Mastering Extractables Scaling for Complex Assemblies with Just a Click
Sartorius developed the Extractables Simulator to transform E&L validation from a purely empiric to a software-supported approach.
This article is posted on our Science Snippets Blog
Biopharmaceutical manufacturers and food manufacturers must demonstrate that contaminants from plastics used in the production process are not leaching into the product in quantities that exceed patient safety thresholds (such as TTC or PDE). This is essential to maintain the integrity of the product and avoid the potentially harmful effects of plastic in drug products.
The challenge for many companies is that the process of validating single-use systems (SUS) is increasingly complex, especially for single-use products made out of more than one polymer material. Manufacturers that want to streamline the process can do so with a comprehensive validation solution and support from Sartorius.
Moving Toward Software-Supported Validation
Some companies are still relying on empirical and manual validation only. In the case of extractables scaling, it requires a lot of manual calculation and intervention, which gets more difficult as the number of potential polymers in the production process increases. An advanced software-supported validation system can utilize algorithms to automatically perform process-customized extractables scaling with just a single click.
Sartorius’ Confidence® Validation Services now uses our proprietary Extractable Simulator (ExSim) to combine extractables, substance, plastics, and toxicological data in a single system.
The three main elements of the ExSim include Database, Scaling Algorithms, and Reporting.
Database
The database houses all the up-to-date source information and structures that data on extractables, substance, and toxicological information in a single place. It consists of:
- Analytical extractables results: Sartorius gathers the extractables data from experiments conducted with the Sartorius extractables methodology, the BPOG protocol, and/or USP <665> (draft) protocol
- Compound-specific information: the database summarizes all qualitative information, physical-chemical and toxicological properties, and key parameters for over 600 identified compounds.
- Device-related information: more than 8,000 components are included in the ExSim, enabling flexible and individual combinations according to customer process.
- Supportive information: Sartorius provides a description of the analysis methods and, equipment & material of construction (MoC) of single-use systems (SUS).
Scaling Algorithms
Each process’s physical or chemical parameters differ based on the component(s) in the SUS device and the assumed contact times. We implemented two algorithms based on physical principles – one for short (diffusion-controlled) and one for long (equilibrium-controlled) contact times. This provides the closest simulation to actual migration behavior.
The workflow below illustrates the working mode of the algorithms for complex assemblies, such as Configure-to-Order (CTO) and Engineer-to-Order (ETO):
- Phase 1: Identify the appropriate lab report in the database for every component and match it with the process-related configuration.
- Phase 2: Select the appropriate algorithms to perform the analysis – either diffusion-controlled or equilibrium-controlled scaling – and calculat each compound identified across all analytical methods (GC-MS, UV-HPLC, LC-MS).
- Phase 3: Document the results and the sources affecting the quantities, operation, calculation. The system records and preserves results to ensure traceability.
Reporting
Once the analysis is complete, the report displays the concentration of each compound (specific to your process) considering:
- Device size(s)
- Batch volume
- Contact time
- Product formulation
For further processing, we supplement this information with a risk assessment and optionally a safety evaluation. All of this information is made available in our Confidence® Extractables Assessments. The scaled extractables concentration is equal or worst-case to the information that would have been obtained from an extractables study in the laboratory. Still, it’s available at a much lower cost, and you can view the results in as little as a week. Reports are also qualified to support the submission of drug products to regulatory authorities
Get More Flexibility in Scaling and Combination of Extractables for Complex SUS
The ExSim from Sartorius helps biopharmaceutical manufacturers move to software-supported validation systems with process-customized extractables for increasingly complex single-use systems. It takes the exaggerated worst-case assumptions and manual calculations out of the process and provides broader insights at an earlier stage of process development.
Want to Learn More About Our ExSim?
- Schedule your live demonstration by emailing confidence.validation-services@sartorius.com
- Download the Extractables Simulator Whitepaper
- Watch our Webinar: Confidence® Extractables Assessments powered by ExSim