EX-10.162 6 dex10162.htm API SUPPLY AGREEMENT CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTIONS OF THIS DOCUMENT HAVE BEEN REDACTED AND HAVE BEEN FILED SEPARATELY WITH THE U.S. SECURITIES AND EXCHANGE COMMISSION Execution Copy API SUPPLY AGREEMENT
EXHIBIT 10.162
CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTIONS OF THIS
DOCUMENT HAVE BEEN REDACTED AND HAVE BEEN FILED SEPARATELY
WITH THE U.S. SECURITIES AND EXCHANGE COMMISSION
Execution Copy
This API Supply Agreement (this “Agreement”) is made as of this 22nd day of November, 2006 (“Effective Date”), by and between INDEVUS PHARMACEUTICALS INC., a corporation organized and existing under the laws of the State of Delaware, United States of America, and having an office at 00 Xxxxxx Xxxxxx, Xxxxxxxxx, XX 00000-0000, Xxxxxx Xxxxxx (“Indevus”) and HELSINN CHEMICALS SA and HELSINN ADVANCED SYNTHESIS SA, both corporations organized and existing under the law of Switzerland and having their registered office at Xxx Xxxxxxxxx 00, 0000 Xxxxxx, Xxxxxxxxxxx (“Helsinn”). Indevus and Helsinn hereinafter are collectively referred to as the “Parties” and individually as a “Party”.
NOW, THEREFORE, the Parties hereto, intending to be legally bound, agree as follows:
I. | DEFINITIONS |
As used in this Agreement:
1.1 | “Act” means the United States Food, Drug, and Cosmetic Act of 1938, as amended, and the rules and regulations promulgated thereunder, or any successor act, as the same shall be in effect from time to time. |
1.2 | “Active Pharmaceutical Ingredient” or “API” means the compound [*] which is more commonly known as TROSPIUM CHLORIDE, described in and conforming to the Specifications. |
1.3 | “Adverse Experience” or “AE” means any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with any use of a product or of a derivative thereof containing API, whether or not the adverse experience is considered to be related to the use of such product, including but not limited to any of the following: an unexpected side effect, injury, toxicity or sensitivity reaction, which may include an experience of unexpected incidence and severity; an adverse |
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experience occurring in the course of the use of a drug product in professional practice; an adverse experience occurring in clinical studies; an adverse experience occurring from drug overdose, whether accidental or intentional; an adverse experience occurring from drug abuse; an adverse experience occurring from drug withdrawal; and any significant failure of expected pharmacological action; but in any event shall mean adverse drug experiences, as defined by 21 CFR Section 314.80.
1.4 | “Affiliate” means with respect to a Party, any corporation or other business entity which, directly or indirectly, is controlled by, controls, or is under common control with such Party. For this purpose, “control” shall be deemed to mean direct or indirect ownership of fifty percent (50%) or more of the stock or other equity of such entity. |
1.5 | “Batch” means a specific quantity of API that is produced according to a single manufacturing order during the same cycle of manufacture. |
1.6 | “Business Day” shall mean any day that is not a Saturday, a Sunday, a day on which the New York Stock Exchange is closed, or other day on which banks are required or authorized by law to be closed in Biasca, Switzerland. |
1.7 | “CFR” means the United States Code of Federal Regulations. |
1.8 | “Commercially Reasonable Efforts” means, with respect to a Party, the efforts and resources which would be used (including without limitation the promptness in which such efforts and resources would be applied) by such Party, consistent with generally-accepted industry standards for a company of comparable size and business in the industry, with regard to the diligent manufacture and commercialization of pharmaceutical products of similar market and profit potential at a similar stage in development or product life. The term “Commercially Reasonable” shall have a corresponding meaning. |
1.9 | “Confidential Information” means all information, data, know-how and all other business, technical and financial data disclosed hereunder by one Party or any of its Affiliates to the other Party or any of its Affiliates, except any portion thereof which: |
(a) | at the time of disclosure, is public knowledge; |
(b) | after disclosure, becomes public knowledge by publication or otherwise, except by breach of this Agreement by the recipient; |
(c) | the recipient can demonstrate by its written records was in the recipient’s possession at the time of such disclosure, and which was not acquired, directly or indirectly, from the disclosing Party or its Affiliates; |
(d) | is lawfully disclosed to the recipient on a non-confidential basis by a third party who is not obligated to the disclosing Party or any other third party to retain such Confidential Information in confidence; |
(e) | results from research and development by the recipient independent of such disclosure as shown by competent evidence; or |
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(f) | is required to be disclosed by legal process; provided, in each case the Party so disclosing information timely informs the other Party and uses its reasonable efforts to limit the disclosure and maintain confidentiality to the extent possible and, if possible, permits the other Party to attempt by appropriate legal means to limit such disclosure, subject to the provisions of Section 4.6. |
All information exchanged pursuant to this Agreement shall be considered Confidential Information. Confidential Information disclosed orally, visually and/or in another intangible form shall be identified by the disclosing Party to the receiving Party as confidential at the time of such disclosure and confirmed in writing to the receiving party within thirty (30) days after such disclosure.
1.10 | “Current Good Manufacturing Practices” or the letters “GMP” or “cGMP” means current good manufacturing practice and standards as provided for (and as amended from time to time) in European Community Directive 91/356/EEC (Principles and guidelines of good manufacturing practice for medicinal products for human use) and in the Current Good Manufacturing Practice Regulations of the U.S. Code of Federal Regulations Title 21 (21 C.F.R. Parts 210 and 211) in relation to the production of pharmaceutical intermediates and active pharmaceutical ingredients, and applicable ICH Harmonised Tripartite Guideline Q7a, Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients, and subject to any arrangements, additions or clarifications agreed in writing from time to time between the Parties in the Quality Technical Agreement. |
1.11 | “DMF” means a Drug Master File as defined in 21 C.F.R. §314.420 in the United States, including all supplements and amendments thereto or any foreign counterpart of a U.S. DMF. |
1.12 | “FDA” means the United States Food and Drug Administration and any successor agency having substantially the same functions. |
1.13 | “Finished Product” means any drug product containing or comprising API, in its finished, labeled and packaged form, ready for sale to the market, including all samples thereof. |
1.14 | “HCI” means [*], an Affiliate of Helsinn. |
1.15 | “Helsinn Facility(ies)” means any Helsinn or HCI manufacturing facility(ies) that is qualified or approved in the NDA to manufacture API and that is used for the manufacture of API pursuant to this Agreement. |
1.16 | “Helsinn Payment” means [*]. |
1.17 | “In Bulk” means quantities of API formulated and packaged in non-retail size containers. |
1.18 | “Launch Period” means the period commencing on the launch date of SANCTURA XR™ in the United States and expiring on (a) December 31 of the calendar year in which such launch date occurs if the launch date occurs in the first three months of |
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such year; or (b) December 31 of the calendar year immediately following the calendar year in which the launch date occurs if the launch date occurs after the first three months of such year.
