equipment qualification

Equipment Qualification: Regulatory requirement,

Business need or Common Sense

Swapnil BallalIntas Biopharmaceuticals

Ltd.Nov 09

Apr 8, 2023 S.Ballal, Intas Biopharmaceuticals Ltd. 2 of 28

FDA Warning Letters related to EQ Inadequate laboratory equipment calibration program: failure to have

written procedures describing specific calibration instructions and limits . Failure to conform to the USP section «41» for weight and balance

determination. The inspection revealed that erroneous values are being used to perform

the minimum weight studies. No certification to a recognized standard for the weights set used for checking the balance.

The calibration procedure for HPLC systems is inadequate in that it did not include integrator and detector’s linearity, injector’s reproducibility, and accuracy of temperature settings for column heater and detector.

There are no predetermined acceptance criteria for the HPLC auto sampler calibration.

Procedures for UV/VIS Spectrophotometer only assesses linearity using alkaline potassium chromate solution at one wavelength when analytical tests are performed at various wavelengths. The procedures does not include functional tests such as wavelength accuracy, photometric accuracy, and reproducibility within ranges of intended use for the instrument.

Calibration raw data and results obtained for the performance qualification of analytical instruments is not being checked for accuracy and completeness by a second analyst or laboratory supervisor.


So What is Equipment Qualification?

Equipment Qualification is used as an umbrella term covering the steps that ensure an instrument or equipment is

appropriate for its intended use.

The user has the ultimate responsibility for the accuracy of results and for the qualification of his/her equipment.


And What is QUALIFICATION?

Qualification involves testing equipment to demonstrate that they do what they are suppose to do.

QUALIFICATION= TESTING

It must be first stipulated “This is what it is suppose to be” and then tested to show “This is what it is”

And not “This is what it is, which must be what it is suppose to be”


Why Test ?When a system is tested a BASELINE is achieved

For a given set of inputs- system gives predictable response and known output

Valid over time Till the system is not changed Once changed, the results may not be valid.

Test after each change or Manage Change ??


RequirementsIn order to formulate meaningful testing, there must be pre-determined requirements – “This is what it is suppose to be” and corresponding tests “This is what it is” No specified Requirement- No meaningful testing No meaningful testing- No tested baseline No tested baseline – Nothing to manage Nothing to manage – System not under Control

Requirements are Fundamental to Qualification


User Requirement The document exits to be read not written

To convey information on what is required

Defines “Process” Requirements – What is required Simple Short statements Describe what is needed Keep each premise/idea separate Stick to the facts Don’t copy Vendor Specifications ! Need not be technical.


The Qualification Model

ISSUE THE URS TO SUPPLIERS !!!!

Its NOT for QA or Audiors

UserRequirements


Functional Requirements What has to be done to implement the process,

Does not define how to do it Also referred to as Conceptual Design Can result in multiple solution for a requirement

at design stage

We generally have both the Functional Requirement and User Specification in one



UserRequirements

Functional Requirements


Design Qualification Defines how the Specification defined in user

requirements are to be implemented Define what objects to be used and their

configuration and orientation Ensures that instruments have all the necessary

functions and performance criteria that will enable them to be successfully implemented for the intended application and to meet user requirements.

Can be carried out by Vendor?Can you allow your car dealer to select the suitable

make and model for you?



UserRequirements


Design Qualification


Factory Acceptance Testing (FAT)- Factory Acceptance Testing – Larger Custom

designed equipment

- Predefined protocol and acceptance criteria

- Several FAT – at different critical stage of manufacturing

- Generally not for Commercial Off the Shelf equipment (COTS)




Factory Acceptance Testing

Build

UserRequirements



Pre Installation Checks Vendor provided/Self Generated Check for

Space / Environment Power – Type, Quality, connections Utility connections – flow, end connections Drains IT needs Travel Path



Pre Installation Checks


Factory Acceptance Testing Build

UserRequirements



Installation Qualification Instrument is received as designed and specified It is properly installed in the selected

environment The environment is suitable for the operation and

use of the instrument.

Verify Static Attributes






UserRequirements


InstallationQualification


Operational Qualification

Demonstrates that an instrument will function according to its Operational Specification (as described by manufacturer) in the selected

environment.

Testing may be quite extensive if the instrument is to be used for all types of applications like in

Development Labs


Operational Qualification OQ for a centrifuge

Does the centrifuge turn on and off Spin at programmed speed & temperature Brake as set Retain programming

Describe specifications to be tested Accuracy of settings, maintenance of temperature etc.

Has the equipment been calibrated: By whom (Attach calibration documents)

Has an SOP been written: If no, then must be done before equipment put into use

Individual completing this section Training






UserRequirements



OperationalQualification


Performance Qualification Does the equipment function correctly and consistently for

the Intended Application

Important here is the word consistently.

PQ should always be performed under conditions that are similar operation.

The test frequency is much higher than for OQ.

In practice, OQ and PQ frequently blend together. Example: linearity and repeatability tests

Analogous to Validation - emphasis on a piece of equipment and not a process

Holistic approach is Acceptable & Preferred

System suitability test – Part of PQ


The V -Model of EQ




UserRequirements



OperationalQualification

PerformanceQualification


Requalification Not required if PQ or alternative modes in

place to verify qualified state Required for

Repairs Relocation Change in application/ user requirement

Extent of Requalification – Decided on case to case- can be limited to module


Current Approaches Impact Assessment

ISPE initiated To define Focus & Extent of Qualification

Risk Based Qualification Identify the risky areas, components Set up tests to address/ control Minimal or no testing for low risk components

Combined CQV (Commissioning,Qualification & Validation) Use of test carried out in earlier testing for EQ


Definition Review Design qualification (DQ)

The documented verification that the proposed design of the facilities, systems and equipment is suitable for the intended purpose.

Installation Qualification (IQ)The documented verification that the facilities, systems and equipment, as installed or modified, comply with the approved design and the manufacturer’s recommendations.

Operational Qualification (OQ)The documented verification that the facilities, systems and equipment, as installed or modified, perform as intended throughout the anticipated operating ranges.

Performance Qualification (PQ)The documented verification that the facilities, systems and equipment, as connected together, can perform effectively and reproducibly, based on the approved process method and product specification.

Ref: Qualification and validation, Annex 15 to the EU Guide to Good Manufacturing Practice


Visual Review


Further Reading All are hyperlinked to the files.

Risk-Based Commissioning & Qualification Benchmarking

Equipment Qualification Guide

Validation Part 6 -WHO

Equip. Qualification - PACT Webinar January 29, 2009

Equipment Qualification: Meeting Your Demands

The Process of Equipment Qualification

equipment qualification

Documents