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CALIBRATION MASTER PLAN

CALIBRATION MASTER PLAN

    TABLE OF CONTENTS 

SECTION TITLE                                                                     

1.0  Calibration Master Plan Approval

2.0  Introduction

2.1   Objective

2.2   Scope

2.3   Key Calibration Requirements.

2.4   Periodic Review

3.0  Calibration Policy

3.1   Procedure for Criticality Assessment of Instrument

3.2   Criticality Assessment Team (CAT)

3.3   Ranges and Limits.

3.4   Periodicity.

3.5   Change Related to Calibration.

3.6   Standard Operating Procedures.

3.7 Guidance for the method of Instrument Calibration.

3.8 Life Cycle Phases.

4.0 Calibration Process

4.1   Specification of the Instrument

4.2   Non-Conformance

4.3   Third Party Calibration

4.4   Labeling

5.0  Documentation

5.1   Calibration Records

5.2   Certificate of Calibration

6.0  Abbreviations

7.0 Definitions

8.0 List of Annexure

8.1   List of Annexure

1.0 Calibration Master Plan Approval

This Calibration Master Plan is a master document, which describes the entire scope and details of the calibration activities to be carried out at the dosage form facility .

This Calibration Master Plan has been approved by the following:

  Name Department Signature Date
Prepared By  

 

 

 

 

 

   
Checked By  

 

 

 

 

 

 

 

 

 

 

 

       
Reviewed By  

 

 

 

 

 

 

 

 

 

 

Final Approval: 

Final approval to this Calibration Master Plan has been given by the following: 

  Name Signature Date
Approved By

(Plant Head)

 

 

 

 

   
Approved By

(Head – QA)

 

 

 

 

 

 

 

 

 

 

2.0 Introduction

This Calibration Master Plan is a written document that describes the company’s policy for Calibration of the instruments, at the formulation Plant. The Calibration Master Plan describes the approach of Calibration, responsibilities, general guidelines for Calibration, stepwise Calibration activities and frequency of re-calibration.

The document states the elements of the Calibration Program. This document establishes calibration plan for the entire formulation Plant, to be used as guidance for resource and technical planning. It defines the responsibilities of the various functional groups in performance of Calibration and presents a Calibration schedule. The design and layout of Calibration Master Plan has been prepared in line with the current standards and industrial practices.

2.1 Objective:

The Calibration Master Plan is written to provide an approach to the calibration management. Calibration of the Instrument is prerequisite for the initial qualification and ongoing performance of any equipment or system. Therefore it is necessary to check the instruments for its calibration during installation of equipment or system and further re-calibration at a prescribed frequency.

2.2  Scope

The scope of the Calibration Master Plan includes calibration of all the instruments of the Facility. The Calibration Master Plan does not cover the detail of test methodology but concentrates on calibration management. The Calibration Master Plan is intended for use by engineers, Quality Assurance (QA), and personnel involved in the management of calibration.

2.3 Key Calibration Requirements

The Calibration Master Plan shall address the Calibration requirements of the critical instruments based on impact assessment for the product quality.  The impact assessment is the process of evaluating the impact of operating, controlling, alarming and failure conditions of a system on the quality of a product.  Depending on the facility & Resource available the Instruments are categorised as Internal (In-House) & External Calibration. From these both categories, The Instruments shall be further classified as critical, non-critical Instruments.

Critical instrument is an instrument within an equipment/system where the operation, contact, data, control, alarm or failure may have a direct impact on the quality of a product.

Applicability of any of the following criteria to a given instrument/component will provide an indication that the component is critical.

  1. The instrument/component controls critical process that may affect product quality.
  2. The instrument/component is used to monitor the parameters of the manufacturing process.
  3. Failure or alarm of the instrument/component will have a direct impact on product quality.

Non-critical instrument is an instrument within an equipment/system where the operation, contact, data, control, alarm or failure will have an indirect impact or no impact on the quality of the product.

