Elango Minnoor, Ph.D., M.B.A.,Sr. Manager, Quality Control, Biocon Ltd

AgendaIntroductionEquipment/Instrument Qualification

Equipment/Instrument Calibration

Conclusion

Equipment/Instrument - ClassificationAll analytical devices can be classified under 2

categories viz. Equipment and Instrument.

Lab’s Goal - Reliable ResultsReliable instruments

Buying the right instrumentEnsuring its performance (accuracy, precision, etc)

Validity of analytical methodsProper training of analysts

Choosing the Right InstrumentStart with Accurate Monitoring Instruments:

No matter how sophisticated the calibration procedure is, it cannot compensate for the inherent performance limits of the instruments it calibrates.

No amount of calibration or re-calibration will improve the accuracy of an instrument as a measuring device.

Choosing the Right Instrument - ContdIs the instrument calibration NIST traceable?

Tells about the instrument/standard that was used for calibration

Nothing about the performance of the test instrument itself

Components of Analytical Instruments• The collective analytical measurement instruments, in

conjunction with firmware, assembled to perform a mechanical process.

• A device or collection of components that perform a process to produce a result

Instrument Procurement and Life Cycle

Why is Qualification & Calibration Necessary?Qualification

It basically proves that the equipment works correctly and actually leads to accurate and reliable results

CalibrationEnsures that on an on-going basis that the equipment is

performing properlyOften times, these tests are sub-set of the qualification

tests performed

Responsibility• "Users are ultimately responsible for instrument

operations and data quality. The user's group encompasses analysts, their supervisors, instrument specialists and organization management.”

• "Users should also be responsible for qualifying/calibrating their instruments, because their training and expertise in the use of instruments make them the best-qualified groups to design the instrument test(s) and specification(s) necessary for successful AIQ."

Classification of instrumentsClassify instruments into Group A, B and CGroup A

No measurement capability or requires calibration

Mixers, centrifuges, etcGroup B

Providing measurements or controlling physical parameters such as temperature, pressure,etc

Balance, thermometer, pH meterGroup C

Sophisticated instruments such as HPLC, GC, etc

Qualification - Four QsDesign Qualification (DQ)Installation Qualification (IQ)Operational Qualification (OQ)Performance Qualification (PQ)

Design Qualification• Documented collection of activities that defines

functional and operational specifications/requirements

• Criteria for selecting the vendor• Details the conscious decisions of the selection

of the supplier

Design Qualification - URSDefine location, shape and area neededDefine equipment (shelves, drawer needed?)Define safety and environmental aspects (fire

detector)Define security requirements (on-line

monitoring, locking system)Define budgetDefine basis and scale of qualification

Installation Qualification - IQ• Establishes that the instrument is delivered

as designed and specified, that it is properly installed in the selected environment, and that this environment is suitable for the operation and use of the instrument

• When to do:• After system reconfiguration

-Addition of modules-After system relocation.

 

Installation Qualification - IQRequirements

Description: Provides a description of the instrument including all components including serial number, hardware version, location, etc

Delivery: Ensure that all the components, manual and spares have arrived as per PO

Utility/Facility/Environment: Installation site meets manufacturer’s requirement

Assembly & Installation: Assemble, install and do preliminary diagnostics

Network & Data Storage: Connect to network and check functionality

Operational Qualification• The goal of this test is to demonstrate that the

system operates as intended after placement in a user's environment

• OQ verifies key aspects of instrument performance without the aspects of any contributory effects that could be introduced by a method.

• Verify that the main operating parameters—injection volume, flow rate, mobile-phase mixing, column thermostating temperature, and detection wavelength are within their specified limits for accuracy and precision.

Performance Qualification - PQDemonstrate that instrument performs

consistently as per specifications defined by the user and is appropriate for the intended use

Requirements Set up experiments to verify the performance

of the instrumentWhen to do:

• After Preventive Maintenance• After major module service• After system reconfiguration

Calibration Program – Quality System

System must be in place to ensure that all instruments are calibrated and also to prevent use of an instrument that is not calibrated, unusable due to damage or malfunction, or has exceeded its established calibration interval

System must be in place that identifies instruments that do not require calibration to be performed beyond the original or factory calibration to distinguish from those instruments that do require scheduled calibrations

Calibration Frequency

manufacturer’s recommendationsrelevant procedures – sensitive?instrument performance historyoverall impact of non-compliances in the

calibration process and previous experience of the laboratory technical staff.

