MANUFACTURING AND SUPPLY AGREEMENT

Confidential Materials omitted and filed separately
with the Securities and Exchange Commission. Asterisks denote omission.

Exhibit 10.1

Execution Copy

MANUFACTURING AND SUPPLY AGREEMENT

This MANUFACTURING & SUPPLY AGREEMENT (this “Agreement”), dated as of August 20, 2007 by and among (i) Critical Therapeutics, Inc. , a Delaware corporation having a place of business at 60 Westview Street, Lexington, MA 02421, USA (“CRTX”), (ii) Jagotec AG , a Swiss company having a place of business at Eptingerstrasse 51, CH-4132 Muttenz, Switzerland (“Jagotec”) and (iii) for the purposes of clause 20 only, SkyePharma PLC , an English company having a place of business at 105 Piccadilly, London W1J 7NJ (Jagotec and CRTX individually referred to as a “Party” and together as the “Parties”).

WITNESSETH:

WHEREAS , by an agreement dated 3 October 1996 (the “Abbott Licence”) Jagotec granted Abbott Laboratories (“Abbott”) an exclusive, worldwide right and licence under certain patents and know-how to make, have made, import, use, offer for sale, market, distribute and sell the Product (as defined below) with the right, subject to Jagotec’s consent, to sub-licence such rights.

WHEREAS, Abbott has granted CRTX a licence (the “CRTX Licence”) to develop and commercialise the Product under intellectual property owned by or licensed to Abbott including intellectual property licensed to Abbott under the Abbott Licence.

WHEREAS, Jagotec consented to the CRTX Licence and agreed to provide certain services to CRTX in connection with obtaining registrations for products and the manufacture of clinical supplies and samples of Product on the terms of an agreement dated December 3, 2003 (the “Support Agreement”).

WHEREAS , in the Support Agreement, CRTX and Jagotec agreed to enter into a manufacturing agreement for the manufacture and supply of commercial supplies of the Product.

WHEREAS, this Agreement is the manufacturing agreement referred to in the Support Agreement.

NOW, THEREFORE , for and in consideration of the premises, mutual covenants and agreements contained herein, and intending to be legally bound hereby, the Parties hereby agree as follows:

1.		Definitions
1.1		For purposes of this Agreement, the following terms shall have the following meanings:
		“ Act ” means the US Federal Food, Drug and Cosmetic Act of 1938, the Public Health Service Act of 1944 and the regulations promulgated under those Acts, as may be amended from time to time.
		“Active Material Cost” means the value to be attributed to the API for the purposes of Schedule 3 (line item G) of this Agreement, as set forth in Schedule 4 hereto.
		“ API ” means the active pharmaceutical ingredient, zileuton.
		“ Affiliate ” means any entity in which a Party has a direct or indirect equity or income interest ownership of at least fifty percent (50%) or more, or any entity which, directly or indirectly, through one or more intermediaries, controls, is controlled by or is under common control with that Party. For the purpose of this definition, “control” means the possession, directly or indirectly, of the power to direct the management or policies of an entity, whether through the ownership of voting securities, by contract relating to voting rights or corporate governance, or otherwise and the terms “controlled by” and “under common control with” have corresponding meanings. The term Affiliate shall include in particular with respect to Jagotec AG, its manufacturing affiliate Skye-SAS.
		“ Agency ” means any applicable supra-national, federal, national, regional, state, provincial or local regulatory agencies, departments, bureaus, commissions, councils or other government entities regulating or otherwise exercising authority with respect to the manufacture or distribution, use or sale of the Product, including the FDA.
		“ Applicable Laws ” means the Act and other laws, rules and regulations, (including any rules, regulations, guidelines or other requirements of any Agency) applicable to the manufacture of pharmaceutical products, as may be in effect from time to time in the US and in such other countries for which CRTX has (i) obtained a Registration for the Product and (ii) provided Jagotec with not less than nine months written notice that the Product must be manufactured in accordance with the Applicable Laws in that country.
		“ Auxiliary Materials ” means any and all material, ingredients and components required and/or necessary for the manufacture and bulk packaging of Product by Jagotec hereunder, except API.

“ Batch ” means a specific quantity of the Product (batch target size of approximately [**] tablets, or such other target batch size as approved in writing by the Parties) that is intended to be of uniform character and quality, within specified limits, and is produced during the same cycle of manufacture and is designated by a batch number.

“ Complete Batch Documentation ” shall have the same meaning as set forth in the Quality Agreement.

“ Batch Instructions ” shall have the meaning as set forth in the Quality Agreement.

“ cGMP ” means the Current Good Manufacturing Practices as defined from time to time under the Act and other Applicable Laws including the Current Good Manufacturing Practices set forth in 21 C.F.R. 210 and 21 C.F.R. 211 and relevant FDA guidance documents; and to the extent applicable European Community Directive 91/356/EEC, Directive 2001/83/EC and all relevant implementations of such directives and relevant guidelines including the EC Guidelines.

