1-5 Equipment Qualification

EQUIPMENT AND ITS QUALIFICATION

Rutendo Kuwana

Technical Officer, WHO, Geneva

Training workshop: Training workshop on regulatory requirements for registration of Artemisinin based combined medicines and assessment of data submitted to regulatory authorities, February 23-27, 2009, Kampala, Uganda.

Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 2 |

Basic Principles of GMPBasic Principles of GMP

Equipment

13


EquipmentEquipment

Objectives

To review the requirements for equipment – selection – design – use – Maintenance


ValidationValidation

Objectives (2)

To discuss the principles of qualification of equipment, with specific focus on:

The different stages of qualification

Requalification and

Qualification of “in use” equipment


EquipmentEquipment

Principle

Equipment must be – located– designed– constructed– adapted– maintained

to suit the operations to be carried out

13.1


EquipmentEquipment

Principles

Equipment layout and design must aim:

– to minimize risks of error

– to permit effective cleaning and maintenanceTo avoid:

– cross-contamination, dust and dirt build-up

– any adverse effect on the quality of productsEquipment must be installed to:

– minimize risks of error

– minimize risks of contamination13.1, 13.2


13.5

EquipmentEquipment

Balances and Measuring Equipment

Appropriate range and precision available

In production and quality control

Calibrated– scheduled basis– checks – records maintained


EquipmentEquipment

Production equipment

Appropriate design– easily and thoroughly cleaned on a scheduled basis– procedures and records

No hazard to the products– contact parts of suitable non-reactive materials– non additive and – not absorptive

Defective equipment– removed, or– labelled to prevent use

13.9, 13.10


13.11 – 13.13

EquipmentEquipment

Production equipment

Closed equipment used when possible

Open equipment, or when equipment opened, precautions taken to prevent contamination

Non-dedicated equipment cleaned according to validated cleaning procedures between different products

Current drawings of critical equipment and support systems maintained


EquipmentEquipment

Control laboratory equipment

Equipment and instruments– suitable for the tests to be performed

Defective equipment – removed– labelled

13.7, 13.10


13.6, 13.8

EquipmentEquipment

Washing, cleaning and drying

Equipment used for washing and drying – not the source of contamination

Equipment design should promote easy cleaning

Cleaning on scheduled basis, procedures and records

Washing and cleaning– manual– automated (Clean in place (CIP), Steam in place (SIP))




EquipmentEquipment

Possible Issues

Poor design

Lack of safety

Poor quality finishes

Lack of cleaning

Lack of maintenance

No usage log or record

Use of inappropriate weighing equipment

Open-plan location of compressing machines



Remember to look at punches and dies

Are there specifications for these?

How are they cleaned, stored, issued for use and returned to storage?

Are they in a good condition and checked at regular intervals?



General

Qualification policy for systems and equipment

To include instruments used in production and quality control

New systems and equipment: All stages of qualification applicable (DQ, IQ, OQ and PQ)

In some cases: Not all stages of qualification may be required– e.g. electrical supply systems

3.1 – 3.4



General

Qualification policy for systems and equipment

To include instruments used in production and quality control

New systems and equipment: All stages of qualification applicable (DQ, IQ, OQ and PQ)

In some cases: Not all stages of qualification may be required– e.g. electrical supply systems

3.1 – 3.4



General (continued)

Qualification should be done in accordance with predetermined and approved qualification protocols

The results of the qualification should be recorded and reflected in qualification reports

The extent of the qualification should be based on the criticality of a system or equipment, e.g.

– Blenders, autoclaves or computerized systems

3.10 – 3.11



General (continued)

Qualification should be done in accordance with predetermined and approved qualification protocols

The results of the qualification should be recorded and reflected in qualification reports

The extent of the qualification should be based on the criticality of a system or equipment, e.g.

– Blenders, autoclaves or computerized systems

3.10 – 3.11


Qualification and ValidationQualification and Validation

Definitions

Validation

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

It is a process using documented evidence that provides a high degree of assurance that a specific process will consistently produce the predetermined outcome.

