Calibration and Preventive Maintenance Program

Regulations of the regulatory authorities like FDA and EU require that all the firms have program for calibration and preventive maintenance for test as well as measurement equipments. Preventive maintenance program is one of the most importance aspects for GMP inspection as it ensures the efficient GMP operations. Any equipments either it is automatic or manually operated will perform its functions properly and are used for manufacturing, processing, packaging, labeling or holding of drug products; it is mandatory that it will be timely calibrated, inspected and checked for errors according to the written program which is specially designed to assure the best performance of the equipments. This paper mainly discusses the importance of the calibration and Preventive Maintenance program for any industry because it is very important for any firm that the equipments produce the products having its predetermined specification.

Introduction

Definition of Calibration: – “It is a set of operation that performs under specific conditions to verify the values/data obtained by comparison of two instruments or measuring devices one of which is a standard of known accuracy (Traceable to national standards). It is used to detect, correlate, report or eliminate any of the discrepancy in accuracy of instruments or measuring devices when being compared to the standard.” [1]

Calibration is one type of comparison but it is not an adjustments.

Definition of Preventive Maintenance: “It is a care or service provided by personnel to maintain the equipment or facility in satisfactorily working conditions by providing inspections, detection and correction of failures before they occur. Basically they are conducted to keep the instrument in working conditions and to extend the life of the instrument.”[2]

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Background Information

Today lots of equipment and measuring systems are used in pharmaceutical industry. During pharmaceutical manufacturing operations, these equipments are used to control and record the GMP process parameters because these parameters are mandatory to fulfill the quality requirements of the particular process as well as product. As I earlier mentioned that calibration is just a comparison and to document the record of differences when calibration is performed between the actual equipment and the standard equipment. But it is mandatory to calibrate the equipments timely to get the best results and minimizations of errors.

For PM, its one type of maintenance of measuring system or equipments before any error will occur. Basically PM is divided into two subparts. (1) Planned PM and (2) condition based. The key difference between these two subparts is time required for maintenance. The risks which are involved during performing PM are human errors and product failure. Preventive Maintenance is performed by repairing the equipments or by the replacing the defective part of the equipment before any error or product failure will occur. [1]

Main advantages of PM are: improvement in the reliability of system, decrease in replacement cost and time, and inventory management system is also improved.

Requirements of Regulatory Authorities

Calibration program is required by the regulatory authority (FDA) under section 21 CFR part 211.68 and Preventive maintenance and calibration program is required by FDA under section 21 CFR part 211.67.

Calibration requirements for Lab instruments under section 21 CFR part 211.67 are: specific directions, schedule, limit of accuracy and precision remedial action and system to prevent usage of instrument which are failed to calibrate. [2]

Requirements for manufacturing area:

FDA requires that each manufacturing area of the facility has written calibration and written preventive maintenance procedures. They must have qualified personnel to calibrate and maintain the equipments which are again rechecked by other qualified person. They must have one representative to monitor the calibration and PM program. And finally the whole process of calibration and PM is reviewed and approved in the terms of quality.

Requirements for equipment master list: [1]

In any manufacturing area or any laboratory, lots of instruments are used that’s why FDA requires that there should be a system in facility that can identify the instruments which are related to GMP. For identification purpose it must have serial no. model no. and location but if the instruments are tracked by configuration then this information is not mandatory. And there should be a written procedure that area used to determine whether calibration and PM is required for particular instrumentation or not.

Instrument Identification and calibration status[1]

Initial step for the calibration & PM program is to identify the instrument. Instruments are identified and characterize in the terms of criticality. Some instruments are critical and some are non critical. Some instruments have effects on environment so identified as environmental critical instrument. In the same way some has direct impact on product quality known as GMP critical instruments. Step by step process to identify an instrument and calibration status is:

Each instrument is given unique identification number.

Details for instrument (model no, serial no, location) are available and documented

Every instrument is labeled with its unique identification number.

Calibration history (calibration status, date of calibration, date for next calibration, details of person who is performing calibration)

Use of calibration logs, calibration sticker and MAXIMO to document calibration status.

There should be a system which prevent the use of non-qualified instruments, damaged instruments and non-calibrated and those who expired the calibration period to minimize the errors. Also some instruments do not require calibration or factory calibrated for certain period of time so there should be a system to identify those instruments.

Traceability of standards and calibration tolerance

Reference equipment or calibration equipment which is used as standard should be traceable to national standard. In the absence of recognized standards, an independent reproducible standard can be used. The tolerance of the reference standard is higher than the other equipment which is going to be calibrated. And there should be a system available to monitor the expiration date of reference standard and other re-certification requirements. Two types of tolerance level in calibration: (1) Alert level: Up to this level the instrument can be adjust to its required range.

(2) Action level: It’s known as out of tolerance limit. At this level investigation is required for because we can’t make any adjustment at this level. If tolerance is between the Alert and Action level than that’s fine and investigation is not required. [1.6]

7. Calibration and Maintenance Frequency

After consideration of traceability of reference standard and calibration tolerance, the thing we need to know is frequency of calibration and maintenance because some instruments need frequent calibration. Basically the frequency of calibration depends on the type and nature of instruments. Some important criteria which we can take in the consideration during calculation of frequency of calibration and maintenance are listed below.

