Exhibit 1.25
- --------------------------------------------------------------------------------
Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
- --------------------------------------------------------------------------------
SPECIALTY PRODUCTS DIVISION
DEVELOPMENT AND SUPPLY AGREEMENT
This Agreement is entered into this May 1, 2001, and effective January 12,
2001 by and between Abbott Laboratories, an Illinois corporation having a
principal place of business at 100 Abbott Park Road, Abbott Park, Illinois
60064-3500 ("Abbott"), and AltaRex US Corp., a Delaware corporation, having a
principal place of business at 610 Lincoln Street, Waltham, Massachusetts 02451
("AltaRex").
WHEREAS, AltaRex is the owner of certain technology and patent rights
regarding the compound OvaRex(R) monoclonal antibody ("Mab"), which is used as a
drug for ovarian and other cancers;
WHEREAS, AltaRex will file for approval with the United States Food and
Drug Administration (and its foreign equivalents), a Biologics License
Application ("BLA") (and its foreign equivalents), for certain formulations
containing Bulk Drug Substance, as defined below;
WHEREAS, AltaRex has certain process information relating to the synthesis
of Bulk Drug Substance and desires to have Abbott evaluate such information and
to scale-up and adapt the current manufacturing process for the preparation of
Bulk Drug Substance;
WHEREAS, AltaRex desires for Abbott to perform process justification and
process validation for the manufacture of Bulk Drug Substance;
WHEREAS, Abbott possesses process engineering capabilities and operates
process development facilities, which include small scale facilities and a pilot
plant for the manufacture of developmental and clinical quantities of Bulk Drug
Substance, as well as large scale facilities for manufacture of commercial
quantities of certain Bulk Drug Substance;
WHEREAS, Abbott desires to manufacture for AltaRex developmental, clinical
and commercial quantities of Bulk Drug Substance and AltaRex desires to purchase
from Abbott such quantities.
NOW, THEREFORE, in consideration of the premises and the mutual covenants
and agreements contained herein, the parties hereto agree as follows:
1. DEFINITIONS
As used in this Agreement, the following words and phrases shall have the
following meanings:
1.1 "ABBOTT KNOW HOW" means all non-patented technical data, drawings,
documentation, analytical and regulatory information and other information,
including all improvements thereto, not included in Abbott Patent Rights, as
defined below, covering manufacturing and process and Bulk Drug Substance
operations covering or relating to the manufacture of Bulk Drug Substance
according to the process developed hereunder by Abbott for AltaRex, that is
owned by Abbott, or licensed to Abbott, with the right to sublicense, as of the
Effective Date, as defined below, or generated or acquired by Abbott during the
term of this Agreement.
1.2 "ABBOTT PATENT RIGHTS" means United States and foreign patents and
patent applications, including divisions, continuations, continuations-in-part,
additions, renewals, extensions, re-examinations and reissues of all such
patents and patent applications, all as are owned by Abbott, or licensed by
Abbott, with the right to sublicense, claiming manufacturing and/or process
development operations relating to the manufacture of Bulk Drug Substance
according to the process adapted hereunder by Abbott for AltaRex.
1.3 "AFFILIATE" of a party hereto means any entity that controls, is
controlled by, or is under common control with such party. For purposes of this
definition, a party shall be deemed
2
to control another entity if it owns or controls, directly or indirectly, at
least fifty percent (50%) of the voting equity of the other entity (or other
comparable ownership interest for an entity other than a corporation).
1.4 "ALTAREX KNOW HOW" means all non-patented technical data, drawings,
documentation, analytical and regulatory information and other information,
including all improvements thereto, not included in AltaRex Patent Rights, as
defined below, relating to the manufacture, use or sale of Bulk Drug Substance
that is owned by AltaRex, or licensed to AltaRex, with the right to sublicense,
as of the Effective Date or generated or acquired by AltaRex during the term of
this Agreement.
1.5 "ALTAREX PATENT RIGHTS" means United States and foreign patents and
patent applications, including divisions, continuations, continuations-in-part,
additions, renewals, extensions, re-examinations and reissues of all such
patents and patent applications, all as are owned by AltaRex, or licensed to
AltaRex, with the right to sublicense, covering Bulk Drug Substance, and or
processes for making and methods for using such Bulk Drug Substance under which
Abbott would need a license or sublicense to lawfully manufacture Bulk Drug
Substance for AltaRex under this Agreement.
1.6 "BLA" means the Biologics License Application (or its foreign
equivalents) filed with the FDA, seeking authorization to market Bulk Drug
Substance in the Territory.
1.7 "BULK DRUG SUBSTANCE" means the bulk form of OvaRex(R)MAb as more
fully described in Exhibit A.
1.8 "BULK DRUG SUBSTANCE SPECIFICATIONS" means the written specifications
for Bulk Drug Substance set forth in Exhibit B as may be modified in writing
from time to time by AltaRex pursuant to Section 8.8.
3
1.9 "CGMP" means the then FDA current good manufacturing practice, as
specified in the Code of Federal Regulations and FDA guidance documents, and all
successor regulations and guidance documents thereto, including, but not limited
to, ICH guidelines and points-to-consider documents issued by Regulatory
Authorities.
1.10 "CMC" means the Chemistry Manufacturing and Controls (or its foreign
equivalents) filed with the FDA in support of the Bulk Drug Substance BLA.
1.11 "CONFIDENTIAL INFORMATION" means all information disclosed pursuant to
this Agreement in writing (or all information disclosed orally, visually and/or
in another tangible form that is summarized in writing as to its general content
within thirty (30) days after original disclosure and identified as being
confidential), except any portion thereof that:
(a) is known to the recipient, as evidenced by its written records before
receipt thereof under this Agreement;
(b) is disclosed to the recipient without restriction after acceptance of
this Agreement by a third person who has the right to make such
disclosure;
(c) is or becomes part of the public domain through no fault of the
recipient; or
(d) is independently developed by or for the recipient by individuals or
entities who have not had access to Confidential Information, as
evidenced by its written records.
1.12 "CONTRACT YEAR" shall mean a period of twelve (12) consecutive months
commencing on January 1 and ending on December 31; provided, however, that the
first Contract Year of this Agreement shall commence on Launch Date and shall
end, (i) in the case of the Launch Date occurring on or prior to June 30, on the
December 31 following the Launch Date, and (ii) in the case of the Launch Date
occurring after June 30, on the second December 31 following the Launch Date.
1.13 "EFFECTIVE DATE" means January 12, 2001.
4
1.14 "EMEA" shall mean the European Agency for the Evaluation of Medicinal
Products, or any successor entity thereto. 1.15 "FDA" means the United States
Food and Drug Administration (or its foreign equivalents), or any successor
entity thereto.
1.16 "LAUNCH DATE" means the date on which the first commercial sale of
Product following approval by a Regulatory Authority is made in the Territory by
AltaRex or one of its licensees.
1.17 "PRODUCT" means any pharmaceutical product containing Bulk Drug
Substance as its active ingredient.
1.18 "PROJECT" means a multi-stage project to adapt the process for the
manufacture of Bulk Drug Substance.
1.19 "PROPOSAL" means the description of the Project, as set forth in
Exhibit C.
1.20 "QUALITY ASSURANCE DEPARTMENT" shall mean the department within the
Specialty Products Division of Abbott that oversees quality control of products.
1.21 "REGULATORY FILINGS" means the governmental filings required to obtain
approval to market Product in a given country of the Territory, including, but
not limited to, Product registration(s) and marketing approval(s), as
applicable, in each country.
1.22 "REGULATORY AUTHORITIES" means the FDA, the EMEA, or any comparable
national or territorial regulatory entity.
1.23 "TERRITORY" means the entire world.
1.24 "VALIDATION RUNS" means [**] consecutive production batches of Bulk
Drug Substance that are manufactured by Abbott, or on behalf of or for Abbott,
pursuant to and in accordance with the requirements set forth in Exhibit C.
5
2. BULK DRUG SUBSTANCE DEVELOPMENT PROJECT
2.1 PROJECT INITIATION. Promptly after the Effective Date, Abbott shall
undertake the Project. The Project shall consist of research and development
activities described in the Proposal in accordance with Exhibit C. Abbott shall
use its reasonable efforts in performing its research and development activities
hereunder, but AltaRex understands that, because the Project involves research
from which the results are inherently uncertain, Abbott cannot and does not make
any representation, warranty or guarantee of any kind that the Project will
result in a commercially-viable process.
2.2 PROJECT CONTINUATION OPTION.
(a) PROJECT STAGES. At the completion of each of Stage Ia, Ib, II and III
(as defined in Exhibit C), or sooner if both parties agree (unless
otherwise terminated as provided herein), AltaRex shall determine in
its sole discretion whether (i) to proceed with the Project; (ii) to
conduct further development work under the then-current Stage in
addition to those activities described in the Proposal for the then
current Stage; or (iii) to terminate this Agreement.
(b) PROJECT COMPLETION. Abbott shall be under no obligation to reserve
manufacturing capacity during the Stages contemplated under this
Agreement and as defined in Exhibit C. Upon completion of Stages Ia
and Ib, however, Abbott shall reserve capacity sufficient to meet the
Minimum Purchase Obligation of [**] (as defined in Section 7.2(a)) and
AltaRex shall commit to [**] in writing. If at any time during the
Stages 1a or 1b Abbott determines, at its sole discretion, that it
will not have sufficient capacity to meet AltaRex' Minimum Purchase
Obligation due to another product's needs, Abbott will notify AltaRex
in
6
writing and shall give AltaRex thirty (30) days to commit to either
[**] or [**] (as defined in Section 7.2(a)). Abbott will then be
obligated to reserve that capacity accordingly.
