Common use of Manufacture Clause in Contracts

Manufacture. (a) Nektar shall Manufacture the Product, and prior to shipment to Amgen, store at the Facility, Release and Deliver the Product, as specified in Orders, all in compliance with the terms of this Supply Agreement including without limitation the terms of the Quality Agreement. Nektar shall meet the Standard of Care in the performance of its obligations under this Supply Agreement. Nektar shall provide all that is required or necessary to perform its obligations under this Supply Agreement including without limitation providing all permits, licenses, authorizations, registrations, labor, supervision, facilities, machinery, equipment, materials (including without limitation Raw Materials), supplies, intellectual property rights, maintenance, calibration, validation and resources. Nektar has submitted to Amgen, and Amgen has approved in writing concurrently with entering into this Supply Agreement, copies of the Manufacturing Documents. (b) Subject to the provisions of this Section 4.1, including without limitation the provisions governing Agreed Improvements and Agreed Change Costs, Amgen shall have the right, in its reasonable discretion, to make changes to any of the Amgen-Approved Manufacturing Documents and Specifications. Amgen shall submit to Nektar a Change Notification with respect to [***] that, on the Effective Date, is set forth in the Specification on Appendix G to the Quality Agreement. No later than [***] after Nektar’s receipt of each Change Notification or such longer period as specified, or agreed to (such agreement not to be unreasonably withheld or delayed), in writing by Amgen, Nektar shall revise pursuant to the Change Notification the documents that are the subject to the Change Notification and submit such revised documents to Amgen for review and approval. Concurrently and in addition, Nektar shall notify Amgen (each a “Response Notice”) of (i) any Proposed Improvements (including the schedule for undertaking and completing any Proposed Improvements which schedule may take into consideration Nektar’s other manufacturing activities at the Facility to the extent that implementation of the Proposed Improvements would result in [***] interruption of or interference with such other activities) and Proposed Change Costs and (ii) any and all intellectual property rights of Third Parties of which Nektar has knowledge that might be relevant to the Change Notification. Unless Amgen specifies or agrees in writing to a longer period, within [***] after Amgen’s receipt of each timely submitted Response Notice (the “Response Notice Review Period”), in good faith, the Parties shall discuss the Proposed Improvements and Proposed Change Costs and attempt to reach agreement on the scope and schedule of the Proposed Improvements and the Proposed Change Costs to be reimbursed to Nektar by Amgen (the aspects of the Proposed Improvements and Proposed Change Costs, and any modifications thereto, agreed in writing by the Parties shall be referred to as, respectively, the “Agreed Improvements” and “Agreed Change Costs”). With respect to each Response Notice submitted pursuant to this Section 4.1(b) on which the Parties do not reach agreement as to the scope of the Proposed Improvements or the Proposed Changes Costs to be reimbursed to Nektar by Amgen before the end of the Response Notice Review Period, a Party may escalate the review of such Response Notice and the associated Change Notification pursuant to the escalation process set forth in Section 12.18 and, if the Parties do not reach agreement as part of such escalation, then the Parties shall refer the matter to an independent Third Party with expertise in manufacturing facility operation and mutually agreed upon by the Parties, such agreement not to be unreasonably withheld or delayed (“Manufacturing Change Evaluator”). Within [***] after referral to the Manufacturing Change Evaluator, Amgen shall submit to the Manufacturing Change Evaluator the Change Notification and Response Notice, and Amgen shall cause the Manufacturing Change Evaluator to determine the scope of the Proposed Improvements and the Proposed Change Costs to be reimbursed to Nektar by Amgen. Unless Amgen withdraws or modifies the Change Notification that is the subject of the evaluation of the Manufacturing Change Evaluator, the determination of the Manufacturing Change Evaluator shall be binding on the Parties. The determination of the Manufacturing Change Evaluator shall be deemed Confidential Information hereunder. The fees and expenses of the Manufacturing Change Evaluator shall be borne by [***]. Amgen may at any time, by notice to Nektar, withdraw or modify any Change Notification, and if Amgen withdraws a Change Notification that is subject to review by a Manufacturing Change Evaluator before such evaluator makes a determination, then Amgen shall pay the fees and expenses of such Manufacturing Change Evaluator. With respect to changes to the Manufacturing Documents and the implementation thereof and changes to the Specifications, Amgen shall only be obligated to reimburse Nektar for the Agreed Change Costs and, to the extent consented to in writing and in advance by Amgen, such consent not to be unreasonably withheld, the actual costs incurred by Nektar to secure intellectual property rights from Third Parties. (c) After approval by Amgen and, as applicable and pursuant to Section 4.1(b), after establishing the Agreed Improvements and Agreed Change Costs, Nektar shall do all that is necessary or required to comply with the Amgen-Approved Manufacturing Documents. Duplicate originals of the most current Amgen-Approved Manufacturing Documents shall be maintained by each Party and shall be automatically incorporated into this Supply Agreement by reference. In Manufacturing the Product, Nektar shall comply in all respects with the most current Amgen-Approved Manufacturing Documents along with all other terms and conditions of this Supply Agreement. (d) After Nektar’s receipt of each Change Notification related to the Specifications and after establishing, as applicable and pursuant to Section 4.1(b), the Agreed Change Costs and Agreed Improvements, each such changed Specification shall be automatically incorporated into this Supply Agreement by reference.

