TRU-015 for the Treatment of Rheumatoid Arthritis. According to Datamonitor, rheumatoid arthritis, or RA, is estimated to affect approximately 4.3 million people in the United States, Japan and Europe. Total reported 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-10.35 17 v18917a3exv10w35.txt EXHIBIT 10.35 EXHIBIT 10.35 CONFIDENTIAL PORTSMOUTH QUALITY AGREEMENT RELATING TO THE MANUFACTURING SERVICES AGREEMENT DATED NOVEMBER 21, 2005 BETWEEN LONZA BIOLOGICS, INC. AND TRUBION PHARMACEUTICALS, INC. CONFIDENTIAL TREATMENT Page 1 of 15 CONFIDENTIAL 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 INC., the registered office of which is at INTERNATIONAL DRIVE, PORTSMOUTH, NH 03801 USA (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. CONFIDENTIAL TREATMENT Page 2 of 15 CONFIDENTIAL SPECIFIC RESPONSIBILITIES RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------- ITEM LB CUSTOMER(1) - ------------------------- -------------------------------- ----------------------------- 1.0 Organisation and - Ensure adequate number of - Right to audit Personnel personnel with appropriate training, skills, knowledge and experience to manufacture and test Product in accordance with cGMP 2.0 Facilities, - Ensure facilities, - Right to audit Utilities and environment, utilities, Equipment equipment, computerised systems and software are properly designed, validated and maintained in accordance with cGMP - Ensure Product is - Right to audit manufactured and tested only at sites as agreed with Customer - Make available for review - Right to audit by Customer relevant SOPs of LB related to the Agreement and services of LB - Provide Customer with Site - Include Drug Master File Master File reference that reference into will allow regulatory regulatory submissions, agencies the ability to as appropriate cross-reference 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
CONFIDENTIAL TREATMENT Page 3 of 15 CONFIDENTIAL RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------- ITEM LB CUSTOMER(1) - ------------------------- -------------------------------- ----------------------------- 3.0 Raw Materials for - Source, test and release - Right to audit; right to Process and raw materials and primary review all raw material Packaging of packaging of appropriate specifications, grades Product / Vendor quality for processing of and vendors used in Qualification Product manufacture of Product Process - Customer to provide LB with list of critical raw materials used in Customer process; update with changes as necessary - Propose and jointly agree - Right to approve vendor, to specifications, vendors grade and specifications and grade of critical raw of critical raw materials used in Customer materials used in process in accordance with Customer process, LB policy, with preference including excipients, for non-animal and and raw materials of non-human derived raw animal or human origin 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 - Right to audit samples
(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 CONFIDENTIAL TREATMENT Page 4 of 15 CONFIDENTIAL 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 - Jointly agree on testing specifications and test specifications and test methods to enable release methods to enable of cell banks for use in Product manufactured LB's multi-product from cell banks to be manufacturing facility used in the clinic - Perform stability testing - Right to audit of cell bank(s) if contracted by Customer and share data with Customer IF CELL BANK SUPPLIED BY CUSTOMER - Review and approve - Supply cell bank characterisation data. characterisation data Store working stock or cell for review and approval. bank Transfer cell bank (or portion thereof) to LB - Provide shipping validation - Right to audit data if requested by Customer IN ALL CASES - Provide inventory levels periodically upon request by Customer 5.0 Product - With the Customer determine - With LB determine and Specification and approve the following approve the following Product specification(s) as Product specification(s) required: as required: - Drug substance (including - Drug substance testing performed on (including testing fermenter contents for performed on fermenter adventitious agents) contents for adventitious agents)
