1. Purpose
The purpose of this Guideline is to provide guidance on qualification of laboratory equipment within R&D.
2. Scope and Applicability
This Guideline is applicable to analytical equipment, and its operating software, used for GMP activities in R&D laboratories focusing on Commercial Off The Shelf Instruments (COTS).
3. Definitions
3.1 Analytical Equipment Qualification
Analytical equipment qualification is the collection of documented evidence, which demonstrates that specific equipment performs suitably for its intended purpose.
3.2 Commercial off The Shelf Systems (COTS)
Tried and tested equipment with a broad spectrum of commercial users supplied by a manufacturer / vendor to an already available design / specification.
3.3 Complexity
For the purposes of this document complexity refers to the technical complexity of the system, mechanically or in the software used as part of the system. The more complex, the more tests may need to be run to determine that the functionality works as intended.
3.4 Operational Qualification (OQ)
A process, which ensures that, the equipment as installed, operates according to the specification.
3.5 Performance Qualification (PQ)
A process, which ensures/verifies the equipment’s continued suitability for its intended use.
3.6 Quality Control Checks
In addition to calibration or standardizations, some analyses also require the inclusion of quality control check samples to prove an in-process or ongoing assurance of the analytical procedure’s suitable performance.
3.7 System Suitability Test
System suitability tests verify that the analytical equipment will perform according to the criteria laid down in the analytical procedure.
3.8 User Requirement Specification – (URS)
Documentation, which defines the functionality required from analytical equipment by the user.
4. Responsibilities
4.1 R&D Line Management
Line Management, as defined in local procedures, is responsible for:
– Authoring local SOPs regarding analytical equipment qualification.
– Ensuring that analytical equipment qualification is carried out, documented, technically reviewed by someone sufficiently competent in the equipment and approved prior to use in GMP activities, including seeking QA review/approval where required.
– Ensuring that there is an up to date record of equipment qualification.
– Reviewing with R&D QA any qualification report where the work/results are not in line with the plan.
– In conjunction with R&D QA assuring, by assessment, the capability of suppliers to provide, validate and maintain equipment as suitable for GMP use.
4.2 R&D QA
R&D QA is responsible for:
– Assuring that an appropriate documentation for analytical equipment qualification is in place prior to use in GMP activities.
– Approving local SOPs regarding analytical equipment qualification.
– Approving qualification protocol/plan and modifications as required.
– Approving qualification reports where actual work/results are not in line with the plan.
– In conjunction with R&D involvement in all stages of qualification for critical equipment. This involvement shall be decided on a case-by-case basis and defined in the qualification plan.
– In conjunction with R&D assuring, by assessment, the capability of suppliers to provide, validate and maintain equipment as suitable for GMP use.
5. Guideline
5.1 Qualification
There are four critical components involved in the generation of reliable and consistent analytical data. The diagram below shows these components as layered activities within a quality triangle. Each layer adds to the overall quality of the data.
Analytical equipment qualification forms the foundation / base of these layered activities. This document considers the various activities, which demonstrate analytical equipment qualification.
5.2 Analytical Equipment Qualification
Analytical equipment qualification is the collection of documented evidence, which demonstrates that specific equipment performs suitably for its intended purpose. Qualification is a logical step-wise process, which generally consists of the following stages:
– User Requirement Specifications and/or Design Qualification
– Installation Qualification
– Operational Qualification
– Performance Qualification
The amount of documentation and level of detail may vary depending upon the criticality to GMP and complexity of the new or modified equipment.
5.3 Overall Quality of Generated Data
The overall quality of generated data following analytical equipment qualification is controlled by:
– Analytical Method Validation
– System Suitability Tests
– Quality Control Checks
5.4 Categorization
5.4.1 Equipment Categories
Laboratories within R&D typically contain equipment varying from simple nitrogen evaporators to complex automated equipment or system.
Therefore, applying a single set of principles to qualify such dissimilar equipment would be scientifically inappropriate. On the basis of the level of qualification required, it is convenient to categorize equipment into groups: Non-Critical or Critical, Commercial Off The Shelf (COTS).
5.4.1.1 Non-Critical
This type of equipment is defined as equipment, which may or may not generate data, which will not be used in regulatory documentation or to make GMP decisions and does not directly impact on patient safety, any problems would be easy to detect. Examples of this type of equipment would be: Evaporators, Stirrers, Ultrasonic baths
5.4.1.2 Critical
Critical equipment generate data which may/will be used within a regulatory documentation or which may impact on patient safety. Within this category there are other considerations as to the level of complexity, the level of qualification (IQ, OQ and PQ) required may vary depending on this.
5.4.1.3 Commercial Off The Shelf (COTS)
Commercial Off The Shelf equipment/ (COTS) may be non-critical or critical. When critical this type of equipment will place a greater reliance on the manufacturer / vendor qualification documents. Examples of this type of equipment would be:
At the lower level
pH meters (checked using buffers prior to use) NMR Spectrometers (self calibrating)
At the upper level
GC systems HPLC systems
5.4.1.4 Other
Some equipment generate data which may/will be used within a regulatory documentation or which may impact on patient safety. They are, however, should be customized by a manufacturer to specific company requirements. As such they will always require the highest level of qualification for both the hardware and software. And a greater reliance on internal documentation to define the criteria and limits required.