Glossary



Definition

Qualification

Action of proving that any premises, systems and items of equipment work correctly and actually lead to the expected results

(Validation usually incorporates the concept of qualification)

A process of establishing confidence that the equipment is capable of consistently operating within established limits and tolerances. Studies therefore done prior to use


Qualification Vs. ValidationQualification Vs. Validation

Qualification

- confirm compliance with specified requirements or criteria (Do you have the right tool for the job?)

- Performed on one element or component of the process to be validated

- Conduct tests to establish if the component of a process has the attributes to produce a specified outcome.

Validation

- Proof. Document that the process will consistently produce a predetermined outcome.



Stages of qualification

3.11

Design qualification

Installation qualification

Operational qualification

Performance qualification



Stages of qualification

3.11.




Performance qualification Change control



General

Systems: Qualified before equipment

Equipment: Qualified before routine use

Systems and equipment: Periodic requalification, as well as requalification after change

Certain stages done by the supplier or a third party

Maintain the relevant documentation, e.g.– standard operating procedures (SOPs), specifications and

acceptance criteria, certificates and manuals 3.5 – 3.9




User requirements should be considered when deciding on the specific design of a system or equipment

A suitable supplier should be selected for the appropriate system or equipment (approved vendor)

4.1 – 4.2




Verifies that the correct equipment has been received and installed as per plan and protocol. Also that it is complete and undamaged (parts, services, controls, gauges and other components)

- Normally advised to prepare requirements for calibration, maintenance and cleaning at this stage

Verifies that equipment has been properly installed and calibrated including connections to utilities.

Calibrate the measuring, control and indicating devices– against appropriate, traceable national or international standards

5.1 – 5.4



Installation qualification (2)

Documented records for the installation– installation qualification report

Indicate satisfactory installation

Include details, e.g.– The supplier and manufacturer– System or equipment name, model and serial number– Date of installation– Spare parts, relevant procedures and certificates

5.5




Systems and equipment should operate correctly – operation verified as in the qualification protocol

Verifies that the equipment operates consistently within established limits and tolerances over the defined operating ranges. Studies on critical variable to include conditions encompassing upper and lower operating limits and circumstances (i.e. “worst case conditions”)

Challenges equipment functionally to verify compliance with manufacturer’s specifications and end – user defined requirements. To include verification of operation of all system elements, parts, services, controls, gauges and other components

6.1 – 6.3



Operational qualification (2)

Documented records (Operational qualification report)

Finalize and approve SOP (operation)

Training of operators provided – training records

Systems and equipment released for routine use after completion of operational qualification, provided that:

– All calibration, cleaning, maintenance, training and related tests and results were found to be acceptable

6.4 – 6.7


How may runs are to be performed during Operational Qualification (OQ) testing?

How may runs are to be performed during Operational Qualification (OQ) testing?

Guidelines stress the importance of equipment qualification simulating actual production conditions, including 'worst case' situations and that "tests and challenges should be repeated a sufficient number of times to assure reliable and meaningful results."

"three consecutive batches" is recommended for process validation rather than for equipment qualification. No specific number of "runs" for equipment qualification, but multiple tests to simulate actual operating ranges and to establish consistency are expected


Qualification of EquipmentQualification of Equipment

IF ONE TYPE AND MODEL OF EQUIPMENT IS QUALIFIED, CAN IT BE USED IN A DIFFERENT PROCESS WITHOUT ADDITIONAL

QUALIFICATION?

For IQ document whether each equipment is installed correctly and operates consistently according to established limits and

tolerances. OQ should also be performed for each different use of the equipment or system to document the suitability for that use

Not be required for additional pieces of the same type/model of equipment when used in the same process or for each piece of the same type/model of equipment used in the same process, provided

installation qualification has been performed



Performance qualification

Verifies that the equipment performs according to design specifications and user defined requirements in a reliable and reproducible manner under normal production conditions.

