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EXHIBIT 10.7
AGREEMENT
This Agreement, is by and between Advanced Corneal Systems, Inc., (hereinafter
"ACS"), with offices at 00000 Xxxxx Xxxxxxx, Xxxxx 000, Xxxxxx, XX 00000 and
CoMedica Global Inc., (hereafter "CoMedica") located at 000 Xxxx Xxxxxx,
Xxxxx 000, Xxxxxxxx, Xxxxxxx Xxxxxxxx X0X 0X0.
WHEREAS, ACS intends to submit the results of the Investigation to the Food and
Drug Administration ("FDA") and other international regulatory agencies in
support of marketing approval;
WHEREAS, ACS desires to have certain research conducted (as described herein)
with respect to the compound known as Vitrase(TM) a hyaluronidase solution (the
"Investigation") in accordance with the protocol attached hereto as Exhibit A,
which is incorporated herein together with all amendments thereto,
(hereinafter, the "Protocol"); and
WHEREAS, CoMedica is experienced in such research and has the qualified
personnel available to perform these services for ACS;
WHEREAS, ACS has entered into a contract substantially similar to this
Agreement with Covance Clinical and Periapproval Services, Inc., having its
principal place of business at 000 Xxxxxxxx Xxxxxx, Xxxxxxxxx, Xxx Xxxxxx
("COVANCE"), for the purpose of having COVANCE assist ACS with the execution of
substantially the same investigation in North America and Europe; and
NOW THEREFORE, in consideration of the premises and of the mutual promises and
undertakings herein contained, the parties intending to be legally bound do
hereby agree as follows:
I. SCOPE OF SERVICES
The Investigation shall consist of the services set forth in
Attachment 1 (Scope of Services) which is incorporated herein.
COMEDICA shall not undertake any additional work without a written
modification of this Agreement pursuant to Section XVIII
(Modifications). To the extent that any conflict exists between the
terms of this Agreement and Attachment 1 (Scope of Services), the
terms of this Agreement shall take precedence.
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CroMedica agrees to conduct, and to cause its employees, officers, directors and
representatives to conduct, the Investigation in accordance with the terms of
this Agreement (as applicable to the particular Investigation), the Protocol,
and in full compliance with all applicable Federal, State, and local laws and
regulations, including without limitation FDA guidelines pertaining to clinical
investigations and the use of investigational drugs in humans.
CroMedica hereby certifies that it has not and will not use in any capacity the
services of any individual, corporation, partnership or association which has
been debarred under 21 U.S.C. 306(a) or (b). In the event that CroMedica
becomes aware of the debarment or threatened debarment of any individual,
corporation, partnership or association providing services to CroMedica or to
an Investigator retained by CroMedica which directly or indirectly relate to
Investigator's activities under this Agreement, CroMedica shall notify ACS
immediately. Any Investigator retained by CroMedica will understand that ACS
shall have the right to terminate this Agreement immediately upon receipt of
such notice.
CroMedica will undertake to assure that Investigators retained by CroMedica in
the INVESTIGATION certify that they have not been debarred under the provisions
of the Generic Drug Enforcement Act of 1992, 21 U.S.C. 306(a) or (b). In the
event that an Investigator:
(i) becomes debarred; or
(ii) receives notice of action or threat of action with respect to debarment,
during the term of this Agreement, CroMedica agrees to notify ACS
immediately. In the event that Investigator becomes debarred as set forth
in clause (I) Investigators retained by CroMedica understands that this
Agreement shall automatically terminate without any further action or
notice by either party. In the event that an Investigator receives notice
of action or threat of action as set forth in clause (ii) above, CroMedica
and Investigators retained by CroMedica understands that ACS shall have
the right to terminate this Agreement immediately.
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CroMedica understands that the results from its Investigation will be
incorporated with the results from the COVANCE investigation into
regulatory submissions, or parts thereof, as contemplated herein.
CroMedica understands that COVANCE is responsible for the timely and
proper preparation of portions of the regulatory submissions.
Therefore, CroMedica will cooperate to the full extent necessary to
insure that the Protocol is properly implemented, and that the data
from the Investigation is delivered to COVANCE in a timely manner as
required under the Protocol. Such cooperation shall include, but not
be limited to, providing COVANCE and ACS with timely notice of any
issues with the Protocol or Investigation, delays in delivering the
data and/or deficiencies in the data itself.
