Common use of Specification Changes Clause in Contracts

Specification Changes. In the event that ORPHAN wishes to change the Specifications, or in the event that ORPHAN is required to change the Specifications pursuant to applicable law or regulation or in response to the order or request of a governmental authority or regulatory body, the following provisions will apply. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED. (1) ORPHAN shall promptly advise Catalytica in writing of any such change(s) to the Specifications, and Catalytica shall promptly advise ORPHAN as to any scheduling and/or Product Price adjustments which may result from any such change(s), if any. The notification and approval procedure shall be in accordance with APPENDIX F, as well as any additional standard operating procedures (i.e., change control procedures) agreed upon by ORPHAN and Catalytica in writing from time to time. (2) Prior to implementation of such change(s) to the Specifications, ORPHAN and Catalytica shall negotiate in good faith in an attempt to reach agreement on (i) the new Product Price, if any, for any Drug Product and/or Finished Product provided hereunder by Catalytica which embodies such change(s) to the Specifications, giving due consideration to the effect of such change(s) on Catalytica’s manufacturing costs for Drug Product and/or Finished Product and (ii) any other amendments to this Agreement which may be necessitated by such changes (e.g., an adjustment to the lead time for Firm Orders). Implementation of such change(s) to the Specifications shall be as set forth in APPENDIX F. (3) ORPHAN will reimburse Catalytica for the reasonable and necessary expenses incurred by Catalytica as a result of any such change(s) to the Specifications [ * ]. (4) If any such change(s) to the Specifications renders obsolete or unusable any materials or components for Drug Product or Finished Product, and to the extent such materials or components may not be returned to the appropriate vendor for a credit [ * ] that amount of inventory of materials or components, as the case may be, so rendered obsolete or unusable, not to exceed the amount of such materials or components which would have been required for [ * ]. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED.

Specification Changes. In the event that ORPHAN wishes Immunex and Wyeth wish to change the Specifications, or in the event that ORPHAN is Immunex and Wyeth are required to change the Specifications pursuant to applicable law law, rule or regulation or in response to the order or request of a governmental authority or regulatory body, the following provisions will apply. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED. (1) ORPHAN Buyer shall promptly advise Catalytica BIP in writing of any such change(s) to the Specifications, and Catalytica BIP shall promptly advise ORPHAN Buyer as to any scheduling and/or Product Price adjustments which may result from any such change(s), if any. The notification and approval procedure shall be in accordance with APPENDIX F, as well as any additional standard operating procedures (i.e.I.E., change control procedures) agreed upon by ORPHAN Buyer and Catalytica in writing BIP from time to time. (2) Prior to implementation of such change(s) to the Specifications, ORPHAN and Catalytica shall the Parties agree to negotiate in good faith in an attempt to reach agreement on (i) the new Product Price, if any, for any Bulk Drug Substance, Drug Product and/or Finished Product provided manufactured hereunder by Catalytica BIP which embodies such change(s) to the Specifications, giving due consideration to the effect of such change(s) on Catalytica’s BIP's direct manufacturing costs for Bulk Drug Substance, Drug Product and/or Finished Product and (ii) any other amendments to this Agreement which may be necessitated by such changes (e.g.E.G., an adjustment to the lead time for Firm Orders). Implementation of such change(s) to the Specifications shall be as set forth in APPENDIX F.. (3) ORPHAN Buyer will reimburse Catalytica BIP for the reasonable and necessary expenses incurred by Catalytica BIP as a result of any such change(s) to the Specifications [ * ]Specifications, including, but not limited to, reimbursing BIP for its validation and analytical development costs and capital expenditure costs. (4) BIP shall cooperate with Immunex and Wyeth in good faith to implement all changes to the Specifications as soon as practicable after notice thereof, but in any event within [*] ([*]) days' "lead time," unless otherwise agreed upon by the Parties or required by an applicable regulatory authority. Buyer shall not unreasonably require BIP to implement changes to the Specifications within such [*] ([*])-day period if such changes would typically require BIP a longer period of time to implement. (5) If any such change(s) to the Specifications renders obsolete or unusable any raw materials for Bulk Drug Substance or packaging components for Drug Product or Finished Product, and to the extent such raw materials or packaging components may not be either returned to the appropriate vendor for a credit [ * ] or utilized by BIP for its other manufacturing operations, Buyer shall purchase from BIP, at BIP's Acquisition Cost, that amount of inventory of such raw materials or and/or packaging components, as the case may be, so rendered obsolete or unusable, not to exceed the amount of such raw materials or and/or packaging components which would have been required for [ * ]. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENTBIP to manufacture and supply the total quantity of Bulk Drug Substance, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDEDDrug Product and/or Finished Product specified in Firm Orders issued hereunder.

