How process temperature, pressure, contact time, surface area, solvent system, process duration and removal steps can influence process-driven extractables and leachables.
Extractables and leachables are not only a packaging issue. Manufacturing operations can also create, transfer or remove potential leachables before the final drug product is packaged.
Temperature and pressure
More severe process conditions can increase material stress, diffusion, extraction or chemical transformation, depending on the contacting material and process fluid.
Contact time
Longer exposure between the process stream and equipment or components increases the opportunity for chemical transfer.
Surface area-to-volume relationship
The amount of contacting surface relative to process volume can influence the potential contribution of process-contact materials to the product.
Solvent system
Water, organic solvents, mixed solvents, buffers and other process fluids can interact differently with materials and can change extraction efficiency.
Downstream removal
Filtration, diafiltration, purification and other downstream steps may reduce or change the final exposure to process-derived leachables. Their relevance should be understood rather than assumed.
Process duration and lifecycle changes
Long manufacturing or hold times, equipment changes and process modifications can alter the E&L profile and should be considered in lifecycle risk management.
Frequently asked questions
Can manufacturing equipment be an E&L source?
Yes. Product-contact manufacturing systems can contribute potential leachables before final packaging.
Why does surface area matter?
A larger contacting area relative to process volume can increase the opportunity for chemical transfer.
Can downstream purification remove leachables?
Potentially, depending on the compound and process step; the effect should be supported by process knowledge or data.
Do process solvents affect extraction from materials?
Yes. Solvent composition can strongly influence material compatibility and extraction behavior.
Should process changes trigger E&L review?
Yes, when they change contact materials, conditions or exposure in a way that could affect the chemical profile.
