Elango Minnoor, Ph.D., M.B.A.

,
Sr. Manager, Quality Control, Biocon Ltd
Agenda
Introduction
Equipment/Instrument
Qualification
Equipment/Instrument
Calibration
Conclusion
Equipment/Instrument - Classification
 All analytical devices can be classified under 2 categories
viz. Equipment and Instrument.

A device used to collect the scientific

Instrument
data and measurement of results
Analytical
Device
Refers to the various supporting tools
Equipment used for performing analysis in the
laboratory
Lab’s Goal - Reliable Results
 Reliable instruments
 Buying the right instrument
 Ensuring its performance (accuracy,
precision, etc)
 Validity of analytical methods
 Proper training of analysts
Choosing the Right Instrument
 Start 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 -
Contd
 Is 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
 Calibration
 Ensures that on an on-going basis that the equipment is
performing properly
 Often 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 instruments
 Classify instruments into Group A, B and C
 Group A
 No measurement capability or requires calibration
 Mixers, centrifuges, etc
 Group B
 Providing measurements or controlling physical
parameters such as temperature, pressure,etc
 Balance, thermometer, pH meter
 Group C
 Sophisticated instruments such as HPLC, GC, etc
Qualification - Four Qs
 Design 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 - URS
 Define location, shape and area needed
 Define equipment (shelves, drawer needed?)
 Define safety and environmental aspects (fire
detector)
 Define security requirements (on-line monitoring,
locking system)
 Define budget
 Define 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 - IQ
 Requirements
 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 - PQ
 Demonstrate 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
instrument
 When 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 recommendations
 relevant procedures – sensitive?
 instrument performance history
 overall 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 Specification
 Instrument 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 Calibration
Success of calibration depends on the following :
 Consistency of results obtained
 Recognition and mitigation of outlier/potential
outliers
 Scientifically designed calibration frequency
Calibration – Quality System
 Specific Directions
 Schedules
 Limits of accuracy & precision
 Remedial Actions
 Systems to prevent usage of instruments failing
calibration
 Tracking Instruments for
Calibration Status
 Each instrument given a unique identifier
 Instrumentation 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 Process
 Written 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 tests
 Qualified individuals responsible for monitoring the
calibration
 Ensure the calibration program and procedures are
reviewed and approved by Quality
Calibration Process - Contd
 Each calibration & maintenance procedure should include
the following:
 Identification of department responsible to perform the
calibration or maintenance
 Step-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 Causes
 Training 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 Calibration
 All calibration records must be retained per document
retention procedures
 Should include “as found” measurements, results of
adjustments (“as left”) and appropriate review &
approval of all results
 Tolerance or limit for each calibration point
 Identification of standard or test instrument used
 Identification of persons performing the work and
checking the results with dates
After Calibration
 Review 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 Tests
 Injection Volume
 Accuracy
 Precision
 Linearity
 Mobile phase
 Flow rate precision
 Accuracy
 Precision
HPLC – Calibration Tests - Contd
 Column Oven
 Thermostat accuracy
 Thermostat precision
 Detectors
 Wavelength accuracy
 Response linearity
 Signal-to-noise ratio
Conclusion
 Qualification/Calibration are not optional but needed
for regulatory compliance
 A strong calibration program ensures:
 Highly Efficient Lab
 Reliable Results
 Quality Product
 Patient Safety
Thank You
Any Questions?