Specification Changes. In the event that ORPHAN wishes to change the Specifications, or in the event that ORPHAN is required to change the Specifications pursuant to applicable law or regulation or in response to the order or request of a governmental authority or regulatory body, the following provisions will apply. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED. (1) ORPHAN shall promptly advise Catalytica in writing of any such change(s) to the Specifications, and Catalytica shall promptly advise ORPHAN as to any scheduling and/or Product Price adjustments which may result from any such change(s), if any. The notification and approval procedure shall be in accordance with APPENDIX F, as well as any additional standard operating procedures (i.e., change control procedures) agreed upon by ORPHAN and Catalytica in writing from time to time. (2) Prior to implementation of such change(s) to the Specifications, ORPHAN and Catalytica shall negotiate in good faith in an attempt to reach agreement on (i) the new Product Price, if any, for any Drug Product and/or Finished Product provided hereunder by Catalytica which embodies such change(s) to the Specifications, giving due consideration to the effect of such change(s) on Catalytica’s manufacturing costs for Drug Product and/or Finished Product and (ii) any other amendments to this Agreement which may be necessitated by such changes (e.g., an adjustment to the lead time for Firm Orders). Implementation of such change(s) to the Specifications shall be as set forth in APPENDIX F. (3) ORPHAN will reimburse Catalytica for the reasonable and necessary expenses incurred by Catalytica as a result of any such change(s) to the Specifications [ * ], including, but not limited to, reimbursing Catalytica for its validation and development costs and capital expenditure costs. (4) If any such change(s) to the Specifications renders obsolete or unusable any materials or components for Drug Product or Finished Product, and to the extent such materials or components may not be returned to the appropriate vendor for a credit [ * ] , ORPHAN shall purchase from Catalytica, at Catalytica’s Acquisition Cost, that amount of inventory of materials or components, as the case may be, so rendered obsolete or unusable, not to exceed the amount of such materials or components which would have been required for [ * ]. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDEDCatalytica to manufacture and supply the total quantity of Drug Product and/or Finished Product specified in Firm Orders currently pending and not yet filled hereunder.

