TRU-015 for the Treatment of Rheumatoid Arthritis. Rheumatoid arthritis, or RA, is estimated to affect between 2 and 2.5 million people in the United States, with approximately 100,000 new cases diagnosed each year. It is estimated that approximately 4.3 million people are affected by RA in the United States, Japan and Europe. Total worldwide sales of protein therapeutics used for the treatment of RA were $7.6 billion in 2005 and are expected to grow to $10 billion in 2010
EX-10.38 41 v18917orexv10w38.txt EXHIBIT 10.38 Exhibit 10.38 CONFIDENTIAL PORTSMOUTH QUALITY AGREEMENT RELATING TO THE MANUFACTURING SERVICES AGREEMENT DATED NOVEMBER 21, 2005 BETWEEN LONZA BIOLOGICS ***. AND TRUBION PHARMACEUTICALS, INC. Page 1 of 15 PORTSMOUTH QUALITY AGREEMENT This Portsmouth Quality Agreement ("Portsmouth Quality Agreement") is dated effective as of November 21,2005, and it defines the roles and responsibilities for the quality operations between LONZA BIOLOGICS ***, the registered office of which is at *** (herein after referred to as ("LB") and TRUBION PHARMACEUTICALS, INC., of 2401 4th Avenue, Suite 1050, Seattle, WA 98102, USA (herein referred to as the "Customer") with respect to manufacture of Customer's proprietary Small Modular lmmunoPharmaceutical (SMIP) known as TRU-015 ("TRU-015") under that certain manufacturing services agreement between the parties of even date herewith (the "Services Agreement") in preparation for regulatory filings and for human clinical use. When used in this Portsmouth Quality Agreement, the term "Product" shall have the meaning given in the Service Agreement, and refers to TRU-015 and/or to the form of TRU-015 manufactured under the Services Agreement, as the context requires. This is the Portsmouth Quality Agreement referred to in Exhibit A of the Services Agreement. Capitalized terms used but not defined in this Portsmouth Quality Agreement shall have the meaning given in the Services Agreement. This Portsmouth Quality Agreement may be amended by written agreement of the parties. In the event of a conflict between the Portsmouth Quality Agreement and the Services Agreement, the Services Agreement shall control. This Portsmouth Quality Agreement may be executed in any number of counterparts, each of which shall for all purposes be deemed an original and all of which, taken together, shall constitute one and the same instrument. A facsimile signature shall be deemed to be and shall be as effective as an original signature. The responsibilities and rights of the parties under this Portsmouth Quality Agreement are set forth below. A. OVERALL RESPONSIBILITIES This Portsmouth Quality Agreement outlines the responsibilities of the Customer and LB with respect to the quality assurance of Product manufactured and supplied by LB for the Customer under the terms of the Agreement. This Portsmouth Quality Agreement takes the form of a detailed list of activities associated with the manufacture, testing and disposition of Product. Responsibility for each activity is assigned to either the Customer or LB, or is assigned to both the Customer and LB. Additional details are provided in the Services Agreement and in the SOP's referred to in this Portsmouth Quality Agreement. This detailed list describes generic quality activities that would be performed by both parties for Product used in clinical trial supply. The specific services to be provided by LB are set out in the Services Agreement (and any Amendments to the Agreement). LB is responsible for ensuring that the quality requirements for Product are as specified in the approved Product Specifications, and that Product is manufactured, tested and stored by LB in accordance with current Good Manufacturing Practices (cGMP) and all applicable US and EU laws, regulations and ICH guidelines. The Customer is responsible for shipping and the final review, approval, and disposition of product for use in the clinic. The Customer is responsible for Product development, technical oversight, product specifications and regulatory agency filings. Page 2 of 15 SPECIFIC RESPONSIBILITIES RESPONSIBILITIES AND RIGHTS ------------------------------------------------------------------------------------------ ITEM LB CUSTOMER(1) - ------------------------------------ ----------------------------------------------- ---------------------------------------- 1.0 Organisation and Personnel - Ensure adequate number of personnel with - Right to audit appropriate training, skills, knowledge and experience to manufacture and test Product in accordance with cGMP 2.0 Facilities, Utilities and - Ensure facilities, environment, utilities, - Right to audit Equipment equipment, computerised systems and software are properly designed, validated and maintained in accordance with cGMP - Ensure Product is manufactured and tested - Right to audit only at sites as agreed with Customer - Make available for review by Customer - Right to audit relevant SOPs of LB related to the Agreement and services of LB - Provide Customer with Site Master File - Include Drug Master File reference reference that will allow regulatory into regulatory submissions, as agencies the ability to cross-reference appropriate other products that are manufactured at LB's manufacturing and testing locations - Provide Customer with Lonza Policy that no penicillin is manufactured or tested at site
