Low pH inactivation is commonly used in monoclonal antibody purification processes to inactivate large enveloped viruses. Adjusting the pH to achieve this as part of a single-use biomanufacturing workflow usually requires manual manipulation of the product and vessel by a skilled operator.
The adjustment comprises a number of steps including off-line sampling, pH measurement, and the accurate addition of the required amounts of acid and/or base—all the while ensuring that the pH does not exceed the required value.
In addition, manual interventions introduce additional risk to the process from operator error, microbial or viral contamination, pH overshoot, time-to-process deviations, and operator deviations.
Recording all the elements of these manual processes is an additional burden on the operator and a potential source of inaccuracy. Such inaccuracies can make identification of the cause of batch-to-batch variations more difficult, and a lack of electronic batch records, data storage, and trending in manual processing further complicates documentation and regulatory compliance.
Viral inactivation by low pH has been reliably demonstrated to inactivate more than >4log10 of large enveloped viruses (e.g., X-MuLV) in several commercial purification processes. This clearance step can be applied to monoclonal antibodies that have purification process steps that include a low pH step.
Relying on an automated single-use mixing platform that is able to contain, mix, and monitor the product, in addition to automating the pH adjustment steps, will simplify the viral inactivation steps and thereby mitigate the risks associated with manual adjustment.
To investigate viral inactivation using this method, two studies were performed to assess the performance of such a device, the Xcellerex™ XDUO™ 500 L mixer. The first study assessed the mixing capability of the system, vital for effective pH adjustment; the second investigated the ability to automate pH adjustment within the required parameters to successfully perform the viral inactivation step in a purification process for a monoclonal antibody.