Manufacture. (aWithout limiting the other rights and obligations of the Terminating Party(ies) Nektar under this Part 1 of Schedule D, each Terminating Party that is Manufacturing an Active Product on the effective date of termination with respect to such Terminating Party(ies) shall continue to comply with its obligations to Manufacture the applicable Active Product under Article 10 herein and the Manufacturing and Supply Agreement(s), unless it provides written notice to Tanox that it does not intend to continue to Manufacture and supply to Tanox such Active Product. After such Terminating Party(ies) provides such notice to Tanox, such Terminating Party(ies) will supply Tanox with Clinical Requirements and prior to shipment to Amgen, store Commercial Requirements of such finished and packaged Active Product(s) at the Facilitysame price and other terms and conditions as the Terminating Party(ies) was supplying, Release or in the absence of termination, would have been required to supply of such finished and Deliver the Productpackaged Active Product (under Article 10 hereof), as specified in Orders, all in compliance with the terms of this Supply Agreement including without limitation the terms until ***** of the Quality Agreement. Nektar date of Tanox’s receipt of such notice, and, if Tanox so requests no more than ***** after the date it received such notice, for *****, provided that the price at which such Active Products will be supplied for such ***** and other terms and conditions on which such Active Products will be supplied for ***** shall meet be reasonable and customary as determined by good faith negotiations between the Standard of Care in Parties, provided further that such ***** is subject to the performance of its obligations under this Supply Agreement. Nektar shall provide all that is required or necessary to perform its obligations under this Supply Agreement including without limitation providing all permits, licenses, authorizations, registrations, labor, supervision, facilities, machinery, equipment, materials (including without limitation Raw Materials), supplies, intellectual property rights, maintenance, calibration, validation and resources. Nektar has submitted to Amgen, and Amgen has approved in writing concurrently with entering into this Supply Agreement, copies reasonable cooperation of the Manufacturing Documents. (b) Subject to Party. Notwithstanding the provisions of this Section 4.1, including without limitation the provisions governing Agreed Improvements and Agreed Change Costs, Amgen shall have the rightforegoing, in its reasonable discretion, no event shall a Terminating Party be obligated to make changes to any Manufacture a higher volume of Active Product than (A) the reserved Manufacturing capacity in the Manufacturing facility(ies) of the Amgen-Approved Manufacturing Documents and Specifications. Amgen shall submit to Nektar a Change Notification with respect to [***] thatTerminating Party, on the Effective Dateor its Affiliate(s) or sublicensee(s), is as set forth in the Specification on Appendix G Manufacturing and Supply Plan or other equivalent three year Manufacturing plan, with respect to the Quality Agreement. No later than [***] after Nektar’s receipt of each Change Notification or such longer period as specified, or agreed to (such agreement not to be unreasonably withheld or delayed), in writing by Amgen, Nektar shall revise pursuant to the Change Notification the documents that are the subject to the Change Notification and submit such revised documents to Amgen for review and approval. Concurrently and in addition, Nektar shall notify Amgen (each a “Response Notice”) of (i) any Proposed Improvements (including the schedule for undertaking and completing any Proposed Improvements which schedule may take into consideration Nektar’s other manufacturing activities at the Facility to the extent that implementation ** of the Proposed Improvements would result in [transition period, and (B) the average of such Manufacturing capacity reserved for the ***] interruption ** of or interference the transition period, with such other activities) and Proposed Change Costs and (ii) any and all intellectual property rights of Third Parties of which Nektar has knowledge that might be relevant respect to the Change Notification. Unless Amgen specifies or agrees in writing to a longer period, within [***] after Amgen’s receipt of each timely submitted Response Notice (the “Response Notice Review Period”), in good faith, the Parties shall discuss the Proposed Improvements and Proposed Change Costs and attempt to reach agreement on the scope and schedule ** of the Proposed Improvements transition period. Subject to the foregoing, Genentech’s obligations under the Manufacturing and Supply Agreement, and the Proposed Change Costs to be reimbursed to Nektar by Amgen (the aspects Terminating Party’s obligations under Section 10.3 of this Agreement and Sections 5.2(a) and 5.2(c) of the Proposed Improvements JCA and Proposed Change Costs, all other related provisions (if any) under the Ancillary Agreements shall terminate. The applicable Manufacturing and any modifications thereto, agreed in writing by the Parties Supply Agreement shall be referred to as, respectively, the “Agreed Improvements” and “Agreed Change Costs”). With respect to each Response Notice submitted pursuant to this Section 4.1(b) on which the Parties do not reach agreement as to the scope of the Proposed Improvements or the Proposed Changes Costs to be reimbursed to Nektar by Amgen before terminate at the end of the Response Notice Review Period, a Party may escalate the review of such Response Notice and the associated Change Notification pursuant to the escalation process set forth in Section 12.18 and, if the Parties do not reach agreement as part of such escalation, then the Parties shall refer the matter to an independent Third Party with expertise in manufacturing facility operation and mutually agreed upon by the Parties, such agreement not to be unreasonably withheld or delayed (“Manufacturing Change Evaluator”). Within [***] after referral to the Manufacturing Change Evaluator, Amgen shall submit to the Manufacturing Change Evaluator the Change Notification and Response Notice, and Amgen shall cause the Manufacturing Change Evaluator to determine the scope of the Proposed Improvements and the Proposed Change Costs to be reimbursed to Nektar by Amgen. Unless Amgen withdraws or modifies the Change Notification that is the subject of the evaluation of the Manufacturing Change Evaluator, the determination of the Manufacturing Change Evaluator shall be binding on the Parties. The determination of the Manufacturing Change Evaluator shall be deemed Confidential Information hereunder. The fees and expenses of the Manufacturing Change Evaluator shall be borne by [***]. Amgen may at any time, by notice to Nektar, withdraw or modify any Change Notification, and if Amgen withdraws a Change Notification that is subject to review by a Manufacturing Change Evaluator before such evaluator makes a determination, then Amgen shall pay the fees and expenses of such Manufacturing Change Evaluator. With respect to changes to the Manufacturing Documents and the implementation thereof and changes to the Specifications, Amgen shall only be obligated to reimburse Nektar for the Agreed Change Costs and, to the extent consented to in writing and in advance by Amgen, such consent not to be unreasonably withheld, the actual costs incurred by Nektar to secure intellectual property rights from Third Parties. (c) After approval by Amgen and* period, as applicable and pursuant to Section 4.1(b), after establishing the Agreed Improvements and Agreed Change Costs, Nektar shall do all that is necessary or required to comply with the Amgen-Approved Manufacturing Documents. Duplicate originals of the most current Amgen-Approved Manufacturing Documents shall be maintained by each Party and shall be automatically incorporated into this Supply Agreement by reference. In Manufacturing the Product, Nektar shall comply in all respects with the most current Amgen-Approved Manufacturing Documents along with all other terms and conditions of this Supply Agreementapplicable. (d) After Nektar’s receipt of each Change Notification related to the Specifications and after establishing, as applicable and pursuant to Section 4.1(b), the Agreed Change Costs and Agreed Improvements, each such changed Specification shall be automatically incorporated into this Supply Agreement by reference.