3. ABBOTT'S RESEARCH AND DEVELOPMENT ACTIVITIES
3.1 ABBOTT ACTIVITIES. The objective of the Project shall be for Abbott to
develop and manufacture Bulk Drug Substance and to support AltaRex' and its
licensees' Regulatory Filings as appropriate. Therefore, Abbott shall conduct
and perform what will be reasonably anticipated to achieve such objectives,
including, but not limited to, the following:
(a) Sourcing raw materials, supplies and necessary equipment for use in
manufacturing Bulk Drug Substance;
(b) Performing pilot scale evaluation of AltaRex' manufacturing process;
(c) Adapting AltaRex' manufacturing process to Abbott's equipment and
systems;
(d) Preparing suitable manufacturing instructions and manufacturing
controls for inclusion in Regulatory Filings;
(e) Providing appropriate Regulatory Authorities with letters of
authorization referencing the CMC and containing process validation
data, batch documents and other data required to support Regulatory
Filings and to assist AltaRex in responding to questions from
Regulatory Authorities concerning the Bulk Drug Substance;
(f) Conducting material contact and cleaning validation studies,
engineering and Validation Runs, process validation studies, viral
clearance studies, and preparing process justification and validation
summary reports, in a timely manner, to pass FDA pre-approval and
other appropriate Regulatory Authority inspections to
7
support manufacture of the Bulk Drug Substance in the Abbott
manufacturing facility;
(g) Permitting AltaRex to conduct all necessary cGMP and quality assurance
reviews of Abbott documentation, including review and receipt of
copies of Abbott manufacturing work orders;
(h) Permitting AltaRex to approve manufacturing directions and changes to
these documents, nonconforming materials reports, and process
validation reports, with receipt of copies.
(i) Permitting AltaRex to use and access Abbott's data, including the CMC
and compounds as they relate to Bulk Drug Substance manufacture only;
(j) Providing AltaRex with acceptable environmental impact statements for
inclusion with Regulatory Filings, if required;
(k) Providing AltaRex with appropriate pilot and commercial scale batch
record manufacturing documentation for Regulatory Filings;
(l) Preparation for and administration of the FDA pre-approval inspection;
(m) Manufacturing development supplies, clinical supplies, stability
supplies and process validation batches of Bulk Drug Substance in
accordance with current cGMP's and pursuant to protocols to which the
parties shall mutually agree; and
(n) Using reasonable efforts to comply with ex-U.S. regulatory
requirements as they pertain to the manufacture, sale and use of Bulk
Drug Substance.
8
4. ALTAREX' RESEARCH AND DEVELOPMENT ACTIVITIES
4.1 ALTAREX ACTIVITIES. AltaRex shall conduct and perform research and
development activities, including, but not limited to the following:
(a) Providing Abbott with applicable and available analytical methods and
viral titration and viral detection assays, as appropriate, validated
to Abbott's standards for raw materials, in-process tests, validation
studies and manufacture of Bulk Drug Substance and all available
reference materials;
(b) Providing Abbott with technical data on Bulk Drug Substance that
includes, but is not limited to, the following: (i) material safety
data sheets with environmental and safety information, and (ii)
additional detailed data, if necessary, to define potential hazards
and establish employee exposure levels;
(c) Providing Abbott with copies of Regulatory Filings as necessary for
Abbott to obtain regulatory pre-approval inspection;
(d) Maintaining a stability program for, and retain samples of, the
Product;
(e) Selecting and managing a third party to perform the final release
testing; and
(f) Participating with Abbott in development and validation activities.
5. PAYMENT FOR ABBOTT'S DEVELOPMENT EFFORTS
5.1 RESEARCH AND DEVELOPMENT FEE. As consideration to Abbott for its
participation in the Project, AltaRex shall pay Abbott a non-refundable research
and development fee (the "Research and Development Fee") of Twenty-One Million
Nine Hundred and Thirty-Five Thousand Dollars (U.S. $21,935,000) provided all
stages are completed per Section 2.2. Such Research and Development Fee shall be
paid to Abbott as outlined in the Proposal in Exhibit C.
9
5.2 CHANGES IN PROJECT SCOPE. If (1) changes occur in (a) the Project, (b)
the Project Assumptions (as outlined in Exhibit F) or (c) the Bulk Drug
Substance Specifications, or if (2) technical difficulties require that Abbott
perform either additional work or repeat work, and such technical difficulties
are unrelated to Abbott's fault or negligence, Abbott shall provide AltaRex with
a new or revised timeline, project scope, or test protocol with additional cost
estimates for such additional or repeat work. If AltaRex approves such
additional costs and protocols, Abbott shall perform such work and AltaRex shall
pay Abbott's additional costs for such work as specified in the revised
estimate.
5.3 ADDITIONAL COSTS. AltaRex shall pay Abbott for its direct costs for
any external testing (excluding in-process assays [**]), raw materials, process
specific capital equipment and/or process specific modifications if necessary,
and supplies. See Exhibit G for a current estimate of additional costs. Abbott
shall submit to AltaRex a quarterly estimate of such costs broken down by month.
If any item is in excess of [**] U.S. Dollars (U.S. $[**]), such cost will be
approved by AltaRex prior to purchase. AltaRex shall be responsible for all
additional costs under this Section and will either remit to Abbott within
thirty (30) days of the date of invoice in the event Abbott incurs the costs or
shall pay the vendor directly.
6. PILOT SCALE AND NON-CLINICAL AND CLINICAL AND VALIDATION BULK DRUG
SUBSTANCE
6.1 PILOT SCALE AND NON-CLINICAL BULK DRUG SUBSTANCE. Abbott shall provide
to AltaRex pilot scale Bulk Drug Substance from each non-cGMP 100 liter, and
non-clinical Bulk Drug Substance from the [**] 1000 liter run, less any material
needed by Abbott for process justification studies or pre-validation work. The
cost of these runs are [**]
6.2 CLINICAL AND VALIDATION BULK DRUG SUBSTANCE. Abbott shall provide to
AltaRex Bulk Drug Substance suitable for clinical studies from each cGMP 100
liter run, and [**] cGMP
10
1000 liter engineering run and validated Bulk Drug Substance from [**] cGMP
commercial scale lots suitable for clinical or commercial use, less any material
needed for process justification studies or pre-validation work. The cost of
these runs are [**]
7. MANUFACTURE AND COMMERCIAL SUPPLY OF BULK DRUG SUBSTANCE
7.1 PURCHASE AND SALE OF BULK DRUG SUBSTANCE. Pursuant to the terms and
conditions of this Section 7.1 and for the duration of this Agreement, Abbott
shall manufacture, or have manufactured, sell and deliver exclusively to AltaRex
Bulk Drug Substance as identified in purchase orders delivered to Abbott from
time to time by AltaRex. AltaRex shall exclusively purchase Bulk Drug Substance
in the Territory from Abbott so long as Abbott can provide Bulk Drug Substance
that meets the cGMP regulations in the Territory and Abbott provides back up
validated manufacturing capacity to AltaRex at no additional expense to AltaRex.
Abbott shall manufacture, or have manufactured, Bulk Drug Substance in
accordance with the Bulk Drug Substance Specifications as defined in Exhibit B,
and applicable cGMP regulations. Pursuant to Section 8.8, AltaRex may alter the
Bulk Drug Substance Specifications from time to time during the term of this
Agreement by written notification to Abbott without the necessity of formally
amending this Agreement.
7.2 MINIMUM PURCHASE REQUIREMENT.
(a) MINIMUM PURCHASE OBLIGATION. AltaRex covenants to purchase a minimum
amount of Bulk Drug Substance each Contract Year commencing with the
first Contract Year. Within thirty (30) days of BLA approval, AltaRex
shall determine at its sole discretion whether to select [**] or [**]
(as set forth below) as the Minimum Purchase Obligation. The minimum
amount to be purchased during a Contract Year (the "Minimum Purchase
Obligation" or "MPO") shall be:
11
- ------------------------------------------------------------
Contract Year 1 2 3 4 5
- ------------------------------------------------------------
Gram Amount [**] [**] [**] [**] [**]
[**]
- ------------------------------------------------------------
- ------------------------------------------------------------
Contract Year 1 2 3 4 5
- ------------------------------------------------------------
Gram Amount [**] [**] [**] [**] [**]
[**]
- ------------------------------------------------------------
If AltaRex does not purchase the Minimum Purchase Obligation during
any Contract Year, within thirty (30) days after the end of such
Contract Year, AltaRex shall pay to Abbott the purchase price per gram
of Bulk Drug Substance multiplied by any shortfall amount in grams.
The shortfall shall be calculated by taking the Minimum Purchase
Obligation for such Contract Year less the amount of Bulk Drug
Substance actually purchased by AltaRex for such Contract Year. The
purchase price per gram shall be determined at the rate at which
AltaRex would have been invoiced had the Minimum Purchase Obligation
been provided by Abbott pursuant to Section 8.7(a). Abbott may agree,
solely at Abbott's option, to waive such Minimum Purchase Obligation
for any contract year. Example: If the Minimum Purchase Obligation is
[**] and AltaRex only purchases [**] U.S. Dollars (U.S. $[**] per
gram, the shortfall would be [**] at [**] U.S. Dollars (U.S. $[**], or
[**] U.S. Dollars (U.S. $[**]
(b) ALTERNATIVE PURCHASE OBLIGATION. At any time during the term of this
Agreement, when AltaRex provides Abbott with its twenty-four (24)
month rolling forecast, AltaRex may commit to this forecast for the
applicable Contract
12
Year as its new Minimum Purchase Obligation, (the "Alternative
Purchase Obligation"), provided, however, that its twenty-four (24)
month forecast exceeds the Minimum Purchase Obligation or their most
recent Alternative Purchase Obligation. Any shortfall in purchases by
AltaRex from their Alternative Purchase Obligation shall be calculated
as described in Section 7.2(a) with the Minimum Purchase Obligation
now being the Alternative Purchase Obligation.
