Rising Allure And Critical Considerations Of Point-Of-Care Processing
By Maik Jornitz, principal consultant, BioProcess Resources LLC
Point-of-care (POC) facilities, especially in cell and gene therapy applications, are experiencing a significant surge in interest because of an increased focus on capacity needs and specialized processing facilities close to the actual patient. The typical small footprint of such processing units is the key enabler to installing such facilities at the POC level. However, these therapies require unique processing infrastructure with specific containment capabilities as these processes are highly critical aseptic processing applications.
Since the demand for rapid implementation to keep pace with evolving requirements is paramount, scalability of cleanroom infrastructures and capacities necessitates the development of autonomous systems that can operate independently. In response to these needs, innovative cleanroom designs have emerged in recent years, offering solutions that range from mobile units for point-of-care applications to integration into cost-effective shell buildings. These advancements not only meet quality and containment standards but also enable a faster capacity expansion than previously achievable. Looking ahead, standardization of cleanroom infrastructure designs may further accelerate capacity implementation, allowing for efficient mass production of prefabricated units and resulting in lower costs, improved product quality, and enhanced delivery time certainty.
Challenges And Considerations In Point-of-care Manufacturing
Successfully implementing point-of-use manufacturing of drug products poses various challenges that must be carefully addressed. These challenges include the imperative task of adhering to cGMP regulations, upholding stringent quality and containment standards, implementing effective contamination control strategies, and addressing concerns related to cleanroom classification, material flow, and personnel gowning. Emphasizing the importance of regulatory compliance and maintaining high-quality standards over cost-cutting measures is crucial to avoid repeating past mistakes and vulnerabilities within point-of-care manufacturing.
In the past, instances showed that the emphasis was on the cost of the processing environment, meaning the POC processing unit had to be as specced down as possible, and even refurbished shipping containers became an option. However, experience showed that such units not only were highly inflexible from a dimensional standpoint, but they also failed to fulfill requirements of a true cleanroom or classified space, including cleanliness, appropriate insulation and surfaces, tightness, personnel and material flows, and robustness, to name a few. Since these applications are highly critical, the quality of all components of the process must be at the highest level. If any chance of contamination arises, the regulatory authorities will add emphasis and stricter requirements to be able to use such POC processing units.
In 2022, FDA requested feedback on distributed manufacturing and POC drug manufacturing, which shows the interest but also the care that needs to be attained to satisfy not just the necessary quality attributes but also the regulatory authorities. As regulators will assess such processing systems on a risk basis, the risk must be minimal for both quality and safety, including the point-of-care unit itself. The thought that cheap will create the required quality has been seen as an ultimate failure in many examples.
COVID-19’s Effect On Point-of-care Manufacturing
The global impact of the COVID-19 pandemic accelerated the innovation and adoption of POC manufacturing practices in the biopharmaceutical industry and pandemic preparedness. This unprecedented crisis brought to light the crucial need for agile and responsive manufacturing solutions that can swiftly address emerging public health challenges. The pandemic served as a catalyst for innovation, highlighting the effectiveness of flexible processing systems that can be rapidly deployed to meet the evolving demands of the healthcare landscape.
One of the key outcomes of the COVID-19 pandemic was the need for rapid deployment of mobile sampling and testing units, instead of sampling and shipping the samples to a centralized lab, delaying the receipt of results. Sampling and rapid testing can be a preventive measurement to contain a spread and realize infection pools. The lack of rapid sampling/testing capabilities was highlighted by the pandemic and required corrective actions to be able to activate these units when the next epidemic or pandemic arises.
Furthermore, on-site compounding and filling are necessary. These mobile units have played a pivotal role in addressing critical shortages of essential medical supplies and facilitating timely treatment processes. By bringing manufacturing capabilities closer to the point of care, these adaptable solutions have demonstrated their value in enhancing healthcare delivery and response efforts during a crisis. Current process intensification, smaller footprint processing systems in nanoparticle and LNP processing, filling units, single-use assemblies, etc., all support the implementation of agile, mobile units.
The pandemic underscored the importance of adaptability and responsiveness in manufacturing operations, emphasizing the need for point-of-use facilities that can quickly scale up and adjust production in response to changing circumstances. By positioning manufacturing capabilities closer to where they are needed most, organizations can minimize logistical challenges, reduce turnaround times, and improve access to essential medical products and treatments.
In conclusion, the COVID-19 pandemic not only accelerated the adoption of point-of-use manufacturing practices but also demonstrated the critical importance of flexible and agile manufacturing solutions in addressing public health emergencies. By embracing innovative manufacturing approaches that prioritize agility, responsiveness, and proximity to the point of care, organizations can enhance their capacity to deliver timely and effective healthcare interventions, ultimately improving patient outcomes and strengthening the resilience of healthcare systems worldwide.
Ensuring Controlled Environments In Modular Facilities For Consistent Drug Quality
To maintain a controlled environment within modular facilities across various climates and constrained production spaces, meticulous consideration in design and execution is imperative. Robust management of temperature, pressure, and humidity controls, coupled with stringent containment practices, is vital for upholding consistent drug quality and safety standards. Appropriate air handling systems, insulation methods, and uncompromising oversight of personnel and material flows are crucial elements in ensuring the sanctity of the processing environment while minimizing risks associated with external contaminants.