1.19 | “Losses” means any and all damages, awards, deficiencies, settlement amounts, defaults, assessments, fines, dues, penalties (including penalties imposed by any governmental authority), costs, fees, liabilities, obligations, taxes, liens, losses, and expenses (including without limitation court costs, interest and reasonable fees of attorneys, accountants and other experts) awarded or otherwise paid or payable to third parties. |
1.20 | “NDA” means a New Drug Application pursuant to Section 505 of the Act submitted to the FDA or any successor application or procedure or any foreign counterpart of a U.S. New Drug Application for approval to market, including, where applicable, applications for pricing and reimbursement approval. |
1.21 | “Purchase Price” shall have the meaning set forth in Section 6.3 hereof. |
1.22 | “Quality Technical Agreement” means the quality assurance/quality control agreement to be entered into by Indevus and Helsinn in accordance with Schedule 1.22 and as contemplated by Section 3.7 and to be appended to this Agreement as Exhibit 1.22. |
1.23 | “Regulatory Authority” means (i) the FDA and/or (ii) any regulatory body with similar regulatory authority in any other jurisdiction anywhere in the Territory. |
1.24 | “Regulatory Standards” means (i) obtaining and maintaining any and all permits, licenses, filings and certifications required by the FDA or other Regulatory Authorities, and compliance with cGMPs, applicable to the Helsinn Facilities or Helsinn’s activities hereunder, and (ii) any laws, rules, regulations and standards of any Regulatory Authority, whether within or outside the United States that apply to such activities. |
1.25 | “SANCTURA XR™” means the once-daily formulation of SANCTURA® currently under development by Indevus. |
1.26 | “Specifications” means the quality assurance and quality release specifications for API as set forth on Schedule 1.26, subject to such modifications to the Specifications agreed between Indevus and Helsinn in writing and set forth in an amendment to this Agreement as a restated Schedule 1.26. |
1.27 | “Territory” means worldwide. |
Where words and phrases are used herein in the singular, such usage is intended to include the plural forms where appropriate to the context, and vice versa. The words “including”, “includes” and “such as” are used in their non-limiting sense and have the same meaning as “including without limitation” and “including but not limited to”. References to Articles, Sections, subsections, and clauses are to the same with all their subparts as they appear in this Agreement.
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II. | PURCHASE AND SALE |
2.3 | Specific Duties. In addition to its general obligations relating to the manufacture and supply of API, Helsinn shall be responsible for performing the following services at Helsinn’s cost: |
(a) | quality control and testing of all API in order to monitor compliance with all applicable Regulatory Standards, the Specifications and this Agreement; |
(b) | conducting stability testing of API in accordance with the procedures set forth in the Quality Technical Agreement; |
(c) | summarizing implemented changes and supplying latest versions of approved critical documentation, and providing other information necessary for Indevus to prepare, submit, obtain and maintain all regulatory filings relating to the manufacture of the API under the terms of this Agreement; and |
(d) | performing such other services as agreed upon in writing by the Parties. |
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III. | API QUANTITY, QUALITY AND MANUFACTURING PROCESSES; TECHNICAL ASSISTANCE |
3.3 | Improvements |
(a) | Except as set forth in sub-section 3.3 (b), for changes, including, but not limited to process changes, site changes and supplier changes intended to improve operational efficiency, effectiveness and risk-management (the “Improvements”), both Parties shall agree in writing whether to implement such Improvement or not. If the Parties agree to implement such Improvement, the Parties shall also agree in writing on an Improvement program including an assessment of the costs of implementation of the program and of the expected financial impact of the Improvement. Upon completion of the Improvement program, should the Improvement have been demonstrated to be feasible, the Parties shall agree in writing which Party will be responsible to pay documented costs and expenses for the implementation of said Improvement, being understood that should Indevus be responsible for all such costs and expenses the Purchase Price will be reduced by an amount equal to [*]% of the amount of the decrease, if any, in the costs of starting and raw materials due to the implementation of the Improvement, while should Helsinn be responsible for all such costs and expenses the Purchase Price will be reduced by an amount equal to [*]% of the amount of the decrease, if any, in the costs of starting and raw materials. |
(b) | The Parties acknowledge that (i) [*], and (ii) [*]/kg (the “[*]”). Helsinn agrees to use its best efforts to [*] and to [*]. The Purchase Prices set forth on Part B of Schedule 6.3 shall be effective [*]; provided, however, that in the event that the actual [*], the Purchase Prices set forth on Part B of Schedule 6.3 [*]. For example, if the [*] is [*], the Purchase Price set forth on Part B of Schedule 6.3 [*] |
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IV. | CONFIDENTIAL INFORMATION |
4.1 | The Parties acknowledge that they have provided Confidential Information to each other in connection with the manufacture and supply of the API, and further acknowledge that all such Confidential Information (as well as any additional Confidential Information provided by one Party to the other hereunder) shall be subject to the provisions of this Section IV. Any and all confidential information, knowledge, technology and trade secrets relating to the API and provided by Indevus and/or Helsinn to the other shall be deemed Confidential Information. |
4.2 | During the term of this Agreement and for ten (10) years thereafter, all Confidential Information disclosed and confirmed in writing and designated as confidential by the disclosing party within thirty (30) days from oral disclosure, including confidential information so designated that was disclosed by either Party prior to the Effective Date, shall be held in confidence by the receiving party, shall not be used by the receiving party for any purpose except as provided hereunder and |
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shall not be disclosed to third parties except for disclosure to its Affiliates or governmental authorities, in connection with pre-clinical or clinical development activities or the manufacturing of Finished Product, or except as otherwise necessary to carry out the receiving party’s obligations under this Agreement. If a receiving party finds it necessary to disclose such Confidential Information to a third party, the receiving party will not do so without first obtaining the written consent of the disclosing party (which shall not be unreasonably withheld) and entering into an agreement with the third party which binds the third party to obligations of restricted use and disclosure no less stringent than those undertaken by the Parties in this Agreement.