II. PERFORMANCE SCHEDULE
The Performance Schedule by which CROMEDICA shall perform the services
specified in this Agreement is set forth in Attachment 2 (Payment and
Performance Schedule), which is incorporated herein.
III. COMPENSATION
A. CROMEDICA Compensation
This is a fixed unit price contract. ACS shall pay to
CROMEDICA in the manner specified in Attachment 2 (Payment and
Performance Schedule), as compensation for all services
performed under this Agreement, the sum of US $409,790. This
amount represents all of CroMedica's professional fees, and
all expenses other than Reimbursable Expenses as described
below.
B. Payment Schedule
CroMedica shall invoice ACS on a milestone-completion basis,
according to the Payment Schedule set forth in Attachment 2
(Payment and Performance Schedule), which is incorporated
herein.
C. Reimbursement of Expenses
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1. ACS will reimburse CroMedica for the "actual cost" (defined
below) of expenses incurred by CroMedica for:
(a) travel; provided that such expenses are (i) reasonable
and necessary; and (ii) incurred consistent with
CroMedica's travel policy.
As used herein, "actual cost" means the dollar cost paid by
CroMedica, without any management fee, commission or xxxx-up
by CroMedica, and less any discount, rebate or other
allowance paid to CroMedica by a supplier, whether reflected
on the original billing or thereafter.
2. Expenses reimbursable under (a) above are referred to
herein as "Reimbursable Expenses". Except for Reimbursable
Expenses, all costs incurred by CroMedica in performing this
Agreement shall be the responsibility of CroMedica.
3. CroMedica shall submit monthly invoices for travel expenses
paid in the preceding month, together with back-up
documentation as requested by ACS, to the person identified
on Attachment 3 (Contact Persons).
IV. PROTOCOL
The Investigation shall be conducted in full accordance with the
Protocol and any Protocol amendments. CroMedica shall make no change
in the Protocol during the course of the Investigation without the
prior written approval of ACS, except where necessary to eliminate
apparent immediate hazards to human subjects. ACS shall have the right
at any time to initiate such changes in the Protocol, as ACS deems
necessary or appropriate, including suspending the Investigation
temporarily or permanently.
V. CROMEDICA MANAGEMENT OF CLINICAL INVESTIGATIONS
A. Investigator Brochure/Product Monograph
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Before the Investigation begins, and from time to time throughout the
course of the Investigation, as determined by ACS, ACS shall provide
CroMedica and all Investigators with a current Investigator Brochure
and Product Monograph for the study compound.
B. Field Monitoring Guidelines
Unless supplied by ACS, in consultation with ACS, CroMedica shall
develop, Protocol-specific Field Monitoring Guidelines to facilitate
study monitoring.
c. On-Site Monitoring
1. Before the commencement of the Investigation at each site,
CroMedica shall conduct an on-site study initiation visit to
each Investigator site. During the study initiation visit,
CroMedica shall inspect and inventory clinical supplies and
review the Protocol and CRF form with site staff to ensure
understanding and compliance.
2. CroMedica shall conduct periodic on-site monitoring visits to
each Investigator site during the course of the Investigation
at a frequency to be directed by ACS, but in no event less
than one visit every eight weeks. During each such visit,
CroMedica shall ensure, by review of relevant investigator
records, and otherwise, that the investigator and the
investigational site continue to meet all applicable federal,
state, and local laws, statutes and ordinances and
regulations, and FDA Guidelines for the Conduct of Clinical
Investigations. CroMedica will promptly notify ACS of any
investigator that is not complying with their agreement, and
attempt to obtain compliance. If compliance is not promptly
obtained, and after approval is received from ACS, CroMedica
will end the investigators participation in the study.
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3. CroMedica shall conduct an on-site, close-out visit at
the conclusion of the study. During the close-out
visit, CroMedica shall ensure that the Investigator has
maintained the standards specified in Paragraph 2,
above, and, in addition, shall:
a. Obtain a reconciliation of all drug inventories;
b. Resolve any final inquiries concerning CRF
issues; and
c. Confirm that the Investigator has maintained all
required documentation.