Specification Changes. (i) In the event that ORPHAN wishes to change the BioHorizons changes any Specifications, or then the Parties will negotiate any appropriate change in pricing based on such changes. In the event that ORPHAN is required to change the Specifications Parties cannot agree on revised pricing, BioHorizons shall be relieved of its obligation pursuant to applicable law or regulation or in response to the order or request of a governmental authority or regulatory body, the following provisions will apply. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDEDSection 1(m). (1ii) ORPHAN shall promptly advise Catalytica In the event that BioHorizons changes any Specifications such that inventory stored at Manufacturer’s facility pursuant to (i) becomes obsolete, then within ninety (90) days of the date BioHorizons notified Manufacturer of such change, BioHorizons will (x) order any Products that were finished product stored at Manufacturer’s facility pursuant to (i) or (y) pay Manufacturer for such Products and request that Manufacturer discard or destroy such Products at no charge to BioHorizons. With respect to any Products that were work in writing progress based on a purchase order or compliance with (i) on the date BioHorizons notified Manufacturer of any such change(schange, BioHorizons will make payment, within ninety (90) days of the date BioHorizons notified Manufacturer of such change, of the price of such Products less a discount to be determined in good faith by Manufacturer based on its cost savings from not having to finish such Products. BioHorizons will notify manufacturer of its decision to have Manufacturer deliver such work in progress to BioHorizons or have Manufacturer discard or destroy such Products at no charge to BioHorizons. (iii) In no event will BioHorizons be liable to Manufacturer pursuant to this Section 1(p) for inventory in excess of the sum of (x) the minimum required to be maintained by Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the SpecificationsRegistrant’s application requesting confidential treatment pursuant to Rule 406 of the Securities Act of 1933, and Catalytica shall promptly advise ORPHAN as to any scheduling and/or Product Price adjustments which may result from any such change(s), if anyamended. The notification and approval procedure shall be Manufacturer in accordance with APPENDIX F, as well as any additional standard operating procedures Section 1(i) plus (i.e., change control procedures) agreed upon by ORPHAN and Catalytica in writing from time to time. (2) Prior to implementation of such change(s) to the Specifications, ORPHAN and Catalytica shall negotiate in good faith in an attempt to reach agreement on (iy) the new Product Price, if any, for any Drug Product and/or Finished Product provided hereunder by Catalytica which embodies such change(s) amount subject to an open purchase order at the Specifications, giving due consideration to time of the effect of such change(s) on Catalytica’s manufacturing costs for Drug Product and/or Finished Product and (ii) any other amendments to this Agreement which may be necessitated by such changes (e.g., an adjustment to the lead time for Firm Orders). Implementation of such change(s) to the Specifications shall be as set forth in APPENDIX F. (3) ORPHAN will reimburse Catalytica for the reasonable and necessary expenses incurred by Catalytica as a result of any such change(s) to the Specifications [ * ]Specification change. (4) If any such change(s) to the Specifications renders obsolete or unusable any materials or components for Drug Product or Finished Product, and to the extent such materials or components may not be returned to the appropriate vendor for a credit [ * ] that amount of inventory of materials or components, as the case may be, so rendered obsolete or unusable, not to exceed the amount of such materials or components which would have been required for [ * ]. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED.

Specification Changes. In the event that ORPHAN wishes to change 5.6.1 If AMAG changes the Specifications, or in the event that ORPHAN is required to change the Specifications pursuant to applicable law or regulation or in response to the order or request of a governmental authority or regulatory body, the following provisions will apply. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED. (1) ORPHAN AMAG shall promptly advise Catalytica DSM in writing of any such change(s) to the Specificationschanges; and if such changes directly impact DSM’s scheduling or costs, and Catalytica DSM shall promptly advise ORPHAN AMAG as to any scheduling and/or Product Price price adjustments which may result from any caused by such change(s), if anychanges. The notification and approval procedure shall be in accordance with APPENDIX F, as well as any additional standard operating procedures (i.e., change control procedures) agreed upon by ORPHAN and Catalytica in writing from time to time. (2) Prior to implementation of such change(s) changes, the Parties agree to the Specifications, ORPHAN and Catalytica shall negotiate in good faith in an attempt to reach agreement on (ia) the new Product Priceprice for any Product, if any, for any Drug Product and/or Finished Product provided hereunder by Catalytica which embodies such change(s) changes, reflecting any direct increases to DSM in the Specificationscost or quantities of materials consumed, giving due consideration to provided that the price shall not change more than the direct effect of such change(s) changes on CatalyticaDSM’s manufacturing costs for Drug Product and/or Finished Product the Product, and (iib) any other amendments to this Agreement which may be necessitated by such changes (e.g.i.e., an adjustment to the lead time for Firm Purchase Orders). Implementation of such change(s) In no event shall DSM withhold its consent for any proposed change to the Specifications