“ Confidential Information ” in relation to a party, means any and all technical and commercial materials and information and know-how, which is proprietary or confidential or non-public in nature including, without limitation, know how, trade secrets, specifications, Batch Instructions, products, processes, services, contracts, business methods or practices, pricing techniques and information, financial information, intellectual property and ideas which, at the time or times concerned, are not generally known to third persons and or is identified by that party as confidential.

“ Contract Vendor ” means a company or facility which is contracted by Skye-SAS or Jagotec to supply Auxiliary Materials or to manufacture or test the Product, other than Skye-SAS or CRTX. For the avoidance of doubt, the [**], would be considered a Contract Vendor.

“Critical Batch Documentation” shall have the same meaning as set forth in the Quality Agreement.

“Defect” means (a) the failure of a Product to comply in any material respect with the Specifications, cGMP and Applicable Laws (to the extent that such failure to comply with Applicable Laws results in the Product being unable to sold in the relevant part of the Territory for which it was manufactured), or (b) a manufacturing defect which would be discoverable upon reasonable physical inspection or testing performed within customary timelines upon receipt of a shipment of Product.

“ EC Guidelines ” means Volume 4 of the Rules Governing Medicinal Products in the European Union: Medicinal Products for Human and Veterinary Use: Good Manufacturing Practices.

“Effective Date” means May 22, 2007.

“ Executed Batch Record ” shall have the same meaning as set forth in the Quality Agreement.

“ Facility ” means Skye-SAS’s manufacturing facilities in St-Quentin-Fallavier, France.

“ FDA ” means the United States Food and Drug Administration and/or any successor agency.

“Finished Product” means Product further worked, labelled and packaged by or on behalf of CRTX for commercial supply.

“ Fully Allocated ” means the fully-burdened cost of manufacturing the Product, including the cost of (i) raw materials other than API used in the actual production, bulk labelling and bulk packaging of Product, (ii) direct labour of Jagotec employees or its Affiliate’s employees (including basic wages, labour and related payroll taxes and benefits) incurred or spent in the actual production, bulk labelling and bulk packaging of Product, including without limitation for quality assurance and manufacturing facility operations, and (iii) overhead of Jagotec and its Affiliates (including operating expenses, indirect labour and related payroll taxes and benefits, depreciation, applicable taxes, insurance, repairs and maintenance, supplies) incurred or spent in support of the actual production, bulk packaging and bulk labelling of Product, but not for cost of any unused manufacturing capacities that Jagotec may have in excess of the requirements contained in the forecasts provided by CRTX, and, in the case of (ii) and (iii) above, excluding taxable benefits, remuneration based on profitability or bonuses, and (iv) (without prejudice to delivery being Ex Works hereunder) any transportation, storage, non-reimbursable import or export taxes of or for Product as may be incurred or spent by Jagotec or its Affiliates in connection with the supply of Product pursuant to the terms of this Agreement, all as determined in accordance with generally accepted accounting principles consistently applied; provided, however, any increase in the overhead of Jagotec and its Affiliates shall not exceed [**]% of their overhead of the previous Year.

“ Geomatrix System ” has the meaning ascribed to such term in the Support Agreement.

“ Latent Defect” means a Defect which would not be discoverable upon reasonable physical inspection of a shipment of the Product when testing is performed.

“Launch Phase” means the period of time immediately before and immediately following receipt of a Marketing Approval in the US, whereupon the supply of the Product by Jagotec to CRTX is ramped-up with a view to ensuring the commercial availability of the Finished Product and during which time the shelf-life of the Product will be less than [**] months but more than [**] months from date of manufacture by Jagotec.

“ Manufacturing Sub-License ” means a sub-license under the Support Agreement and the Abbott Licence, subject to the prior written consent of Jagotec which shall not be unreasonably withheld or delayed, from CRTX to a manufacturer other than Jagotec (such third party manufacturer, a “Manufacturing Sub-Licensee”) to manufacture the Product on the terms hereof. As of the Effective Date, the only Manufacturing Sub-License has been granted to Patheon Pharmaceuticals Inc. to which Jagotec has consented by letter dated 19 July 2005 in respect of quantities set out therein.

“Marketing Approvals” means the approvals issued by any Agency in accordance with any procedures as may be required by Applicable Law to market the Finished Product in the relevant country.

“ Price” means the price expressed in U.S. dollars of Product supplied by Jagotec hereunder calculated in accordance with Schedule 1, excluding VAT (or similar taxes) where applicable.

“ Product ” means the bulk packaged uncoated tablets for a finished product containing API as the sole therapeutic or prophylactic active ingredient, in a controlled release tablet using the Geomatrix System supplied by Jagotec to CRTX hereunder.