Page 3 of 15 RESPONSIBILITIES AND RIGHTS ------------------------------------------------------------------------------------------ ITEM LB CUSTOMER(1) - ------------------------------------ ----------------------------------------------- ---------------------------------------- 3.0 Raw Materials for Process and - Source, test and release raw materials and - Right to audit; right to review all Packaging of Product / Vendor primary packaging of appropriate quality raw material specifications, grades Qualification Process for processing of Product and vendors used in manufacture of Product - Customer to provide LB with list of critical raw materials used in Customer process; update with changes as necessary - Propose and jointly agree to - Right to approve vendor, grade and specifications, vendors and grade of specifications of critical raw critical raw materials used in Customer materials used in Customer process, process in accordance with LB policy, with including excipients, and raw preference for non-animal and non-human materials of animal or human origin derived raw materials - Acknowledge and support Customer's goal not to use any raw materials of animal or human origin in the development of Customer process - Retain representative samples - Right to audit
(1) Throughout the Portsmouth Quality Agreement, Customer's column includes the phrase "right to audit" - the use of this phrase in certain instances but not in others does not and shall not imply that Customer's audit rights pursuant to Clause 15 below are limited to those boxes where "right to audit" appears Page 4 of 15 RESPONSIBILITIES AND RIGHTS ------------------------------------------------------------------------------------------ ITEM LB CUSTOMER(1) - ------------------------------------ ----------------------------------------------- ---------------------------------------- 4.0 Cell Banks - Prepare, characterise and store cell bank(s) if contracted by Customer - Jointly agree on testing specifications - Jointly agree on testing and test methods to enable release of cell specifications and test methods to banks for use in LB's multi-product enable Product manufactured from manufacturing facility cell banks to be used in the clinic - Perform stability testing of cell bank(s) - Right to audit if contracted by Customer and share data with Customer IF CELL BANK SUPPLIED BY CUSTOMER - Review and approve characterisation data. - Supply cell bank characterisation Store working stock or cell bank data for review and approval. Transfer cell bank (or portion thereof) to LB - Provide shipping validation data if - Right to audit requested by Customer IN ALL CASES - Provide inventory levels periodically upon request by Customer 5.0 Product Specification - With the Customer determine and approve - With LB determine and approve the the following Product specification(s) as following Product specification(s) required: as required: - Drug substance (including testing - Drug substance (including performed on fermenter contents for testing performed on fermenter adventitious agents) contents for adventitious agents)
Page 5 of 15 RESPONSIBILITIES AND RIGHTS ------------------------------------------------------------------------------------------ ITEM LB CUSTOMER(1) - ------------------------------------ ----------------------------------------------- ---------------------------------------- 6.0 Production and Process - Make available for review by Customer - Right to review Control documents relating to facility, equipment, Process and test methods, and GMP systems - Jointly review and approve Process descriptions - Jointly review and approve Process descriptions - Agree in-process testing strategy - Define and perform an in-process control - Right to review and comment on and testing program strategy master batch records - Using LB templates prepare master batch - Right to audit records for each processing step and provide to Customer for review and - Right to audit comment. Retain final master batch record on site at LB - Relevant sections of Customer's regulatory submissions to be made - Designate unique batch numbers for raw available to LB as appropriate materials, process materials and Product - Right to audit - Manufacture of Product in accordance with Product Specifications, cGMP standards, - Right to designate 1 of its batch records, in-process controls and employees or consultants as in-progress specifications Customer's person on plant, to be present in LB's facility during - Ensure QA representatives on-site or normal business hours to observe available at all times during manufacture the Runs and observe LB's and testing of Product performance, at times and for durations to be agreed. While at - Permit Customer's person on plant to be LB's facility, Customer's present in LB's facility during normal representative shall comply with business hours to observe the Runs and all of LB's applicable policies and observe LB's performance, at times and for procedures, and, at LB's option, durations to be agreed. While at LB's shall be escorted by LB personnel. facility, Customer's representative shall Lonza must agree to all consultants comply with all LB's applicable policies used by Trubion for person on plant and procedures, and, at LB's option, shall activities be escorted by LB personnel - Review and comment on LB's policy - Perform Product changeover testing of for Product changeover testing of Product-contacting equipment in accordance Product-contacting equipment with LB policy