shall be as set forth in APPENDIX F.required by a Regulatory Authority if AMAG agrees to bear the direct cost incurred by DSM necessary to comply with such Specification change. (3) ORPHAN will 5.6.2 AMAG agrees to reimburse Catalytica DSM for the reasonable expenses addressed in the applicable Specification Change amendment and necessary expenses incurred by Catalytica DSM as a result of such changes, including, but not limited to, reimbursing DSM for its validation and development costs, capital expenditure costs and costs for any such change(s) to the Specifications [ * ]. (4) If any such change(s) to the Specifications renders obsolete packaging components or other materials rendered unusable any materials or components for Drug Product or Finished Product, and to the extent such materials or components may not be returned to the appropriate vendor for by AMAG as a credit [ * ] that amount of inventory of materials or components, as the case may be, so rendered obsolete or unusable, not to exceed the amount result of such materials or components which would have been required for [ * ]changes. [ * [***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF 24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 19331934, AS AMENDED. 5.6.3 If during the term of this Agreement AMAG amends or is required by law to amend the Specifications so as to render the Active Pharmaceutical Ingredients, Excipients and/or packaging components for any Product obsolete, AMAG shall, at AMAG’s option, (a) purchase from DSM, at DSM’s Acquisition Cost, that amount of inventory of Excipients and packaging components so rendered obsolete, or (b) accept DSM’s return of such materials to AMAG and reimburse DSM any restocking fees incurred; and AMAG shall also purchase from DSM, at the applicable Product Price, any amounts of Product ordered under a Firm Purchase Commitment (plus any agreed long lead-time material) which is rendered obsolete. AMAG shall reimburse DSM for its reasonable shipping and handling costs for returned or destroyed obsolete inventories. 5.6.4 DSM shall not make any change to the Specifications without AMAG’s prior written consent. Any change to the Specifications requested by DSM that is not the result of a Regulatory Authority requirement, shall be at DSM’s sole expense, unless otherwise agreed upon in writing.

Specification Changes. In the event that ORPHAN wishes to change 5.5.1 If, for whatever reasons, Discovery Labs changes the Specifications, or in the event that ORPHAN is required to change the Specifications pursuant to applicable law or regulation or in response to the order or request of a governmental authority or regulatory body, the following provisions will apply. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED. (1) ORPHAN Discovery Labs shall promptly advise Catalytica DSM in writing of any such change(s) to the Specificationschanges; and if such changes directly impact DSM’s scheduling or costs, and Catalytica DSM shall promptly advise ORPHAN Discovery Labs as to any scheduling and/or Product Price price adjustments which may result from any caused by such change(s), if anychanges. The notification and approval procedure shall be in accordance with APPENDIX F, as well as any additional standard operating procedures (i.e., change control procedures) agreed upon by ORPHAN and Catalytica in writing from time to time. (2) Prior to implementation of such change(s) changes, the Parties agree to the Specifications, ORPHAN and Catalytica shall negotiate in good faith in an attempt to reach agreement on (ia) the new Product Price, if any, price for any Drug Product and/or Finished Product provided hereunder by Catalytica which embodies such change(s) changes, reflecting any increases to DSM in the Specificationscost or quantities of materials consumed, giving due consideration to provided that the price shall not change more than the direct effect of such change(s) changes on CatalyticaDSM’s manufacturing costs for Drug Product and/or Finished Product the Product, and (iib) any other amendments to this Agreement which may be necessitated by such changes (e.g., an adjustment to the lead time for Firm Purchase Orders). Implementation of such change(s) , said changes to the Specifications shall be as set forth in APPENDIX F.writing and signed by both parties. (3) ORPHAN will 5.5.2 Discovery Labs agrees to reimburse Catalytica DSM for the reasonable and necessary expenses incurred by Catalytica DSM as a result of such agreed-upon changes, including, but not limited to, reimbursing DSM for its validation and development costs, capital expenditure costs and costs for any packaging components or other materials rendered unusable as a result of such change(s) changes. 5.5.3 If during the term of this Agreement Discovery Labs amends or is required by law to amend the Specifications [ * ]. (4) If any such change(s) so as to render the Specifications renders obsolete or unusable any materials or Active Pharmaceutical Ingredients, Excipients and/or packaging components for Drug any Product or Finished Productobsolete, and to the extent such materials or components may not be returned to the appropriate vendor for a credit [ * ] Discovery Labs shall at Discovery Labs option, purchase from DSM, at DSM’s Acquisition Cost, that amount of inventory of materials or components, as the case may be, Excipients and packaging components so rendered obsolete obsolete, or unusable, not to exceed the amount accept DSM’s return of such materials or components to Discovery Labs and reimburse DSM any restocking fees incurred; and Discovery Labs shall also purchase from DSM, at the applicable Product Price, that amount of inventory of Product which would have been required for is rendered obsolete. [ *** ]. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED 5.5.4 DSM shall not make any change to the Specifications without Discovery Labs prior written consent.

