MASTER CLINICAL TRIAL AGREEMENT

Transcription

1 MASTER CLINICAL TRIAL AGREEMENT THIS MASTER CLINICAL TRIAL AGREEMENT ( Agreement ), is effective as of the latest date that a Party hereto signs this Agreement (the Effective Date ), by and between ALLERGAN SALES, LLC, a Delaware limited liability company and certain of its affiliates, controlling companies and subsidiaries, having a principal place of business at 2525 Dupont Drive, Irvine, California ( Sponsor ), and THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, having a principal place of business or an address at Clinical Trial Contracting Unit, Office of Clinical Research, Perelman School of Medicine, 322 Anatomy-Chemistry Building, 3620 Hamilton Walk, Philadelphia, Pennsylvania ( Institution ). Sponsor and Institution are collectively referred to herein as the Parties and individually as a Party. WHEREAS, Sponsor is in the business of developing, manufacturing and distributing pharmaceutical, biotechnology and medical device products and desires to conduct one or more clinical trials (each a Study ) governed by an applicable protocol (a Protocol ); WHEREAS, the research programs contemplated under this Agreement are of mutual interest and benefit to the Institution and Sponsor, and will further the Institution s instructional and research objectives in a manner consistent with its status as a non-profit, tax-exempt, educational institution; WHEREAS, Institution is in the business of providing certain clinical services and wishes to participate in at least one Study under the applicable Protocol(s); and WHEREAS, the Institution represents that it has the experience, capability and resources to efficiently and expeditiously perform each Study in strict adherence to the applicable Protocol. NOW, THEREFORE, in consideration of the foregoing premises and the following mutual promises, covenants and conditions contained herein, and for other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the Parties hereto agree as follows: 1. SCOPE OF WORK. 1.1 Individual Studies. With respect to each Study in which Institution participates, Institution, Principal Investigator (as defined in Section 2 hereof) and Sponsor will enter into an agreement (a Study Agreement ) generally in the form of Exhibit A attached hereto. Each Study Agreement will include information regarding the Principal Investigator for the Study, a copy of the applicable Protocol, the Study budget and any other information or terms specific to the Study that the Parties deem necessary or appropriate. 1.2 Performance. Institution shall ensure that each Study is conducted in compliance with (a) the Protocol; (b) this Agreement; (c) Good Clinical Practice ( GCP ), the standards for which are set forth in the U.S. Code of Federal Regulations and the International Conference on Harmonization (E6) Guidelines for Good Clinical Practice or the International Organization for Standardization Clinical Investigation of Medical Devices for Human Subjects with the exception of sections and 3.4, as applicable; and (d) all applicable federal, state, and local laws and regulations (subsections (c) and (d) shall be collectively referred to as Regulations ). JS / Axiom / University of Pennsylvania / MCTA Page 1 of 15

2 1.3 Protocol. Each Protocol shall be written by Sponsor and accepted by Institution. A Protocol will be considered effective after it has been approved by Sponsor and Institution s Institutional Review Board ( IRB ). Only Sponsor may modify a Protocol and any modification to a Protocol must be approved by the IRB to become effective. 1.4 Facilities. Institution certifies that each Study will be performed only at the facility(ies) qualified by Sponsor as adequate and listed on the U.S. Food and Drug Administration ( FDA ) 1572 form or the Investigator Agreement for device studies. Institution will ensure that the listed facility(ies) remains adequate during the applicable Study and will notify Sponsor in writing within five (5) business days of a significant detrimental change in a facility s adequacy or a change of location. 1.5 Materials. In connection with a Study, Institution agrees to hold, store and transport any materials, including dry ice, biological specimens, the applicable Study Drug or Study Device and other chemical compounds in accordance with the applicable Protocol, Sponsor s instructions and all applicable Regulations. 2. PRINCIPAL INVESTIGATOR. 2.1 Appointment. Each Study will be conducted by a principal investigator named in the applicable Study Agreement (each, a Principal Investigator ). The Principal Investigator for any Study may not be changed without Sponsor s prior written approval, which shall not be unreasonably withheld. 2.2 Performance. (a) The Principal Investigator will be responsible for the conduct of the Study and shall conduct the Study in compliance with this (i) this Agreement, (ii) the Study Agreement, (iii) the Protocol, and (iv) the Regulations. (b) At Sponsor s request and expense, Principal Investigator will participate in reasonable clinical investigator meeting(s) or protocol related training as required. (c) Institution shall ensure that all employees, agents and permitted subcontractors who are assigned to perform services under this Agreement and any Study Agreement(s) (collectively Study Staff ) are medically qualified, have sufficient expertise, training, and experience, are made aware of the obligations contained in this Agreement and those in the applicable Study Agreement, and are bound by such obligations. (d) Should Sponsor become dissatisfied with the performance of a Principal Investigator or any Study Staff, Sponsor will send written notice to Institution terminating such individual. Upon receipt of such notice, Institution and Sponsor shall seek a replacement for such individual acceptable to both Parties. 3. MONITORING, INSPECTIONS, RECORD KEEPING, AND REPORTING. 3.1 Monitoring. Institution agrees that Sponsor and/or Sponsor s authorized representative(s) may monitor each Study. Without limiting the generality of the foregoing, Sponsor and/or Sponsor s authorized representative(s) may, during Institution s regular business hours and upon reasonable prior notice to Institution, inspect and audit Institution s, Principal Investigator s and Study Staff s activities under a Study Agreement, including the following (except to the extent prohibited by law): (a) examining and inspecting Institution s facilities to monitor compliance with (i) this Agreement, (ii) the Study Agreement, (iii) the applicable Protocol, and (iv) the Regulations; and (b) inspecting and JS / Axiom / University of Pennsylvania / MCTA Page 2 of 15

