EXHIBIT 10.20
AGREEMENT BETWEEN ENDO PHARMACEUTICALS INC.
AND
KUNITZ AND ASSOCIATES, INC.
DATED
June 1, 1999
The confidential portions of this exhibit have been filed separately with the
Securities and Exchange Commission pursuant to a confidential treatment request
in accordance with Rule 406 of the Securities Act of 1933.
REDACTED PORTIONS OF THIS EXHIBIT ARE MARKED BY AN ***.
This agreement ("Agreement") dated as of June 1, 1999 by and between Kunitz and
Associates, Inc., a Maryland corporation with its principal offices at 0000
Xxxxxxxx Xxxx, Xxxxx 000, Xxxxxxxxx, Xxxxxxxx 00000-0000 ("KAI") and Endo
Pharmaceuticals Inc., a Delaware corporation, with its principal offices at 000
Xxxxxxxxxx Xxxx Xxxxxxx Xxxx, Xxxxxx Xxxx, XX 00000 ("ENDO")
W I T N E S S E T H:
WHEREAS, KAI has certain expertise in providing pharmacovigilance, medical
communications, and other pharmaceutical regulatory services to the
pharmaceutical industry; and
WHEREAS, ENDO is an integrated pharmaceutical company which requires
pharmacovigilance, medical communications, and pharmaceutical regulatory
services for its pharmaceutical products; and
WHEREAS, KAI and ENDO desire to enter into an agreement for the provision of
such services for all ENDO products for the United States, its commonwealths,
possessions, and territories, and the District of Columbia;
NOW, THEREFORE, in consideration of the foregoing premises and the mutual
promises, covenants and conditions contained herein, KAI and ENDO agree as
follows:
1. DEFINITIONS
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1.1 "Adverse Drug Experience" means all reported data, from all countries,
concerning any serious or unexpected adverse event associated with the use
of a drug in humans, whether or not considered drug-related, with regard to
any Product and which is of such a nature and magnitude that it is required
under the laws and regulations of the FDA to be collected, maintained, and
reported to the FDA.
1.2 "Adverse Drug Experience Database" means all data and derivative materials
(in whatever format) concerning any Adverse Drug Experience which is stored
and maintained in an electronic format in KAI's computer system.
1.3 "Affiliate" means any corporation, association or other entity, which
directly or indirectly controls, is controlled by or is under common
control with the party in question. As used herein the term "control" means
control with possession of the power to direct, or cause the direction of,
the management and policies of a corporation, association, or other entity.
1.4 "Best Efforts" means those efforts which would be made by a reasonably
prudent business person acting in good faith, in the exercise of reasonable
commercial judgment and in a manner consistent with those efforts a party
in the pharmaceutical industry
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devotes to providing pharmacovigilance, medical communications, and other
regulatory services for its own pharmaceutical products.
1.5 "ENDO Operating Procedure" means all operating procedures and work
instructions prepared by KAI, at the direction of and with input from ENDO,
which are to be used by the Project Manager, Product Information
Specialist, Staff Physician, and all other KAI personnel responsible for
providing the Services to ENDO in the Territory. ENDO Operating Procedures
shall not include KAI's proprietary standard operating procedures.
1.6 "FDA" means the Food and Drug Administration of the United States.
1.7 "Fee" means the compensation to be paid, on an annual basis, by ENDO to
KAI, for Years 1 through 3 of the Initial Term, and if ENDO exercises its
Option, for Years 4 and 5 of the Option Term, for the Services to be
provided by KAI under this Agreement as set forth in Schedule A, attached
hereto and made a part hereof, as the same may be amended from time to time
by mutual consent of the parties. Such Fee shall be paid to KAI in
accordance with the payment terms set forth in Article 6.2.
1.8 "Operating Committee" means the committee which will oversee and manage the
day-to-day operations of KAI personnel, including, but not limited to, the
Product Information Specialist, the Project Manager, and the Staff
Physician, dedicated to providing the Services by KAI to ENDO in the
Territory. The Committee shall be comprised of ENDO's Director of Medical
Affairs, KAI's President, KAI's Vice President, and Project Manager, as
well as other appropriate representatives from KAI and ENDO as mutually
determined by the parties.
1.9 "Operating Phase" means the period from August 1, 1999 to July 31, 2002 for
the Initial Term. If ENDO exercises its Option for Years 4 and 5 of the
Option Term, the Operating Phase means the period August 1, 2002 to July
31, 2003 and August 1, 2003 to July 31, 2004, respectively.
1.10 "Option" means, upon expiration of the Initial Term of this Agreement,
ENDO, at its discretion, may extend the Agreement for a fourth year and if
desired by ENDO, a fifth year for the Fees set forth in Schedule A for
Years 4 and 5, respectively. If ENDO exercises the Option, all other terms
of this Agreement shall remain the same for Year 4 and if the Option for
Year 5 is exercised, Year 5 of the Option Term, unless the parties mutually
agree otherwise.
1.11 "Option Term" means Years 4 and 5, individually and collectively, where
applicable.
1.12 "Product" means all ENDO pharmaceutical products and all product extensions
(including single and combination products), all product improvements,
including, but not limited to, all dosage forms (including placebos),
strengths, and package sizes of such Products, sold, at any time, by ENDO.
Such Products are listed in Schedule X. XXXX may delete or add a Product to
Schedule B and KAI shall provide Services for such Products at no
additional cost or reduction in cost unless the Product additions or
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deletions materially change the scope of Services to be provided by KAI to
ENDO under this Agreement.
1.13 "Product Literature" means the medical, informative, and other written
information concerning the Products provided to KAI by ENDO, at ENDO's
expense.
1.14 "Product Information Database" means all data, including, without
limitation, historical data and all derivative materials (in whatever
format) regarding Product responses, including the Product response, and
all information regarding inquiries from professional representatives,
healthcare professionals, and consumers which is stored and maintained in
an electronic format in KAI's computer database.
1.15 "Product Information Specialist" means an individual employed by KAI who is
responsible for triaging and/or handling all inquiries regarding Adverse
Drug Experiences and/or Products and providing Product responses, prepared
by ENDO, to professional representatives, healthcare professionals, and
consumers. The Product Information Specialist shall have the requisite
skills, knowledge, a minimum of a Bachelor of Science degree, and a minimum
of two (2) years of experience in connection with the provision of
identical or similar Services to the pharmaceutical industry or
alternatively, a minimum level of experience as mutually agreed to by the
parties. The Product Information Specialist will be solely dedicated to
ENDO in connection with the provision of Services by KAI to ENDO in the
Territory. ENDO shall have the right to review the qualifications of any
Product Information Specialist prior to hiring of such person (and any
subsequent replacement) by KAI to provide Services to ENDO in the Territory
under this Agreement.
1.16 "Project Manager" means an individual employed by KAI who is responsible
for the management and supervision of the Product Information Specialist,
Staff Physician, and any other KAI personnel responsible for providing
Services to ENDO in the Territory, managing the day-to-day operations of
the KAI personnel responsible for providing the Services to ENDO in the
Territory, and the coordination and implementation of all support services
provided by KAI to ENDO in the Territory. The Project Manager shall have
the requisite skills, knowledge, a minimum of a Bachelor of Science degree,
and a minimum of five (5) years experience in connection with the provision
of identical or similar Services to the pharmaceutical industry or
alternatively, a minimum level of experience as mutually agreed to by the
parties. ENDO shall have the right to review the qualifications of any
Project Manager prior to hiring of such person (and any subsequent
replacement) by KAI to provide Services to ENDO in the Territory under this
Agreement.
1.17 "Report" means a report, summary, or analysis, requested by ENDO, regarding
Products and/or Services provided by KAI to ENDO in the Territory, as set
forth in Schedule X. XXXX may delete or add a Report to Schedule C and KAI
shall provide such Reports at no additional cost or reduction in cost
unless the Report additions or deletions materially change the scope of
Services to be provided by KAI to ENDO in the Territory under this
Agreement.
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1.18 "Services" means the pharmacovigilance, product information support,
medical communications, Adverse Drug Experience, medical literature search
support, and pharmaceutical regulatory services to be provided by KAI to
ENDO in the Territory as described in Schedule A.
1.19 "Staff Physician" means a healthcare professional with a medical degree who
is employed by KAI to provide the Services set forth in Schedule A in the
Territory. Such an individual shall have the requisite skills, knowledge, a
minimum of a medical degree and a minimum of seven (7) years experience in
connection with the provision of identical or similar Services to the
pharmaceutical industry or alternatively, a minimum level of experience as
mutually agreed to by the parties. ENDO shall have the right to review the
qualifications of any Staff Physician prior to hiring of such person (and
any subsequent replacement) by KAI to provide Services to ENDO under this
Agreement.
