The Authority on Drug Development & Manufacturing PharmTech.com 2012 Supplement to the February 2012 Issue of PREFERRED PROVIDERS Finding the Right Partner s2 Pharmaceutical Technology PREFERRED PROVIDERS 2012 PharmTech.com Project Management P roject management underpins successful relation- ships between contract technology and service pro- viders and their sponsor companies. As pharmaceuti- cal companies increase their level of outsourcing, it becomes increasingly important for contract technology and service providers to provide not only the technical capabili- ties needed to execute a given project, but the management skills to deliver a project on time, to specifications, and with the necessary communication to prevent or mitigate project delays. To illustrate the importance of project management in outsourcing, several industry members provided case studies on how to coordinate, organize, and implement a successful project. Blow/fill/seal manufacturing Norman Weichbrodt, strategic account manager at Catalent Pharma Solutions Catalent Pharma Solutions is a provider of drug and biologic development services, delivery technologies, and supply so- lutions. Effective project management is the cornerstone of being a complete provider of services ranging from devel- opment of new products to technical transfer of existing products. Building the proper project team and employing the correct methodology for handling a complex project is the foundation on which success is achieved. In July 2010, Catalent was approached by a major pharma- ceutical customer to transfer an ophthalmic product approved for sale in Europe to Catalent’s blow/fill/seal (BFS) manufac- turing site in Woodstock, Illinois. The successful technical transfer of the manufacturing process for this product would potentially lead, following FDA approval of the product al- ready made in the European facility, to approval of the drug for manufacture and sale in the United States. Project scope. The actual scope of this project was much larger for the Woodstock facility than a simple technical transfer. The project required the following: •A complete renovation of a formulation and filling suite, including a new separate air-handling system Case Studies in Pharmaceutical Project Management A Technical Forum Moderated by Patricia Van Arnum Effective project management is an invaluable competency in a successful outsourcing relationship. GREGOR SCHUSTER/GETTY IMAGES •Designing, building, and qualifying an automated for- mulation skid •Upgrading an existing BFS filling machine to match the capacity requirements for the product •Designing, building, and qualifying new vial molding and filling systems to duplicate the existing European design •Qualifying the room, formulation skid, BFS machine, and secondary packaging to produce stability and process-validation batches to support the customer’s submission and approval timeline •Developing and approving the required documentation for supply-chain, manufacturing, and quality assurance functions to meet the production timeline •Analytical-method transfer for chemistry and microbial testing •Complete process-validation protocols, test plans, and final reports to meet the submission timeline. Cross-functional teams. To manage a project of this scope, the Catalent New Product Development (NPD) group and the site-management team agreed to form a group of cross-functional resources. The team members served as the primary representative of their functional area for the project and were assigned for the duration of the project. The project team consisted of a project manager from NPD, an engineering project manager, a development scientist, an operations specialist, a validation specialist, a quality- assurance product specialist, a technical writer, and various contract resources as required. A strategic account man- ager had overall responsibility for the project team. The establishment and use of an expanded core project team of cross-functional resources was a new approach for Catal- ent’s Woodstock facility, but the scope and timeline for this project and the Catalent goal of meeting customer needs required an innovative solution. The project was divided into six major activities: the room, the formulation skid, the BFS machine, method transfer, secondary packaging, and documentation. The NPD project manager was the owner of the overall project timeline. Each major activity was included in a Microsoft project schedule and maintained by the project manager. The engineering project manager handled all activities in- volving the renovation of the filling suite, making use of contractors from design through construction and qualifi- cation. He also participated in the design and construction of the formulation skid, primarily focusing on the software development. The development scientist and the opera- tions specialist focused on the design of the formulation skid and the interface of the skid with the BFS machine to ensure the system had the proper design and controls to replicate the process already being used in Europe. The validation specialist developed the installatoin qualifica- tion, operational qualification), and product qualification protocols and had oversight of all factory acceptance test- ing (FAT) and site-acceptance (SAT) activities. The tech- nical writer and the quality-assurance product specialist