LUBIPROSTONE EXCLUSIVE MANUFACTURING AND SUPPLY AGREEMENT

Requirements Supplier Agreement

You are currently viewing:

This Requirements Supplier Agreement involves

SUCAMPO PHARMACEUTICALS, INC. | R-Tech Ueno, Ltd

. RealDealDocs™ contains millions of easily searchable legal documents and clauses from top law firms. Search for free - click here.

Title: LUBIPROSTONE EXCLUSIVE MANUFACTURING AND SUPPLY AGREEMENT
Governing Law: Delaware Date: 3/16/2009
Industry: Biotechnology and Drugs Sector: Healthcare

LUBIPROSTONE EXCLUSIVE MANUFACTURING AND SUPPLY AGREEMENT, Parties: sucampo pharmaceuticals inc. , r-tech ueno ltd

[*] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

Exhibit 10.44

LUBIPROSTONE EXCLUSIVE MANUFACTURING AND SUPPLY AGREEMENT

THIS LUBIPROSTONE EXCLUSIVE MANUFACTURING AND SUPPLY AGREEMENT (“Agreement”) is made this 23th day of February, 2009 (the “Effective Date”), by and among Sucampo Pharma, Ltd., a corporation organized and existing under the laws of Japan and a wholly-owned subsidiary of Sucampo Pharmaceuticals, Inc., a corporation organized and existing under the laws of the state of Delaware, U.S.A., and having its principal office at Sakurabashi Toyo Building, Fourth Floor, 2-2-16 Sonezakishinchi, Kita-ku, Osaka 530-0002 (“SPL”), R-Tech Ueno, Ltd., a corporation organized and existing under the laws of Japan and having its registered office at 1-1-7 Uchisaiwaicho, Chiyoda-ku, Tokyo 100-0011 (“RTU”) (each referred to herein as a “Party” and collectively as the “Parties”).

WHEREAS, RTU has expertise in the manufacture of drug substances and drugs for preclinical, clinical and commercial use;

WHEREAS, SPL is a Japan-based pharmaceutical company that seeks a supply source for Drug Substance and Drug Product (defined below) for SPL clinical evaluation and commercial sale in the SPL Territory (defined below);

WHEREAS, SPL may, from time-to-time, and in accordance with this Agreement, enter into Third Party (as defined below) agreements with Persons (as defined below) for joint clinical evaluation and joint commercial sale of Drug Substance and Drug Product in the SPL Territory;

WHEREAS, RTU has in the past supplied to SPL LUBIPROSTONE (also known as RU-0211, SPI-0211, and AMITIZA®) for preclinical and clinical development, and as such RTU has developed a substantial level of expertise in the manufacture of Drug Substance and Drug Product;

WHEREAS , RTU desires to be the exclusive clinical and commercial supplier of Drug Substance and Drug Product; and

WHEREAS, SPL seeks to have RTU supply Drug Substance and Drug Product as further defined herein for use in SPL clinical development and for future commercial sale in the SPL Territory and desires to have RTU be SPL’s exclusive supplier of Drug Substance and Drug Product.

NOW, THEREFORE, in consideration of the mutual promises herein, the Parties agree as follows:

ARTICLE 1. DEFINITIONS

Article 1.1. “Additional Materials” means all raw materials, resins, chemical intermediates, components, excipients, and other ingredients and packaging materials and supplies, needed to manufacture the Drug Substance and Drug Product for use in SPL Territory, including costs for relevant in-bound freight.

Article 1.2 “Applicable Law” mean all federal, state, local, national and supra-national laws, statutes, rules and regulations, including any rules, regulations, or requirements of Regulatory Authorities, major national securities exchanges or major securities listing organizations, that may be in effect from time to time during the Term and applicable to a particular activity hereunder.

Article 1.3 “Certificate of Analysis” means a certificate provided by RTU to SPL with each shipment of the Drug Substance and the Drug Product, which sets forth: (a) the results of any quality assurance testing; and (b) the manufacturing date.