Specification Changes. In Upon any change in the event that ORPHAN wishes to change the Product Specifications, stability protocols, QC laboratory methods raw material specification or in the event that ORPHAN is required to change the Packaging Specifications pursuant to applicable law (whether initiated by Horizon or regulation or made in response to a request by sanofi-aventis that is agreed to by Horizon), including the order addition of new packaging configurations, new SKUs, new formulations, or request of a governmental authority change in either raw materials or regulatory bodyPackaging Component supply, the following provisions will apply. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED. (1) ORPHAN Horizon shall promptly advise Catalytica sanofi-aventis in writing of any such change(s) to the Specificationschanges, and Catalytica sanofi-aventis shall promptly advise ORPHAN Horizon as to any scheduling and/or Product Price price adjustments which may result from any such change(s), if anychanges. The notification and approval procedure shall be in accordance with APPENDIX F, as well as any additional standard operating procedures (i.e., change control procedures) agreed upon by ORPHAN and Catalytica in writing from time to time. (2) Prior to implementation of such change(s) to changes, the Specifications, ORPHAN and Catalytica Parties shall negotiate in good faith in an attempt to reach agreement on (ia) the new Product Price, if any, Price for any Drug Product and/or Finished Product provided hereunder by Catalytica which embodies such change(schanges, (b) any amounts to be reimbursed by Horizon to sanofi-aventis as described in the Specificationsnext sentence of this paragraph, giving due consideration to the effect of such change(s) on Catalytica’s manufacturing costs for Drug Product and/or Finished Product and (iic) any other amendments to this Agreement which may be necessitated by such changes (e.g.i.e., an adjustment to the lead time for Firm Orderspurchase orders). Implementation of such change(s) to the Specifications Horizon shall be as set forth in APPENDIX F. (3) ORPHAN will reimburse Catalytica sanofi-aventis for the mutually agreed upon reasonable and necessary expenses incurred by Catalytica sanofi-aventis as a result of such changes, including, but not limited to, reimbursing sanofi-aventis for its mutually agreed validation and development costs, capital expenditure costs, costs for any Packaging Components or other materials rendered unusable as a result of such change(schanges, and cost of required stability to support a change. If during the Term Horizon amends the Product Specifications or Packaging Specifications (whether voluntarily or as required by law) so as to render obsolete quantities of the Active Ingredient, Excipients and/or Packaging Components for the Product on hand at sanofi-aventis, Horizon shall (i) accept the return of all such obsolete Active Ingredient and (ii) purchase from sanofi-aventis, at sanofi-aventis’ Acquisition Cost, all such obsolete Excipients and Packaging Components obtained by sanofi-aventis pursuant to its normal procurement policies to manufacture quantities of the Product pursuant to Horizon forecasts under Section 6.1. Sanofi-aventis’ normal procurement policies for purposes of the preceding sentence of this Article 5 shall be considered to be quantities of Excipients and Packaging Components corresponding to the immediately following […***…] months of Horizon’s most recent forecasted Product demand. If a change in Specifications [ * ]. is initiated by sanofi-aventis and approved by Horizon, any cost associated with said change shall be borne by sanofi-aventis. In the event that a change in Specifications is initiated by Horizon or driven by a regulatory or business change, the costs associated with qualification of the change shall be paid by Horizon. The amount of the change shall be reasonable and customary and subject to written approval by Horizon, such approval not to be unreasonably withheld. Sanofi-aventis, with written agreement and approval from Horizon, will be responsible for the appropriate (4cGMP) If any such change(s) to the Specifications renders obsolete or unusable destruction of any materials or components for Drug Product or Finished Productcovered under this Article 5, and to sanofi-aventis shall be reimbursed by Horizon at the extent such materials or components may not be returned to the appropriate vendor for a credit [ * ] that amount of inventory of materials or components, as the case may be, so rendered obsolete or unusable, not to exceed the amount of such materials or components which would have been required for [ * ]. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDEDreasonable and customary approved rate.