Manufacture. (a) Nektar shall Manufacture 4.1 The parties hereby acknowledge that the Productcommercial embodiment of BIOSTATIC COATING has not been finalized by HYDROMER as of the EFFECTIVE DATE. HYDROMER agrees to use its reasonable efforts to finalize the commercial embodiment of BIOSTATIC COATING, at its expense, and agrees to notify BARD within thirty (30) days of finalization of such commercial embodiment. Promptly after receipt by BARD of the notice issued by HYDROMER pursuant to the immediately preceding sentence, if BARD notifies HYDROMER that BARD or any AFFILIATE is interested in purchasing BIOSTATIC COATING hereunder, the parties shall promptly amend and supplement the SPECIFICATIONS to include mutually acceptable specifications for BIOSTATIC COATING. 4.2 The parties hereby acknowledge that, while there is a commercial embodiment of STAY WET COATING existing on the EFFECTIVE DATE, the parties have not included the specifications relating thereto on EXHIBIT 2 as neither BARD nor any AFFILIATE has a current intention to purchase the same from HYDROMER. In the event BARD notifies HYDROMER that BARD or any AFFILIATE is interested in purchasing STAY WET COATING hereunder, the parties shall promptly amend and supplement the SPECIFICATIONS to include mutually acceptable specifications for STAY WET COATING. 4.3 If HYDROMER, at any time deems, it necessary to change any of the SPECIFICATIONS applicable to any of the COATING or applicable to any NEW COATING on which BARD exercises its right of first refusal pursuant to Section 2.3 of the LICENSE AGREEMENT, HYDROMER shall notify BARD in writing of such proposed change prior to implementation of the same. Any change to any of the SPECIFICATIONS may only be implemented upon BARD's prior written consent thereto. 4.4 At the time of shipment to Amgenof any COATING or NEW COATING ordered by BARD or any AFFILIATE hereunder, store HYDROMER shall furnish BIOSEARCH and BARD or its ordering AFFILIATE with a Certificate of Analysis, signed by an authorized representative of HYDROMER, certifying that each COATING and NEW COATING, if any, included in such shipment: (i) has been manufactured in conformity with applicable SPECIFICATIONS and, (ii) conformed with applicable SPECIFICATIONS at the Facilitytime of tender by HYDROMER to the selected carrier. 4.5 During the term of this Agreement: (i) HYDROMER shall manufacture, Release sell and Deliver the Productdeliver all SUPERSLIP COATING, as specified in OrdersSTAY WET COATING (if any) and BIOSTATIC COATING (if any ) ordered by BARD or any AFFILIATE, all in compliance accordance with the terms of this Supply Agreement including without limitation Agreement, (ii) HYDROMER shall manufacture, sell and deliver (except where HYDROMER merely possesses distribution rights in which case it shall sell and deliver) all quantities of NEW COATING on which BARD exercised its right of first refusal under Section 2.3 of the LICENSE AGREEMENT, as ordered by BARD or any of its AFFILIATES, all in accordance with the terms of the Quality Agreement. Nektar shall meet the Standard of Care in the performance of its obligations under this Supply Agreement. Nektar shall provide all that is required or necessary to perform its obligations under this Supply Agreement including without limitation providing all permits, licenses, authorizations, registrations, labor, supervision, facilities, machinery, equipment, materials (including without limitation Raw Materials), supplies, intellectual property rights, maintenance, calibration, validation and resources. Nektar has submitted to Amgen, and Amgen has approved in writing concurrently with entering into this Supply Agreement, copies of the Manufacturing Documents. (b) Subject to the provisions of this Section 4.1, including without limitation the provisions governing Agreed Improvements and Agreed Change Costs, Amgen shall have the right, in its reasonable discretion, to make changes to any of the Amgen-Approved Manufacturing Documents and Specifications. Amgen shall submit to Nektar a Change Notification with respect to [***] that, on the Effective Date, is set forth in the Specification on Appendix G to the Quality Agreement. No later than [***] after Nektar’s receipt of each Change Notification or such longer period as specified, or agreed to (such agreement not to be unreasonably withheld or delayed), in writing by Amgen, Nektar shall revise pursuant to the Change Notification the documents that are the subject to the Change Notification and submit