Biotech: How CO.DON ensures stable processes and high quality

About CO.DON

CO.DON was founded in 1993 as a biotech company and has developed a process for the production of personalized cell therapies for cartilage defects. In state-of-the-art and currently unique facilities worldwide, patients' cartilage cells are cultured based on a taken sample and subsequently implanted back into them. The patients' bodies accept the cultivated cartilage as their own, effectively healing joint defects.

Various isolators are used in CO.DON's production that isolate the cartilage cells from the patients' sample under a protective atmosphere. When a serum is added, the cartilage cells are then cultured for about 30-60 days in incubators. Compliance with limit values within the facility is a mandatory requirement for guaranteed quality, high efficacy, and compatibility of the produced cartilage cells.

Initial Situation

As a company in the pharmaceutical industry, CO.DON is bound to strict guidelines that mandate, among other things, a comprehensive monitoring of production and documentation obligations. Compliance with these GMP guidelines (Good Manufacturing Practices) is regularly audited by official bodies.

For monitoring production parameters and environmental variables, CO.DON opted for digital tools from the beginning, but the implemented solution from the equipment manufacturer proved to be inadequate in everyday use and also from the perspective of the certification body.

CO.DON's Objectives

Mathias Striese - Head of Engineering at CO.DON - became aware of ENLYZE in November 2022 to realize a solution for seamless recording, documentation, and monitoring of all critical plant parameters.

It was clear from the outset that GMP compliance must be ensured. In addition to the verifiability of data validity, long-term storage of data for over 30 years in redundant data storage must be included. At the same time, the software should be intuitively usable and customizable to the individual needs of users.

In particular, the qualified person should receive visual support in the context of batch release to easily recognize process anomalies and deviations of parameters over the course of production for a batch. This should ensure traceability of process deviations based on the batch number. Therefore, the ability to link with the data from the quality management software of MasterControl, which is currently still under construction, was crucial.

Due to the dynamic corporate culture and upcoming audits, a timely implementation without significant internal resource deployment was also crucial for CO.DON.

In summary, CO.DON focused on the following points in their search for a new process monitoring and traceability solution:

Speed of implementation

• High service level and low internal resource commitment

• Reliable, redundant data recording along with validation of data correctness to comply with GMP guidelines

• Ease of use and adaptability to user needs

• Automated monitoring of limit values

• Future viability of the solution through enrichment of process parameters with additional contextual information from the MasterControl system

The Solution

At the end of February 2023, ENLYZE visited CO.DON's production site in Leipzig for the first time and connected all 24 controls of the entire production facility on the same day. The integration effort on CO.DON's side was limited to configuring the firewall. ENLYZE handled the rest within 5 hours without interrupting the operational process.

"The use of Grafana was a real game changer for us. Especially with the ENLYZE infrastructure in the background, we were able to visualize our data and set up alerts as needed with high speed and within an intuitive environment. The possibilities with Grafana are virtually limitless. My team was also thrilled by the agility: changes based on new findings were implemented with just a few clicks."

- Mathias Striese, Head of Engineering CO.DON

Just a week later, ENLYZE had identified the necessary data from the controls and, where necessary, corrected them through appropriate scaling. There were no further obstacles to the validation of the recorded values according to GMP guidelines. Initial versions of a Grafana dashboard were already used for this validation.

All collected data is standardly stored by ENLYZE in two different cloud systems at two different providers. Thus, long-term, redundant data storage was ensured.

The expansion of data recording to include additional plant parameters could be carried out independently by Mathias Striese using the “ENLYZE Variable Selection Flows” and “Variable Contextualization.” He was finally able to further modify the initial Grafana dashboards and adapt them to CO.DON's needs.

In particular, the input from colleagues in production and quality management was decisive. For production, a clear plant monitoring was essential. Deviations of individual parameters and impending limit value breaches should be recognized early so that corrective actions can be taken in production.

The quality assurance needed a visual preparation of the plant parameters over the time periods of specific production batches. This preparation serves both documentation and validation of process conformity, i.e., that the plant parameters behaved within the defined limit values. The ease of use now saves the qualified person time, and the visual preparation also provides an additional safety layer for error prevention.

"Since establishing our site, we have not experienced such a fast and smooth implementation of a digital solution. ENLYZE came to us and was able to connect directly with our controls without any problems. Colin, Clemens, and Henning immediately understood what we needed, and within a few days, they were able to present us with a working solution. I was then able to make further adjustments myself with just a few clicks. We had already resigned ourselves to a lengthy process. But the speed and competency of ENLYZE showed us that it can be done differently."

- Mathias Striese

Outlook

In the further course, CO.DON will also feed the alarms for process deviations into dedicated MS Teams channels. These notifications are intended to further increase response speed. There are also discussions about how the rules underlying the alarms can be adjusted to provide early indications of impending instabilities.

In addition, local data storage is also important as an additional security measure for seamless data recording to meet GMP guidelines alongside the redundant cloud storage. The technical implementation is to be realized with another edge device from ENLYZE and local databases that receive the data via MQTT.