4. CroMedica shall prepare and maintain reports of each
on-site visit performed pursuant to this sub-Section
(On-Site Monitoring). The monitoring visit reports
shall be in a format mutually agreed upon by the
parties.
D. Supply of Drug
1. Supply of Drug to Investigators
ACS shall supply all of the drug to be used in the
Investigation.
2. Return of Unused Drug Supplies
CroMedica shall ensure that each investigator whose
participation in the Investigation has been completed
or discontinued shall either (a) return any unused drug
supplies to CroMedica or ACS, as directed by ACS; or
(b) dispose of the unused drug supplies as directed by
ACS. CroMedica shall require that each Investigator
account for any drug supplies that are missing.
3. Non-Diversion; Labeling
All drug supplied to CroMedica and to Investigators
shall remain the exclusive property of ACS until
administered or dispensed to patients during the course
of the
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Investigation. In no event shall any drug supplied to CroMedica for
use in the Investigation be used by CroMedica for any purpose other
than as contemplated by the Protocol and this Agreement, or be
delivered to any person other than an Investigator and, CroMedica
shall use all reasonable efforts to ensure that the Investigators
comply with the terms of this Agreement, the Attachments hereto and
the Protocol in all material respects.
4. Study Drug Disposition Records
Unless otherwise specified by ACS, CroMedica shall maintain records
relating to the disposition of the drug, which shall include, without
limitation: (1) the amounts of drug supplies received from ACS (with
respective dates); (2) the Investigator sites to which the drug has
been delivered (with respective dates and amounts); (3) the amount of
the drug spilled or otherwise lost (with respective dates, if known);
(4) the amount of the drug returned to CroMedica (with respective
dates); and (5) the amount of the drug returned by CroMedica to ACS
(with respective dates).
E. Maintenance and Inspection of Records
CroMedica shall prepare and maintain complete, accurate, legible written
records, accounts, notes, reports and data on the Investigation in a timely
fashion. CroMedica shall maintain all records under this Section (CROMEDICA
Management of Clinical Investigation) pertaining to the management of the
Clinical Investigation for a period of 15 years from the date of creation.
ACS authorized representative(s), and regulatory authorities to the extent
permitted by law, may, during regular business hours, arrange in advance
with CroMedica to inspect and copy all data and work products related to
the Investigation. CroMedica shall cooperate with
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any regulatory authority and allow them access to relevant
records and data to the extent permitted by law.
VIII. CONTACT PERSONS AND STAFFING
CROMEDICA shall assign a sufficient number of personnel to complete
the Scope of Services set forth on Attachment 1 (Scope of Services).
In the event that ACS determines that any CROMEDICA personnel are not
performing to ACS satisfaction, ACS shall have the right to request
that such personnel be replaced by personnel acceptable to ACS. ACS
and CROMEDICA have designated appropriate personnel to be available to
CroMedica to answer questions and resolve problems relating to the
Investigation. The names of these individuals, and the respective
subjects on which they may be consulted, are set forth in Attachment 3
(Contact Persons).
IX. PERIOD OF PERFORMANCE
This Agreement shall take effect as of the last date of execution by
the last of the parties to execute this Agreement, and shall remain in
effect until the completion of the services performed by CroMedica
under the Agreement, or until earlier termination in accordance with
the Section on Termination, below.
X. TERMINATION
A. ACS Right to Terminate
ACS reserves the right to immediately terminate this Agreement in
whole or in part, with or without cause, upon written notice to
CroMedica. In the event this Agreement is terminated by ACS prior
to completion, CroMedica shall use its best efforts to conclude
or transfer the project, as directed by ACS, as expeditiously as
possible. CroMedica shall not undertake further work, incur
additional expenses, or enter into further commitments with
regard to the Investigation after receiving such notice upon of
termination from ACS, except as mutually agreed upon by the
parties. Upon termination of the Agreement, CroMedica shall
return to ACS all of ACS property (as defined in the Section
covering
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Property Ownership) in CroMedica's possession, unless
otherwise agreed to in writing.
B. CROMEDICA's Right to Terminate
CroMedica may terminate this Agreement upon default of any
material provision of this Agreement; provided, however, that
prior to terminating, CroMedica shall notify ACS in writing of
such default, and shall allow ACS thirty (30) days to remedy
such default. In the event that ACS fails to remedy the
default within the 30-day period, CroMedica may terminate the
Agreement effective immediately.