“ Quality Agreement ” means that certain Technical and Quality Assurance Agreement by and among Skye-SAS, Jagotec and CRTX dated June 29, 2007, describing the obligations of the Parties with regards to compliance, quality systems, and testing and release of Product as may be required by Applicable Laws and as agreed upon in writing by the Parties; the Quality Agreement is incorporated into and made a part of this Agreement.

“ Quarter ” means a period of 3 months starting on a Quarter Day.

“ Quarter Day ” means each of 1 January, 1 April, 1 July and 1 October in each Year.

		“Recall” shall have the meaning as set forth in the Quality Agreement and “Recalled” shall be construed accordingly.
		“ Registrations ” means any and all technical, medical and scientific licences, registrations, authorisations and/or approvals of the Product or Finished Product (including clinical research authorization, manufacturing approvals and authorisations, Marketing Approvals, manufacturing facility approvals or authorizations, and pricing, third party reimbursement and labelling approvals) that are required by any Agency for the manufacture, distribution, use or sale of the Product or Finished Product in any country, as amended or supplemented from time to time.
		” Release ” shall have the same meaning as set forth in the Quality Agreement.
		“SEC” means the U.S. Securities and Exchange Commission.
		“ Skye-SAS ” means SkyePharma Production S.A.S.
		“ Specifications ” shall have the same meaning as set forth in the Quality Agreement.
		“ Territory ” means all countries of the world.
		“ US ” means the United States of America.
		“ $ ” and “ US$ ” shall mean United States Dollars.
		“ Working Day” means Monday to Friday of each week excluding public holidays in France, Switzerland or the US.
		“ Year ” means a calendar year running from 1 January to 31 December.
1.2		Unless otherwise expressly stated, reference to, a Section, Schedule or Exhibit is to a Section of, or a Schedule or Exhibit to, this Agreement and references in any Schedule to a Paragraph is to a paragraph in that Schedule.
1.3		The Recitals, Schedules and Quality Agreement form part of this Agreement and will have the same force and effect as if expressly set out in the body of this Agreement and any reference to this Agreement will include the Recitals, Schedules and Quality Agreement.
1.4		The Section headings are for convenience only and will not affect the interpretation of this Agreement.

1.5		In this Agreement, any phrase introduced by the terms include, including, in particular or any similar expression will be construed as illustrative and will not limit the sense of the words proceeding them.
1.6		In this Agreement, unless the context otherwise requires:
		a)use of the singular is deemed to include the plural and vice versa;
		b) use of any gender is deemed to include every gender; and
		c) reference to a person includes a natural person, a firm, a corporation, a partnership, a trust, an association, an organisation and any other body or entity whether or not having separate legal personality.
1.7		Any undertaking by any of the parties not to do any act or thing shall be deemed to include an undertaking not to permit or suffer or assist the doing of that act or thing.
2.		Subject Matter and Grant of License
2.1.		CRTX hereby appoints Jagotec with effect from the Effective Date, and Jagotec hereby accepts such appointment under the terms and conditions contained in this Agreement, to manufacture only for CRTX the Product in bulk and to deliver and/or sell such Product only to CRTX.
2.2.		CRTX hereby grants to Jagotec with effect from the Effective Date the royalty-free right and sub-license under the CRTX Licence, without the right to grant sublicenses (except to Skye-SAS, to which CRTX hereby consents for so long as Jagotec uses Skye-SAS to manufacture Product for CRTX hereunder), solely to manufacture Product for, and supply Product to, CRTX all in accordance with the provisions contained in this Agreement. The terms and conditions of this Agreement shall apply to all Batches manufactured from the Effective Date.
2.3.		Nothing herein shall confer upon Jagotec any authority to sell or distribute the Product on its own account or for any other person or entity other than CRTX, but authorises Jagotec only to manufacture the Product in accordance with the terms hereof. During the Term Jagotec shall not, and shall procure that its Affiliates do not, either directly or indirectly, market, sell or distribute the Product, or sell the Product to any person who it believes or ought reasonably to know intends to sell the Product . During the Term and for a period of [**] years after the Term, Jagotec shall not, and shall procure that Jagotec’s Affiliates do not, use any CRTX Intellectual Property, CRTX Product Developments or Confidential Information provided by CRTX to manufacture, produce, market or sell any product containing zileuton for any company or person other than CRTX.