7.3 PROCESS IMPROVEMENT PROGRAM. After the Launch Date, the parties shall
mutually determine whether to conduct an optional Process Improvement Program,
the terms and conditions of which shall be negotiated in good faith between the
parties.
8. MANUFACTURE OF BULK DRUG SUBSTANCE
8.1 RELEASE AND ACCEPTANCE OF BULK DRUG SUBSTANCE. AltaRex shall be
obligated to accept Bulk Drug Substance from Abbott if it meets the Bulk Drug
Substance Specifications and was manufactured in full compliance with cGMP
regulations. A third party testing organization selected and managed by AltaRex
shall be further obligated to provide final release test results to Abbott in
accordance with Bulk Drug Substance specifications, as is necessary for Abbott
to fulfill its manufacturing obligations under this Agreement. Such test results
shall be provided to Abbott directly from the third party.
8.2 BULK DRUG SUBSTANCE TITLE AND SHIPMENT. Any Bulk Drug Substance
manufactured by Abbott pursuant to this Agreement shall be shipped F.O.B.
Abbott's manufacturing facility in North Chicago, Illinois. Abbott is
responsible for all activities through packaging Bulk Drug Substance. Title and
risk of loss shall pass to AltaRex upon delivery of Bulk Drug Substance to the
carrier. Shipment shall be via a carrier designated by AltaRex. Costs of
shipping and insurance thereon shall be borne by AltaRex.
13
8.3 BULK DRUG SUBSTANCE STORAGE. AltaRex shall pay Abbott at a rate of
[**] U.S. Dollars (U.S. $[**]) per month for any Bulk Drug Substance storage
costs incurred by Abbott in excess of sixty (60) days after release of the last
campaign, provided that such Bulk Drug Substance was forecasted by AltaRex.
Abbott shall be under no obligation to store such forecasted Bulk Drug Substance
beyond the sixty (60) days.
8.4 QUALITY CONTROL. Abbott shall apply its quality control procedures and
in-plant quality control checks on the manufacture of Bulk Drug Substance for
AltaRex in the same manner as Abbott applies such procedures and checks to bulk
drug substance of similar nature manufactured for sale by Abbott. In addition,
if AltaRex requests, Abbott may test and release Bulk Drug Substance to AltaRex
in accordance with the Bulk Drug Substance Specifications described in Exhibit B
for an additional cost.
8.5 QUALITY ASSURANCE. Within sixty (60) days after the date of the
signing of this Agreement, representatives of the parties' Quality Assurance
departments shall meet to develop and approve a Quality Agreement outlining
responsibilities and key contacts for quality and compliance related issues.
Items to be included in the Quality Agreement include, but are not limited to
recalls, annual product reviews, returned goods, regulatory audits, compliance
with cGMP, compliance with such other quality related concerns deemed
appropriate
8.6 AUDITS. Upon Abbott's written approval, which approval shall not be
unreasonably withheld, AltaRex, shall have the right, upon thirty (30) days'
prior written notice to Abbott, to conduct during normal business hours a
quality assurance audit and inspection of Abbott's records and Bulk Drug
Substance facilities relating to the manufacture of Bulk Drug Substance, and to
perform follow-up audits as reasonably necessary. Such audits and inspections
may be conducted from time to time on a reasonable basis prior to Bulk Drug
Substance
14
production of the first commercial Bulk Drug Substance order placed by AltaRex
and thereafter once each Contract Year. The duration of such audits [**] and
such audits shall be performed by no [**], unless both parties reasonably
believe that a longer audit or additional auditors are necessary and AltaRex
provides its reasons for such belief to Abbott in writing. Abbott will not
unreasonably withhold approval for such additional time and/or auditors and will
not charge AltaRex for this request. If AltaRex wishes to perform audits more
often than once per year or over a period in excess [**], AltaRex shall pay
Abbott [**] U.S. Dollars (U.S. $[**] per additional audit day. If more [**] any
given audit, AltaRex shall pay [**]U.S. Dollars (U.S. $[**] additional auditor
per day. Abbott may, in its sole discretion, waive the additional payment for
the additional audit, the additional day(s) and/or the additional auditor.
Notwithstanding the foregoing, in the event that an audit is required by AltaRex
due to quality issues that arise during any Contract Year, AltaRex shall be
entitled to conduct such audit free of charge. In addition, AltaRex shall have
the right at any time during the term of this Agreement, upon five (5) business
days prior written notice to Abbott, to conduct any audits specifically mandated
by any Regulatory Authority or to respond to specific questions from any
Regulatory Authority at no charge. AltaRex may, at Abbott's sole discretion,
permit one of its licensees to assist in conducting an audit. Such licensee
shall be required to execute an agreement protecting the confidential
information of Abbott prior to being permitted at Abbott's facilities.
Visits by AltaRex to Abbott's Bulk Drug Substance facilities may involve
the transfer of Confidential Information, and any such Confidential Information
shall be subject to the terms of Article 11 hereof. The results of such audits
and inspections shall be considered Confidential Information under Article 11
and shall not be disclosed to third persons, including but not limited to a
Regulatory Authority, unless required by law and upon prior written notice to
Abbott. If
15
AltaRex utilizes auditors that are not employees of AltaRex, each of such
auditors shall execute a non-disclosure agreement with confidentiality terms at
least as stringent as those set forth herein. Abbott shall be responsible for
inspections of its North Chicago manufacturing facility by FDA or an equivalent
Regulatory Authority and shall notify AltaRex if such inspections are directly
related to the manufacture of AltaRex' Bulk Drug Substance. AltaRex shall have
the right to be on site and available for participation in such inspections if
both parties mutually agree that AltaRex' presence would be beneficial. Abbott
will not unreasonably withhold access to its facility and/or documentation
relating to the development and manufacture of Bulk Drug Substance.
8.7 PAYMENT TERMS.
(A) PRICE. The target baseline purchase price for Bulk Drug Substance is
set forth in Exhibit D and assumes [**] full scale, executed
validation runs. In the event that such validation runs differ
significantly from the assumptions of Exhibit D, a new target baseline
purchase price for Bulk Drug Substance will be established accordingly
by Abbott to reflect the cost impact of those differences. The actual
purchase price for any purchase order will be based on the annual
quantity of Bulk Drug Substance set forth in the Contract Year portion
of AltaRex' rolling twenty-four (24) month forecast for Bulk Drug
Substance. Within thirty (30) days following the end of the Contract
Year, Abbott will reconcile the amount of Bulk Drug Substance actually
purchased by AltaRex against the amount forecasted by either issuing a
credit against future purchases for the upcoming Contract Year, or by
invoicing AltaRex for the additional amount owed to Abbott
16
for the previous Contract Year as based on the amount of Bulk Drug
Substance actually purchased, as applicable.
(b) PAYMENT TERMS. Abbott shall invoice AltaRex upon the earlier of
acceptance of the Bulk Drug Substance or lot release of Bulk Drug
Substance by Abbott at the prices determined pursuant to Section
8.7(a). AltaRex shall make payment net thirty (30) days from the date
of receipt of Abbott's invoice. All payments due under this Agreement
shall be paid in dollars by wire transfer or by such other means
agreed upon by the parties, in each case at the expense of the payor,
for value no later than the due date thereof (with twenty four (24)
hours advance notice of each wire transfer) to the following bank
account or such other bank accounts as the payee shall designate in
writing within a reasonable period of time prior to such due date:
17
Account Name: Abbott Laboratories
Account Number: [**]
Bank: Citibank N.A.
New York, New York
ABA Number: 021000089
(c) TAXES. Any federal, state, county or municipal sales or use tax,
excise, customs charges, duties or similar charge, or any other tax
assessment (other than that assessed against income), license, fee or
other charge lawfully assessed or charged on the manufacture, sale or
transportation of Bulk Drug Substance sold pursuant to this Agreement
shall be paid by AltaRex.
(d) CAPITAL EXPANSION/ THIRD PARTY. Abbott will reserve capacity based on
AltaRex' Minimum Purchase Obligation until AltaRex commits to an
Alternative Purchase Obligation. In the event that AltaRex' forecast
exceeds AltaRex' Minimum Purchase Obligation or its Alternative
Purchase Obligation such that Abbott determines, solely due to
AltaRex' forecast, that it is necessary for Abbott to expand its
capacity, contract with a third party, or buy new process dedicated
equipment in order to meet AltaRex' increased demand, AltaRex will
fund such costs of capital associated with the capital expansion,
capital improvement, or capital equipment purchase, and/or all costs
incurred as a result of Abbott contracting with a third party to meet
AltaRex' expanded contract requirements under this Agreement. At
AltaRex' sole discretion, the costs (prorated in accordance with the
estimated usage of the capital expansion or equipment for Bulk Drug
Substance compared to the total estimated usage potential of the
capital expansion or equipment as estimated by Abbott) may be
amortized over
18
the remaining term of the Agreement and if both parties mutually
decide to extend the term of the Agreement, the costs may be amortized
over the extended Agreement term as well. Any third party supplier
utilized by Abbott in the manufacture of Bulk Drug Substance shall be
approved in advance by the Quality Assurance Department. AltaRex shall
have the right to reduce its forecasted amounts to eliminate the need
for Abbott to make capital improvements or capital expansion, or
AltaRex shall have the right to terminate the exclusivity requirements
of Section 7.1 and may purchase Bulk Drug Substance from a third party
in the amount that exceeds Abbott's then contemplated capacity.