Verified in accordance with a performance qualification protocol

Documented records – performance qualification report

Show satisfactory performance over a period of time i,e. carried out long enough to prove that the equipment is under control and turns out product of specified quality consistently.

Manufacturers to justify the selected period 7.1 – 7.2


Qualification PlanQualification Plan

To ensure that requirements are met and confirm by examination and collection of objective evidence

- Challenges to equipment to be designed

- Re-create intended use

- Test, Test, Test



1. Purpose

2. Scope

3. Equipment Description

4. Operational Specifications

5. Acceptance Criteria

6. Testing Results

7. Discrepancies/Corrective Actions

8. Conclusions/Final Report



The next slide shows a typical format for:

"A qualification protocol / report"

It reflects the minimum information that should be included

This is an example – and should be used as such

Specific formats need to be designed for a specific system or piece of equipment

7.2




Worst Case ScenariosWorst Case Scenarios

Conditions that include upper and lower processing limits

Circumstances that present the highest chance of process or product failure relative to ideal situations

Identify those conditions that are likely to be experienced during routine manufacture/process


More ExamplesMore Examples

The following case illustrates the importance of performing adequate equipment qualification on each piece of processing equipment

A pharmaceutical firm used two blenders to produce a tablet. Both blenders from same equipment manufacturer, same model number and same design. Supplier told the drug manufacturer that the units were "identical." though one was older. Manufacturer did not include the older blender as part of its process validation.

Company marketed about 100 batches of tablets using the old blender. Retention samples showed some batches failed content uniformity

investigation showed out of specification batches were from one of the two "identical" blenders – the old one. The older blender had a slightly smaller capacity and different operational characteristics (RPMs) when run at the same settings as the newer blender.

Subsequently, the firm recalled its total production of the product it made using the older blender. The firm decided to qualify the old blender using production size lots.


Qualification of “Old” EquipmentQualification of “Old” Equipment

What about "old manufacturers" who have not performed DQ, or IQ for existing, in-use systems and/or equipment?

It is not always possible to have all details for IQ or OQ for established equipment. The manufacturer should however have data that verifies the operating parameters and limits for the critical variables of the equipment. In addition, calibration, cleaning, preventative maintenance, operating procedures and operator training procedures for the use of the equipment should be documented and used as SOPs ……. PIC/S



Qualification of “in-use” systems and equipment

Data to support and verify the suitable operation and performance of systems and equipment

Should include operating parameters and limits for critical variables, calibration, maintenance and preventive maintenance, standard operating procedures (SOPs) and records

9.1 – 9.2


Risk assessment of operations or functions

Risk assessment of operations or functions

If any question is answered “Yes”, the operation/function should be considered as GMP relevant. During risk assessment, the probability of occurrence and detectability should be considered and measures to reduce the risk identified.


Qualification flow Scheme(extracted from CEFIC Guidance)

Qualification flow Scheme(extracted from CEFIC Guidance)


Example of Document MatrixExample of Document Matrix


RequalificationRequalification

Required for:

- significant change in batch size

- change in operating parameters

- component specifications have changed

- new accessories or components are added to previously qualified equipment

- process changes that potentially impact product effectiveness or quality


Some ExperiencesSome Experiences

What if the results are not good?

Study report destroyed and manufacturer pretends it never happened

So what should be done?

Document the study, but don’t approve it

Identify and describe any corrective actions needed or any noteworthy observations or deviations

Start another study using the findings and conclusions from the failed study


More experiences – poor qualification reports

More experiences – poor qualification reports

Specifications not approved

Failure to provide clear, complete instructions in the protocol

Instrument calibration records or status not included

Full range of intended operating parameters not challenged

Inadequate sample sizes

Atypical data points

Unexplained deviations from protocol

Inconsistencies between final report and data collection/recording forms


Annex 6


WHO References

Good manufacturing practices (GMP): guidelines on the validation of manufacturing processes

Validation of analytical procedures used in the examination of pharmaceutical materials

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