3.		Obligations of Jagotec
3.1.		Jagotec will manufacture Product and perform quality control testing in compliance with:
		a) the Specifications;
		b) the Quality Agreement; and
		c) cGMP and all other Applicable Laws.
3.2.		Jagotec will maintain all records, including Complete Batch Documentation, required by the Specifications, Applicable Laws and the Quality Agreement which are to be maintained in connection with the manufacture of Product.
3.3		Without prejudice to its obligations under Sections 3.10 and 3.11, Jagotec makes no warranty as to compliance with Specifications, Applicable Laws and the Quality Agreement regarding or with respect to Auxiliary Materials or API furnished to it by CRTX or by any third party instructed by CRTX to supply such materials to Jagotec.
3.4		Jagotec is responsible for obtaining all Registrations necessary to manufacture Product under this Agreement.
3.5		Jagotec is responsible for conducting all manufacturing and testing related to the Product and Auxiliary Materials in compliance with the Specifications, the Quality Agreement, Applicable Laws and cGMP. Jagotec warrants that any Auxiliary Materials supplied by Jagotec or any Contract Vendor, and all manufacturing and testing processes used by Jagotec or any Contract Vendor complies with all relevant Specifications, Applicable Laws and the Quality Agreement.
3.6		Jagotec will notify CRTX of any deviations that may occur relating to the Product as defined in the Quality Agreement upon becoming aware thereof.
3.7		Jagotec will notify CRTX of any Agency audit or inspections in respect of any part of the Facility used to manufacture the Product within [**] Working Days of receipt of notice by Skye-SAS thereof, to allow CRTX to be present at any audit that deals specifically with the Product and promptly make available any comments from such audit or inspection as they relate to the Jagotec’s compliance with the Specifications, any applicable Quality Agreement, Applicable Laws, cGMP or any other regulatory requirements. Jagotec will promptly inform CRTX of any other material communications to or from an Agency relating to the Product. The Parties will consult with each other regarding any issues raised in

		such communications and will attempt in good faith to agree upon any action to be taken or response to be made in connection with such communications.
3.8		Jagotec shall maintain accurate records of all API supplied by CRTX for use in the manufacture of the Product and records of work-in-process and finished Product. Accurate records of any losses of API supplied by CRTX shall be documented for each lot. Such records shall be accessible to CRTX for inspection during regular business hours on CRTX giving Jagotec not less than [**] Working Days notice of such inspection.
3.9		Without prejudice to Section 3.7 above, Jagotec shall permit duly authorized representatives of CRTX or its third party designees, [**] every Year (or more frequently if an audit reveals significant concerns from the perspective of CRTX, acting reasonably, that require appropriate additional audit follow-up) during normal business hours and upon reasonable prior written notice, and in any event on not less than [**] Working Days notice, to conduct general cGMP audits. At such audits CRTX can inspect the formulation processes and work practices relating to the Product and inventory of Auxiliary Materials, API, and Product, all Registrations necessary for Jagotec to manufacture the Product, the Complete Batch Documentation and/or Facility, including the equipment used in the manufacturing and testing of Product, and inspect and take reasonable quantities of Product manufactured by Jagotec for examination purposes to verify Jagotec’s compliance with the Specifications, Applicable Laws, cGMP and the Quality Agreement.
3.10.		Jagotec shall use any and all API supplied by CRTX under Section 4.3 exclusively for the performance of its obligations under this Agreement, and Jagotec shall, upon receipt of any supply of API, perform the quality control procedures as provided for in the Quality Agreement. In the event that any supply of API received from CRTX, or any part thereof, does not meet the requirements set forth in the Specifications, the applicable Quality Agreement or Applicable Laws, then Jagotec shall promptly notify CRTX thereof in writing and CRTX will promptly supply replacement API that does comply with such requirements. Notwithstanding the foregoing or any contrary provision of the Quality Agreement, the provisions of Schedule 6 hereto shall apply in the circumstances set out therein.
3.11		Jagotec shall store all API received from CRTX, all Auxiliary Materials and all Product manufactured hereunder, in a suitable warehouse in accordance with cGMP, the Specifications, the Quality Agreement or Applicable Laws and shall use commercially reasonable endeavours to prevent the deterioration, theft or damage of API, all Auxiliary Materials and Product until delivered to CRTX in accordance with Section 7. Jagotec shall insure all API delivered by CRTX until delivery of Product containing such API to CRTX in accordance with Section 7

		below, against such risks provided the insurable value thereof shall be the Active Material Cost.
3.12		API Yield.
		(a) Reporting. Within [**] Working Days after the end of each Quarter, Jagotec shall provide CRTX with a Quarterly inventory report of the API held by Jagotec in accordance with the inventory report form annexed hereto as Schedule 2, which shall contain the following information for such month:
		Quantity Received: “Quantity Received” shall mean the total quantity of API that is received at the Facility during the applicable period, which complies with such part of the Specifications applying thereto, which has been tested by Jagotec in accordance with clause 3.10 and which Jagotec has not provided a notice in accordance with clause 3.10.
		Quantity Dispensed: The Quantity Dispensed is calculated by adding the Quantity Received to the inventory of API that complies with such part of the Specifications applying thereto and is held at the beginning of the applicable period, less the inventory of API that complies with such part of the Specifications applying thereto and is held at the end of such period. The Quantity Dispensed shall only include Quantity Received in connection with commercial manufacturing of Product and, for certainty, shall not include any Quantity Received in connection with technical transfer activities or development activities during the applicable period, including, without limitation, any regulatory, stability, validation or test batches manufactured during the applicable period.
		Quantity Converted: Quantity Converted shall mean the total amount of API contained in the Products produced with the Quantity Dispensed (including any additional Product produced in accordance with Section 7.9), delivered by Jagotec, and not rejected, recalled or returned in accordance with Section 6.8 as a result of a failure by Jagotec to provide the Product in accordance with Specifications, Quality Agreement and cGMP. Furthermore Quantity Converted shall include any quantities of API contained in Product retained as samples pursuant to the Quality Agreement and also for compliance with cGMP.
		Within [**] days after the end of each Year, Jagotec shall prepare an annual reconciliation of API in accordance with the reconciliation report form annexed hereto as Schedule 3 including the calculation of the “ Actual Annual Yield ” or “ AAY ” for the Product at the Facility during the Year, which AAY is the percentage of the Quantity Dispensed that was converted to Product and is calculated as follows, expressed as a percentage:

Quantity Converted during the Year

Quantity Dispensed during the Year

		After Jagotec has produced a minimum of [**] commercial production Batches of Product and has produced commercial production Batches for at least [**] months at the Facility (collectively, the “ Target Yield Determination Batches ”) pursuant to this Agreement, the Parties will reasonably agree on the target yield in respect of such Product at the Facility (each, a “ Target Yield ”); provided, however, that the Target Yield Determination Batches shall not include any Batches that, in Jagotec’s reasonable judgment, were produced in production runs involving technical difficulties or involving an extraordinary loss of API. Thereafter, Jagotec shall use commercially reasonable efforts to maintain Actual Annual Yield levels for each Product at or above the applicable Target Yield.
		(b) Shortfall Calculation . If the Actual Annual Yield falls more than [**] percent below the applicable respective Target Yield in a Year, then the shortfall for such Year (the “Shortfall”) shall be determined based on the following calculation:
		[**]
		The Shortfall shall be disclosed by Jagotec on the reconciliation report prepared in the form annexed hereto as Schedule 3.
		(c) Shortfall Reimbursement . Jagotec shall reimburse CRTX for any Shortfall of API as calculated in Section 3.12 (b) provided however, (i) Jagotec’s entire liability for Shortfall shall not exceed $[**] in any single Year and (ii) and such reimbursement is not eligible for reimbursement under Section 3.12(d). Each payment under this Section 3.12 (c) shall be summarized on the reconciliation report prepared in the form attached hereto as Schedule 3 and shall be made [**] days following the end of each Year.
		(d) Batch Failure Reimbursement : Jagotec shall promptly issue to CRTX a credit in the amount of (i) the cost of Active Material Cost of the API and (ii) the full amount of the Price for Batches which fail to meet the Specifications, Batch Instructions, cGMP, Applicable Laws, and the Quality Agreement, and which are reasonably rejected, recalled or returned by CRTX, but only to the extent that (i) such failure is due to any act or omission of Jagotec, and Jagotec’s Affiliates, agents, employees, or assigns, which is not in accordance with this Agreement and (ii) such reimbursement has not already been made under Section 3.12(c).
		(e) No Material Breach . It shall not constitute a material breach of this Agreement by Jagotec, for the purposes of Section 10.2, if the Actual Annual Yield is less that the Target Yield; provided that Jagotec has used commercially reasonable efforts to maintain Actual Annual Yield levels for the Product above the applicable Target Yield.
3.13		Cost Accounting . Jagotec shall keep a full accounting of how the Fully Allocated cost is calculated and shall maintain such accounting and all of the records upon which it is based for no less than [**] years after the Year to which the Fully

		Allocated cost relates. Within [**] Working Days after the end of each Year from the Year ending December 31, [**] onwards, Jagotec shall provide such accounting to CRTX and any increase in Price shall be implemented only after [**] Working Days after such accounting is delivered to CRTX but shall be backdated once implemented to the beginning of the current Year.
3.14		Inspection . CRTX may itself inspect [**] in any one Year (or more frequently if an audit reveals a material deficiency or quantitative error that is in CRTX’s reasonable opinion is unresolved after such annual visit from the perspective of CRTX and requires appropriate additional audit follow-up) Jagotec Product-specific reports, records, and API and Product inventory (excluding financial data not attributable to the pricing of the Product and subject to third party confidentiality obligations) relating to this Agreement, during normal business hours and with reasonable advance notice and in any event on not less than [**] Working Days notice. A Jagotec representative shall be present during any such inspection. Notwithstanding any other provision of this Agreement, from the Year ended December 31, [**] onwards, CRTX may appoint an independent auditor to review the calculation of the Fully Allocated cost and the records upon which the Fully Allocated cost is based, during normal business hours and with reasonable advance notice. A Jagotec representative shall be present during any such inspection.
3.15		Jagotec will be responsible for handling and disposing of any and all wastes generated as a result of the manufacturing of the Product or any cleaning of any equipment involved, in compliance with Applicable Laws, rules and regulations, including environmental laws and regulations relating to such handling and disposal.
3.16		Save as set out hereafter, Jagotec shall use reasonable commercial efforts to maintain an annual average inventory of Auxiliary Materials required to manufacture [**] months supply of Product quantities or such lower quantity as the Parties may agree. The Parties shall separately agree upon the amount of inventory to be held during the Launch Phase.
3.17		Jagotec shall notify CRTX within [**] Working Days of Jagotec determining that they cannot or will not (i) manufacture according to the Firm Order delivery schedule or the Pro Forma delivery schedule or (ii) meet the annual requirements set forth in Section 7.2 of the Agreement.
3.18		During the Launch Phase, Jagotec shall permit CRTX or representatives of CRTX with not less than [**] Working Days notice to conduct review of original Complete Batch Documentation held by Jagotec. From time to time after the Launch Phase, Jagotec shall permit CRTX or CRTX representatives with not less than [**] Working Days notice to conduct on-site “for cause” technical and/or