Specification Changes. In the event that ORPHAN wishes to change the Specifications, or in the event that ORPHAN is required to change the Specifications pursuant to applicable law or regulation or in response to the order or request of a governmental authority or regulatory body, the following provisions will apply. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED. (1) ORPHAN shall promptly advise Catalytica in writing of any such change(s) to the Specifications, and Catalytica shall promptly advise ORPHAN as to any scheduling and/or Product Price adjustments which may result from any such change(s), if any. The notification and approval procedure shall be in accordance with APPENDIX F, as well as any additional standard operating procedures (i.e., change control procedures) agreed upon by ORPHAN and Catalytica in writing revised from time to time. time as mutually agreed in writing between the parties (2either by execution of an amended BUSA Attachment A that references the new revision level or other writings of the parties). Supplier shall not unreasonably withhold approval to Specifications changes proposed in writing by Medtronic (each change a “PCN”). Supplier will use commercially reasonable efforts to evaluate the feasibility of the PCN requested by Medtronic within ten (10) Prior Business Days of receipt and respond to implementation Medtronic in writing with the potential impact of such change(s) the PCN on current on-hand or on-order component inventory, work-in-progress Products (“WIP”), finished goods Products, and/or the delivery schedule. In addition to the Specificationswritten response provided above, ORPHAN and Catalytica shall negotiate in good faith in an attempt Supplier will use commercially reasonable efforts to reach agreement on respond to Medtronic within ten (10) business days with a written evaluation of the PCN including: (i) engineering time to implement the new Product PricePCN, if any, for any Drug Product and/or Finished Product provided hereunder by Catalytica which embodies such change(s) to the Specifications, giving due consideration to the effect of such change(s) on Catalytica’s manufacturing costs for Drug Product and/or Finished Product and (ii) the cost to modify tools or test fixtures or similar non-recurring expenses, (iii) the quantity of components Supplier has on hand and/or on order with its suppliers related that can no longer be used due to the PCN, (iv) the cost to rework WIP (if applicable) and any other amendments impacts to this Agreement which may be necessitated by such changes Product price resulting from the PCN, (v) the expected effect on the delivery schedule to include (if applicable) the effect on all in-process work (e.g., re-workable, repairable, etc.), and (vi) the manner in which the PCN will be implemented by Supplier. Supplier will not proceed to implement the PCN until Medtronic has approved the charges and Supplier actions described in the Supplier evaluation that is provided to Medtronic. The price for a Product covered by a revised Specification shall remain the same as before the revision, unless the revisions will result in an adjustment to the lead time for Firm Orders). Implementation of such change(s) to the Specifications shall be as set forth increase or decrease in APPENDIX F. (3) ORPHAN will reimburse Catalytica for the reasonable and necessary expenses incurred by Catalytica as a result costs at least +/- 5% of any such change(s) to cost element of the Specifications [ * ]. applicable quote (4) If any such change(s) to e.g. materials, components, labor, test); in that case, the Specifications renders obsolete or unusable any materials or components for Drug Product or Finished ProductSupplier will notify Medtronic of the anticipated change in costs, and to the extent such materials parties will negotiate a new price (based on the increase or components may not decrease in costs) and the BUSA Attachment A will be returned to the appropriate vendor for a credit [ * ] that amount of inventory of materials or components, as the case may be, so rendered obsolete or unusable, not to exceed the amount of such materials or components which would have been required for [ * ]. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDEDamended accordingly.