Article 1.4. “Confidential Information” means all information, whether in tangible form or not, provided by either party hereunder to the other, including but not limited to: financial information, including but not limited to current and projected financials and funding needs; information on research and development compounds, products, and processes; trade secrets; technical know-how; formulas; studies; regulatory submissions and records; research data and information; sales and marketing information (including, without limitation, customer lists); inventions; patent information and all other information pertaining to a party’s intellectual property; in any form (including but not limited to information provided orally, electronically, or in writing). It shall further include the existence and nature and terms of this Agreement, and any and all attachments or exhibits thereto.

Article 1.5. “Drug Substance” means the LUBIPROSTONE active ingredient, prior to formulation as a final drug product.

Article 1.6. “Drug Product” means a finally formulated LUBIPROSTONE drug product PRIOR to packaging for clinical use or commercial sale, as appropriate.

Article 1.7 “Good Manufacturing Practices” or “GMP” means quality systems and current good manufacturing practices applicable to the manufacture, labeling, packaging, handling, storage, and transport of active pharmaceutical ingredients, bulk dosage forms and packaged dosage forms, as set forth in the Pharmaceutical Affairs Law and its related Ordinances including the MHLW Ordinance No. 179, December 24, 2004, any update thereto and any other laws, regulations, policies, or guidelines applicable to the manufacture, labeling, packaging, handling, storage, and transport of pharmaceutical products in the Territory, and/or any applicable foreign equivalents thereof, and any updates of any of the foregoing.

Article 1.8 “Latent Defect” means Drug Substance or Drug Product not conforming to RTU’s obligation for Drug Product pursuant to Article 2.1 and pursuant to batch testing and release such that the related non-conformance of Drug Product is not readily discoverable based on SPL’s or SPL designee’s normal incoming-goods inspections, as the case may be.

Article 1.9 “LUBIPROSTONE” means the compound known as RU-0211, SPL-0211, or SPI-0211 or Amitiza® as described in more detail in Appendix A.

Article 1.10 “NDA” refers to a New Drug Application, as defined by laws for such

application within the SPL Territories (as defined below) and applicable regulations promulgated in the countries or territories there under, or other appropriate marketing authorization in Japan, or any counterpart application or marketing authorization in any country of the SPL Territory.

Article 1.11 “Order” means, with respect to clinical or commercial supply of Drug Product, a written communication from SPL to RTU of SPL’s need for a particular supply period, issued in accordance with Articles 2.4 and 2.5.

Article 1. 12 “Person” means any individual, trust (or any of its beneficiaries), estate, partnership, limited partnership, association, limited liability company, corporation, any other enterprise engaged in the conduct of business or operating as a non-profit entity, however formed or wherever organized, or any governmental body, agency or unit.

Article 1.13 “Product Defect” means Drug Product not conforming to RTU’s obligations for Drug Product pursuant to Article 2.1 and pursuant to batch testing and release such that the related non-conformance of Drug Product may be readily discovered based on SPL’s or its designee’s normal incoming-goods inspections procedures, as the case may be.

Article 1.14 “Regulatory Approval” means any and all approvals, licenses (including product and establishment licenses), registrations, or authorizations of any Regulatory Authority necessary to develop, manufacture, commercialize, promote, distribute, transport, store, use, sell or market the Drug Substance or Drug Product for use in the SPL Territory.

Article 1.15 “Regulatory Authority” means any national, supra-national, regional, federal, state, provincial or local regulatory agency, department, bureau, commission, council or other governmental entity (including, without limitation, the Minister of Health, Labour and Welfare of Japan, the National Health Insurance Plan, and any prefecture having jurisdiction over the manufacture of the Product in the Territory) regulating or otherwise exercising authority over the distribution, importation, exportation, manufacture, use, storage, transport, clinical testing or sale of the Drug Substance or Drug Product.

Article 1.16 “Regulatory Filings” means, with respect to the Product in the Territory, all applications, registrations, licenses, authorizations and approvals (including all Regulatory Approvals), all correspondence submitted to or received from the Regulatory Authorities (including minutes and official contract reports relating to any communications with any Regulatory Authority) and all supporting documents, and all data contained in any of the foregoing.

Article 1.17. “SKU(s)” means Stock Keeping Unit(s) and are the smallest unit of measure to identify manufacturing and distribution of the Drug Product.

