WHITE PAPER FACILITY FOCUS: GMP Facility Modernization By: David M. Marks, P.E. July 2017
Introduction In recent years, intensified industry competition and cost pressures have renewed interest in modernizing legacy facilities effectively extending the usable life of legacy facilities while implementing new technologies that offer the promise of improved manufacturing flexibility, quality, and cost of goods. Confronting the issue and reality of aging facilities, how will your operations stay lean and competitive? In this Facility Focus survey report, you ll learn about the trends, technologies, and tactics manufacturers are using to modernize their legacy facilities in order to enhance manufacturing reliability, efficiency, and flexibility as well as the benefits, challenges, and risks involved in facility upgrades. About the Facility Focus Survey DME invited engineers, manufacturers, and other life sciences professionals to participate in their second annual Facility Focus GMP Facility Modernization survey to share their views on the latest trends and technologies affecting the pharmaceutical manufacturing industry. The survey consisted of twelve questions covering areas of cgmp manufacturing, new technologies, single use, continuous processing, facility renovations, and compliance. Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 2
Survey Participants The survey enjoyed high levels of participation from GMP Manufacturers. Participants from pharmaceutical and biopharmaceutical manufacturers were the most highly represented, comprising nearly half of the respondents. Q1: What is your primary affiliation? Figure 1 - Survey Participant Affiliation Overview Figure 2 - Survey Participant Affiliation Breakdown Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 3
Q2: Which best describes your facility s primary area of cgmp manufacturing? Figure 3 - Primary Area of Manufacturing of Survey Participants Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 4
cgmp Manufacturing Q11: What is the biggest challenge associated with multiproduct manufacturing in GMP facilities? Preventing cross-contamination between product campaigns was cited most often. Figure 4 - Biggest Challenge Associated with Multiproduct Manufacturing Overview Figure 5 - Biggest Challenge Associated with Multiproduct Manufacturing Mfr Breakdown Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 5
Q12: What aspect of GMP facility flexibility do you consider the most valuable? Quick changeover between product runs was the number one response, followed closely by the ability to easily adapt for new products and processes. Figure 6 - Most Valuable Aspect of Facility Flexibility Overview Figure 7 - Most Valuable Aspect of Facility Flexibility Mfr Breakdown Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 6
Q10: What is the most promising long-term strategy for future cgmp manufacturing of large-volume drug substance? Almost half of respondents felt continuous manufacturing held the most promise as a future long-term strategy for large-volume drug manufacturing. Figure 8 - Most Promising Long-term Strategy for Large-Volume Drug Overview Figure 9 - Most Promising Long-term Strategy for Large-Volume Drug Mfr Breakdown Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 7
Manufacturing Technology Q3: What new technologies have you introduced as part of a GMP facility modernization project? The leading new technology most manufacturers have introduced is process automation, followed by single use. Figure 10 - New Technologies Introduced Overview Figure 11 - New Technologies Introduced Mfr Breakdown Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 8
Q4: What do you believe to be the most formidable obstacle to the adoption of new technologies for GMP facility modernization? Respondents felt process validation was the biggest obstacle to adopting new technologies. Regulatory acceptance and general industry conservatism followed closely. Figure 12 - Biggest Obstacle for New Technology Adoption Overview Figure 13 - Biggest Obstacle for New Technology Adoption Supplier vs. Manufacturer Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 9
Q5: How would your company benefit if you converted all of your open GMP operations to closed processing (i.e., manufacturing under conditions where the product is never exposed to the surrounding environment)? Almost half of respondents said reduced gowning would be the biggest benefit to closed processing, with vaccine manufacturers seeing the greatest benefit. Figure 14 - Benefit of Converting to Closed Processing Overview Figure 15 - Benefit of Converting to Closed Processing Mfr Breakdown Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 10
Single Use Technology Q6: In what areas of your cgmp process are you currently using single use technology exclusively (i.e., disposables in all product-contact applications)? Most GMP manufacturer respondents were not using single use technology exclusively, but of those that were, the highest process area was fermentation and cell culture. Figure 16 - Process Areas Where Single Use Technology Used Exclusively - Manufacturers Figure 17 - Process Areas Where Single Use Technology Used Exclusively - Biopharmaceuticals Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 11
Q7: What has been your most significant challenge associated with single use technology? Across all manufacturers, cost of disposables was the greatest challenge associated with single use technology. Figure 18 - Most Significant Challenge with Single Use Technology - Supplier vs. Manufacturer Figure 19- Most Significant Challenge with Single Use Technology - Mfr Breakdown Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 12
Continuous Processing Q8: Where does your company currently use continuous (non-batch) processing? Most manufacturer respondents were not using continuous processing, but for those that were, it is most used in process development. Figure 20 Where Continuous Processing is Currently Used Small Molecule Drugs vs. Biopharmaceuticals Figure 21 Where Continuous Processing is Currently Used Mfr Breakdown Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 13
Q9: What do you see as the most significant challenge with continuous processing? Most manufacturer respondents see the greatest continuous processing challenges in process development. Figure 22 - Most Significant Challenge with Continuous Processing Overview Figure 23 - Most Significant Challenge with Continuous Processing - Mfr Breakdown Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 14