8.8 MODIFICATION OF BULK DRUG SUBSTANCE SPECIFICATIONS. If the Bulk Drug
Substance Specifications are modified by AltaRex hereunder or the Bulk Drug
Substance Specifications must be modified by requirement of a Regulatory
Authority, or a process change would be required under the CMC, or other
applicable governmental application, and such modification or process change
increases or decreases Abbott's cost to manufacture Bulk Drug Substance, Abbott
shall submit to AltaRex a revised price for either the current or future stage
of development or Bulk Drug Substance that reflects such cost increase or
decrease. If applicable, Abbott and AltaRex shall mutually agree on the
allocation of such additional costs. If such modification results in the
requirement to reprocess and/or retest previously manufactured and otherwise
acceptable Bulk Drug Substance, any additional costs incurred by Abbott in such
reprocessing and/or retesting shall be paid by AltaRex upon submission by Abbott
of documentation and justification of such costs.
19
9. ORDERS AND FORECASTS
9.1 FIRST ESTIMATE. AltaRex shall, within thirty (30) days after
acceptance of its BLA for Bulk Drug Substance, provide Abbott with an update of
its Preliminary Five Year Forecast outlined in Exhibit H, consisting of AltaRex'
first firm order for the first three (3) months and quarterly anticipated
quantities of Bulk Drug Substance to be supplied by Abbott for the remaining
twenty-one (21) months of initial twenty-four (24) month forecast. Abbott
acknowledges that such quantities are estimates only and are nonbinding. All
forecasts and orders shall be in increments of [**], based on Abbott's
anticipated batch size. In the event that the batch size differs significantly
from the assumptions as outlined in Exhibit D, Abbott and AltaRex shall mutually
determine new incremental amounts for purposes of forecasting and ordering.
9.2 FIRST PURCHASE. Abbott and AltaRex shall cooperate fully in estimating
and scheduling production for the first commercial order of Bulk Drug Substance
to be placed by AltaRex with Abbott in anticipation of regulatory approval of
Bulk Drug Substance. AltaRex shall place its first firm purchase order for the
first three (3) months approximately six (6) months in advance of the
anticipated Bulk Drug Substance regulatory approval date or desired Bulk Drug
Substance availability date. At the same time, AltaRex shall provide to Abbott
AltaRex' estimate of its quarterly requirements of Bulk Drug Substance to be
supplied by Abbott for the next twenty-one (21) months of the initial
twenty-four (24) calendar month period. The first firm purchase order shall be
for no less than [**] and no more than [**] of the first estimate as provided in
Section 9.1.
9.3 ROLLING FORECAST. Thereafter, on the first day of each quarter,
AltaRex shall provide quarterly to Abbott a rolling twenty-four (24) month
projection of requirements of Bulk
20
Drug Substance to be supplied by Abbott, with the first nine (9) months of such
projection consisting of firm purchase orders and the remaining fifteen (15)
months of such projection consisting of AltaRex' best estimate forecast of its
Bulk Drug Substance requirements. Each updated forecast shall be for [**] of the
most recent forecast for the same quarter and shall not exceed [**] of the most
recent forecast for that same quarter. Abbott shall not be obligated to accept a
forecast in excess of [**] of the most recent forecast for that same quarter;
provided, however, that Abbott shall use its reasonable efforts to accommodate
AltaRex' increased needs for Bulk Drug Substance.
9.4 PURCHASE ORDER ACCEPTANCE. Within thirty (30) days after receipt of
AltaRex' firm purchase orders for Bulk Drug Substance, Abbott shall confirm to
AltaRex its acceptance of the purchase order of Bulk Drug Substance ordered by
AltaRex. Such purchase order shall identify delivery date and quantity of Bulk
Drug Substance ordered by AltaRex. Abbott shall be obligated to accept all firm
purchase orders that are [**] than [**] the previous forecasted amount for such
period.
9.5 FIRM PURCHASE ORDER CHANGES. If, due to a significant unforeseen
circumstance, AltaRex requests changes to firm orders within the nine (9) month
firm purchase order timeframe, Abbott shall attempt to accommodate the changes
within reasonable manufacturing capabilities and efficiencies. Abbott shall
advise AltaRex of the costs, if any, associated with making any such change and
AltaRex shall be deemed to have accepted the obligation to pay Abbott for such
costs if AltaRex indicates to Abbott that Abbott should proceed to make the
change.
9.6 PURCHASE ORDER TERMS. Each purchase order or any acknowledgment
thereof, whether printed, stamped, typed, or written shall be governed by the
terms of this Agreement and
21
none of the provisions of such purchase order or acknowledgment shall be
applicable except those specifying Bulk Drug Substance and quantity ordered,
delivery dates, special shipping instructions and invoice information. In the
event of any discrepancy between any purchase order and this agreement, the
terms of this Agreement shall govern.
10. PROPRIETARY OWNERSHIP OF DEVELOPMENT WORK, PREEXISTING TECHNOLOGY AND
LICENSE
GRANTS
10.1 RIGHTS AND TITLES. With respect to rights and title to inventions,
discoveries and know-how developed under this Agreement, each party shall have
and retain sole and exclusive right and title, with respect to the other party,
to all such inventions, discoveries and know-how that are made, conceived,
reduced to practice and/or otherwise generated solely by its employees, agents,
or other persons acting for such party in the course of this Agreement, and such
party shall, at its sole discretion and expense, without any obligation to the
other party, take such actions and obtain such protection as it deems
appropriate with respect to such inventions, discoveries and know-how. Each
party shall own a fifty percent (50%) undivided interest in all such inventions,
discoveries and know-how made, conceived, reduced to practice and/or otherwise
generated jointly by at least one employee, agent, or other person acting for
each party in the course of this Agreement. The parties shall collaborate on any
actions with respect to the protection of their joint rights in such inventions,
discoveries and know-how, at equally shared expense, and thereafter each party
may make, use, sell, keep, license, assign, or mortgage such jointly-owned
inventions, discoveries and know-how, and otherwise undertake all activities a
sole owner might undertake with respect to such inventions, discoveries and
know-how, without the consent of and without accounting to the other party, but
shall inform the other party of its activities with respect to such
jointly-owned property.
22
10.2 EXISTING PROPRIETARY INFORMATION. Except as otherwise provided herein,
neither party hereto shall be deemed by this Agreement to have been granted any
license or other rights to patent rights existing as of the date hereof, or
know-how relating to compounds, formulations, or processes which are owned or
controlled by the other party.
10.3 ABBOTT INVENTIONS. With respect to any ideas, innovations or
inventions (whether or not patentable) developed by Abbott during the term of
this Agreement and relating to the manufacturing process of Bulk Drug Substance,
Abbott shall own all proprietary rights to such ideas, innovations and
inventions, and may obtain patent, copyright, and/or other proprietary
protection relating to such ideas, innovations and inventions; provided however,
that Abbott shall grant to AltaRex a worldwide nonexclusive license with the
right to grant sublicenses, to any ideas, innovations or inventions developed
hereunder as they relate to the manufacturing process of the Bulk Drug
Substance. Such license shall be granted in exchange for a royalty equal to
between [**] percent ([**]%) and [**] percent ([**]%) of the dollar volume of
Bulk Drug Substance purchased by AltaRex from a third party utilizing such
licensed technology solely for the manufacture of Bulk Drug Substance for
AltaRex, depending on the quality and quantity of Abbott inventions so used, as
determined by Abbott. Total royalties paid by AltaRex to Abbott shall not exceed
[**] percent ([**]%) of the dollar volume of Bulk Drug Substance. In the event
that Abbott files a patent application on such ideas, innovations or inventions,
then Abbott shall so notify AltaRex within thirty (30) days of the filing of
such patent application.
10.4 ALTAREX INVENTIONS. During the term of this Agreement, AltaRex hereby
grants to Abbott a royalty-free, worldwide, nonexclusive license, with the right
to grant sublicenses at Abbott's sole expense to satisfy Abbott's manufacturing
obligations hereunder, to AltaRex
23
Confidential Information, AltaRex Know-How, AltaRex Patent Rights, and other
proprietary rights reasonably necessary to conduct the research and development
work described in Articles 2, 3 and 4 hereof, and to make, have made, import,
sell and supply Bulk Drug Substance hereunder, but only for such purposes. In
the event that Abbott utilizes a third party in the manufacture of Bulk Drug
Substance, Abbott shall notify AltaRex in writing and in at least sixty (60)
days in advance of such use, and AltaRex shall have the right to approve
Abbott's selection, with the approval not being unreasonably withheld. Such
third party shall be an Abbott Quality Assurance Department approved third
party. Any third party contract entered into by Abbott and that third party
shall contain a provision that allows AltaRex to audit such third party's
facilities.