3 copying all data and records relating to the applicable Study. Institution shall immediately take appropriate action to address any violation or deficiency noted by Sponsor or Sponsor s authorized representative(s). 3.2 Regulatory Inspections. Institution shall cooperate with any regulatory authority with appropriate jurisdiction that conducts an inspection pertaining to a Study. In addition, Institution shall immediately; (a) Notify Sponsor in writing if any regulatory authority requests an inspection of, inspects, or makes written or oral inquiries regarding, any aspect of Institution s, Principal Investigator s or Study Staff s activities pertaining to a Study and/or pursuant to this Agreement or a Study Agreement; (b) Provide Sponsor with a written report of any regulatory inspection related to a Study, noting with specificity each Study-related record or document reviewed by any regulatory authority; authority; and (c) Notify Sponsor in writing of any violation or deficiency noted by any regulatory (d) Take immediate, appropriate action to address any violation or deficiency noted by any regulatory authority. 3.3 Record Keeping. Institution and the Principal Investigator shall maintain all records, accounts, notes and data relating to or generated as a result of conducting a Study (including case report forms, case histories, laboratory work sheets, slides, reports, biological samples/specimens and photos/video/images) and any additional records required to be maintained under the applicable Protocol, this Agreement, the Study Agreement, or the Regulations (collectively, Study Data ). Such record keeping obligations shall include the following: (a) Preparation and maintenance (whether in paper or electronic format) of all Study Data, in such manner so that its quality and integrity can be verified; (b) Completion and documentation of applicable consents and authorizations (including those under 42 U.S.C et seq. enacted by the Health Insurance Portability and Accountability Act of 1996 and the regulations promulgated thereunder ( HIPAA )) from each subject participating in a Study ( Study Subject ); (c) Preparation of all original case report forms or electronic case report forms (individually or jointly, CRFs ) for each Study Subject as provided in the applicable Protocol and submission of all CRFs, or copies thereof, to Sponsor in a timely manner throughout the performance of a Study, and in no event later than ten (10) business days after the date of termination of the applicable Study Agreement or Sponsor s request; (d) Preparation and submission of all safety, progress, interim, and final reports; the final summary (for example, an IRB close-out report) will be submitted to Sponsor promptly following completion of a Study; (e) Preparation and submission of initial and updated financial disclosure reports for all clinical investigators involved in the applicable Study and acting on behalf of Institution, pursuant to 21 C.F.R. Part 54. Such financial interest information shall include any equity interests in (i) any potential product for regulatory approval that is the subject of a Study; (ii) Sponsor, its affiliates or subsidiaries; and (iii) any other significant financial interest as defined in the above regulation; JS / Axiom / University of Pennsylvania / MCTA Page 3 of 15

4 (f) Maintenance of records of the receipt, use, and disposition of Sponsor s Study drug or device referenced in the applicable Study Agreement ( Study Drug or Study Device, as applicable); (g) Maintenance of copies of all correspondence with Sponsor, the IRB, the FDA or any other regulatory authority; and (h) Retention of all Study Data and CRFs for the period(s) required by the Regulations (e.g. at least two (2) years following the last approval of a marketing application for the Study Drug) or such longer period as requested by Sponsor (at Sponsor s expense). 3.4 Reporting. (a) Institution and the Principal Investigator shall promptly report to Sponsor any adverse event specified in a Protocol or any adverse event that may reasonably be regarded as caused by a Study Drug, Study Device or a Study procedure. If the adverse event is serious, as defined in the applicable Protocol or the Regulations ( Serious Adverse Event ), Institution and the Principal Investigator shall report it to Sponsorimmediately, but in no case later than twenty-four (24) hours after learning of the occurrence of such Serious Adverse Event. (b) Sponsor shall promptly report to Institution and/or Principal Investigator findings of Study monitors that could affect the safety of Study Subjects, affect the willingness of Study Subjects to continue participation, influence the conduct of the Study, or alter the IRB s approval to continue the Study. Sponsor acknowledges that Institution may communicate any of the aforementioned findings to both current and formerstudy Subjects. The obligations of this provision apply during the Study for two (2) years after the completion of the Study. It is the responsibility of the Sponsor to notify the Institution of any findings that would affect the safety and welfare of the subjects participating in the Study. 4. WORK PRODUCT AND OWNERSHIP. 4.1 Definition of Work Product. Work Product means any discovery, invention, technology, result, data, Study Data, specimen, material, information, concept or idea, whether or not patentable, resulting from reduced to practice as a result of conducting a Study, or made using a Study Drug, Study Device or Sponsor Confidential Information (as defined below), together with all intellectual property rights relating thereto. Work Product shall include, but not be limited to, processes, compositions, methods, programs, compounds, formulas and techniques, patents, copyrights and know how, and any improvements related thereto, but shall exclude Study Subjects medical records. 