4.3 | Neither Party shall distribute any Confidential Information of the other except to its employees, agents or consultants who have a need to know exclusively in connection with the performance of their duties in satisfying the obligations of such Party hereunder. Any employee, agent or consultant who receives Confidential Information shall be advised as to the confidential nature thereof and the prohibitions contained herein. All copies of any portions of any Confidential Information distributed as provided in this Section will be identified as confidential. Upon termination of this Agreement, and upon the request of the disclosing party, the receiving party shall return or destroy all such Confidential Information and any copies thereof in its possession, except that each Party may retain one copy of Confidential Information solely for archival purposes. |
4.4 | Termination of this Agreement shall not operate to extinguish either Party’s obligation to treat Confidential Information as provided herein, and the same shall continue in effect in accordance with this Section. |
4.5 | Nothing contained herein shall be deemed to grant to either Party, either expressed or implied, a license or other right or interest in the Confidential Information of the other or in any patent, trademark or other similar property of the other. |
4.6 | Neither Party shall use the name of the other, nor disclose the existence of this Agreement for any purpose, without the prior written consent of the other, which shall not be unreasonably withheld or delayed provided, however, it is understood that Indevus may make disclosure of this Agreement and the terms hereof, in any filings required by the United States Securities and Exchange Commission (“SEC”) and may file this Agreement as an exhibit to any filing with the SEC. In connection with any such filing, Indevus shall endeavor to obtain confidential treatment of economic and trade secret information and shall deliver to Helsinn in advance of any filing a redacted copy of this Agreement to enable Helsinn to give comments and suggestions on economic and trade secret information to be kept confidential. |
V. | FORECASTS AND ORDERS |
5.1 | Forecasts. |
(a) | Not later than [*] prior to the estimated launch date of SANCTURA XR™ [*], Indevus shall provide Helsinn with a forecast of its estimated requirements for API for the period [*] calendar quarters from the estimated launch date, broken down on a quarterly basis. Within [*] prior to the estimated launch date of |
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SANCTURA XR™, Indevus shall provide Helsinn with an updated forecast of its estimated requirements of API for the [*] calendar quarters commencing after [*] after the launch date, broken down on a quarterly basis. Within [*] days after the launch date, and thereafter on a quarterly basis during the term of this Agreement, Indevus shall provide Helsinn with a rolling forecast of its estimated requirements of API, broken down on a quarterly basis, for [*] consecutive calendar quarters (commencing at the beginning of the [*] complete calendar quarter that commences after the date of such forecast).
(b) | The first [*] calendar quarters of each forecast provided after the launch date of SANCTURA XR™ (the “Binding Portion”) shall represent a binding forecast and the remaining [*] calendar quarters of each forecast shall be non-binding and shall represent Indevus’s reasonable estimates only. Except as set forth in the preceding sentence and the first sentence of Section 5.2, all forecasts made hereunder shall be made to assist Helsinn in planning its production and shall not be binding purchase orders, and shall be without prejudice to Indevus’s subsequent purchase orders for the API in accordance with the terms of this Agreement. Each forecast provided by Indevus shall supersede any previous forecast and may be expressed in a reasonable range. |
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reasonable belief that it cannot fulfill the forecast or purchase order if such date is after such five (5) Business Day period), (ii) if such inability is partial, fulfill purchase orders with such quantities of API as are available and supply the remaining quantities of API through HCI on a timely basis and (iii) if such inability is total, fulfill purchase orders of API through HCI, provided that all API manufactured and supplied by HCI is in accordance with the Specifications, applicable Regulatory Standards, and the terms and conditions of this Agreement and the Quality Technical Agreement. In addition, in the event neither Helsinn nor HCI can fulfill such purchase orders in accordance with such requirements, Helsinn shall take all Commercially Reasonable steps including as set forth under Section 5.4, to enable Indevus to procure adequate quantities of API from a second source. In the event of any failure to supply by Helsinn, Indevus shall be relieved from its obligations under this Agreement to purchase any quantities of API identified in any Binding Portion of a forecast or outstanding purchase orders and of the Minimum Purchase Requirements. Nothing in this Section 5.3, Section 5.4 or Section 7.7, shall limit any contractual rights or remedies that may be available to Indevus on account of any failure to supply API pursuant to the terms of this Agreement.
5.4 | Second Source. |
At the request of Indevus, Helsinn shall take all Commercially Reasonable steps to procure all necessary licenses, permits, certifications and approvals relating to the qualification of HCI and/or another Helsinn Facility as a second manufacturer of API, and to comply and cause HCI or such other Helsinn Facility, as applicable, to comply with such other requirements, obligations and responsibilities as are necessary to fully enable HCI or such other Helsinn Facility, as applicable to undertake the manufacturing and supply of API in accordance with the Specifications, applicable Regulatory Standards, and the terms and conditions of this Agreement and the Quality Technical Agreement. Such alternative production site and all related costs and expenses shall be approved by Indevus before commencement of routine production and all actions required to have a DMF for API approved by the FDA will be put in place and agreed between both Parties. Costs and expenses related to obtainment and maintenance of the above mentioned licenses, permits, certifications and approvals shall be borne by Indevus, provided, however, that Helsinn shall bear or reimburse Indevus for all such costs and expenses incurred in the event or as a result of Helsinn’s inability to supply or fulfill its requirements under this Agreement.