1.20 "Start-Up Fee" means the compensation which ENDO shall pay to KAI for the
initial planning and preparation activities performed by KAI during the
Start-Up Phase as well as for the provision of Services by KAI in the
Territory during the Test Phase as more fully described in Schedule A. Such
Start-Up Fee shall not exceed ***.
1.21 "Start-Up Phase" means the period from March 22, 1999 to May 31, 1999
during which KAI shall provide planning and preparation activities for
Products in the Territory as more fully described in Schedule A.
1.22 "Term" means (a) for the Start-Up Phase, the period from March 22, 1999 to
May 31,1999, (b) for the Test Phase, the period from June 1, 1999 to July
31, 1999, and (c) for the Operating Phase, the period August 1, 1999 to
July 31, 2002 (collectively "the Initial Term"), (d) for Years 4 and 5 of
the Option Term, the period from August 1, 2002 to July 31, 2003 and August
1, 2003 to July 31, 2004, respectively and (e) upon renewal of the
Agreement, any subsequent one (1) year period(s) ("the Additional Term").
The word Term shall refer, individually and collectively, where applicable,
to the Initial, Option, and any Additional Terms.
1.23 "Territory" means the United States, its territories, commonwealths, and
possessions and the District of Columbia.
1.24 "Test Phase" means the period from June 1, 1999 to July 31, 1999 during
which KAI shall provide planning and preparation activities for ENDOCET,
ENDODAN, PERCOCET, PERCODAN, PERCODAN-DEMI, and PERCOLONE in the Territory
as more fully described in Schedule A.
1.25 "Year 1" means the period from August 1, 1999 to July 31, 2000.
1.26 "Year 2" means the period from August 1, 2000 to July 31, 2001.
1.27 "Year 3" means the period from August 1, 2001 to July 31, 2002.
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1.28 "Year 4" means the period from August 1, 2002 to July 31, 2003.
1.29 "Year 5" means the period from August 1, 2003 to July 31, 2004.
2. APPOINTMENT
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2.1 During the Term of this Agreement, ENDO shall appoint KAI exclusively to
provide the Services, as set forth in Schedule A, in the Territory. KAI
agrees to exclusively provide such Services to ENDO in the Territory.
During the Initial Term, any Option Term, or if renewed, any Additional
Term of this Agreement, it is understood that ENDO shall have the right to
simultaneously provide such Services in-house.
2.2 (a) Personnel. KAI shall use its Best Efforts to recruit and retain skilled
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and trained personnel to exclusively provide the Services to ENDO in the
Territory. Specifically, KAI shall dedicate three and one-half full-time
equivalents ("FTEs") to provide the Services to ENDO in the Territory. Such
KAI FTEs shall consist of a minimum of one (1) Product Information
Specialist, one (1) Project Manager, one (1) Staff Physician, and an
apportioned amount of time, as mutually agreed by the parties, of
appropriate staff personnel with a healthcare degree or relevant
pharmacovigilance, clinical research, or product information experience. In
addition, KAI shall provide supporting personnel, on an ongoing basis, to
supplement the Services provided by the Product Information Specialist, the
Project Manager, and the Staff Physician.
(b) During the Term of this Agreement, if the Product Information
Specialist, the Project Manager, and/or Staff Physician positions are
vacant for greater than four (4) calendar weeks, at any point in time, KAI
shall (a) notify ENDO within one (1) calendar week after such vacancy
occurs and (b) provide a refund to ENDO, in an amount equal to KAI's fully
allocated cost per individual less any actual expenses (noncancellable and
nonreimburseable) incurred by KAI for any recruitment efforts expended to
fill such vacancy, calculated from the start date of the vacancy for each
vacant position which is vacant for greater than four (4) calendar weeks.
KAI shall provide such a refund within thirty (30) days of the receipt of
ENDO's written request for such a refund. This refund provision shall not
be applicable if the vacancy is due to ENDO's recruitment and hiring of the
Product Information Specialist, the Project Manager, and/or Staff Physician
for an in-house Medical Affairs department.
3. TERM
----
3.1 Agreement Term.
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(a) Start-Up Phase. For the Start-Up Phase, this Agreement shall commence on
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March 22, 1999 and shall remain in effect through and including May 31,
1999.
(b) Test Phase. For the Test Phase, this Agreement shall commence on June 1,
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1999 and shall remain in effect through and including July 31, 1999.
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(c) Operating Phase. For the Operating Phase for the Initial Term, this
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Agreement shall commence on August 1, 1999 and shall remain in effect
through and including July 31, 2002.
(d) Operating Phase for Any Option Term. Upon the exercise of the Option by
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ENDO under Article 7, this Agreement shall commence, for Year 4 of the
Option Term, on August 1, 2002 through July 31, 2003 and for Year 5 of the
Option Term, on August 1, 2003 through July 31, 2004.
(e) Additional Terms. After the expiration of the Initial Term and if ENDO
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exercises its Option, any Option Terms, this Agreement may be renewed, for
an Additional Term(s) upon ninety (90) days written notice by a party to
the other party of its desire to renew this Agreement. Such renewal may be
for identical, similar, or renegotiated terms mutually agreed to by the
parties.
3.2 Commencement of Services.
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(a) The Start-Up Phase. Services to be provided by KAI to ENDO during the
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Start -Up Phase shall commence in the Territory on March 22, 1999.
(b) The Test Phase. Services to be provided by KAI to ENDO during the
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Test Phase shall commence for *** in the Territory on June 1, 1999.
(c) Operating Phase for Initial, Option, or Additional Terms. Services to
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be provided by KAI to ENDO during the Operating Phase of such Terms shall
commence in the Territory on the first day of August of the applicable
Term.
4. SERVICES
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The Services to be provided by KAI to ENDO under this Agreement are set
forth in Schedule A. Schedule A includes a detailed description of the
pharmacovigilance, product information support, medical communications,
Adverse Drug Experience, medical literature search support, and
pharmaceutical regulatory Services to be provided by KAI to ENDO and the
Fee for such Services.
5. BEST EFFORTS
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KAI shall use its Best Efforts to meet its obligations with respect to the
provision of Services to ENDO in the Territory, including, but not limited
to, its duties set forth in Article 11.1.
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6. COMPENSATION AND REIMBURSEMENT
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6.1 Compensation.
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(a) The Start-Up and Test Phases. ENDO shall pay KAI a Start-Up Fee for the
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Services to be provided for the Start-Up and Test Phases. The Start-Up Fee
for such Services, which are described in Schedule A, shall not exceed ***.
For such Services, ENDO shall pay KAI only for actual work performed and
expenses incurred for the preparation and planning activities included in
the Start-Up and Test Phases. No Start-Up Fee shall be due and owing for
any Option or any Additional Term of this Agreement.
(b) Operating Phase for Initial and Option Terms.
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(1) ENDO shall pay KAI, on an annual basis, the Fee for all Services
provided by KAI for Years 1, 2, and 3 of the Initial Term of this
Agreement as set forth in Schedule A. In no event shall such Fee
exceed *** for Year 1, *** for Year 2, *** in Year 3. If ENDO
exercises its Option for any Option Term, ENDO shall pay KAI
compensation for all Services provided by KAI which in no event shall
exceed *** for Year 4 and *** for Year 5.
(2) During the Initial and Option Term of this Agreement, if there is a
material increase, change, or reduction in Services provided by KAI to
ENDO under this Agreement, or if Services are discontinued in a
material aspect, including, but not limited to, any material increase,
reduction or change in the computer hardware and other related
technology, the telephone system and or computer software and computer
software licenses that may be required to provide the Services to ENDO
in the Territory, the Fees as set forth in Article 6.1(b)(1) shall be
adjusted accordingly, by mutual consent of the parties.
(c) Additional Term(s). For any Additional Term, ENDO shall pay KAI for all
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Services provided by KAI in accordance with the terms negotiated by the
parties for such Additional Term, which negotiations must be concluded at
least ninety (90) days prior to the end of any Option Term or any
Additional Term.
6.2 Payment Terms
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Fees: ENDO shall pay the Fee for the Initial, Option, or Additional Term
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in equal monthly installments. KAI shall provide an invoice by the fifth
business day of each calendar month for the prior calendar month to ENDO
and ENDO shall pay KAI within thirty (30) days of receipt of such invoice.
