 
 Email
for more information
Company's
other products
Email
to a colleague
Printer
friendly format
|
|
How Much Instrumentation Risk Can Your Process Tolerate?
By George Rodrigues, Ph.D., Senior Scientific Manager, ARTEL
Risk is a part of everyday life and we all take precautions to minimize its negative effects. Stringent efforts are often employed to offset those recognized risks that could have severe consequences. However, until a risk is identified, acknowledged and analyzed, the real threat of that risk is not always apparent.
The Importance of Liquid Delivery Instrumentation
Most pharmaceutical companies own more individual pipettes and liquid delivery instruments than any other type of calibrated equipment. In fact, some pharmaceutical laboratories have more pipettes in their equipment inventory than all other types of calibrated equipment combined. Despite (or perhaps because of) this abundance, liquid delivery is one of the most overlooked processes in pharmaceutical processing. Isn’t it true that we often take for granted those things that are most common in our lives?
Liquid Delivery Risk?
Why would we think of liquid delivery instruments as sources of risk? Because experience and research show that they are. Liquid delivery is the foundation of analytical chemistry processes. Whether it is sample collection and preparation, dilution, standards preparation, reagent addition, or sample injection, accuracy and repeatability in liquid delivery processes are critical.
Sometimes, however, liquid delivery processes fail. It has been estimated that the error rate for complex, manual analytical processes is 10 to 30 percent. Boredom and fatigue in repetitive pipetting are factors, and a high rate of instrument malfunction and inaccurate calibration of very small volumes also contribute to the problem.
It is not just the analytical laboratory manager that pays the price when liquid delivery performance is substandard. Reliable liquid delivery processes are critical throughout the entire drug development cycle. Whether we work in drug discovery, development, manufacturing, or quality control, the integrity of our data, and our ability to reproduce and defend it, rests on a liquid delivery foundation. Is that foundation solid?
One factor in liquid delivery risk is the equipment reliability level. This is a mathematical probability, represented by a number between zero and one, that estimates the likelihood that a given piece of equipment is performing properly at the end of its calibration interval. Surveys across industries show that equipment reliability levels for all calibrated equipment average about 92 percent. Unfortunately, pharmaceutical companies are on the low end of the group, reporting reliability levels lower than their peers in the chemical, aerospace, automotive and electronics sectors. With all the attention and resources spent on pharmaceutical quality assurance and equipment calibration, how is it possible that the pharmaceutical industry ranks lower than other industries?
Let’s dig into the numbers. Recall that pipettes make up the largest fraction of calibrated equipment at most pharmaceutical companies. Yet surveys of pipette service companies show reliability levels for these devices at just 80 percent or lower for all makes and models across all industries.
Could it be that the overall equipment reliability level in the pharmaceutical industry is being pulled down by large numbers of inadequately performing liquid delivery instruments?
Equipment Reliability and Process Reliability
Poor equipment reliability is multiplied in complex processes. Consider a process with three critical liquid delivery steps, where an error at any of the critical steps will invalidate the results. If each critical instrument is operating at a 95 percent reliability level, then each instrument has a five percent probability of error. However, the probability that at least one of the three instruments is out of tolerance grows to nearly 15 percent. So, while each piece of equipment has 95 percent reliability, the overall process operates at only an 85 percent reliability level. In complex processes, extremely high equipment reliability levels are required so that none of the critical pieces fail and disrupt the process chain.
Process reliability levels alone do not tell the whole story. Process criticality is an even more important factor in the risk equation. A critical process is one where severe consequences arise from process failure. Categories and consequences of failure can include:
To avoid these negative consequences, a growing number of pharmaceutical companies are becoming proactive in offsetting liquid delivery instrumentation risk. Calibration frequency adjustments and interim checks are two tools for better managing these risks.
Calibration is the first and most traditional response. For compliance purposes alone, calibration is essential. But too often calibration data are simply put in files and not analyzed for trends. How many of us know the actual failure rates for the various types, makes and models of equipment in our own areas of responsibility? More likely our impressions of equipment reliability are emotional reactions based on a particular recent experience or a general idea.
A mathematical analysis of equipment reliability levels and process risks might change our preconceptions and cause us to increase our calibration frequency. Roughly speaking, calibrating twice as often will cut the failure rate in half.
While more frequent calibration does improve reliability levels, it’s not always the most cost-effective solution. In the pharmaceutical world, “calibration” is a loaded word that carries regulatory and administrative baggage. Documentation, review, scheduled maintenance, compliance, calibration stickers, and other requirements make calibration an expensive activity.
What if I just want to know that my instrumentation is working? This is where interim checks can be effective. For some types of equipment, interim checks have become habit. Balances are one example. These are typically serviced and calibrated once or twice each year, but in many laboratories they are checked each day or week.
Interim checks should be quick and low-cost in comparison to calibration, but they also provide another advantage. On the one hand, calibration is generally conducted under ideal conditions in a controlled environment to obtain the best performance possible from the equipment being calibrated. In contrast, interim checks are by nature a more representative test of actual process performance.
The amount of liquid dispensed by pipettes and other instruments depends on a host of factors including fluid properties, operator technique and skill, temperature and other environmental conditions. Because interim checks are conducted under actual conditions, data obtained during these checks enable a scientist or engineer to assess true process performance. Furthermore, frequent interim checks permit the laboratory to detect and fix problems before collecting critical analytical data.
Field experience shows that the increasing prevalence of liquid handling instrumentation in laboratories has not been supported by an increase in the ability of organizations to adeptly calibrate and maintain these devices at a high level of reliability. Rather, the familiarity and perceived simplicity of these instruments seem to have lulled us into taking liquid handling for granted. While the low equipment reliability levels encountered in many organizations are evidence that management of liquid handling inventories is not yet optimized, the good news is that much of the risk from these devices is preventable. Analysis of existing calibration data, adjustment of calibration frequency, and an appropriate system of interim checks are popular means of handling this challenge.
In the end, it’s up to each organization and their responsible scientists and engineers to ask this question: How much liquid delivery instrumentation risk can my process tolerate?
About the Author:
George Rodrigues, Ph.D., is Senior Scientific Manager at ARTEL. Rodrigues is responsible for developing and delivering communications and consulting programs designed to maximize laboratory quality and productivity through science-based management of liquid delivery. Rodrigues earned his BS in Chemical Engineering at the U.C. Berkeley, and a Ph.D. in Chemical Engineering at the University of Wisconsin. Dr. Rodrigues can be contacted at (207) 854-0860 or grodrigues@artel-usa.com.
This article is part of a series titled “Liquid Delivery Instrumentation Insight,” in which the authors will examine common risks in the pharmaceutical laboratory and attempt to overturn old misconceptions about liquid delivery quality assurance.
The next article will appear in the June issue of Pharmaceutical Processing in and will focuson the various options available to laboratories for better management of liquid delivery risk.
Pharmaceutical Processing
Advantage Business Media
|
