DISTRIBUTION AGREEMENT
This Agreement is made as of August 4, 1997 by and between Matrix
Pharmaceutical, Inc., 00000 Xxxxxx Xx., Xxxxxxx, Xxxxxxxxxx 00000, a company
duly organized and existing under the laws of Delaware, United States of
America, ("Matrix") and Altana, Inc., Melville, New York, a company duly
organized and existing under the laws of New York ("Altana").
WITNESSETH:
Whereas, Matrix is the owner and manufacturer of the Product (hereinafter
defined) and is interested in having its Product marketed, sold and distributed
in the Field and in the Territory (each as hereinafter defined); and
Whereas, Altana has facilities, distribution systems and sales personnel capable
of selling the Product and is interested in marketing, selling and distributing
the Product in the Territory, and
Whereas, Matrix and Altana jointly agree that it is mutually desirable to enter
into this Agreement with respect to the supply, marketing, distribution and sale
of the Product.
NOW, THEREFORE, THE PARTIES HERETO AGREE AS FOLLOWS:
1. DEFINITIONS.
1.1. The term "Product" shall mean formulations of Matrix's AccuSite(TM)
(fluorouracil/epinephrine) injectable gel and any future formulations
involving fluorouracil/epinephrine) collagen for the treatment of
condyloma acuminata (genital warts) in commercial quantities and in
finished dosage form, as further described in Supplement A hereto.
1.2. The term "Field" shall mean the treatment of condyloma acuminata by
dermatologists and OB/GYN specialists.
1.3. The term "Territory" shall mean the United States of and Puerto Rico
for dermatology and OB/GYN markets.
1.4. The term "Parties" shall mean Matrix and Altana.
1.5. The term "Agreement" shall mean this document and any and all
supplements, schedules and amendments hereto.
1.6. The term "Net Sales" shall mean with respect to Product, the aggregate
amount invoiced by Altana (including by its Affiliates) for or on
account of any sale to a non-affiliated purchaser of such Product in
the Territory,
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less deductions for: a) normal and customary trade, quantity and cash
discounts allowed; and b) allowances or credits to customers on account
or return of Product.
1.7. The term "Distribution Period" shall mean the period beginning on the
date of the first offer for commercial sale of Products in the
Territory and ending five (5) years thereafter. This Agreement may be
extended beyond the original five (5) year term as set forth in section
11.2 below.
1.8. The term "Specifications" shall mean the specifications (including
methods package from NDA) for Products set forth and contained in the
FDA approval which authorizes the marketing of the Product for use by
humans in the Territory.
1.9. The term "Affiliate" shall mean any corporation, association, company,
organization or other entity which is directly or indirectly
controlling, controlled by, or under common control with Matrix or
Altana (as applicable). For the purpose of this definition, the term
"control" means the direct or indirect ownership of 50% or more of the
voting power of the subject entity.
1.10. The term "GMP" means those manufacturing practice regulations set forth
in Good Manufacturing Practices for Finished Pharmaceuticals, as
required by the applicable regulations in the Territory.
1.11. The term "FDA" means the United States Food and Drug Administration or
any successor agency.
1.12 The term "Year One" shall mean the date of product introduction through
the end of the next calendar year. However, Year One shall not exceed
18 months.
2. GRANT OF RIGHTS.
Altana shall have exclusive rights during the term of this Agreement to
promote, distribute, sell and resell the Product in the Field and in
the Territory and shall purchase its requirements therefor exclusively
from Matrix in accordance with the terms and conditions of this
Agreement. Altana shall seek or otherwise solicit orders for the
Product only from persons and entities located and taking delivery and
intending to sell within the Territory.
Prior to granting a license to market and sell the Product in the field
of urology to a third party, Matrix will grant Altana the exclusive
right, for a period of 90 days, to negotiate terms and conditions under
which Matrix would enter into such a license with Altana provided that
if Matrix and Altana do not agree on mutually satisfactory terms and
conditions within
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such 90 day period, despite good faith efforts to do so, then Matrix
shall ultimately be free to license such rights to third parties on
such terms and conditions as it deems appropriate.
3. PLACING OF ORDERS AND DELIVERY.
3.1. Matrix shall supply Altana with and Altana shall purchase from Matrix
all of Altana's requirements for Product for resale in the Territory in
accordance with the terms and conditions set forth in this Agreement.
3.2. Altana shall place orders with Matrix for the finished Product. Matrix
agrees to deliver the Product, as specified in such orders, to Altana
at the address agreed upon at the delivery date specified in each order
on the condition that each order is received by Matrix at least two (2)
months prior to the delivery date in question.
3.3. In consideration for the rights granted herein, Altana shall use its
diligent efforts, commensurate with those it would use for its own
products, to market, create a demand for and continuously develop sales
of the product in the Territory throughout the life of this Agreement.
3.4. Supplement C sets forth Altana's good faith estimate of the initial
sales forecast for quantities of Products that Altana expects to
market, sell and distribute during each of the first five (5) years of
this Agreement (the "Initial Forecast"). The Initial Forecast shall
apply to the first three years of the original term of this Agreement.
Thereafter, Altana shall in good faith prepare and annually provide to
the Marketing and Sales Committee its revised estimates of Net Sales of
Products for the then upcoming three year period. If accepted by
Matrix, such new forecasts shall become Accepted forecasts and shall
govern the Parties responsibilities for the period they cover. If not
accepted by Matrix, the Initial Forecast shall control.
3.5. All firm orders for Product placed by Altana shall be deemed to
incorporate Matrix's standard Terms and Conditions of Purchase in force
at the time of order placement, except where such terms or conditions
are varied or inconsistent with this Agreement. In the event of any
such inconsistency, this Agreement shall control. Altana shall place
firm orders for Product consistent with the Initial Forecast or the
then applicable Accepted Forecast, as applicable, at least sixty (60)
days prior to the scheduled delivery dates therefor. Any such orders
shall be deemed accepted by Matrix as of the date of their receipt,
unless within fifteen (15) days of its receipt, Matrix advises Altana
to the contrary, setting forth alternative delivery dates no later than
thirty (30) days from the original delivery date in accordance with
Matrix's then current delivery schedule for the Product in comparable
volumes.
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3.6. Matrix warrants that it shall fill each Altana firm order submitted in
accordance with this Agreement. Matrix shall supply Altana with at
least the quantities of Product set forth on Supplement C (the
applicable Forecasts) and shall use its commercially reasonable efforts
to supply Altana with any quantities ordered in excess of the
applicable Forecast requirements. If there is a shortfall in Matrix's
ability to supply Product, it shall immediately notify Altana of such
shortfall and provide an indication of the likely duration thereof. In
the event of any shortfall, Matrix will provide Altana with an
allocation of Product pro rata to its worldwide sales.
3.7. Product is to be delivered FOB Matrix manufacturing facilities,
California, after which Altana will pay all charges, including without
limitation transportation charges and insurance premiums. Title to, and
risk of loss of, the Product shall remain with Matrix until delivery at
the FOB point, at which time Altana shall assume title to and risk of
loss of the Product.