7. OPTION
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ENDO, at its discretion, may extend this Agreement, for the same terms, for
a fourth year and if desired by ENDO, a fifth year for an amount, on an
annual basis, not to exceed the
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Fees set forth in Article 6.1(b)(1). ENDO shall notify KAI of its intent to
exercise this Option sixty (60) days prior to the expiration of the Initial
or any Option Term.
8. RECORDS AND INSPECTIONS
-----------------------
ENDO may inspect and audit any and all records, books, and documents
related to KAI's performance of its obligations under this Agreement,
during normal business hours, provided, however, that ENDO shall first
provide KAI with reasonable notice of any such intended inspection and/or
audit. Further, KAI shall permit, during normal business hours,
representatives of the FDA, state, or local regulatory agency or their
agents to visit and inspect and audit any and all records, documents, or
facilities related to or used in the provision of Services to ENDO by KAI
in the Territory.
9. RETENTION OF RECORDS
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All documentation and records pertaining to this Agreement shall be held by
KAI for the length of time specified by the applicable laws, rules, and
regulations, including, but not limited to, FDA laws, rules and
regulations.
10. WARRANTIES AND REPRESENTATIONS
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10.1 Legal Authority. Each party represents and warrants to the other that it
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has the legal power, authority and right to enter into this Agreement and
to perform its respective obligations set forth herein.
10.2 No Conflicts. Each party represents and warrants that as of the date of
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this Agreement it is not a party to any agreement or arrangement with any
third party or under any obligation or restrictions, which in any way
limits or conflicts with its ability to fulfill any of its obligations
under this Agreement.
10.3 Each party currently has in force and shall maintain insurance policies
with reputable, financially sound insurance carriers in the amounts and
types of policies (with the deductibles or retentions) as set forth in
Schedule D, attached hereto and made a part hereof, as the same may be
amended from time to time, by mutual consent of the parties. ENDO shall be
named as an additional insured on the applicable KAI insurance policies.
10.4 KAI further represents and warrants that it has the requisite expertise,
experience and skill to render the Services set forth in Schedule A and
that it shall use its Best Efforts to perform such Services in a competent,
efficient and professional manner.
10.5 Survival. The foregoing representations and warranties shall survive the
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execution, delivery, and performance of this Agreement, notwithstanding any
due diligence investigation by or on behalf of either party.
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11. DUTIES OF THE PARTIES
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11.1 KAI'S DUTIES
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(a) On or by June 1, 1999, KAI shall initiate and finalize the recruitment
and hiring of a Product Information Specialist, Project Manager, and
Staff Physician which have the pharmaceutical experience required by
this Agreement to effectively and economically provide the Services to
ENDO in the Territory.
(b) During the Term of this Agreement, KAI shall expeditiously and
economically train all KAI personnel responsible for providing the
Services to ENDO in the Territory, including, but not limited to, the
Product Information Specialist, Project Manager, and Staff Physician,
regarding Products. The initial training expenses for such personnel
are included in the Start-Up Fee paid by ENDO to KAI. During the Term
of this Agreement, KAI shall continue to train such personnel on a
periodic basis. All expenses for subsequent training of such personnel
for the Initial and Option Terms are included in the Fee for such
Terms as set forth in Schedule A.
(c) KAI shall develop and maintain policies and procedures governing the
day-to-day management of all KAI personnel who are responsible for
providing the Services to ENDO in the Territory, including but not
limited to policies and procedures regarding postmarketing Adverse
Drug Experience reporting and recordkeeping for Adverse Drug
Experiences as set forth in Schedule A.
(d) KAI shall ensure compliance by the Product Information Specialist,
Project Manager, the Staff Physician, and any other KAI personnel
involved in providing Services to ENDO in the Territory with the ENDO
Operating Procedures, including, without limitation, the ENDO
Operating Procedures entitled "Postmarketing Safety Surveillance of
Human Drugs," "Product Information Call Center," "Quality Assurance
for the Product Information Call Center," "Quality Assurance Post-
Marketing Safety Surveillance of Human Drugs," and "Literature Search,
Retrieval, and Review" which are attached hereto as Schedule E, as it
may be amended from time to time, by ENDO.
(e) No adjustments to the ENDO Operating Procedures shall be made without
the prior written consent of ENDO.
(f) KAI shall ensure that the Product Information Specialist, the Project
Manager, the Staff Physician, and any other KAI personnel responsible
for providing Services to ENDO in the Territory comply with all
applicable federal, state, and local laws, rules, and regulations
governing the provision of Services to ENDO in the Territory,
including, but not limited to, the FDA's laws, rules, and regulations,
governing the provision of Services to ENDO in the Territory.
(g) KAI shall only utilize the Product Literature provided by ENDO, at
ENDO's expense, or written information, including new Product
responses, regarding the
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Products which have been prepared by KAI, at ENDO's direction and with
ENDO's consent, for use in connection with the performance of KAI's
obligations under this Agreement and the provision of Services to ENDO
in the Territory.
(h) Federal, State, and Local Regulatory Agency Communications. KAI, at
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ENDO's request and expense, shall provide assistance, including
information, records, analyses, and reports, to ENDO so that ENDO may
promptly and in a timely manner, respond to any federal, state, and/or
local regulatory agency inquiry regarding the Products. KAI shall
immediately notify ENDO of any significant regulatory action which
impacts or may impact upon the ability of KAI and/or ENDO to provide
Services to ENDO in the Territory or to perform KAI's obligations
under this Agreement.
(i) At ENDO's request, and expense, KAI shall be responsible for
preparation and completion of any written report, including, but not
limited to, periodic and annual reports with respect to an Adverse
Drug Experience, data, information, filing, and/or submission to the
FDA and /or any other state or local regulatory agency, and retention
of any forms and/or reports in accordance with any applicable federal,
state, and/or local laws, rules, and regulations with respect to the
provision of Services to ENDO in the Territory. Such expenses are
included in the Fee for the Initial and Option Terms as set forth in
Schedule A.
(j) KAI shall provide to ENDO all Reports on a monthly basis, via email in
Word or Excel format, as set forth in Schedule C.
(k) KAI shall immediately investigate and take action, if necessary,
against any and all KAI personnel involved in providing Services to
ENDO in the Territory, including the Product Information Specialist,
the Project Manager, and the Staff Physician, in connection with any
violation or noncompliance with any federal, state, or local laws,
rules and regulations, including but not limited to, any FDA laws,
rules, and/or regulations, any ENDO Operating Procedure, and/or any
KAI policy and/or procedure governing the provision of Services to
ENDO in the Territory.
(l) Within fourteen (14) business days of such occurrence, KAI shall
notify ENDO of any material violation, or act of noncompliance with
any federal, state, or local laws, rules and regulations, including
but not limited to, any FDA laws, rules, and/or regulations any ENDO
Operating Procedure, and/or any KAI policy and/or procedure governing
the provision of Services to ENDO in the Territory by any KAI
personnel involved in providing Services to ENDO in the Territory,
including the Product Information Specialist, the Project Manager, and
the Staff Physician and the corrective action taken by KAI to prevent
such reoccurrence.
(m) KAI shall be responsible for the payment of any and all fines,
penalties, and/or any other corrective actions which may be taken by
federal, state, or local regulatory agencies, including but not
limited to the FDA, in connection with and to the extent
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of KAI and/or its personnel's failure to comply with any federal,
state, or local laws, rules, and regulations.
(n) Commencing with the calendar quarter ending December 31, 1999,within
sixty (60) days after June 30 and December 31 of each calendar year
for the Term of this Agreement, KAI shall provide to ENDO its income
statement, statement of cash flows, and balance statements, setting
forth in comparative form the figures for the corresponding period of
the previous calendar year, all certified by its Chief Financial
Officer as presenting fairly in all material respects the financial
condition and results of operations of KAI.
(o) During the Term of this Agreement, KAI shall xxxxx XXXX the right to
contact KAI's bank of record, on an annual basis and upon thirty (30)
days prior written notice to KAI, to verify, the financial status of
KAI.
(p) KAI shall purchase, at ENDO's expense, the computer software programs
required for the provision of Services to ENDO in the Territory as
described in Schedule A. In addition, KAI shall obtain, at ENDO's
expense, the necessary licenses, subscriptions, consents, permits, and
/or permissions for all computer software programs used by KAI in
connection with the provision of Services to ENDO in the Territory and
the performance of KAI's obligations under this Agreement, including
all KAI-owned and third-party-owned computer software programs, in
order that ENDO may have the right to use such computer software
programs in connection with the Services provided by KAI to ENDO in
the Territory. For the Term of this Agreement, KAI shall xxxxx XXXX a
non-exclusive, royalty-free license, where necessary, to use such
computer software programs in connection with the Services provided by
KAI to ENDO in the Territory. The cost of obtaining such rights to
such computer software programs are included in the Fees for the
Initial and any Option Terms set forth in Schedule A.