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VI. | PRICE, SHIPMENT AND PAYMENT |
6.1 | Helsinn’s Responsibilities. Helsinn will properly manufacture the API so that it may be lawfully and safely shipped to Indevus or its designee worldwide. Helsinn will prepare and execute all reasonably necessary shipping documents, consisting of Packing List, Dangerous Goods Declaration, MSDS, Certificate of Analysis and Certificate of GMP compliance. Indevus will choose the carrier and the designee by indicating both on its purchase order provided to Helsinn. |
6.2 | Terms of Shipment. Upon receipt from Indevus of an authorization for release as set forth in Section 7.1, Helsinn will invoice API [*] (Incoterms 2000). Transportation to final destination will be carried out at the care of Helsinn, according to Indevus’s written instructions, by common carrier designated by Indevus. If Indevus does not designate a common carrier, Helsinn may select the common carrier. Risk of loss shall pass from Helsinn to Indevus [*]. All transport and insurance costs will be borne by [*]. All API to be delivered pursuant to this Agreement shall be delivered in accordance with this Section 6.2, suitably packed in bulk containers for shipment, and marked for shipment to the final destination point indicated in Indevus’ purchase order. The shipping packaging used in connection with API deliveries shall be in accordance with cGMP with respect to protection of the API during transportation, taking into consideration the mode(s) of transport Indevus has elected to use for each such shipment, the final destination point of each such shipment and reasonable expectations regarding shipment time duration and possible delays associated therewith. |
6.3 | Price. Helsinn shall invoice Indevus the Purchase Price for all API delivered as set forth in Schedule 6.3 attached hereto, as such schedule is amended as provided for herein and therein. Helsinn shall send its invoice at the time of shipment. For purchase orders and invoices during any particular year, the Purchase Price shall be calculated on a cumulative basis based on the quantities of API purchased during that year up to and including API purchased under the purchase order for which the calculation is being made, giving effect to any applicable credit due to volume discounts, provided, however, that within [*] days after the end of each year, the Parties shall calculate the actual Purchase Price for such year based on a calculation of the total quantities of API purchased for that year and the applicable Purchase Price for such quantities of API in accordance with Schedule 6.3 and, at Indevus’ request, Helsinn shall either refund to Indevus within ten (10) days after such reconciliation or credit against future purchases of API any amounts due Indevus for any excess payment of the Purchase Price. |
6.4 | Terms of Payment. Indevus will pay Helsinn the Purchase Price within [*] days after the date on which Indevus receives the invoice from Helsinn. All payments required by this Agreement shall be made in United States dollars. In the event of any late payment of any payment due hereunder, the amount of the late payment shall bear interest at the Prime Rate commencing on the date such payment is due until such date as the payment is made. “Prime Rate” for purposes of this Section 6.4 shall mean the prime rate of Citibank, N.A. in New York, New York as published in the Wall Street Journal computed on a daily basis and shall change when and as the Prime Rate changes. |
6.5 | Tax Withholding. If laws, rules or regulations require withholding of income taxes or other taxes imposed upon payments set forth in this Agreement, Helsinn shall provide Indevus, prior to any such payment, annually or more frequently if required, with all |
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forms or documentation required by any applicable taxation laws, treaties or agreements to such withholding or as necessary (including, but not limited to, Form W8-BEN and any successor form) and Indevus shall make such withholding payments as required and subtract such withholding payments from the payments set forth in this agreement. Indevus shall submit appropriate proof to Helsinn of payment of the withholding taxes within a reasonable period of time. Indevus will use efforts consistent with its usual business practices to ensure that any withholding taxes imposed are reduced as far as possible under the provisions of the current or any future taxation treaties or agreements between foreign countries, and Helsinn shall cooperate with such efforts.
VII. | INSPECTION AND ANALYSIS |
7.1 | Inspection by Helsinn. Helsinn will analyze each API lot for compliance with the Specifications. Helsinn will send to Indevus a certificate of analysis and a certificate of compliance (together with any other documentation required under the Quality Technical Agreement) prior to each shipment of API and will not release any shipment for delivery unless and until it receives from Indevus an authorization for release based on such certificates and other documents required under the Quality Technical Agreement. |
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(i) replace said API with API that meets the Specifications and the warranties set forth in Article IX as soon as practicable at no charge to Indevus and Helsinn shall pay all round-trip shipping and other charges to and from the destination of the original shipment, (ii) refund the Purchase Price to Indevus, or (iii) credit Indevus’s account in an amount equal to the Purchase Price for the rejected API. Helsinn shall reimburse Indevus for the reasonable costs incurred by Indevus in properly disposing of such non-conforming API. Any notice given hereunder shall specify the manner in which the API fails to conform to the purchase order therefor or fails to meet such warranty or the Specifications.