C. Compensation to CroMedica upon Termination
In the event of a termination under this Section, CroMedica
shall be entitled to compensation as follows:
1. All payments due and owing under this Agreement at
the time of CroMedica's receipt of the notice of
termination for work completed and in progress;
2. Reimbursement for any noncancelable services and
commitments entered into by CroMedica in order to
carry out this Agreement, provided CroMedica provides
ACS with documentation of completion of work or
expenses incurred.
3. CroMedica shall credit or return to ACS any funds not
expended or obligated by CroMedica in connection with
the Investigation prior to the effective termination
date indicated in the notice of termination.
Termination of this Agreement by either party shall
not affect the rights and obligations of the parties
accrued prior to the effective date of termination.
The rights and duties under Articles III, V, VI, X,
XI, XII, XIII, XIV, XVI, XVIII, XX, XXI, XXII, XXIII,
and XXIV shall survive the termination or expiration
of this Agreement.
XI. CONFIDENTIAL INFORMATION
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A. Definition
For purposes of this Agreement, "Confidential Information" means any
knowledge or information that is (1) acquired by CroMedica from ACS prior
to or during the course of the Investigation whether written, graphic or
oral, or (2) prepared, developed or generated by CroMedica during the
course of the Investigation; provided, however, that "Confidential
Information" does not, whether written, graphic or oral, include knowledge
or information that CroMedica can demonstrate by written records was known
by it prior to the receipt of such knowledge or information from ACS, or
that is publicly disclosed by ACS either prior to or subsequent to receipt
of the knowledge or information by CroMedica.
B. Non-Disclosure
CroMedica (1) shall not publish, disseminate, or otherwise disclose to any
third party (except as may be required by this Agreement or by law) any
Confidential Information without the prior written consent of ACS; (2)
shall use the same care and discretion in maintaining the confidentiality
of the Confidential Information that CroMedica uses with similar
information that it considers confidential; provided that such care and
discretion shall not be less than the standard of care and discretion that
would be employed by a prudent person under similar circumstances; (3)
shall restrict the dissemination of the Confidential Information within its
own organization to persons who have a need to know; and (4) shall not,
without the prior written consent of ACS, make any use whatever of the
Confidential Information except for the purpose of conducting the
Investigation. In the event CroMedica is required by applicable law to
disclose Confidential Information to a proper authority, CroMedica shall
first notify ACS, and CroMedica and ACS shall then attempt in good faith to
agree upon a mutually satisfactory way to disclose such Confidential
Information as necessary for this limited purpose. CroMedica shall ensure
that its employees, officers,
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directors, affiliates, agents and representatives
comply with the terms of this Article XI and
otherwise with there terms of this Agreement.
C. Return of Confidential Information
At the expiration or earlier termination of this
Agreement, CroMedica shall return to ACS all
written Confidential-Information, and all written
material that incorporates any Confidential
Information.
D. Survival of Obligation of Confidentiality
The obligation of confidentiality set forth in
this Section shall continue for ten years
following the date of expiration or earlier
termination, for any reason, of this Agreement,
and shall be binding upon permitted assignees,
administrators and other legal representatives of
CroMedica.
E. CroMedica shall obtain ACS prior written
permission before using ACS name, symbols and/or
marks in any form of publicity in connection with
the Investigation. The foregoing sentence shall
not exclude legally required disclosure by
CroMedica or reports generated in the normal
course of business by CroMedica.
XII. PROPERTY OWNERSHIP
A. Rights in Property
All materials, documents, data, software and
information of every kind and description supplied
to CroMedica by ACS or prepared, developed, or
generated by CroMedica pursuant to this
Agreement, (except for CroMedica procedural
manuals, personnel data, methods, procedures, and
policies) shall be the sole and exclusive property
of ACS and ACS shall have the right to make
whatever use it deems desirable of any such
property. CroMedica shall not, without the prior
written consent of ACS, publish, disseminate, or
otherwise disclose to any third party any such
property (except such disclosure as may be
required by law), or use any such property for any
purpose other than the
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performance of this Agreement. CroMedica warrants by the
execution of this agreement that they have not entered, and
will not enter into any contractual agreement or relationship
which would in any way conflict with or compromise ACS's
proprietary interest in, or rights to any inventions,
discoveries or technology existing at the time of the
execution of this Agreement or arising out of or related to
the performance thereunder.
