agreement for any material breach
of this Agreement, if such breach is not cured within 90 (ninety)
days following receipt by the party committing the breach of
written notice of the intent to terminate. Such termination shall
become effective immediately upon further notice to the defaulting
party.
(PAGE 9)
8.4 Premature Termination
8.4.1 This Agreement may be terminated by MEDIMMUNE at any time if
MEDIMMUNE shall withdraw the Product from all relevant markets.
8.4.2 In this case MEDIMMUNE will pay to THOMAE the Product-price for the
firm ordered quantities (see Article 2.4 above) of the Product.
8.4.3 (CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
8.4.4 These payments shall be due within 1 (one) month after receipt by
THOMAE of the notice of premature termination from MEDIMMUNE and
receipt by MEDIMMUNE of the respective invoice of THOMAE.
8.5 Introduction of the Euro
The introduction of the Euro as the legal currency or legal tender
in Germany (see Article 5.4 above) shall in no way affect the
validity of this Agreement and shall not entitle any party hereto
to terminate, or to require any amendment to, this Agreement.
9. MISCELLANEOUS
9.1 Force Majeure.
Neither party shall be in breach of this Agreement if there is any
failure of performance under this Agreement (except for payment of
any amounts due hereunder) occasioned by any act of God, fire, act
of government or state, war, civil commotion, insurrection,
embargo, prevention from or hindrance in obtaining energy or other
utilities, labor disputes of whatever nature or any other reason
beyond the control of either party; provided, however, that if a
party is not able to perform becomes of a force majeure pursuant to
this Article 8.1 for a period of 6 (six) months, the other party
may terminate this Agreement with immediate effect.
9.2 Publicity.
No press release or other form of publicity regarding the work
performed hereunder or this Agreement shall be permitted by either
party to be published unless both parties have indicated their
consent to the form of the release in writing.
Nothing in this Article 9.2 shall prevent the parties from
disclosing this Agreement as required by applicable laws, rules or
regulations.
(PAGE 10)
9.3 Notices.
Any notice required or permitted to be given hereunder by either
party shall be in writing and shall be (i) delivered personally,
(ii) sent by registered mail, return receipt requested, postage
prepaid or (iii) delivered by facsimile with immediate telephonic
confirmation of receipt, to the addresses or facsimile numbers set
forth below:
<TABLE>
<S> <C>
If to THOMAE: Dr. Karl THOMAE GmbH
Birkendorfer Strabe 65
88397 Biberach an der Riss
Federal Republic of Germany
Attention: Prof. Dr. Rolf G. Werner
Fax: 0 73 51/54-51 31
Phone: 0 73 51/54-48 00
If to MEDIMMUNE: MEDIMMUNE Inc.
35 West Watkins Mill Road
Gaithersburg, Maryland 20878
U.S.A.,
Attention: President
Fax: 301/527-4201
Phone: 301/417-0770
</TABLE>
Each notice shall be deemed given (i) on the date it is received if
it is delivered personally, (ii) 3 days after the date it is sent
by Federal Express, UPS,DHL, MSAS, World Courier or similar service
if receipt is immediately confirmed in writing (iii) on the date it
is received if it is sent by facsimile with immediate telephonic
confirmation of receipt.
9.4 Applicable Law/Jurisdiction.
This Agreement shall be governed by and construed in accordance
with the laws of Germany without regard to its choice of law
principles. The courts of the place of domicile of THOMAE shall
have exclusive jurisdiction over all legal matters and proceedings
hereunder.
9.5 Compliance
with Laws.
THOMAE shall
perform the work hereunder in conformance with current GMP, as
applicable, and all German and/or EEC laws, ordinances and
governmental rules or regulations pertaining thereto.
(PAGE 11)
9.6 Relationship
THOMAE shall not incur any liabilities on behalf of MEDIMMUNE nor
pledge the credit of MEDIMMUNE nor make any representations or
warranties on behalf of MEDIMMUNE nor hold itself out to third
parties as having any such rights.
MEDIMMUNE shall not incur any liabilities on behalf of THOMAE nor
pledge the credit of THOMAE nor make any representations, or
warranties on behalf of THOMAE nor hold itself out to third parties
as having any such rights.
9.7 Waiver.
No waiver of any term, provision or condition of this Agreement
whether by conduct or otherwise in any one or more instances shall
be deemed to be or construed as a further or continuing waiver of
any such term, provision or condition or of any other term,
provision or condition of this Agreement.
9.8 Severability.
If any provision of this Agreement is held to be invalid or
unenforceable by a court of competent jurisdiction all other
provisions shall continue in full force and effect. The parties
hereby agree to attempt to substitute for any invalid or
unenforceable provision a valid or enforceable provision which
achieves to the greatest extent possible the economic legal and
commercial objectives of the invalid or unenforceable provision.
9.9 Entirety.
This Agreement, including any exhibits and appendices attached
hereto and referenced herein , constitutes the full understanding
of the parties and a complete and exclusive statement of the terms
of their agreement, and no terms, conditions, understandings or
agreements purporting to modify or vary the terms thereof shall be
binding unless they are hereafter made in writing and signed by
both parties.
9.10 Assignment.
This Agreement shall be binding upon the successors and assigns of
the parties and the name of a party appearing herein shall be
deemed to include the names of its successors and assigns provided
always that nothing herein shall permit any assignment by either
party. However, THOMAE may assign this Agreement to an affiliated
company taking over the operative biotech business of THOMAE and
MEDIMMUNE may assign this Agreement in the case of a merger or
acqusition or transfer of its assets related to this Agreement to a
third party without the prior written consent of THOMAE.
(PAGE 12)
IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
executed by their duly authorized representatives on the day and year first
above written.
<TABLE>
<S> <C> <C>
Gaithersburg, Biberach,
MEDIMMUNE, INC. DR. KARL THOMAE GMBH
ppa.
/s/David M. Mott /s/Dr. Jacob /s/Dr. H. Michelberger
David M. Mott Dr. Jacob Dr. H. Michelberger
(Member of Board) (Head of Legal Department)
</TABLE>
Appendix 1:
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
Appendix 2:
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
Appendix 3:
(CONFIDENTIAL TREATMENT HAS BEEN REQUESTED)
(PAGE 13)