such revised documents to Amgen for review and approval. Concurrently and in addition, Nektar shall notify Amgen (each a “Response Notice”) of (i) any Proposed Improvements (including the schedule for undertaking and completing any Proposed Improvements which schedule may take into consideration Nektar’s other manufacturing activities at the Facility to the extent that implementation of the Proposed Improvements would result in [***] interruption of or interference with such other activities) and Proposed Change Costs and (ii) any and all intellectual property rights of Third Parties of which Nektar has knowledge that might be relevant to the Change Notification. Unless Amgen specifies or agrees in writing to a longer period, within [***] after Amgen’s receipt of each timely submitted Response Notice (the “Response Notice Review Period”), in good faith, the Parties shall discuss the Proposed Improvements and Proposed Change Costs and attempt to reach agreement on the scope and schedule of the Proposed Improvements and the Proposed Change Costs to be reimbursed to Nektar by Amgen (the aspects of the Proposed Improvements and Proposed Change Costs, and any modifications thereto, agreed in writing by the Parties shall be referred to as, respectively, the “Agreed Improvements” and “Agreed Change Costs”). With respect to each Response Notice submitted pursuant to this Section 4.1(b) on which the Parties do not reach agreement as to the scope of the Proposed Improvements or the Proposed Changes Costs to be reimbursed to Nektar by Amgen before the end of the Response Notice Review Period, a Party may escalate the review of such Response Notice and the associated Change Notification pursuant to the escalation process set forth in Section 12.18 and, if the Parties do not reach agreement as part of such escalation, then the Parties shall refer the matter to an independent Third Party with expertise in manufacturing facility operation and mutually agreed upon by the Parties, such agreement not to be unreasonably withheld or delayed (“Manufacturing Change Evaluator”). Within [***] after referral to the Manufacturing Change Evaluator, Amgen shall submit to the Manufacturing Change Evaluator the Change Notification and Response Notice, and Amgen shall cause the Manufacturing Change Evaluator to determine the scope of the Proposed Improvements and the Proposed Change Costs to be reimbursed to Nektar by Amgen. Unless Amgen withdraws or modifies the Change Notification that is the subject of the evaluation of the Manufacturing Change Evaluator, the determination of the Manufacturing Change Evaluator shall be binding on the Parties. The determination of the Manufacturing Change Evaluator shall be deemed Confidential Information hereunder. The fees and expenses of the Manufacturing Change Evaluator shall be borne by [***]. Amgen may at any time, by notice to Nektar, withdraw or modify any Change Notification, and if Amgen withdraws a Change Notification that is subject to review by a Manufacturing Change Evaluator before such evaluator makes a determination, then Amgen shall pay the fees and expenses of such Manufacturing Change Evaluator. With respect to changes to the Manufacturing Documents and the implementation thereof and changes to the Specifications, Amgen shall only be obligated to reimburse Nektar for the Agreed Change Costs and, to the extent consented to in writing and in advance by Amgen, such consent not to be unreasonably withheld, the actual costs incurred by Nektar to secure intellectual property rights from Third Parties. (c) After approval by Amgen and, as applicable and pursuant to Section 4.1(b), after establishing the Agreed Improvements and Agreed Change Costs, Nektar shall do all that is necessary or required to comply with the Amgen-Approved Manufacturing Documents. Duplicate originals of the most current Amgen-Approved Manufacturing Documents shall be maintained by each Party and shall be automatically incorporated into this Supply Agreement by reference. In Manufacturing the Product, Nektar shall comply in all respects with the most current Amgen-Approved Manufacturing Documents along with all other terms and conditions of this Supply Agreement. (d) After Nektar’s receipt of each Change Notification related to the Specifications and after establishing, as applicable and pursuant to Section 4.1(b), the Agreed Change Costs and Agreed Improvements, each such changed Specification shall be automatically incorporated into this Supply Agreement by reference.

