Equipment and Its Qualification: Rutendo Kuwana Technical Officer, WHO, Geneva

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
Basic Principles of GMP
Equipment
13
2|
Artemisinin based combined medicines

February 23-27, 2009, Kampala, Uganda
Equipment
Objectives
To review the requirements for equipment
3|
selection
design
use
Maintenance

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
4|

Equipment
Principle
Equipment must be
located
designed
constructed
adapted
maintained
to suit the operations to be carried out
13.1
5|

Equipment
Principles
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
6|

13.1, 13.2
Equipment
Balances and Measuring Equipment
Appropriate range and precision available
In production and quality control
Calibrated
scheduled basis
checks
records maintained
13.5
7|

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 use
8|

13.9, 13.10
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
13.11 13.13
9|

Equipment
Control laboratory equipment
Equipment and instruments
suitable for the tests to be performed
Defective equipment
removed
labelled
13.7, 13.10
10 |

Equipment
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))
13.6, 13.8
11 |

12 |

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
13 |


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?
14 |

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
3.1 3.4
15 |

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
3.1 3.4
16 |

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
3.10 3.11
17 |

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
3.10 3.11
18 |

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.
Glossary
19 |


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
20 |

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.
21 |

Validation
Stages of qualification
Design qualification
Installation qualification
Operational qualification
Performance qualification
3.11
22 |

Validation
Stages of qualification
Change control
3.11.
23 |

Validation
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
24 |

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 appropriate
system or equipment (approved vendor)
4.1 4.2
25 |

Validation
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
26 |

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
27 |

Validation
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 manufacturers
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
28 |

Validation
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
29 |

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
30 |

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
31 |

Validation
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
32 |

7.1 7.2
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
33 |

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
34 |

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 example and should be used as such
Specific formats need to be designed for a specific system or
piece of equipment
7.2
35 |

Qualification Plan
36 |

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
37 |

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 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.
38 |

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
39 |

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 critical
variables, calibration, maintenance and preventive maintenance,
standard operating procedures (SOPs) and records
9.1 9.2
40 |

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.
41 |

Qualification flow Scheme

(extracted from CEFIC Guidance)
42 |

Example of Document Matrix
43 |

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
44 |

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
45 |

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
46 |


WHO References
Good manufacturing practices (GMP): guidelines on the
validation of manufacturing processes
Validation of analytical procedures used in the examination of
pharmaceutical materials
Annex 6
47 |


Equipment and Its Qualification: Rutendo Kuwana Technical Officer, WHO, Geneva

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EQUIPMENT AND ITS

Basic Principles of GMP

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Basic Principles of GMP

Artemisinin based combined medicines

Artemisinin based combined medicines

Basic Principles of GMP

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Qualification and Validation

Artemisinin based combined medicines

Qualification and Validation

Artemisinin based combined medicines

Qualification Vs. Validation

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

How may runs are to be performed during Operational

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

Worst Case Scenarios

Conditions that include upper and lower processing limits

Artemisinin based combined medicines

Artemisinin based combined medicines

Qualification of Old Equipment

Artemisinin based combined medicines

Artemisinin based combined medicines

Risk assessment of operations or

If any question is answered Yes, the operation/function should be considered as

Artemisinin based combined medicines

Qualification flow Scheme

Artemisinin based combined medicines

Example of Document Matrix

Artemisinin based combined medicines

Artemisinin based combined medicines

Artemisinin based combined medicines

More experiences poor qualification

Artemisinin based combined medicines

Qualification and Validation

Artemisinin based combined medicines