June 22, 2010

Improve pH Control in Pharmaceutical Manufacturing

Hi — my name’s Dave Anderson. This week I’m blogging about pain points in pH and, from an analytical perspective, there are a number of them within a biopharmaceutical plant where effective analytical monitoring can improve operations. First and foremost, the Process Analytical Technology (PAT) Initiative has opened the door to take traditional off-line, laboratory measurements and put those methodologies in the process or at the process. The customers benefit through real time measurements of key parameters. By automating the process, customers can capture the data as well as document the calibration logs electronically.

One particular pain point is with pH control in bioreactors. Customers are asking for tighter pH control, some as tight as +/- .01 pH units. One customer mentioned if they can improve pH tolerances by 10%, they estimate savings of $250,000 per batch.  The problem with maintaining tight pH measurement is how the sensors are used in the process. Prior to a batch, the pH sensors are calibrated with pH buffers to ensure the sensors will accurately respond to real process changes. After the sensors are calibrated, those chemicals must be cleaned from the sensor. The typical cleaning process is to steam sterilize the vessel at a minimum of 121º C for 30 minutes.  Some processes require steam cleaning at 145º C for 60 minutes.  The pH-sensitive glass will become stressed from the exposure to high temperatures and subsequent cooling. This stress can result in significant offsets in the pH readings or critical failures in the form of cracked glass. Because of these concerns, redundant sensors are often utilized.

To optimize plant productivity, there are new pH sensors with Accuglass® technology that can withstand the thermal stresses from the cleaning process. For example, comparison testing with competitive sensors proved the Model 3800 steam sterilizable pH sensor will withstand more steam-in-place cycles than any sensor on the market.

Additionally, today’s transmitters can deliver real-time diagnostics at the operator’s work station. Monitoring one pH loop locally at a transmitter is simple, but when operators have hundreds to thousands of I/O points with different measuring technologies to manage, it can be overwhelming. Diagnostic information such as “glass impedance” and “zero offset” will update the operators whether a sensor has a critical failure or is beginning to drift. For those operators with less experience, there can be Embedded Help Menus that explain in detail what the conditions mean and appropriate actions to take. This is easy to access in AMS® Suite by clicking and dragging the question mark over the field in question.

These two technologies allow plants to confidently automate pH measurement, greatly minimizing operator interface. When an operator needs to get involved, these tools allow them to make informed decisions with the assurance of accuracy and stability in the process.