Manufacture. (a) Nektar shall Manufacture the Product, Without limiting Novartis’ other rights and prior to shipment to Amgen, store at the Facility, Release and Deliver the Product, as specified in Orders, all in compliance with the terms of this Supply Agreement including without limitation the terms of the Quality Agreement. Nektar shall meet the Standard of Care in the performance of its obligations under this Supply Agreement. Nektar Part 3 of Schedule D, if Novartis is Manufacturing an Active Product on the effective date of termination, it shall provide all that is required or necessary continue to perform comply with its obligations to Manufacture the applicable Active Product under this Article 10 herein and the Manufacturing and Supply Agreement including without limitation providing all permits, licenses, authorizations, registrations, labor, supervision, facilities, machinery, equipment, materials (including without limitation Raw MaterialsAgreement(s), suppliesunless it provides written notice to Genentech and Tanox that it does not intend to continue to Manufacture and supply to Novartis such Active Product. In the event that Novartis provides such notice to Genentech and Tanox, intellectual property rightsNovartis will supply Genentech and Tanox with Clinical Requirements and Commercial Requirements of such finished and packaged Active Product(s) at the same price and other terms and conditions as Novartis was supplying, maintenanceor in the absence of termination, calibrationwould have been required to supply of such finished and packaged Active Product (under Article 10 hereof), validation and resources. Nektar has submitted to Amgen, and Amgen has approved in writing concurrently with entering into this Supply Agreement, copies of the Manufacturing Documents. (b) Subject to the provisions of this Section 4.1, including without limitation the provisions governing Agreed Improvements and Agreed Change Costs, Amgen shall have the right, in its reasonable discretion, to make changes to any of the Amgen-Approved Manufacturing Documents and Specifications. Amgen shall submit to Nektar a Change Notification with respect to [until ***] that** the date of Genentech’s and Tanox’s receipt of such notice, and, if Genentech and Tanox both so request no more than ***** after the date it received such notice, for *****, provided that the price at which such Active Products will be supplied for such ***** and other terms and conditions on which such Active Products will be supplied for ***** shall be reasonable and customary as determined by good faith negotiations between the Effective DateParties, provided further that such ***** is subject to the reasonable cooperation of Novartis. Notwithstanding the foregoing, in no event shall Novartis be obligated to Manufacture a higher volume of Active Product than (i) the reserved manufacturing capacity in the manufacturing facility(ies) of Novartis, its Affiliate(s) or sublicense(s) as set forth in the Specification on Appendix G Manufacturing and Supply Plan, with respect to the Quality Agreement. No later than [***] after Nektar’s receipt of each Change Notification or such longer period as specified, or agreed to (such agreement not to be unreasonably withheld or delayed), in writing by Amgen, Nektar shall revise pursuant to the Change Notification the documents that are the subject to the Change Notification and submit such revised documents to Amgen for review and approval. Concurrently and in addition, Nektar shall notify Amgen (each a “Response Notice”) of (i) any Proposed Improvements (including the schedule for undertaking and completing any Proposed Improvements which schedule may take into consideration Nektar’s other manufacturing activities at the Facility to the extent that implementation ** of the Proposed Improvements would result in [***] interruption of or interference with such other activities) and Proposed Change Costs transition period, and (ii) any and all intellectual property rights the average of Third Parties of which Nektar has knowledge that might be relevant to such manufacturing capacity reserved for the Change Notification. Unless Amgen specifies or agrees in writing to a longer period, within [***] after Amgen’s receipt ** of each timely submitted Response Notice (the “Response Notice Review Period”)transition period, in good faithwith respect to the ***** of the transition period. Subject to the foregoing, Novartis’ obligations under Section 10.3 of this Agreement, the Parties shall discuss the Proposed Improvements Manufacturing and Proposed Change Costs Supply Agreement and attempt to reach agreement on the scope Sections 5.2(a) and schedule 5.2(c) of the Proposed Improvements JCA and all other related provisions (if any) under the Proposed Change Costs to be reimbursed to Nektar by Amgen (the aspects of the Proposed Improvements Ancillary Agreements shall terminate. The applicable Manufacturing and Proposed Change Costs, and any modifications thereto, agreed in writing by the Parties Supply Agreement shall be referred to as, respectively, the “Agreed Improvements” and “Agreed Change Costs”). With respect to each Response Notice submitted pursuant to this Section 4.1(b) on which the Parties do not reach agreement as to the scope of the Proposed Improvements or the Proposed Changes Costs to be reimbursed to Nektar by Amgen before terminate at the end of the Response Notice Review Period, a Party may escalate the review of such Response Notice and the associated Change Notification pursuant to the escalation process set forth in Section 12.18 and, if the Parties do not reach agreement as part of such escalation, then the Parties shall refer the matter to an independent Third Party with expertise in manufacturing facility operation and mutually agreed upon by the Parties, such agreement not to be unreasonably withheld or delayed (“Manufacturing Change Evaluator”). Within [***] after referral to the Manufacturing Change Evaluator, Amgen shall submit to the Manufacturing Change Evaluator the Change Notification and Response Notice, and Amgen shall cause the Manufacturing Change Evaluator to determine the scope of the Proposed Improvements and the Proposed Change Costs to be reimbursed to Nektar by Amgen. Unless Amgen withdraws or modifies the Change Notification that is the subject of the evaluation of the Manufacturing Change Evaluator, the determination of the Manufacturing Change Evaluator shall be binding on the Parties. The determination of the Manufacturing Change Evaluator shall be deemed Confidential Information hereunder. The fees and expenses of the Manufacturing Change Evaluator shall be borne by [***]. Amgen may at any time, by notice to Nektar, withdraw or modify any Change Notification, and if Amgen withdraws a Change Notification that is subject to review by a Manufacturing Change Evaluator before such evaluator makes a determination, then Amgen shall pay the fees and expenses of such Manufacturing Change Evaluator. With respect to changes to the Manufacturing Documents and the implementation thereof and changes to the Specifications, Amgen shall only be obligated to reimburse Nektar for the Agreed Change Costs and, to the extent consented to in writing and in advance by Amgen, such consent not to be unreasonably withheld, the actual costs incurred by Nektar to secure intellectual property rights from Third Parties. (c) After approval by Amgen and* period, as applicable and pursuant to Section 4.1(b), after establishing the Agreed Improvements and Agreed Change Costs, Nektar shall do all that is necessary or required to comply with the Amgen-Approved Manufacturing Documents. Duplicate originals of the most current Amgen-Approved Manufacturing Documents shall be maintained by each Party and shall be automatically incorporated into this Supply Agreement by reference. In Manufacturing the Product, Nektar shall comply in all respects with the most current Amgen-Approved Manufacturing Documents along with all other terms and conditions of this Supply Agreementapplicable. (d) After Nektar’s receipt of each Change Notification related to the Specifications and after establishing, as applicable and pursuant to Section 4.1(b), the Agreed Change Costs and Agreed Improvements, each such changed Specification shall be automatically incorporated into this Supply Agreement by reference.