Ultimately, a POC processing unit must maintain the same quality of the internal environment no matter whether it is positioned in the tropics or the Arctic Circle. These systems must be mobile and maintain strict environmental cleanliness, no matter the location. It has to be reiterated that the regulators want to see such units being ultimately consistent and reliable to ensure that any critical quality attributes are not compromised. Only when experiences show that such mobile or POC placed systems perform as demanded, rapid scaling and regulatory approval can be achieved.
This means, prior to embarking on POC manufacturing within a modular facility context, manufacturers must emphasize key engineering considerations to uphold the integrity of the processing environment. The preservation of containment integrity, maintenance of stable environmental conditions, and adherence to rigorous regulatory standards are fundamental in achieving high-quality and dependable drug production processes. A comprehensive focus on detail in the design and construction of modular facilities is essential to meet the strict quality and regulatory prerequisites necessary for the safe and effective execution of manufacturing operations.
Technological Advancements Driving Progress In Point-of-care Manufacturing
As highlighted, technological progressions have significantly influenced the landscape of POC manufacturing, with notable advancements in single-use process technologies, continuous bioprocesses, and mobile cleanroom units reshaping industry capabilities. The integration of closed processes and the mobility of cleanroom units have transformed the operational dynamics of POC manufacturing, allowing for enhanced efficiency and adaptability. These innovations have not only streamlined processing but have also expanded the reach of manufacturing activities to various locations, thus addressing the need for localized production. This is a pivotal aspect, as the pandemic showed that in country/for country vaccine manufacturing is essential to serve the global communities. Small footprint, high-yield processing equipment, intuitive automation and controls, and robust processing environments are the enablers to meet these needs.
Moreover, the move toward handling lower but highly critical processing volumes, particularly evident in autologous cell therapy applications, has added another level of criticality to manufacturing practices. Each batch could be a patient’s last lifeline. There can be no failure, as it would be detrimental to the patient. Processing a patient sample means not just maximizing cost efficiencies but doing so in an unconditionally controlled process stream and environment. Smaller volumes have also enabled process intensification, allowing for the execution of complex procedures within reduced spaces. Using smaller footprints and adopting innovative process technologies have further optimized the feasibility and efficiency of POC manufacturing processes. Examples of continuous processes in cell culture processing, oral solid dosages, and mRNA encapsulation processes, to name a few, evidently show excellent results in footprint compression without the sacrifice of yield and capacity output.
By embracing these technological breakthroughs, the industry has unlocked new possibilities for agile and cost-effective manufacturing solutions. The ability to intensify processes, reduce operational footprints, and enhance flexibility through mobile cleanroom deployments including innovative process equipment signifies a momentous leap toward achieving seamless and quality-driven POC manufacturing operations. Such advancements not only streamline production activities but also pave the way for enhanced product quality, accelerated innovation, and reduced cost-of-goods-sold within the realm of cell and gene therapies.
Future Trends Impacting Point-of-care Manufacturing
The future of point-of-use manufacturing is poised to witness a divergence between cost-driven, low-quality solutions and high-quality containment systems designed for POC applications. While experimental attempts may prioritize cost-cutting measures, the industry's focus on quality and compliance is expected to prevail, ensuring patient safety and delivering positive health outcomes. By prioritizing quality over cost-saving measures, advancements in POC manufacturing are expected to usher in improved drug production processes and enhance patient care standards meeting the regulatory requirements.
The option to reduce costs must not compromise the quality of the processing units. Instead, the cost-cutting can be done by cloning such processing systems. Once a detailed design for a small-footprint, mobile system has been established, the need to invent the wheel again is gone. Avoiding unnecessary redesign phases, understanding the value of a standard design, and starting to mass produce POC processing suites will ultimately bring the costs down to the needed level.
The automobile industry is a good role model for POC production and supply reliability. It shows that properly designed systems can be produced and delivered at a high-quality level and at the right cost. It is a matter of adopting creative ideas and challenging expensive traditions.
Conclusion
The rising importance of POC facilities in many applications, including cell and gene therapy manufacturing, pandemic preparedness, and in country/for country supplies, underscores the critical need for innovative solutions that address capacity demands while maintaining high quality standards. By prioritizing compliance with regulatory requirements, implementing top-tier contamination control strategies, and emphasizing the quality of cleanroom infrastructure, manufacturers can navigate the complexities of point-of-use manufacturing and deliver safe, effective therapies to patients.
Looking ahead, advancements in technology, engineering, and regulatory compliance will continue to shape the evolution of point-of-use manufacturing, driving improvements in drug production processes and ultimately benefiting patient care and outcomes.
About The Author:
Maik W. Jornitz is a technical expert with over 35 years of experience in bioprocesses, especially sterilizing grade filtration and single-use technologies, including regulatory requirements, integrity testing, systems design, and optimization. Jornitz has published 11 books, 18 book chapters, and more than 100 scientific papers. He is a member of multiple PDA Task Forces, a former chair of the PDA Board of Directors, and the PDA’s Science Advisory Board.