CONFIDENTIAL TREATMENT Page 5 of 15 CONFIDENTIAL RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------- ITEM LB CUSTOMER(1) - ------------------------- -------------------------------- ----------------------------- 6.0 Production and - Make available for review - Right to review Process Control by Customer documents relating to facility, equipment, Process and test methods, and GMP systems - Jointly review and approve - Jointly review and Process descriptions approve Process descriptions - Define and perform an - Agree in-process testing in-process control and strategy testing program strategy - Using LB templates prepare - Right to review and master batch records for comment on master batch each processing step and records provide to Customer for review and comment. Retain final master batch record on site at LB - Designate unique batch - Right to audit numbers for raw materials, process materials and Product - Manufacture of Product in - Right to audit accordance with Product Specifications, cGMP - Relevant sections of standards, batch records, Customer's regulatory in-process controls and submissions to be made in-progress specifications available to LB as appropriate - Ensure QA representatives - Right to audit on-site or available at all times during manufacture and testing of Product - Permit Customer's person on - Right to designate 1 of plant to be present in LB's its employees or facility during normal consultants as business hours to observe Customer's person on the Runs and observe LB's plant, to be present in performance, at times and LB's facility during for durations to be agreed. normal business hours to While at LB's facility, observe the Runs and Customer's representative observe LB's shall comply with all LB's performance, at times applicable policies and and for durations to be procedures, and, at LB's agreed. While at LB's option, shall be escorted facility, Customer's by LB personnel representative shall comply with all of LB's applicable policies and procedures, and, at LB's option, shall be escorted by LB personnel. Lonza must agree to all consultants used by Trubion for person on plant activities - Perform Product changeover - Review and comment on testing of LB's policy for Product Product-contacting changeover testing of equipment in accordance Product-contacting with LB policy equipment
CONFIDENTIAL TREATMENT Page 6 of 15 CONFIDENTIAL RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------- ITEM LB CUSTOMER(1) - ------------------------- -------------------------------- ----------------------------- 7.0 Product Storage, - Store, label and package - Right to audit Labelling and the Product (including Packaging Prior to samples) as defined in the - Provide information on Shipment Product Specification shipping requirements 8.0 Shipment - Ship Product on behalf of - Jointly agree with LB on Requirements Customer to locations process for shipping designated by Customer in requirements accordance with jointly agreed process for shipping - Right to audit requirements - Acknowledge receipt of Product - With Customer agree on shipment date for Product - Provide shipping - Right to audit validation data for Product if contracted by Customer 9.0 Laboratory Controls - Perform Product release - Right to audit (QC) testing against Bulk Drug Substance Specifications - Jointly agree on SOP's - Jointly agree on SOP's describing Product-specific describing analytical testing methods Product-specific analytical testing methods - Provide LB with Product-specific information as it relates to sample storage, handling and testing requirements - Retesting, where required, - Review and comment on LB will be performed in retest procedure. Review accordance with LB's retest OOS reports; comment on procedure. Out of corrective and specification (OOS) Product preventative actions release testing results will be notified to the Customer as soon as possible within 3 business days of the OOS being confirmed - Send samples to Customer - Perform Product potency for additional testing testing and provide data (including potency testing) to LB; such data will be in accordance with jointly provided for LB's approved SOP information only and not for inclusion into LB's Certificate of Analysis. Customer to create Certificate of Analysis for potency testing results.