5.4.2 Level of Qualification
The level of qualification for each type of equipment can be summarized as shown in
| No Qualification Documents | Company documents but relying on contractor qualification documents, if appropriate | Company documents |
5.5 Qualification Phases
Qualification is a logical step-wise process; which may be risk assessed but which generally consists of the stages below. The outcome of all these stages must be summarized and reported(as a single document/report).
– The work required to perform the qualification and the acceptance criteria must be outlined in measurable terms in a protocol/plan.
– A qualification protocol/plan for each type of equipment must be written and approved in accordance with section 4.It should include a reference to the GAMP classification of the equipment.
This qualification protocol/plan may be valid for qualification of future equipment of the same type purchased at the originating site or at other sites within the same company and hence may become a ‘generic’ protocol/plan. * If modifications are required to a ‘generic’ protocol/plan for equipment bought later, then a modified document outlining the changes must be produced. R&D QA must approve this modified protocol/plan.
5.5.1 User Requirement Specification – Design Qualification (URS – DQ)
This step ensures that the design complies with the user requirement specification. Compliance with GMP includes reviewing the design documentation against the URS. Commercial off The Shelf equipment (COTS) As the equipment design is already in place for commercial off-the shelf (COTS) equipment, the URS – DQ is met by the suppliers specification. (this type of equipment is usually GAMP Categories A to F). Therefore, it is not necessary for design qualification to be repeated. Users should, however, ensure that all COTS instruments are suitable for their intended use. Non Standard Systems For non-standard systems it is preferable that the equipment vendor or manufacturer performs design qualification. When required, vendor audits/technical discussions involving R&D QA should be undertaken (this type of equipment are often GAMP Category G and as such require full software validation.
5.5.2 Installation Qualification (IQ) Installation
Qualification provides documented verification that the analytical equipment as installed or modified; comply with the supplied design documentation, the manufacturers specifications and /or the User Requirement Specification. A vendor supplied operation verification documentation / plan which identifies the tests / checks required is acceptable. The IQ will ensure that the analytical equipment, operating software, documentation and its accessories have been delivered and configured correctly.
5.5.3 Operational Qualification (OQ)
Important equipment parameters should be tested. A vendor supplied operation verification documentation / plan which identifies the tests / checks required is acceptable. These however should be reviewed to ensure that they contain satisfactory limits for each measured parameter. The extent of OQ testing any particular analytical equipment undergoes depends on the intended application and the type of equipment. Therefore, no specific OQ tests are cited here. As a guide to the type of tests to be considered during OQ the following are examples of tests, which may be undertaken for an HPLC system:
– Pump Flow
– Gradient Linearity
– Detector wavelength accuracy, linearity, drift and noise
– Injector repeatability
The successful completion of the operational qualification will normally be sufficient to confirm the correct operation of any installed operating software as indicated in GAMP 4.
As already stated in Section 5.5 a single operational qualification plan may be used for multiple purchases of the same type of equipment. The amount of qualification tests for subsequent purchase of the same type of equipment may be reduced. The option to carry out reduced testing must be included in the original plan. However, if modifications are required to an already approved plan, then a reduced document outlining the changes must be produced and approved by R&D QA as stated in section.
5.5.4 Performance Qualification (PQ)
Performance qualification provides documented verification that the analytical equipment function as intended and produce results repeatedly and reliably. For commercial off the shelf equipment PQ may be satisfied by calibration, system suitability tests and the routine maintenance of the analytical equipment (GAMP categories from A to E) For more complex equipment (GAMP Category F) more detailed PQ testing (e.g. a PQ program recommended by the system vendor) may be appropriate.
In these circumstances it may be appropriate for scheduled preventative maintenance of the system to comprise full or partial execution of the PQ program. The initial PQ should be included in the report outlined in section 5.5, and a record of all subsequent PQ/preventative maintenance should be collated.
5.6 Replacement of Modules
Within a modular system, individual modules may be changed from time to time. (i.e. a detector in a HPLC ). In these cases only the module, which has been replaced, requires additional OQ. If the system is already covered by an OQ plan then that part of the plan should be used. If the replacement module has already been qualified then a system suitability test may be sufficient and it is not required that a new plan is written. For more complicated systems (COTS) it may be appropriate for scheduled preventative maintenance of the system to comprise full or partial execution of the PQ program.
5.7 Maintenance of qualified status
Systems and documentation must to be present / maintained to ensure that equipment is suitable for its’ intended use. Such systems for Critical equipment shall include: SOPs, calibration, maintenance and replacement of modules. In order to maintain the qualified status of equipment, an assessment of the need to re-qualify as part of the maintenance and/or calibration work shall be carried out and documented.