Page 6 of 15 RESPONSIBILITIES AND RIGHTS ------------------------------------------------------------------------------------------ ITEM LB CUSTOMER(1) - ------------------------------------ ----------------------------------------------- ---------------------------------------- 7.0 Product Storage, Labelling - Store, label and package the Product - Right to audit and Packaging Prior to (including samples) as defined in the Shipment Product Specification - Provide information on shipping requirements 8.0 Shipment Requirements - Ship Product on behalf of Customer to - Jointly agree with LB on process locations designated by Customer in for shipping requirements accordance with jointly agreed process for shipping requirements - Right to audit - With Customer agree on shipment date for - Acknowledge receipt of Product Product - Right to audit - Provide shipping validation data for Product if contracted by Customer 9.0 Laboratory Controls (QC) - Perform Product release testing against - Right to audit Bulk Drug Substance Specifications - Jointly agree on SOP's describing - Jointly agree on SOP's describing Product-specific analytical testing Product-specific analytical testing methods methods - Provide LB with Product-specific - Retesting, where required, will be information as it relates to sample performed in accordance with LB's retest storage, handling and testing procedure. Out of specification (OOS) requirements Product release testing results will be notified to the Customer as soon as - Review and comment on LB retest possible within 3 business days of the OOS procedure. Review OOS reports; being confirmed comment on corrective and preventative actions - Send samples to Customer for additional testing (including potency testing) in - Perform Product potency testing and accordance with jointly approved SOP provide data to LB; such data will be provided for LB's information only and not for inclusion into LB's Certificate of Analysis. Customer to create Certificate of Analysis for potency testing results.
Page 7 of 15 RESPONSIBILITIES AND RIGHTS ------------------------------------------------------------------------------------------ ITEM LB CUSTOMER(1) - ------------------------------------ ----------------------------------------------- ---------------------------------------- 9.0 Laboratory Controls QC - Retain representative samples of bulk - Right to audit (Continued) Product from each batch in accordance with LB SOP - Right to receive copies of raw data and testing records - If requested by Customer, provide copies of raw data and testing records - Request additional samples to be shipped as required - Take additional representative samples if requested and ship to Customer - Jointly approve Product reference standard Protocol - Prepare and characterise Product reference standard in accordance with jointly agreed - Right to audit Protocol, if contracted by Customer - Jointly approve Product reference - Jointly approve Product reference standard standard report report 10.0 Use of Contract Testing - Qualify Contract Testing Laboratories for - Right to jointly audit Laboratories Product release testing in accordance with LB policy - Consent or reject to the proposed use of Contract Testing - Notify Customer of Contract Testing Laboratories Laboratories intended to be used for Product release testing - Right to audit - Facilitate audit by Customer if requested - Right to request, receive and use from time to time copies of LB's audits of Contract Testing Laboratories when possible, - If not prohibited by Contract Testing unless prohibited by Contract Laboratory, provide Customer with copies Testing Laboratories of LB's audits of Contract Testing Laboratories when possible, if requested 11.0 Product Release and Lot - Review batch record for compliance with - Right to review completed and Review cGMP, manufacturing controls, and with the reviewed Product batch records Product Specifications - Right to review - Provide Customer with an electronic copy of the Process documentation including, main operational steps from the completed batch record. This will include Product analysis, a summary of batch related deviations and environmental monitoring summaries, as well as process data, as requested