CONFIDENTIAL TREATMENT Page 7 of 15 CONFIDENTIAL RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------- ITEM LB CUSTOMER(1) - ------------------------- -------------------------------- ----------------------------- 9.0 Laboratory Controls - Retain representative - Right to audit QC (Continued) samples of bulk Product from each batch in accordance with LB SOP - If requested by Customer, - Right to receive copies provide copies of raw data of raw data and testing and testing records records - Take additional - Request additional representative samples if samples to be shipped as requested and ship to required Customer - Prepare and characterise - Jointly approve Product Product reference standard reference standard in accordance with jointly Protocol agreed Protocol, if contracted by Customer - Right to audit - Jointly approve Product - Jointly approve Product reference standard report reference standard report 10.0 Use of Contract - Qualify Contract Testing - Right to jointly audit Testing Laboratories Laboratories for Product release testing in accordance with LB policy - Notify Customer of Contract - Consent or reject to the Testing Laboratories proposed use of Contract intended to be used for Testing Laboratories Product release testing - Facilitate audit by - Right to audit Customer if requested from time to time - If not prohibited by - Right to request, Contract Testing receive and use copies Laboratory, provide of LB's audits of Customer with copies of Contract Testing LB's audits of Contract Laboratories when Testing Laboratories when possible, unless possible, if requested prohibited by Contract Testing Laboratories 11.0 Product Release - Review batch record for - Right to review and Lot Review compliance with cGMP, completed and reviewed manufacturing controls, and Product batch records with the Product Specifications - Provide Customer with an - Right to review 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 11.0 Product Release - If requested by Customer, - Right to request and send full receive full
CONFIDENTIAL TREATMENT Page 8 of 15 CONFIDENTIAL RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------- ITEM LB CUSTOMER(1) - ------------------------- -------------------------------- ----------------------------- and Lot Review electronic copies of actual copies of actual (Continued) deviation deviations - Prepare manufacturer's - Prepare Certificate of Certificate of Analysis, Analysis and Certificate including related of Compliance for release Certificate of Compliance 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 - Initiate investigations, - Right to audit Failed Run evaluate and define follow Investigations and up actions and final Reports approval of deviations and failure investigations - Notify Customer of all - Review significant significant deviations deviations; comment on within 24 hours or at least corrective and 3 business days of the preventative actions event being assigned as significant, and send Customer the 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 - Review failure runs within 24 hours or at investigation report and least 3 business days of comment on corrective failure being identified and preventative actions - 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
CONFIDENTIAL TREATMENT Page 9 of 15 CONFIDENTIAL RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------- ITEM LB CUSTOMER(1) - ------------------------- -------------------------------- ----------------------------- 13.0 Change Control CUSTOMER PROPOSED CHANGES Procedures - Process Product-specific - Propose Customer change through change Product-specific changes control and notify Customer and provide rationale in of change approval. If writing change rejected, discuss reasons for rejection with Customer - Approve proposed Product-specific changes prior to implementation LB PROPOSED CHANGES - Propose Product-specific - Process Product-specific changes and provide change through change rationale for change to control and notify LB of process descriptions; test change approval. methods; sampling plans; Customer approval for specifications for key raw change controls will be materials (animal and / or needed 10 days from human derived raw receipt If change materials, , chromatography rejected, discuss resins and final reasons for rejection formulation excipients); with LB Product specification(s) and stability programme, - Approve proposed in-process controls and Product-specific change other key processing steps prior to implementation - Inform Customer of changes - Right to audit to key personnel as identified in Appendix 1 - Inform Customer of changes - Right to audit to major items of equipment, premises and utilities used for manufacture of Product ALL CHANGES - With Customer define - With LB define strategy strategy for notifying for notifying change to change to Regulatory. Regulatory. Agency as Agency as appropriate (see appropriate (see Section Section 20.0, below, 20.0, below, Regulatory Regulatory Submissions) Submissions) - Inform Customer of Product - Ensure Product is not batches manufactured with distributed until the change until regulatory Regulatory approval approval obtained, if obtained, if required required - Cooperate with Customer in - Cooperate with LB in connection with change connection with change controls; respect controls; respect LB's Customer's change controls, change controls, and, as and, as appropriate, use it appropriate, use it to to initiate LB's change initiate Customer's controls change controls