Specification Changes. In Upon any change in the event that ORPHAN wishes to change the Product Specifications, stability protocols, QC laboratory methods raw material specification or in the event that ORPHAN is required to change the Packaging Specifications pursuant to applicable law (whether initiated by Horizon or regulation or made in response to a request by sanofi-aventis that is agreed to by Horizon), including the order addition of new packaging configurations, new SKUs, new formulations, or request of a governmental authority change in either raw materials or regulatory bodyPackaging Component supply, the following provisions will apply. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED. (1) ORPHAN Horizon shall promptly advise Catalytica sanofi-aventis in writing of any such change(s) to the Specificationschanges, and Catalytica sanofi-aventis shall promptly advise ORPHAN Horizon as to any scheduling and/or Product Price price adjustments which may result from any such change(s), if anychanges. The notification and approval procedure shall be in accordance with APPENDIX F, as well as any additional standard operating procedures (i.e., change control procedures) agreed upon by ORPHAN and Catalytica in writing from time to time. (2) Prior to implementation of such change(s) to changes, the Specifications, ORPHAN and Catalytica Parties shall negotiate in good faith in an attempt to reach agreement on (ia) the new Product Price, if any, Price for any Drug Product and/or Finished Product provided hereunder by Catalytica which embodies such change(schanges, (b) any amounts to be reimbursed by Horizon to sanofi-aventis as described in the Specificationsnext sentence of this paragraph, giving due consideration to the effect of such change(s) on Catalytica’s manufacturing costs for Drug Product and/or Finished Product and (iic) any other amendments to this Agreement which may be necessitated by such changes (e.g.i.e., an adjustment to the lead time for Firm Orderspurchase orders). Implementation of such change(s) to the Specifications Horizon shall be as set forth in APPENDIX F. (3) ORPHAN will reimburse Catalytica sanofi-aventis for the mutually agreed upon reasonable and necessary expenses incurred by Catalytica sanofi-aventis as a result of such changes, including, but not limited to, reimbursing sanofi-aventis for its mutually agreed validation and development costs, capital expenditure costs, costs for any Packaging Components or other materials rendered unusable as a result of such change(schanges, and cost of required stability to support a change. If during the Term Horizon amends the Product Specifications or Packaging ***Confidential Treatment Requested MANUFACTURING AND SUPPLY AGREEMENT PAGE 7 Specifications (whether voluntarily or as required by law) so as to render obsolete quantities of the Active Ingredient, Excipients and/or Packaging Components for the Product on hand at sanofi-aventis, Horizon shall (i) accept the return of all such obsolete Active Ingredient and (ii) purchase from sanofi-aventis, at sanofi-aventis’ Acquisition Cost, all such obsolete Excipients and Packaging Components obtained by sanofi-aventis pursuant to its normal procurement policies to manufacture quantities of the Product pursuant to Horizon forecasts under Section 6.1. Sanofi-aventis’ normal procurement policies for purposes of the preceding sentence of this Article 5 shall be considered to be quantities of Excipients and Packaging Components corresponding to the immediately following […***…] months of Horizon’s most recent forecasted Product demand. If a change in Specifications [ * ]. is initiated by sanofi-aventis and approved by Horizon, any cost associated with said change shall be borne by sanofi-aventis. In the event that a change in Specifications is initiated by Horizon or driven by a regulatory or business change, the costs associated with qualification of the change shall be paid by Horizon. The amount of the change shall be reasonable and customary and subject to written approval by Horizon, such approval not to be unreasonably withheld. Sanofi-aventis, with written agreement and approval from Horizon, will be responsible for the appropriate (4cGMP) If any such change(s) to the Specifications renders obsolete or unusable destruction of any materials or components for Drug Product or Finished Productcovered under this Article 5, and to sanofi-aventis shall be reimbursed by Horizon at the extent such materials or components may not be returned to the appropriate vendor for a credit [ * ] that amount of inventory of materials or components, as the case may be, so rendered obsolete or unusable, not to exceed the amount of such materials or components which would have been required for [ * ]. [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDEDreasonable and customary approved rate.