3.8. At the time of each Product shipment, Matrix shall invoice Altana an
amount equal to * per unit of finished Product shipped to Altana.
Altana shall pay each such invoice within thirty days of its date.
4. REVENUE SHARING AND PAYMENT.
4.1. Within forty-five (45) days after the end of each calendar quarter, and
starting with the first calendar quarter for which there are sales of
Product recorded, Altana shall deliver to Matrix a cash payment (or
Matrix shall deliver to Altana a cash payment), in U.S. dollars, in
each case equal to the applicable percentage of Altana's aggregate Net
Sales revenues from sales of Product during the prior quarter less the
amount previously paid to Matrix for Product sold during such quarter
(such that if the deduction for Product payments results in a negative
sum, the payment shall be made by Matrix to bring such sum to $0.00):
(a) For year one, fifty percent (50%) (to help defray Altana start-up
and marketing expenses; (b) years two and three (except as provided
below) (i) seventy percent (70%) (to repay Matrix for its foregoing the
upfront licensing fee) until such time as Net Sales revenue during such
second and third years has reached $50.0 million; (ii) thereafter and
for all subsequent years, sixty percent (60%) until Net Sales for each
such year exceeds the Initial Forecast or the Accepted Forecast Net
Sales amounts for such year; and (iii) once the Initial Forecast or
Accepted Forecast Net Sales Amount has been exceeded fifty percent
(50%) through the end of each such year.
4.2. Matrix and Altana agree that prior to any FDA approval for the Product
for use in the treatment of basal cell cancer and other future
indications, they shall develop a marketing plan (the "Expanded
Marketing Plan") for
* Indicates that material has been omitted and confidential treatment has
been requested therefor. All such omitted material has been filed
separately with the Commission pursuant to Rule 24b-2.
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such indication and shall thereafter appropriately revise the Minimum
Net Sales amounts set forth in Supplement C to include appropriate
sales revenues therefor. Upon such agreement, the definition of Product
shall be expanded to include the treatment of basal cell cancer. As
part of such expanded marketing plans, Matrix and Altana shall agree to
the appropriate compensation to be paid to Matrix for its efforts in
developing and registering such new indications with the objective of
sharing the incremental costs for such indications on the same basis as
the Parties share revenues, resulting from such new indications.
4.3. Altana and its Affiliates shall keep and maintain detailed and accurate
books and records with regard to Net Sales, marketing expenses, and the
calculation thereof. Such books and records shall be in at least
sufficient detail to permit a third party auditor to verify the Net
Sales and marketing expenses for the Product and the quantities of
Product shipped during each calendar quarter. An independent auditor of
national standing shall be entitled, on Matrix' behalf, not more than
once each year and during normal business hours, to review and audit
such books and records. Such audit and review shall be contingent upon
one week's advance notice from Matrix to Altana and such audit and
review shall be at Matrix's expense; however, Altana shall bear any
such expense if the review or audit shows an underpayment of more than
five percent (5%) for the applicable period, in which case Altana shall
promptly reimburse Matrix for such expenses and pay the deficiency.
4.4 Any payments made by either party for Medicare or Medicaid rebate will
be shared by the parties based on the then applicable revenue sharing
percentage.
4.5. All payments to Matrix shall be made in U.S. dollars in the United
States to such account and bank as Matrix shall specify to Altana in
writing.
5. ALTANA OBLIGATIONS. Altana warrants and/or covenants, as applicable,
that it shall:
5.1. Meet or exceed at least fifty percent (50%) of the then applicable
annual Net Sales amounts set forth in the Initial Forecast or in any
Accepted Forecast, as then applicable. In the event that Altana fails
to meet such Minimum Net Sales amounts after Year One for any two
consecutive years, Matrix shall have the right to terminate this
Agreement provided that Matrix materially has fulfilled its obligations
under Section 3.6.
5.2. Use its diligent efforts to promote the sale of Product in the Field
and in the Territory and will furnish a detailed marketing and sales
plan with respect to the Product, three (3) months prior to the
beginning of each calendar year. Such plan shall be reviewed by the
Marketing and Sales Committee (as described in Section 12 below).
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In all instances, the Product shall be marketed under Matrix's
trademarks therefor, provided that Altana shall also be entitled to
display its name and logo thereon. Matrix shall grant Altana an
exclusive license to use the trademarks described in Supplement D, in
the Territory, upon the terms and conditions set forth in the Trademark
License Agreement entered into by the parties of even date herewith,
attached hereto as Supplement D and made a part hereof. All packaging,
labels, labeling, and marketing materials for the Product shall be in
accordance with applicable regulations in the Territory and shall be
approved in advance in writing by Matrix or a Matrix appointed
designee. Altana shall not distribute or have distributed any written
information regarding the Product which bears any Matrix trademark
without the prior written approval of Matrix. Permission to use the
Matrix trademarks in marketing the Product is granted solely for
purposes of this Agreement and shall immediately lapse upon any
termination of this Agreement. Altana acknowledges that in utilizing
such trademarks it shall be Altana's responsibility to promote the
goodwill associated with such trademarks and that Altana shall in all
cases comply with all applicable governmental requirements relating to
the sale or marketing of pharmaceutical products in the Territory.
Nothing herein grants Altana any other rights, title or interest in any
such trademarks, and Altana recognizes that Matrix is the sole owner
thereof and covenants that it will not take any action which might
prejudice or adversely affect the validity or Matrix's ownership
thereof.
5.3. Maintain a sales force of approximately seventy five (75), but in no
event less than sixty-five (65), sales persons each of whom shall be
predominantly directed at dermatology or OB/GYN sales opportunities and
are trained to sell the Product.
5.4. Present the Product in a first-call position to the appropriate
relevant target physicians in its sales calls for at least twelve (12)
months after its launch in the Territory. Altana will launch the
product in the Territory within ninety (90) days of regulatory
approval.
5.5. Expend not less than the amounts set forth on Exhibit B for each year
listed thereon in actual out-of-pocket marketing expenses related to
sales of the Product in the Field and in the Territory.
Supplement B sets forth Altana's Marketing expenses that Altana shall
incur to market, sell, and distribute during each of the first five (5)
years of this Agreement (the "Initial Forecast"). The Marketing
expenses shall apply to the first three (3) years of the original term
of this Agreement. Thereafter, Altana shall in good faith prepare and
annually provide to Marketing and Sales Committee its revised estimates
of marketing expenses for the then upcoming three (3)-year period. If
accepted by
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Matrix, such new Marketing expenses shall govern the Parties
responsibilities for the period they cover. If not accepted by Matrix,
the Initial Forecast shall control.
5.6. Ascertain and comply with all applicable laws and regulations and
standards of industry or professional conduct in connection with the
use, distribution or promotion of the Product, including without
limitation, those applicable to product claims, labeling, approvals,
registrations and notifications. To use commercially reasonable
efforts, at its sole expense, to obtain and maintain any applicable
approvals, registrations, notifications or the like with regard to
marketing, using (for therapeutic use), selling, reselling, labeling or
otherwise promoting or making claims regarding the Product or its use.