4.2 Ownership. Institution shall promptly disclose to Sponsor in writing all Work Product. Institution agrees and acknowledges that Sponsor shall own all right, title, and interest in and to all Work Product. Institution will and hereby does assign, transfer and convey to Sponsor all of Institution s (and will cause the Principal Investigator and all Study Staff to assign, transfer and convey all of their) right, title and interest in and to the Work Product, together with all intellectual property rights relating thereto. Institution shall (and will cause the Principal Investigator and all Study Staff to), upon Sponsor s request and at Sponsor s expense, execute such documents and take such other actions as Sponsor deems necessary for Sponsor to obtain such ownership and to apply for, secure and maintain patent or other proprietary protection of such Work Product. All Work Product and any information with respect thereto shall be Sponsor Confidential Information (as defined below) subject to the confidentiality, nondisclosure and non-use obligations set forth in Section 9. If any intellectual property rights, including moral rights, in any of the Work Product cannot (as a matter of law) be assigned by Institution to Sponsor as provided in this Section then (a) Institution unconditionally and irrevocably waives the enforcement of JS / Axiom / University of Pennsylvania / MCTA Page 4 of 15

5 such rights and all claims and causes of action of any kind against Sponsor with respect to such rights; and (b) to the extent Institution cannot (as a matter of law) make such waiver, Institution unconditionally grants to Sponsor an exclusive, perpetual, irrevocable, worldwide, fully-paid license, with the right to sublicense through multiple levels of sublicenses, under any and all such rights to exercise any and all present or future rights in the Work Product. Notwithstanding the foregoing, Sponsor hereby grants to Institution a perpetual, non-exclusive, non-transferable, paid-up license, without right to sublicense, to use Study Data it generates hereunder (i) subject to the obligations set forth in Section 9, for internal, noncommercial research and educational purposes, and (ii) for preparation of publications in accordance with Section 10. Any license of other rights granted to Sponsor pursuant to this Agreement shall be subject, if applicable, to the rights of the United States government reserved under Public Laws , and , codified at 35 U.S.C and to Institution rights to use inventions for internal, noncommercial research. 4.3 Pre-existing Intellectual Property. Notwithstanding the foregoing, this Agreement does not affect the ownership of inventions (whether patentable or unpatentable), discoveries, works of authorship, and other developments existing as of the effective date of the applicable Study Agreement, and all patents, copyrights, trade secret rights and other intellectual property rights in and to such inventions, discoveries, works of authorship and other developments (collectively, Pre-existing Intellectual Property ). Neither Party shall have any rights to any Pre-existing Intellectual Property of the other Party, except as may be otherwise expressly provided in any other written agreement between the Parties. Institution represents and certifies that it will not, without Sponsor s prior written approval, use in the performance of a Study, any of its own intellectual property (including any of its Pre-existing Intellectual Property) or that of a third party that may interfere with Sponsor s rights to any Work Product or Sponsor s ability to fully utilize and capitalize the Work Product. 5. DEBARMENT. 5.1 Certification of No Debarment. Institution certifies that neither it, nor any Principal Investigator or any Study Staff have been (a) convicted of an offense related to healthcare; (b) listed by a federal agency as debarred, excluded, disqualified or otherwise ineligible for federal program participation or has otherwise been disqualified from participation in any clinical investigation; or (c) to the best of Institution s knowledge, has been engaged in any acts that could be considered for any such disqualification. In addition, Institution certifies that Principal Investigator s and any Study Staff s license(s) to practice medicine in any jurisdiction is not currently suspended, revoked, on probation or otherwise restricted. In addition, Institution hereby certifies that it will not use in any capacity the services of any individual, corporation, partnership or association which has been debarred. In the event that the Institution becomes debarred, this Agreement and any Study Agreement(s) shall automatically terminate without any further action or notice by any Party hereto. In the event that Sponsor receives notice from Institution or otherwise becomes aware that a debarment action has been brought against Institution, then Sponsor shall have the right to terminate this Agreement and/or any related Study Agreement immediately. 5.2 Notification. Institution shall notify Sponsor in writing immediately, but in no case later than two (2) business days after initially becoming aware of any of the following: (a) A Principal Investigator s or any Study Staff s license to practice medicine in any jurisdiction is denied, suspended, revoked, terminated, relinquished (under threat of disciplinary action) or made subject to terms of probation or other restriction; JS / Axiom / University of Pennsylvania / MCTA Page 5 of 15

