title: Design-for-Six-Sigma for Development of a Bioprocess Quality-by-Design Framework.
abstract: An initial quality-by-design (QbD) framework was assembled for biopharmaceutical product, process, and analytical development using the design-for-six-sigma (DFSS) methodology. This technique was both streamlined and efficient, which permitted development of a QbD framework with minimized team leader and member resources. DFSS also highly emphasized voice-of-the-customer, information considered crucial to development and implementation of a bioprocess QbD framework appropriate for current development needs of the organization and its regulatory environment. The bioprocess QbD final design and implementation plan was comprised of seven teams, constructed from six QbD elements plus a communication/training team. Each element's detailed design was evaluated against internal and external established best practices, the QbD charter, and design inputs. Gaps were identified and risks mitigated to assure robustness of the proposed framework. Aggregated resources and timing were estimated to obtain vital implementation sponsorship. Where possible, existing governance and information technology efforts were leveraged to minimize additional bioprocess resources required. Finally, metrics were selected to track success of pilots and eventual implementation.
  An initial quality-by-design (QbD) framework was assembled to guide biopharmaceutical product, process, and analytical development. QbD starts by defining the patient requirements which then are translated into required quality attributes for the product. The production process then is designed to consistently meet these quality requirements by identifying and understanding those parameters which influence them. A control strategy is developed that specifically relates each point of control to a desired quality measure. Overall, this approach results in a robust process, capable of reliably producing quality product. The bioprocess QbD framework was developed to guide implementation of the desired QbD strategy. It was comprised of seven teams, constructed from six QbD elements plus a communication/training team. Each element's detailed design was evaluated against internal and external established best practices, the charter, and design inputs. Gaps were identified and risks mitigated to assure robustness of the proposed framework. Aggregated resources and timing were estimated to obtain vital implementation sponsorship. Where possible, existing governance and information technology efforts were leveraged to minimize additional bioprocess resources required. Finally, metrics were selected to track success of pilots and eventual implementation.
authors.affiliation: Bioprocess Development, Vaccines Research and Pre-Clinical Development, Biologics Manufacturing Sciences & Commercialization, Global Vaccines Technology and Engineering/Global Biologics Quality, Merck and Co, Inc.
authors.forename: Beth
authors.initials: B
authors.lastname: Junker
authors.forename: Mike
authors.initials: M
authors.lastname: Kosinski
authors.forename: David
authors.initials: D
authors.lastname: Geer
authors.forename: Rajiv
authors.initials: R
authors.lastname: Mahajan
authors.forename: Michel
authors.initials: M
authors.lastname: Chartrain
authors.forename: Brian
authors.initials: B
authors.lastname: Meyer
authors.forename: Peter
authors.initials: P
authors.lastname: Dephillips
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Randy
authors.initials: R
authors.lastname: Henrickson
authors.forename: Katie
authors.initials: K
authors.lastname: Ezis
authors.forename: Mark
authors.initials: M
authors.lastname: Waskiewicz
mesh_terms: D015195:Drug Design; D006801:Humans; D011358:Product Surveillance, Postmarketing; D011786:Quality Control; D013678:Technology, Pharmaceutical