VIII. | REGULATORY MATTERS; REGULATORY FILINGS AND APPROVALS |
8.1 | General. |
(a) | Helsinn shall (i) be responsible for obtaining and maintaining all site licenses and registrations for the manufacture of the API at the Helsinn Facility where the API is manufactured and will make copies of such registrations and all related documents available to Indevus and its designee for inspection upon Indevus’ reasonable request; (ii) take all steps necessary to pass inspection by and shall comply with other applicable regulations promulgated by, but not limited to, the FDA and [*] and any other applicable Regulatory Authority in connection with Helsinn’s manufacture of the API; and (iii) file with the FDA and any other applicable Regulatory Authority DMFs relating to the API. Helsinn hereby grants Indevus and/or Indevus’ designees the rights to reference any such DMF in Indevus’ and/or Indevus’ designees regulatory submissions and, upon Indevus’ request, will provide Indevus and/or Indevus’ designees with a letter of authorization authorizing Indevus and/or Indevus’ designees to reference such DMF. |
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(b) | Indevus shall be responsible for obtaining and maintaining all regulatory approvals for the use of the product incorporating the API for all the purposes set forth in Section 2.1 above. |
IX. | REPRESENTATIONS AND WARRANTIES |
9.1 | General. |
(a) | Helsinn represents and warrants to Indevus that (i) it has the full corporate power and authority to enter into this Agreement and to perform its obligations hereunder; (ii) it has and will maintain throughout the term of this Agreement, the expertise, with respect to personnel and equipment, to fulfill the obligations established hereunder; (iii) the production facility, equipment and personnel to be employed will be qualified to manufacture API according to cGMP at the time each such batch of API is produced, and that the production facility to be employed is in compliance with all applicable material laws and regulations; (iv) neither Helsinn nor any of its employees engaged in performing Helsinn’s obligations under this Agreement, is, nor shall it or any of such individuals be at the time of performing any of the activities to be performed by Helsinn hereunder, disqualified or debarred by the FDA or any other Regulatory Authority for any purpose pursuant to 21 U.S.C Section 355a or any foreign equivalent thereof; (v) there are no pending or uncorrected citations or adverse conditions noted in any inspection of the production facility to be employed which would cause the API to be misbranded or adulterated within the meaning of the Act or other applicable laws; (vi) the execution, delivery and performance of this Agreement by Helsinn does not conflict with, or constitute a breach of any order, judgment, agreement, or instrument to which Helsinn is a party; (vii) the execution, delivery and performance of this Agreement by Helsinn does not require the consent of any person or the authorization of (by notice or otherwise) any governmental or Regulatory Authority (other than those relating to the granting of approval to commercialize the product containing the API); and (viii) to Helsinn’s knowledge, the use by Helsinn, complying with the terms and conditions of this Agreement, of Helsinn Confidential Information, of any information related to the API that was not supplied by Indevus to Helsinn, or of any procedures, processes and/or other manufacturing know-how that were independently known by Helsinn or that were invented, discovered or developed by Helsinn or any Helsinn Affiliate or agent, does not infringe upon any third party’s intellectual property rights. |
(b) | Indevus represents and warrants to Helsinn that (i) it has the full corporate power and authority to enter into this Agreement and to perform its obligations hereunder; (ii) the execution, delivery and performance of this Agreement by Indevus including the delivery and disclosure to Helsinn of the Specifications, the Confidential Information, Indevus’ know-how and any other information disclosed by Indevus in writing specifically for use in connection with the manufacture of the API does not conflict with, or constitute a breach of any order, judgment, agreement, or instrument to which Indevus is a party; (iii) the execution, delivery |
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and performance of this Agreement by Indevus including the delivery and disclosure to Helsinn of the Specifications, the Confidential Information, Indevus’ know-how and any other information disclosed by Indevus in writing specifically for use in connection with the manufacture of the API does not require the consent of any third party or the authorization of (by notice or otherwise) any governmental or regulatory authority (other than those relating to the granting of approval to commercialize the product containing the API); (iv) all Indevus Confidential Information (including but not limited to Indevus’s know-how) necessary to allow Helsinn to manufacture the API has been made available to Helsinn, subject to confidentiality obligations and solely for the purpose of manufacturing such API; such Confidential Information is accurate and complete in all material respects and Indevus has not, up to and including the Effective Date, omitted to furnish Helsinn with any information in its possession concerning the API or the transactions contemplated by this Agreement, which would be material to Helsinn’s decision to enter into this Agreement and to undertake the commitments and obligations set forth herein; (v) to Indevus’ knowledge, the use by Helsinn, complying with the terms and conditions of this Agreement, of the Specifications, the Indevus Confidential Information (including but not limited to Indevus’s know-how) or any other information supplied by Indevus to Helsinn in writing specifically for use in connection with the manufacture of the API and that was not independently known or invented, discovered or developed by Helsinn or any Helsinn Affiliate or agent, does not infringe upon any third party’s intellectual property rights; and (vi) any and all materials (including raw materials) supplied by or on behalf of Indevus to Helsinn specifically for use in connection with the manufacture of the API, comply with all applicable specifications, laws and regulations (including any applicable regulatory requirements) and fit for the purpose of allowing Helsinn to perform the activities provided for hereunder.
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X. | QUALITY CONTROL, RECORDS AND INSPECTIONS |
10.7 | Regulatory Communications and Inspections. Helsinn will promptly, but in any event not later than three (3) Business Days after notice or the same day as any unannounced contact, inspection or audit commences, inform Indevus of any contact, inspection or audit by any Regulatory Authority or governmental agency (other than ISO 14001 and FCOS inspections), related to or affecting the API or a Helsinn Facility where the API is manufactured. Authorized representatives of Indevus shall have the right to be present during the inspection and/or during the close-out session with any Regulatory Authority inspectors. Helsinn will promptly provide Indevus with copies of any government-issued inspection observation reports (including without limitation FDA Form 483s, warning letters, citations and/or equivalent or similar forms from other Regulatory Authorities) and/or agency correspondence that may reasonably be expected to affect the API or a Helsinn Facility where the API is manufactured, or that |
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relates to any related license or permit issued to Helsinn in connection with the API manufacture. Helsinn and Indevus will cooperate in resolving any concerns with any Regulatory Authority and Helsinn will provide Indevus with a written copy of any proposed response at least five (5) Business Days prior to submitting such response and of the actual responses submitted to any Regulatory Authority and with a summary of the corrective action(s) taken or planned by Helsinn. Helsinn will do all its best efforts to rectify or resolve any deficiencies noted by any Regulatory Authority that relate to Helsinn’s ability to supply API hereunder. Helsinn will also inform Indevus of any action taken by any governmental agency against Helsinn or any of its officers and employees which may reasonably be expected to adversely affect the API or Helsinn’s ability to supply API hereunder within 24 hours after the action is taken. Helsinn will also provide Indevus with copies of all other communications or correspondence between Helsinn and any Regulatory Authority relating to Helsinn’s activities under this Agreement within forty-eight (48) hours after receiving or providing such communication or correspondence.
