October 17, 2023
ASTRAZENECA (HTTPS://WWW.ASTRAZENECA.COM)
Biopharmaceutical manufacturing companies create life-saving medications and treatments that are crucial to global healthcare. It is an industry in which minor production issues can lead to dire consequences, including compromised product quality and regulatory noncompliance, not to mention danger to patients. Thus, proactive equipment maintenance is indispensable. Below, I investigate why proactive maintenance is vital to pharmaceutical manufacturing operations and highlight its role in securing regulatory compliance, reducing facility downtime, improving product quality, and managing risks.
Understanding Proactive Maintenance
Throughout its many complex processes, biomanufacturing demands strict quality adherence. To meet the highest standards consistently, the biopharmaceutical industry is turning to a strategy of proactive maintenance.
Definition and Explanation: Proactive maintenance is a way to anticipate and resolve potential problems before they crop up in manufacturing equipment. It involves regular checks, systematic inspections, and timely system upgrades to prevent unexpected downtime, enhance efficiency, and prolong the life of valuable equipment.
Proactive maintenance differs from the traditional “run-to-failure” model in which action is taken only after problems arise. Such reactive maintenance may seem cost-effective over the short term, but it always increases overall costs in the long run through unexpected production halts, hefty repair or replacement bills, and potential quality issues.
In contrast, proactive maintenance prioritizes continual improvement and risk reduction. This approach takes into account not only the current condition of equipment and instrumentation, but also their future performance. By identifying and addressing potential problems in advance, proactive maintenance aims to reduce downtime and maintain consistent process performance and product quality, safety, and efficacy in pharmaceutical manufacturing.
Relevance to the Biopharmaceutical Industry: The value of proactive maintenance to biomanufacturing cannot be denied. This sector’s intricate, highly regulated production systems can turn minor inconsistencies into major quality issues, even posing risks to patient safety. A proactive-maintenance approach facilitates efficiency in production scheduling and capacity use, providing cost savings and improving a development company’s profitability. Preventing instrument and equipment failure also reduces emergency repair costs and lengthens the useful lifetime of expensive systems, further contributing to long-term cost savings.
Five Key Benefits
The following five cornerstones illuminate the crucial role that proactive maintenance can play in manufacturing operations. It acts as a driving force for efficiency, regulatory compliance, risk mitigation, and most important, the delivery of safe, high-quality biologics to patients who need them.
Ensuring Compliance with Regulatory Requirements: Pharmaceutical manufacturing falls under the purview of several regulatory bodies such as the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO) (1). Those and other organizations impose a host of regulations and standards to ensure the safety, efficacy, and quality of pharmaceutical products for populations around the globe.
Regulations such as good manufacturing practice (GMP) guidelines demand that companies maintain strict control over their manufacturing processes and environments (2). Biomanufacturers must validate their processes regularly, oversee their production settings and facilities, and keep all equipment in optimal working condition. Deviations from those requirements can lead to noncompliance, potentially triggering regulatory actions such as fines, warning letters, product recalls, and even total shutdowns.
In this heavily regulated environment, proactive maintenance is crucial for maintaining GMP compliance. Regular inspections and preventive equipment maintenance help to ensure that all systems operate within necessary parameters and are in control — key aspects of such compliance around the world. Additionally, a proactive approach helps pharmaceutical manufacturers maintain comprehensive documentation of all related activities. That provides evidence of regulatory compliance for reviewers and helps companies spot trends, monitor equipment performance over time, and make data-driven decisions to improve operations.
Detecting and Preventing Equipment Issues: Proactive maintenance in biopharmaceutical manufacturing relies heavily on continuous monitoring and regular inspection of key equipment, using advanced condition-based techniques. Those can include vibration analysis, infrared imaging, oil analysis, and ultrasonic inspection — each method targeted to uncover early signs of wear or performance decline before equipment failure occurs.