(q) KAI shall purchase, at ENDO's expense, the computer hardware and other
equipment required for the provision of Services to ENDO in the
Territory as described in Schedule A. Upon expiration or termination
of this Agreement, KAI may retain such hardware and equipment.
(r) KAI shall be responsible for providing the Services to ENDO in the
Territory for all Adverse Drug Experiences which occur anywhere in the
world in order that ENDO may report such Adverse Drug Experiences to
the FDA, state, and/or local regulatory agencies in the Territory. KAI
shall not be responsible for providing any information, data,
analyses, summaries, and/or reports regarding such Adverse Drug
Experiences to any regulatory agency outside the Territory.
(s) KAI shall be responsible for modifying and/or repairing, at its
expense and as expeditiously as possible, any problems with KAI
computer software and/or hardware, including any third-party-owned
computer software and/or hardware, which is used by KAI in connection
with the performance of KAI's obligations
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under this Agreement and in the provision of Services by KAI to ENDO
in the Territory. Notwithstanding the preceding sentence, ENDO shall
be responsible for the cost of any material computer software
modifications requested by ENDO. Further, ENDO shall be responsible
for the cost of repairs for normal wear and tear and/or replacement of
equipment, and for material computer hardware and software upgrades
and updates requested by ENDO.
(t) During the Term of this Agreement, KAI shall maintain, at an off-site
facility, backup files of all ENDO information and data obtained by
KAI in the performance of Services under this Agreement in the
Territory, including, without limitation, the Adverse Drug Experience
and Product Information Databases. ENDO shall have the right to access
such backup files, upon reasonable prior notice to KAI and at ENDO's
discretion, at any time during the Term of this Agreement or upon
expiration or termination of this Agreement.
11.2 ENDO'S DUTIES
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(a) ENDO shall pay for all expenses approved in advance and incurred in
connection with the training of KAI personnel, including the Product
Information Specialist, the Project Manager, and the Staff Physician
and any other KAI personnel responsible for providing Services to ENDO
in the Territory. Such expenses for the Initial and Option Terms of
this Agreement are included in the Fees set forth in Schedule A.
(b) ENDO shall provide to KAI, at ENDO's expense, all Product Literature
for each Product to be utilized by KAI personnel, including the
Product Information Specialist, the Project Manager, and the Staff
Physician and any other KAI personnel responsible for providing
Services to ENDO in the Territory. Such expenses for the Initial and
Option Terms are included in the Fees set forth in Schedule A.
(c) FDA Communications. Endo shall be responsible, with assistance from
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KAI, if requested by ENDO, for all written and/or verbal
communications with the FDA regarding the marketing, promotion, sale,
and/or use of Products, including, but not limited to, any action,
request, order, instruction, communication, complaint, notice, public
announcement or inquiry by the FDA or any submission, filing, letter,
or other communication by ENDO with respect to the Products, which is
received by KAI or which comes to KAI's attention or any
communications regarding field actions, investigations, or recalls of
Products in the Territory.
(d) ENDO shall be responsible for developing, with input from KAI, if
requested by ENDO, written medical information, including, without
limitation, new Product responses and Product Literature, regarding
the use of Products in the Territory to be used in connection with the
provision of Services by KAI to ENDO in the Territory.
13
(e) Adverse Drug Experiences and Field Alerts. ENDO, with the assistance
------------------------------------------
of KAI, shall be responsible for submission to the FDA, state, or
local regulatory agency of any forms and/or reports, including
periodic and annual reports with respect to an Adverse Drug Experience
involving Products or any complaint that would require a field alert,
as and when appropriate.
12. JOINT DUTIES
------------
12.1 Within five (5) days of the execution of this Agreement, KAI and ENDO shall
appoint members of the Operating Committee.
12.2 The Operating Committee will meet periodically but no less than once per
calendar quarter at a location to be mutually agreed to by the parties.
12.3 During the Term of this Agreement, KAI and ENDO shall regularly provide
input to the other party regarding the quality of and any issues related to
their respective performance of this Agreement.
13. CONFIDENTIALITY
---------------
13.1 All information disclosed by one party to the other under this Agreement
shall be deemed to be confidential information ("Confidential
Information"). The parties hereby agree to hold in strictest confidence any
and all Confidential Information disclosed by one party to the other under
this Agreement or obtained by either party as a result of performing its
obligations under this Agreement. The parties hereby agree that the
following shall not be considered Confidential Information subject to this
Agreement:
(a) information which at the time of disclosure by one party to the other
is in the public domain;
(b) information which, after disclosure by one party to the other becomes
part of the public domain by publication or otherwise, provided that
such publication is not in violation of this Agreement or any other
confidentiality agreement;
(c) information which the receiving party can establish in writing was
already known to it or was in its possession at the time of disclosure
by the other party and was not acquired, directly or indirectly, from
the disclosing party;
(d) information which the receiving party lawfully receives from a third
party, provided, however, that such third party was not obligated to
hold such information in confidence;
(e) information which the receiving party is compelled to disclose by a
court or other tribunal of competent jurisdiction, or the FDA,
provided however, that in such case the receiving party shall
immediately give notice to the disclosing party to enable the
disclosing party to exercise its legal rights to prevent and/or limit
such
14
disclosure. In any event, the receiving party shall disclose only that
portion of the Confidential Information that, in the opinion of the
disclosing party's legal counsel, is legally required to be disclosed
and will exercise reasonable efforts to ensure that any such
information so disclosed will be accorded confidential treatment by
said court or tribunal.
13.2 The receiving party shall not use Confidential Information for any purpose
other than for the purposes set forth in this Agreement.
13.3 The receiving party will not disclose Confidential Information to any
person other than to its employees, officers, agents, and consultants that
have a need to know such information to effectuate the purpose of this
Agreement and that such employees, officers, agents, and consultants shall
be informed of this Confidentiality Agreement and shall, in writing, be
bound by its terms. All Confidential Information will contain a statement
indicating that the information is confidential and should not be
disclosed to unauthorized individuals.
13.4 Upon written request from the disclosing party or termination or
expiration of this Agreement, whichever comes sooner, the receiving party
shall either promptly return to the disclosing party all Confidential
Information provided to the receiving party pursuant to this Agreement
including any copies thereof and notes, extracts based thereon, other
derivative documents or information; or in the alternative, provide the
disclosing party with a notarized certification by the General Counsel or
an Executive Officer of the receiving party that all such documents have
been duly destroyed by the receiving party; except that the receiving
party may keep one (1) copy of such documents for archival purposes.
13.5 The terms of this confidentiality provision shall remain in effect until
five (5) years after the expiration or termination of this Agreement.
13.6 Publicity. ENDO and KAI agree not to make any public announcements
----------
regarding the existence of this Agreement or its terms without the prior
review and written consent of the other party, unless such disclosure is
required by law. In which event, the disclosing party will provide the
non-disclosing party with sufficient prior notice of such legally required
disclosure as well as the nature of the information to be disclosed prior
to disclosing such information.
14. INDEPENDENT CONTRACTOR
----------------------
14.1 KAI and its directors, officers, and the persons providing Services under
the Agreement are at all times independent contractors with respect to
ENDO. Persons provided by KAI to perform Services shall not be deemed
employees of ENDO. ENDO shall not be responsible for KAI's acts or the
acts of its officers, agents and employees while performing the Services
whether on ENDO premises or elsewhere.
15
14.2 KAI shall not be responsible for any cost, however, attributable to: (i)
any actions by ENDO that caused a person(s) provided by KAI to perform
Services under this Agreement to be reclassified as an employee of ENDO,
(ii) any unlawful or discriminatory acts of ENDO, and (iii) language in
any ENDO benefit plan that is deemed to extend coverage to a person (s)
provided by KAI to perform Services under the Agreement based on their
activities under this Agreement.
15. INTELLECTUAL PROPERTY OWNERSHIP
-------------------------------
15.1
(a) Assignment of Intellectual Property.
-----------------------------------
(1) ENDO information in KAI computer databases. KAI agrees that all
------------------------------------------
ENDO information contained in paper or electronic format in any
KAI computer database, such as the information contained in the
Adverse Drug Experience and Product Information Databases, which
KAI may solely or jointly conceive or develop or reduce to
practice, or cause to be conceived or developed or reduced to
practice, in the performance of KAI's obligations under this
Agreement shall be the property of ENDO.