5.7. Provide medical affairs service for the Territory on behalf of Matrix
with respect to the Product. Altana's responsibilities shall include,
but are not limited to, the following:
(A) Altana shall operate a service that will provide prompt and
accurate responses to all inquiries. Such responses shall be
made verbally by phone or in writing by letter, facsimile or
electronic means as appropriate. Altana responses will be
consistent with Matrix specifications and standard operating
procedures to be mutually agreed upon.
(B) Matrix shall provide Altana with an initial set of anticipated
questions and approved responses.
(C) Altana shall be responsible for ensuring compliance of
responses with the appropriate requirements of regulatory
authorities.
(D) Altana shall follow appropriate reasonable standard operating
procedures agreed by both Parties, for collecting information
from calls concerning Adverse Events (as defined below), and
for reporting and transferring such information to Matrix.
(E) Altana shall maintain accurate and complete records of all
inquiries and responses, both verbal and written. Within five
(5) business days after the end of each month. Altana shall
provide Matrix with reports detailing the number and type of
responses handled during that month, as well as any additional
reports agreed upon by both Parties, and provide these in a
format agreed upon by both Parties.
(F) Altana shall ensure that the information database to be used
in providing medical affairs services is compatible with
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specifications as set forth in Supplement E. Upon termination
of this Agreement, Altana shall immediately transfer all
database records to Matrix in a useable and organized form.
5.8. Keep for five years after termination of this Agreement records of all
product sales and customers sufficient to adequately administer any
recall of the Product and to fully cooperate in any decision by the FDA
or any other regulatory body having jurisdiction to recall, retrieve
and/or replace the Product.
5.9. Maintain proper facilities for the storage and transport of Product
pursuant to the Specifications, including, without limitation, storage
at temperatures between 2 and 8 degrees Celsius, protected from light.
5.10. Refrain from establishing or maintaining any branch, warehouse or
distribution depot for the Product outside the Territory, and shall not
engage in any advertising or promotional activities relating to the
Product directed primarily to potential customers located outside the
Territory.
5.11. Facility Inspection. Upon reasonable written notice, Matrix shall have
the right from time to time to inspect Altana's Product distribution
facility(ies) and medical affairs database to verify its compliance
with the terms of this Agreement.
5.12. Inspections by Government Agencies. Altana shall promptly notify Matrix
of any inspections by any regulatory representatives of any facility at
which the Product is being or will be distributed, to the extent such
inspections pertain to the Product or the distribution thereof, and
shall send Matrix copies of the results of any such inspections,
including actions taken by the inspected party or any other entity to
remedy conditions cited in such inspections.
6. MATRIX OBLIGATIONS. Matrix warrants and/or covenants that it shall:
6.1. Obtain the registration for commercial sale in the Territory for the
Product, including carrying out any clinical studies required by
regulatory authorities for such registration. Notwithstanding the
foregoing, if any new studies required by such regulatory authorities
are in Matrix's judgment too expensive to warrant commercialization of
the Product in the Territory, then Matrix may terminate this Agreement
without further liability.
6.2. Supply Altana with packaged, labeled, finished Product F.O.B.
California.
6.3. Be responsible for testing clearance to the F.O.B. point.
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6.4. Expend not less than $1 million in year one for marketing the product,
$750,000 in year two for marketing the product, $600,000 in year three,
$500,000 in year four, and $400,000 in year five.
6.5. Be responsible for all Adverse Event reporting to the FDA and other
government agencies outside of the Territory with respect to the
Product. Matrix shall advise Altana of any adverse event reporting done
by Matrix on the Product outside the Territory.
6.6. Hold and maintain the Product license application for the registration
for sale of the Product in the Territory and be responsible for
establishing the Product price, after consulting with Altana.
6.7. Supply the Product to Altana in accordance with the provisions set
forth in Section 3.6.
6.8 Be responsible for disposal of Product packaging materials which are
deemed unusable due to changes imposed by the FDA or as agreed by the
parties.
6.9 Facility Inspection. Upon reasonable written notice, Altana shall have
the right from time to time to inspect Matrix's Product manufacturing
facility(ies) and medical affairs database to verify its compliance
with the terms of this Agreement.
6.10 Inspections by Government Agencies. Matrix shall promptly notify Altana
of any inspections by any regulatory representatives of any facility at
which the Product is being or will be distributed, to the extent such
inspections pertain to the Product or the distribution thereof, and
shall send Altana copies of the results of any such inspections,
including actions taken by the inspected party or any other entity to
remedy conditions cited in such inspections.
7. PATENTS.
7.1 Matrix represents and warrants that it has the right to grant the
licenses granted to Altana herein, that it has no knowledge of any
rights of third parties that would interfere with the practice of any
Matrix patent licensed hereunder or require the payment of any royalty
by Matrix or Altana to any such third party. Matrix further agrees that
it shall indemnify and hold Altana harmless from any liability, cost or
expense resulting from any breach of the foregoing representation.
8. WARRANTIES/LIABILITIES.
8.1. Matrix warrants that the Product delivered hereunder shall comply in
all material respects with the specifications set forth on Supplement A
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hereto and shall comply with Good Manufacturing Practices. If the
Product needs to meet additional specifications due to new government
requirements in the Territory, Altana will inform Matrix of such
specifications and both Parties will study the best way to fulfill said
requirements.
8.2. Altana warrants to Matrix that all of the Product units distributed by
Altana hereunder shall have been distributed and stored in conformance
with the regulations of the applicable regulatory authority at the time
of such distribution and storage.
8.3. DISCLAIMER. EXCEPT THOSE REPRESENTATIONS MADE TO ALTANA IN THIS
AGREEMENT, MATRIX MAKES NO OTHER REPRESENTATION OR WARRANTY, EXPRESS OR
IMPLIED, AS TO THE PRODUCT AND MATRIX HEREBY EXPRESSLY DISCLAIMS ANY
WARRANTIES IMPOSED BY STATUTE OR LAW, SUCH AS WARRANTIES OF
MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, EXCEPT WHERE SUCH
WARRANTIES MAY NOT BE DISCLAIMED BY LAW OR STATUTE APPLICABLE TO THIS
AGREEMENT.
8.4. Limited Liability. NEITHER PARTY WILL BE LIABLE FOR ANY SPECIAL,
INCIDENTAL OR CONSEQUENTIAL DAMAGES UNDER THIS AGREEMENT, EXCEPT TO THE
EXTENT THAT APPLICABLE LAWS DO NOT PERMIT SUCH LIMITATION.