Unplanned Calibration

“Unplanned” Calibration can be called for:

When the instrument is physically moved to a different location within a lab

Questionable or ambiguous results are obtained – perhaps as a part of investigation

Calibration SpecificationInstrument calibration tolerance limits should be

established so problems are identified and corrected in a timely manner

When assigning tolerances, considerations given to: Capability of the instrument being calibrated (what

the manufacturer claims the instrument can achieve).Parameters at which the instrument operates (ex: if

testing accuracy of + 0.5% is required, the instrument calibration tolerances should be <0.5%)

Work environment - environmental conditions can affect the performance of the instrumentation

Success of CalibrationSuccess of calibration depends on the

following :Consistency of results obtainedRecognition and mitigation of

outlier/potential outliersScientifically designed calibration

frequency

Calibration – Quality SystemSpecific DirectionsSchedulesLimits of accuracy & precisionRemedial ActionsSystems to prevent usage of instruments

failing calibration

Tracking Instruments for Calibration Status

Each instrument given a unique identifierInstrumentation details associated with this

number must be documented and available (e.g. serial number, model number, location, etc.)

Each instrument should be labeled with the unique identifier

Calibration status of each instrument , the date of calibration, the next calibration date and the identification of person performing calibration should be readily available

Appropriate systems to document calibration status include calibration logs and calibration stickers

Calibration ProcessWritten calibration procedures that use

traceable calibration standards or calibration equipment.

Qualified individuals (having the appropriate education, training, background and experience) responsible for calibrating & maintaining instrumentation

Second person check of all calibration testsQualified individuals responsible for monitoring

the calibrationEnsure the calibration program and procedures

are reviewed and approved by Quality

Calibration Process - ContdEach calibration & maintenance procedure should

include the following:Identification of department responsible to perform the

calibration or maintenanceStep-by-step calibration instructions, reference to

appropriate calibration procedures or instrument manuals

Methods for preventive maintenance or reference to appropriate instrumentation manuals

Calibration equipment used in the calibration are valid (e.g. spectroscopy filters, voltmeters, digital thermometers, etc)

Calibration parameter and tolerance ( + )

Out-of-Calibration Procedure

If calibration is not complete within time.Results from the calibration do no meet set criteria.

Identification of CausesTraining of analyst for calibration procedures.Glassware/Standards – Cleanliness, Validity etc.History of malfunction/breakdown and

maintenance.Review of previous calibration report.

Out-of-Calibration Procedure - Contd

Data generated from the successful calibration till the next calibration is evaluated for the “Impact”. If Impact analysis reveals suspect results, random batches/products are picked up and analyzed and results are compared to the ones obtained from OOC instrument.

If the results are different, then appropriate evaluation and justification need to be provided (QC/QA).

Based on the outcome of the investigation, CAPA is implemented and the re-calibration is performed.

Records for CalibrationAll calibration records must be retained per

document retention proceduresShould include “as found” measurements,

results of adjustments (“as left”) and appropriate review & approval of all results

Tolerance or limit for each calibration pointIdentification of standard or test instrument

usedIdentification of persons performing the work

and checking the results with dates

After CalibrationReview must ensure the approved activities

have been completed and all results have passed the established acceptance criteria

Actions to be taken if instrumentation cannot be calibrated (e.g. contact appropriate service people, label and remove from service)

A step to record all calibration & maintenance activities

Periodic review of historic calibration & maintenance data to evaluate appropriateness of established frequencies

HPLC – Calibration TestsInjection Volume

AccuracyPrecisionLinearity

Mobile phaseFlow rate precisionAccuracyPrecision

HPLC – Calibration Tests - ContdColumn Oven

Thermostat accuracyThermostat precision

DetectorsWavelength accuracyResponse linearitySignal-to-noise ratio

ConclusionQualification/Calibration are not optional but

needed for regulatory complianceA strong calibration program ensures:

Highly Efficient LabReliable ResultsQuality ProductPatient Safety

Thank YouAny Questions?