It’s time for pharma to embrace “Industry 4.0.” So says the FDA¹, which is urging the industry to accelerate the adoption of next-generation technologies. To encourage the transition, the agency is giving pharma a seat at the table to help it solve regulatory process issues and set strategies to remove other barriers to innovation.

This proactive and collaborative approach is tied to the long list of benefits the agency says patients and pharma can derive from next-generation drug manufacturing. It says novel technologies will²:

• Rapidly scale manufacturing capabilities for vaccines and other medical countermeasures to respond faster to emerging threats and public health emergencies, such as pandemic influenza and natural disasters;
• Shorten supply chains and increase manufacturing resilience to disruption by emerging threats and public health emergencies by creating a distributed network of small manufacturing sites that can provide reserve capacity for centralized manufacturing facilities;
• Accelerate therapy development for orphan diseases by improving the cost-efficiency of small-scale manufacturing processes;
• Speed availability of emerging therapies by enabling manufacturing process and standards development, including for cell and gene-therapies, supporting goals of the 21st Century Cures Act; and
• Provide new tools to address drug shortages and other challenges, including pharmaceutical quality.

Double the power
In January of this year, the FDA began a collaboration with the National Institute of Standards and Technology (NIST) to strengthen its case. NIST evaluates the quality, safety and efficacy of a wide range of drugs and medical devices. Its measurement and testing facilities focus on the processes, controls and modeling used in modern manufacturing.

The two agencies’ memorandum of understanding (MOU)3 is written to strengthen the U.S. medical supply chain and enable and accelerate pharma’s adoption of advanced drug manufacturing technologies. Among the technologies: artificial intelligence, machine learning and emerging manufacturing processes. The MOU also outlines the institutions’ commitment to modernize their own regulatory frameworks as they ask pharma to transition to “Industry 4.0.”

Curia—formerly AMRI—is venturing into this 4.0 territory with its first rapid microbiological methods (RMM) sterility testing facility, set to open in the first quarter of 2022. Widely used in the biologics and food industries, RMMs facilitate more accurate, much faster means of product testing. As one of Curia’s forays into next-generation technologies, the sterility suite in Lebanon, N.J., will meet existing demand for RMM testing. Additionally, this expansion will open the door for smaller biologics manufacturers to leverage cutting edge technologies without the initial capital required to build these laboratories.

RMM’s track record
In the food industry, RMM is applied to help cut production time through rapid testing that detects pathogens that could cause outbreaks of foodborne diseases. It can also provide the agriculture and biologics industries with quicker and more accurate results than are provided by the conventional testing methods used in pharma.

Curia, which has more than 30 years of experience in pharma research, development and manufacturing, is taking a step forward with RMM. We are adopting rapid detection because it’s been proven to be more sensitive, specific, time-efficient, labor-saving and reliable than standard methods. It’s a more analytical approach to the test and offers turnaround times as short as one day versus what currently can take up to a month.

With RMM, batches don’t sit on hold in a warehouse. This is why biologics companies already are using RMM. They can’t sit on a cell therapy. It needs to be used right after it’s made.

Readying regulators
As the FDA promotes these RMM efficiencies, it also acknowledges the technical and regulatory challenges that stand in the way of adopting the technology and other innovative approaches.

For that reason, the Office of Pharmaceutical Quality within the FDA’s Center for Drug Evaluation and Research (CDER) has created the Emerging Technology Program (ETP). The program will put industry members together with Emerging Technology Team (ETT) members to resolve potential technical and regulatory issues during development and implementation of novel technologies and before a regulatory submission is filed.

The FDA says pharma firms that participate in the ETP can expect these benefits⁴:

• Pre-submission, face-to-face interactions with ETT members and review staff to answer technical and regulatory questions during the development and adoption of the proposed technology; and
• Opportunity for early interactions with the ETT and review staff on the proposed technology to gather feedback in preparation for a regulatory submission.

The FDA says pharma firms should participate in the ETP⁵ when a proposed technology is expected to improve product safety, identity strength, quality/purity and has at least one element subject to quality assessment that may be unfamiliar to the agency.

Virtually any next-generation technology implemented in drug production would meet one or more of the criteria. Curia’s RMM initiative applies because it’s aimed at improving product safety, quality and purity.

Finding the right fit
The FDA cites the following activities as examples of the emerging technologies its ETT members will consider:

For small molecules

• Continuous manufacturing of drug substance
• Continuous manufacturing of drug product
• Model-based control strategy for continuous manufacturing
• Continuous aseptic spray drying
• 3D printing manufacturing
• Ultra-long-acting oral formulation

For biological molecules

• Controlled ice nucleation for lyophilization processes
• Advanced process control such as predictive modeling for process monitoring and closed loop bioreactor control
• Multi-attribute method
• Next-generation sequencing
• Continuous manufacturing for downstream processes
• Pharmacy on demand (a small manufacturing platform for continuous bioprocesses)

For multiple products

• Closed aseptic filling system
• Isolator and robotic arm for aseptic filling
• Novel container and closure systems for injectable products

Rewards worth the risk
The FDA is eager to move advanced manufacturing forward. That takes early adopters willing to manage through the associated complexity to reap the rewards. 

References

1. Hahn, S. M., & Rom, C. (2021, January 15). Accelerating the adoption of advanced manufacturing technologies. U.S. Food and Drug Administration. https://www.fda.gov/news-events/fda-voices/accelerating-adoption-advanced-manufacturing-technologies-strengthen-our-public-health
2. FDA. (2021, August 30). Advanced manufacturing. U.S. Food and Drug Administration. https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/advanced-manufacturing
3. FDA. (2021, January 15). MOU 225-21-006 with NIST for collaboration in Advanced Manufacturing. U.S. Food and Drug Administration. https://www.fda.gov/about-fda/domestic-mous/mou-225-21-006
4. FDA. (2019, October 10). Emerging technology program. U.S. Food and Drug Administration. https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/emerging-technology-program
5. FDA. (2019, October 10). Emerging technology program. U.S. Food and Drug Administration. https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/emerging-technology-program