SUCCESS STORY ON PRODUCTION SHUTDOWN

Transcription

1 SUCCESS STORY ON PRODUCTION SHUTDOWN Fast-Track Consult on Qualification & Validation for Increased Capacity

2 With the expertise of the Biotech Quality Group (BQG), a major pharmaceutical company successfully started up a new production line, while dramatically shortening the required shutdown period and achieving high compliance in the quality and documentation requirements, following the verification approach according to the ASTM E2500.

3 BACKGROUND In pharmaceutical manufacturing, shutdown periods of production operations affect time to market, manufacturing capacity, supply of product, manufacturing cost, and profitability. Impacted stakeholders are the company and patients. A major pharmaceutical company needed to increase the production capacity of an antihemophilic factor, its flagship biotechnology product. In order to do so, the company had to build a new production line, while shutting down the whole facility until the new line (B) was up and running. The pharmaceutical company hired the Biotech Quality Group (BQG) to shorten the duration of the shutdown (i.e., complete stop of production operations) and ensure proper start-up of the new line. As there is no substitute for the recombinant factor, supply of the therapeutic biological is essential for patients with a severe disease. This business case describes BQG s successful trimming of the shutdown period by using a dynamic approach, yet achieving high quality requirements. CHALLENGE Need for shorter duration of shutdown The pharma company faced a tight deadline. To increase and continue the supply of the market in recombinant antihemophilic factor, the pharmaceutical company had to upgrade its production line A before its new line B was up and running. The shutdown period originally was planned to be 36 weeks. BQG s ambition was to shorten the duration of the shutdown to reduce the postponement of the therapeutic, which is key for patients with the severe disease. Manufacturing cost of labor, equipment, and documentation, as well as product revenue for the pharma company, also were impacted. Therefore, trimming the shutdown period was essential. BQG S SOLUTION Conduct fast-track project utilizing proprietary, readyto-use tools, templates, and processes and incorporating ASTM E

4 Before any work could be done, BQG had to assess the readiness and maturity of the pharma client to support a fast-track, ASTM E2500 based project. A maturity assessment was performed by BQG following the Apollo Maturity TM model designed specifically to measure the maturity of verification practices. As a result of the assessment, a set of actions were defined and implemented to ensure the client had the pre-requisites to use BQG s methodology. BQG s objective was to reduce the duration of shutdown from 36 to 20 weeks. The shorter shutdown period represented a 45% reduction of the product s time to market. Finding a feasible solution was a challenge due to the following issues, which had never been integrated into a single project before : Drastic optimization of the schedule with all the stakeholders. Change in shifts of pharma workers over several months. Incorporation of a new qualification methodology : the ASTM E2500. Continuous follow-up/management of projects by advisors. BQG commitment on results via a fixed-price contract. 4

5 To realize the commissioning and the qualification of the production line of the recombinant factor in maximum 20 weeks, BQG deployed a fast-track project, including a complete package of BQG ready-to-use tools, templates, and processes. BQG, whose advisors were located at the pharma s facility during the project, committed to achieving pre-defined results within a prespecified timeframe. BQG adopted a dynamic qualification approach involving the ASTM E2500, instead of the classical V-cycle qualification approach. The ASTM E2500 is an innovative, risk-based and science-based approach to the specification, design, and verification of manufacturing systems and equipment that have the potential to affect product quality and patient safety. In collaboration with all partners, the timeframe for the shorter shutdown period was agreed upon. The project was accomplished in two phases : 1 A preparation and development phase involving commissioning, writing the risk-based quality and performance documents including product qualification, and preparing for the shutdown period. This phase was conducted from July 2015 to January ASTM E2500 concepts were utilized. BQG s staffing involved 10 experts advisors in charge of the writing of protocols and SOPs according to ASTM E2500 and the pre-writing of reports. BQG partnered with a process engineering firm for the planning, building, and installation, as well as collaborating with the pharmaceutical client. Daily meetings and reports facilitated communication between all involved parties. 2 A performance phase, including qualification of product and execution documents, was accomplished, starting in February 2016 and ending in June BQG increased its staffing of advisors to work on 4 fronts : automation, equipment, CIP/SIP and project management. ASTM E2500 practices and daily meetings and reports were implemented in partnership between BQG and the pharmaceutical client. 5