The following statements are related to critical / non critical instruments, they outline the regulatory requirements for a successfully managed instrument calibration program,

  • All instrumentation shall be assigned a unique number and all critical/non critical product, process, and other instruments should be physically tagged.
  • The calibration method shall be defined by Standard Operating Procedures .if having the in house resources for calibration otherwise all instruments shall be calibrated from external agency
  • There shall be a means of readily determining the calibration status of each instrument.
  • Each measuring standard shall be traceable to a nationally, or internationally, recognized standard, as well as external or in-house calibration.

2.4 Periodic Review

The Calibration Master Plan shall be reviewed once in one year to ensure compliance and to determine whether a change is required due to following reasons.

  1. Changes in the Calibration Approach
  2. Changes in Key Calibration Requirements.
  • Modification or renovation of existing facility.

3.0 Calibration Policy

Calibration Program is typically applied to Instruments/components of all equipments/systems within the Facility, regardless of the impact on the product quality.  Components, which have been determined to be critical to product quality, will have more frequent calibration schedules.

The calibration of the critical instruments will be verified in IQ (or as a pre-requisite of OQ) before undergoing qualification testing, to ensure that the test results are valid.  This verification, along with the calibration certificates and procedures, provides the documented evidence required to demonstrate that a system operates in a controlled state.

The calibration of instruments attached to process, testing and utility equipment shall be undertaken by the Engineering Department as a part of the Calibration exercise. The instruments to be calibrated shall be identified and calibrated during the IQ stage. The specific parameters to test, as well as the relevant specifications, shall be defined in the Standard Operating Procedure for the instruments.

After completion of operational qualification, the recalibration of the Instrument shall continue at the predefined frequency as per the respective Standard Operating Procedures for Instrument Calibration or as per the calibration calendar.

However there are instruments at the location which don’t have link with IQ / OQ documents, will be covered under the calibration calendar.

3.1 Procedure for Criticality Assessment of Instrument

All instruments directly, or indirectly, involved with the process shall be individually assessed for their criticality to the process. Annual calibration calendar of all the instrumentation pertaining to each equipment or system shall be listed and uniquely identified.

Once identified, further details shall be added to the schedule including measurement range, location, and any other information, which is necessary.

3.2 Criticality Assessment Team (CAT)

The representatives of following disciplines shall represent the CAT:

  • Engineering / Instrumentation
  • Quality Assurance

Manufacturing

The manufacturing person shall sign the Calibration calendar to accept that the specification of the listed instrument and its limits are appropriate to the related product and process.

Engineering

The Engineering representative shall confirm that all instruments are recorded and scheduled for calibration appropriately, as defined within the Calibration calendar. The engineering representative shall sign the Calibration calendar to qualify that the specification of the listed instrument and its limits have been defined and checked as appropriate to the related product and process.

Quality Assurance

The QA representative shall also sign the Calibration calendar to qualify that the specification of the listed instrument and its limits are appropriate to the related product and process.  QA have the final signature to approve the Calibration calendar fit for use. The QA representative shall verify that all calibration records and procedures are maintained and updated.

3.3 Ranges and Limits

While deciding on calibration ranges and limits, the manufacturer’s accuracy and the process requirements shall be taken into account.  For example, an instrument would normally be calibrated across its operating or full range.

Calibration Accuracy:  The agreed specific working accuracy of the instrument.

This is usually set at the manufacturer’s accuracy, but could be relaxed or increased to reflect the process requirements.

Calibration Failure Limits:  The limits set for instrument failure, as determined by the process requirements or results go beyond the acceptance criteria.

If the calibration failure limits are exceeded then a possible non-conformance has occurred, and the response should be documented.

Calibration Acceptance Limits:      The limits set for instrument Acceptance

If the readings are go beyond calibration acceptance limits then a possible non-conformance has occurred, and the response should be documented.

3.4 Periodicity

The periodicity of calibration shall be based on the Category of instrument Critical instrument, Non Critical Instrument.

In-house calibration

The frequency of calibration is once in a year for non critical Instruments & once in half year for critical Instruments or as defined in the respective sop of the instruments.