Vibration analysis can detect early problems in rotating equipment such as pumps, preventing them from wearing prematurely. Infrared imaging can identify potential electrical failures, which must be prevented in an industry where unexpected downtime can be catastrophic. Oil analysis maintains high-performance machinery by detecting contamination or abnormal wear early on to prevent friction and machine failure. Ultrasonic inspection detects leaks in pressure systems, which is crucial for maintaining sterility in upstream production processes, for example.
Minimizing Downtime and Maximizing Productivity: Equipment downtime can disrupt pharmaceutical manufacturing severely. Not only does it halt production, causing delayed orders and lost revenue, but it also can compromise the quality and integrity of products made. In certain cases, equipment failure might lead to the loss of an entire product batch, incurring substantial financial loss and possible damage to a company’s reputation.
Proactive maintenance greatly mitigates the risk of unplanned downtime. Spotting potential problems early and planning maintenance during scheduled production breaks helps biomanufacturers prevent unexpected equipment failures. That helps to ensure uninterrupted production and boosts the efficiency and productivity of manufacturing operations.
Connected-worker technology is revolutionizing proactive maintenance (3). It uses predictive analytics, industrial internet of things (IIoT) devices, and machine-learning algorithms to collect and analyze vast amounts of real-time data from manufacturing equipment. Such tools enable users to detect minor changes in equipment performance that could indicate impending problems. Connected-worker technology also enhances real-time communication and information exchange among maintenance staff, improving the efficiency of their activities. Integration of advanced information technologies into proactive maintenance enables biopharmaceutical manufacturers to minimize downtime, increase productivity, and uphold stringent quality standards.
Enhancing Overall Product Quality: Keeping equipment in peak operating condition ensures that manufacturing processes function consistently as intended. That limits drug-substance and drug-product variation, improving product quality and consistency. Proactive maintenance also can thwart cross-contamination. Detecting and resolving issues such as leaks or equipment wear can prevent contamination that would jeopardize product quality or even prompt product recalls.
Without regular proactive maintenance, equipment will degrade over time, resulting in process deviations that can compromise product quality. For instance, a minor fluctuation in the temperature or pressure of a unit operation due to equipment malfunction could cause significant variations in final products, potentially making them ineffective or unsafe.
Reducing Risks: Biopharmaceutical manufacturing incurs numerous risks, including equipment failure, production delays, compliance breaches, and product recalls. The potential for cross-contamination, deterioration of active pharmaceutical ingredients (APIs) from equipment malfunction, or loss of entire batches to unexpected breakdowns poses significant financial and reputational risks.
A proactive maintenance strategy can alleviate those risks significantly. Regular inspections and condition monitoring lead to early detection and resolution of potential issues before they can escalate into severe problems. That lowers the risk of equipment failure and related production delays and helps companies to maintain process and product integrity, reducing the risk of costly recalls or compliance violations.
Insurance providers acknowledged the value of proactive maintenance. Biopharmaceutical manufacturers that can demonstrate a robust program can negotiate lower insurance premiums, bringing an additional financial incentive to adopting this approach.
A Real-World Example
Proactive maintenance is shaping how the biopharmaceutical industry addresses the concerns described above (4). AstraZeneca (AZ) showcases the power of proactive maintenance at its manufacturing facility in Mt. Vernon, IN. The critical first step of implementation in that location involved separating the reliability team from everyday operations, underlining a significant distinction between maintenance and reliability.
Facilities engineer Andrew Carpenter has highlighted the importance of this difference, with maintenance attending to daily tasks and reliability focusing on understanding and mitigating underlying equipment problems. This shift required a significant cultural change and backing from top management. The company propelled that transformation by investing in specialized training in advanced predictive technologies such as vibration analysis, infrared thermography, and ultrasound for the reliability team. Alongside those, other new technologies play a crucial role in predicting and addressing potential issues before they can spiral into significant problems.
AZ prioritizes quality, which is evident in its meticulously designed cleanrooms housing crucial equipment, airlocks preventing potential contamination, and even storerooms and warehousing. Chris Nolan (senior building and reliability manager) underscores the storeroom’s importance as a mirror of such a facility’s health: “What goes out of your storeroom is a huge check and balance of your maintenance process.”