Page 8 of 15 RESPONSIBILITIES AND RIGHTS ------------------------------------------------------------------------------------------ ITEM LB CUSTOMER(1) - ------------------------------------ ----------------------------------------------- ---------------------------------------- 11.0 Product Release and Lot - If requested by Customer, send full - Right to request and receive full Review (Continued) electronic copies of actual deviation copies of actual deviations - Prepare manufacturer's Certificate of - Prepare Certificate of Analysis and Analysis, including related Certificate of Certificate of Compliance for Compliance release of product for use in human clinical trials - Release or reject Product - Release or reject Product for use in human clinical trials 12.0 Deviations and Failed Run - Initiate investigations, evaluate and - Right to audit Investigations and Reports define follow up actions and final approval of deviations and failure - Review significant deviations; investigations comment on corrective and preventative actions - Notify Customer of all significant deviations within 24 hours or at least 3 - Review failure investigation report business days of the event being assigned and comment on corrective and as significant, and send Customer the preventative actions related action plan. (A significant deviation is defined in Trubion standard operating procedure 3150 and Lonza SOP USPO1698) - If requested by Customer, send full copies of deviation and investigation reports. - Notify Customer of failed runs within 24 hours or at least 3 business days of failure being identified - Immediately and within at least 3 business days of event being identified, notify Customer of any events which may impact batches previously shipped or released
Page 9 of 15 RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------------------------- ITEM LB CUSTOMER(1) ----- ----------------------------------------- ------------------------------------- 13.0 Change Control Procedures CUSTOMER PROPOSED CHANGES - Process Product-specific change - Propose Customer through change control and notify Product-specific changes and Customer of change approval. If provide rationale in writing change rejected, discuss reasons for rejection with Customer - Approve proposed Product-specific changes prior to implementation LB PROPOSED CHANGES - Propose Product-specific changes and - Process Product-specific change provide rationale for change to through change control and process descriptions; test methods; notify LB of change approval. sampling plans; specifications for Customer approval for change key raw materials (animal and / or controls will be needed 10 days human derived raw materials, , from receipt If change rejected, chromatography resins and final discuss reasons for rejection formulation excipients); Product with LB specification(s) and stability programme, in-process controls and - Approve proposed other key processing steps Product-specific change prior to implementation - Inform Customer of changes to key - Right to audit personnel as identified in Appendix 1 - Inform Customer of changes to major - Right to audit items of equipment, premises and utilities used for manufacture of Product ALL CHANGES - With Customer define strategy for - With LB define strategy for notifying change to Regulatory. notifying change to Regulatory. Agency as appropriate (see Section Agency as appropriate (see 20.0, below, Regulatory Submissions) Section 20.0, below, Regulatory Submissions) - Inform Customer of Product batches manufactured with the change until - Ensure Product is not regulatory approval obtained, if distributed until Regulatory required approval obtained, if required - Cooperate with Customer in connection with change controls; - Cooperate with LB in connection respect Customer's change controls, with change controls; respect and, as appropriate, use it to LB's change controls, and, as initiate LB's change controls appropriate, use it to initiate Customer's change controls
Page 10 of 15 RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------------------------- ITEM LB CUSTOMER(1) ---- ----------------------------------------- ------------------------------------- 14.0 Reprocessing / Rework - Processing to be performed in - Review and comment on LB's accordance with LB SOP. With reprocessing / rework SOP; with Customer agree on and approve LB agree on reprocessing / reprocessing / rework procedures, rework procedures, where where possible prior to execution possible prior to execution - Provided documented reason and - Right to audit justification for reprocessing / rework event - With Customer agree on the - With LB agree on the appropriate appropriate testing required prior testing required prior to to Product release Product release 15.0 Audit - Permit Customer representatives - Provide reasonable notice of access as reasonably required to intention to audit conduct a cGMP compliance audit, including access to warehousing, - Right to 2 standard cGMP manufacturing areas, laboratories, compliance audits per year, plus and manufacturing records and right to additional "for cause" documents, including SOPS (unless audits they contain specific LB proprietary information eg media formulations), - Right to audit each batch record and personnel, for audit purposes. Customer representatives to be - Hold an exit meeting to discuss accompanied at all times by LB observations personnel - Provide an audit report within - *** cGMP compliance audits permitted 30 days of completion of audit per year, with an audit not to exceed *** and a maximum of ***. Additionally the Customer may request "for cause" audits to address production of Product quality issues - *** audit for each batch record if requested by Customer - Allow the Customer to observe operations related to Product manufacturing and testing providing other Customer's confidentiality is respected - Provide a written response to all audit findings that require corrective action within 30 days of receipt of the audit report. Response to include expected timelines 16.0 Product Complaints - Respond to requests for data to - Receive and investigate Product