External agency calibration

The frequency of calibration is once in a year for non critical Instruments & once in half year for critical Instruments or as defined in the respective sop of the instruments.

3.5 Change Related to Calibration

There are circumstances where instrument criticality and its associated calibration details may change regularly, such as in multi-purpose plants.

Any change to the instrument Calibration Calendar, SOP, frequency of calibration shall be documented in support of these amendments as a part of change management procedure.

3.6 Standard Operating Procedures

Sop for Engineering Departmental Accountability: these SOPs are applicable only if the Instruments calibrated in-house.

SOP Title
calibration of vacuum gauges
calibration of thermometer
calibration of RTD Sensor
calibration of TRH Sensor
calibration of Pressure Gauges
calibration of temperature Gauges
calibration of Thermocouple
calibration of Temperature Indicator
calibration of Temperature Transmitter
calibration of Level Transmitter
calibration of Flow Meter
calibration of Conductivity Meter
calibration of ORP Meter
calibration of TDS Meter
calibration of pH Meter
SOP for calibration of RPM Indicator
SOP for calibration magnehelic gauge
calibration of Manometer
calibration of Timer
calibration of counter
calibration sling Psycrometer
calibration of flow transmitter
calibration of pressure switch
calibration of pressure transmitter

Sop for QC Departmental Accountability: these SOPs are applicable only if the Instruments calibrated in-house.

SOP Title

SOP On Operation, Calibration, Cleaning and Maintenance of Bacteriological Incubator
SOP On Operation, Calibration, Cleaning and Maintenance of BOD Incubator
SOP On Operation, Calibration, Cleaning and Maintenance of M Air T Air Sampler
SOP On Operation, Calibration, Cleaning and Maintenance of M Air T Isolator Air Sampler
SOP On Operation, Calibration, Cleaning and Maintenance of LAF
SOP On Operation, Calibration, Cleaning and Maintenance of HPHV Steam Sterilizer
SOP On Operation, Calibration, Cleaning and Maintenance of LBP Counter
SOP On Operation, Calibration, Cleaning and Maintenance of TOC
SOP On Operation, Calibration, Cleaning and Maintenance of Vertical Autoclave
SOP On Operation, Calibration, Cleaning and Maintenance of Micropipettes
SOP On Calibration of Balance.
SOP On Calibration of PH Meter.

3.7  Guidance for the method of Instrument Calibration

Instrument shall be calibrated against reference standard as per SOP.  Reference standard shall be calibrated to or traceable to any national standard. Calibration of the reference standard shall be carried out in NPL or NABL accredited laboratory. Calibration of the instrument and reference instrument shall be carried out at a predetermined frequency. Instruments are checked for its calibration through out its operating range. Instrument is considered calibrated when output of the instrument is within the acceptable range of deviation from the expected output. If test of calibration shows deviation more than acceptable range, instrument is replaced or subjected for the maintenance. After maintenance it is again calibrated prior to use.

The instruments, which cannot be calibrated in-house due to unavailability of the facility & Resources, are sent for calibration to an outside calibrating agency.

3.8 Life Cycle Phases

The life cycle of an instrument can be split into three distinct phases:

Phase 1   >                                  Project Phase

Phase 2   >                                  Operational Phase

Phase 3   >                                  Periodic Recalibration

3.8.1        Project Phase

The new instruments which are the part of new project or new equipment will have following stages.

  1. Responsibilities
  2. Specification of the instrument
  3. Labelling
  4. Calibration Process
  5. Installation Qualification sign off

It is not essential that bench calibrations are performed at IQ stage.  The purpose of bench calibrations is to ensure that instruments delivered from manufacturers are not damaged and are working.  This is commercial requirement to ensure no delays in the project occur.

If bench calibrations are performed, the party’s supplier’s calibration certificate shall be readily used.

The Installation Qualification (IQ) shall be signed off before progression to the next stage. The calibration certificate shall be tied along with IQ document.

