Equipment Qualification: Regulatory requirement, Business need or Common Sense

Swapnil Ballal Intas Biopharmaceuticals Ltd. Nov 09

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 detectors linearity, injectors 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.

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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.

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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

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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 ??

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Requirements
In 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

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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 Dont copy Vendor Specifications ! Need not be technical.

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The Qualification Model

User Requirements

ISSUE THE URS TO SUPPLIERS !!!! Its NOT for QA or Audiors

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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

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The Qualification Model

User Requirements

Functional Requirements

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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?

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The Qualification Model

User Requirements

Functional Requirements

Design Qualification

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Factory Acceptance Testing (FAT)

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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)

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The Qualification Model

User Requirements

Functional Requirements

Design Qualification Factory Acceptance Testing

Build

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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

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The Qualification Model

User Requirements

Functional Requirements Design Qualification

Factory Acceptance Testing

Pre Installation Checks

Build

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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

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The Qualification Model

User Requirements

Functional Requirements

Design Qualification

Installation Qualification
Pre Installation Checks

Factory Acceptance Testing

Build

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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

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Operational Qualification

OQ for a centrifuge

Does the centrifuge turn on and off Spin at programmed speed & temperature Brake as set Retain programming Accuracy of settings, maintenance of temperature etc.

Describe specifications to be tested

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

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The Qualification Model

User Requirements

Functional Requirements

Operational Qualification

Design Qualification

Installation Qualification
Pre Installation Checks

Factory Acceptance Testing

Build

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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

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The V -Model of EQ
User Requirements

Performance Qualification

Functional Requirements

Operational Qualification

Design Qualification

Installation Qualification
Pre Installation Checks

Factory Acceptance Testing

Build

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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

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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
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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 manufacturers 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

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Visual Review

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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

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