Recently, BPOG (Biophorum Operations Group) has published a guide that relates to mitigating risk in bio manufacturing processes when using single use systems components. A key aspect of the risk mitigation strategy is to consider the potential for chemical entities to migrate from the single use component material into the drug product. Suppliers could aid drug manufacturers with their risk mitigation strategies by generating extractables data on their single use materials. Extractables are typically ‘worst case’ indicators of potential leachables and provide a drug manufacturer with useful information on how to approach future leachables studies.
Key definitions to understand are listed below:
Extractables chemical entities that are able to be extracted from a component of a process system into a solvent under controlled conditions which are usually more aggressive than the normal operating conditions
Leachable’s chemical entities which come from single-use system components that migrate into the drug product during normal use. The single use system consumable qualification process must demonstrate that processing components do not impact the quality of the drug product.
It is important to understand that the product quality should be maintained throughout the drug product lifecycle to ensure that the attributes deemed important to the quality of the drug product are consistent with those evaluated during clinical studies.
One aspect detailed by BPOG and other industry bodies is how to perform risk evaluation. Risk evaluation is based on assessing the risk to patient safety, product impact manufacturing and regulatory approval. The regulations for drug manufacturers specifically detail that the equipment used in manufacturing of the drug substance shall be constructed so that the surfaces that contact the process material or drug product shall not be, reactive, additive or absorptive.
Risk assessment can be focused on either testing of every single use system component or by taking a risk-based approach where only critical single use system components are tested. The approach taken can be determined by considering the following key attributes
- Distance of the single use component to the final drug product or API
- Process temperature
- Process time
- Process fluid interaction
- Dilution effects
If you have additional questions about extractables, leachables, or any single use components, contact a Holland Sales Engineer today.
*A Special thanks to Sade Mokuolu @ WMFTG BioPure for her help in putting this blog together