3.8.2        Operational Phase

Standard Operating Procedures (SOPs) shall be established and at this point information shall be entered on to the Maintenance Management Systems. All instruments shall have calibration certificates at the Pre-Operational phase before moving to the Operational Phase. On completion, a check shall be made to ensure that the relevant documentation is correct and the current status of the equipment is clear.

3.8.3        Periodic Re calibration

The periodic recalibration of the instrument shall be done as per the frequency mentioned below.

In-house calibration

The frequency of calibration is once in a year for non critical Instruments & once in half year for critical Instruments or as defined in the respective sop of the instruments.

External agency calibration

The frequency of calibration is once in a year for non critical Instruments & once in half year for critical Instruments or as defined in the annual calibration calendar.

Equipment/Instruments requiring scheduled calibration will have a standard grace period. As given below:

Annual calibrations will have a grace period of ±14 days.

Half-yearly calibrations will have a grace period of ±10 days.

Quarterly calibration will have a grace period of ±7 days.

Monthly calibration will have a grace period of ±4 days.

Daily calibration will have no grace period and should be done on every working day.

3.8.4  Key Requirements

While carrying out calibrations the following shall be considered:

  1. The calibration should be performed under optimum / required ranges.
  2. The test equipment is traceable to accepted national standards.

4.0 Calibration Process

4.1  Specification of the Instrument

There is a very large range of instruments available in the market that makes selection difficult, and simply relying on the high accuracy claims of a manufacturer is not the answer.  There are other important factors and influences to consider, which shall be taken into account before any decisions are made, including:

  • Accumulative errors due to non-linearity
  • Hysteresis
  • Temperature effects
  • Repeatability

Important questions to consider include:

  • What does the instrumentation have to do?
  • What are the required calibration failure limits and across what range?

An instrument can then be selected which shall, ideally, be at least two times more accurate than the process requirements.

4.1.1  Range

The range of an instrument shall not exceed the required operating range.  Where an instrument is used for more than one process, it may be necessary to set a larger range so that it exceeds the process requirements.  It is also a regulatory expectation that at least one test point is within the operating range of an instrument used in a product critical application and it is, therefore, vital that the operating range is defined.

4.1.2   Accuracy

Once the required Acceptance limit for a measurement has been defined in the criticality assessment process, the instrument details shall be checked to ensure that it is capable of meeting that requirement consistently and without deviation that would result in a failure between two calibrations.

4.2 Non-Conformance

A non-conformance investigation shall be conducted when a critical instrument has failed to meet the acceptance criteria for the calibration.

If the ‘as found” results indicate that the instrument is outside the calibration limits, then the following actions are taken:

  1. Previous calibration labels shall be removed, where applicable.
  2. An ‘out of calibration’ label shall be attached.
  3. A non-conformance report shall be raised for all failed critical instruments.
  4. The action to repair, adjust, or replace the instrument shall be followed.
  5. The impact study shall be done as per the current version of SOP on corrective & Preventive action.

In the event of non-conformance, on the basis of impact study the QA department shall be informed to recall of approved / dispatched products.

4.3  Third Party Calibration

Calibration may be carried out by third parties (e.g., contractors or instrument suppliers), but the responsibility for ensuring that calibration procedures have been correctly followed shall remain with the instrument owner (i.e., the equipment user and the maintenance Personnel)

The competence of the contractors (the Contract Acceptors) shall maintain suitable premises, equipment, knowledge, experienced, and competent personnel, and may not pass to a sub-contractor any of the work entrusted to him, nor change any of the agreed tests, standards, or limits, without the Contract Giver’s prior evaluation and approval.

There shall be a written contract with the Contract Acceptor and any technical arrangements made concerning it.  This contract shall include:

  1. Specify the respective responsibilities of the Contract Giver and Contract Acceptor.
  2. Describe (or reference) the tests to be done and the standards and limits to be applied.
  3. Specify the documentation to be used, produced, and retained by the Contract Acceptor, and to be supplied by the Contract Giver.
  4. Describe any hazards associated with the use or testing of the item(s)
  5. Be drawn up with the involvement of suitably qualified and experienced Personnel
  6. Sharing of information of any change (s) done at the contract acceptor’s end.