10.8 | Indevus Inspections and Audits. Indevus employees or Indevus authorized representatives will have the right during normal business hours, at reasonable intervals and upon giving Helsinn at least thirty (30) Business Days advance notice (two (2) Business Days in the event of a recall attributable to the API) to inspect and audit at Indevus’s sole expense, (a) the Helsinn Facilities used in the manufacturing, bulk packaging, storage, testing, shipping or receiving of API and (b) manufacturing and quality control records and other documentation relating to such activities for the purpose of verifying the compliance of the API manufacture with the requirements provided for in this Agreement, the Quality Technical Agreement and with current Good Manufacturing Practices, provided, however that, if circumstances arise that in Indevus’s reasonable judgment require that its representatives inspect the Helsinn Facilities more than once per calendar year, the Parties shall discuss such circumstances and agree in good faith upon additional inspections and appropriate means for addressing such circumstances. All such employees and representatives shall be bound by the same confidentiality obligations as contained herein and shall abide at all times with Helsinn’s rules and regulations, including without limitation safety rules and regulations. Such inspections may include cGMP inspections and system audits. Persons conducting such inspections will have access only to documents, records, reports, data, procedures, facilities, regulatory submissions and communications, and all other information required to be maintained by applicable government regulations relating to the API. Helsinn shall take appropriate actions to adopt reasonable suggestions of Indevus to correct any deficiencies identified by such inspection or audit and shall provide Indevus with reasonable documentary and other evidence of such correction. The duration of each inspection or audit will be limited to no more than five (5) days, being however understood that in any case said inspections and audits may not interfere with Helsinn’s normal operations. |
XI. | COMPLAINTS, ADVERSE EVENTS AND RECALLS |
11.1 | API Complaints and AEs. Indevus shall maintain complaint files with respect to the product containing API in accordance with cGMPs. In the event that Helsinn should receive any API complaints and/or AEs notices from third parties, Helsinn will promptly notify Indevus by facsimile or other electronic transmission within two (2) Business Days of its receipt thereof. All such notices shall be sent to the attention of Xxxxx Xxxxxxx, M.D., |
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Senior Vice President-Clinical Development and Regulatory Affairs at Indevus, facsimile number 000-000-0000. Indevus shall promptly provide Helsinn with copies of any complaints received by Indevus relating to the manufacture or bulk packaging of the API. Indevus shall have the exclusive responsibility for responding to all complaints, and for promptly providing Helsinn with a copy of any responses to complaints relating to the manufacture or bulk packaging of the API. Indevus or its affiliates shall have responsibility for reporting all complaints relating to the product containing API to the FDA and any other Regulatory Authorities, including, but not limited to, complaints relating to the manufacture or bulk packaging of the API as well as adverse experience (AE) reports. Indevus will correspond with complainants as to any complaints associated with product containing API, whether received during or after the term hereof. Helsinn will reasonably assist Indevus in investigating API complaints relating to the manufacture or bulk packaging of the API by analyzing API and manufacturing processes to determine the nature and cause of an alleged API manufacturing defect or alleged API failure. Helsinn will also reasonably assist Indevus, if so expressly required by Indevus from time to time, in the investigation of any Adverse Experience (AE) reported to either Party when such AEs are reasonably believed to be attributable to the manufacture or bulk packaging of the API. If Indevus determines that any reasonable physical, chemical, biological or other evaluation should be conducted in relation to an AE or API complaint relating to the manufacture or bulk packaging of the API, Helsinn will reasonably conduct the evaluation and use its reasonable effort to provide Indevus with a written report of such evaluation within thirty (30) days from receipt of Indevus’s written request for same, together with samples of the API from the relevant lot. The obligations and responsibility in connection with the above AEs and the management of the same shall pertain exclusively to Indevus.
11.2 | Recall Action. If Indevus should elect or be required to initiate a recall, withdrawal, stock recovery or field correction (each, or collectively, a “Recall”) of API or product containing API because of supply by Helsinn of API that does not conform to the Specifications and warranties established by this Agreement, subject in any case to Section 14.1 hereunder, Indevus will notify Helsinn and provide Helsinn a copy of its recall letter prior to initiation of the recall. Helsinn will assist Indevus (and its designee) in an investigation to determine the cause and extent of the problem. All regulatory authority contacts and coordination of any recall activities will be initiated by, and will be the sole responsibility of, Indevus. |
11.3 | Recall Expenses. If a Recall of any product containing API is necessary, requested by any Regulatory Authority or otherwise advisable for any reason, Helsinn and Indevus shall each bear the costs of the Recall in proportion to each Party’s responsibility for the error necessitating the recall or withdrawal. For purposes of this Agreement, such costs shall include the expenses of notification and destruction or return of the recalled or withdrawn API or Finished Product and all other documented out-of-pocket costs incurred in connection with such Recall but shall not include lost profits or opportunity costs of either Party. |
11.4 | Recall Records. Helsinn will maintain complete and accurate records for such periods as may be required by applicable law or regulation. |
11.5 | Discontinuation of Sales. Indevus, at any time and without liability to Helsinn, shall be entitled to cease, permanently or temporarily, sales of Finished Product in any country if continued sales of Finished Product in such country would be in violation of any applicable laws or regulations, or if Indevus determines that there is an ethically valid reason to cease such sales based on medical or scientific concerns relating to such Finished Product. |
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XII. | INSURANCE |
12.1 | During the term hereof, Helsinn shall maintain in full force and effect valid and effective insurance policies, including product liability insurance policies, in connection with its obligations, liabilities, representations and warranties as contemplated herein. In particular, Helsinn’s product liability coverage shall be not less than US$ [*] (United States Dollars [*]) (or the equivalent amount in other currency) per loss occurrence and per aggregated loss occurrences per year provided such coverage is available at commercially reasonable rates. If such coverage is not so available, Helsinn will immediately provide notice thereof to Indevus. Helsinn will provide to Indevus, upon Indevus’s written request, evidence of liability insurance coverage and the amounts thereof. Such coverage shall be maintained for not less than seven (7) years following expiration or termination of this Agreement for any reason. |
12.2 | During the term hereof, Indevus agrees to maintain in full force and effect valid and effective insurance policies, including product liability insurance policies, in connection with its obligations, liabilities, representations and warranties as contemplated herein. In particular, Indevus’s product liability coverage shall be not less than US$ [*] (United States Dollars [*]) per loss occurrence and per aggregated loss occurrences per year provided such coverage is available at commercially reasonable rates. If such coverage is not so available, Indevus will immediately provide notice thereof to Helsinn. Indevus will provide to Helsinn, upon Helsinn’s written request, evidence of adequate liability insurance coverage and the amounts thereof. Such coverage shall be maintained for not less than seven (7) years following expiration or termination of this Agreement for any reason. |
XIII. | INVENTIONS |
13.1 | Subject to Section 13.2 hereunder, any information, inventions, improvements or the like derived or coming from Indevus’ Confidential Information or from any other information related to the API, howsoever gained or obtained by Helsinn, will be automatically considered as Confidential Information under the terms of the Section IV and will have to be immediately communicated and delivered to Indevus, and will be considered the exclusive property of, and all right, title and interest will be owned by, Indevus. |
13.2 | It is expressly agreed that Section 13.1 above is not applicable to those works, information and improvements (and relevant intellectual property rights) related exclusively to procedures, processes and manufacturing know-how of Helsinn’s factories which may be developed by Helsinn in the course of API manufacture hereunder but which relate to manufacturing operations generally. In this case, therefore, any resulting information, and the relevant intellectual property rights, shall belong to Helsinn. |
[*] | CONFIDENTIAL TREATMENT REQUESTED |
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XIV. | INDEMNIFICATION |
14.1 | By Helsinn. |
(A) Helsinn will indemnify and hold harmless Indevus, its Affiliates, directors, officers, employees, agents, successors, and assigns (collectively, “Indevus Indemnified Parties”) from and against any and all Losses arising out of, attributable to or resulting from any third party claim, suit or action related to or alleging (i) any failure of the quality of the API supplied hereunder, including any failure of the API to conform to the Specifications; (ii) any negligent or wrongful act or any breach by Helsinn of any of its obligations, representations and/or warranties hereunder; or (iii) the infringement of third parties’ intellectual property rights due to the use by Helsinn of any Helsinn Confidential Information in each case except to the extent caused by the negligence or willful misconduct of Indevus or any breach by Indevus of any of its obligations, representations and/or warranties hereunder.
