Our New Product Introduction (NPI) program maps out your entire journey to commercialization. It accounts for each key milestone with checkpoints to ensure you meet all required quality standards as your therapy progresses towards commercialization. The NPI program leverages our heritage and longstanding experience in establishing cGMP manufacturing standards, combining both corporate and local quality standards, customized for cell and gene therapies, to de-risk your journey to commercialization.
You will also maintain complete oversight during your product’s lifecycle journey, enabling you to assess and validate the quality of process robustness, raw materials, analytical methods, sterility, facility, equipment, and tissue acquisition throughout this journey.
Our established, compliant facilities and processes enable you to leverage facility layouts, airflows, material storage, documentation processes and quality systems that have already proven to be suitable for commercial manufacturing and have passed regulatory agency inspections for other cell and gene therapies.
As a result, you can focus on your product’s manufacturing process to withstand the scrutiny of regulatory inspections, while relying on us to complete the regulatory compliance checkpoints at the facility where it is hosted. By minimizing risks to commercialization in this way, you will be able to avoid major rework, delays and related costs that could lead to a significant business loss.
Our cGMP manufacturing capabilities span three technologies – autologous and allogeneic cell therapies and viral vector gene therapy and our footprint spreads across three continents. We can support you at all stages of clinical development and commercialization to help you drive your pioneering therapies to market.
| Preclinical and early phase | Late phase and commercial | Support for optimized path to market |
|---|---|---|
| Manufacturability assessment | Global cGMP manufacturing capacity across 3 continents | Tissue acquisition services, Cell and viral banking |
| Process improvement & development | Global tech transfers | Customized business and operation models, facility build-out |
| Analytical assay development, qualification & validation | Commercialization readiness | Quality and regulatory set up for successful commercialization |
| Media optimization & development | Formulation & fill / finish | Regulatory consulting and services |
| Formulation & fill / finish | Storage & distribution | |
In manufacturing CGT products, the operational complexity of handling and tracking individual patient or donor samples from the clinic to the manufacturing site and back to the patient poses an unprecedented level of logistical challenges. As each product needs to be tracked to the corresponding patient, maintaining a chain of custody and traceability across the entire manufacturing pipeline is indispensable.
These challenges are especially acute for autologous Cell Therapy products with typical timelines ranging from 10 to 14 days, schedules in CGT manufacturing are tight, further adding pressure on the supply chain. Any delays in delivering the therapy can directly affect the patient’s health outcomes. Along every step, the involved parties — patients, sponsor companies, hospitals, manufacturers, and couriers — need to receive regular updates on the manufacturing status. “It’s important that we’re able to provide the right information to the right audience at the right time, without additional burden and cost to the site,” says Walter Bagni, CGT Center of Excellence Lead at Lonza. Incidentally, most of these time-sensitive manufacturing activities are recorded on paper or spreadsheets. Technicians manually fill out the details in a document, while approvers review and verify the information in person. These records are then copied and physically stored. Manufacturing timelines are tracked on spreadsheets, while schedules are set over phone calls or emails. Unsurprisingly, when an entire operation, from sample receipt to product shipment, is held together by manual tasks, errors and omissions are inevitable. In addition, managing documents that hold sensitive and confidential patient information requires regular administrative upkeep, making the entire process highly resource intensive.
The fact that paper records are physical entities increases the risk of losing or misplacing them...they can also increase the risk of contamination when taken into clean rooms.
- Walter Bagni, CGT Center of Excellence Lead at Lonza
In early 2019, Lonza’s CGT manufacturing sites in Houston and Portsmouth (USA), Geleen (the Netherlands) and Singapore underwent a phase-by-phase digitization process using the MODA-ES® Platform. During the first phase, the goals of the project were to digitize the chain of custody/identity and traceability at the Houston and Portsmouth sites. The MODA® Implementation Team provided hands-on support to install, configure and validate the platform to best suit each site’s needs. Next, the ‘flexible recipe modeler’ was used to customize the site’s manufacturing workflows, i.e., the sequence of events, materials, schedules and other details. Progressing simultaneously, both Houston and Portsmouth sites underwent performance checks and went fully digital with ‘track and trace’ by early 2020.
