E&L Assessments for Single and Multi-Use Manufacturing Equipment

April 30, 2018

Did you know that leachables testing is the exception and not the rule for evaluating and qualifying pharmaceutical manufacturing equipment?  Most equipment vendors have a full set of extractables testing data for their manufacturing components generated in many different model solvent systems that bracket the pH, polarity, and ionic strength of most aqueous based drug products.  The vendor extractables testing is typically performed according to the “white papers” issued by the Bioprocess Systems Alliance (BPSA) and the BPOG.  A scientific based assessment comparing the extractive power of the drug product that will be manufactured using the equipment to the vendors conditions of contact in the extractables testing has to be performed to demonstrate that the vendor extractables profiles were generated under “worst case” conditions.  At the PharmaEd Resources E&L Conference in Philadelphia on March 28-29, Dr. Edwin Jao, from FDA, confirmed this practice in his presentation entitled “Equipment Compatibility Issues for Manufacturing of Liquid Dosage Forms— FDA/OPF’s Perspective.”  Any “gaps” identified in the correlation of the vendor extractables data to the conditions used in manufacturing the drug substance and/or drug product can be addressed utilizing a simulated-use extraction study.  This testing subjects a given component used in the equipment train to a model solvent or placebo under the typical conditions of contact encountered during manufacturing.  Pro-active flushing of filters and tubing, points of dilution in the manufacturing process, and purification techniques (such as recrystallization and diafiltration) can also be used to reduce the leachables risk for manufacturing equipment.