11. CONFIDENTIAL INFORMATION
Neither party shall use or disclose any Confidential Information received
by it pursuant to this Agreement without the prior written consent of the other
party. Except as provided in the following sentence, nothing contained in this
Article shall be construed to restrict the parties from disclosing Confidential
Information as is reasonably necessary to perform acts permitted by this
Agreement. However, if either party is required or feels it necessary to
disclose any Confidential Information received by it pursuant to this Agreement
(whether by audit or otherwise) to any third party or governmental agency in
compliance with any federal, state and/or local laws and/or regulations, or
pursuant to an order of a court of competent jurisdiction, the disclosing party
shall notify the party owning such Confidential Information immediately, prior
to any such disclosure, in order to enable the owning party to protect its
Confidential Information. In any event, the disclosing party shall make any
disclosures of Confidential Information received by it pursuant to this
Agreement only to the extent required, and only to
24
such persons who have a need to know. The obligations of the parties relating to
Confidential Information shall expire five (5) years after termination of this
Agreement.
12. TERM AND TERMINATION
12.1 TERM. This Agreement shall become effective as of the Effective Date,
and unless sooner terminated hereunder, shall continue in effect until the
completion of the fifth (5th) Contract Year following the Launch Date; provided,
however, that a party may terminate this Agreement for any reason by giving to
the other party eighteen (18) months prior written notice and all obligations
shall be performed prior to the termination date. In the event any purchase
orders or forecasts come in during the eighteen (18) month termination period,
Abbott shall use its reasonable best efforts to perform under such forecasts and
purchase orders, but shall be under no obligation to accept any forecasts or
purchase orders that require delivery outside of the termination date. UNLESS
OTHERWISE TERMINATED AS SET FORTH ABOVE, THIS AGREEMENT SHALL STAY IN EFFECT FOR
ADDITIONAL TWO (2) YEAR PERIODS UNLESS EIGHTEEN (18) MONTHS' PRIOR WRITTEN
NOTICE OF A PARTY'S INTENT TO TERMINATE IS GIVEN TO THE OTHER PARTY.
12.2 ALTAREX TERMINATION RIGHTS. AltaRex may terminate the Project upon, if
the termination is post-Launch Date, ninety (90) days prior written notice to
Abbott, and if the termination is pre-Launch Date, thirty (30) days prior
written notice to Abbott, if AltaRex determines in good faith that the clinical,
development and/or commercial stage of the Bulk Drug Substance, before or after
the Launch Date, is not technically, clinically or commercially feasible as
solely determined by AltaRex. If AltaRex terminates this Agreement prior to the
Launch Date, AltaRex shall pay a pro-rated, based on actual work completed,
amount of the quarterly payment due for such time period plus any additional
costs incurred by Abbott in accordance with Section 5.3. If AltaRex terminates
after the Launch Date, AltaRex shall pay for the amount
25
of Bulk Drug Substance specified in the AltaRex firm purchase order for such
time period plus any costs actually incurred for (i) manufacturing of Bulk Drug
Substance per the most recent forecast, and/or (ii) capital expansion as
outlined in accordance with Section 8.7(d). Abbott, if requested by AltaRex,
shall provide to AltaRex a summary of costs payable pursuant to this Section
12.2. Upon payment of any adjustment required by this Section 12.2, this
Agreement shall terminate. In the event that AltaRex terminates this Agreement
pursuant to this Section 12.2, AltaRex shall grant to Abbott a right of first
offer for the development and manufacture of all other new products being
developed by AltaRex.
12.3 ABBOTT TERMINATION RIGHTS. In the event AltaRex elects not to launch
the Product by [**], Abbott shall have the right to terminate this Agreement
upon thirty (30) days advance written notice. In such event, AltaRex shall be
entitled to request that Abbott transfer Bulk Drug Substance technology to
AltaRex , or AltaRex' agent, at AltaRex' expense. If within one (1) year from
termination pursuant to Section 12.3, AltaRex subsequently elects to launch the
Product, AltaRex shall grant to Abbott a right of first refusal to match any
bona fide offer to manufacture Bulk Drug Substance that AltaRex receives from a
bona fide, FDA approved, non-Affiliate third party. A bona fide offer from a
bona fide, FDA approved non-Affiliate third party shall include a term of not
less than five (5) years and a commitment to produce AltaRex' requirements for
Bulk Drug Substance. Abbott shall have sixty (60) days from the date of notice
of such offer to match any offer in writing. If Abbott matches such offer in
writing, as to price, quality, quantity, delivery dates and other relevant
factors, AltaRex and Abbott shall in good faith enter into a Supply Agreement,
to be finalized and executed within thirty (30) days of such match by Abbott,
reflecting the terms of such offer, or such longer period as agreed upon by the
parties.
26
12.4 GENERAL TERMINATION RIGHTS. Upon the occurrence of the following
events, either party may terminate this Agreement by giving the other party
thirty (30) days prior written notice:
(a) Upon the bankruptcy or insolvency of the other party; or
(b) Upon the material breach of any provision of this Agreement by the
other party if the breach is not remedied prior to the expiration of
such sixty (60)-day notice period.
12.5 TERMINATION IN EVENT OF HARDSHIP. In the event that during the term of
this Agreement the general situation and/or the data and/or economic
appropriateness on which this Agreement is based are substantially changed such
that it is not commercially, technically, or financially reasonable for a party
to proceed towards commercialization of the Bulk Drug Substance, such party may,
after good faith negotiations between the parties, terminate this Agreement with
thirty (30) days' prior written notice to the other party; provided, however,
that AltaRex shall remain obligated to pay Abbott for all work performed or
purchases made pursuant to Sections 5.3 or 8.7(d) under this Agreement to date
and further provided, that in the event that within one (1) year AltaRex
subsequently proceeds toward the commercialization of Bulk Drug Substance,
Abbott shall manufacture the Bulk Drug Substance for such Bulk Drug Substance at
the price and upon the terms and conditions set forth in this Agreement.
12.6 SURVIVAL PROVISIONS. Termination, expiration, cancellation or
abandonment of this Agreement through any means and for any reason shall not
relieve the parties of any obligation accruing prior thereto, including, but not
limited to, the obligation to pay money, and shall be without prejudice to the
rights and remedies of either party with respect to the antecedent breach of any
of the provisions of this Agreement. Further, Articles 10, 11, 12, 13, 14, 18
and 24 shall survive the termination of this Agreement.
27
13. WARRANTIES
13.1 ALTAREX WARRANTIES. AltaRex warrants to Abbott that, to the best of
AltaRex' knowledge, AltaRex Patent Rights, AltaRex Know-How, and Confidential
Information provided by AltaRex to Abbott for use in the research and
development work described in this Agreement and for Abbott to manufacture and
supply Bulk Drug Substance under this Agreement do not, and will not for the
term hereof, infringe any patent or other proprietary right of any third party.
AltaRex further warrants that it owns or controls all of the rights, title and
interest in and to the AltaRex Patent Rights, AltaRex Know-How, and Confidential
Information provided by AltaRex to Abbott hereunder, and that it has the full
right and authority to grant to Abbott the license described in Section 10.4.
AltaRex further warrants that such license constitutes the only license that
Abbott shall need to manufacture and supply Bulk Drug Substance for AltaRex, its
Affiliates, subsidiaries, licensees and sublicensees.
13.2 ABBOTT WARRANTIES. Abbott warrants to AltaRex that, Bulk Drug
Substance delivered to AltaRex pursuant to this Agreement shall conform to the
Bulk Drug Substance Specifications, cGMP and shall be in full compliance with
applicable laws and regulations promulgated by Regulatory Authorities in the
Territory. ABBOTT MAKES NO OTHER WARRANTIES, EXPRESS OR IMPLIED, WITH RESPECT TO
BULK DRUG SUBSTANCE. ALL OTHER WARRANTIES, EXPRESS OR IMPLIED, INCLUDING WITHOUT
LIMITATION, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A
PARTICULAR PURPOSE ARE HEREBY DISCLAIMED BY ABBOTT. IN NO EVENT SHALL ABBOTT BE
LIABLE FOR INDIRECT, INCIDENTAL OR CONSEQUENTIAL DAMAGES, INCLUDING WITHOUT
LIMITATION, LOST REVENUES OR PROFITS.
28
14. INDEMNIFICATION
14.1 ALTAREX INDEMNIFICATION. AltaRex shall defend, indemnify and hold
Abbott and its Affiliates and their respective employees, directors and agents
harmless against any liability, judgment, demand, action, suit, loss, damage,
cost and other expense (including reasonable attorney's fees) ("Liability")
arising from (i) AltaRex' negligence or willful act or omission in the
development, testing, use, manufacture, promotion, marketing, sale,
distribution, packaging, labeling, handling, storage, and/or disposal of Bulk
Drug Substance and/or formulations containing Bulk Drug Substance; or (ii) any
action brought by a third party alleging infringement of any patent or other
proprietary rights of such third party; or (iii) AltaRex' and/or any AltaRex'
Affiliate's, material breach of this Agreement, except to the extent Abbott is
liable under Section 14.2.
14.2 ABBOTT INDEMNIFICATION. Abbott shall defend, indemnify and hold
AltaRex, its Affiliates, licensees and sublicensees and their respective
employees, directors and agents harmless against any Liability arising from (i)
Abbott's negligence or willful act or omission in the development, testing, use,
handling, packaging, labeling, manufacture, storage or delivery of Bulk Drug
Substance or its raw materials; or (ii) Abbott's material breach of this
Agreement, except to the extent AltaRex is liable under Section 14.1.
14.3 CLAIMS AND PROCEEDINGS. Each party shall notify the other promptly of
any threatened or pending claim or proceeding covered by any of the above
Sections in this Article 14 and shall include sufficient information to enable
the other party to assess the facts. Each party shall cooperate fully with the
other party in the defense of all such claims. No settlement or compromise shall
be binding on a party hereto without its prior written consent.
