Precision and accuracy are two critical words (but with different meanings*) in pharmaceutical, food processing and other industries that come under continuous scrutiny by the FDA, the Code of Federal Regulations Title 21 and other standards. In brief IQ, OQ and PQ mean Installation Qualification, Operational Qualification and Performance (or Process) Qualification. The letter V for verification can be used in place Q.
But we promised a PDQ explanation, so let’s take a quick look at IQ, OQ and PQ.
The Purpose of IQ, OQ and PQ
A purpose of IQ, OQ and PQ is ensuring that sensitive laboratory and processing equipment meet strict standards as those mentioned above. An example of such equipment is an HPLC system, including its pumps. These systems must precisely and accurately analyze pharmaceutical compounds as they proceed from R&D into manufacturing. More simply stated IQ, OQ and PQ mean that equipment performs “as … Read the rest
Flow meters are used to measure flow rates in pipelines, for pumps at filling stations, on trucks delivering fuel oil for your furnace and myriad other applications. While important in all cases, accuracy is especially critical when a flow meter is used in high performance liquid chromatography (HPLC ) pumping systems. This post focuses on how to calibrate a flow meter used in HPLC pumping systems.
What’s Special about Calibrating a Flow Meter for HPLC Pumping Systems?
The answer in a few words: Instead of measuring flow rates in gallons per minute, flow meters for HPLC pump systems measure rates in fractions of milliliters per minute.
As described in our post on how a digital flow meter works they are used to measure the accuracy of HPLC pumping systems in order to meet FDA and other regulations regarding installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ) of … Read the rest
Fast, accurate calibration of flow rates used in HPLC (high performance liquid chromatography) pump systems can be compromised if HPLC flow meter cleaning recommendations are not followed. Technicians know that while GLP (good laboratory practices) call for annual flow meter recalibration by the manufacturer, improper use of these precision instruments can soon render them inaccurate if HPLC flow meter cleaning recommendations are not followed.
What HPLC Flow Meters Do
The role and importance of HPLC pump systems is described in a Process Instrumentation article that describes a digital HPLC flow meter, the advantage of this system, and specification recommendations to measure and maintain pump system accuracy. Included are recommendations on flow meter cleaning.
This post focuses on the importance of HPLC flow meter cleaning, how to do it, and the role of flow meter cleaning in maintaining accuracy. We use as an example the FlowCal 5000 flow meter offered by … Read the rest
Before explaining how a HPLC digital flow meter works here’s an explanation of what digital flow meters do:
Digital flowmeters performing high performance liquid chromatography are used to measure the accuracy of HPLC pumping systems in order to meet FDA and other regulations regarding installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ) of equipment used in the pharmaceutical and biopharmaceutical industries as well as other analytical labs.
The process demands accurate, reproducible column retention time as an analyte (what is being analyzed) is pumped through the HPLC system.
These precision digital flow meters are not to be likened to flow meters used on process lines measuring flow rates in, for example, thousands of gallons per minute but instead in fractions of milliliters per minute. … Read the rest
Accuracy checks on high performance liquid chromatography (HPLC) pump systems should be performed frequently as part of a laboratory’s standard operating procedures. Uniform and reproducible retention time is extremely important and relies on uniform and reproducible HPLC pump flow rates.
Checking the accuracy of an HPLC system can be done manually – an extremely time consuming and laborious process – or by using the digital FlowCal 5000 liquid flowmeter from Tovatech. But as we’ve noted in a companion post on traceable calibration flowmeters themselves must be periodically checked for accuracy.