Manufacture. (a) Nektar 6.1. The final sentence of Clause 11.1 of the Original Agreement is hereby amended by replacing the references to “Clause 11.3” in each case with the phrase “Clause 11.3 or Clause 11.6”. 6.2. Clause 11.2 of the Original Agreement is hereby amended by deleting the clause following Clause 11.2.2 and replacing it with the following text: “ and where this Clause 11.2 applies Licensor shall Manufacture the Product, and prior continue to shipment to Amgen, store at the Facility, Release and Deliver the Product, as specified in Orders, all in compliance with supply Product under the terms of this Supply Agreement including without limitation Agreement, unless and until such Second Source has been validated and has commenced and scaled up manufacture to satisfy the requirements for Product of Licensee. Licensee shall provide Licensor with written notice no later than [*] ([*]) Business Days after the Second Source has been validated and has commenced and scaled up manufacture to satisfy the requirements for Product of Licensee, following which notice (or, in the absence of such notice, the date on which such notice ought to have been given) Licensor shall have the option (but not the obligation) at any time thereafter upon service of not less than [*] ([*]) days notice in writing to cease to supply Product to Licensee. Licensee shall use Commercially Reasonable Efforts to cause Novel to qualify, validate and scale up manufacture, and Actavis to supply, by [*]. For the avoidance of doubt, Licensor (i) hereby expressly consents to and acknowledges the appointment by Licensee pursuant to this Clause 11.2 of Novel as the Second Source and of Novel and Actavis as Licensee’s sub-contractors and to the terms of the Quality Agreement. Nektar shall meet Supply Agreement (excluding those provisions of the Standard of Care Supply Agreement that have been redacted in the performance of its obligations under this Supply Agreement. Nektar shall provide all that is required or necessary version supplied to perform its obligations under this Supply Agreement including without limitation providing all permits, licenses, authorizations, registrations, labor, supervision, facilities, machinery, equipment, materials (including without limitation Raw MaterialsLicensor), suppliesprovided that, intellectual property rights, maintenance, calibration, validation and resources. Nektar has submitted to Amgen, and Amgen has approved notwithstanding any provisions in writing concurrently with entering into this the Supply Agreement, copies of Licensee shall have the Manufacturing Documents. right to select and use a Second Source other than Novel only in accordance with this Clause 11, and (bii) Subject agrees to comply with the provisions of this Section 4.1Clause 11 relating to assistance with technology transfer and the obtaining of Regulatory Approvals necessary for Novel to act as Second Source, including and agrees to do so on a reasonably timely and expeditious basis so as to facilitate and enable the qualification, validation and scale up of Novel as Second Source by [*], or as soon thereafter as possible, but in any event by [*]. For avoidance of doubt, (i) no consent is granted by Licensor to any amendment to or waiver of the Supply Agreement, except as may be subsequently provided by Licensor in a written agreement with Licensee; (ii) Novel and Actavis shall be deemed Licensee’s sub-contractors, and not Licensor’s sub-contractors, for purposes of this Agreement and, without limitation limiting or qualifying Licensor’s obligations pursuant to clause (ii) of the provisions governing Agreed Improvements preceding sentence, as between Licensor and Agreed Change CostsLicensee, Amgen Licensee shall be responsible for arranging and coordinating the technology transfer to Novel and for obtaining any Regulatory Approvals necessary for Novel to act as a Second Source and Actavis to supply Product; and (iii) without limiting Licensor’s obligation to comply with this Clause 11, Licensor makes no representations, warranties or promises that Novel will be qualified, validated or commence and scale up manufacture, or that Actavis will commence supply, to satisfy the requirements of Licensee for Product.” 6.3. Clause 11.4.2 of the Original Agreement is hereby amended to read in its entirety as follows: “All Product and Authorized Generic Product shall be manufactured in the manner specified in the Initial NDA and in accordance with GMP and the Specifications and the Packaging and Labelling for any Product or Authorized Generic Product shall accurately identify Licensee or the Second Source as the manufacturer of such Product or Authorized Generic Product, as the case may be;” 6.4. Clause 11.4.4 of the Original Agreement is hereby amended by deleting the term “NDA” and replacing it with the term “Initial NDA”. 6.5. Clause 11.5 of the Original Agreement is hereby amended to read in its entirety as follows: “Without limiting Licensor’s right to cease supply of Product under Clause 11.2, from and after [*], Licensor shall have the right, in its reasonable discretion, to make changes to any option (but no obligation) upon service of the Amgen-Approved Manufacturing Documents and Specifications. Amgen shall submit to Nektar a Change Notification with respect to [***] that, on the Effective Date, is set forth in the Specification on Appendix G to the Quality Agreement. No later not less than [***] after Nektar’s receipt of each Change Notification or such longer period as specified, or agreed to (such agreement not to be unreasonably withheld or delayed), in writing by Amgen, Nektar shall revise pursuant to the Change Notification the documents that are the subject to the Change Notification and submit such revised documents to Amgen for review and approval. Concurrently and in addition, Nektar shall notify Amgen (each a “Response Notice”) of (i) any Proposed Improvements (including the schedule for undertaking and completing any Proposed Improvements which schedule may take into consideration Nektar’s other manufacturing activities at the Facility to the extent that implementation of the Proposed Improvements would result in [***] interruption of or interference with such other activities]) and Proposed Change Costs and (ii) any and all intellectual property rights of Third Parties of which Nektar has knowledge that might be relevant months notice in writing, to the Change Notification. Unless Amgen