B. Retention of Property
Unless otherwise required by law or the terms of this
Agreement, any property specified in Subsection A, above, that
CroMedica shall have in its possession shall be maintained by
CroMedica for a period of not less than five (5) years from
the date of receipt thereof and shall be organized in such
manner that it will be ready for immediate reference. ACS
shall have the right at any time to examine or obtain from
CroMedica copies of any or all such property. After five (5)
years, CroMedica may dispose of such property in accordance
with instructions provided by ACS. If ACS fails to provide
such instructions, CroMedica shall so notify ACS, and if
instructions are still not forthcoming within thirty (30) days
of such notification, CroMedica may destroy such property.
C. Survival of Obligation
The rights and obligations set forth in this Section shall
survive the expiration or earlier termination, for any reason,
of this Agreement, and shall be binding upon permitted
assignees, administrators and other legal representations of
CroMedica.
XIII. RIGHTS IN INTELLECTUAL PROPERTY AND PATENTS
A. Inventions, Discoveries, and Know-How
With respect to any and all inventions, discoveries, and
know-how (including, without limitation, all ideas,
improvements, and creations) that are conceived, gained, or
reduced to practice by
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CroMedica in the course of performing its obligations under
this Agreement, CroMedica agrees:
1. To disclose promptly to ACS or its nominee any such
inventions, discoveries and know-how;
2. To assign and transfer to ACS all rights, title, and
interest in and to any and all such inventions,
discoveries, and know-how upon the request of ACS;
and
3. To perform any and all lawful acts that in the
judgment of ACS are necessary or desirable to secure
or maintain for the benefit of ACS adequate patent
and other property rights in the United States and
all foreign countries with respect to any such
inventions, discoveries and know-how, including,
without limitation, making or delivering to ACS
United States and foreign patent applications, powers
of attorney, assignments, oaths and affirmations, and
applications for securing, protecting or registering
any property rights relating to such inventions,
discoveries and know-how, and cooperating with ACS in
the defense of patents related to such inventions,
discoveries and know-how in infringement actions.
ACS shall compensate CroMedica at standard hourly rates for
the time devoted to said activities and reimburse it for all
reasonable expenses incurred.
B. Copyrights
CroMedica agrees to assign to ACS all right, title, and
interest in and to any Work, as defined below, including
without limitation all right, title, and interest in and to
copyright of the Work, in the United States or anywhere
throughout the world, in the name of ACS (or otherwise, as
directed by ACS), for the sole benefit of ACS, and to secure
renewals or extensions of such copyrights in ACS name (or
otherwise, as directed by ACS). CroMedica shall execute any
assignments or other documents that ACS deems necessary to
effectuate the purposes of this
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Subsection B. For purposes of this Section, "Work" means all reports,
documents, research, drafts, materials, computer software, and data
that are recorded in any form (including, without limitation, written,
electronic, or photographic form) and that are prepared, developed, or
generated by CroMedica in the course of performing its obligations
under this Agreement.
C. Survival of Obligations
The obligations imposed by this Section shall survive the expiration
or earlier termination, for any reason, of this Agreement with respect
to inventions, discoveries and know-how conceived, gained or reduced
to practice by CroMedica, and Work prepared, developed, or generated
by CroMedica, in the course of performing this Agreement. Such
obligations shall be binding upon permitted assignees, administrators
and other legal representatives of CroMedica. It is agreed that
neither CroMedica nor ACS transfers to the other by operation of this
Agreement any patent right, copyright, or other proprietary right of
either party, except as specifically set forth in this Agreement.
XIV. INDEMNIFICATION
A. Indemnification of ACS
CroMedica shall hold harmless and indemnify ACS, its employees, agents
and assigns, from and against all claims, complaints, or lawsuits for
damages that arise or are alleged to arise as a result of the
intentional misconduct, negligence, malfeasance or violation of law,
statute or regulation of CroMedica, or any of its employees, agents,
or representatives, in conducting the Investigation, or from
CroMedica's failure to adhere to the terms of the Protocol or this
Agreement or fails to comply with all applicable Provincial, Federal,
state and local laws, and guidelines and regulations. For purposes of
this Article XIV only, Investigators are not agents or representatives
of CroMedica.