(2) Inventions, discoveries, and improvements conceived or made by
--------------------------------------------------------------
KAI. KAI agrees that all inventions, if any, discoveries, and
---
improvements conceived or made by KAI during the Term of this
Agreement, which (1) result, to any extent, from the use of
ENDO's premises, property, Confidential Information, or
documents/materials shall be the property of ENDO.
(3) Original works of authorship. KAI agrees that all original works
----------------------------
of authorship, such as ENDO Operating Procedures, which are (1)
created by KAI (solely or jointly with others) during the Term
of this Agreement, (2) in the performance of its obligations
under this Agreement, (3) which are primarily related to
Products, and (4) which are protectable by copyright and are
"works made for hire" as that term is defined in the United
States Copyright Act shall be the property of ENDO. However, to
the extent that any such work may not, by operation of any
applicable law, be a work made for hire, KAI hereby assigns,
transfers and conveys to ENDO all of its worldwide right, title
and interest in and to such work, including all intellectual
property rights therein and appurtenant thereto.
(4) For purposes of this Agreement, the intellectual property
described in subparagraphs 15.1(a) (1), (2), and (3) are
collectively "ENDO Property."
(b) Notwithstanding subparagraph 15.1 (a), ENDO acknowledges that KAI
possesses certain inventions, processes, know-how, trade secrets,
improvements, other intellectual properties and other assets,
including but not limited to business methods, clients, vendors,
financial information, procedures, and techniques, procedure manuals,
personnel data, computer technical expertise, customized
16
computer software programs, computer software applications, computer
software designs, computer software source codes and research methods
which (1) directly and primarily relate to KAI's business or
operations and (2) which do not primarily relate to the Products or
ENDO's Confidential Information (collectively "KAI Property"). ENDO
and KAI agree that any KAI Property or improvements thereto, which
are used, improved, modified, or developed by KAI during the Term of
this Agreement are the sole and exclusive property of KAI.
Notwithstanding the preceding sentence, KAI Property does not include
ENDO Property, including without limitation, ENDO Operating
Procedures, the Adverse Drug Experience, or Product Information
Databases.
15.2 Further Assurances. Upon the request and at the expense of ENDO, KAI
------------------
shall execute and deliver any and all instruments and documents and take
such other acts as may be necessary or desirable to document the
assignment and transfer described in Article 15.1 (a) above or to enable
ENDO to secure its rights in the ENDO Property and any patents,
trademarks, copyrights or other intellectual property rights relating
thereto in any and all jurisdictions, or to apply for, prosecute and
enforce patents, trademark registrations, copyrights or other
intellectual property rights in any and all jurisdictions with respect to
any ENDO Property, or to obtain any extension, validation, reissue,
continuance or renewal of any such intellectual property rights. Without
limiting the foregoing, KAI shall disclose to ENDO all pertinent
information and data with respect thereto and shall execute all
applications, specifications, oaths and all other instruments which ENDO
shall deem necessary in order to apply for and obtain such rights and in
order to assign and convey to ENDO the sole and exclusive right, title and
interest in and to such ENDO Property and any patents, copyrights,
trademarks or other intellectual property rights relating thereto. KAI
further agrees that KAI's obligation to execute or cause to be executed,
when it is in KAI's power to do so, any such instrument or papers shall
continue after the expiration or termination of this Agreement.
15.3 Maintenance of Records. KAI agrees to keep and maintain adequate and
----------------------
current records of all ENDO Property during the Term of this Agreement and
unless otherwise required by law, for a period of not less than five (5)
years from the effective date of termination or expiration of this
Agreement and all such records shall be organized in such manner that they
will be ready for immediate reference. Unless otherwise required by law,
at the expiration of such five (5) year period, KAI shall dispose of such
records in accordance with ENDO's instructions. If ENDO fails to give said
instructions, KAI shall so notify ENDO; and if said instructions are still
not forthcoming within thirty (30) days of said notification, then KAI
shall immediately destroy such records.
15.4 Survival. The provisions of this Article 15 shall survive the expiration
---------
or termination of this Agreement.
16. NONCOMPETITION
--------------
During the Term of this Agreement, KAI shall not provide services
identical to or similar to Services provided to ENDO in the Territory for
any third party's products that directly
17
compete with any Product in the prescription pain management therapeutic
category. In addition, for thirty (30) days after the expiration or
termination of this Agreement, KAI's Project Manager and Product
Information Specialist shall not provide such Services.
17. INDEMNIFICATION
---------------
17.1 KAI shall indemnify, defend, and hold harmless ENDO, its officers, agents,
Affiliates, subsidiaries, parent companies, and employees, from and
against any and all damage, claim, injury, cost or expenses, including
reasonable attorneys' fees and expenses of litigation, by third parties,
in connection with any illness or personal injury, including death, or
property damage, that arises out of: (1) any negligent act or willful
misconduct of KAI with respect to Services provided to ENDO in the
Territory, including but not limited to any breach of any statutes, rules,
and/or regulations applicable to the Services provided by KAI to ENDO in
the Territory, or (2) KAI 's breach of the terms of this Agreement,
provided, however, KAI shall, under no circumstances be obligated to
indemnify ENDO where claims, causes of action, losses or liabilities arise
out of ENDO's sole negligence, willful misconduct, breach of the Agreement
or breach of any statutes or regulations applicable to the provision of
Services by KAI to ENDO in the Territory.
17.2 ENDO shall indemnify, defend, and hold harmless KAI, its officers, agents,
Affiliates, subsidiaries, parent companies, and employees, from and
against any and all loss, damage, claim, injury, cost or expense,
including reasonable attorneys' fees and expenses of litigation, by third
parties, in connection with any illness or personal injury, including
death, or property damage, that arises out of: (1) any use, marketing,
promotion, sale, or distribution of the Product; (2) the negligence or
willful misconduct of ENDO with respect to ENDO's obligations under this
Agreement; or (3) breach of the terms of this Agreement by ENDO, provided,
however, ENDO shall not be obligated to indemnify KAI to the extent that
any loss, damage, claim, injury, cost or expense arises out of KAI's sole
negligence, willful misconduct, or breach of this Agreement or breach of
any statutes or regulations applicable to the use, marketing, promotion,
sale, and/or distribution of Products in the Territory.
17.3 Indemnification Process. Any indemnity available hereunder shall be
-----------------------
dependent upon the party seeking indemnity providing prompt notice to the
indemnitor of any claim or lawsuit giving rise to the indemnity.
Thereafter, the indemnitor shall have exclusive control over the handling
of the claim or lawsuit, and the indemnitee shall provide reasonable
assistance to the indemnitor, at the indemnitor's expense, in defending
the claim.
18. TERMINATION
-----------
18.1 This Agreement may be terminated by either KAI or ENDO for the following
reasons:
(a) Material Breach. Either party may terminate this Agreement in the
---------------
case of a material breach by one of the other parties which is not
cured within thirty (30) days after written notice of the breach by
the terminating party.
18
(b) Bankruptcy. Either party may terminate this Agreement immediately in
----------
its entirety if the other party is declared insolvent by a court of
competent jurisdiction, files a petition of bankruptcy, is adjudged
bankrupt, takes advantage of any insolvency act, is in receivership,
or executes a xxxx of sale, deed of trust, or assignment for the
benefit of creditors.
18.2 This Agreement may be terminated by ENDO for no cause upon ninety (90)
days written notice to KAI. In the event of termination of this Agreement
under this Article 18.2, the parties shall mutually determine how best to
wind down the Services provided by KAI to ENDO in the Territory, including
the timetable for the winding down and transfer of such activities, all
ENDO Confidential Information, ENDO Property, and all relevant
documentation to ENDO.
18.3 Effect Of Termination.
---------------------
(a) Termination of this Agreement shall have no effect on, or relieve any
party from the obligation to make any payment for any monies due and
owing one party from the other party prior to the effective date of
termination and any actual costs and expenses incurred which are
noncancellable or nonreimburseable up to the effective date of
termination or perform any actions arising prior to the effective
date of termination. Further, any rights and obligations of the
parties which by their intent are meant to survive the termination or
expiration of this Agreement shall survive the expiration or
termination of this Agreement.
(b) Upon termination or expiration of this Agreement, at ENDO's request,
KAI shall provide all information, reports, data, summaries and
analyses, including, but not limited to, the Adverse Drug Experience
and Product Information Databases, prepared by KAI in connection with
the provision of Services to ENDO in the Territory in an electronic,
readily accessible format.