specifies or agrees in writing to a longer period, within [***] after Amgen’s receipt of each timely submitted Response Notice (the “Response Notice Review Period”), in good faith, the Parties shall discuss the Proposed Improvements and Proposed Change Costs and attempt to reach agreement on the scope and schedule of the Proposed Improvements and the Proposed Change Costs to be reimbursed to Nektar by Amgen (the aspects of the Proposed Improvements and Proposed Change Costs, and any modifications thereto, agreed in writing by the Parties shall be referred to as, respectively, the “Agreed Improvements” and “Agreed Change Costs”). With respect to each Response Notice submitted pursuant to this Section 4.1(b) on which the Parties do not reach agreement as to the scope of the Proposed Improvements or the Proposed Changes Costs to be reimbursed to Nektar by Amgen before expire at the end of a Year, to cease to supply Product to Licensee, under the Response Notice Review Period, terms of this Agreement.” 6.6. Clause 11 of the Original Agreement is hereby amended by adding a Party may escalate new Clause 11.6 and a new Clause 11.7 at the review of such Response Notice and the associated Change Notification pursuant to the escalation process set forth in Section 12.18 and, if the Parties do not reach agreement as part of such escalation, then the Parties shall refer the matter to an independent Third Party with expertise in manufacturing facility operation and mutually agreed upon by the Partiesend thereof, such agreement not new clauses to be unreasonably withheld or delayed (“Manufacturing Change Evaluator”). Within [***] after referral to the Manufacturing Change Evaluator, Amgen shall submit to the Manufacturing Change Evaluator the Change Notification and Response Notice, and Amgen shall cause the Manufacturing Change Evaluator to determine the scope of the Proposed Improvements and the Proposed Change Costs to be reimbursed to Nektar by Amgen. Unless Amgen withdraws or modifies the Change Notification that is the subject of the evaluation of the Manufacturing Change Evaluator, the determination of the Manufacturing Change Evaluator shall be binding on the Parties. The determination of the Manufacturing Change Evaluator shall be deemed Confidential Information hereunder. The fees and expenses of the Manufacturing Change Evaluator shall be borne by [***]. Amgen may at any time, by notice to Nektar, withdraw or modify any Change Notification, and if Amgen withdraws a Change Notification that is subject to review by a Manufacturing Change Evaluator before such evaluator makes a determination, then Amgen shall pay the fees and expenses of such Manufacturing Change Evaluator. With respect to changes to the Manufacturing Documents and the implementation thereof and changes to the Specifications, Amgen shall only be obligated to reimburse Nektar for the Agreed Change Costs and, to the extent consented to in writing and in advance by Amgen, such consent not to be unreasonably withheld, the actual costs incurred by Nektar to secure intellectual property rights from Third Parties. (c) After approval by Amgen and, read as applicable and pursuant to Section 4.1(b), after establishing the Agreed Improvements and Agreed Change Costs, Nektar shall do all that is necessary or required to comply with the Amgen-Approved Manufacturing Documents. Duplicate originals of the most current Amgen-Approved Manufacturing Documents shall be maintained by each Party and shall be automatically incorporated into this Supply Agreement by reference. In Manufacturing the Product, Nektar shall comply in all respects with the most current Amgen-Approved Manufacturing Documents along with all other terms and conditions of this Supply Agreement. (d) After Nektar’s receipt of each Change Notification related to the Specifications and after establishing, as applicable and pursuant to Section 4.1(b), the Agreed Change Costs and Agreed Improvements, each such changed Specification shall be automatically incorporated into this Supply Agreement by reference.follows:

Manufacture. Recordati (aand Recordati's Nominee or the Second Source, if applicable) Nektar will comply in all material respects with the good manufacturing practices set forth in (U.S.) 21 C.F.R. Part 211 or, to the extent not conflicting therewith, any other Regulatory Authority in an applicable country ("GMP") and consents to inspection of its manufacturing facilities and shall Manufacture obtain the Productright for an inspection of any manufacturing facilities of Recordati's Nominee or the Second Source by representatives of the FDA or by the Regulatory Authority in any country where the Finished Product(s) are sold. All Finished Product supplied to Ascent by Recordati (or Recordati's Nominee or the Second Source, if applicable) hereunder will be manufactured, packaged, tested and released for Clinical Testing and sale under GMP. Recordati shall supply the Finished Product in strict accordance with the specifications set forth in Schedule 2 attached hereto (Schedule 2 "Finished Product Specifications") which shall be specified by Ascent initially during human clinical/pharmacokinetic trials and be finalized prior to shipment or upon the grant of Regulatory Approval in each country of the Territory with Ascent having the right to Amgenreasonably request changes to the Finished Product Specifications from time to time. Recordati shall manufacture and supply the Finished Product strictly in accordance with all applicable laws, store at rules and regulations, including without limitation laws, rules and regulations that may be applicable as a result of Ascent's Clinical Testing or sale of the FacilityFinished Product for use in humans, Release such as the current GMP. Recordati shall ensure and Deliver be responsible for the Product, as specified existence and maintenance of quality control/quality assurance procedures designed to ensure that the Finished Product is manufactured in Orders, all in compliance accordance with the terms of this Supply Agreement including without limitation Section 2.4. Recordati shall also establish procedures that will permit lot traceability and shall be responsible for post-approval stability testing for marketed batches of Finished Product as defined in the terms applicable PLA submission to the FDA. Recordati, Recordati's Nominee or the Second Source shall immediately notify Ascent in the event that Recordati or Recordati's Nominee