[*]
14.2 | By Indevus. |
(A) Indevus will indemnify and hold harmless Helsinn, its Affiliates, directors, officers, employees, agents, successors, and assigns (collectively, “Helsinn Indemnified Parties”) from and against any and all Losses arising out of, attributable to or resulting from any third party claim, suit or action in any way related to or alleging (i) any failure in the quality of the API supplied hereunder which (a) is due to any defect in the Indevus Confidential Information, or the Specifications supplied to Helsinn by or on behalf of Indevus for use in connection with the manufacture of the API, or (b) results from any API quantities which have been adulterated or otherwise mistreated by Indevus; (ii) the processing of said API into Finished Product and/or the distribution and sale of said Finished Product to clients; (iii) any negligent or wrongful act or any breach by Indevus of any of its obligations, representations and/or warranties hereunder, or (iv) the infringement of third parties’ intellectual property rights due to the use by Helsinn, in accordance with the terms and conditions of this Agreement, of the Specifications and/or of the Indevus Confidential Information (including but not limited to Indevus’ know-how) supplied by Indevus to Helsinn for use in connection with the manufacture of the API; in each case except to the extent caused by the negligence or willful misconduct of Helsinn, or any breach by Helsinn of any of its obligations, representations and/or warranties hereunder.
[*]
14.3 | By Each Party. In the event that negligence or willful misconduct of both Helsinn and Indevus contribute to or is determined to have contributed to, any such loss, damage, claim, injury, cost or expense, Helsinn and Indevus will each indemnify and hold harmless the other with respect to that portion of the loss, damage, claim, injury, cost or expense (including costs of defense thereof) attributable to its negligence or willful misconduct. |
[*] | CONFIDENTIAL TREATMENT REQUESTED |
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indemnified shall cooperate fully with the indemnifying party throughout the pendency of the claim, lawsuit or liability, and the indemnifying party shall have complete control over the conduct and disposition of the claim, lawsuit, or liability including the retention of legal counsel engaged to handle such matter provided, however, that, (a) neither Party shall, without the written consent of the other Party, which shall not be unreasonably withheld, as part of any settlement (i) admit to liability on the part of the other Party; (ii) agree to an injunction against the other Party; or (iii) settle any matter in a manner that separately apportions fault to the other Party and (b) the indemnified party shall be entitled to participate in any such action, suit or proceeding with counsel of its own choice, but as its own expense. If the indemnifying Party fails to assume the defense within a reasonable time, the indemnified party may assume such defense and the reasonable fees and expenses of its attorneys will be covered by the indemnifying party pursuant to the indemnity provisions provided for herein. Neither Party shall be liable for any costs resulting from any settlement made by a Party without the prior consent of the other Party to such settlement, which consent shall not be unreasonably withheld or delayed.
XV. | LIMITATION OF LIABILITY |
NOTWITHSTANDING ANY OTHER PROVISION OF THIS AGREEMENT, IN NO EVENT SHALL HELSINN OR INDEVUS BE LIABLE TO THE OTHER FOR ANY SPECIAL, INCIDENTAL, CONSEQUENTIAL OR INDIRECT DAMAGES INCLUDING, WITHOUT LIMITATION, LOSS OF PROFITS OR REVENUES, ARISING OUT OF OR IN ANY WAY RELATED TO THIS AGREEMENT WITH THE EXCEPTION OF DAMAGES ARISING OUT OF AND/OR CONNECTED WITH: (A) BREACH BY INDEVUS OF SECTION 9.1(b) POINTS (ii) AND (v) OR (B) BREACH BY HELSINN OF SECTION 9.2 DUE TO THE NON COMPLIANCE OF THE API PRODUCED BY HELSINN WITH THE SPECIFICATIONS, cGMPs AND THE QUALITY TECHNICAL AGREEMENT IN EFFECT AT THE TIME OF MANUFACTURE.
