At its core, continuous data monitoring in process control enables biomanufacturers to identify variability within individual process steps before compromising product specifications. That in turn allows for real-time adjustments to keep an overall process operating within established critical process parameters (CPPs). As a result, manufacturers can minimize the loss of valuable materials and products by preventing unnecessary rejections.

However, the advantages of digitalized process control extend well beyond simple cost savings. Rapid intervention based on process data enables a deeper understanding of how different factors influence both a manufacturing process and resulting product quality. Such knowledge can drive sustainable process improvements over time. Ultimately, optimized process control should ensure a reliable supply chain that can meet patient needs through timely product delivery.

Although implementing advanced monitoring requires initial investment, the cumulative efficiencies across quality, compliance, continuous improvement, and supply-chain reliability can yield considerable returns on that investment over a product’s life cycle. For combination-product manufacturers, the inherent complexity of developing and commercializing multicomponent systems with intersecting materials, processes, and quality requirements amplifies the need for process control.

Whereas medical-product manufacturers might anticipate benefits such as improved quality and compliance, rigorous process monitoring also can unlock unexpected and far-reaching efficiencies. From reinforcing supply-chain continuity to accelerating speed to market, integrated process-control capabilities enable strategic advantages across the full product life cycle. Environmental sustainability factors also come into play through carbon-footprint reductions. Optimized processes have ripple effects that permeate quality management systems (QMS), operational cost structures, and marketplace competitiveness.

Improved Supply Chains

The supply chain for combination products is inherently complex, with multiple components and materials converging into an integrated final product. Rigorous process controls are crucial for mitigating risks and preventing disruptions throughout such an intricate network, from raw-materials sourcing and product manufacturing to distribution and delivery to patients.

Continuous monitoring and data-driven adjustments during manufacturing can ensure consistent quality of finished combination products. Such efforts minimize defects and reduce the likelihood of faulty units entering the supply chain and ultimately reaching the market — thus preventing compromises to patient safety, therapeutic efficacy, and brand reputation.

Process control also improves traceability of components, materials, and manufacturing lots used in each batch. If problems arise, their source(s) can be identified and isolated rapidly to prevent larger disruptions from defective items propagating further through the supply chain. Rapid root-cause analysis facilitates targeted corrective actions to address core problems.

Process controls that are centered on monitoring CPPs such as temperature, pressure, and statistical process capability will provide a robust framework for risk mitigation. By keeping those factors within specified limits and swiftly correcting deviations, manufacturers can prevent quality issues before they occur. Minimizing deviations from a validated process helps to limit disruptions to both reliable product supply and fulfillment of market demand for combination products.

Additionally, by implementing predictive analytics driven by process data, manufacturers can foresee potential supply-chain bottlenecks and address them proactively before they can cause delays or shortages. Such foresight is invaluable for maintaining a smooth, uninterrupted supply chain. Intelligent process monitoring provides a critical advantage for companies seeking to meet market demands and provide steady supplies of combination products to patients who depend on them.

Fewer Quality Systems To Review

Rigorous process controls embedded throughout the manufacture of combination products can streamline quality oversight through early detection and trending of deviations. By catching issues early on, companies can contain problems before they propagate and trigger larger, more resource-intensive investigations and reviews downstream. Such a proactive approach addresses root causes and prevents costly remediation campaigns. Tightly controlling processes within validated parameters ensures consistently reliable product quality from batch to batch. Preventing quality discrepancies will obviate disruptive reviews, investigations, and delays in manufacturing campaigns.

Optimized process control is central to ensuring adherence with current good manufacturing practices (CGMPs) and other regulatory standards governing combination product quality. Maintaining compliance through comprehensive, data-driven process monitoring reduces the likelihood of intensive audits and reviews by regulatory agencies. Meeting stringent requirements through robust process control helps to facilitate and expedite regulatory approval processes and prevents costly delays that stem from noncompliance findings to set programs back.

Perhaps the most important role that rigorous process controls play is in minimizing process variability, therefore mitigating a key source of quality risk. Keeping variables from drifting out of specification limits potential triggers for quality-related investigations, reviews, and remediation efforts that drain resources. By using advanced data analytics and machine-learning (ML) algorithms, manufacturers can optimize processes continuously based on detected patterns and anomalies, ultimately leading to fewer instances of noncompliance and enhanced overall product quality over time.

Moreover, with strong process controls and continuous monitoring, operators can react to all issues that arise, which fosters a system of autonomous maintenance. Continuous learning empowers operators to maintain their operations independently, identifying and addressing deviations before they can escalate. Autonomous maintenance not only helps to ensure consistent quality but also reduces the need for specialized intervention, allowing high-level engineers to focus on more complex tasks. Operators equipped with standard processes and real-time monitoring tools can escalate issues efficiently when necessary, contributing to a resilient and self-sustaining manufacturing environment.