29
15. ASSIGNMENT
Neither party shall assign this Agreement or any part thereof without the
prior written consent of the other party, which consent shall not be
unreasonably withheld. Any permitted assignee shall assume all obligations of
its assignor under this Agreement. No assignment shall relieve any party of
responsibility for the performance of any accrued obligation that such party
then has hereunder.
16. NOTICES
All notices hereunder shall be in writing and shall be delivered
personally, registered or certified mail, postage prepaid, mailed by express
mail service or given by facsimile, to the following addresses of the respective
parties:
If to Abbott: Abbott Laboratories
President
Specialty Products Division
Department 390, Building A1
1401 Sheridan Road
North Chicago, IL 60064-6312
Fax Number: 847/938-2315
with copy to: Abbott Laboratories
Senior Vice President and General Counsel
Department 364, Building AP6D
100 Abbott Park Road
Abbott Park, IL 60064-6049
Fax Number: 847/938-6277
If to AltaRex: AltaRex Corp.
Senior Vice President, Operations
610 Lincoln Street
Waltham, MA 02451
Fax Number: 781/466-8740
30
with copy to: Stuart Falber
Hale & Dorr
60 State Street
Boston, MA 02109
Fax Number: 617-525-5000
Notices shall be effective upon receipt if personally delivered, on the third
(3rd) business day following the date of mailing if sent by certified or
registered mail, and on the second business day following the date of delivery
to the express mail service if sent by express mail, or the date of transmission
if sent by facsimile. A party may change its address listed above by notice to
the other party.
17. ENTIRE AGREEMENT
This Agreement, and the Confidential Disclosure Agreement dated September
28, 1999, between Abbott Laboratories and AltaRex, constitutes the entire
agreement between the parties concerning the subject matter hereof and
supersedes all written or oral prior agreements or understandings with respect
thereto.
18. ALTERNATIVE DISPUTE RESOLUTION AND APPLICABLE LAW
18.1 CHOICE OF LAW. This Agreement shall be construed, interpreted and
governed by the laws of the State of Illinois, excluding its choice of law
provisions.
18.2 ALTERNATIVE DISPUTE RESOLUTION. The parties recognize that bona fide
disputes may arise that relate to the parties' rights and obligations under this
Agreement. The parties agree that any such dispute shall be resolved by the
Alternative Dispute Resolution ("ADR") in accordance with the procedure set
forth in Exhibit E.
19. FORCE MAJEURE
Any delay in the performance of any of the duties or obligations of any
party (except the payment of money due hereunder) caused by an event outside the
affected party's reasonable
31
control shall not be considered a breach of this Agreement, and unless provided
to the contrary herein, the time required for performance shall be extended for
a period equal to the period of such delay. Such events shall include without
limitation, acts of God; acts of the public enemy; insurrections; riots;
injunctions; embargoes; labor disputes, including strikes, lockouts, job
actions, or boycotts; fires; explosions; floods; earthquakes; shortages of
material or energy; delays in the delivery of raw materials, or other
unforeseeable causes beyond the reasonable control and without the fault or
negligence of the party so affected. The party so affected shall give prompt
notice to the other party of such cause, and shall take whatever reasonable
steps are necessary to relieve the effect of such cause as rapidly as reasonably
possible.
20. SEVERABILITY
If any term or provision of this Agreement shall for any reason be held
invalid, illegal or unenforceable in any respect, such invalidity, illegality or
unenforceability shall not affect any other term or provision hereof, and this
Agreement shall be interpreted and construed as if such term or provision, to
the extent the same shall have been held to be invalid, illegal or
unenforceable, had never been contained herein.
21. WAIVER
No waiver or modification of any of the terms of this Agreement shall be
valid unless in writing and signed by an authorized representative of each party
hereto. Failure by either party to enforce any rights under this Agreement shall
not be construed as a waiver of such rights, nor shall a waiver by either party
in one or more instances be construed as constituting a continuing waiver or as
a waiver in other instances.
22. EXHIBITS
All Exhibits referenced herein are hereby made a part of this Agreement.
32
23. COUNTERPARTS
This Agreement may be executed in any number of separate counterparts, each
of which shall be deemed to be an original, but which together shall constitute
one and the same instrument.
24. PRESS RELEASES
Neither party shall issue any press release related to this Agreement
without the prior approval of the other party, wherein such approval shall not
be unreasonably withheld or delayed. Language in an approved press release by
both parties can be used in other forums. Neither party shall use the name of
the other party in any publicity or advertising without the other party's prior
written consent. Neither party shall make any public announcement concerning the
transactions contemplated herein, or make any public statement that includes the
name of the other party or any of its Affiliates or subsidiaries, or otherwise
use the name of the other party or any of its Affiliates or subsidiaries in any
public statement or document, except as may be required by law or judicial
order, without the written consent of the other party, which consent shall not
be unreasonably withheld. Subject to any legal or judicial disclosure
obligation, any such public announcement proposed by a party that names the
other party shall first be provided in draft to the other party.
IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
executed by their duly authorized representatives on the later day and year
written below.
ABBOTT LABORATORIES ALTAREX CORP.
By: /s/ Chris M. Kolber By: /s/ Peter C. Gonze
-------------------------------- ------------------------------
Chris M. Kolber Peter C. Gonze
Title: Divisional Vice President Title: Senior VP Operations
----------------------------- ---------------------------
Date: May 4, 2001 Date: May 1, 2001
------------------------------- -----------------------------
33
EXHIBIT A
BULK DRUG SUBSTANCE
Immunoglobulin G1, anti-(human CA125 (carbohydrate antigen))
(mouse monoclonal B43.13 gamma 1-chain), disulfide with mouse
monoclonal B43.13 .kappa-chain, dimer.
EXHIBIT B
BULK DRUG SUBSTANCE SPECIFICATIONS
These Specifications include all release testing, comparability assays, and
adventitious agent testing. The release tests required for Bulk Drug Substance
will be a subset and later defined by both parties.
Abbott Certificate of Analysis Tests
- ------------------------------------------------------------------
PARAMETER TEST TYPE SOURCE Specification
- ------------------------------------------------------------------
ID [**] [**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
- ------------------------------------------------------------------
PURITY [**] [**] [**]
- ------------------------------------------------------------------
i
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
- ------------------------------------------------------------------
POTENCY [**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**]
- ------------------------------------------------------------------
- ------------------------------------------------------------------
SAFETY [**] [**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**] [**]
- ------------------------------------------------------------------
- ------------------------------------------------------------------
Adventitious [**] [**] [**] [**]
AGENTS
- ------------------------------------------------------------------
[**] [**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**] [**]
- ------------------------------------------------------------------
[**] [**] [**] [**]
- ------------------------------------------------------------------
ii
EXHIBIT C
PROPOSAL
ALTAREX
PROCESS DEVELOPMENT/ SCALE-UP AND VALIDATION PROPOSAL
FOR OVAREX(TM) MAB PRODUCTION
Prepared By:
Maureen Clayton
Specialty Products Division
Abbott Laboratories
April 25, 2001
i
Objective: The project objective is to adapt AltaRex' process to a stirred tank
batch process, scale up the process for commercial runs, perform three
validation runs at commercial scale under CBER cGMPs, and supply CMC for BLA
submission.
STAGE Ia: DEVELOPMENT AND CLINICAL PRODUCTION
The goal of Stage Ia is to transfer process technology, develop a process
suitable for Abbott equipment, scale-up the process, perform a [**] 100 liter
and [**] 100 liter runs, and complete a two virus viral clearance study.
Assumptions:
- Assume SP2/0 cell line received is fully characterized and testing
documentation supporting this statement is provided prior to cell line
receipt.
- Abbott will not perform any characterization testing or viral
titration assays.
- Abbott will not perform any product specific assays (other than those
stated below). Assays developed by AltaRex can be transferred to
Abbott for additional charge.
- All raw materials, including consumables, are to be supplied by
AltaRex or purchased by Abbott. Materials purchased by Abbott will be
billed to AltaRex at Abbott's purchase cost plus tax, shipping and
handling.
Abbott to Provide:
- Technology transfer kick-off meeting and technical review of current
procedures.
- Perform small-scale cell culture experiments to convert air-lift
production to stirred tank in batch or fed-batch mode.
- Reproduce downstream purification process to demonstrate capability
and assure scalability to 1000-L batch size.
- Perform [**] 100-L non-cGMP run and the first [**] 100L cGMP runs
- Perform the following in-process assays according to protocols
provided by AltaRex:
- [**}
- [**}
- [**}
- [**}
- [**}
- [**}
- Assays will not be validated at Abbott as part of this stage, but
must be prior to cGMP runs if in-process assays are to be used for
decision making during cGMP production. This assay validation cost is
not included in this proposal.
- Create, approve and issue of manufacturing documentation for 100 L
cGMP runs.
- Create and implement raw material documentation system which includes
vendor audits and approval, testing plan, storage specifics, etc for
pilot facility only.
- Order and inventory all raw materials, consumables, disposables, and
commodities utilized by the process for pilot facility. Perform
commodity identification and setup for pilot facility.
- Specify and procure equipment necessary for development and 100 L
pilot plant.
- Perform some scale-down models for required unit operations.
- Assist AltaRex with CRO selection and perform preliminary assay
development for single viral clearance study.
ii
- Complete CMC information for IND update.
AltaRex to Provide:
- Technology transfer kick-off meeting to transfer process procedures
and all relevant materials, equipment and information.
- Vials of the WCB.
- Assay support to evaluate material produced by Abbott.
- Raw materials and equipment as necessary.