8.5. During the term of this Agreement, each party shall within the time
periods prescribed from time to time by applicable laws, notify the
other party of all information coming into its possession concerning
any Adverse Event to a Product. In addition, Matrix shall provide
Altana with copies of periodic or expedited Adverse Event, safety or
recall correspondence with any governmental agency regarding the
Product, excluding any manufacturing information constituting Matrix
trade secrets. Matrix and Altana will derive a schedule for timeliness
of copying routine safety correspondence to Altana. Non-routine,
expedited safety correspondence will be copied promptly by Matrix and
sent to Altana. Matrix and Altana shall each notify the other promptly
if any batch or lot of Product is alleged or proven to be the subject
of a recall, market withdrawal or correction; provided, however, in the
event of any disagreement as to any matters relating to such recall,
market withdrawal or correction, Matrix shall have final authority on
such matters. All costs of any such recall, market withdrawal or
correction shall be borne by Matrix, unless such recall, market
withdrawal or correction is the result of an action or inaction by
Altana or its Affiliates inconsistent with its obligations under this
Agreement.
8.6. If Altana determines that the Product does not conform to the
Specifications, it shall promptly so notify Matrix in writing within
sixty (60)
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days of its receipt of such Product shipment. Altana and Matrix shall
confer on the matter and within sixty (60) days after receipt of
Altana's notice, Matrix shall notify Altana as to whether it concurs
with Altana's determination. If Matrix concurs then Matrix shall
promptly replace the nonconforming shipment with a like quantity of
conforming Product. If Matrix disagrees with Altana's determination,
the Parties will attempt to resolve the dispute through a meeting of
their respective Chief Executive Officers. If such dispute is not
resolved within thirty (30) days, then the Parties shall agree to
submit the allegedly nonconforming Product and original lot samples
retained by Matrix to a mutually agreeable independent laboratory for
testing. The determination of such laboratory shall be binding on the
Parties, provided that Matrix shall at any time have the right to deem
Product nonconforming, which Matrix determination shall be final.
Altana shall hold all nonconforming Product for Matrix's review and
disposal thereof.
9. INFRINGEMENT; INDEMNIFICATION.
9.1. Obligations in Case of Infringing Third Party.
9.1.1. Matrix and Altana shall each promptly inform the other
following the discovery of any infringement or unauthorized
use by a third party of any patent or other proprietary right
or other intellectual property right ("Proprietary Right")
owned or controlled by Matrix or Altana relating to the
manufacture, sale or use of the Product in the Territory. The
Parties shall undertake such efforts to obtain a
discontinuance of such infringement or unauthorized use as are
mutually agreed, and, if not successful, Matrix shall have the
first right but not the obligation to bring an infringement
action or file any other appropriate action or claim directly
related to the infringement of a Matrix Patent. The costs of
patent enforcement and related recoveries in the Territory
incurred by Matrix shall be included as shared costs or
revenues and allocated between the parties on the basis then
applicable to revenues pursuant to Section 4 above. If Matrix
does not commence a particular infringement action within 90
days after it first received written notice thereof, Altana,
after notifying Matrix in writing, shall be entitled to bring
such infringement action or any other appropriate action or
claim, the expense and recoveries of which shall again be
shared as set forth above. Matrix and Altana shall each pay
50% of any related out-of-pocket costs for any such suit
relating to infringement in the Territory, and shall share in
the same proportion any sums received, obtained, collected or
recovered, whether by judgment, settlement or otherwise as a
result of such suit in the same proportion.
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9.1.2. If either Altana or Matrix elects not to participate in such
an infringement suit, then such party shall give prompt notice
to the other. The other party may, but is not required to,
obtain a discontinuance of the alleged infringement or
unauthorized use or bring an infringement suit. Any
infringement suit shall be in the name of the party electing
to bring action or jointly as may be required by the law of
the forum. The party electing not to bring suit shall execute
such legal papers and shall render all reasonable assistance
necessary for the prosecution of such suit as may be
reasonably required by the other party; provided that the
party proceeding with such suit shall reimburse the
out-of-pocket expenses incurred by the other party in
connection with such assistance. Any such expenses and
compensation must be approved in advance.
9.1.3. It is understood that the party that institutes suit or action
pursuant to paragraph 9.1.2 above shall bear solely all costs
and expenses in connection therewith and shall be entitled to
retain and keep any and all sums received, obtained, collected
or recovered, whether by judgment, settlement or otherwise as
a result of such suit.
9.2. Indemnification.
9.2.1. Subject to Altana's compliance with its obligations as set
forth below, Matrix agrees to indemnify and hold harmless
Altana, its Affiliates, officers, directors and agents from
and against any and all losses, claims, damages, liabilities
and expenses, ("Liabilities") arising out of, relating to or
resulting from any action, suit or claim alleging that the
manufacture, use or sale of Product infringes, contributorily
infringes or induces the infringement of any patent, trade
secret or other Proprietary Right held by a third party (an
"Infringement Claim") or any action, suit or claim alleging
any product liability or similar claim relating to or arising
out of the manufacture, use or sale of the Product (a "Product
Claim" and together with an Infringement Claim, an
("Indemnified Claim"), except to the extent any such Liability
arises out of Altana's or its Affiliates' (i) negligence or
intentional misconduct, or (ii) storage, handling or
distribution of the Product other than in compliance with the
Specifications therefor or GMP regulations. In the event of
any patent infringement, Matrix shall use its commercially
reasonable efforts to obtain a license under any such patent.
9.2.2. Subject to Matrix's compliance with its obligations as set
forth below, Altana agrees to indemnify and hold harmless
Matrix its Affiliates, officers, directors and agents from and
against all Liabilities arising out of, relating to or
resulting from any product
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liability or similar claim relating to or arising out of
Altana's or its Affiliates' (i) negligence or intentional
misconduct, or (ii) storage, handling or distribution of the
Product or improper training of physicians in the use of the
Product, in each case other than in compliance with the
Specifications therefor or GMP regulations.
9.2.3. Each party agrees to notify the other within ten (10) days of
notification of any Indemnified Claim. Each party shall
consult with the other party, and keep the other party
reasonably informed, as to material developments with respect
to any Indemnified Claim for which a party seeks
indemnification hereunder. Any related correspondence sent to
other parties-in-interest in such indemnified Claim, and any
documents filed or served in connection with such Indemnified
Claim, by or on behalf of a party hereto (or the third party
that is the subject of such Indemnified Claim), shall be
provided to the other party promptly after such items are
sent, filed or served (as the case may be), and any related
correspondence or documents that a party (or such third party)
receives in connection with such Indemnified Claim shall
promptly be provided to the other party. The defendant named
in the Indemnified Claim shall retain decision-making
authority in defending the Indemnified Claim, but in no event
shall a party be responsible for any amounts paid in
settlement of an Indemnified Claim unless such party approves
the settlement. Notwithstanding anything herein to the
contrary, all costs of litigation or similar proceedings
(including legal fees, court costs, related travel fees, etc.)
shall be solely and completely the obligation and liability of
the party which bears the risk, and such party shall hold the
other party hereto harmless from and against the same.