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B. Indemnification of CroMedica
ACS shall indemnify and hold harmless CroMedica, its
representatives and employees, from and against all claims,
complaints, or lawsuits for damages that arise as a result of
personal injury or death that is alleged to have been caused by
or attributed to any substance provided by ACS and dispensed or
administered in accordance with the provisions of the Protocol;
provided that:
1. ACS shall be promptly notified of any such claim,
complaint, or lawsuit;
2. ACS shall have the right, in its sole discretion, to
undertake the defense, compromise, or settlement, at its own
expense and by its own counsel, of any such claim,
complaint, or lawsuit; and
3. CroMedica shall cooperate fully in the investigation and
defense of any such claim, complaint, or lawsuit.
The indemnification provided for in this Subsection B shall not
apply to any loss, damage, cost or expense that is caused by or
attributable to the intentional misconduct, negligence,
malfeasance or violation of law, statute or regulation of
CroMedica, or any of its employees, agents, or representatives.
XV. INSURANCE
A. CROMEDICA shall maintain in force at all times during the term of this
Agreement, with an insurance company acceptable to ACS, the following
insurance, including any special terms indicated and shall, prior to
signing this Agreement, provide to ACS certificates of insurance for
each type of insurance specifying that ACS will receive no less than
thirty (30) days' notice of cancellation, non-renewable or material
change.
1. Comprehensive General Liability insurance including products and
completed operations, personal injury,
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broad form property damage including completed operations, independent
contractors, and blanket contractual liability with the
product/completed operations exclusion removed. ACS will be named as
additional insured. Combined Single Limit for bodily injury and
property damage - $1,000,000.
2. Workers' Compensation Insurance Coverage - statutory.
3. Employers' Liability Coverage - $500,000.
4. Professional Liability Insurance - Covering all claims for damages
arising out of errors and omissions in the performance of professional
duties of CROMEDICA under this Agreement. The Limits of Liability shall
be $1 million per claim subject to a $2 million annual aggregate.
XVI. NOTICES AND PAYMENTS
Except as otherwise provided herein, any notice or other communications
or any payment required under this Agreement shall be delivered by
hand, first class mail, a nationally recognized overnight courier
service, or facsimile transmission, to the party at the address listed
below:
If to Advanced Corneal Systems: Xxxx Xxxxx Xxxxxxxxxxx
------------------------------
ADVANCED CORNEAL SYSTEMS, INC.
00000 Xxxxx Xxxxxxx, Xxxxx 000
Xxxxxx, XX 00000
If to CROMEDICA: Xxx Xxxxxxx
------------------------------
CroMedica Global Inc.
000-000 Xxxx Xxxxxx
Xxxxxxxx, Xxxxxxx Xxxxxxxx
X0X 0X0
Any such notice shall be effective (1) in the case of a hand delivery,
when received; (2) in the case of an overnight delivery service, on the
next business day after being placed in the possession of such delivery
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service, with delivery charges prepaid; (3) in the case of the mail,
three days after deposit in the postal system, first class postage
prepaid; and (4) in the case of facsimile transmission, when electronic
indication of receipt is received.
XVII. MODIFICATIONS
No changes shall be made in this Agreement except by written agreement
of the parties, signed by authorized representatives. ACS authorized
representative shall be designated in Attachment 3 (Contact Persons).
XVIII. ENTIRE AGREEMENT
This Agreement, together with its Attachments, including the Protocol,
shall be the entire and complete understanding between the parties in
regard to the covered subject matter. This Agreement merges all prior
discussions between the parties and neither party shall be bound by
conditions, definitions, warranties, understandings, or representations
concerning such subject matter except as provided in this Agreement or
as specified on or subsequent to the effective date of this Agreement
in a writing signed by properly authorized representatives of both the
parties.