- Technical support.
- Review and approval of manufacturing documentation.
- Payment for raw materials, supplies, and equipment as needed.
- Stability and product specific cleaning assays if needed.
- Bulk drug stability program.
Length of Stage: [**] including line items 3-8, 11, 33, and part of lines 12,
15, 29, 34, and 40
Deliverables:
- Delivery of [**] 100 L non-GMP run (less material needed for
development, justification, etc.)
- cGMP documentation
- Delivery of the first [**] 100 L cGMP runs (less material needed for
development, justification, etc.)
- Two virus viral clearance study on [**] unit operations on one 100 L
cGMP run
- CMC information for IND update
Price: [**]
iii
Stage Ib: Pilot Scale Process Justification and Manufacturing Facility
Preparation
The goal of Stage Ib is to complete development documentation, perform necessary
PV scale-down studies, procure manufacturing equipment and supplies, and
complete assay development.
Abbott to Provide:
- Provide a development report summarizing all activities associated
with the project development.
- Begin cGMP documentation for 1000 L runs.
- Create and implement raw material documentation system which includes
vendor audits and approval, testing plan, storage specifics, etc for
manufacturing facility.
- Order and inventory all raw materials, consumables, disposables, and
commodities utilized by the process for manufacturing facility.
Perform commodity identification and setup for manufacturing facility.
- Specify and procure equipment necessary for manufacturing plant.
- Initiation of PV scale-down studies (assuming Stage II has been
undertaken).
- Complete justification of cleaning validation approach.
- Transfer technology from R&D to Manufacturing.
AltaRex to Provide:
- Raw materials and equipment as necessary.
- Technical support.
- Stability and product specific cleaning assays if needed.
Length of Stage: [**] including line items 16, and part of line items 15, 29 and
34
Deliverables:
- Development reports including technology transfer and process
development completion
- Documentation of justification for cleaning validation approach
Price: [**]
iv
STAGE II: RANGE FINDING, PROCESS JUSTIFICATION, AND PROCESS VALIDATION
The goal of Stage II is to perform necessary range finding, process
justification, and process validation studies to support the BLA filing.
Abbott to Provide:
- Completion of [**] 100 L cGMP runs.
- PV scale-down studies for required unit operations.
- Range finding and process justification studies for entire process.
- Process validation package for [**] 1000L cGMP runs.
- Impurity clearance studies for isolation process.
- Column cleaning and lifetime studies for [**] only.
- Hold time studies for key process hold points.
- Initiation of viral clearance studies.
AltaRex to Provide:
- Technical support as needed.
Length of Stage: [**] including line items 30-31, and part of lines 12, 29, and
34-36
Deliverables:
- Material from [**] 100 L cGMP runs (less material needed for testing
or studies)
- Documentation from completed PV scale-down studies
Price: [**]
v
STAGE III: cGMP MANUFACTURING AND CMC FILING
The goal of Stage III is to produce material at 1000 liter scale under cGMP and
complete CMC package for BLA submission.
Assumptions:
- Cell culture process duration of [**], purification [**].
- Single use [**] membranes.
Abbott to Provide:
- Installation of manufacturing equipment, including any modifications
to existing equipment, and necessary validation.
- Implementation of the Quality Assurance program for cGMP production.
This includes batch record review, exception documentation procedures,
and process monitoring.
- Completion of necessary cGMP documentation for 1000 L runs.
- Operator training.
- Media runs to evaluate any modifications to bioreactors.
- [**] 1000 L non-cGMP and [**] 1000L cGMP engineering runs to
demonstrate scalability. All cGMP material produced will be sent to
AltaRex (less any material needed for testing).
- cGMP production of [**] validation lots at 1000 liter scale. Delivery
of al from validation runs to AltaRex, less any material used for
viral studies, testing, etc.
- Viral clearance studies for [**].
- Completion of the CMC section for BLA filing.
AltaRex to Provide:
- Raw materials as necessary.
- Stability and product specific cleaning assays if needed.
- Viral titration assays.
- Technical support.
- Bulk drug stability program.
Length of Stage: [**] including line items 18-26 and part of lines 35-36, and 41
vi
Deliverables:
- Material from all 1000 L runs (less material used in studies or
testing)
- Copies of cGMP documentation including production batch records and
other relevant activities.
- A completed CMC section for filing
Price: [**]
NOT INCLUDED:
- Raw materials, supplies, new equipment and equipment modifications as
required and/or needed. Abbott can purchase necessary raw materials
directly and invoice AltaRex at cost less any applicable discount.
AltaRex would own any new equipment purchased, but Abbott will own
equipment modifications.
- Proposal does not include product specific cleaning assay work or
product release or characterization testing.
- Proposal includes no long-term storage of material, no stability
program, no lot release testing or analytical characterization of
product.
- No optimization or changes to cell culture media.
- Abbott can expand the 1000 L cGMP virus study to include [**] virus
[**] for [**] unit operations on [**] lots for an additional
charge of [**], at AltaRex' sole discretion.
PAYMENT SCHEDULE:
[**] [**]
Month [**]: [**]
Month [**]: [**]
Month [**]: [**]
Month [**]: [**]
Month [**]: [**]
Month [**]: [**]
Month [**] [**]
Month [**]: [**]
Month [**]: [**]
vii
Stage Ib Month [**]: [**]
Month [**]: [**]
Month [**]: [**]
Month [**] [**]
Month [**] [**]
Month [**] stage completion [**]
Stage II Month [**]: [**]
Month [**] [**]
Month [**] or stage completion: [**]
Stage III Month [**]: [**]
Month [**]: [**]
Month [**]: [**]
Month [**] [**]
Month [**] [**]
Month [**] or stage completion: [**]
TIMING:
Stage Ia and Ib: Months [**]
Stage II: Months [**]
Stage III: Months [**]
At the end of each Stage (or sooner if both parties agree) a decision can be
made to proceed to the next Stage. As indicated in Proposal, Stage II should
begin prior to the completion of Stage I and Stage III should begin prior to the
completion of Stage II, but if the parties elect to wait until previous Stage
completions, the overall timeline will be delayed.
Attachment// AltaRex Timeline displaying associated Line Items listed above
(Note that timeline does not show impact of technology transfer delays)
viii
EXHIBIT D
PRICING
Annual Volume (grams) Price ($000/gram)
--------------------- -----------------
[**] [**]
Baseline Pricing does not include impact of process improvement programs, but
does include impact of [**] which will require a supplemental BLA. [**]
anticipated to be initiated when forecast exceeds [**] grams/ year.
If Abbott cannot implement a [**] due to the supplemental BLA not being approved
or until its approval, the price per gram for any quantity greater than [**] per
year will remain fixed at [**].
Based on [**].
Prices will be annually adjusted by [**] issued by the Bureau of Labor
Statistics, U.S. Department of Labor.
Prices above are based on the following assumptions:
Productivity of [**].
Recovery of [**]
Raw materials, supplies, consumables, solvents, testing, are not
included in price.
EXHIBIT E
ALTERNATIVE DISPUTE RESOLUTION
------------------------------
The parties recognize that from time to time a dispute may arise relating
to either party's rights or obligations under this Agreement. The parties agree
that any such dispute shall be resolved by the Alternative Dispute Resolution
("ADR") provisions set forth in this Exhibit, the result of which shall be
binding upon the parties.
To begin the ADR process, a party first must send written notice of the
dispute to the other party for attempted resolution by good faith negotiations
between their respective presidents (or their designees) of the affected
subsidiaries, divisions, or business units within twenty-eight (28) days after
such notice is received (all references to "days" in this ADR provision are to
calendar days). If the matter has not been resolved within twenty-eight (28)
days of the notice of dispute, or if the parties fail to meet within such
twenty-eight (28) days, either party may initiate an ADR proceeding as provided
herein. The parties shall have the right to be represented by counsel in such a
proceeding.
1. To begin an ADR proceeding, a party shall provide written notice to the
other party of the issues to be resolved by ADR. Within fourteen (14) days
after its receipt of such notice, the other party may, by written notice to
the party initiating the ADR, add additional issues to be resolved within
the same ADR.
2. Within twenty-one (21) days following receipt of the original ADR notice,
the parties shall select a mutually acceptable neutral to preside in the
resolution of any disputes in this ADR proceeding. If the parties are
unable to agree on a mutually acceptable neutral within such period, either
party may request the President of the CPR Institute for Dispute Resolution
("CPR"), 366 Madison Avenue, 14th Floor, New York, New York 10017, to
select a neutral pursuant to the following procedures:
(a) The CPR shall submit to the parties a list of not less than five (5)
candidates within fourteen (14) days after receipt of the request,
along with a Curriculum Vitae for each candidate. No candidate shall
be an employee, director, or shareholder of either party or any of
their subsidiaries or affiliates.
(b) Such list shall include a statement of disclosure by each candidate of
any circumstances likely to affect his or her impartiality.
(c) Each party shall number the candidates in order of preference (with
the number one (1) signifying the greatest preference) and shall
deliver the list to the CPR within seven (7) days following receipt of
the list of candidates. If a party believes a conflict of interest
exists regarding any of the candidates, that party shall provide a
written explanation of the conflict to the CPR along with its list
i
showing its order of preference for the candidates. Any party failing
to return a list of preferences on time shall be deemed to have no
order of preference.
(d) If the parties collectively have identified fewer than three (3)
candidates deemed to have conflicts, the CPR immediately shall
designate as the neutral the candidate for whom the parties
collectively have indicated the greatest preference. If a tie should
result between two candidates, the CPR may designate either candidate.