Facility Renovations Q13: From your experience, please rank the following risk factors associated with GMP facility renovations. Across all respondents, process validation and/or regulatory issues were ranked as the greatest risk factors associated with facility renovations. Broken down by respondent type, GMP manufacturers ranked process validation and regulatory issues highest, while suppliers ranked legacy facility unknowns highest. Figure 24 - Ranking of Facility Renovations Risk Factors Overview Figure 25 - Ranking of Facility Renovations Risk Factors - Supplier vs. Mfr Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 15
Facility Compliance Q14: What typically triggers an internal assessment of facility or equipment compliance to current GMP standards at your company? More than half of GMP manufacturers cited quality-driven assessments prompted by manufacturing deviations as the most common trigger for conducting internal GMP standards compliance reviews. Figure 26 - GMP Compliance Assessment Triggers - GMP Mfrs Only Figure 27 - GMP Compliance Assessment Triggers - Mfr Breakdown Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 16
Facility Modernization In many ways, modernization projects are more difficult than greenfield designs of new facilities. Projects in legacy facilities typically involve: Poorly-documented facilities and manufacturing processes Obsolete equipment and dated process systems Manufacturing processes that are not risk-optimized Construction adjacent to ongoing GMP operations Limited construction and commissioning schedule windows When technology upgrades are added to the mix, it s even more challenging. The clearest take-home from our Facility Focus survey is that the implementation of new technologies in GMP manufacturing is going mainstream. The benefits of closed process systems, single-use technology and continuous processing are widely recognized. It s not unusual to see these technologies in greenfield projects, but renovation projects in legacy facilities are also using these tools with increasing frequency to improve reliability and performance. Compliance-Driven Outcomes Modernizing your plant is not only a smart investment, it may very well be a mandatory one. A facility that may have been top-of-the-line just a couple decades ago might not even be compliant by today s regulatory standards. This presents an interesting opportunity for facility managers with the foresight to anticipate regulatory issues and extrapolate trending manufacturing deviations. Ideally, facility modernization projects are defined through a robust conceptual design process that considers all of the opportunities for improving process reliability and product protection. This is informed by a thorough assessment of existing technologies, equipment reliability and opportunities for process improvement. It s hard to overstate the value of front-end engineering in projects of this type. In our experience at DME, the development of conceptual design options that are wellinformed by process subject matter expertise is extremely valuable to manufacturers. Remember, your investment is not solely to achieve current GMPs; Modernized facilities need to maintain compliance for decades to come. It is in assessments of this nature that the trends identified in DME s Facility Focus series are most useful. Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 17
About the Author David M. Marks, P.E. Principal, DME David Marks is principal and founder of DME. He has 30 years of experience with process systems and facilities in biotechnology, pharmaceutical, medical device, food and chemical industries. His background includes roles in engineering management, process design, project management, equipment design, commissioning and qualification. His professional experience is concentrated in the design of bioprocess systems and FDAlicensed commercial manufacturing facilities. Marks is an active member of the ASME Bioprocess Equipment (BPE) standard committee, and serves as chair of the process systems design subcommittee. He is a frequent author, speaker and consultant on bioprocess technology, facility design and cgmp regulatory compliance topics. Contact David at dmarks@dmeforlife.com, or 610-366-1744 x139 Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 18
About DME Facility Focus DME Facility Focus was designed to create a dialog within the industry regarding how we are going to meet the challenges presented by aging facilities, evolving regulatory requirements, new technology solutions and market changes in the pharmaceutical industry. It creates an opportunity to take good concepts and turn them into practical facility designs. DME s surveys were designed to touch on areas of both pain and opportunity areas being transformed by technologies into the future facilities for cgmp manufacturing. They were also developed to help DME and other facility design professionals understand what manufacturers value most in the design of their facilities. About DME Celebrating its 16th year in business, DME provides a wide array of engineering solutions for regulated life sciences industries. Our services include advanced technology facility design, MEP engineering, process engineering, operations improvement, and related consulting services. We are an excellent fit for projects requiring GMP manufacturing, cleanroom environments, or hygienic process technology. Our company leverages strong relationships with process architecture and construction management partners to deliver engineering solutions for life. Clients select DME because of our deep industry knowledge, professionalism, and team approach. For more information, visit www.dmeforlife.com or call 610-366-1744. Advantages of Working with DME The DME team has extensive experience in planning and executing renovations, upgrades, and expansions of legacy facilities. They reduce project risks by knowing how to ask the right questions early on, so unpleasant design compromises or change orders don t come to light later on. When you re looking at a manufacturing facility renovation or expansion, DME has the expertise to develop the optimum design approach. DME s experienced engineers will carefully analyze your operation, identifying the most effective means of refitting and repurposing your existing infrastructure. DME will work with you to analyze your user requirements, equipment needs, and operational changes, and will collaborate with you to create a facility that not only meets today s regulatory and safety parameters, but is also well positioned to accommodate future growth and changes. Copyright DME Alliance Inc. All rights reserved Do not reproduce without written permission Page 19
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