“I truly appreciate the CGT knowledge that the MODA® Implementation Team brings,” says Bagni, who oversaw the entire digitization operation. “Because of their expertise and dedication, we were able to shorten the implementation timelines to less than nine months, one of the fastest deployments I’ve seen in my career.” Upon completing Phase one, Phase two commenced at the above US sites. This time, he goal this time was to digitize the entire manufacturing process and implement electronic batch recording. Meanwhile, phase one was initiated at the Singapore and the Netherlands sites.
Capacity expansion
The main reason behind prioritizing ‘Track and Trace’ digitization was to facilitate open phase parallel processing at the CGT manufacturing sites. Previously, with paper-based tracking, the Lonza sites could only process one batch in a clean room at any given time due to higher risks of cross-contamination or mix-ups. Enforcing a systemized, digital chain of custody has now made it possible to run multiple open phases in parallel, either for the same patient or for multiple patients, within the same clean room. As a result, the degree of equipment utilization has also increased. By expanding the manufacturing capacity on-site without additional overhead, the MODA-ES® Platform has helped decrease the overall cost of production.
Paper elimination
Electronic record-keeping for traceability has eliminated the use of paper on the manufacturing floor at the Houston and Portsmouth CGT sites, where data is now captured and stored digitally. Instead of writing on pre-printed labels, technicians can print labels on-demand. Dedicated clean room barcode scanners help input or retrieve information. With no more transcription errors or inadvertent omissions stemming from paper-based documentation, the number of batch rejections on-site has drastically reduced, making the operations more cost-effective. Most important of all, technicians can now focus on the task at hand instead of manually filling out paperwork while juggling everyday activities. The ability to queue electronic signatures for approvals on the MODA-ES® Platform eliminates frequent interruptions during the workflow. Patient records remain safe and secure and can be readily accessed by authorized personnel at any time, without having to request physical files. Finally, the manufacturing status of the drug product is now recorded in real-time to allow couriers, sponsors and patients to receive timely notifications.
Real-time updates
Digital ‘track and trace’ using the MODA-ES® Platform provides a complete overview of the facility’s operations by the minute. Even if production volumes increase in the near future, site managers can easily monitor progress or troubleshoot issues from one platform. The CGT sites now digitally provide near-real-time updates to all stakeholders instead of sharing spreadsheets or making phone calls. Scheduling pick-ups and coordinating deliveries are hassle-free, eliminating logistical delays from an already tight timeline.
Flexible workflows to meet business needs. The MODA-ES® Platform is specifically designed to serve CGT manufacturing needs. As such, it’s easy to make process modifications when the project moves from clinical to commercial, or if a technology change is implemented during a project. Based on the latest regulatory requirements, instructional text can be updated to capture new information at any point during the workflow.
Highly efficient operations enhance product quality. Rapid and accurate data entry using digital tools expedites the review and approval process, thereby advancing projects faster. As handwritten notes and manual calculation get replaced with digital ‘track and trace’ methods, human errors are eliminated, and consequently, protocol deviations or batch rejections are reduced. All around, the reliable chain of custody maintained using the MODA-ES® Platform directly upholds data integrity to keep the entire operation compliant with regulations.
Tangible reduction in production costs. Digitized operations using the MODA-ES® Platform can reduce data entry and review times by 50–70%, thereby allowing technicians and supervisors to focus on higher-value tasks. Implementing electronic batch recording can shrink production hours on the manufacturing floor by 10-20%, directly reducing the overhead costs of the operation. Finally, even if deploying an MES system can seem like an investment upfront, the multifaceted applications of a single platform to expedite all aspects of the manufacturing workflow, from sample arrival to product release, lowers the total cost of ownership.
Maintaining paper-based records, although a deeply rooted practice in manufacturing, can negatively impact the overall efficiency of the site, especially in CGT operations where delivery times are short and data accuracy is paramount. Implementing an MES, such as the MODA-ES® Platform, not only eliminates manual errors but also accelerates production timelines. With the added ability to perform open phase parallel processing, the site’s manufacturing capacity expands without any additional overhead costs. To learn more about the MODA-ES® Platform deployment project at our four CGT manufacturing sites, watch our webinar ‘Digitizing Cell and Gene Therapies Manufacturing - A Lonza Case Study ”.
