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INCOG BioPharma Services is a new standard of CDMO (Contract Development and Manufacturing Organization), whose management team has decades of experience in the pharmaceutical industry and the CDMO sector. To begin, the company opted for a highly flexible turnkey MultiUse system with an isolator from Optima Pharma.
High flexibility – probably the most important feature for an isolated filling and capping line for a newly founded CDMO. The INCOG founders, including Cory Lewis and Tedd Green, worked for many years in managerial positions in pharmaceutical companies and managed well-known CDMOs to growth and success. According to Lewis, the INCOG team had already commissioned more than six Optima systems during their time at other CDMOs. From the beginning of the project, the requirements for the new MultiUse system were clearly defined: The machine configuration had to cover production capabilities ranging from clinical studies to commercial production of medium and large batch sizes. Vials, pre-filled syringes, cartridges, RTU, and bulk containers must be processed. November 2020 was the project start for the turnkey system at Optima Pharma.
Two processing paths were set up for vials so that the system could handle very small batch sizes of approximately 500 containers, as well as large batch sizes. Bulk vials are less expensive but more time-consuming and expensive to process since they require washing (washing machine) and sterilizing (sterilization tunnel).
This is adequate for larger batch sizes but not for smaller batch quantities. For smaller batch sizes, pre-sterilized RTU containers are the more economical choice. In addition, there is no glass-to-glass contact during the vial processing. The system offers filling with peristaltic pumps or a time/pressure system, including CIP/SIP cleaning and sterilization functions.
Therefore, INCOG is strategically well-prepared to handle different batch sizes and diverse container and drug types from the beginning. The system reaches outputs of up to 9,000 vials and up to 7,200 pre-filled syringes per hour.
“The company’s objective is to offer customers not just good but outstanding services,” says Cory Lewis. A closer look reveals an in-depth connection with the system technology. With the MultiUse system, INCOG has 100% in-line quality control. In terms of patient safety, this is a fundamental requirement. However, the unique feature of the MultiUse system is to correct deviations immediately. Containers that do not meet the specifications are not simply ejected but reprocessed in-line.
For example, the weight-dosing function of the Optima filling machine is designed to have the correct filling volume from the first container. To ensure that no containers are rejected during the priming of the product path, the containers are filled directly on the load cells until the target weight is reached. The redosing function can also be used to correct under-filled containers in the regular filling mode. The stoppering station has the same function, and if a stopper is not picked-up, the system will return to pick the stopper again and ensure the container is closed.
INCOG thus produces significantly more commercial product from the amount of liquid processed compared to systems without these product-saving features. These features of the MultiUse become even more critical for costly pharmaceutical products. In addition, even with large batches of less expensive drugs, the overall result is a profitable effect.
INCOG also benefits from the system’s modular design if a freeze-drying process has to be added later. INCOG chose a separate capping machine, connected downstream, that offers the opportunity to return the freeze-dried product to the line and close it easily. Syringe and cartridge processing or liquid filling in vials could then take place on a parallel path during freeze-drying.
A recently introduced innovation by Optima provides INCOG the opportunity to meet high machine outputs with the MultiUse. To individually process the objects, an XTS oval conveyor transports the objects to the infeed at the beginning of the process. Background: Individual processing is a prerequisite for all product-saving functions, including 100% inprocess control.
The presterilized and nested RTU containers are prepared for further processing. A robot peels off the Tyvek and then removes the lid liner.
Vials are crimped. This station is located downstream so that INCOG can add a freeze drying process later.
The oval conveyor is a module for vials, pre-filled syringes, and cartridges. Both vials, after sterilization, and all RTU containers are removed from the nest and safely transported to the individual stations, corresponding to the highly flexible MultiUse concept. Thereby, the oval conveyor ensures high performance across all container types.
Another oval conveyor at the end of the line returns the pre-filled syringes and cartridges to the nest. This oval conveyor closes potential gaps (the productsaving functions already minimize gaps) created by any rejects that would lead to empty spaces in the nest. This is prevented by transferring the containers from the isolator-protected area to individually controllable shuttles of the oval conveyor. If necessary, the arrangement of the shuttles is configured to allow each shuttle to take over an object. Potential gaps between the shuttles are closed on the transport route in the oval conveyor. On the opposite side, a robotic arm takes over a complete row of containers and puts them back into the nest. All vials are placed in trays after crimping. Apart from the crimping path, the containers are processed without glass-to-glass contact.
INCOG benefited from Comprehensive Scientific Process Engineering (CSPE) during the design and implementation phases. An approach that Cory Lewis describes as “a simplified, improved installation and maturity phase.” These included, among others, simulations of the laminar airflow for bulk vials and RTU containers and their respective product paths. For example, the simulation for the sterilization tunnel was also included for bulk vials.