CONFIDENTIAL TREATMENT Page 10 of 15 CONFIDENTIAL RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------- ITEM LB CUSTOMER(1) - ------------------------- -------------------------------- ----------------------------- 14.0 Reprocessing / - Processing to be performed - Review and comment on Rework in accordance with LB SOP. LB's reprocessing / With Customer agree on and rework SOP; with LB approve reprocessing / agree on reprocessing / rework procedures, where rework procedures, where possible prior to execution possible prior to execution - Provided documented reason - Right to audit and justification for reprocessing / rework event - With Customer agree on the - With LB agree on the appropriate testing appropriate testing required prior to Product required prior to release Product release 15.0 Audit - Permit Customer - Provide reasonable representatives access as notice of intention to reasonably required to audit conduct a cGMP compliance audit, including access to - Right to 2 standard cGMP warehousing, manufacturing compliance audits per areas, laboratories, and year, plus right to manufacturing records and additional "for cause" documents, including SOPS audits (unless they contain specific LB proprietary - Right to audit each information eg media batch record formulations), and personnel, for audit - Hold an exit meeting to purposes. Customer discuss observations representatives to be accompanied at all times by - Provide an audit report LB personnel within 30 days of completion of audit - *** cGMP compliance audits permitted 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 - Receive and investigate data to Product
CONFIDENTIAL TREATMENT Page 11 of 15 CONFIDENTIAL RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------- ITEM LB CUSTOMER(1) - ------------------------- -------------------------------- ----------------------------- and Recall assist Customer in complaints and their investigation. Agree instigate Product recall a time scale for response as appropriate 17.0 Batch Records - Retain records associated - Right to audit with manufacture and testing records of Product including records associated with the inspection and release of 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 - Customer to approve to destroy records with destruction or request option to send records to receipt of records Customer 18.0 Process Validation / - With Customer define - With LB define process Stability Studies process validation plans validation plans for for Product including Product including analytical validation and 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) protocol(s) for approval including stability prior to execution protocols - Provide Customer with draft - Review and comment on Product-specific validation Product-specific report(s) for review and validation report(s) comment including stability reports - Issue Customer with copy of final Product specific validation report(s) WHERE PROCESS VALIDATION IS PERFORMED BY CUSTOMER - Incorporate specifications - Provide LB with process in cGMP documentation and validation reports regulatory submissions
CONFIDENTIAL TREATMENT Page 12 of 15 CONFIDENTIAL RESPONSIBILITIES AND RIGHTS --------------------------------------------------------------- ITEM LB CUSTOMER(1) - ------------------------- -------------------------------- ----------------------------- 19.0 Regulatory Agency GMP INSPECTIONS Inspection - Inform Customer of - For Regulatory Agency Regulatory Agency inspections of inspections or regulatory regulatory action action affecting affecting Product, manufacture, testing or provide assistance when storage of Product requested by LB - Notify Customer of - Common on proposed inspection observations inspection responses to (including Deficiency observations relevant to Letters) affecting the Product Product, process or systems relating to the Product 20.0 Regulatory WHERE A DATA PACK IS PROVIDED BY Submissions LB TO SUPPORT CUSTOMER'S CLINICAL TRIAL APPLICATION INITIAL APPLICATION, AMENDMENTS AND RESPONSES TO QUESTIONS - Provide Customer with data - Prepare and provide LB pack covering activities with copy of relevant performed by LB sections of clinical trial application for - Review and comment on review and comment prior relevant sections of to submission to clinical trial application Regulatory Agency - Provide LB with copy of relevant sections as submitted to Regulatory Agencies TELECONFERENCES AND MEETINGS WITH THE REGULATORY AGENCIES - Attend teleconferences and - Arrange for LB personnel meetings between the to have option to attend Customer and Regulatory teleconferences and Agencies arranged to meetings between specifically discuss topics Customer and Regulatory relating to LB's Agencies to specifically responsibilities discuss topics relating to LB's responsibilities
[signatures on following page] CONFIDENTIAL TREATMENT Page 13 of 15 CONFIDENTIAL QUALITY APPROVAL LONZA BIOLOGICS, Inc. Name: S. Kutzer Signature: /s/ S. Kutzer ----------------------------- Title: President Date: December 5, 2005 TRUBION PHARMACEUTICALS, INC. Name: Sally Gould Signature: /s/ Sally Gould ----------------------------- Title: Senior Director Date: December 1, 2005 CONFIDENTIAL TREATMENT Page 14 of 15 CONFIDENTIAL 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: _____________________
CONFIDENTIAL TREATMENT Page 15 of 15