Article 1.18 “Specifications” mean the manufacturing, quality control, packaging, labeling, shipping and storage specifications as separately set out for Drug Product in Appendix B and as updated from time to time on mutual agreement in writing by the parties.

Article 1.19. “SPL Territory” means all of the countries located in Japan, Asia and Oceania,

and their territories and possessions.

Article 1.20 “Third Parties” means any Person other than SPL and RTU and their respective affiliates and subsidiaries.

ARTICLE 2. GENERAL TERMS OF MANUFACTURING AND SUPPLY

Article 2.1. Supply. Subject to the terms of this Agreement, and to the terms and conditions of agreements related to development and commercialization of Drug Substance and Drug Product with Third Parties, RTU agrees to manufacture and supply the Drug Substance and the Drug Product to SPL and SPL agrees to purchase said Drug Substance and Drug Product in all such quantities as required by SPL for SPL’s clinical and commercial purposes. All such Drug Substance and Drug Product manufactured or supplied by RTU in accordance with this Agreement shall:

	(a)		be manufactured in accordance and in compliance with Applicable Law, including GMP;

	(b)		be manufactured in accordance with the applicable Regulatory Filings and Regulatory Approvals;

	(c)		upon delivery, not be adulterated or misbranded as defined by Applicable Law;

	(d)		upon delivery, have a minimal shelf life of the longer of [] ([]) months or [] percent ([]%) of the shelf life registered in the underlying Regulatory Approval;

	(e)		be free from defects in materials and workmanship; and

	(f)		be in compliance with all Specifications for the Drug Substance and Drug Product.

Article 2.2. Cost to Produce. RTU, at its sole expense, will provide all labor, utilities, equipment, personnel, facilities, raw materials and components necessary for manufacturing, development and implementation of all appropriate quality control measures, shipping, and storage of the Drug Substance and the Drug Product in compliance with the Specifications and the warranties contained in Article 9 and the Regulatory and Legal requirements of Article 7. RTU shall also be responsible for all process development and validation, including manufacturing process improvements, and scale-up. SPL, at its sole expense, will provide all resources necessary to ship, store, and otherwise handle such Drug Substance and Drug Product in a manner necessary to meet applicable Regulatory and Legal requirements, after delivery of the Drug Substance and the Drug Product to SPL as described in Article 2.8. RTU shall purchase all Additional Materials (as referred to in the relevant Regulatory Approvals) which are needed for the manufacture of the Drug Substance and Drug Products as per the current regulatory files, under its own liability and costs. If RTU wishes to change suppliers and the change will have an impact of a Regulatory Filing, such change shall be subject to SPL’s prior written approval, such approval not to be unreasonably withheld.

Article 2.3. Quality Assurance. RTU, at its sole expense, will (i) conduct the commercial stability program with respect to the Drug Product pursuant to Applicable Law, and (ii) perform all testing for compliance with the Specifications and the applicable GMPs and will supply a chemical Certificate of Analysis with each batch of Drug Substance and Drug Product and any other documentation required by law or regulation. Complete copies of all test results and/or assays and/or batch records will be submitted to SPL promptly following any reasonable request therefor during the term of this Agreement. RTU shall make available their facilities and relevant records for inspection

by the appropriate government authorities, SPL or its licensee for regulatory or quality assurance purposes upon reasonable notice and at reasonable times during normal business hours; provided, however, that the inspection by SPL or its licensee hereunder shall be within the scope of inspection that is allowed under the relevant statutes and regulations.

Article 2.4. Clinical Supply; Order. During the term of this Agreement, SPL shall grant RTU the exclusive right to manufacture and supply Drug Substance and Drug Product to SPL for clinical development purposes. During the term of this agreement, RTU and SPL shall from time to time confer and agree on SPL’s drug supply needs for SPL’s ongoing clinical development program. SPL shall inform RTU of its final requirements in advance of needing clinical supply in such timing as RTU shall reasonably need to duly perform its obligations hereunder, which shall constitute SPL’s Order to RTU and which, subject to the terms and conditions of this Agreement, RTU agrees to supply.