Documentation, supplied by the Contract Acceptor to the Contract Giver on completion of calibration, shall clearly identify the item(s) concerned, show the initial test results, indicate any adjustments made, and (where relevant) the test results after adjustment.

When the Contract Giver receives the item(s) returned from the Contract Acceptor, the item(s) should be carefully examined for possible damage in transit.  An appropriately qualified and trained person should review and approved the given by Contract Acceptor.

Technical Agreement:  Make a technical Agreement with the contract Acceptor and furnish following details of the Instruments to calibration agency.

  1. Name of the instrument
  2. Make of the instrument
  3. Instrument Identification Number
  4. Acceptance Limit.
  5. Range

After receiving the calibrated Instruments from Contract Acceptor or after calibration of instrument at our location ensure/check the following details.

  1. Date of calibration.
  2. Reference standard used for calibration & its traceability with national/international standards
  3. Calibration results & error with remarks, if any
  4. Next due for calibration.

4.4 Labeling

It is a minimum requirement that all product, process, and Utility instruments are uniquely labelled. This Guide recommends that for critical /non critical instruments Calibration tag shall detail the next calibration due date.

Function: Labelling of Instrument will be performed to serve the following functions:

– Alert the user to its calibration and operating status.

– Show that the instrument is part of the inventory and scheduling system.

– Demonstrate that each piece of Instrument has been studied regarding its need for calibration or maintenance.

– Location: Where practical, all Calibration status tag will be placed in a prominent place on the instrument. This alerts the user of its calibration status.

– Types of labels. The different types of labels that will be used are:

– Calibration Tag: These labels are placed on instruments calibrated, as required, on a periodic basis.

– Under Maintenance: These labels indicate that the instrument is under maintenance and cannot be used.

– Daily Calibration: These labels indicate that the calibration is done on a daily basis and respective entries are made on logbook.

– Calibration label for external agency: Place the tag given by external agency in case external agency could not provide, the calibration Status tag should be as per detail mentioned by certificate.

5.0 Documentation

5.1  Calibration Records

Calibration records shall demonstrate the capability of a measuring instrument or system to measure a variable to a required accuracy over a specific range of values. The calibration record, including the prime data, shall be unambiguous and retrievable. Handwritten data should be in pen, with mistakes crossed out with a single line. The amended data should be singed and dated. Calibration information shall be recorded on the calibration certificate to enable the calibration to be reproduced under similar conditions.

Calibration calendar: The calibration calendar is prepared the calendar content of Instruments with calibration Due Dates & location / Machine at which the Instrument has installed. The periodicity of recalibration shall be based on the category of the Critical instrument, Non Critical Instrument.

5.2  Certificate of Calibration

Certificates of calibration shall contain:

  • Unique identification of the instrument under test
  • The ‘as found’ readings and, if adjusted, the ‘as left’ readings
  • The date of the calibration
  • Name of the person carrying out the calibration.
  • Due Date of calibration
  • Refererence SOP Number.
  • Due Date/Validity of calibration for Master Instruments
  • Calibration certificate no of Master Instruments.

6.0     Abbreviations

SOP  : Standard Operating Procedure

NC    : Non Conformance

CI      : Critical Instruments

NCI   : Non Critical Instruments

IQ      : Installation Qualification

OQ     : Operation Qualification

DQ     :  Design Qualification

PQ      :  Performance Qualifications

CAT   :  Criticality Assessment Team 

7.0       Definitions:

Appropriately Trained Personnel: Persons who have been trained and their competence assessed to a suitable level of expertise to carry out defined activities.

Calibration: The set of operations, which establish, under specified conditions, the relationship between values indicated by a measuring instrument or measuring system, or values represented by a material measure, and the corresponding known values of a reference standard.

Calibration Accuracy: The agreed specified working accuracy of the instrument.