Another pillar of the company’s proactive-maintenance approach is root-cause analysis. Instead of just addressing an immediate issue, the team digs into its underlying cause to prevent future occurrences. Carpenter says that applying such a long-term focus on solutions — rather than quick fixes — has transformed operations.
The proactive-maintenance strategy initially found application in maintenance of utilities and purified water production; GMP maintenance; and heating, ventilation, and air conditioning (HVAC) systems. That allowed for persistent monitoring of critical aspects for ensuring product quality. The insights gained thereby have been crucial to the company’s pursuit of process refinement and failure prevention — particularly by demonstrating the value of recognizing and analyzing problems early on.
AZ’s Mount Vernon site primarily manufactures oral-solids medicines for type 2 diabetes treatment. AZ received early assistance from a consultant group (Life Cycle Engineering) to identify tools for showing overall criticality in terms of business cost, quality, and mean time between failures.
Means to an End
From guaranteeing compliance with stringent regulatory standards to enabling early identification of equipment issues, proactive maintenance’s crucial role in biopharmaceutical manufacturing facilities is evident. Not only does this strategy minimize downtime and optimize productivity, but it also ensures the consistent production of top-quality drug and biologic products. Outstanding performance at AZ is a strong testament to these benefits.
More than a mere operational strategy, proactive maintenance serves as a tool for quality assurance, a risk management measure, and a compliance enabler (5). The approach is indispensable for continued smooth functionality of biopharmaceutical manufacturing processes, which supports the industry’s duty to produce safe and effective drugs.
References
1 Stanton D. US FDA Publishes Final Continuous Manufacturing Guidance. BioProcess Insider 6 March 2023; https://bioprocessintl.com/bioprocess-insider/upstream-downstream-processing/us-fda-publishes-final-continuous-manufacturing-guidance.
2 Good Manufacturing Practice (GMP) Resources. ISPE: North Bethesda, MD, 2023; https://ispe.org/initiatives/regulatory-resources/gmp.
3 The Connected Worker Guide. L2L: Salt Lake City, UT, 2023; https://www.l2l.com/the-connected-worker-guide.
4 Ecker DM, Crawford TJ, Seymour P. Biomanufacturing from 2002 to 2022: How Far the Biopharmaceutical Industry Has Come. BioProcess Int. 20(7–8) 2022: 31–33, 67; https://bioprocessintl.com/manufacturing/information-technology/biomanufacturing-from-2002-to-2022-how-far-the-biopharmaceutical-industry-has-come.
5 Schoukroun-Barnes L, et al. Pharmaceutical Manufacturing Quality Assurance Programs: Transitioning from Research and Development to the Clinic. BioProcess Int. 21(5) 2023: 20–22; https://bioprocessintl.com/analytical/qa-qc/pharmaceutical-manufacturing-quality-assurance-programs-transitioning-from-research-and-development-to-the-clinic.
Further Reading
Segrest M. AZ Puts Proactive in Reliability. Efficient Plant 15 June 2017; https://www.efficientplantmag.com/2017/06/az-puts-proactive-reliability.
Tips for Transitioning from Reactive to Proactive Maintenance. UE Systems Inc.: Elmsford, NY, 2021; https://www.uesystems.com/tips-for-transitioning-from-reactive-to-proactive-maintenance.
Christiansen B. Proactive Maintenance Demystified: Meaning, Examples, Pros and Cons. Limble 29 August 2023; https://limblecmms.com/blog/proactive-maintenance.
Chan J. Reactive Maintenance Explained: Common Challenges and Solutions. Limble 30 August 2023; https://limblecmms.com/blog/reactive-maintenance.
Eric Whitley is director of smart manufacturing at L2L, 299 South Main Street, Suite 1300, PMB 96928, Salt Lake City, UT 84111; 1-877-225-5201; [email protected]; https://www.l2l.com.
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