How Robust Is Your Process Capability Program? Part 1

This article was originally published in the January-February 2018 issue of Pharmaceutical Engineering® magazine

Catch up on this series by reading:

By:  Philippe Cini, PhD; Gretchen Allison; Gerald Leister; Eda Ross Montgomery, PhD; Julia O’Neill; Paul Stojanovski; Michael Thomas; and Arne Zilian, PhD

ISPE’s Process Capability team has developed an industry-specific maturity model that can help companies design a robust process-capability program and compare it to those of their peers. The model has been substantiated by surveying 15 companies.

Process capability is an index that compares quantitative process variability to its specification limits over a predefined period. Typically, the higher the index, the tighter that process property has remained within its specifications.

There are different types of process-capability indices (Table A). Some predict future capability while others describe past performance. Some are based on long-term variability, others on short-term variability. While all serve the same high-level purpose, different indices are better suited to certain situations.∗

* To learn more about the mathematical and technical considerations of process indices, refer to references 1–3 and Table A.

Table A
Table A

Process capability indices can help identify opportunities to improve manufacturing process robustness, which ultimately improves product quality and product supply reliability; this was discussed in the November 2016 FDA "Submission of Quality Metrics Data: Guidance for Industry." For optimal use of process capability concept and tools, it is important to develop a program around them. We have identified nine areas that should be considered and for which a certain level of proficiency or understanding is recommended:

  • Policy: A framework that provides direction and sets process-capability expectations in an organization
  • Data management: A system for collecting, managing, and assessing data
  • Frequency: How often process-capability indices are calculated
  • Basis for specification: How specifications are developed and linked to clinical studies
  • Calculation consistency: Process capability calculation methodology.
  • Response: Thresholds that specify required action(s) and shift attention to low-capability products
  • Organization skill set and execution: Process capability knowledge across the organization
  • Risk-based approach: How process capability supports an overall risk-management program
  • Commercialization: The stage at which product life cycle monitoring and variability sources are optimized

These focus areas have been assembled into the ISPE Process Capability Model (Figure 1). Foundational areas constitute the base of the pyramid, while more advanced areas geared toward manufacturing optimization constitute the second and third tiers. This identifies organizational strengths and weaknesses and helps prioritize efforts.

How Robust Is Your Process Capability Program? Figure 1 - Pharmaceutical Engineering Magazine
Figure 1

Each focus area has a five-stage maturity continuum: initial, repeatable, defined, managed, and optimizing. These are summarized in the tables at the end of this article.

We do not recommend using process capability as a reportable compliance metric, due mainly to associated statistical issues and complexities. There is no industry consensus, for example, on how specifications should be set. Process capability values could therefore differ between two pharmaceutical companies that use the same manufacturing process to produce the same product; specifications established and negotiated with regulatory agencies could be different.

We conducted a survey asking companies to rate their organizations on a scale of 1 (basic) to 5 (advanced) in each area, both as they are today (current state) and as they intend to be in 2–3 years (future state). This survey may help the biotech and pharmaceutical industries to:

  • Increase familiarity with process capability, enable a process improvement mind-set, and socialize the process-capability model
  • Assess the efficiency and effectiveness of process-capability program
  • Develop a consistent approach for calculating process-capability indices, and conduct a systematic assessment to measure and compare process-capability maturity within and across organizations
  • Determine which level of maturity is appropriate for an organization based on its business needs and desired risk profile

The results of that study are shown in Figure 2. Colors indicate the gap between the current state (delta) and the desired future state (2–3 years away); green represents the smallest difference and red the greatest. Users can focus on foundational areas first, then shift to optimization areas.

How Robust Is Your Process Capability Program? Figure 2 - Pharmaceutical Engineering Magazine
Figure 2


About the Authors

Philippe Cini, PhD, an ISPE member since 2004, is Team Leader of Tunnell Consulting’s subsidiary, Turesol Staffing Solutions. With his team, he helps pharmaceutical and biotech companies find exceptional technical, scientific, and QA/QC talent. Dr. Cini brings more than 20 years of experience across a wide range of areas that are critical to the life sciences industry such as R&D, technical services, and quality and manufacturing operations. Prior to joining Tunnell, he was a principal in the life sciences practice at Capgemini Consulting, with a particular focus on supply chain management. He was also a partner in the life sciences practice of IBM, where he was responsible for supply chain solutions. Dr. Cini earned his PhD in chemical engineering from University of Massachusetts and his MSc in chemical engineering from Université Nancy, France.