Calibration Acceptance Limits: The limits set for instrument Acceptance, as determined by the process requirements.

Calibration Periodicity: Frequency of scheduled calibrations.

Calibration Range: Specified range over which the instrument is calibrated.  This should be greater than the process range.

Calibration Report: Document summarizing the results of a calibration activity.

Calibration Status: Indication of instrument compliance at a fixed point in time.

Change Control: Documented process for the control of change that is traceable.

Contract Giver: Person(s) responsible for awarding calibration contracts to third party contractors (Contact Acceptor).

Contract Acceptor: Third party carrying out the contract on behalf of the Contract Giver.

Customer: A recipient of a product provided by the supplier.

Installation Qualification (IQ): Establishing documented evidence that the key aspects of the purchased item or installation conform to approved written specifications and/or drawings.

Instrument: Device or devices used to carry out a measurement.

Instrument Loop: A group of instruments connected together to monitor, or control, a process variable.

National Standard: Reference standard for a particular country or community, traceable to a specific reference.

Non-Critical: An instrument whose failure is deemed to have no effect on product quality, process/system performance, safety, or the environment.

Non-Conformance: A deviation from defined procedures.  Failure to meet defined criteria may also be referred to as exception or deviation report.

Primary Element: Device used to convert the process parameter into a measured signal.

Critical Instrument: A process/system critical instrument is an instrument whose failure may have a direct effect on process or system performance without affecting final product quality, or safety.

Process Limits: Extent of the process range

Process Range: Specified range within which the process should operate.

Product Contact Parts: A part used for a qualified item of equipment or system that is in direct contact

Qualification: The process of demonstrating whether an entity is capable of fulfilling specified requirements.

Qualification Protocol: A Plan for use in Qualification activities

Supplier: Any organization or individual contracted directly by the customer to supply a product or service.

Test Equipment: Instrument or device used to calibrate other instruments, which is traceable back to accepted national standards.  The test equipment should have precision, accuracy, and repeatability that is higher than that of the instrument being calibrated.

Validation: The action of proving, in accordance with the principles of GMP, that any procedure, process, equipment material, activity or system actually leads to the expected results.  See also Qualification.

Validation Master Plan: A quality Plan for a project with validation requirements, which describes the overall strategy for validating a system within its operating environment, seen from the user’s perspective.  Sometimes called a Validation Plan or a Validation Master Plan.  See also Quality Plan.

Validation Protocol: A Test Plan for use in Validation activities.

Verification: Confirmation by examination and provision of objective evidence that specified requirements has been fulfilled.  Verification is confirmation for a particular use whereas Validation is confirmation for a more general and intended use.

8.0  List of Annexure

Annexure No. Annexure Title
01
Instruments Acceptance Criteria
02 Annual Calibration calendar


Annexure – I

Instruments acceptance CRITERIA 

S.No NAME OF INSTRUMENT ACCEPTANCE CRITERIA
1 PRESSURE / TEMPERATURE GAUGE / THERMOMETERS + 1D OF LEAST COUNT.
2 VACUUM GAUGE + 1D OF LEAST COUNT OF GAUGE
3 TEMP.INDICATOR / CONTROLLER + 1 DEGREE CENTIGRADE
4 THERMOCOUPLE + 0.5 MILLI VOLT
5 RTD + 0.5 OHMS
6 TRANSMITTERS + 0.5 MILLI AMP
7 PRESSURE / VACUUM CONTROLLER +  0.5 BAR
8 CONDUCTIVITY +  0.5 MICRO SIEMENS / CM.
9 RESISTIVITY +  0.5  MEGA OHM- CM
10 ROTA METER / FLOW INDICATOR +  0.2 M3 / HOUR
11 HOUR METER +  O1 MINUTES
12 MAGNEHELIC GAUGE + 01D OF LEAST COUNT

 

 

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About Pharmaceutical Guidanace

Mr. Shiv Kumar is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 14 years of rich experience in pharmaceutical field. During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube

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