Article 2.5. Commercial Supply; Exclusivity; Forecasting; Order. During the term of this Agreement, SPL shall grant RTU the exclusive right to manufacture and supply Drug Product to SPL for commercial purposes subject to appropriate marketing authorization in Japan or any counterpart marketing authorization in any country of the SPL Territory in respect of the Drug Product. Commencing from the date of filing of the first NDA for a particular Drug Product, SPL shall provide to RTU in writing a 12 month forecast of its requirements for Drug Product which forecast will be updated quarterly until SPL’s first commercial sale. Thereafter, SPL shall provide RTU a forecast in accordance with the following:

	(a)		No later than the last business day of each calendar month during the Term SPLwill provide RTU with an updated twenty-four (24) month rolling forecast of the Drug Product to be manufactured and supplied by RTU (each a “Rolling Forecast”) for the twenty-four (24) month period commencing at the beginning of the following month with the first three (3) months considered an Order. Each Rolling Forecast will be broken down for each month of such period into the quantity (by SKU, packaging and size of Drug Product) and shipping dates. The first two (2) months of each Rolling Forecast will restate the balance of the purchase order period of the prior Rolling Forecast, and the third month of the Rolling Forecast will constitute the new Order for which SPL will be obligated to purchase and take delivery of the Drug Product.

	(b)		Except as set forth herein, all months of the Rolling Forecast other than the first three (3) months will set forth SPL’s best estimate of its requirements for the supply of Drug Product, and the Rolling Forecast for the months four (4) through twenty-four (24) of each Rolling Forecast will not be binding.

	(c)		The Rolling Forecast for the months four (4) through twenty-four (24) of each Rolling Forecast shall not increase or decrease by more than [] percent ([]%) on a month-to-month basis.

	(d)		Increases or decreases in the Rolling Forecast beyond those set out in Section 2.5(c) shall be at RTU’s discretion.

Article 2.6. Promotional Sample Supply. During the term of this agreement, RTU and SPL shall from time to time confer and agree on SPL’s Drug Product supply needs for promotional purpose. SPL shall inform RTU of its final requirements in advance of needing promotional sample shall reasonably need to duly perform its obligations hereunder, which shall constitute SPL’s Order to RTU and which, subject to the terms and conditions of this Agreement, RTU agrees to supply.

Article 2.7. Placement and Acceptance of an Order.

	2.7.2		Placement. All purchases of Drug Products shall be pursuant to written Orders consistent with Article 2.5(a), which shall be placed by SPL and/or its distributors at least sixty (60) days prior to the date of which Drug Products shall be delivered to SPL or the applicable distributor. Each such purchase order will be in agreement with the purchase order period of the most recent Rolling Forecast. If an Order for any month is not submitted by the above deadline, SPL will be deemed to have submitted an Order in that month for the amount of Drug Product set forth in the most recent Rolling Forecast for such month. Each Order hereunder shall specify the desired quantities of each of the Drug Products, in finished forms and samples, and the delivery dates therefore.

	2.7.3		Acceptance. RTU shall have ten (10) Business Days from receipt of an Order from SPA to reject or propose to modify an Order. RTU may only reject an Order that (a) lists products that are not covered by this Agreement, or (b) that is in excess of the amount permitted by Article 2.5 and Section 2.7.2.

Article 2.8. Delivery; Risk of Loss. The Drug Products hereunder shall be delivered per SPL specifications for the relevant Drug Product on or up to three (3) days before the delivery date specified in the order accepted by RTU, subject to the release of the relevant Drug Products as per Article 2.3. SPL shall designate to RTU the carrier which will take delivery of the Drug Products. RTU shall contact such carrier when the Drug Products are ready for shipping and shall arrange for collection, and transportation of the Drug Products. RTU shall inform SPL two (2) Business Days prior to pick-up by the carrier. SPL or a designated Third Party shall bear the costs for transport of the Drug Product and will be invoiced directly by the carrier. The quantity of each Drug Product actually delivered by RTU with respect to each accepted Order shall not exceed a range of minus [*] percent ([*]%) up to plus [*] percent ([*]%) of the quantity of the relevant Drug Product specified in the Order, unless agreed differently by SPL or its designated Third Party. Delivery documents shall include Order, quantity, copy of the Certificate of Analysis, items codes and description, lot number, expiry date of Products, number of shippers, weight, number of pallets.