Manufacturer’s recommendations and process requirements

Environmental conditions like temp, pressure, humidity and vibration.

History of calibration and history of repair.

8. Calibration and maintenance procedure (SOP)

There should be a documented SOP for conducting the calibration and preventive maintenance for each type of instrumentation. Most of the time during calibration, measurement of errors is found exceeded to its limit by one or more designated point as it was shown in figure: 1 as “As found” and secondly calibration is carried out to verify its predetermined tolerance limit which is shown in the figure: 1 as “As left”. The SOP for calibration must includes accuracy and precision limits and what are the remedial actions should be taken if this limits do not meet with each other. There should be an authorized department to perform and monitor calibration and maintenance. The SOP must contain the step by step calibration instructions, instrumentation manual, proper calibration procedures, provisions for adjustments, provisions for record and document the actual measurement reading before and after doing adjustment.

Record/Documentation for calibration and maintenance

Documentation for calibration and PM is very important as from this historical data we are able to minimize errors for future perspective. Actual measurements and the data obtained after adjustment are recorded as shown in the Figure: 1. Documentation must includes the tolerance limit, full details of the reference standard used and complete details of the person who did the calibration. All these documentations are reviewed periodically by authorized person to make the adjustment in the frequency of calibration when recalibration of the instruments will be carried out in future.

Today most of the pharmaceutical companies are using computerized calibration management system to plan and record the calibration activities in their firm. Computerized system is more convenient and efficient than the traditional paper work. You can save the data for longer time. At the beginning, the computerized system is not popular much but after the introduction of 21 CFR part 11 – electronic records and electronic signature, most of the organizations adopted it.

Out of tolerance (OOT) calibration result

When we found that the particular instrument is outside of its predetermined calibration limits which is also known as Action limit or OOT. If we found OOT calibration result, first scenario is to take corrective actions as soon as possible. We can take corrective actions like repair, re-calibration, and replacement of defective part or permanent removal of instrument if the errors cannot be corrected by above actions. Firm can issue OOT notification to the vendor and the notification must includes current calibration data, severity of OOT error and full details of last successful calibration. It is mandatory that QA department immediately stop the production for a while till the issue is solved. Here the role of PM is important as it will stop the reoccurrence of the error. As OOT results highly impact on the quality of the product and also responsible for batch failure, it is mandatory to find out the root cause for the occurrence of these errors. At least it will help us to prevent the re-occurrence of particular error.

Change control management and CAPA approach

Under change control management program, we are able to make changes in calibration tolerance, frequency and procedure. Also we can add another new program to avoid errors or permanent removal of current program to avoid inconvenience. Change in the environment or change in the location is also solution suggested by this program. Each and every step should be documented properly. This program also suggests revalidation, re-execution and revision of IQ, OQ and PQ of the instruments. Timely revision, periodic review and approval by authorized person at every stage are the key points of this program.

CAPA stands for corrective actions and Preventive actions. CAPA is an important analytical tool to solve lot of issues. CAPA is a concept of Good Manufacturing practice (GMP). CAPA mainly concentrate on the systematic investigation of the failures and deviations occurred during process to prevent their reoccurrence in the terms of corrective actions and also prevent from reoccurrence in terms of preventive action. [5] CAPA ensures that the corrective actions and Preventive actions that are under taken to prevent failure are highly effective and reliable. CAPA is an important tool of the overall Quality Management System (QMS). If any company wants to have best quality management system in their firm, they should implement CAPA to their firm. CAPA ensures the best quality products with the lower cost and less time.

Software used for calibration and PM

Lots of softwares are used for calibration and PM at industrial scale. This computerized system has more efficiency and guaranteed the best results.

Calibration software

Quality Calibration Management system (QCMS) is complete instrument and designed according to the requirements of 21 CFR part 11. This software ensures regulatory compliance and also traceability. It will help to improve the reliability of plant and optimize the administrative costs. It will help to increase in the productivity as well as efficiency.

12.2 Preventive maintenance software

RCM turbo is very popular PM software. Traditional approach took years to complete just one PM but by using this RCM turbo, anyone can quickly go for PM. This software directs us through EMEA process. But the thing is it will go through quickly and efficiently. It is 100 % reliable and will allow you do risk assessment

Conclusion

In conclusion, I would like to say that calibration and preventive maintenance are very important aspects of any instrument. To get the best results with the instruments, it is mandatory to inspect and calibrate the instruments periodically as it is also required by regulatory authorities. Preventive maintenance definitely improves the life of the instruments but timely implementation of PM is very important. Non-calibrated instruments and lack of PM has directly impact on the product quality, so it required that every manufacturing area in the firm has proper program for validation and PM. We can’t neglect the importance of PM because it will prevent the re-occurrence of errors. SOP for calibration and PM is also valuable aspect as it will help to record data, minimize the severity of risk and provides step by step procedure to follow. CAPA approach is one of the most important quality management tools as it will help to correct the errors and to prevent the re-occurrence of errors by preventive actions. Implementation of CAPA tool in calibration will definitely good for instruments. Revision of 21CFR part 11 strongly suggests adopting computerized software system to every firm because of its convenience and efficiency. Softwares used for calibration and PM as I discussed in the paper like QCMS and QMS turbo etc. are 100 % reliable, so I would like to suggest every firm to adopt this computerized software system for their calibration and PM program.