6 (b) A Principal Investigator or any Study Staff becomes the subject of a disciplinary proceeding by the FDA or any other governmental or regulatory authority or any professional, medical staff or peer review body; (c) A Principal Investigator s or any Study Staff s Drug Enforcement Administration (DEA) number is revoked or terminated; or (d) A Principal Investigator or any Study Staff is convicted of an offense related to healthcare or listed by a federal agency as being debarred, excluded, disqualified or otherwise ineligible for federal program participation or has otherwise been disqualified from participation in any clinical investigation. 6. STUDY SUBJECT INJURY. Sponsor shall reimburse Institution for any reasonable and necessary costs it incurs for diagnostic and therapeutic medical treatment, including hospitalization of a Study Subject as the result of any injury, illness or condition directly caused by a Study Drug, Study Device or procedures performed under a Study in accordance with the applicable Protocol ( Treatment ); provided, however, Sponsor will not be responsible for Treatment costs to the extent (a) such costs are covered by medical, third party or government insurance or programs; (b) attributable to the Study Subject s primary disease or any concurrent disease not caused by the administration of the Study Drug or Study Device in accordance with the Protocol; or (c) the injury, illness or condition is attributable to or arises out of (i) the negligence, willful misconduct or nonfeasance of Institution, the Principal Investigator or any Study Staff, or (ii) the failure by Institution, the Principal Investigator or any Study Staff to comply with this Agreement, the applicable Study Agreement, the applicable Protocol, any reasonable written instructions of Sponsor concerning the applicable Study, or the Regulations. 7. PROTECTED HEALTH INFORMATION AND USE OF DATA. 7.1 Protected Health Information. Institution acknowledges that it is or may be subject to the requirements of HIPAA and/or other applicable state or federal laws and regulations governing the use, disclosure, confidentiality, security or privacy of personally identifiable information (collectively, the Privacy Regulations ). Institution further acknowledges that in connection with the performance of a Study, it will or may collect, create, receive, use or disclose protected health information as that term is defined in 45 C.F.R ( PHI ). Institution represents and warrants that it shall comply with the Privacy Regulations, and shall (a) obtain valid authorizations meeting all of the requirements of the Privacy Regulations which authorize Institution to collect, create, receive, use or disclose (including to Sponsor) PHI; and/or (b) make an informed and good faith determination that it is not required to obtain authorization under the Privacy Regulations for such collection, creation, receipt, use or disclosure (including to Sponsor). Institution acknowledges that Sponsor represents that no component of Sponsor is a Covered Entity (as defined by HIPAA), shall become a Business Associate of a Covered Entity by performing its obligations under this Agreement, or is otherwise governed by HIPAA. Notwithstanding the foregoing, Sponsor agrees to protect the confidentiality of any PHI it may receive under this Agreement, and shall use such PHI only as authorized in the informed consent forms signed by Study Subjects. 7.2 Informed Consent. The authorization and/or the informed consent form(s) signed by the Study Subjects shall permit access to the Study Subjects medical records by Sponsor, the FDA or any other regulatory authority with appropriate jurisdiction. Institution agrees that the content of the authorization and/or the informed consent form(s) will be pre-approved by Sponsor prior to use. In the event that Sponsor notifies Institution of any inconsistency between this Agreement, a Study Agreement and that of the informed consent form(s), and Institution does not correct such inconsistency within a JS / Axiom / University of Pennsylvania / MCTA Page 6 of 15

7 reasonable time after Sponsor s notification, Sponsor shall be entitled to terminate the Study Agreement without further obligation to Institution. 8. REPRESENTATIONS AND WARRANTIES. Each Party hereby separately represents and Institution certifies that: (a) such Party has all the power and authority necessary to enter into this Agreement and each Study Agreement and to fully perform every covenant and obligation herein and therein contained; (b) such Party has duly executed and delivered this Agreement; (c) the performance of this Agreement or any Study Agreement is not restricted by, and does not and will not conflict with, any arrangements, obligations, contracts, agreements or other instruments to which such Party is a party or otherwise committed, bound or subject, however nothing in this Agreement shall be construed as limiting the freedom of the Institution or Principal Investigator from engaging in similar research made under other grants, contracts or agreements with parties other than Sponsor; and (d) such Party will comply with all laws, regulations and ordinances applicable to its performance under this Agreement and each Study Agreement. 9. CONFIDENTIALITY. 9.1 Confidential Information. Subject to the limitations set forth in Sections 9.2 and 9.3, all information that is: (a) disclosed by Sponsor to Institution and/or the Principal Investigator (Institution and/or Principal Investigator, as the case may be, Recipient ) regarding a Study, including the applicable Protocol; (b) developed or generated by Institution and/or a Principal Investigator as a result of performing a Study under a Study Agreement, including Study Data; or (c) related to a Study Drug or Study Device shall be deemed to be Sponsor Confidential Information. Sponsor shall endeavor to mark tangible Sponsor Confidential Information provided to Institution as Confidential and to confirm verbally disclosed Confidential Information as such, in writing within thirty (30) days after the disclosure, provided however, that Institution and/or Principal Investigator confirm and agree that Sponsor s failure to identify any information as Confidential Information in writing shall not constitute a designation of non-confidentiality when the confidential nature is apparent from context and subject matter, when the information relates to the terms hereof, or when the information is such that a reasonable person experienced in the conduct of clinical trials would consider it to be the proprietary or confidential property of the Sponsor. Sponsor Confidential Information may include ideas, patent applications, data, processes, formulae, programs, compounds, know-how, improvements, designs, information regarding plans for research development, business plans and budgets, whether disclosed in