9.2.4. Notwithstanding the foregoing, the obligation to share
reimbursements or contributions from third parties shall not
apply to proceeds under insurance policies that Altana or
Matrix, respectively, receives from its insurance carriers
(including, if applicable, a captive insurance carrier).
9.3. The foregoing obligation of Matrix does not apply with respect to
Product or portions or components thereof (i) not supplied by Matrix,
(ii) which are modified after shipment by Matrix, if the alleged
infringement or liability relates to such modification, (iii) combined
with other products, processes or materials where the alleged
infringement or liability relates to such combination, (iv) where
Altana continues allegedly the infringing or liability causing activity
after being notified thereof or after being informed of modifications
that would have avoided the alleged infringement or liability, or (v)
where Altana's use of the Product is not in accordance with the License
and the liability or infringement arises from
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such misuse; Altana will indemnify Matrix and its officers, directors,
agents, and employees from all damages, settlements, attorneys' fees
and expenses related to a claim of infringement, misappropriation or
liability excluded from Company's indemnity obligation by this
sentence.
9.4. The Parties acknowledge that the ultimate liability of the Parties
hereto to third parties for Infringement and Personal Injury Claims
will be decided by the court or other ruling entity having jurisdiction
over the matter under the laws of the relevant country. The provisions
of this Section 9 are not intended to modify such finding of ultimate
liability but, rather, reflect an agreed upon cost sharing arrangement
between the Parties hereto.
10. CONFIDENTIALITY.
10.1. All documents and information made available by or on behalf of Matrix
to Altana shall be kept secret and confidential by Altana and shall not
be disclosed to any persons except employees, government authorities
and parties appointed or approved by Matrix, which are directly engaged
in operations relating to the Product.
10.2. Altana shall take all steps as are reasonably necessary to ensure that
its staff is aware of and complies with the provisions of this Section
10.
10.3. The restrictions herein contained shall not extend to information that:
(i) was already known to Altana and not directly or indirectly received
from Matrix; or (ii) was in the public domain at the time of its
receipt, or entered the public domain thereafter through no fault of
Altana.
10.4. The provisions of this Section 10 shall remain in force during the term
of this Agreement and for a further period of five (5) years following
the termination hereof.
11. DURATION AND TERMINATION.
11.1. This Agreement shall become effective upon signing of the Parties on
the day first above written.
11.2. If not earlier terminated, this Agreement shall remain in force for a
period of five (5) years after the first shipments for sale of the
Product in the Territory. Thereafter, this Agreement may be renewed (a)
by mutual written consent of the Parties or (b) automatically for a
three (3)-year periods if Altana has met eighty percent (80%) Accepted
Forecast sales level for the prior two (2) years (with the Parties
agreeing to determine in good faith the forecast sales levels for a
three (3) year period on a rolling annual basis beginning after the
third year of the original five year term. Once accepted by Matrix,
such new or revised forecasts shall be referred to as "Accepted
Forecasts").
14
11.3. Either party shall be entitled to terminate this Agreement at any time
in the event of a material breach of any terms or conditions of this
Agreement by the other Party which has not been remedied within thirty
(30) days after written notice thereof.
11.4 In the event of the insolvency or adjudication in bankruptcy or the
making of an assignment for the benefit of creditors by either Party,
this Agreement may be terminated immediately, at the option of the
other Party, by providing written notice.
11.5. Upon expiration or termination of this Agreement each Party shall
ensure that all Information disclosed to the other Party by it and any
documentation or duplications thereof in its possession shall promptly
be returned to the other Party.
12. MARKETING AND SALES COMMITTEE.
Within thirty (30) days of the date of this Agreement, Altana and
Matrix shall each appoint two (2) persons to an AccuSite(TM) marketing
and sales advisory committee (the "Committee") for the Territory. This
Committee will make recommendations regarding the Product launch plan
including marketing introduction, the sales plan for specific target
audiences in the Field (i.e., dermatologists, or OB / GYN). The role of
the Committee will be advisory only to review the marketing plan and
clinical program designed to support marketing and sales efforts. With
respect to the advice given by the Committee, the party charged with
the obligation to which such advice applies shall reasonably and in
good faith consider such advice, but such party shall be entitled
ultimately to proceed as it reasonably deems appropriate in view of its
obligations under this Agreement.
The Marketing and Sales Committee will be responsible for reviewing and
making recommendations to Matrix on matters relating to sales forecasts
and marketing expenses as set forth in Sections 3.4 and 5.1
respectively.
13. FORCE MAJEURE.
A party shall be excused from performing its obligations (other than an
obligation for paying sums when due) under this Agreement if its
performance is restricted or prevented by any cause beyond its control,
including but not limited to, Acts of God, fire, explosion, weather,
war insurrection, riots, or government action. Performance shall be
excused only to the extent of and during the reasonable continuance of
such disability.
15
14. INSURANCE.
Both Parties shall maintain comprehensive insurance policies in the
Territory covering Product liability in an amount customary in the
industry for Products competing with or similar to the Products. The
Parties agree to exchange Certificates of Insurance each year during
the term of the Agreement.
15. ASSIGNABILITY.
This agreement shall be binding upon and inure to the benefit of the
Parties and their respective successors and assigns. Altana shall not
assign, delegate, sublicense or otherwise transfer its rights or
obligations hereunder or any interest herein (including any assignment
or transfer occurring by operation of law) without the prior written
consent of Matrix except that this agreement and the rights and
obligations hereunder may be freely transferable in the Territory by
Altana to companies under the control of Altana or under the same
control as Altana.
Matrix may freely assign or transfer any or all of its rights,
obligations or interest herein in connection with the sale, assignment,
or transfer of all or substantially all of Matrix's business or to an
Affiliate provided, however, that Matrix may only assign its
manufacturing obligations hereunder to another FDA approved
manufacturing facility.
16. NOTICES.
Notices and other communications provided for hereunder shall be in
writing and mailed by registered mail or sent by facsimile or telex to
the address set forth below or at such address as the receiving party
shall have previously notified the sending party, and shall be deemed
received (i) fifteen (15) business days after mailing (with postage
prepaid) or (ii) upon transmission if sent by facsimile or telex and
promptly confirmed in writing by mail:
MATRIX ALTANA
------ ------
Matrix Pharmaceutical, Inc. Altana, Inc.
00000 Xxxxxx Xx. 00 Xxxxxx Xxxx
Xxxxxxx, Xxxxxxxxxx 00000 Xxxxxxxx, Xxx Xxxx 00000
17. REFORMATION AND SEVERABILITY.
If any provision of this Agreement is declared invalid by any tribunal
of competent jurisdiction, then such provision shall be deemed
automatically adjusted to conform to the requirements for validity as
16
declared at such time, and, as so adjusted, shall be deemed a provision
of this Agreement as though originally included herein. In the event
that the provision invalidated is of such nature that it cannot be so
adjusted, the provision shall be deemed deleted from this Agreement as
though the provision had never been included herein. In either case,
the remaining provisions of this Agreement shall remain in effect.