XVI. | TERMINATION |
[*] | CONFIDENTIAL TREATMENT REQUESTED |
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16.6 | Upon termination or expiration of this Agreement, Helsinn shall return to Indevus or Indevus’ nominee any and all materials in its stock and belonging to Indevus and shall deliver to Indevus, any remaining API subject to outstanding purchase orders or any Binding Portion of a forecast. Indevus shall pay Helsinn [*] of the applicable Purchase Price of such API if [*] or [*] of the Purchase Price [*]. |
XVII. | GOVERNING LAW AND ALTERNATIVE DISPUTE RESOLUTION |
17.1 | This Agreement shall be governed by and construed in accordance with the laws of the State of New York, United States, without giving effect to the conflict of laws provisions thereof. |
17.2 | The Parties agree to attempt initially to solve all claims, disputes, or controversies arising under, out of, or in connection with this Agreement (a “Dispute”) by conducting good faith negotiations. Any Disputes which cannot be resolved by good faith negotiation within sixty (60) days, shall be referred, by written notice from either Party to the other, to the Chief Executive Officers of the Parties. Such persons shall negotiate in good faith to achieve a resolution of the Dispute referred to them within thirty (30) days after such notice is received by the Party to whom the notice was sent. If such persons are unable to settle the Dispute between them within thirty (30) days, they shall so report to the Parties in writing. The Dispute shall then be referred to arbitration as set forth below. Any Dispute, controversy or claim arising out of or in connection with this Agreement, including the validity, invalidity, breach or termination thereof, which cannot be settled amicably by the Parties, shall be settled by arbitration in accordance with the rules of the International Chamber of Commerce, Paris (“ICC”) in force on the date when the Notice of Arbitration is submitted in accordance with these rules. |
The arbitration proceedings shall be held in the English language in New York City (NY, USA). The arbitral tribunal shall consist of three arbitrators with appropriate experience in the pharmaceutical industry: one arbitrator shall be appointed by each
[*] | CONFIDENTIAL TREATMENT REQUESTED |
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of Helsinn and Indevus and the third arbitrator, who shall be the Chairman of the tribunal, shall be appointed by the two Party-appointed arbitrators. The arbitrators shall not have the power to award or assess punitive damages against either Party. The arbitrators shall have the authority to grant specific performance. Any award so rendered shall be final and binding and judgment upon the award so rendered may be entered in any court having jurisdiction or application may be made to such court for judicial acceptance of any award and an order of enforcement, as the case may be. In no event shall a demand for arbitration be made after the date when institution of a legal or equitable proceeding based on such Dispute would be barred by the applicable statute of limitations. Each Party shall bear its own costs and expenses incurred in connection with any arbitration proceeding and the Parties shall equally share the costs of the arbitration levied by the ICC.
XVIII. | MISCELLANEOUS |
18.1 | Headings. The headings and captions used herein are for the convenience of the parties only and are not to be construed to define, limit or affect the construction or interpretation hereof. |
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18.11 | Counterparts. This Agreement may be executed in any number of counterparts, each of which shall be deemed an original and which together shall constitute one instrument. |
If to Indevus:
Indevus Pharmaceuticals, Inc.
00 Xxxxxx Xxxxxx
Xxxxxxxxx, XX 00000-0000, Xxxxxx Xxxxxx
Attn: Chief Executive Officer
Fax: +1 781. 862. 3859
All Helsinn invoices and/or charges in billing should be directed to the Accounting Department at:
Indevus Pharmaceuticals, Inc.
00 Xxxxxx Xxxxxx
Xxxxxxxxx, XX 00000-0000, Xxxxxx Xxxxxx
Attn: Corporate Controller
Fax: +1 781. 674.2448
If to Helsinn:
Helsinn Chemicals SA
Xxx Xxxxxxxxx 00
0000 Xxxxxx
Xxxxxxxxxxx
Attention: Commercial Division
Facsimile: + 41 91 873 01 11
All Indevus purchase orders shall be sent to:
Helsinn Chemicals SA
Xxx Xxxxxxxxx 00
0000 Xxxxxx
Xxxxxxxxxxx
Attention: Commercial Division
Facsimile: + 41 91 873 01 11
[Remainder of page intentionally left blank]
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HELSINN CHEMICALS SA | INDEVUS PHARMACEUTICALS, INC. | |||||||
/s/ Xx. Xxxxx Xxxxxxxxx | /s/ Xxxxx X. Xxxxxx, M.D. | |||||||
By: | Xx. Xxxxx Xxxxxxxxx | By: | Xxxxx X. Xxxxxx, M.D. | |||||
General Manager | Title: | Chairman and Chief Executive | ||||||
Officer |
HELSINN ADVANCED SYNTHESIS SA | ||
/s/ Xx. Xxxxxx Xxxxxxx | ||
By: | Xx. Xxxxxx Xxxxxxx | |
Managing Director |
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Schedule 1.22
Helsinn undertakes to comply with cGMP, where applicable, the Specifications, the relevant DMF in the country to which API shall be delivered, the know-how and any other requirements agreed in writing between the Parties applicable to the manufacture, storage (including raw materials) and delivery of the API. The respective responsibilities of Helsinn and Indevus with regard to applicable cGMP regulations shall be defined in detail in the Quality Technical Agreement, which shall be attached hereto as Exhibit 1.22.
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Schedule 1.26
API Specifications
The Parties have agreed upon the Specifications for the API as set forth herein. The Parties shall agree upon any modifications to the Specifications set forth herein in writing.
I. Specifications |
[*]
II. Specifications |
[*]
[*] | CONFIDENTIAL TREATMENT REQUESTED |
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Schedule 3.1
Helsinn Reserve Capacity
The minimum annual capacity to be reserved by Helsinn for the Initial Term of this Agreement is the greater of [*] batches (approximately [*] kg per batch) or [*] of the Binding Portion of any forecast. [*] months before the expiry of the Initial Term the Parties shall meet and discuss to seek an agreement in good faith on the minimum annual capacity to be reserved by Helsinn for the further term of this Agreement following the Initial Term.
[*] | CONFIDENTIAL TREATMENT REQUESTED |
Schedule 6.3
Purchase Price (1)
Subject to the terms and conditions of this Agreement, the Purchase Price/kg of API [*] shall be as follows:
A. Assuming [*]: | ||||
Number of Batches purchased per year: | Purchase Price/kg: | |||
[*] | ||||
B. Assuming [*]: | ||||
Number of Batches purchased per year: | Purchase Price/kg: | |||
[*] (2) |
(1) Based on:
(a) an exchange rate range of [*], subject to adjustment in the event the exchange rate is outside the range, based solely on the difference between the actual exchange rate and the applicable end of the range;
[*]
(c) [*]; and
(d) pricing does not include [*], which are being paid by Indevus pursuant to [*]
(2) The Parties agree to amend this schedule to provide for appropriate Purchase Prices, consistent with the overall terms and conditions of this Agreement, for purchases of other than [*] batches of API as soon as practicable after [*]
[*] | CONFIDENTIAL TREATMENT REQUESTED |