Our comprehensive range of testing solutions supports your pyrogen and endotoxin testing programs. Pyrogens are fever-inducing substances primarily derived from microorganisms such as bacteria, viruses, yeasts, molds or chemical substances. The most potent type of pyrogens are bacterial endotoxins which are derived from the cell wall of gram-negative bacteria. All parenteral pharmaceutical products, including cell and gene therapies, are required to be free of pyrogens that may induce life-threatening systemic reactions in a patient.
Lonza offers in vitro assays, instrumentation and data analysis software to fit your raw material, in process and final release testing needs. These solutions can be globally harmonized and scaled to fit your company’s changing business. Our team of global QC testing experts can help you find the solutions most suitable for your products. No matter where you are in your process, Lonza’s testing solutions, optimized with our world-class software, and supported by our experts, will help streamline your work flows, meet regulatory requirements and deliver safe drugs to your patients.
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There are four main types of bacterial endotoxin test (BET) methods that are used for required QC safety testing during the manufacture of parenteral medicines and implantable devices. All are based on the enzymatic cascade exhibited by specialized cells (amebocytes) found in the blue blood of horseshoe crabs which form a clot in the presence of endotoxin. The newer assays utilize recombinant versions of the proteins, providing a sustainable solution that reduces the reliance on natural resources.
Lonza offers qualitative tests that measure gel clot formation, such as the PYROGENT® Gel Clot Assay, and quantitative tests that measure turbidity with the PYROGENT® 5000 Kinetic Turbidimetric Assay, a color change with the Kinetic-QCL® Kinetic Chromogenic LAL Assay or a fluorescence change with the sustainable PyroGene® rFC Assay.
Early detection of pyrogens in a pharmaceutical preparation is critical for quality control programs and an essential product safety measure. Pyrogens may originate from microorganisms such as bacteria and fungi and also from viruses, genome components or other organic particles from the environment. With the evolution of manufacturing technologies that deliver for example, vaccines, bioprocessed proteins or cell and gene therapy products, new contamination risks may arise in production. Pyrogens initiate inflammatory reactions when injected into a patient.
Instead of relying on rabbit-based pyrogen testing, you can now utilize an in vitro Monocyte Activation Test to help ensure drug product safety and compliance Though the Monocyte Activation Test principle was established decades ago, its adoption for life-saving biologics has only accelerated recently. Lonza offers the PyroCell® Monocyte Activation Test Systems to provide the perfect solution for life-saving drugs that are unethical to test in experimental rabbits or cannot be tested with standard bacterial endotoxin tests.
Endotoxin testing traditionally involves a number of manual laboratory preparation steps that are inherently prone to human error. To address these issues, Lonza created the PyroTec® PRO Automated Robotic Solution. Now compatible with the PYROGENT® 5000 Assay, Kinetic-QCL® Assay and the PyroGene® rFC Assay, the PyroTec® PRO System provides laboratories the ability to reduce errors and increase throughput using rFC and LAL assays to suit all your testing needs. The PyroTec® PRO Automated Solution is fully integrated with the WinKQCL® Endotoxin Detection and Analysis Software ensuring that data integrity requirements are met.
For labs with lower testing throughput, Lonza offers a range of microplate readers that are optimized for use with our WinQCL® Endotoxin Analysis Software. These readers include the new Nebula® Multimode Reader, capable of running both absorbance- and fluorescence-based endotoxin and pyrogen assays, the PyroWave® XM Fluorescence Reader, and the Elx808™ Absorbance Reader.
Our WinKQCL® 6 Software offers a fully integrated solution for your quantitative endotoxin detection testing, data management and reporting needs and can be utilized with the various endotoxin test methods. The WinKQCL® Software guides the user through the process of setting up a microplate template and running an assay to determine the amount of endotoxin in a sample solution. WinKQCL® Software can be used with a compatible microplate reader to run the template and perform common endotoxin tests such as initial qualification, routine tests, inhibition/enhancement tests and an RSE/CSE test. The WinKQCL® Software uses the run data to calculate the results for the sample solutions and their associated positive product controls. All data is displayed in an easy to read configurable report, can be electronically reviewed and signed.
The WinKQCL® Software Package can be easily ordered on line and e-delivered along with any additional workgroup or reader licenses required to expand database access and management in your specific laboratory, across your facility or within your entire global microbiology QC organization.
Vice President, Sales and Program Management, CGT Business Unit