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Release driven and controlled by visual management
When you are a CDMO (Contract Development and Manufacturing Organization), customized production and release of a batch of active substance is the culmination, for the customer, of one year of development of its process and production, on average. It is the long-awaited Holy Grail required to start clinical trials or indeed to continue them. The product is finally available!
Release therefore presents two major challenges:
• Ensuring quality. Quality is governed by the Good Manufacturing Practices (GMP) frame of reference which provides an overall guarantee with regard to compliance with the expected standards throughout the chain from supplier management onwards, including manufacturing and product inspection. Release is based on the quality systems in place and the batch record in order to ensure efficacy and safety for the patient.
• Respecting time frames or “lead times”. Release time frames have to be both optimized and as short as possible. All process deviations are a sword of Damocles for the project as a time lag of one day can constitute a misstep for the customer in their race against the clock to make their material available.
So the release process must allow the activity to be controlled in its entirety and potential problems that could arise to be anticipated. In this context, implementing a visual release management tool is essential. The whole process must be mapped in order to visualize the expected deliverables. The release process is an activity shared between production, quality control and quality assurance. All must intervene at the right moment to allow the authorised individual to finally release the batch.
Needless to say, things can get complicated rapidly as the process involves entire teams and that is when the conductor of the orchestra must put everyone on the same page with a common management tool.
The tool installed at Merck is called FINISH and is inspired by the theory of constraints. It allows the partial reduction of time frames and, above all, the visual identification of obstacles throughout the process. Bottlenecks can change regularly depending on the batch, and the whole strength of the tool lies in having this vision in real time, and on a continuous basis.
It breaks down into several parts, first of all an overall process map of what is expected at each step versus timings. Then, there is a detailed focus on the production and quality control dossier review cycle, the production report and finally the actions identified or points to be monitored in connection with the batch that could compromise release.
The overall process lets us know at a glance and in an instant how the release process is progressing. Each deliverable is visualised by a label placed on the flow chart. If the label is present the activity is finished, otherwise the activity is in progress and is indicated in the subsection. At each management session, an update is given on timing. If this is consistent with expectations, the release process is under control.
The subsection that deals with the review cycle of each dossier provides greater detail on what stage each part is at as regards substeps and expected timings:
• The dossier is being verified by production: verification is carried out by a technician and then by a Production Team Leader.
• The dossier is being verified by quality assurance. The dossier is verified by a specialist who checks the key points of the dossier and ensures that the dossier is complete and consistent with expectations.
• Consolidation: depending on the comments made by the Quality Assurance specialist, the dossier is corrected by production. And finally, the dossier is finalised by the Quality Assurance teams in order to ensure that the dossier is complete and finished.
There is a 30 min follow-up session every week with the departments involved in release, allowing a check to be made on what has happened during the past week, and which sets the goal for the coming week. In just 30 min, all current batches are reviewed in this way.
This tool has been in place at Merck now for several months and is enabling releases to be implemented more calmly for everyone and within the allotted time frames defined beforehand within projects. It provides visibility on deliverables versus expected timings for each step of the process. At a glance, obstacles or points to be monitored that must be tracked closely can be seen and the actions necessary to deal with any obstacles put in place.
All the teams have the same level of information and can thus take collegial decisions together very quickly in order to achieve the final goal of delivering a high-quality Drug Substance within the allotted time frames.
Marine Tarche – Merck Biodevelopment
Responsable Assurance Qualité Opérationnelle chez Merck Biodevelopment, entreprise du Groupe Merck. Elle travaille depuis 8 ans sur le site de Martillac et a occupé plusieurs fonctions en Production, Compliance, Amélioration Continue et en Assurance Qualité dans les formes injectables classiques et dans les produits issus des biotechnologies.