ROUTINE OPERATION PHASE

9.4 ROUTINE OPERATION PHASE

9.4.1 SOP

After the instrument is qualified, it can be used to generate analytical data. A standard operating procedure (SOP) has to be written for the new instrument.

ROUTINE OPERATION PHASE

The operation instruction, maintenance, and calibration should be included in the SOP. It is not necessary to copy the entire operation manually into the SOP. Writing simple instructions with references to the related sections in the manual is a better way. The frequency and tasks to be performed during maintenance should be stated in the maintenance section. The tests required to calibrate the instrument, the acceptance criteria, and the frequency for each test should be included in the calibration section of the SOP. Definitions of major and minor repairs which necessitate partial or full system requalification should be included as well. For example, the replacement of a UV lamp in a UV detector does not require full requalification whereas replacement of a circuitry board will.

Good system maintenance starts with the users. Proper care, which can be as simple as a good system rinsing and cleanup after use, can reduce unwanted system failure in the middle of a run and extend the useful life of the instrument. Preventive maintenance is a good investment that will save valuable time and money in the long run.

9.4.2 Calibration and Maintenance

The cGMP requirements dictate that the calibration of instruments should be per- formed at suitable intervals in accordance with an established written program. Instruments not meeting established specifications must not be used. Each instru- ment should have a calibration sticker with information related to the status of the system, when the calibration was performed, who did the calibration, and the next calibration date. A systematic program is required to maintain the instru- ments in a state of calibration. The following points should be considered when setting up an instrument calibration and maintenance program.

ž Responsibilities of the personnel involved in the calibration of the equipment ž Frequency of calibration for each type of instrument if it is not covered in

the operation SOP of the instrument ž Review and approval of calibration data ž Procedure to issue calibration stickers (database application can be used to

track the status of the instrument and help coordinate the calibration date) ž Documentation requirements of the calibration and record keeping ž Central filing for instrument-related records ž Remedial actions in the event of calibration failure ž Procedure to notify users and obtain impact assessment in case of calibration

failure It is very important to maintain good use and service records for the instrument

for cGMP purposes. CFR 211.194 [8] specifically requires complete records to

be maintained of the periodic calibration of laboratory instruments, apparatus, gauges, and recording devices. The records of use allow users to be notified in case of system or calibration failure. The user may have to do an impact

PROCUREMENT, QUALIFICATION, CALIBRATION

assessment to determine whether the failure would have affected the reliability of the results generated by the system. The service records will also provide useful information about the system, which may simplify the troubleshooting effort in some instances.

The terms calibration and performance verification are very often used inter- changeably. Calibration involves measuring and adjusting the instrument response using known standards. Performance verification verifies the operation and per- formance characteristics of an instrument against a predetermined set of require- ments. Calibration is a part of performance verification.

There is a common misconception that running system suitability before the analysis can replace the need for regular instrument calibration. System suitability demonstrates only that the instrument is suitable for a particular application at the time of analysis. It cannot reveal marginal system performance. For example, the system suitability test for an HPLC assay using UV detection is not likely to pick up a wavelength accuracy problem since both the standards and the samples are quantitated at the same wavelength. System suitability testing is method specific, whereas system calibration verifies the general performance of the instrument.

9.4.3 Periodic Review

The performance of an instrument should be reviewed on a regular basis to ensure that the instrument is reliable and continues to comply with the require- ments specified in the user requirements. The review should determine whether the instrument is maintained in a validated state. The review should include records for use, maintenance, services, and performance verification testing. In case the records indicate that the instrument is more prone to certain types of failure, preventive maintenance may be desirable to avoid system failure during operation. The review can also provide useful information to prioritize instrument replacement.

9.4.4 Change Control

Changes to the hardware, software, and firmware should be evaluated for the potential impact that the changes may introduce. The overall planing, evalua- tion, justification, implementation, testing, and approval processes are generally referred to as change control. Change control provides supporting evidence that the results expected from the changes have been achieved, and that the system complies with the specifications and remains in a validated state. The change control plan should be approved by laboratory management and quality assur- ance personnel prior to its implementation. Upon the completion of the change and related testing, the entire process has to be reviewed and approved prior to releasing the system for routine use.

9.4.5 System Decommissioning

When an instrument is no longer required in the laboratory and has to be decom- missioned, all related records, such as the instrument binder or logbook, manuals,

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and operation software should be archived. Record in the equipment binder or logbook the reason for the decommissioning and the effective date of removal.