XIX. ASSIGNMENT
Neither party may assign, delegate or otherwise transfer any of its
rights or obligations under this Agreement without the prior written
consent of the other party. Notwithstanding the previous sentence, ACS
may assign its obligations under this Agreement to any affiliate of ACS
or in connection with the transfer or sale of all or substantially all
of its assets or business relating to the drug(s) being studied
hereunder or its merger or consolidation with another organization,
provided that the rights of CroMedica under this Agreement are not
materially prejudiced.
XX. INDEPENDENT CONTRACTOR
CroMedica shall function as an independent contractor and shall not
hold itself out as an agent of ACS in any way.
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XXI. GOVERNING LAW
This Agreement shall be construed, interpreted and enforced under the
laws (excluding the laws governing conflicts of laws) of the State of
California.
XXII. WAIVER
The failure of a party in any instance to insist on the strict
performance of the terms of this Agreement shall not be construed to
be a waiver or relinquishment of any of the terms of this Agreement,
either at the time of the party's failure to insist upon strict
performance or at any subsequent time.
XXIII. SEVERANCE
Each clause of this Agreement is a distinct and severable clause and
if any clause is deemed illegal, void, or unenforceable, the validity,
legality, or enforceability of any other clause or portion of this
Agreement shall not be affected thereby.
XXIV. HEADINGS
All headings contained in this Agreement appear only for convenience
and reference. They do not define, limit, extend, or describe the
scope of this Agreement or the intent of any of its provisions.
ACCEPTED AND AGREED:
ADVANCED CORNEAL SYSTEMS, INC. CROMEDICA GLOBAL INC.
BY: /s/ [ILLEGIBLE] BY: /s/ [ILLEGIBLE]
--------------------------- ----------------------
TITLE: VICE PRESIDENT TITLE: PRESIDENT & C.F.O.
DATED: SEPTEMBER 8, 1998 DATED: AUGUST 24, 1998
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CROMEDICA PROPOSAL FOR ADVANCED CORNEAL SYSTEMS, PHASE III VITRASE(TM) STUDY
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STUDY SPECIFICATIONS AND TIME ESTIMATES
(based on protocol synopsis and other information received)
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Product Vitrase(TM) a hyaluronidase solution
Indication Intravitreal hemorrhage
Study Design Phase III, prospective, randomized, parallel,
double-masked, dose-response study with 4
arms
Study Objectives To investigate the safety and efficacy of
hyaluronidase (intravitreal injection) for
clearance of severe vitreous hemorrhage
Estimated # and Location of Sites 00, Xxxxx Xxxxxx
# of Patients Global enrolment 800 patients, competitive
enrolment
# of Visits/Patient 9 (baseline, randomization, day 1, day 7,
months 1, 2, 3, 6, 12)
Estimated # of CRF Pages/Patient Not known
Estimated Enrolment Period 20 months as indicated: October 1998-May 2000
Follow-up Period 12 months
Estimated Time Study Conduct Total 32 months Oct. 1998-May 2001
Enrolment and 6 month follow-up complete: 26 months Oct. 1998-Nov. 2000
12 month follow-up complete: an additional 6 months Dec. 2000-May 2001
Total CroMedica Involvement 3 years
July-Sept 1998: regulatory and site selection
Oct. 1998-May 2001: study conduct
June 2001: study close-out
Estimated # Monitoring Visits/Site Initiation, 24 regular visits, close-out
(Visits every 4-6 weeks for 26 months;
visits every 3 months for another 6 months)
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ASSUMPTIONS
Fee Schedules
o Fee schedules are based on the study specifications noted above and the
assumptions noted below.
o Fees are in U.S. funds.
o All travel-associated costs including transportation, accommodation and
meals connected with meetings, monitoring and other site visits will be
passed directly through to ACS.
o All shipping and printing costs of study-related materials will be the
responsibility of ACS.
Investigator Meeting
o For this proposal we have assumed that CroMedica will organize and
conduct an investigator meeting in S. Africa, including logistics,
correspondence with participants and agenda in consultation with ACS,
with presenters from CroMedica and ACS. Medica expertise for the
meeting will be provided by ACS as discussed.
o Pass-through costs include transportation, accommodation and meals for
CroMedica staff, including the project manager, a clinical operations
assistant and CRAs.