oral, written, graphic or electronic form. 9.2 Nondisclosure Obligations. Recipient agrees to (a) hold Sponsor Confidential Information in confidence using the same standard of care it uses to protect its own confidential information of a similar nature, but in no event less than reasonable care; (b) not disclose Sponsor Confidential Information to any third party without Sponsor s prior written consent, except as expressly permitted under this Agreement or the applicable Study Agreement; and (c) limit access to Sponsor Confidential Information to those of its employees or agents (including Study Staff) having a need to know for purposes of performance under a Study Agreement and who are bound by confidentiality obligations at least as restrictive as those set forth herein. Notwithstanding the foregoing, Recipient may make disclosures as required by a court of law or any governmental entity or agency, provided that, when permissible by the applicable court of law, governmental entity or agency, Recipient provides Sponsor with reasonable prior notice to enable Sponsor to seek confidential treatment of such information. 9.3 Exclusions. The restrictions on the use and disclosure of Sponsor Confidential Information shall not apply to any of Sponsor Confidential Information (or portion thereof) which (a) is or becomes publicly known through no act or omission of Recipient; (b) is lawfully received from a third party without restriction on disclosure; (c) is already known by Recipient at the time it is disclosed by Sponsor, JS / Axiom / University of Pennsylvania / MCTA Page 7 of 15

8 as shown by Recipient s written records; (d) is independently developed by Recipient without reference to Sponsor Confidential Information, as shown by Recipient s written records; or (e) is published in accordance with Section Injunctive Relief. Recipient acknowledges that a breach or threatened breach of this Section 9 would cause irreparable harm to Sponsor, the extent of which would be difficult to ascertain. Accordingly, Recipient agrees that, in addition to any other remedies to which Sponsor may be legally entitled, Sponsor may have the right to seek immediate injunctive or other equitable relief in the event of a breach of this Section 9 by Recipient or any of Recipient s employees or agents. 9.5 Return of Confidential Information. Upon Sponsor s request and at Sponsor s expense, or upon the completion or termination of a Study Agreement or this Agreement, Recipient will promptly (a) return to Sponsor or, if so directed by Sponsor, destroy all tangible embodiments of Sponsor Confidential Information (in every form and medium); (b) permanently erase all electronic files containing or summarizing any of Sponsor Confidential Information (except for any computer records or files that have been created pursuant to Recipient s automatic archiving and back-up procedures and the removal of which is not technically reasonable); and (c) if so directed by Sponsor, certify to Sponsor in writing that Recipient has fully complied with the foregoing obligations. Notwithstanding the foregoing, Recipient shall be permitted to retain one (1) copy of Sponsor Confidential Information for its legal archives (subject to a continuing obligation of confidentiality) or as otherwise required by the Regulations. 9.6 Survival. Recipient s confidentiality obligations as set forth above shall continue in full force and effect for seven (7) years from the expiration or termination of the applicable Study Agreement. 9.7 Use of Names. Institution and Sponsor will obtain prior written permission from the other before using the names, symbols and/or marks of said other Party in any form of publicity in connection with a Study. This shall not include any legally required disclosure by Institution or Sponsor that identifies the existence of this Agreement or a Study Agreement; provided, however, any such required disclosure by Sponsor shall be limited to identification of Institution as the Study site and the Study Staff as participants in a Study. Without limiting the foregoing, Sponsor will not use, nor authorize others to use, the name, symbols or marks of Institution in any advertising or publicity material or make any form of representation or statement in relation to a Study which would constitute an expressed or implied endorsement by Institution of any commercial product or service without prior written approval from Institution. In order to preserve the publication rights for a Study, Institution gives permission to Sponsor to provide a Principal Investigator s contact information as a part of a clinical trial registry (e.g., or other comparable registry). For the sake of clarity, the preceding sentence does not prohibit Institution from disclosing the financial and federal reporting requirements or any report generated in the normal course of business or acknowledgement of sponsorship as required by the guidelines of a scientific or academic organization. 10. PUBLICATIONS Study Publications. At least sixty (60) days prior to any proposed submission for publication or presentation of Study Data or other findings related to a Study, Institution or Principal Investigator will provide Sponsor with a manuscript of such submission(s) for review and comment. Expedited reviews for abstracts or poster presentations may be arranged if mutually agreeable to Sponsor and Institution or the Principal Investigator. Under no circumstances shall Institution or the Principal Investigator publish or disclose Sponsor Confidential Information without Sponsor s prior written approval, except that Institution or the Principal Investigator may publish Study Data without Sponsor s consent, subject to the requirements of this Section. Institution or the Principal Investigator will withhold JS / Axiom / University of Pennsylvania / MCTA Page 8 of 15