If the parties collectively have identified three (3) or more
candidates deemed to have conflicts, the CPR shall review the
explanations regarding conflicts and, in its sole discretion, may
either (i) immediately designate as the neutral the candidate for whom
the parties collectively have indicated the greatest preference, or
(ii) issue a new list of not less than five (5) candidates, in which
case the procedures set forth in subparagraphs 2(a) - 2(d) shall be
repeated.
3. No earlier than twenty-eight (28) days or later than fifty-six (56) days
after selection, the neutral shall hold a hearing to resolve each of the
issues identified by the parties. The ADR proceeding shall take place at a
location agreed upon by the parties. If the parties cannot agree, the
neutral shall designate a location other than the principal place of
business of either party or any of their subsidiaries or affiliates.
4. At least seven (7) days prior to the hearing, each party shall submit the
following to the other party and the neutral:
(a) a copy of all exhibits on which such party intends to rely in any oral
or written presentation to the neutral;
(b) a list of any witnesses such party intends to call at the hearing, and
a short summary of the anticipated testimony of each witness;
(c) a proposed ruling on each issue to be resolved, together with a
request for a specific damage award or other remedy for each issue.
The proposed rulings and remedies shall not contain any recitation of
the facts or any legal arguments and shall not exceed one (1) page per
issue.
(d) a brief in support of such party's proposed rulings and remedies,
provided that the brief shall not exceed twenty (20) pages. This page
limitation shall apply regardless of the number of issues raised in
the ADR proceeding.
Except as expressly set forth in subparagraphs 4(a) - 4(d), no discovery
shall be required or permitted by any means, including depositions,
interrogatories, requests for admissions, or production of documents.
5. The hearing shall be conducted on two (2) consecutive days and shall be
governed by the following rules:
ii
(a) Each party shall be entitled to five (5) hours of hearing time to
present its case. The neutral shall determine whether each party has
had the five (5) hours to which it is entitled.
(b) Each party shall be entitled, but not required, to make an opening
statement, to present regular and rebuttal testimony, documents or
other evidence, to cross-examine witnesses, and to make a closing
argument. Cross-examination of witnesses shall occur immediately after
their direct testimony, and cross-examination time shall be charged
against the party conducting the cross-examination.
(c) The party initiating the ADR shall begin the hearing and, if it
chooses to make an opening statement, shall address not only issues it
raised but also any issues raised by the responding party. The
responding party, if it chooses to make an opening statement, also
shall address all issues raised in the ADR. Thereafter, the
presentation of regular and rebuttal testimony and documents, other
evidence, and closing arguments shall proceed in the same sequence.
(d) Except when testifying, witnesses shall be excluded from the hearing
until closing arguments.
(e) Settlement negotiations, including any statements made therein, shall
not be admissible under any circumstances. Affidavits prepared for
purposes of the ADR hearing also shall not be admissible. As to all
other matters, the neutral shall have sole discretion regarding the
admissibility of any evidence.
6. Within seven (7) days following completion of the hearing, each party may
submit to the other party and the neutral a post-hearing brief in support
of its proposed rulings and remedies, provided that such brief shall not
contain or discuss any new evidence and shall not exceed ten (10) pages.
This page limitation shall apply regardless of the number of issues raised
in the ADR proceeding.
7. The neutral shall rule on each disputed issue within fourteen (14) days
following completion of the hearing. Such ruling shall adopt in its
entirety the proposed ruling and remedy of one of the parties on each
disputed issue but may adopt one party's proposed rulings and remedies on
some issues and the other party's proposed rulings and remedies on other
issues. The neutral shall not issue any written opinion or otherwise
explain the basis of the ruling.
8. The neutral shall be paid a reasonable fee plus expenses. These fees and
expenses, along with the reasonable legal fees and expenses of the
prevailing party (including all expert witness fees and expenses), the fees
and expenses of a court reporter, and any expenses for a hearing room,
shall be paid as follows:
(a) If the neutral rules in favor of one party on all disputed issues in
the ADR, the losing party shall pay 100% of such fees and expenses.
iii
(b) If the neutral rules in favor of one party on some issues and the
other party on other issues, the neutral shall issue with the rulings
a written determination as to how such fees and expenses shall be
allocated between the parties. The neutral shall allocate fees and
expenses in a way that bears a reasonable relationship to the outcome
of the ADR, with the party prevailing on more issues, or on issues of
greater value or gravity, recovering a relatively larger share of its
legal fees and expenses.
9. The rulings of the neutral and the allocation of fees and expenses shall be
binding, non-reviewable, and non-appealable, and may be entered as a final
judgment in any court having jurisdiction.
10. Except as provided in paragraph 9 or as required by law, the existence of
the dispute, any settlement negotiations, the ADR hearing, any submissions
(including exhibits, testimony, proposed rulings, and briefs), and the
rulings shall be deemed Confidential Information. The neutral shall have
the authority to impose sanctions for unauthorized disclosure of
Confidential Information.
iv
EXHIBIT F
PROJECT ASSUMPTIONS
GENERAL
- --------------------------------------------------------------------------------
- No internal in-house assays needed for GMP runs, all outsourced other
than the specified in-process assays listed in Section 5.3. Analytical
methods development and validation will be performed by CRO. If
necessary to support project timelines, analytical methods will be
transferred from CRO to Abbott at AltaRex's expense. Assays so
transferred will be performed for in-process use at no additional cost
to AltaRex; methods used for specification testing or lot release will
be billed to AltaRex.
- No product specific assays for cleaning need to be developed,
validated and transferred.
- All raw materials and consumables will be supplied by AltaRex or
Abbott. If bought by Abbott, AltaRex will be billed at cost plus
shipping/handling.
- Run stability for both bulk drug and drug product on 100L pilot
material
- No optimization or changes to cell culture media
RUN DELIVERABLES
- --------------------------------------------------------------------------------
- [**] 100L non-GMP run
- [**] 100L GMP runs
- [**] 1,000L Engineering runs ([**])
- [**] 1,000L Process Validation (PV) runs
BLA DELIVERABLES
- --------------------------------------------------------------------------------
- Viral clearance study for [**] viruses on [**] operations [**] 100 L
cGMP run
- Scale down models for required unit operations
- Viral clearance studies for [**] viruses x [**] unit operations [**]
lots
|X| New vs. used resin [**]
|X| Virgin resin for [**]
- Range finding and Process Justification (PJ) studies for entire
process
- Process validation package for [**] 1,000L GMP runs
- Impurity clearance studies for isolation process
- Column cleaning and lifetime studies for [**] only
- Hold time studies for key process hold points
- No stability program
i
DEVELOPMENT
- --------------------------------------------------------------------------------
- Cell line received is fully characterized and documentation is
provided prior to cell line receipt.
- No product or cell line characterization done by Abbott.
- Viral titration or molecular assays used to support viral clearance
studies will be performed at a CRO at AltaRex's expense
- Validated analytical methods will be used to support scale-down, PJ,
viral clearance studies, and stability protocol at AltaRex's expense.
- Process development to convert airlift fermentation to stirred tank.
- Reproduce downstream purification process and assure scaleability to
1,000L batch size.
- Specify and procure any equipment needs for 100L & 1000L GMP runs.
AltaRex will pay for such equipment and Abbott will maintain it.
MANUFACTURING
- --------------------------------------------------------------------------------
- Best case timeline, allowed to be adjusted, if needed, after process
development is completed
|X| Timeline does not show current impact of technology transfer
delay
- Single use [**] membranes
- No cleaning validation assay development/validation
- End-of-production bulk harvest testing will be performed on all GMP
runs at AltaRex's expense
- After launch, if volumes are projected to exceed [**] per year, Abbott
will perform process validation for [**] and provide AltaRex with
information for a supplemental BLA.
ii
EXHIBIT G
ADDITIONAL COSTS
The following estimates can be adjusted throughout the Development portion of
the Agreement as more information relating to the process is discovered.
Estimates are worst case and based on preliminary technology transfer
information and Abbott's knowledge of similar product requirements.
PER GRAM
--------
RAW MATERIALS TBD
SUPPLIES [**]
RESIN TBD
RELEASE TESTING Paid by AltaRex to Vendor
Following validation runs, the average per gram price for raw materials,
supplies, resin and testing will be incorporated into the overall per gram price
for commercial product. Exhibit D will be amended to incorporate these costs
into the per gram price.
PROCESS CAPITAL--DEVELOPMENT/ PILOT PLANT [**]
Items over [**] are estimated to be: [**] chromatography system
[**] chromatography system
PROCESS CAPITAL--MANUFACTURING FACILITY [**]
Items over [**] are estimated to be: [**]
[**] chromatography system / tank
[**] anion exchange
chromatography
system / tank
[**] gel filtration
chromatography
system Bioreactor
modifications Cold
storage units
AltaRex shall own any stand-alone equipment purchased and Abbott shall maintain
it. Any modifications, alterations, or additions to existing Abbott equipment
will be owned and maintained by Abbott.
EXHIBIT H
PRELIMINARY FIVE YEAR FORECAST OF
BULK DRUG SUBSTANCE
--------------------------------------------------------
CONTRACT YEAR GRAMS
------------- -----
--------------------------------------------------------
YEAR 1 [**]
--------------------------------------------------------
YEAR 2 [**]
--------------------------------------------------------
YEAR 3 [**]
--------------------------------------------------------
YEAR 4 [**]
--------------------------------------------------------
YEAR 5 [**]
--------------------------------------------------------
--------------------------------------------------------
--------------------------------------------------------
--------------------------------------------------------