ACS Responsibilities
o Investigator budget negotiations, fees and fee administration are not
included in the budget, and will be the responsibility of ACS.
o It is assumed that ACS will provide the protocol, CRFs, laboratory
services and biometry services.
o It is assumed that ACS has in place a Medical Monitor to whom CroMedica
will report all serious adverse events and refer questions about
inclusion/exclusion criteria and protocol interpretation.
IRBs
o CroMedica has assumed the use of individual institutional IRBs.
Site Responsibilities
o It is assumed that sites will provide all necessary regulatory
documentation, transcribe data on to CRFs, provide adequate resources
for the conduct of the study, provide source documentation, remain in
compliance with the protocol and report all adverse events.
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Project Management and Monitoring
o CroMedica will provide comprehensive management of the study to include:
-leadership, direction and problem-solving
-ensuring all regulatory requirements are met
-site selection and initiation
-provision and supervision of CRAs
-scheduling of visits
-review of trip reports
-supply tracking
-timeline preparation and updates
-progress reports to ACS
-meetings and communications with ACS and monitors
-weekly teleconferences with CRAs for status up-dates
o All trial related activities undertaken by the CroMedica project team
are conducted in accordance with CroMedica SOPs and ICH/GCP guidelines.
Where requested, ACS SOPs can be used.
o CroMedica policy dictates that an indication- and protocol-specific CRA
training seminar occur as an adjunct to the investigator meeting.
Otherwise, a training seminar will be planned before commencement of the
study.
o CroMedica will prepare a monitoring plan, define the scope of work for
the monitors, and distribute all relevant study materials to monitors.
o Time allotted for monitoring visits includes preparation, time on-site,
travel time and trip report.
o Monitoring visits include all monitoring activities, specifically:
-review of patient eligibility and consent
-data review for accuracy and completeness, including 100% source
verification of CRF data
-protocol and GCP adherence
-recruitment assessment
-study file maintenance, including regulatory documentation as needed
-adverse event and serious adverse event reporting
-supply tracking and accountability
-data query resolution and transfer of data
-trip report
-all communications with site staff and project manager
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ATTACHMENT 2
PAYMENT AND PERFORMANCE SCHEDULE
PAYMENT SCHEDULE
Sponsor shall reimburse reasonable costs and expenses at net thirty (30) days
terms upon receipt of invoice and any associated original receipts, and/or at
the occurrence of the below incidents enacted at Sponsor's request, pending
review for acceptableness and/or completeness. All figures are in US dollars:
FIXED-UNIT PRICE PAYMENT STRUCTURE
--------------------------------------------------------------------------------
UNIT COST STUDY MAXIMUM
--------- -------------
Up-front (20%) $81,958. $ 81,958.
-------------- --------
Site recruitment including IRB
submission and collection of
pre-Study documentation $ 731. X 10 $ 7,310.
-------------- --------
Regulatory Submission $ 1,360. $ 1,360.
-------------- --------
Investigator Meeting $ 5,240. $ 5,240.
-------------- --------
Site Initiation Visit $ 1,428. X 10 $ 14,280.
-------------- --------
Interim Monitoring Visit $ 1,190. X 240 $285,600.
-------------- --------
Site Close Out Visit $ 1,020. X 10 $ 10,200.
-------------- --------
Management fee paid at study $ 3,842. $ 3,842.
completion
-------------- --------
Total Contract $409,790.
========
Pass-through Costs: SPONSOR shall reimburse CONTRACTOR for reasonable
pass-through costs (e.g., travel, lodging, meals) at net thirty (30) days term
upon receipt of original receipt(s)/invoice. Interest at 15% shall apply in net
thirty (30) days terms are not satisfied.
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ATTACHMENT 3
CONTACT PERSONS
Advanced Corneal Systems, Inc. Contractual/Financial Matters:
X.X. XxxXxx
Vice President
00000 Xxxxx Xxxxxxx, Xxxxx 000
Xxxxxx, XX 00000
Clinical/Investigation Matters:
Xxxx Xxxxx Xxxxxxxxxxx
00000 Xxxxx Xxxxxxx, Xxxxx 000
Xxxxxx, XX 00000
CroMedica Xxx Xxxxxxx
CroMedica Global Inc.
000 Xxxx Xxxxxx, Xxxxx 000
Xxxxxxxx, Xxxxxxx Xxxxxxxx
X0X 0X0
20