19. MISCELLANEOUS
-------------
19.1 ASSIGNMENT
----------
Neither party may assign its interests, rights, duties, and obligations
under this Agreement without the prior written consent of the other party,
which shall not be unreasonably withheld, provided, however, that both
parties may assign their respective interests, rights, duties, and
obligations hereunder to any Affiliate or any successor in business,
including as a result of a merger or acquisition by a third party of
substantially all or all of the assigning party's assets, or acquisition
of fifty percent (50%) of any equity in the assigning party, or any
reorganization or change in control of the assigning party so long as the
acquirer and/or surviving organization/entity (i) is a financially capable
business entity , (ii) expressly assumes in writing those interests,
rights, duties, and obligations, and (iii) is capable of competently
performing all the duties and obligations under this Agreement to the
satisfaction of the non-assigning party.
19
19.2 INTEGRATION
------------
This Agreement, including all attachments, schedules, or exhibits entered
into hereunder, constitutes the complete agreement and understanding of
the parties with respect to the subject matter hereof and supersedes all
prior and/or contemporaneous arrangements and understandings between the
parties hereto with regards to the subject matter hereof, including the
letter agreement dated March 22, 1999.
19.3 FORCE MAJEURE
-------------
Noncompliance with the obligations of this Agreement due to a state of
force majeure, the laws or regulations of any government, regulatory or
judicial authority, war, civil commotion, destruction of facilities and
materials, fire earthquake or storm, labor disturbances, shortage of
materials, failure of public utilities or common carriers, and any other
causes beyond the reasonable control of the applicable party, shall not
constitute a breach of this Agreement; provided, however, that if one
party to this Agreement claims, for a period of forty-five (45) days, that
it is unable to fulfill its obligations hereunder due to the existence of
a state of force majeure, then the other party may elect to terminate this
Agreement with immediate effect.
19.4 SEVERABILITY
------------
If any provision of this Agreement is finally declared null and void, or
found to be illegal or unenforceable by a court of competent jurisdiction,
both parties shall be relieved of all obligations arising under such
provision, but, if capable of performance, the remainder of this Agreement
shall not be affected by such declaration or finding.
19.5 PUBLICATION
-----------
Reports, findings, conclusions, work papers, notebook records, raw data,
analyses and any other information arising out of the performance of this
Agreement by KAI will not be released, published, or otherwise disclosed
by KAI without the express permission of ENDO. Neither party will use the
name of the other in any advertisement, press release, or publicity which
reference this Agreement, without the prior written approval of the other
party.
19.6 AMENDMENT
---------
No modification, extension or release from any provision hereof shall be
affected by mutual agreement, acknowledgment, acceptance of documents, or
otherwise, unless the same shall be in writing signed by the other party
and specifically described as an amendment or extension of this Agreement.
20
19.7 ARBITRATION
-----------
(a) All disputes over the meaning and interpretation of this Agreement
shall be resolved by conciliation and non-binding mediation and if
such mediation is unsuccessful then such disputes shall be finally
settled by an Arbitration Panel comprised of one (1) arbitrator
appointed by KAI, one (1) arbitrator appointed by ENDO, and a
Chairman of the Arbitration Panel appointed by the first two (2)
arbitrators. Any such arbitration proceeding shall be conducted in
accordance with the arbitration rules of the American Arbitration
Association, shall be held in the Commonwealth of Pennsylvania,
unless otherwise agreed by the parties; and the arbitration award
shall be final and nonappealable and such award may be entered in any
court having jurisdiction.
(b) In order to initiate procedures for dispute resolution by
conciliation, mediation and arbitration either party may give written
notice to the other of its intention to resolve a dispute, and absent
satisfactory resolution, then to arbitrate. Such notice shall contain
a statement setting forth the nature of the dispute and the
resolution sought. If, within thirty (30) days of such notice a
resolution by conciliation between the parties themselves or by
mediation has not been achieved to the satisfaction of both parties,
and if within sixty (60) days from said written notice an Arbitration
Panel has not been appointed with an arbitration schedule
satisfactory to both parties, then either party may proceed with
judicial remedies.
19.8 NOTICES
-------
All notices required under this Agreement shall be in writing and shall be
effective if delivered to the party entitled to receive the same by hand
or if deposited in the United States Mail addressed to such party at the
address set forth below.
If to: Endo
Endo Pharmaceuticals Inc.
000 Xxxxxxxxxx Xxxx Xxxxxxx Xxxx
Chadds Ford, Pennsylvania 19317, U.S.A.
Attn: Xxxxx Xxx, M.D., Ph.D., Senior Vice President, Research and
Development
with a copy to: Xxxxxx Xxxxxxxx, General Counsel
If to: XXX
Xxxxxx and Associates, Inc.
0000 Xxxxxxxx Xxxx, Xxxxx 000
Xxxxxxxxx, Xxxxxxxx 00000-0000
Attn: Xxxxx Xxxxxx, President
21
19.9 TAXES
-----
KAI shall be responsible for all taxes, including federal, state, and
local taxes assessed or assessable against it for the Services performed
under this Agreement.
19.10 GOVERNING LAW
-------------
This Agreement shall be construed according to the laws of the
Commonwealth of Pennsylvania, without reference to its conflict of law
rules.
19.11 COUNTERPARTS
------------
This Agreement may be executed in any number of counterparts, each of
which, when executed, shall be deemed to be an original and all of which
together shall constitute one and the same document.
19.12 SURVIVAL
--------
The provisions of this Agreement which by their intent and/or effect are
meant to survive the termination or expiration of this Agreement shall
survive the termination or expiration of this Agreement.
19.13 NONSOLICITATION
---------------
Both parties agree that they shall not solicit or hire any employee of the
other party, either directly or indirectly, during the Term of this
Agreement.
19.14 YEAR 2000 COMPLIANCE
--------------------
(a) Each party agrees to request from those of its suppliers whose
performance may materially affect such party's performance hereunder,
or to receive assurance from such supplier's Web site, that each such
supplier agrees that it will not permit a Year 2000 Problem to
computer systems, software or equipment owned by it, its Affiliates
or subsidiaries, or leased or licensed to it, its Affiliates or
subsidiaries, to interfere with such supplier's performance. The
parties will use their Best Efforts to cooperate and share
information to further comply with this section, and to minimize the
impact of any Year 2000 Problem on the parties' respective
performance under this Agreement. Each party will inform the other
party of any material circumstance indicating a potential obstacle to
such compliance, and the steps being taken to avoid or overcome the
obstacle.
(b) Provided a party complies with this section, such party will not be
liable to the other party for any failure to perform obligations
under this Agreement to the extent such failure arises from a Year
2000 Problem (1) affecting one of the non-performing party's
suppliers or (2) beyond that party's reasonable control (e.g., a
22
Year 2000 Problem affecting a governmental entity). In particular, to
the extent a non-performing party is not liable to the other party
under this section, such non-performing party shall have no liability
to the other party for any damages, including direct, indirect,
incidental, special, consequential, punitive or exemplary.
WHEREFORE, the parties hereto have caused this Agreement to be executed by their
duly authorized representatives on the date first above written.
KUNITZ AND ASSOCIATES, INC. ENDO PHARMACEUTICALS INC.
By: /s/ XXXXX XXXXXX By: /s/ XXXXX XXX
__________________________ ____________________________
Name: Xxxxx Xxxxxx Name: Xxxxx Xxx
________________________ __________________________
Title: President Title: Senior Vice President, Research and
Development
23
SCHEDULE A
----------
FEES AND DESCRIPTION OF SERVICES
--------------------------------
APPROACH
This section outlines tasks, assumptions and our approach to conducting this
project. Tasks are grouped into three major activity areas: 1) preparation and
planning; 2) ongoing support; and 3) transfer of responsibilities. These three
task groups correspond to the budget projections.
Preparation and Planning (March 22, 1999 - May 31, 1999)
KAI will work with Endo to review current procedures, propose refinements, and
detail requirements. Figure 1 provides an overview of Endo's requirements.
Specifically, KAI will work with Endo to review activities and databases,
discussed below under operational activities. The review will serve to identify
needed refinements, detail Call Center and Adverse Event Tracking System
requirements, system validation procedures, Endo Operating Procedures (EOPs),
KAI's Standard Operating Procedures (SOPs), data transfer specifics, time line
projections, and the monthly administrative reports. We will provide
specifications for these products for approval by Endo. Once approved, we will
customize and/or develop applications and procedures for review by Endo.