This too is a time-consuming and laborious process involving multiple measurements and calculations for each flow rate being tested. That’s why we strongly recommend returning the FlowCal 5000 to us on an annual basis to have it tested in conformance to UKAS standards and returned with a calibration certificate traceable to the UKAS (United Kingdom Accreditation Service). UKAS is equivalent … Read the rest
Pump system accuracy is crucial for equipment used to conduct high performance liquid chromatography (HPLC) analysis in the pharmaceutical and other industries subject to regulatory oversight by the FDA and similar authorities. Among functions performed by HPLC are included checks for purity, monitoring changes in pharmaceutical intermediates during chemical synthesis scale-up, stability and dissolution tests, and performing ongoing quality control procedures.Click to download PDF
A Brief on HPLC Analysis
Identifying an analyte by HPLC is based on accurate and reproducible column retention time as the analyte is pumped through an HPLC system. Reproducible retention time is critical and depends on accurate, uniform, reproducible HPLC pump flow rates.
Note that it is important to distinguish between accuracy and precision. These two terms may seem the same but they are not necessarily so. For example, an HPLC system (or for that matter many other systems such as analytical scales) may … Read the rest
Eluent passing through HPLC pump systems can, over time, impact the accuracy of the system and result in inaccurate flow rates. HPLC pump system impellers, valves, seals, injectors and other components in direct contact with analytes carried in an eluent are subject to wear as well as possible deposition of damaging salts and other substances that interfere with flow rates.
That’s why HPLC pump system flow rates should be checked on a regular basis. Regular accuracy checks contribute to meeting FDA standards for system OQ and PQ validation as well as ongoing performance verification. There are different ways to do this. One we call the hard way, the other the easy way.
An example of the hard way is repeatedly and manually collecting and measuring by weight or volume the solvent as it exits the HPLC system. This is extremely work-intensive and highly subject to operator error.
An easier and … Read the rest
As pointed out in our post on HPLC pump accuracy uniform and reproducible column retention times are critical when analytes are pumped through a high performance liquid chromatography system. One of the most efficient ways of checking on the accuracy of HPLC pump systems is the Flow Cal 5000 digital liquid flow meter available from Tovatech. But how do you check on the accuracy of the checker – namely the Flow Cal 5000?
Flow Cal 5000 HPLC Flow Meter Accuracy Checks
When received from Tovatech the Flow Cal 5000 is accompanied by a UKAS traceable calibration certificate* good for one year. Standard calibration is 1 ml/min but on request it can be supplied at points from 0.5 to 25 ml/min. Multiple readings are taken at each flow rate then averaged on the calibration certificate.
A recalibration procedure should be scheduled annually or immediately if users think the unit is not … Read the rest
As researchers know a critical if not the most critical aspect of an HPLC pump system is providing uniform and reproducible column retention times as analytes are pumped through a liquid chromatography system. This in turn relies on uniform and reproducible HPLC pump flow rates. After initial operational qualification (OQ) periodic calibration checks of HPLC pump systems must be undertaken to confirm OQ and to identify and correct flow rate variances that may develop due to factors such as worn pump seals or sediments that interfere with flow rates. These calibration tests are performed by checking flow rates while pumping solvent through the HPLC system.
HPLC Troubleshooting – the Hard Way and Easy Way
Several of our posts on the FlowCal 5000 digital liquid flow meter explain how the system works in comparison to manual methods. Taking a paragraph from our Flow Meter Buyers Guide researchers “can measure flow rates … Read the rest
High performance liquid chromatography – HPLC – is very often the method of choice for analyzing pharmaceutical compounds starting with R&D and continuing into manufacturing. Among other things it is used to
- Check candidate drugs for purity
- Monitor changes in pharmaceutical intermediates during chemical synthesis scale up
- Test the stability and dissolution of formulations in development and
- Support quality control in final drug products
Identifying an analyte by HPLC is based on accurate and reproducible column retention time as it passes through an HPLC system. Reproducible retention time is critical and depends on uniform, reproducible HPLC pump flow rates. A leak developing or other malfunction in the HPLC system will result in analysis errors. Obviously, then, continuous testing is necessary to insure that the HPLC system is properly calibrated. This is called operational qualification. OQ starts before the HPLC system is put into use and as part of ongoing system … Read the rest