18. COUNTERPARTS AND HEADINGS.
This Agreement may be executed in any number of copies, each of which
when so executed and delivered shall be deemed to be an original and
all of which taken together shall constitute but one and the same
instrument. Headings in this Agreement are included herein for
convenience of reference only and shall not constitute a part of this
Agreement for any other purpose and will not affect in any way the
meaning or interpretation of this Agreement.
19. WAIVER.
If any party should at any time refrain from enforcing its rights
arising from a breach or default by the other party of any of the
provisions of this Agreement, such waiver shall not be construed as a
continuing waiver regarding that breach or default or other breaches or
defaults of the same or other provisions of the Agreement.
20. GOVERNING LAW.
This Agreement shall be governed by and construed in accordance with
the laws of California and the United States of America without regard
to conflicts of laws principles thereof. At any time during the Term of
this Agreement the applicable laws in the Territory will be respected.
21. RELATION OF PARTIES.
The parties are independent contractors and nothing in this Agreement
shall imply any principal or agent relationship or other joint
relationship and neither party shall have the power or authority to
expressly or impliedly obligate the other party.
22. ENTIRE AGREEMENT.
Each of the Parties hereto agrees that there are no other agreements,
understandings, or representations, oral or written, other than as set
forth herein, and that this Agreement supersedes and replaces any and
all prior and contemporaneous agreements, understandings,
representations, statements, or other communications relating to the
subject matter hereof. The Parties hereto further agree that this
17
Agreement constitutes the sole and entire agreement between the Parties
relating to the subject matter hereof.
In witness whereof, the Parties have duly executed the Agreement as of
the date first above set forth.
MATRIX PHARMACEUTICAL, INC. ALTANA, INC.
By: /s/ XXXXX X. XXXXX By: /s/ XXXXXX X. XXXX
-------------------------- ------------------------
Xxxxx X. Xxxxx Xxxxxx X. Xxxx
Title: COO, CFO Title: President
-------------------------- ------------------------
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Exhibit A
IDENTIFICATION OF THE PRODUCT
AccuSite(TM) Injectable Gel is a new combination of previously known active
ingredients, fluorouracil (5-FU) and epinephrine.
AccuSite(TM) (fluorouracil / epinephrine) Injectable Gel is a clear to
opalescent, colorless to slightly yellow, sterile gel containing fluorouracil,
an antineoplastic agent and epinephrine, a vasoconstrictor, in a purified bovine
collagen matrix. The drug product is provided in a kit containing two sterile,
nonpyrogenic, prefilled syringes: one syringe contains a fluorouracil gel and
the other syringe contains an epinephrine solution. The drug product kit also
includes a mixing adapter. The contents of the syringes should be mixed
immediately before use. Each kit will provide on milliliter after mixing.
Each milliliter of AccuSite(TM) Injectable Gel contains 30 mg of fluorouracil
and 0.1 mg of epinephrine. Each milliliter also contains 20 mg purified bovine
collagen, 0.05 mg edetate disodium dihydrate, 1.2 mg monobasic sodium phosphate,
2.9 mg dibasic sodium phosphate, 1.6 mg sodium chloride, and up to 0.15 mg
sodium metabisulfite in water for injection, with sodium hydroxide and / or
hydrochloric acid to adjust the pH.
AccuSite(TM) Injectable Gel is designed for direct intralesional injection
(intradermal injection under target lesions and surrounding tissues). The
chemotherapeutic agent, 5-FU, is delivered in a viscous collagen matrix. The
addition of the vasoconstrictor epinephrine assists in the extent of local
retention of 5-FU.
Fluorouracil Gel: Fluorouracil gel contains 33.3 mg / mL fluorouracil, purified
bovine collagen, monobasic sodium phosphate, dibasic sodium phosphate and sodium
chloride in water for injection with sodium hydroxide and / or hydrochloric acid
to adjust the pH. Fluorouracil (5-fluoro-2,4-(1H,3H)-pyrimidinedione, C4H3FN2O2)
is a white to practically white crystalline powder that is sparingly soluble in
water. The molecular weight of fluorouracil is 130.08.
Fluorouracil is a cytotoxic drug which is believed to act through inhibition of
DNA synthesis by means of blockade of thymidylate synthetase involved in the
formation of thymidine monophosphate. It may also become incorporated into RNA,
and may inhibit uracil utilization in RNA biosynthesis. The activity of 5-FU
against a wide variety of tumors and the expected toxicities following
intravenous administration are well established.
1
Epinephrine Solution: Epinephrine solution contains 1 mg / mL epinephrine,
edetate disodium (dihydrate) and sodium metabisulfite with sodium hydroxide and
/ or hydrochloric acid to adjust pH, in water for injection. Epinephrine is
(R)-4-[1-hydroxy-2(methylamino)ethyl]-1-1-benzenediol, C9H13NO3 (molecular
weight: 183.21). Epinephrine is very slightly soluble in water and in alcohol.
The AccuSite(TM) Injectable Gel formulation is designed to retain therapeutic
concentrations of 5-FU in the tumor, thereby minimizing systemic exposure to the
drug.
AccuSite(TM) Injectable Gel is indicated for the treatment of external
condylomata acuminata (genital warts) by intradermal / intralesional injection
once a week for up to six weeks, or to complete response.
(Other specifications and details to be mutually agreed upon in accordance with
applicable regulatory requirements)
2
Exhibit B
Marketing Expense
(000)
1998 1999 2000 2001 2002
---- ---- ---- ---- ----
* * * * *
* Indicates that material has been omitted and confidential treatment has
been requested therefor. All such omitted material has been filed
separately with the Commission pursuant to Rule 24b-2.
1
Exhibit C
Initial Sales Forecast
(000)
1998 1999 2000 2001 2002
---- ---- ---- ---- ----
Sales * * * * *
Units * * * * *
* Indicates that material has been omitted and confidential treatment has
been requested therefor. All such omitted material has been filed
separately with the Commission pursuant to Rule 24b-2.
1
Exhibit D
TRADEMARK LICENSE AGREEMENT
This Trademark License Agreement ("Agreement") is effective as of this
4th day of August 1997 ("Effective Date"), by and between Matrix Pharmaceutical,
Inc. ("Matrix"), a Delaware corporation, having offices at 00000 Xxxxxx Xxxxx,
Xxxxxxx, Xxxxxxxxxx 00000, U.S.A., and Altana, Inc., a New York corporation
("Altana"), having offices at Melville, New York.
In consideration of the mutual covenants and promises contained herein,
the parties hereto agree as follows:
1. Definitions.
The following terms shall have the meanings set forth below:
a. "Distribution Agreement" shall mean the Distribution Agreement, of
even date herewith, entered into by the parties hereto.
b. "Licensed Xxxx" shall mean the trademark AccuSite(TM) or its
successor; provided however, that the appearance and/or style of the
AccuSite(TM) xxxx xxx change from time to time in Matrix's sole discretion. As
of the Effective Date, the Licensed Xxxx is the subject of the following pending
trademark registration application: RM95C005680 filed on 10/6/95.
c. "Product" shall have the meaning set forth in the Distribution
Agreement.
d. "Territory" shall mean the United States of America and Puerto Rico.