Telephone Calls
---------------
Beginning in April, 1999, Xxxxxxxxxx will receive Endo's Medical Affairs
telephone calls, respond to a small set of these queries, and triage product
information and Pharmacovigilance calls to KAI. Calls may come from health care
providers, detail or sales persons, or consumers. The current total load of
calls averages about 300 calls per month with potentially significant increases
after product launches and product changes.
Based on discussions with Endo staff, Xxxxxxxxxx will triage telephone calls to
KAI's Product Information Desk. Calls pertaining to product information will be
answered by the Product Information staff. Calls related to possible adverse
events will be routed to the Medical Monitor, as necessary, to probe for and
identify potential safety issues. To support telephone triage, KAI proposes
three dedicated lines.
KAI recognizes that telephone calls will increase during product launches and
introduction of new drugs. When we are notified of these events, we will
increase staffing, and, if needed, use additional lines to accommodate the
increased demand. During the phase-in period we will also determine whether a
separate line is needed to respond to professional representatives.
24
Product Information Inquiries
-----------------------------
KAI will respond to approximately 300 telephone inquiries monthly, triaged by
Xxxxxxxxxx. The Call Center will utilize a script and the Product Information
database, where relevant, and will capture caller identifiers, product inquiry,
type of caller, response time and mode (e.g. answered on call), and response.
Features of our Product Information support include the following:
. Inquiry response service will be available 9:00 A.M. to 5:00 P.M.
Eastern time during normal business work days. A voice mail service
will be available on weekends, after hours, and holidays. Emergency
paging service will be provided.
. Up to three simultaneous calls can be answered concurrently. If more
than three simultaneous calls are received, we can capture caller
information in voice mail and call back within one (1) hour. If the
three lines are frequently utilized we will recommend increasing Endo
lines.
. As necessary, KAI will respond to inquiries with a letter or other
documentation that may be requested. If requested by Endo, we can e-
mail or fax responses to the Sir Speedy Print Center.
. KAI will also log and respond to faxes and e-mail inquiries.
. KAI anticipates that
- calls that may be related to an AE will be triaged to our medical
monitor or other clinical staff member;
- with respect to generic products, we can respond to inquiries
about bioavailability; other questions for these products will
generally be referred to the innovator; and
- professional, courteous and timely responses are key "success
factors"
. In the unlikely event of a power outage that would cause our computers
to be unavailable, we would record information manually and enter the
information into the computer when power is restored.
Currently, Endo's Product Information Database is maintained in Microsoft Word.
KAI will review the contents and will determine a cost-effective approach to
facilitating searches of the contents. KAI will periodically review responses
and recommend updates to Endo. We will also review the database responses
including poison control monographs, annually for accuracy and will recommend
changes or deletions as necessary. KAI will track changes to the database and
will maintain a history of responses to specific questions and drugs.
For the Call Center software, KAI will customize Microsoft Access to meet Endo's
requirements. This approach will require the addition of one server. To develop
and implement Pharmacovigilance Endo Call [Center] Software (PECS), KAI will
ensure that our software is validated and FDA compliant. To develop and
implement the system,
KAI will:
. develop user requirements and submit them to Endo for review and
approval;
. design the system, developing specifications, for review by Endo;
25
. build and test system against the design document (verification);
. validate the system against user requirements and submit to Endo for
review and written approval.
. put the system into production to support Endo's
pharmacovigilance activities.
KAI will customize its SOPs to provide an Endo specific Validation Plan,
including scope, staff, methods, inputs and outputs, required reports, deviation
policy and anomaly reporting and resolution; a Test Plan including items/tools
required for testing, features to be tested, procedure, pass/fail criteria,
deliverables, testing roles and responsibilities, risks and contingencies; and
KAI SOPs that specify document and records control, configuration management,
system and change control, security, backup, archive and retrieval, disaster
recovery, operations, training plan and program, software development life
cycle, software control, audit plan. We will write test scripts, create a test
environment, and execute the plan. KAI will also develop and implement a
Training Plan and associated KAI SOPs for the pharmacovigilance system and
operations.
KAI will write a test summary report and a verification summary report that
summarizes the results of the testing.
Adverse Events
--------------
KAI's goals in identifying and reporting AEs are to:
. meet FDA requirements for reporting;
. perform a clinical and scientific assessment of the data for clusters
and trends; and
. effectively communicate the safety information.
KAI will document AEs and SAEs in a timely manner for Endo's submission to the
Food and Drug Administration (FDA), in accordance with ICH Guidance, FDA
Guidelines, and Endo's requirements including Endo's Operating Procedures
(EOPs). Currently there are approximately 35 AEs and 6 SAEs reported per month.
AEs may be communicated to KAI via telephone or some other transmission
mechanism. KAI will also identify such events through literature searches for
all products but not via searches of the internet.
AEs Reported to KAI
-------------------
Potential AE telephone calls triaged from Xxxxxxxxxx will be routed to KAI's
medical monitor. In receiving calls, KAI will provide professional, courteous
responses and will follow an approach, documented in an EOP, that probes the
caller for details regarding the problem.
Using a prepared script, the KAI medical monitor or clinical staff member will
solicit information about the AE being reported, including scope of the problem,
start and stop date, relatedness to drug, and severity. The mechanism of drug
action and pharmacokinetic and
26
pharmacodynamic considerations will be included in the assessment. KAI will
insure that the following is captured:
. administrative and identifying information including identification of
the case safety report, source of information, and information on
sender and receiver of case safety report for follow-up, if necessary;
and
. case information including patient characteristics, reaction/event,
results of tests and procedures relevant to the evaluation of the
event, drug information, and narrative case summary.
This information, along with information compiled by comparing this AE to other
reported AEs, review of the literature, consultation with others familiar with
this drug, and any other information provided by the reporter, will allow the
KAI medical monitor to determine if the event is serious. If the event is not
serious, then the information will be recorded and maintained for submission in
the required periodic report (quarterly for three years, and annually
thereafter).
If a serious or unexpected AE is suspected, information will be captured on an
electronic form that conforms to MedWatch 3500A. All information will be
collected in an iterative process that includes telephone follow-up and
assessment of the temporal relationship of event and drug therapy, dose related
effect, biological plausibility, known class effect, previous animal findings,
and pharmacodynamic and pharmacokinetic mechanism. Specifically, KAI will:
. code AEs using MedDRA 2.1;
. implement software to store AE information;
. comply with E2B and M2 standards when operationally defined and
implemented by the FDA.
27
Once the form is complete, and within seven calendar days, it will be forwarded
to Endo Medical Affairs. If the form is complete, it will be forwarded to the
FDA within 15 calendar days of the AE. If additional information is needed, Endo
will notify KAI within one working day, and KAI will complete the form as
necessary within 10 days of the initial report. KAI will track the status of the
report and will document sign-off at each phase.
For those products for which Endo does not own the (A)NDA, KAI will send the
source information to the appropriate sponsor. For the current drugs for which
Endo owns the NDA and has an obligation to share AEs with another company, KAI
will send the AE information to Endo for filing and will send the source
documents to the appropriate sponsor, at Endo's request, within five calendar
days as per FDA guidance.
Literature Searches
-------------------
Additionally, KAI will perform literature searches to identify AEs and
toxicology information. Currently, literature searches yield about 575 abstracts
per year of which 168 articles are retrieved and reviewed. About 24 SAEs are
identified during the literature review.
KAI recognizes that the comprehensiveness of a search is dependent on the skill
of the person doing the search. KAI's staff members are highly skilled in
conducting routine as well as extremely complex literature searches.
Continuous monitoring of the literature is essential in the Pharmacovigilance
process to identify potential safety issues. In order to obtain information on
scientific articles in the literature, the National Library of Medicine's
MEDLARS biomedical databases will be searched. GratefulMed, a microcomputer
based software package made available to KAI, provides the interface to these
databases. With this package, the user is able to establish search strategies
before going "on line" which minimizes the cost of conducting a search.
Although there are more than 25 databases on the NLM system, MEDLINE is the one
most often used by KAI staff for literature searches. The database is the
computerized counterpart of Index Medicus. Articles on mechanism of action,
preclinical studies, Phase I, II, and III clinical trials, investigational
agents, immunologic or biochemical mechanisms, pharmacology, and toxicity
associated with these agents can be identified and reprints retrieved.
Other databases, including EMBASE and TOXLINE, will be used to identify
potential adverse events or when specialized information on the chemistry or
toxicity of a given agent is required.