worked with the NPD project manager to manage the change-control process for the project and to complete all the required documentation, including material specifica- tions, standard operating procedures, and manufacturing batch records. The NPD Project manager also provided oversight of the analytical method transfer, development of secondary packaging materials, and the documentation of project activities. Technology transfer. The technology-transfer process was initiated by creating a comparability document that detailed every aspect of the manufacturing process. The process used in the European manufacture was listed step by step in the document with Catalent’s suggestions and capabilities side by side. A final agreement for each step was included and served as the approved path forward. The specifications for in-process testing at each stage of the formulation as well as finished-product specifications were included in the docu- ment. The formulation process required bulk sterilization of a multicomponent polymer base with a relatively tight viscosity range. Two APIs were combined in a second part of the formulation and transferred to the polymer solution by sterile filtration. Of course, the entire formulation skid required steam sterilization of the product path through the BFS machine and maintenance of the sterile boundaries for the product during the entire filling process. Electronic documentation of all temperatures, times, and controls for each process step also were also required. Communication. The NPD project manager and the stra- tegic account manager facilitated weekly calls with the original equipment manufacturers of the formulation and BFS equipment as well as construction meetings during that phase of the project. Weekly calls were held with the cus- tomer representatives who were in liaison with the project team. A standard methodology was used to ensure that the meetings had a structured agenda and minutes issued for review in a timely fashion. A joint Project Steering Com- mittee was formed, which was comprised of customer senior leadership members, Woodstock site leadership members, and Catalent business-development members. Project Steering Committee meetings were held every three weeks during the course of the project. A formal pre- sentation was made at each meeting to discuss progress toward major milestones in the project plan. Strategic de- cisions were discussed and developed through the Project Steering Committee meetings, and the decisions were ulti- mately made by the joint project team. This management design reduced the cycle time for critical decision-making between the customer and Catalent. Pharmaceutical Technology PREFERRED PROVIDERS 2012 PharmTech.com s3 An example of such decision mak- ing was approval of a change to the SAT/FAT strategy originally planned for the formulation skid. The formu- lation skid is a fully automated two- tank system with over 100 control and process valves that are actuated in ap- proximately 20 sequences. When the software development lagged behind the construction of the hardware, the opportunity arose to do a mechani- cal FAT, ship the formulation skid to the Woodstock site, complete the installation and mechanical trouble- shooting of the skid and wait for the software to complete the qualification as a SAT. This decision saved as much as six weeks in the project schedule and enabled Catalent to meet the customer’s timeline for stability and process-validation manufacturing. It also resulted in a formulation system that is part of a robust technical trans- fer process from the customer through the NPD group to Catalent’s commer- cial manufacturing team. Execution. To date, all of the engineer- ing, stability, and process-validation batches have met the in-process and final-product test specifications. With nine batches produced, there have been no out-of-specification results for bulk or final product. In addition, no human error deviations have occurred in the formulation and filling of these batches. Figures 1–3 (Catalent) show the fa- cility upgrade and project equipment after installation. In summary, Catalent did not em- ploy new or groundbreaking method- ology for this project. However, supply- ing the proper structure and resources for a project team is the crucial first step in meeting a customer’s timeline and supplying the customer with qual- ity product, reliably supplied. Figure 1 (Catalent): A blow/fill/seal suite at Catalent’s Woodstock, Illinois, facility. Figure 2 (Catalent): A blow/fill/seal cavity fill machine at Catalent’s Woodstock, Illinois, facility. Figure 3 (Catalent): A fully automated formulation skid at Catalent’s Woodstock, Illinois, facility. FIGURES 1-3 (CATALENT) ARE COURTESY OF THE AUTHOR Project Management Excerpted from and posted with permission from the Supplement to the February 2012 issue of Pharmaceutical Technology. Copyright ©2012, an Advanstar publication. All rights reserved. www.pharmtech.com #C6545 Managed by The YGS Group, 800.290.5460. For more information visit www.theYGSgroup.com/content. . renovation of a formulation and filling suite, including a new separate air-handling system Case Studies in Pharmaceutical Project Management A Technical. project schedule and maintained by the project manager. The engineering project manager handled all activities in- volving the renovation of the filling