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Technical Info: Calibration

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CALIBRATION & METROLOGY.

INTRODUCING - CALIBRATION - ....................CLICK HERE FOR BESPOKE READY TO USE VALIDATION PROTOCOLS.......................OR CLICK HERE TO GO STRAIGHT TO OUR DOCUMENT STORE.

THE PROGRAM

The calibration program shall be included in the quality system audits required by the QS regulation. These audits should determine the continuing adequacy of the program and assess compliance with the program.

Many manufacturers use contract laboratories to reference their measurement and test equipment. If this is the case, FDA views the contract laboratory as an extension of the manufacturer's GMP program or quality system. Normally FDA does not inspect contract laboratory facilities, but it does expect the manufacturer to assess the contract lab to verify that proper procedures are being used. Generally, the manufacturer of the finished device is responsiblefor assuring the device is manufactured under an acceptable quality system.

When a medical device manufacturer uses a contract laboratory, FDA expects the manufacturer to have evidence that the equipment was calibrated according to the GMP requirements. The device manufacturer can do this by:

requiring and receiving certification that the equipment was calibrated under controlled conditions using traceable standards ;
maintaining an adequate schedule;
maintaining records of tests; or
periodically auditing the contractor to assure appropriate and adequate GMP procedures are being followed. For example, the contractor should have;
written procedures ;
records of calibration;
trained personnel; and
standards traceable to NIST or other independent reproducible standards.

Certification notes and data should include accuracy of equipment when received by the lab to facilitate remedial action by the finished device manufacturer, if necessary. Certification should also include accuracy after calibration, standards used, and environmental conditions under which the equipment was calibrated. The certification should be signed and dated by a responsible employee of the contract lab. If in-house standards are used by a contractor to calibrate device-related measuring equipment, these standards shall be documented, used, and maintained the same as other standards.

INTERNATIONAL CALIBRATION REQUIREMENTS

ISO 9001:2000, requirements must be incorporated into each manufacturer's calibration program and form the basis of its quality controlling activities. A good program can do more than reduce scrap rates. It can reduce expenditures for measurement instruments and related services, add to the confidence and expertise of the company’s staff, and increase the customer's perception of company performance. A good program can protect the company from big risk, and provide records of internationally standardized metrology that would be hard to dispute.

It can be said that a manufacturer's calibration program is built upon three foundations. First, an understanding of the technical details of the tools in use must be maintained and utilized. Second, the measurement unit in use must be traceable to the internationally agreed upon standard. Third, the program must be managed.

VALID CALIBRATION PROCEDURES.

Measurement instruments and tools differ greatly in construction and intent, and the specific activities necessary to calibrate these tools are just as varied. An understanding of the operation of each tool allows problems to be detected, adjustments to be made properly, and condition of tools to be assessed. These technical details are found in all good metrology procedures.

These procedures, to be effective, have to be valid to the tool that will be calibrated. It is very important for a manufacturer to design its metrology procedures around the specific tools and how they will be used.

There are many sources of historically validated metrology procedures for dimensional metrology tools.

Many valid calibration procedures are available through activities of the United States Government. Standards that are published by different branches of the military may be available to civilian contractors, if they do business with government. Freely distributed standards published by the government and military are readily available online. Trade organizations publish standards that can be purchased.

The manufacturers of dimensional metrology tools can also be a great source of valid, proven calibration procedures. Metrology laboratories used for these services may be willing to share their procedures.

Staff experience can also be an excellent source of data on calibration.

Traceability

The definition of traceability that has achieved global acceptance in the metrology community is contained in the International Vocabulary of Basic and General Terms in Metrology (VIM; 1993):

"…the property of the result of a measurement or the value of a standard whereby it can be related to stated references, usually national or international standards, through an unbroken chain of comparisons, all having stated uncertainties."

Traceability of a measurement unit is really maintained by a dual chain of metrology that goes back to the international standard. Each comparison is accompanied by an estimation of measurement uncertainty. Measurement uncertainty is calculated through an internationally standardized discipline.

While some might consider measurement uncertainty calculations complex or time consuming, the actual process is really not that difficult. “Experience shows that with just a little bit of practice most people who have a basic knowledge of metrology can successfully identify the three to five largest uncertainty contributors. That is all it takes to make an uncertainty budget that is within 20% of the correct value, which is close enough to make it a valuable tool.” (Palumbo, 2006)

Measurement uncertainty calculations are not explicitly required by ISO 9001:2000. This revision’s less proscriptive and more widely applicable foundation leaves it up to the manufacturer to decide what the requirements of the individual measurement processes are. The requirements are then based on real world considerations of law, regulations, safety, customer requirements, applicable standards, and performance of the manufacturer’s measurement process itself.