		cGMP reviews and/or audits if the issues leading to the need to conduct the “for cause” review and/or audit cannot be resolved without such an on-site meeting.
3.19		If CRTX requests on-site reviews, audits, inspections or meetings other than or in addition to those referred to under Sections 3.9, 3.14, 3.18 or 5.1, Jagotec reserves the right to charge CRTX $[**] for each day (to be pro rated for part of a day).
3.20		From [**] and for until expiration or termination of this Agreement, Jagotec shall use commercially reasonable efforts to maintain manufacturing capacity capable of delivering at least [**] tablets of the Product per Year (at a rate of no more than [**] tablets per Quarter). CRTX has a right to request additional capacity for the Product and Jagotec may agree thereto in its absolute discretion if it has additional capacity in its current production line or if it decides to add a second line.
4.		Obligations of CRTX
4.1.		CRTX shall promptly provide to Jagotec all and any information in CRTX’s possession reasonably required by or necessary for Jagotec to perform its obligations hereunder that is not already in the possession of Jagotec.
4.2		In the event that CRTX proposes or intends to amend, alter or change the Specification as is agreed at the Effective Date (an “ Amendment ”), CRTX shall duly notify Jagotec thereof in writing and the date by which the Amendment is to be implemented. CRTX shall allow sufficient time for Jagotec’s due implementation of any Amendment which, unless otherwise agreed by Jagotec in writing shall be not less than [**] days prior to the anticipated delivery date of Product manufactured in accordance with such amended Specification; provided however , that, in the case of Amendments required by the FDA or other Agency (“Agency Imposed Amendments”), Jagotec shall use commercially reasonable efforts to implement such Agency Imposed Amendment immediately or within any timeframe allotted by the FDA or such Agency, whichever is longer. Any such proposed Amendment, so notified by CRTX, shall become binding upon Jagotec on the date specified by CRTX in accordance with the foregoing unless Jagotec notifies CRTX within [**] Working Days of its receipt of CRTX’s proposal of its decision not to approve the Amendment which approval shall not unreasonably be withheld; provided however , that, in the case of Agency Imposed Amendments, Jagotec shall not have the right to reject such amendment. Any and all reasonable costs and expenses incurred by Jagotec in connection with the implementation of any Amendment submitted by CRTX shall be borne exclusively by CRTX. Unless otherwise agreed to in writing by Jagotec and CRTX, if any Agency Imposed Amendment results in a greater likelihood of Batch recall, rejection or return by CRTX than would be associated with the

		Specification agreed at the Effective Date, (i) CRTX shall bear the cost of such recall, rejection or return and (ii) CRTX shall waive any rights in relation to Jagotec’s failure to comply with the Specification from the date of such Agency Imposed Amendment, each except to the extent that such recall, rejection or return is due to any proven negligence or any wilful misconduct of Jagotec, its Affiliates, or their agents in the performance of their activities under this Agreement or any breach by Jagotec of its representations, warranties or obligations pursuant to this Agreement or the Quality Agreement. Any change to the manufacturing process to take account of such Amendment shall be reflected in the Fully Allocated manufacturing cost.
4.3.		CRTX undertakes to supply to Jagotec [**] (a) in the Year during which the Marketing Approval for the Finished Product is received from the FDA, a minimum of [**] months supply, and (b) in each Year thereafter a minimum of [**] months supply of API as required by Jagotec to manufacture quantities of Product, including samples for testing and retains. Any and all supply of API shall be in strict compliance with the requirements set forth in the Specifications, any applicable Quality Agreement and Applicable Laws, and shall be delivered DDP (Incoterms 2000) to the Facility.
		The supply of API referred to in this Section will take into account the following: The production loss is to be determined by the first [**] full-scale Batches (validation/commercial but excluding any Batches with an atypical yield caused by a deviation documented in accordance with the Quality Agreement) and the percentage agreed by both parties, however, CRTX anticipation is that, and, unless otherwise agreed upon by the parties, the production loss should not be greater than [**]% of the Quantity Dispensed after the first [**] full-scale Batches.
4.4.		All supply of API by CRTX hereunder shall be received by Jagotec sufficiently in advance of the expected delivery date for the supply of Product ordered by CRTX in accordance with Section 7.1(b). CRTX shall use commercially reasonable efforts to deliver such API not later than [**] months prior to such expected delivery date. In the event that any such supply of API is received by Jagotec less than such [**] months prior to any requested delivery date, Jagotec shall have no obligation to deliver the Product ordered at such delivery date, but shall nevertheless use commercially reasonable efforts to supply such Product on or as soon after such delivery date as available manufacturing and personnel capacities allow taking into account its other manufacturing commitments.
4.5		CRTX shall, with each order of API supplied to Jagotec, provide Jagotec with a certificate indicating release of API for use in manufacturing of the Product.
		CRTX shall procure that the manufacturer of the API obtains and maintains all permits, licenses or approvals necessary to manufacture the API.