6 The steps for the shutdown of the line at the facility involved : Decommissioning of some existing installations. Modification of some existing installations. Building, assembly, and construction of new installations. 4 Development of the cycles Clean-In-Place (CIP) and Sterilisation-In- Place (SIP). 5 Bringing the shutdown into service during 3 8-hr shifts daily, including weekends, in order to cover most of the possible hazards. 6 Standard approach such as Installation Qualification (IQ), Operational Qualification (OQ), Performance Qualification (PQ) were replaced by ASTM fast track practices. 7 CIP/SIP, and process, according to the ASTM E2500 check mode. 8 Verification of Good Manufacturing Practice (GMP) operation and change management. 9 Shutdown procedures. 6

7 Figure 1 summarizes the ASTM E2500 components for verification of GMP operation and change management. Product knowledge Good engineering practice Process knowledge Regulatory Requirements Specification and design Verification Acceptance and release Operation Company quality Risk management Design review Change management Figure 1: The specification, design, and verification process (source : ASTM E ) BQG utilized the following tools on the project : BQG s proprietary Quality Risk management tool, at the heart of BQG s verification approach. Daily organizational meeting on qualification of installation testing (QIT). Turnover meeting for updating the next shift team. Collaborative meeting with project leaders. SharePoint, an internal website for sharing information among the team. Steerco (visual sharing of project information). 7

8 Figure 2 displays the timeline for the various components of the project, including : Mechanical installation and passivation (cleaning process for equipment). Static SAT, installation validation, operational validation, and validation of SIP and CIP. SD of utilities. Dynamic SAT, verification of operational validation (OV), PQ, SIP PQ, build-up for release of product, and release. Next batch of product. Encountered issues: 18 weeks planned timeline Steam exchanger TC2 explosion Condensate presence in steam distribution line Air presence in site steam generator Mechanical installation/ Passivation 20.8 weeks real timeline SAT static/verification INOV/Validation SIP and CIP SD Utilities SAT Dynamic/Verification OV/PQ Start of first campaign Mechanical installation/ Passivation SAT static/verification INOV/Validation SIP and CIP SD Utilities SAT Dynamic/Verification OV/PQ SIP/PQ Liberation build up Liberation B12/B92 First lot Figure 2 : Project Timeline 8

9 RESULT Successful reduction of duration of shutdown to 20 weeks. The following figure shows the status of specific accomplishments during the project : 600 Results 842 tests were conducted Right the first time: - 83% of equipment tests - 81% of CIP tests - 47% of SIP tests Recorded and corrected: differences in SAT deviations Deviations CIP Equip Planned run Executed run Figure 3 : Results 77 SIP 9

10 The project resulted in : Well detailed standard operating procedures (SOP) and CIP. Revision of qualification procedures according to ASTM E2500 achieved in record time. Good preparation of requirement of each SIP protocol. Good anticipation of redaction and approval of protocols before the execution phase. Preparation of all reports. Good collaboration with the quality team during execution phase. Successful reduction of shutdown duration to the project goal of 20 weeks. All reports produced. IMPACT Expertise in quality, project management, and teamwork resulted in a dramatically shorter shutdown period, benefiting the pharmaceutical company and patients. 10

11 Successful accomplishment of the shorter shutdown period ensured : Quicker start of next lot of product, thereby providing higher capacity and faster time to market. Continued supply of recombinant therapeutic, benefiting patients and the pharma company. Reduction in cost of manufacturing a biological. Increased profitability (reduced cost and greater revenue) for the pharma company. BQG s case study in qualification and verification demonstrates : Achievement of planned goals in a fast-track project. Teamwork and perseverance of all parties. Favorable coaching of the client team by BQG. BQG s expertise in quality, verification, and project management methods. BQG s maturity in collaborating with a commissioning firm and consulting to pharmaceutical companies. 11