9 submission of a manuscript or abstract for publication or presentation for up to sixty (60) days to allow Sponsor to file a patent application or take such other measures as Sponsor deems appropriate to establish and preserve its proprietary rights. Pursuant to 10.2, Sponsor shall be permitted to delay any publication if the same clinical trial set forth in a Protocol is still in progress at any other Study site. In all publications, credit shall be given to Sponsor for sponsorship of a Study and the supply of a Study Drug or Study Device Multi-Center Study Publication. Institution and Principal Investigator agree that if a Study is part of a multi-center study, the first publication of the results of the applicable Study shall be made in conjunction with the results from all Study centers. The manner in which the publication will be generated (but not the content) will be negotiated among Sponsor, Principal Investigator and said other investigators. Sponsor shall be the final arbiter in such negotiations. If the multi-center manuscript has not been submitted for publication within twelve (12) months after completion of the applicable Study and lock of the database at all Study sites or any earlier termination or abandonment of the applicable Study, then Institution thereafter shall be permitted to submit a manuscript for publication and then to publish such manuscript independently, subject to the provisions of this Section and Institution s confidentiality obligations hereunder. 11. TERM. This Agreement shall commence on the Effective Date and shall continue for the latter of five (5) years from the Effective Date or the expiration of the latest Study Agreement entered into prior to the expiration of this Agreement, unless otherwise terminated earlier in accordance with Section 12 of this Agreement. The term of this Agreement may be extended by mutual written agreement of the Parties. 12. TERMINATION Conditions of Termination. (a) Either Party may terminate this Agreement and/or any Study Agreement if the other Party materially breaches this Agreement or a Study Agreement and fails to cure the breach within thirty (30) days after receipt of written notice from the non-breaching Party specifying in detail the nature of the breach. (b) Sponsor may terminate this Agreement and/or any Study Agreement (i) at any time upon giving thirty (30) days advance written notice to Institution; (ii) for good cause immediately upon written notice to Institution, where good cause shall include (a) identification of any medical risk to Study Subjects, (b) a showing that the applicable Study Drug or Study Device is not effective, or (c) receipt of notice of regulatory action by the FDA (or any equivalent oversight body in a country other than the United States) terminating or suspending the applicable Study; or (iii) upon giving five (5) days advance written notice to Institution if for any reason a Principal Investigator is unwilling or unable to continue to serve as an investigator for a Study or is terminated by Sponsor pursuant to this Agreement, and a successor acceptable to both Institution and Sponsor is not available within thirty (30) days. (c) In the event a Principal Investigator leaves Institution and moves to a new facility, Sponsor may, in its sole discretion, deem it in the best interest of the Study Subjects to continue the applicable Study under the care of the original Principal Investigator, and terminate the Study Agreement upon giving five (5) days advance written notice to Institution. In the event of such termination, the Parties will mutually agree upon a written transfer plan and budget close-out, and Institution will cooperate with Sponsor to ensure a smooth and timely transfer of the Study Subjects and related Study documents to the Principal Investigator. JS / Axiom / University of Pennsylvania / MCTA Page 9 of 15

10 12.2 Effects of Termination. (a) In the event a Study Agreement is terminated for reasons other than material breach by Institution, Sponsor shall pay Institution, pursuant to the Study budget, for all services successfully performed prior to such termination and any non-cancelable expenses incurred in connection with Institution s performance thereunder. Institution will use commercially reasonable efforts to minimize any non-cancelable expenses. Notwithstanding anything contained herein to the contrary, upon termination of a Study Agreement for any reason, any amounts prepaid by Sponsor for services not yet performed shall be immediately refunded to Sponsor. (b) Immediately upon receipt of a notice of termination of this Agreement or any Study Agreement, the Principal Investigator shall stop enrolling Study Subjects into the Study and shall cease conducting procedures on Study Subjects already enrolled in the Study as directed by Sponsor, to the extent medically permissible; provided, however, after termination for any reason, both Parties shall continue activities under the Study Agreement solely as deemed necessary by mutual agreement of the Parties based on reasonable medical judgment to protect the health of Study Subjects participating in the Study. Notwithstanding anything contained herein to the contrary, regardless of the reason for early termination, Institution shall retain the responsibility for appointing a Principal Investigator to (i) ensure all Study Subjects are properly exited from the applicable Study and/or transferred to another Study site; and (ii) submit all Study Data to Sponsor, including any data clarifications. (c) Except as required for compliance with Institution s record keeping obligations under Section 3, upon completion or termination of a Study, or as otherwise requested by Sponsor, Institution shall return to Sponsor or, if so instructed by Sponsor, destroy all documents, information and/or supplies relating to the Study (including Study Devices, Study Drug samples, Work Product and CRFs), whether or not completed, and other related materials that were furnished to Institution by or on behalf of Sponsor. If Sponsor requests that such documents and information be destroyed, Investigator agrees to provide Sponsor with written certification of the same. (d) Expiration or termination of this Agreement or any Study Agreement for any reason shall not release either Party from liability which at said time has already incurred to the other Party and nothing herein shall affect or be construed or operate as a waiver of the right of the Party aggrieved by any breach of this Agreement or the applicable Study Agreement to be compensated for any injury or damage resulting therefrom which is incurred before or after such expiration or termination. (e) Except as otherwise expressly set forth herein, the following provisions will survive expiration or termination of this Agreement or any Study Agreement pursuant to their terms, together with any other provisions necessary for their construction and enforcement: Sections 3, 4, 6, 7, 8, 9, 10, 12, 13, 14 and 16, and any other provision of this Agreement that by its terms would survive expiration or termination. 