KAI staff members will search MEDLINE and TOXLINE data bases via Grateful Med
using the Internet and will search EMBASE via Dialog, a commercial online
information service. In addition, we access relevant bulletin board services
such as those available from the FDA which are available online, free of charge.
As information needs arise, we will assess the requirement and the most cost and
time-effective means of acquiring necessary materials.
28
Depending on the goals of the search, the following are generally retrieved:
author(s), publication title, source of the publication, abstract, and key
words. Currently, KAI staff members download the literature search to their
personal computer where they then print the list, review it, and decide which
articles may be of interest. Once articles are identified for retrieval, a
request is sent to a technical support staff member who will retrieve the
requested reprints.
Reports, Bibliographies, and Other Tasks
----------------------------------------
KAI will prepare monthly administrative reports, the contents of which will be
structured during the planning phase; and quarterly and annual reports for Endo
regulatory reporting. We will also:
. prepare clinical bibliographies, based on our literature searches, for
each (A)NDA Endo has the responsibility to maintain; toxicology
bibliographies will be prepared after Year 1 of the project.
. perform requested literature searches and retrieve and transmit the
articles to the requester.
. perform special projects, e.g. report preparation, synthesis of
articles, etc. as requested.
KAI will provide the above services and will respond to additional requirements,
as requested, for a mutually agreed upon fee.
Test Phase (June 1, 1999 - July 31, 1999)
In June, KAI will begin to assume responsibility for certain Endo's products
such as PERCOCET, ENDOCET, ENDODAN, PERCODAN, PERCODAN-DEMI, and PERCOLONE.
During June and July, telephone calls, and triage can be monitored to assure
that calls are handled according to the EOPs. Additionally, AE handling and
report preparation will also be reviewed to ensure operations are progressing
smoothly.
Operating Xxxxx (Xxxxxx 0, 0000-Xxxx 31, 2002)
As of August 1, 1999, KAI will take over full responsibility for Endo's Medical
Affairs services in conjunction with Endo.
Transfer of Responsibilities
KAI believes that we can provide the highest quality of service available and
that importantly, we will respond to changing needs and demands. Nevertheless,
it is prudent for us to provide a plan for smooth transfer of responsibilities
should this be necessary. KAI will provide Endo with its data base contents,
should they request it.
29
================================================================================
ENDO BUDGET - MEDICAL AFFAIRS SUPPORT
START-UP AND TEST PHASE
YEAR 1- (3/22/99 - 7/31//99)
================================================================================
TASK AMOUNT
--------------------------------------------------------------------------------
1. Conduct detailed requirements analysis, client meetings;
customize SOPs, develop management and operational procedures;
develop data transfer and validation plan; detail validation
procedures; develop procedures for transfer of responsibilities;
test transfer with *** ***
--------------------------------------------------------------------------------
2. Design, develop, validate KAI Clinical Information System
Software, prepare routine reports with metrics; develop Technical
Operating Procedures (TOPs); load Product Information files and
validate contents in compliance with FDA guidelines ***
--------------------------------------------------------------------------------
3. Design, develop, test, and validate AE software system and
production of 3500A forms according to 21CFR314.80; design
includes screens for entry of worksheet data, integrity of data
base, and editing of data fields. Validation will be FDA
compliant. ***
--------------------------------------------------------------------------------
4. Data migration planning, execution and quality assurance. ***
--------------------------------------------------------------------------------
5. Develop training materials and train all staff; also
participate in ENDO training on products ***
--------------------------------------------------------------------------------
6. Assuming FDA mandates MEDRA 2.1, E2b, PDF format, etc.,
perform required programming changes. ***
--------------------------------------------------------------------------------
SUBTOTAL - PROFESSIONAL SERVICES - PLANNING AND PREPARATIONS ***
================================================================================
OTHER DIRECT COSTS - Computers (Server) 1, UPS; Windows NT
(***), SQL Server (***) Licenses; Telephone System
Upgrade; high speed full featured scanner ***
================================================================================
TOTAL - PLANNING AND PREPARATIONS ***
================================================================================
30
================================================================================
ENDO BUDGET - MEDICAL AFFAIRS SUPPORT
OPERATIONS PHASE- YEAR 1 (08/01/99-07/31/00)
================================================================================
TASK AMOUNT
--------------------------------------------------------------------------------
1. Project management and administration; conduct call center
operations - respond to product information calls and follow-up
as necessary (*** calls/month); triage AE calls; conduct
literature searches (clinical and toxicology bibliographies for
*** (A)NDA Annual Reports and respond to Endo literature
requests); retrieve articles; prepare routine reports ***
--------------------------------------------------------------------------------
2. Handle AEs - gather information, code, and produce reports;
enter worksheets into system and produce 3500A reports and 15-day
alert follow-up reports according to 21CFR314.80; estimates are
as follows: *** AE calls/month; *** SAE calls/month; *** quarterly
and annual safety reports; *** abstract reviews; *** articles to
review; bibliography preparation. ***
--------------------------------------------------------------------------------
3. Maintain, modify, upgrade computer system as necessary;
computer programming for software modifications, reports, etc. ***
--------------------------------------------------------------------------------
SUBTOTAL - PROFESSIONAL SERVICES - IMPLEMENTATION/ OPERATIONS ***
================================================================================
OTHER DIRECT COSTS - Long Distance Travel (PA: 3 trips*3
persons*1 day/trip; FDA and/or other required software (annual
subscription); Reproduction; Telephone Charges; Computer Usage
Costs; Postage/Delivery; Direct Supplies, etc. ***
================================================================================
TOTAL COSTS - YEAR 1 ***
================================================================================
31
================================================================================
OPERATIONS - YEAR 2 (08/01/00) - 07/31/01)
================================================================================
TASK AMOUNT
--------------------------------------------------------------------------------
1. Same as year 1. ***
--------------------------------------------------------------------------------
2. Same as year 1. ***
--------------------------------------------------------------------------------
3. Same as year 1. ***
--------------------------------------------------------------------------------
SUBTOTAL - PROFESSIONAL SERVICES - OPERATIONS ***
================================================================================
Other Direct Costs ***
================================================================================
TOTAL COSTS - YEAR 2 - OPERATIONS ***
================================================================================
OPERATIONS - YEAR 3 (08/01/01 - 7/31/02)
--------------------------------------------------------------------------------
1. Same as year 1. ***
--------------------------------------------------------------------------------
2. Same as year 1. ***
--------------------------------------------------------------------------------
3. Same as year 1. ***
--------------------------------------------------------------------------------
SUBTOTAL - PROFESSIONAL SERVICES - OPERATIONS ***
--------------------------------------------------------------------------------
Other Direct Costs ***
================================================================================
TOTAL COSTS - YEAR 3 - OPERATIONS ***
================================================================================
OPERATIONS - YEAR 4 (08/01/02 - 07/31/03)
--------------------------------------------------------------------------------
1. Same as year 1. ***
--------------------------------------------------------------------------------
2. Same as year 1. ***
--------------------------------------------------------------------------------
3. Same as year 1. ***
--------------------------------------------------------------------------------
SUBTOTAL - PROFESSIONAL SERVICES - OPERATIONS ***
--------------------------------------------------------------------------------
Other Direct Costs ***
================================================================================
TOTAL COSTS - YEAR 4 - OPERATIONS ***
================================================================================
32
--------------------------------------------------------------------------------
OPERATIONS - YEAR 5 (08/01/03 - 07/31/04)
--------------------------------------------------------------------------------
1. Same as year 1. ***
--------------------------------------------------------------------------------
2. Same as year 1. ***
--------------------------------------------------------------------------------
3. Same as year 1. ***
--------------------------------------------------------------------------------
SUBTOTAL - PROFESSIONAL SERVICES - OPERATIONS ***
================================================================================
Other Direct Costs ***
================================================================================
TOTAL COSTS - YEAR 5 - OPERATIONS ***
================================================================================
33
SCHEDULE B
PRODUCTS
--------
***
34
SCHEDULE B (continued)
PRODUCTS
--------
***
35
SCHEDULE C
TYPE OF REPORTS
***
36
SCHEDULE D
CERTIFICATES OF INSURANCE
37
SCHEDULE E
ENDO OPERATING PROCEDURES
Postmarketing Safety Surveillance of Human Drugs
Product Information Call Center
Quality Assurance for the Product Information Call Center
Quality Assurance Post Marketing Strategy Surveillance of Human Drugs
Literature Search, Retrieval and Review
All other ENDO Operating Procedures
38