2. License Right Granted.
a. In partial consideration of the consideration set forth in the
Distribution Agreement, Matrix hereby grants to Altana, and Altana accepts, upon
the terms and conditions set forth herein, an exclusive, non-transferable,
non-sublicensable, royalty-free license to use the Licensed Xxxx in the
Territory solely in connection with the Product.
b. Altana hereby acknowledges and agrees that, except as set forth
herein, Altana has no rights, title or interest in or to the Licensed Xxxx and
that all use of the Licensed Xxxx by Altana shall inure to the benefit of
Matrix. Altana covenants that it will not take any action that might prejudice
or adversely affect Matrix's rights in the Licensed Xxxx. Altana shall not have
the right to use the Licensed Xxxx as a trade name, company name, trade style or
fictitious business name.
1
c. Altana understands and agrees that it does not have the right to use
the Licensed Xxxx in any manner that conflicts with the rights of any third
party. If, in Matrix's reasonable determination, Altana's use of the Licensed
Xxxx infringes the rights of any third party or weakens or impairs Matrix's
rights in the Licensed Xxxx, then Altana agrees to immediately terminate or
modify such use in accordance with Matrix's instructions. In the event Altana
fails to terminate or modify such use as directed by Matrix, Matrix may
terminate this Agreement.
d. Matrix agrees to defend, indemnify and hold Altana harmless from
liability resulting from infringement by the Licensed Xxxx of any trademark,
service xxxx or trade name right of a third party, provided that (i) Matrix is
promptly notified of any and all threats, claims and proceedings related
thereto, (ii) Matrix shall have sole control of the defense and / or settlement
thereof at its costs and expenses, (iii) upon Matrix's request, Altana
immediately ceases use of the Licensed Xxxx and (iv) upon Matrix's request,
Altana provides Matrix with reasonable assistance and information available to
Altana for such defense. The foregoing obligation of Matrix does not apply if
(a) Altana continues allegedly infringing activity after being notified thereof
or after being informed of modifications that would have avoided the alleged
infringement or (b) Altana's use of the Licensed Xxxx is not strictly in
accordance with the terms and provisions of this Agreement.
3. Quality Standards.
a. All packaging, labels, labeling and marketing materials for the
Product shall be in accordance with applicable regulations and shall be approved
in advance in writing by Matrix or a Matrix appointed designee. Altana shall not
distribute or have distributed any written information regarding the Product
that bears the Licensed Xxxx without the prior written approval of Matrix. If
Matrix believes that the Licensed Xxxx is being used in a manner that could
diminish Matrix's rights in or protection of the Licensed Xxxx, Altana agrees,
at Altana's sole cost and expense, to make whatever changes and / or corrections
Matrix deems necessary to protect the Licensed Xxxx.
b. Altana agrees that it shall not engage, participate or otherwise
become involved in any activity or course of action that diminishes and/or
tarnishes the image and/or reputation of the Licensed Xxxx.
c. Matrix shall have the right to inspect Altana's operations and
facilities during normal business hours upon reasonable prior notice, with the
sole purpose of any such inspection being to verify that Altana is in compliance
with the terms of this Agreement in maintaining the good will of the trademarks.
d. Altana agrees to conduct its activities under this Agreement in a
lawful manner.
e. Altana agrees to use the Licensed Xxxx in accordance with and only
on or in connection with the Product.
2
4. Use and Display of Licensed Xxxx.
a. All usage by Altana of the Licensed Xxxx shall include the trademark
symbol and shall be in the following form, as appropriate: AccuSite(TM). All
literature and materials printed, distributed or electronically transmitted by
Altana and containing the Licensed Xxxx shall include the following notice:
AccuSite(TM) is a trademark of Matrix Pharmaceutical, Inc.
5. Term and Termination.
a. This Agreement shall commence on the Effective Date and shall
continue in effect for a period coterminous with the term of the Distribution
Agreement, unless earlier terminated in accordance with the terms and conditions
set forth herein.
b. This Agreement shall automatically terminate upon termination (for
whatever reason) of the Distribution Agreement.
c. This Agreement and the license granted herein may be terminated by
Matrix if Altana fails to perform or comply with a material provision of this
Agreement and such breach or default is not cured by Altana within thirty (30)
days after written notice of termination is received by Altana.
6. Cooperation and Protection.
a. Altana agrees to reasonably cooperate with and assist Matrix in
protecting and defending the Licensed Xxxx and shall promptly notify Matrix in
writing of any infringements, claims or actions by others (which come to the
attention of Altana) in derogation of the Licensed Xxxx; provided, however, that
Matrix shall have the initial right to determine whether any action shall be
taken on account of any such infringement, claim or action. If Matrix elects not
to pursue such infringement by written notice to Altana, Altana may, but is not
required to, seek to obtain a discontinuance of the alleged infringement or
unauthorized use or bring an infringement suit. The party not bringing such
action or suit shall execute such legal papers and shall render all reasonable
assistance necessary for the prosecution of such suit as may be reasonably
required by the other party; provided that the party proceeding with such suit
shall reimburse the out-of-pocket expenses incurred by the other party in
connection with such assistance. Any such expenses and compensation must be
approved in advance. It is understood that the party that institutes suit or
action shall bear solely all costs and expenses in connection therewith and
shall be entitled to retain and keep any and all sums received, obtained,
collected or recovered, whether by judgment, settlement or otherwise as a result
of such suit.
3
b. Altana agrees not to apply for registration of the Licensed Xxxx (or
any xxxx confusingly similar thereto) anywhere in the Territory.
7. Assignment.
Altana may not assign this Agreement or any of its rights or
obligations under this Agreement without the prior written consent of Matrix,
other than to an Affiliate (as defined in Distribution Agreement) provided that
Altana shall remain liable for its obligations hereunder.
8. Notices.
All notices, requests, demands and other communications required or
permitted to be given under this Agreement shall be in writing and shall be
deemed to have been duly given only if personally delivered, delivered by a
major commercial rapid delivery courier service or mailed by certified or
registered mail, return receipt requested, postage prepaid, to a party at the
address set forth on the first page hereof or such other address as a party last
provided to the other by written notice.
9. General.
a. Amendment, Modification and Waiver. The failure of either party to
enforce its rights or to require performance by the other party of any term or
condition of this Agreement shall not be construed as a waiver of such rights or
of its right to require future performance of that term or condition. Any
amendment or modification of this Agreement or any waiver of any breach of any
term or condition of this Agreement must be in a writing signed by both parties
in order to be effective, and any such waiver shall not be construed as a waiver
of any continuing or succeeding breach of such term or condition, a waiver of
the term or condition itself or a waiver of any right under this Agreement.
b. Governing Law. This Agreement shall be governed and interpreted
under the laws of the State of California, United States of America, without
regard to the conflicts of law provisions thereof.
c. Severability. In the event that any provision of this Agreement
shall be determined by a court of competent jurisdiction to be illegal or
unenforceable, that provision will be limited or eliminated to the minimum
extent necessary so that this Agreement shall otherwise remain in full force and
effect and enforceable.
d. Survival. Sections 7 and 10(b) hereof shall survive the termination
of this Agreement.