Page 11 of 15 RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------------------------- ITEM LB CUSTOMER(1) ---- ----------------------------------------- ------------------------------------- and Recall assist Customer in their complaints and instigate Product investigation. Agree a time scale recall as appropriate for response 17.0 Batch Records - Retain records associated with - Right to audit manufacture and testing records of Product including records associated - Customer to approve destruction with the inspection and release of or request receipt of records raw materials and primary packaging components of the Product for 5 years from the date of manufacture of Product. Date of manufacture is defined as the date Product is dispensed in to the bulk product container) - Notify Customer of intent to destroy records with option to send records to Customer 18.0 Process Validation / - With Customer define process - With LB define process Stability Studies validation plans for Product validation plans for Product including analytical validation and including analytical validation stability studies and stability studies WHERE PROCESS VALIDATION IS PERFORMED BY LB - Provide Customer with - Approve Product-specific Product-specific validation validation protocol(s) including protocol(s) for approval prior to stability protocols execution - Review and comment on - Provide Customer with draft Product-specific validation Product-specific validation report(s) including stability report(s) for review and comment reports - Issue Customer with copy of final Product specific validation report(s) WHERE PROCESS VALIDATION IS PERFORMED BY CUSTOMER - Incorporate specifications in cGMP - Provide LB with process documentation and regulatory validation reports submissions
Page 12 of 15 RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------------------------- ITEM LB CUSTOMER(1) - ------------------------------------ ----------------------------------------- ------------------------------------- 19.0 Regulatory Agency Inspection GMP INSPECTIONS - Inform Customer of Regulatory Agency - For Regulatory Agency inspections or regulatory action inspections of regulatory action affecting manufacture, testing or affecting Product, provide storage of Product assistance when requested by LB - Notify Customer of inspection - Common on proposed inspection observations (including Deficiency responses to observations Letters) affecting the Product, relevant to Product process or systems relating to the Product 20.0 Regulatory Submissions WHERE A DATA PACK IS PROVIDED BY LB TO SUPPORT CUSTOMER'S CLINICAL TRIAL APPLICATION INITIAL APPLICATION, AMENDMENTS AND RESPONSES TO QUESTIONS - Provide Customer with data pack - Prepare and provide LB with copy covering activities performed by LB of relevant sections of clinical trial application for review and - Review and comment on relevant comment prior to submission to sections of clinical trial Regulatory Agency application - Provide LB with copy of relevant sections as submitted to Regulatory Agencies TELECONFERENCES AND MEETINGS WITH THE REGULATORY AGENCIES - Attend teleconferences and meetings - Arrange for LB personnel to have between the Customer and Regulatory option to attend teleconferences Agencies arranged to specifically and meetings between Customer discuss topics relating to LB's and Regulatory Agencies to responsibilities specifically discuss topics relating to LB's responsibilities
[signatures on following page] Page 13 of 15 QUALITY APPROVAL LONZA BIOLOGICS *** Name: *** Signature: *** --------------------------- ----------------------------- Title: Date: December 5, 2005 -------------------------- TRUBION PHARMACEUTICALS, INC. Name: Sally Gould Signature: /s/ Sally Gould ----------------------------- Title: Senior Director Date: December 1, 2005 Page 14 of 15 APPENDIX I TO THE PORTSMOUTH QUALITY AGREEMENT CUSTOMER LONZA SENIOR VICE PRESIDENT, HEAD OF LONZA CONTRACT MANUFACTURING: RESEARCH AND DEVELOPMENT: Kendall M Mohler PhD Senior Vice President Research and Development Trubion Pharmaceuticals Inc 2401 Fourth Avenue. Suite 1050 Seattle, WA 98121 USA Tel: +1 ###-###-#### Tel: + Fax: +1 ###-###-#### Fax: + Email: ***@*** Email: _________ HEAD OF QUALITY: HEAD OF QUALITY: Sally R Gould Senior Director, Regulatory Affairs Trubion Pharmaceuticals Inc 2401 Fourth Avenue, Suite 1050 Seattle, WA 98121 USA Tel: +1 2I0 6 ###-###-#### Tel: _________ Fax: +1 ###-###-#### Fax: _________ Email: ***@*** Email: _________ HEAD OF MANUFACTURING: DIRECTOR OF MANUFACTURING ***: Dale H Scott Vice President, Development Trubion Pharmaceuticals Inc 2401 Fourth Avenue, Suite 1050 Seattle, WA 98121 USA Tel: +1 ###-###-#### Tel: _________ Fax: +1 ###-###-#### Fax: _________ Email: ***@*** Email: _________ QUALITY CONTROL MANAGER: QUALITY CONTROL MANAGER: Raj Dua PhD Director, Product Development Trubion Pharmaceuticals Inc 2401 Fourth Avenue, Suite 1050 Seattle, WA 98121 USA Tel: +1 ###-###-#### Tel: _________ Fax: +1 ###-###-#### Fax: _________ Email: ***@*** Email: _________ Page 15 of 15
