Introduction
The complexity of developing and manufacturing biologics has not deterred their strong growth, and regional manufacturing must keep pace to ensure these modern medicines are available where and when they’re needed. In 2022, the number of approvals of biologics outpaced small molecules for the first time ever, accompanied by a 12%–13% increase in outsourcing to CDMOs (1, 2).
To meet the demands of manufacturing these advanced therapeutics—smaller batch sizes, higher drug substance cost, stricter regulatory guidelines, aseptic fill-finish processes, among others— CDMOs must reframe their production architectures to overcome challenges, guide sponsors through the process, and ensure sufficient supply for patients.
Aseptic filling is a critical make-or-break step in bioproduction, and gloveless robotic isolator filling technology can anchor built-for-purpose biomanufacturing architectures designed to support the production of cutting-edge treatment modalities. Comprehensive manufacturing solutions for advanced therapeutic medicinal products (ATMPs) must support seed-to-fill manufacturing capabilities that meet EU Annex 1 GMP guidelines and overcome the hurdles inherent to the production of advanced therapeutics.
Why robotic gloveless vial filling?
Traditional manual vial filling with restricted access barrier systems and gloved isolators still faces challenges for ensuring the level of aseptic assurance required for ATMP production. Robotic gloveless isolators provide the aseptic consistency and operational precision necessary in the production of therapies like plasmid DNA, viral vectors, mRNA, and recombinant proteins. As an example, after assessing various aseptic isolator options, NorthX Biologics of Matfors, Sweden (Fig 1) selected Cytiva’s Microcell™ vial filler, a first-in-industry robotic gloveless isolator (RGI) (Fig 2). Good manufacturing practices (GMP)-ready design, user-friendly operation, and flexibility in meeting production demands at various scales enable RGI technology to meet the emerging needs of ATMPs as they increasingly enter production. RGIs ensure reliable and consistent manufacturing parameters including:
- Minimized product loss, crucial for clinical trial materials and personalized therapies, where high drug substance manufacturing costs make losses in tubing, filters, and quality control especially expensive.
- Efficiency for small-batch production— for example, batch sizes between 100–1200 vials with an average batch time of 8 h for 1200 unit batches—and ongoing optimization for larger batch sizes.
- Accessible and timely maintenance and support, along with consistent availability of consumables and technical support within Europe.
"Our mission at NorthX Biologics is to bridge the gap between groundbreaking research and scalable clinical solutions. Robotic gloveless isolator technology is a cornerstone of that vision," says Peter Boman, Chief Operations Officer at NorthX Biologics.
Fig 1. NorthX Biologics manufacturing site located in Matfors, Sweden.
Fig 2. Microcell™ vial filler from Cytiva.
Moving from research to the clinic
Therapeutic innovation has historically faced a significant challenge in the biopharmaceutical field: translating academic research into clinical products. Expanding drug substance manufacturing to include the critical final step of drug product simplifies development and production processes for advanced therapeutics, adapting to the growing demands of personalized medicines. These hurdles, especially acute during clinical trials, include technology transfer, engineering fully aseptic workflows, and shifting clinical trial phase needs.
The translation of academic research to clinical-scale production still faces many barriers. ATMPs are fragile and often must use processes that are aseptic from pooling through to filling to maintain drug product integrity. Also, efficacy of ATMPs at smaller effective concentrations means that wasted residual volumes represent lost therapeutic potential. As such, minimizing loss is critical to therapeutic success.
Considering the increasing need for small-to-mid-batch production driven by personalized medicines and single-patient batches, aseptic filling with robotic gloveless isolator technology is an optimal solution that helps derisk ATMP bioproduction and facilitates more precise and efficient manufacturing processes.
Fit-for-purpose implementation and operations
Incorporation of RGI technology into aseptic bioproduction is a straightforward process that can reach key milestones within 15 months. An example for NorthX Biologics with the Microcell™ vial filler:
- Purchase and installation—6 months from acquisition to site acceptance testing.
- Media fill completion—5 months after installation.
- GMP certification (by the Swedish Medicinal Products Agency)—3 months after media fill completion.
- Initiation of first GMP batch production—1 month after GMP certification.
While NorthX Biologics required some room venting modifications for vapor-phase hydrogen peroxide cycle development and humidity control, the installation process was predominantly straightforward. Manufacturers benefit from the support of vendors like Cytiva through internal risk assessments and training, to ensure successful integration.
A future-ready approach
RGI technology, paired with strategic vision, can help transform biopharmaceutical manufacturing. By focusing on personalized medicine and maintaining an agile, fit-for-purpose approach, manufacturers can be prepared and enabled to meet the high demands of the dynamic landscape of small to mid-batch production. RGIs are a key technology designed to safeguard the final critical step in manufacturing modern therapeutics.
Learn more about NorthX Biologics.
Biography
Peter Boman is the Chief Operating Officer at NorthX Biologics, responsible for the manufacturing facilities in Matfors, Sweden. He holds a master’s degree in engineering biotechnology and business administration. Peter has a background in research and development, working primarily with analytical and process development. He joined NorthX Biologics in 2013 and has continuously improved his talented team, resulting in the production of many biological drugs for clinical trials.
References
- Senior M. Fresh from the biotech pipeline: fewer approvals, but biologics gain share. Nat. Biotechnol. 2023; 41:174–182.
- Friedman EL. Top trends in global biomanufacturing: 20 years of analyzing biologics production and supply. BioProcess Int. Feb 8, 2024.