The H2O2 distribution in the isolator-protected area, as the first phase of the VHP cycle development, was also part of the simulation. The injection nozzles in the customized isolator were virtually placed and tested to achieve complete coverage with H2O2 and a homogeneous H2O2 distribution. Subsequently, parameter settings, like the injection rate and time, were optimized in a more detailed model, providing an excellent basis for cycle development using chemical indicators.
The isolator, which includes the very efficient DECOpulse® decontamination system, was set up and ready for operation with the MultiUse system in the CSPE center at Optima Pharma. The software was integrated, and the tightness of the isolator was tested, as well as the signals and all functions, including the CIP/SIP processes. Based on the simulations, the laboratory-based cycle development with chemical indicators was followed at Optima Pharma in the CSPE center. An effective, timesaving decontamination cycle has been fully defined.
In February 2022, Sascha Winter’s team at Optima completed a smooth integrated Factory Acceptance Test (iFAT). The complete system was tested, and various customer requests were implemented, like adjusting the monitoring zones.
The CSPE pre-installation and testing effectively reduced the installation time at INCOG onsite in Fishers (Indiana, USA). After completing the SAT in October 2022 and the IQ and OQ, INCOG could go straight to the PQ and the media fills. Over the course of the project, the CSPE process saved an estimated three to four months. Altogether, the success of the project is a reflection of the close partnership between the project teams from INCOG, Optima Pharma (Schwäbisch Hall, Germany), and Optima Machinery Corporation (Green Bay, USA) – a considerable benefit for turnkey projects.
In December 2022, just 23 months after the groundbreaking of the building in Fishers, Indiana, INCOG achieved GMP-compliant aseptic filling and closing processes for parenteral products. Media fills for a first format were successfully completed, and a commercial Process Performance Qualification (PPQ) started. In March 2023, INCOG announced the start of its first commercial production.
With current and past experiences in mind, the INCOG team already decided to work with Optima Pharma on their next project. In January 2023, the kick-off meeting for another turnkey system took place. The highly flexible MultiUse system is supplemented by an Optima H6-10 highperformance syringe filling and closing machine.
With our services, INCOG strives to position itself as a leading CDMO (Customer Driven Manufacturing Organization) in the market. Our filling line very well supports our customer-driven manufacturing organization approach, as its design allows both small and large batch sizes, clinical studies, and commercial campaigns to be processed, and this, in turn, with different format sizes and container types, such as pre-filled syringes, vials, and cartridges. The variety of process possibilities supported by the flexible MultiUse Filler allows us to shorten the time to clinical applications. At the same time, we can scale up to commercial use and provide lifecycle management across different container designs.
2. Optima has implemented CSPE (Comprehensive Scientific Process Engineering) as a turnkey provider to shorten the customer’s installation phase and support the qualification process. What is your impression of this offer?Our capacities were ready for use more quickly with the CSPE process. We got there in less than six months, from installing the filling and closing line to the media fills. As implemented at the Optima site, the turnkey solution has resulted in a simplified, improved installation and maturity phase of the project from the moment it arrived on site. Excellent service, thank you!
3. What were the most important reasons for choosing Optima as the filling and capping line supplier?There were several reasons. First of all, the industry experience and Optima’s proven expertise. Then the scope of services is integrated into the filling and closing line. Also important to us was the easy access and availability of the service and support team after the installation of the line for ongoing operations in our company. Last, we can look back on a broad partnership between a CDMO and Optima, which we had already achieved before. This shows the partnership approach, in contrast to a customer/supplier relationship.
The system works very well when processing pre-filled syringes or vials. The functionality of the filling and closing line, the integrated robotics, and the integration of the isolator in the line all allow us to take customer requests with great confidence.
5. What is the next step before you start production?Our MultiUse filling line is already in production, and we are continuing to complete qualification activities to ramp up future customer production. We have media fills for the 1mL – 3mL syringe, 2R-10R vials, and 3mL cartridge formats and are completing a commercial PPQ (Process Performance Qualification) batch for one of our commercial customers. We anticipate an FDA regulatory inspection of our facility in early 2024 to begin commercial manufacturing. We are excited to continue to expand our customer base with both clinical and commercial customers because of the flexibility of the MultiUse filling line.
6. How satisfied are you with the project so far?I am extremely satisfied for the reasons mentioned above. Ultimately, Optima met all of our needs on time, on budget – and, more importantly, with successful media fills. Ensuring sterility is the central key performance indicator for success.