13 INDEMNIFICATION Indemnification by Sponsor. Sponsor agrees to defend Institution, its faculty, trustees, officers, directors, employees, contractors and agents, along with the IRB, Study Staff and Principal Investigator (each an Institution Indemnified Party ) from and against any claim, suit or other proceeding brought by a third party (a Claim ) to the extent such Claim arises out of (a) any substance dispensed or procedure administered in the course of a Study in strict accordance with the Protocol and Sponsor s instructions; (b) the negligence, recklessness or willful misconduct of any Sponsor Indemnified Party (as defined below); (c) a breach of Sponsor s obligations, representations or warranties under this Agreement or the applicable Study Agreement or (d) Sponsor s use of of Study Data; and Sponsor will JS / Axiom / University of Pennsylvania / MCTA Page 10 of 15

11 indemnify and hold harmless the Institution Indemnified Party from any liabilities, losses, damages, judgments, awards, fines, penalties, costs and expenses (including reasonable attorneys fees and costs of defense) incurred by or levied against such Institution Indemnified Party as a result of such Claim. Notwithstanding the foregoing, Sponsor shall have no obligations under this Section 13.1 or otherwise to the extent that any Claim arises from: (i) the negligence, recklessness or willful misconduct on the part of any Institution Indemnified Party; (ii) a breach of Institution s, Principal Investigator s or Study Staff s obligations, representations or certificationsunder this Agreement or the applicable Study Agreement; (iii) any injuries occurring at the facility(ies) where a Study is conducted (other than injuries caused by or attributable to any substance dispensed or procedure administered in the course of a Study in accordance with the applicable Protocol); or (iv) a failure of Institution, the Principal Investigator or Study Staff to comply with applicable Regulations Liability of Institution. Institution assumes any and all risks of damage attributable to the negligent acts or omissions of the Institution or its officers, directors, employees, contractors, and agents General Conditions of Indemnification. Sponsor s obligations under this Section 13 are conditioned upon Institution: (a) providing written notice to the Sponsor of any Claim within thirty (30) days after Institution has knowledge of such Claim (except that failure to timely provide such notice will not relieve Sponsor of its obligations, except to the extent Sponsor is materially prejudiced as a direct result of such delay); (b) giving the Sponsor sole control over the defense thereof and any related settlement negotiations; and (c) cooperating and, at the Sponsor s request and expense, assisting in such defense. Notwithstanding the foregoing, Institution may participate at its own expense in the defense and any settlement discussions, and will have the right to approve any settlement agreement that involves an admission of fault by Institution or imposes non-monetary obligations on the Institution; provided, however, that such approval will not be unreasonably withheld. 14 LIMITATION OF LIABILITY. TO THE EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL EITHER PARTY BE LIABLE TO THE OTHER FOR ANY INDIRECT, INCIDENTAL, CONSEQUENTIAL, EXEMPLARY, SPECIAL OR PUNITIVE DAMAGES, INCLUDING ANY DAMAGES FOR LOSS OF PROFIT OR INCOME, ARISING FROM OR RELATING TO THIS AGREEMENT OR ANY STUDY AGREEMENT, WHETHER IN CONTRACT, TORT (INCLUDING NEGLIGENCE) OR OTHERWISE, EVEN IF SUCH PARTY HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES; PROVIDED, HOWEVER, THIS LIMITATION SHALL NOT APPLY TO EACH PARTY S (A) INDEMNIFICATION OBLIGATIONS HEREUNDER; (B) BREACH OF SECTION 4 (WORK PRODUCT AND OWNERSHIP); (C) BREACH OF SECTION 9 (CONFIDENTIALITY); OR (D) GROSS NEGLIGENCE OR WILLFUL MISCONDUCT. 15 INSURANCE Sponsor s Insurance. Sponsor warrants that it maintains a policy or program of insurance or self-insurance at levels it deems sufficient to support its indemnification obligations assumed herein. This includes broad form and contractual liability and product liability, in a minimum of $1,000,000 combined single limit per occurrence and $5, in the annual aggregate with respect to personal injury, bodily injury and property damage. Upon written request, Sponsor will provide evidence of its insurance (certificate of insurance) or self-insurance, and unless Sponsor is self-insured, it will provide to Institution thirty (30) days prior written notice of any cancellation or reduction of coverage Institution s Insurance. During the performance of each Study Agreement, Institution will maintain insurance or self-insurance in amounts no less than that specified below: JS / Axiom / University of Pennsylvania / MCTA Page 11 of 15

12 (d) General liability insurance with limits of not less than $1,000,000 per occurrence and $3,000,000 aggregate for personal injury or death. Institution shall endorse Sponsor as an additional insured during the term of any Study Agreement; (e) Medical malpractice or professional liability insurance for clinical research studies with limits of not less than $1,000,000 per occurrence and $3,000,000 aggregate; (f) Property insurance with minimum limits of not less than $500,000 per occurrence with coverage for business personal property of Sponsor, including Study Drugs or Study Devices while in the care, custody and/or control of Institution and its agents; and (g) Worker s compensation insurance in the amount required by the law of the state in which Institution s personnel are located. In those states where worker s compensation insurance is an elective option by an employer and Institution elects not to provide worker s compensation insurance, then Institution hereby indemnifies Sponsor for any claims, actions or suits, damages, fees, costs, expenses and other liabilities arising out of or in connection with any worker s compensation claims involving Institution. In no event shall Sponsor be liable for such claims. Upon written request, Institution will provide evidence of its insurance (certificate of insurance) or selfinsurance, and unless Institution is self-insured, it will provide to Sponsor thirty (30) days prior written notice of any cancellation or reduction of coverage. 