The requirements for calibration of measurement tools can be found in section 7.6 of ISO 9001:2000. For insight into this section, it is useful to refer to the manufacturing centered 1994 version of ISO 9000. Section 4.11, Control of Inspection, Measuring, and Test Equipment states that measuring equipment is used in a manner that ensures that the measurement uncertainty is known and is consistent with the required measurement capability. The intent of the requirements in both versions is the same. In-house calibrations that are not accompanied by measurement uncertainty estimates have broken the chain of traceability.

Management

An ISO 9001:2000 management system strives to attain customer satisfaction through continual improvement of processes. In manufacturing, accuracy in measurement is one of the most important processes we can define.

The management of the sensor accuracy is accomplished in the same way as management of the other processes identified in the manufacturer’s management system. A cycle of planning, action, measurement and management will complete the solid basis of instrument accuracy verification, both those performed in-house and those outsourced to laboratories.

Some manufacturers may choose to develop a system manual which contains the process description, planned quality objectives, key indicators of process performance and references to the standards and procedures in use. This can become a very valuable document that serves as the roadmap to a dynamic, effective, top notch calibration program.

Good metrology delivers information about the manufacturer’s products. Using this information in an ISO 9000 based management system creates knowledge about the manufacturer’s products, machines and processes, capabilities, and tools.

A good instrument verification program will provide some immediate economic benefits and deliver protection from problems, however this is not a core business for most manufacturers. The immediate economic benefits of good metrology will be very limited or not even seen. However, a good metrology program will develop confidence on the factory floor that the company is dedicated to providing quality product. It will develop capability and expertise. It will develop pride in company staff, knowing fully well that their system is one of the best, and is only getting better. Good metrology practices and procedures, must be a core aptitude of manufacturing organizations. It can only bolster and empower the organization as a whole.

CALIBRATION TECHNIQUES

This section discusses the creation of a correction curve for instruments (gauges) whose responses cover a large range. Topics are:

Models for instrument accuracy testing.
Data collection.

All regulated laboratories, including pharmaceutical, clinical testing, and food and cosmetics testing laboratories, must properly execute the testing of instruments and validation of analytical methods. Following correct procedures ensures the generation of reliable data, which leads to the manufacture of safe and effective products.
Assumptions.
Conditions that can invalidate the accuracy of test procedures.
Data analysis and model validations.
Accuracy of future measurements.
Uncertainties of accuracy values.

Instrument accuracy testing is intended to eliminate or reduce bias in an instrument's readings over a range for all continuous values. For this purpose, reference standards with known values for selected points covering the range of interest are measured with the instrument in question. Then a functional relationship is established between the values of the standards and the corresponding measurements. There are two basic situations.

STANDARDS .

Instrument testing is intended to eliminate or reduce bias in an instrument's readings over the range for all continuous values. For this purpose, reference standards (accuracy targets) with known values for selected points covering the range of interest are measured with the instrument in question. Then a functional relationship is established between the values of the standards and the corresponding measurements. There are two basic situations.

The instrument reads in the same units as the reference standards. The purpose of the testing is to identify and eliminate any bias in the instrument relative to the defined unit of measurement. For example, optical imaging systems which measure the width of lines on semiconductors read in micrometers, the unit of interest. Nonetheless, these instruments must be reference to standards, if line width measurements across the industry are to agree with each other.
The instrument reads in different units than the reference standards. The purpose of the test is to convert the instrument readings to the units of interest. An example are densitometer measurements which act as surrogates for measurements of radiation dosage. For this purpose, reference standards are irradiated at several dosage levels and then measured by radiometry. The same reference standards are measured by densitometer. The results of future densitometer readings on medical devices are the basis for deciding if the devices have been sterilized at the proper radiation level.

The method is the same for both situations and requires the following basic steps:

Selection of reference standards with known values to cover the range of interest.

Measurements of the reference standards with the instrument to be verified.

Functional relationship between the measured and known values of the reference standards (usually a least-squares fit to the data) called a correction curve.

Correction of all measurements by the inverse of the calibration curve.

CALIBRATION