All of that brings a quality-by-design (QbD) approach reinforced by process control that reduces burden of company oversight. With fewer fires to fight, quality resources can focus on high-value initiatives such as process improvements, inspection refinements, and proactive risk management strategies.

Reduced Time to Commercialization

For combination products that involve multiple components and manufacturing steps, stringent process control enables efficiencies from development through commercialization by minimizing the need to transfer materials between facilities. Consolidating formulation, filling, and packaging within one system allows materials to flow seamlessly, which reduces time delays, shipping costs, and material-handling risks. This integrated approach enhances control over scheduling production activities across each manufacturing campaign. Instead of navigating complex coordination among numerous external vendors, combination-product makers can optimize their schedules in a self-contained ecosystem with full visibility.

Clear lines of communication are essential when managing multifaceted production processes such as those for specialized devices that deliver complex biologics. For contract development and manufacturing organizations (CDMOs), designating a single point of contact to serve as project manager provides clients with a unified channel for inquiries and updates. That manager can coordinate cross-functional technical teamwork and effectively triage client needs, streamlining response times and minimizing fragmented communications.

Whether accelerating speed to market, reducing operating costs, or mitigating project risks, centralized process control for combination-product manufacturing confers numerous advantages. An interconnected production system provides efficiencies that tighten sponsors’ control and focus over their assets’ commercialization journey. By reducing the time required for each production phase, manufacturers can speed products to market and obtain a competitive edge. Moreover, shortening time to market gives patients access to new treatments sooner than would have been possible otherwise.

Reduced Carbon Footprint

Beyond direct operational efficiencies, rigorous process control opens opportunities for combination-product manufacturers to reduce their environmental impact. Optimized management of water use is one such avenue. Recycling equipment can redeploy previously cooled or heated water for controlling heat transfer in subsequent manufacturing steps. That lowers the amount of energy required for precise regulation of water temperature.

Fostering collaborations with local utility companies furthers such sustainability efforts. Manufacturers can leverage expert guidance on water-conservation practices, recycling systems, and green-energy strategies such as renewable power sources. An integrated process-control philosophy extends to ecofriendly utilities management.

A key advantage of modern combination-product facilities is a transition toward highly integrated single-use systems across multiple stages of production. With inherent quality-assurance and contamination-control benefits, single-use technologies also significantly reduce the energy footprint of a facility when compared with traditional reusable equipment and materials. The intensive utilities and processing cycles required for cleaning validation of complex reusable components are eliminated by single-use assemblies. Every aspect of manufacturing takes place in a seamless, presterilized, and disposable flow path.

Maximizing the duration over which such systems can operate continuously before turnover minimizes the number of transition periods that consume energy for equipment changeout. Furthermore, specific technologies such as depyrogenation tunnels and autoclaves play important roles in reducing a facility’s carbon footprint. Depyrogenation tunnels can process vials continuously, for example, which cuts down energy consumption significantly compared with traditional batch processes. The tunnels can process vials in as little as two minutes at high temperatures, which drastically reduces the time and energy typically required for depyrogenation cycles.

Integration of such efficient equipment helps manufacturers limit or eliminate the energy use associated with cleaning and validation of reusable components. Additionally, using energy-efficient technologies such as light-emitting diode (LED) lighting and optimized heating, ventilation, and air-conditioning (HVAC) systems further contributes to reducing the overall carbon footprint of manufacturing operations. By adopting advanced technologies and practices, manufacturers not only enhance their own operational efficiencies, but also contribute to sustainability and improve overall environmental impact of their production processes.

Toward an Optimized Future

From reinforcing supply-chain continuity to streamlining quality oversight, optimized monitoring and data-driven interventions reverberate across biopharmaceutical and combination-product life cycles. By catching deviations early and preventing defects, process control mitigates risks that otherwise might disrupt the supply of essential treatments for patients. It fosters an environment of continuous improvement in which quality issues are contained rapidly and remediated at the source.

For combination-product companies, developing robust process-control capabilities is a necessity for realizing the full potential of innovative therapies through reliable commercialization. Manufacturers that embrace advanced process-control strategies can achieve a competitive edge while building and maintaining high-quality, sustainable, and efficient production processes.

With over 13 years of working on liquid and lyophilized sterile injectables, overseeing technical transfer into multiproduct fill–finish sites at phase 1 through commercialization, Kim Brown is director of client portfolio and relationship management at Kindeva Drug Delivery, 1945 Craig Road, St. Louis, MO 63146; https://www.kindevadd.com.