1-5 equipment qualification

5/27/2018 1-5 Equipment Qualification

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EQUIPMENT AND ITSQUALIFICATIONRutendo 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.


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Artemisinin based combined medicines

February 23-27, 2009, Kampala, Uganda2|

Basic Principles of GMP

Equipment

13


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Equipment

Objectives

To review the requirements for equipment

selection

design

use

Maintenance


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Validation

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


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Equipment

Principle Equipment must be

located

designed

constructed adapted

maintained

to suit the operations to be carried out

13.1


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Equipment

Principles

Equipment layout and designmust aim:

to minimize risks of error

to permit effective cleaning and maintenance

To avoid:

cross-contamination, dust and dirt build-up

any adverse effect on the quality of products

Equipment must beinstalledto:

minimize risks of error minimize risks of contamination

13.1, 13.2


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13.5

Equipment

Balances and Measuring Equipment

Appropriate range and precision available

In production and quality control

Calibrated

scheduled basis

checks

records maintained


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Equipment

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 use13.9, 13.10


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13.1113.13

Equipment

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


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Equipment

Control laboratory equipment

Equipment and instruments

suitable for the tests to be performed

Defective equipment

removed

labelled

13.7, 13.10


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13.6, 13.8

Equipment

Washing, cleaning and drying Equipment used for washing and dryingnot 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))


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Basic Principles of GMP


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Equipment

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


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Basic Princ iples of GMP

Remember to look atpunches 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 atregular intervals?


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Validation

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

3.13.4


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Validation

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

3.13.4


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Validation

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

3.103.11


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Validation

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

3.103.11


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Qual if ication and Val idation

DefinitionsVal idat ion

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 processusing documented evidence that provides a high degree

of assurance that a specific process will consistentlyproduce the

predetermined outcome.

Glossary


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Qualification and Validation

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 consistentlyoperating within established limits andtolerances. Studies therefore done prior to use


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Qualification 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.


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Validation

Stages of qualification

3.11

Design qualification

Installation qualification

Operational qualification

Performance qualification


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Validation

Stages of qualification

3.11.


Installation qualification


Performance qualification Change control


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Validation

GeneralSystems: Qualified before equipment

Equipment: Qualified before routine use

Systems and equipment: Periodic requalification, as well asrequalification 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 manuals3.53.9


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Validation


User requirements should be considered when deciding on the

specific design of a system or equipment

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

4.14.2


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Validation

Installation qualification 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

5.15.4


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Validation

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


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Validation


Systems and equipment should operate correctlyoperation 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 toinclude conditions encompassing upper and lower operating limits and

circumstances (i.e. worst case conditions)

Challenges equipment functionally to verify compliance with manufacturers

specifications and enduser defined requirements. To include verification of

operation of all system elements, parts, services, controls, gauges and other

components

6.16.3


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Validation

Operational qualification (2)

Documented records (Operational qualification report)

Finalize and approve SOP (operation)

Training of operators providedtraining records

Systems and equipment released for routine use after

completion of operational qualification, provided that:

All calibration, cleaning, maintenance, training and relatedtests and results were found to be acceptable6.46.7


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How may runs are to be performed during Operational

Qualification (OQ) testing?

Guidelines stress the importance of equipment qualificationsimulating 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


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Qualification of Equipment

IFONETYPEANDMODELOFEQUIPMENTISQUALIFIED, CANITBEUSEDINADIFFERENTPROCESS WITHOUTADDITIONALQUALIFICATION?

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


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Validation

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 period7.17.2


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Qualification Plan

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

- Challenges to equipment to be designed

- Re-create intended use

- Test, Test, Test


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Qualification Plan

1. Purpose

2. Scope

3. Equipment Description

4. Operational Specifications

5. Acceptance Criteria

6. Testing Results

7. Discrepancies/Corrective Actions

8. Conclusions/Final Report


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Validation

The next slide shows a typical format for:

"A qualification protocol / report"

It reflects the minimum information that should be included

This is an exampleand should be used as such

Specific formats need to be designed for a specific system or

piece of equipment

7.2


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Qualification Plan


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Worst 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


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More 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 samplesshowed some batches failed content uniformity

investigation showed out of specification batches were from one of the two "identical"

blendersthe 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 olderblender. The firm decided to qualify the old blender using production size lots.


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Qualification 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 howeverhave 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


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Validation

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 criticalvariables, calibration, maintenance and preventive maintenance,

standard operating procedures (SOPs) and records

9.19.2


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Risk assessment of operations or

functions

Does function/operation directly impact product quality?

Does function/operation create (electronic) data which are the basis forGMP related activities?

Would malfunction impact directly on product quality

Does a measuring instrument control or measure quality critical processingsteps/parameters?

Does operation/installation cause contamination risk or product orenvironment

Are materials of construction in direct contact with the product?

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.

Q f f S


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Qualification flow Scheme(extracted from CEFIC Guidance)


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Example of Document Matrix


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Requalification

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


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Some 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 dont 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


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More experiencespoor 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


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Artemisinin based combined medicines|

Ann ex 6

Qual if ication and Val idation

WHO References

Good manufacturing practices (GMP): guidelines on the validation

of manufacturing processes

Validation of analytical procedures used in the examination of

pharmaceutical materials

1-5 equipment qualification

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