Aggregation
Protein aggregation is a common phenomenon occurring during the manufacture and lifespan of biotherapeutic products
The protein structure is particularly complex and the denaturation due to small disturbances can lead to aggregates and particles
Aggregation is triggered by environmental and technical factors. These aggregates can come from several physicochemical mechanisms and can be classified in different ways:
- Réversible / Non Réversible
- Covalent / Non Covalent
- Soluble / Not Soluble
Agregation in Production
- Troubleshooting
- Technical investigation and root cause analysis
- Support for regulatory documentation and inspections
Aggregation Issues
Aggregation influences the quality of biotherapeutics at all stages: from product development to manufacturing and administration.
- Is a potential cause of immunogenic reactions
- Responsible for adverse events during administration
- May result in reduced product efficacy
Regulatory impacts
- Quantify and measure particles in clinical and commercial batches (USP <788>)
- Perform aggregation risk assessment
- Perform stabilities including aggregation tests
- Generate data to support the process control strategy (PCS)
Financial Risks
- Non-compliance and scrap of commercial lots
- Commercial batch Recalls
Process Developpment
- Technical recommendations for process development or process optimization
- Aggregation risk assessment
- Technical recommendations to avoid and / or eliminate aggregates
- Development of the process control strategy (PCS)
- Development of a QbD approach to define an efficient and effective process (ICH Q8)
Training
- Technologies utilisées pour la récupération et la purification des protéines (extractions cellulaires, chromatographie, filtration, centrifugation, précipitation, etc ...)
- Méthodes analytiques pour le contrôle du procédé et la caractérisation du produit
- Scale-up du laboratoire à la production à grande échelle
- Technologies utilisées pour supprimer / inactiver les Virus et Prions
- Stabilisation du produit
- Transfert technique (Comment réussir son transfert technique)
- Concevoir des procédés de fabrication pour l'avenir