4.6		CRTX shall permit duly authorized representatives of Jagotec [**] every Year during normal business hours and upon reasonable prior written notice, and in any event or not less than [**] Working Days notice, to conduct general cGMP audits of quality systems relating to the release for use of API for production of the Product.
5.		Cooperation
5.1		Each of CRTX and Jagotec hereby appoint [**] and [**] respectively to be their relationship managers responsible for liaison between the parties. The identity of a Party’s relationship managers may be changed upon notice to the other Party made in accordance with Section 14.3 of this Agreement. The relationship managers, or their designated deputies, shall meet not less than [**] per Quarter to review the current status of the business relationship and manage any issues that have arisen; provided that, at least [**] of such meetings shall be “face-to-face” and each of the parties shall have the right to choose the venue for [**] such face-to-face meeting.
5.2		Subject to Jagotec’s obligations under Section 3.4, CRTX shall have the sole responsibility for filing all documents with the FDA or other Agency and taking any other actions that may be required to maintain FDA or other Registration for the commercial manufacture of the Product. Jagotec shall reasonably assist CRTX. CRTX shall provide Jagotec with copies of relevant chemistry, manufacturing and controls (CMC) information regarding the Product and all FDA or other Agency submissions after the filing of such documents.
5.3		Each party may communicate with any governmental agency, including but not limited to Agencies, regarding the Product if in the opinion of that party’s counsel, such communication is necessary to comply with the terms of this Agreement or the requirements of any law, governmental order or regulation; provided, however, that unless in the reasonable opinion of its counsel there is a legal prohibition against doing so, such party shall in addition give notice of such communication to the other party and Jagotec shall permit CRTX to accompany and take part in any communications with the Agency, and to receive copies of all such communications to and/or from the Agency as relates to the Product.
5.4		CRTX is solely responsible for obtaining and maintaining any Marketing Approvals. CRTX shall promptly inform Jagotec of any and all regulatory requirements relating to Jagotec’s manufacturing activities hereunder or amendments or changes thereto and undertakes to provide to Jagotec such information as Jagotec may reasonably require to support any Registration requirements relating to the manufacturing of Product. Jagotec undertakes to provide CRTX such information as CRTX may reasonably require to support any Marketing Approval(s).

5.5		Jagotec shall keep records of the manufacture, testing and shipping of each Batch, and each batch of Auxiliary Materials and API used to manufacture the Product. Copies of such records shall be retained as set out in the Quality Agreement.
5.6		Jagotec shall keep retain samples of the Product, Auxiliary Materials and API as set out in the Quality Agreement.
5.7		Jagotec will supply all Product data, including master documentation, specifications and monographs, release test results, complaint test results, all investigations and deviations (in manufacturing, testing and storage), in English that CRTX reasonably requires in order to complete any FDA or other Agency filing under any applicable regulatory regime, [**] days prior to the due date for such report or filing. CRTX shall provide as much notice as possible to Jagotec of the filing dates. Jagotec will prepare annual Product reviews for the Product, [**] before the anniversary date of May 30, 2007 as set forth in the Quality Agreement and will provide any additional information that CRTX is required to file with the FDA (or other Agency) Annual Report, that is related to Jagotec’s manufacturing of the Product.
5.8		Jagotec shall promptly report to CRTX any information that it has knowledge of concerning any adverse drug experience in connection with the use of the Finished Product, including the incidence or severity thereof, associated with non-clinical toxicity studies, clinical uses, studies, investigations or tests, whether or not determined to be attributable to the Product. Reports of serious adverse drug experiences shall be made available to CRTX within [**] Working Days after Jagotec becomes aware of such adverse drug experience, or [**] hours if the adverse drug experience will require a field alert be submitted to the FDA or any Agency. Upon receipt of any such report of serious adverse drug experience by either Party, the Parties shall make commercially reasonable efforts to take mutually agreed actions as appropriate or required under the circumstances; provided, however, that nothing contained herein shall be construed as restricting the right or duty of either Party to make a required report or submission to the FDA or any Agency, or take any other action that it reasonably deems to be appropriate or required by Applicable Law. In any event, the responsibility of making any reports of adverse drug experience or other required reports to the FDA or any Agency will be upon CRTX (or its licensees) as holder of the Marketing Approval for the Finished Product.
5.9		Jagotec shall provide CRTX with reasonable assistance in the investigation of any adverse drug experience when same is believed to be attributable to the Product. In such event, CRTX shall be responsible to ensure that Jagotec receives samples of the Finished Product to be investigated. The involvement of Jagotec will be limited to the evaluation of manufacturing process activities undertaken by Jagotec and its impact on identified Product quality matters.