Gretchen Allison, an ISPE member since 2005, is Senior Director/Team Leader of Global Quality Validation Services for Pfizer Global Manufacturing. She leads a global team supporting validation activities for commercial manufacturing sites. Gretchen has over 30 years of experience in the pharmaceutical industry, including quality control, auditing, product complaint handling, quality assurance, contract manufacturing quality oversight, technical support, and analytical development and validation. Gretchen has supported development of numerous industry guidance documents, including the revised PDA Technical Report 29 and several ISPE Process Validation Discussion Papers. Gretchen has a BS in chemistry from the University of Florida.

Gerald Leister, an ISPE member since 2017, is a Technical Services/Manufacturing Science Advisor at Eli Lilly and Company. In this role, he is responsible for the development and implementation of global operational control strategy and manufacturing standards. Prior roles have included technical and leadership positions in the areas process validation, cleaning validation, and new product technical transfer. Gerald has 15 years of biotech manufacturing experience. He received a BS in chemical engineering from Rose Hulman Institute of Technology, Terre Haute, Indiana.

Eda Ross Montgomery, PhD, is Senior Director/Technical Steward, Technical Operations, at Shire, where she is responsible for statistical support and for implementing processes to enable continuous improvement of Shire’s products. She held previous leadership positions in both technical (R&D and commercial) and quality at Vertex, Bristol-Myers Squibb, and DuPont Pharmaceuticals. Eda has over 25 years of experience in the pharmaceutical industry and over 10 years’ experience implementing quality by design across all phases of the product life cycle. She obtained her BS in chemistry from Rensselear Polytechnic Institute and PhD in analytical chemistry from the University of North Carolina at Chapel Hill.

Julia O’Neill, an ISPE member since 2015, is a CMC statistician with 30 years of experience bridging statistics and chemical engineering. O’Neill has addressed a broad range of challenges in vaccines, biologics, pharmaceutical and chemical development, and manufacturing. Prior to joining Tunnell Consulting, she was with Merck & Co., where she was responsible for development and deployment of process robustness strategy for manufacturing. Her team also designed and installed continuous process verification for vaccines and biologics, and supported CPV for all human health products. Julia is a Master Black Belt and expert in resolving challenging problems using statistical, engineering, and Six Sigma methods. She obtained her BS in chemical engineering from University of Maine and her MS in statistics from University of Wisconsin.

Paul Stojanovski joined Therapure in August of 2017 as the Vice President of Quality Operations. With over 30 years of quality and operations experience in branded, generic, and CDMO pharmaceuticals, Paul has held senior global quality and compliance executive positions at Mylan and Teva. Through his career, he has worked closely with manufacturing operations, product development, and supply chain to develop partnerships in alignment of quality with regulatory agencies such as Health Canada, USFDA, ANVISA, MHRA, EMA and TGA, client and the business to exceed patient needs. His responsibilities at multiple sites globally has provided in-depth knowledge and working experience to develop and implement product robustness programs utilizing process capability, tools for inspection readiness, training, trending, quality councils, lean manufacturing, LIMS, TrackWise, and many others. Paul holds a BSc in biochemistry from the University of Toronto and is a Charter Chemist of Toronto.

Michael Thomas, a highly skilled senior management consultant for Tunnell Consulting with over 25 years’ experience to the life sciences industry, has global experience and expertise in areas such as applied statistics, Lean Six Sigma, project management, and supply chain management. Prior to joining Tunnell, Thomas spent his career with Teva Pharmaceuticals, Merck & Co. Inc., Johnson & Johnson, and General Foods Corporation. He has considerable experience supporting operations, quality, research & development, technical services and supply chain. He specializes in process optimization, process and product robustness, design of experiments and Lean Six Sigma. He is a Certified Master Black Belt, a Certified Quality Engineer, Certified Project Manager, a senior member of American Society for Quality, and an adjunct professor. He holds an MBA in management, an MS in statistics, and a BA in mathematics.

Arne Zilian, PhD, an ISPE member since 2015, is Global Head, Manufacturing Science and Technology Processes and Standards, Novartis Technical Operations, Novartis AG. He has over 20 years of experience in the pharmaceutical industry, and has worked in analytical development, chemical development, pharmaceutical development, manufacturing operational excellence, and manufacturing science and technology. Zillian serves as the lead author for the cross-divisional quality standards for CPV, and has been instrumental in building the MS&T organization. Arne holds a PhD in analytical chemistry and a master’s degree in chemistry. He is also a certified Kepner Tregoe trainer for situation, decision, and problem analysis.