or the Second Source, if applicable, becomes aware of any failure of the Quality Agreement. Nektar shall Finished Product supplied to Ascent to meet the Standard of Care in the performance of its obligations under this Supply Agreement. Nektar shall provide all that is required Finished Product Specifications or necessary to perform its obligations under this Supply Agreement including without limitation providing all permits, licenses, authorizations, registrations, labor, supervision, facilities, machinery, equipment, materials (including without limitation Raw Materials), supplies, intellectual property rights, maintenance, calibration, validation and resources. Nektar has submitted to Amgen, and Amgen has approved in writing concurrently with entering into this Supply Agreement, copies of the Manufacturing Documents. (b) Subject to the provisions of this Section 4.1, including without limitation the provisions governing Agreed Improvements and Agreed Change Costs, Amgen shall have the right, in its reasonable discretion, to make changes to any of the Amgen-Approved Manufacturing Documents and Specifications. Amgen shall submit to Nektar a Change Notification with respect to [***] that, on the Effective Date, is other standards set forth in this Section 2.4 or in the Specification on Appendix G event that Recordati or Recordati's Nominee or the Second Source becomes aware of any defect in Finished Product supplied to Ascent. It is understood that Recordati's obligations hereunder relate to the Quality Agreement. No later than [***] after Nektar’s receipt manufacture and supply of each Change Notification or such longer period as specified, or agreed to (such agreement not to be unreasonably withheld or delayed), Finished Products in writing by Amgen, Nektar shall revise pursuant to the Change Notification the documents that are the subject to the Change Notification and submit such revised documents to Amgen for review and approval. Concurrently and in addition, Nektar shall notify Amgen (each a “Response Notice”) of (i) any Proposed Improvements (including the schedule for undertaking and completing any Proposed Improvements which schedule may take into consideration Nektar’s other manufacturing activities at the Facility to the extent that implementation of the Proposed Improvements would result in [***] interruption of or interference with such other activities) and Proposed Change Costs and (ii) any and all intellectual property rights of Third Parties of which Nektar has knowledge that might be relevant to the Change Notification. Unless Amgen specifies or agrees in writing to a longer period, within [***] after Amgen’s receipt of each timely submitted Response Notice (the “Response Notice Review Period”), in good faith, the Parties shall discuss the Proposed Improvements and Proposed Change Costs and attempt to reach agreement on the scope and schedule of the Proposed Improvements and the Proposed Change Costs to be reimbursed to Nektar by Amgen (the aspects of the Proposed Improvements and Proposed Change Costs, and any modifications thereto, agreed in writing by the Parties shall be referred to as, respectively, the “Agreed Improvements” and “Agreed Change Costs”). With respect to each Response Notice submitted pursuant to this Section 4.1(b) on which the Parties do not reach agreement as to the scope of the Proposed Improvements or the Proposed Changes Costs to be reimbursed to Nektar by Amgen before the end of the Response Notice Review Period, a Party may escalate the review of such Response Notice and the associated Change Notification pursuant to the escalation process set forth in Section 12.18 and, if the Parties do not reach agreement as part of such escalation, then the Parties shall refer the matter to an independent Third Party with expertise in manufacturing facility operation and mutually agreed upon by the Parties, such agreement not to be unreasonably withheld or delayed (“Manufacturing Change Evaluator”). Within [***] after referral to the Manufacturing Change Evaluator, Amgen shall submit to the Manufacturing Change Evaluator the Change Notification and Response Notice, and Amgen shall cause the Manufacturing Change Evaluator to determine the scope of the Proposed Improvements and the Proposed Change Costs to be reimbursed to Nektar by Amgen. Unless Amgen withdraws or modifies the Change Notification that is the subject of the evaluation of the Manufacturing Change Evaluator, the determination of the Manufacturing Change Evaluator shall be binding on the Parties. The determination of the Manufacturing Change Evaluator shall be deemed Confidential Information hereunder. The fees and expenses of the Manufacturing Change Evaluator shall be borne by [***]. Amgen may at any time, by notice to Nektar, withdraw or modify any Change Notification, and if Amgen withdraws a Change Notification that is subject to review by a Manufacturing Change Evaluator before such evaluator makes a determination, then Amgen shall pay the fees and expenses of such Manufacturing Change Evaluator. With respect to changes to the Manufacturing Documents and the implementation thereof and changes to the Specifications, Amgen shall only be obligated to reimburse Nektar for the Agreed Change Costs and, to the extent consented to in writing and in advance by Amgen, such consent not to be unreasonably withheld, the actual costs incurred by Nektar to secure intellectual property rights from Third Parties. (c) After approval by Amgen and, as applicable and pursuant to Section 4.1(b), after establishing the Agreed Improvements and Agreed Change Costs, Nektar shall do all that is necessary or required to comply accordance with the Amgen-Approved Manufacturing Documents. Duplicate originals of the most current Amgen-Approved Manufacturing Documents shall be maintained by each Party and shall be automatically incorporated into this Supply Agreement by reference. In Manufacturing the Product, Nektar shall comply in all respects with the most current Amgen-Approved Manufacturing Documents along with all other terms and conditions of this Supply AgreementFinished Product Specifications. (d) After Nektar’s receipt of each Change Notification related to the Specifications and after establishing, as applicable and pursuant to Section 4.1(b), the Agreed Change Costs and Agreed Improvements, each such changed Specification shall be automatically incorporated into this Supply Agreement by reference.