		Jagotec shall use commercially reasonable efforts to provide a written report of its determination within [**] days of receipt of CRTX’s written request and samples of the involved Finished Product. CRTX shall be responsible for the costs of any such evaluations conducted by Jagotec, as requested by CRTX. As between CRTX and Jagotec, CRTX shall correspond with the subjects of adverse drug experiences on all adverse drug experiences and Jagotec shall not correspond with such subjects.
6.		Title
6.1		Notwithstanding anything to the contrary herein, CRTX shall retain title to all materials supplied by it to Jagotec pursuant to this Agreement. Jagotec agrees that any API received by it shall only be used by Jagotec to manufacture the Product. Under no circumstances shall this Agreement vest any rights in Jagotec with respect to API supplied by CRTX and Jagotec shall not remove, alter or obscure any proprietary notices from materials supplied by CRTX. Jagotec shall promptly point out to any third party who obtains access to its premises under a court order or any order to seize property, or who acts as a receiver in bankruptcy proceedings, that API supplied by CRTX is owned solely by CRTX.
6.2		Jagotec shall invoice CRTX for the Price upon Shipment of each Batch of Product. Payment Terms shall be [**] days from the date of receipt of an electronic copy of invoice (with a paper confirmatory copy of said invoice being sent by post).
7.		Order and Supply of Product
7.1		(a) Within [**] days of the Effective Date, CRTX shall provide Jagotec with a written non-binding [**] month forecast of the volume of each Product that CRTX then anticipates will be required to be produced by Jagotec and shipped to CRTX during each month of the first [**] months and each [**] thereafter of that [**] month period. The first [**] months of such forecast shall be binding and shall consist of [**] months of Firm Orders (as defined below), the next [**] months shall consist of a non-binding forecast of amounts of Product for such period and the remaining [**] months shall consist of planning horizon. Such forecast will be updated by CRTX monthly on or before the [**] day of each calendar month on a rolling [**] month basis.
(b)		Firm Orders. On or before the [**] day of each calendar month in conjunction with the provision of the rolling forecast outlined in Section 7.1(a), CRTX shall issue firm written orders (“ Firm Orders ”) for the Product to be produced and delivered to CRTX on a date not less than [**] days from the first day of the calendar month immediately following the date that the Firm Order is submitted. Such Firm Orders submitted to Jagotec shall specify CRTX’s purchase order number, monthly delivery schedule, campaign size, and any other elements

		necessary to ensure the timely production and delivery of the Product. The quantities of Product ordered in such written orders shall be firm and binding on CRTX and shall not be subject to reduction by CRTX and the quantity of Product so ordered shall not exceed [**] percent ([**]%) ([**] percent ([**]%) in the twelve months following the Marketing Approval for the Finished Product is received from the FDA) or fall short of [**] percent ([**]%) of the applicable binding forecast for that period provided by CRTX under Section 7.1(a) above. Jagotec shall have [**] days to object (to the extent that such objection is reasonable or is because of a breach of the foregoing sentence) in writing to CRTX to any element of a Firm Order. If Jagotec does not object, then such Firm Order shall be binding on Jagotec and no part shall be subject to change by Jagotec.
7.2		(a) CRTX shall purchase a minimum of [**] tablets of Product to be delivered from May 30, 2007 (the date of Marketing Approval for the Finished Product received from FDA) to May 29, 2008, and CRTX shall purchase a minimum of [**] tablets of Product from Jagotec in each of the subsequent four twelve (12) month periods. If CRTX does not place orders to purchase the relevant minimum order quantity in the applicable twelve month period, it shall in addition to paying the Price for Product purchased, pay Jagotec an amount equal to the result of the following calculation: [**]% of the Price payable for [**] tablets or [**] tablets (as the case may be) less [**]% of the Price paid by CRTX to Jagotec for Product ordered and purchased in such twelve month period.
		(b) For the duration hereof, CRTX shall purchase the