16. MISCELLANEOUS Governing Law. Intentionally Omitted Dispute Resolution. The Parties will in good faith discuss any and all disputes, claims or controversies arising out of or relating to this Agreement ( Dispute(s) ) with the intention of amicable resolution. The Parties agree that any and all Dispute(s) that are not resolved by their mutual agreement shall be submitted for resolution to a state or federal court of competent jurisdiction Relationship of Parties. The relationship of the Parties established under this Agreement and any Study Agreement is that of independent contractors and neither Party is a partner, employee, agent or joint venture partner of or with the other, and neither Party has the right or authority to assume or create any obligation on behalf of the other Party Assignment and Subcontracting. Neither Party shall have the right to assign this Agreement or any Study Agreement or any of the rights or obligations of such agreements without the prior written consent of the other Party; provided, however, Sponsor may assign this Agreement or any Study Agreement to an affiliate or a subsidiary or a successor to that area of its business to which this Agreement or the Study Agreement is related. Institution will not subcontract or otherwise delegate any of its obligations under this Agreement or any Study Agreement without Sponsor s express prior written consent on a case-by-case basis; provided, however, Sponsor hereby consents to Institution s use of the subcontractor(s) listed (if any) in Exhibit C attached to the Study Agreement (as such Exhibit may be updated from time to time upon the mutual written agreement of the Parties). Notwithstanding Sponsor s consent to the use of a subcontractor, before allowing an approved subcontractor to begin performing services related to a Study, Institution shall (a) ensure that such subcontractor is qualified by education, training and experience to perform any delegated tasks, including the administration of the Study Drug or Study Device (if applicable); and (b) enter into a binding written agreement with such subcontractor that protects Sponsor s rights and interests, including protection of Sponsor s intellectual property (including Work Product) and Sponsor Confidential Information, to at least the same degree as this Agreement. JS / Axiom / University of Pennsylvania / MCTA Page 12 of 15

13 Institution and Principal Investigator will be responsible for the direction and coordination of the services of each subcontractor and Sponsor will have no obligation to pay any subcontractor directly Notices. All notices required in connection with this Agreement or any Study Agreement will be in writing and deemed effective given: (a) upon personal delivery to the Party to be notified; (b) on the date on which such notice is delivered by with confirmation that the has been received and read; or (c) one (1) business day after deposit with a nationally/internationally recognized overnight courier that provides tracking and verification of delivery. All notices shall be sent to the following addresses or at such other address(es) as a Party may designate by advance written notice to the other Party. If to Institution: University of Pennsylvania Perelman School of Medicine Office of Clinical Research Clinical Trial Contracting Unit 322 Anatomy-Chemistry Building 3620 Hamilton Walk Philadelphia, PA Attention: Director, CTCU/OCR If to Sponsor: 2525 Dupont Drive Irvine, California Attention: J ne Hinger hinger_jne@allergan.com With a copy to: Allergan, Inc Dupont Drive Irvine, California Attention: General Counsel Not Permitted; Notice to be sent pursuant to (a) or (c) above 16.6 Force Majeure. Neither Party shall be liable for any breach of this Agreement or any Study Agreement or for any delay or failure of performance resulting from any cause beyond such Party s reasonable control, including the weather, civil disturbances, acts of civil or military authorities or acts of God. The Party claiming relief under this Section shall promptly notify the other Party in writing, but in no event later than ten (10) calendar days of the occurrence, should any such cause arise and shall promptly take steps to remedy any delay or failure in performance upon removal of the circumstances causing such delay or failure Severability. If any provision of this Agreement or a Study Agreement is held by an arbitrator or court of competent jurisdiction to be unenforceable, such provision will be deemed modified and will be interpreted to accomplish the objectives of such provision to the greatest extent possible under applicable law and the remaining provisions of this Agreement or the Study Agreement will continue in full force and effect Waiver. Any waiver or failure to enforce any provision of this Agreement or a Study Agreement on one or more occasion will not be deemed a waiver of any other provision or of such provision on any other occasion Construction. The headings used for the sections of this Agreement and the Study Agreement are for information purposes and convenience only and in no way define, limit, construe or describe the scope or extent of the sections. The words such as herein, hereinafter, hereof, and hereunder refer to the agreement as a whole and not merely to a subdivision in which such words appear unless the context otherwise requires. The word including or any variation thereof means including, without limitation and will not be construed to limit any general statement that such word or variation thereof follows. The language used in this Agreement and the or a Study Agreement will be JS / Axiom / University of Pennsylvania / MCTA Page 13 of 15