4
IN WITNESS WHEREOF, the parties hereto have each caused this Agreement
to be executed by their authorized representatives as of the date first above
written.
MATRIX PHARMACEUTICAL, INC. ALTANA, INC.
By: /s/ XXXXX X. XXXXX /s/ XXXXXX X. XXXX
--------------------------------- -------------------------------
Xxxxx X. Xxxxx Xxxxxx X. Xxxx
COO, CFO Title: President
5
Exhibit E
Safety Reporting and Exchange of Safety Information Between
Matrix Pharmaceutical, Inc. and Altana Inc.
Altana Inc. (Altana) will be marketing and selling AccuSite(TM) Injectable Gel
in the United States of America, as outlined in the Distribution Agreement.
Matrix Pharmaceutical, Inc. (Matrix), either directly or through other
licensees, will coordinate pharmacovigilance activities for AccuSite in
allcountries where AccuSite may be commercialized. The purpose of this document
is to outline pharmacovigilance responsibilities between Matrix and Altana.
The following definitions will be used to insure consistency between Altana and
Matrix.
Definitions:
Adverse Event: An adverse event (AE) is any adverse event associated with
the use of a drug in humans, whether or not considered drug related,
including the following: an adverse event occurring in the course of the
use of a drug product in professional practice; an adverse event occurring
from drug overdose, whether accidental or intentional; an adverse event
occurring from drug abuse; an adverse event occurring from drug withdrawal;
and any significant failure of expected pharmacological action.
An AE can therefore be any unfavorable and unintended sign (including an
abnormal laboratory finding), symptom, or disease temporally associated
with the use of a drug product, whether or not related to the drug product.
Adverse Drug Reaction: An adverse drug reaction (ADR) refers to adverse
events for which there is a causal relationship between a drug product and
the event. The causality is at least a reasonable possibility, i.e., the
relationship cannot be ruled out.
All spontaneous AE reports should be considered ADRs for regulatory
reporting purposes.
Serious adverse event or adverse drug reaction: Any untoward medical
occurrence (or event) that at any dose:
o Is fatal: This serious criterion applies if the subject's or
patient's death is suspected as being a direct outcome of the reported
AE.
o Is life threatening: This serious criterion applies if the subject or
patient, in the view of the treating physician, is at substantial risk
of dying from the ADR/AE as it occurs (e.g., gastrointestinal
hemorrhage, bone
1
marrow suppression). It does not apply if an AE hypothetically might
have caused death if it were more severe.
o Requires or prolongs inpatient hospitalization: This serious
criterion applies if the reported AE requires at least a 24-hour
inpatient hospitalization or prolongs an existing hospitalization. A
hospitalization for an elective procedure or routinely scheduled
treatments is not a serious AE because a procedure and/or a treatment
is not an untoward medical occurrence.
o Results in persistent or significant disability/incapacity: This
serious criterion applies if the "disability" caused by the reported AE
results in a substantial disruption of the subject's or patient's
ability to carry out normal life functions (e.g., blindness secondary
to a cerebrovascular accident). Any disability that is permanent is
also serious.
o Is a congenital anomaly/birth defect: This serious criterion applies
if a subject or patient exposed to a medicinal product gives birth to a
child with a congenital anomaly or birth defect.
o Is a new cancer: This serious criterion applies if the patient is
diagnosed with a cancer. If the patient is known to have a cancer prior
to treatment with a Matrix product, then this criterion applies if the
patient develops a new cancer of a different type.
o Is associated with an overdose: This serious criterion applies if an
overdose of the product was associated with an adverse event.
o Necessitates medical or surgical intervention to preclude permanent
impairment of a body function or permanent damage to a body structure:
This serious criterion applies if the reported AE requires treatment to
prevent significant damage to the subject or patient (e.g.,
administration of acetylcysteine to prevent permanent liver damage from
Tylenol(R) overdose-induced liver toxicity). Changes in dosage,
discontinuation of therapy, and routine treatment with a prescription
medication are not in themselves considered serious by this criterion.
Nonserious adverse event or adverse drug reaction: Any untoward medical
occurrence (or event) that at any dose does not meet the criteria as
serious will be classified as nonserious.
Scope of Responsibilities
2
Altana Inc.: Altana will be responsible for the following activities:
o Receipt and follow-up of adverse event information from health
professionals (including physicians, surgeons, pharmacists, nurses,
etc.) and consumers in the U.S. and submission to Matrix.
o Medical verification of any consumer report describing a serious
adverse event. This means contacting the consumer's physician to
verify any report of a serious adverse event and obtaining additional
information, as needed.
o Transfer of individual case information for all reported serious
adverse events to Matrix Pharmaceutical as soon as possible and no
later than 2 calendar days of initial receipt and subsequent receipt
of additional information, if any. Information can be transferred by
paper (via fax) or electronically.
o Transfer of individual case information for all reported nonserious
adverse events to Matrix Pharmaceutical within 5 days of initial
receipt and subsequent receipt of additional information, if any.
Information can be transferred by paper (via fax) or electronically.
o Transfer of individual case information for all product complaints
that may be associated with an adverse event to Matrix Pharmaceutical
as soon as possible and no later than 5 calendar days of initial
receipt and subsequent receipt of additional information, if any.
Information can be transferred by paper (via fax) or electronically.
o Communication of ideas to improve the efficient and economical flow
of adverse event information between Altana and Matrix.
3
Matrix Pharmaceuticals, Inc. Matrix will be responsible for the
following activities:
o Compliance with local pharmacovigilance laws or regulations in the
United States of America.
o Assessment of individual case reporting responsibilities and
coordination of submission to regulatory health authorities,
including FDA and other countries.
o Providing summaries and patient information on reported cases and
facilitating Altana's understanding of safety and pharmacovigilance
information.
o Entry of reports into and maintenance of a safety database for
spontaneous and other postmarketing adverse events collected
worldwide.
o Preparation of periodic safety update reports (e.g., FDA Periodic
Report, CIOMS-II) for submission to multiple regulatory authorities.
o Providing assistance as necessary to answer questions, etc. from
Altana. This includes both assistance to understand and complete
safety reporting responsibilities and providing information that will
allow Altana to answer questions from health professionals, etc.
o Providing assistance, education and guidance for collecting and
processing adverse event reports with AccuSite(TM).
o Coordinating the collection of and providing analysis, processing and
reporting for any clinical trial safety information involving
AccuSite.
o Maintenance of AccuSite package insert and other regulatory
documents.
Transfer of Information
o Information can be transferred by paper (via fax) or electronically.
4