Article 2.9 Inventory; Reports. On a monthly basis, RTU shall provide SPL with a report detailing present inventory of Drug Substance and Drug Product, along with RTU’s schedule for production for the succeeding three months. In the event that Drug Product available to SPL is in short supply, RTU shall notify SPL of such shortage as soon as possible. In the event there is a short supply of Drug Product and RTU cannot supply Drug Product to SPL in an amount equal to SPL’s firm order, then RTU (i) shall indemnify SPL for any loss, including but not limited to loss of profit, arising from such shortage of Drug Product and (ii) shall allocate available Drug Product to SPL in each month that such a shortfall exists (and in each month thereafter until the shortfall to SPL is remedied) in an amount equal to the Drug Product of (a) the amount of available Drug Product for that month, and (b) a

fraction the numerator of which is (i) the aggregate of firm orders made by SPL over the subsequent twelve (12) month period including the shortfall month and the denominator of which is (ii) the sum of (x) the aggregate quantity of firm orders made by SPL over the subsequent twelve (12) month period including the shortfall months and (y) the aggregate quantity of lubiprostone product over the same twelve (12) month period required by other licensees outside the SPL Territory by reference to firm orders placed with RTU for such licensees’ requirements outside the SPL Territory.

Article 2.10. Non-Exclusivity. Nothing in this Agreement shall prohibit RTU, either clinically or commercially, from manufacturing or supplying, either on its behalf or for any third party, drug products containing the Drug Substance, or drug products containing different active ingredients which require the same reagents as the production of LUBIPROSTONE, either in the SPL territory or in other parts of the world, provided, however, that RTU shall be prohibited from supplying the Drug Substance or the Drug Products in the SPL Territory or to those that induce or facilitate sale in the SPL Territory of the Drug Substance or the Drug Products by any party other than SPL.

Article 2.11. Performance Issue. If either party becomes aware of any issue that may materially impact RTU’s ability to fulfill its obligations under this Agreement, it shall immediately notify the other party and both parties shall confer in good faith in order to address such issue.

Article 2.12 Manufacturing Changes. RTU assumes any and all responsibility to make changes to the manufacturing processes, test methods, etc. for the manufacture of products at the manufacturing location, not specific to the Drug Substance and Drug Product, and will solely bear all expenses related thereto. For changes that are not required by a Regulatory Authority, including but not limited to reformulations of the Drug Substance or Drug Product, addition of new strengths to the Drug Product, new presentations and formats of the Product that negatively impacts SPL’s commercialization of the Product, then RTU shall indemnify SPL or its designee for any loss, including but not limited to loss of profit, arising from such change.

ARTICLE 3. ADDITIONAL SERVICES

Article 3.1 Laboratory and Regulatory Consulting Services. From time-to-time, under this Agreement, SPL may request performance of “Additional Services” by RTU, which may include without limitation (i) the formulation and/or process development of Drug Substance and/or Drug Product, or (ii) regulatory consulting in connection with RTU’s supply of such compound and/or product. The resulting work products of Additional Services will be “Deliverables”.

Article 3.2 Placement and Acceptance of an Order for Additional Services.

3.2.1 Placement. SPL shall place an Order for Additional Services at least thirty (30) days prior to the date of which Deliverable shall be due to SPL.

3.2.2 Acceptance. RTU shall have ten (10) Business Days from receipt of an Order for Additional Services from SPL to reject or propose to modify such Order. If such Order is not rejected it shall be deemed accepted and RTU shall, subject to the terms and conditions of this Agreement, be obligated to supply it by its terms.

Article 3.3 Performance of Additional Services. RTU shall perform Additional Services in accordance with the terms of this Agreement, the Order, and all Applicable Laws. RTU shall provide, at its own expense,

SITE SEARCH

AGREEMENTS / CONTRACTS

CLAUSES

Search Contract Clauses >>

Browse Contract Clause Library>>

Get Email Updates