Equipment Validation

Equipment Validation

Objective

At the end
of this session, student will be able to

       Discuss
the principles of qualification of equipment, with specific focus on:

       The
different stages of qualification

       Requalification
and

       Qualification
of “in use” equipment

       Discuss  the requirements for equipment

       Selection

       Design

       Use

       Maintenance

Equipment

Principle  

       Equipment must be

       Located

       Designed

       Constructed

       Adapted

       Maintained

       To suit the operations to be carried
out

       Equipment layout and design must
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 be installed to:

       minimize risks of error                  

       minimize risks of contamination

Balances and Measuring
Equipment

       Appropriate range and precision
available

       In production and quality control

         Calibrated

       Scheduled basis

       Checks

       Records maintained

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

       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

Control laboratory equipment

       Equipment and instruments suitable
for the tests to be performed

       Defective equipment

       Removed

       Labelled

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))

Basic Principles of GMP

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                                                                                   

Basic
Principles of GMP

       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?

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

      
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

       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

Qualification 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.

       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

     – 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.

Validation

Stages of qualification

Design qualification

Installation qualification

Operational qualification

Performance qualification

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

Design qualification

       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)

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

       Documented
records for the installatio

       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

Operational qualification

       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

       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

How many 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 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

Qualification 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

“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

               

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

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.

More Examples

       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”
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

Risk assessment of operations or functions

Qualification flow Scheme
(extracted from CEFIC Guidance)

Example of Document Matrix

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

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 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

       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

WHO References

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

       Validation
of analytical procedures used in the examination of pharmaceutical materials

Summary

       Stages of qualification  are 
design qualification, installation qualification , performance
qualification etc

       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

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

 

                                               

 

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