Introduction
Qualification and validation of laboratory equipment is a very important issue in the pharmaceutical industry. Laboratory equipment can have direct or indirect impact on product quality and must be qualified and validated. What is the difference between qualification and validation, and why is there confusion between qualification and validation of laboratory equipment?
Which equipment in the analytical laboratory should follow qualification and which equipment should follow the validation process to be compliant with FDA regulations? Many laboratory instruments are computerized and run automatically.
Data is collected and transmitted electronically, and reports are electronically signed. Other equipment is not computerized and thus does not utilize software:a non-electronic paper-based report is generated. How may we set up analytical laboratories to be compliant with applicable regulations that govern the Pharmaceutical environment? Which regulations should laboratories follow? How can laboratory instruments be qualified and validated in an efficient manner and with corresponding documentation to address actual regulatory risks? The key is to set up a Quality Manual to define validation processes,inventory all laboratory equipment, classify and categorize equipment, define requirements and the risk with regulatory compliance and conduct validation according to accepted industry best practices.
FDA Regulations
FDA regulations are a considerable foundation for principles of validation and qualification of laboratory equipment.
Process qualification and validation of laboratory equipment must follow regulations of the Food and Drug Administration (FDA). Title 21 Code of Federal Requlations Part 58, known as 21 CFR Part 58, as applicable to laboratories for Nonclinical Studies as follows:
- 21 CFR Part 58, Good Laboratory Practice for Nonclinical Laboratory Studies
- 58.63 Maintenance and calibration of equipment.
- 58.81(b)(11) shall set forth in sufficient detail the methods….
- © Written records shall be maintained of all inspection, maintenance,testing, calibrating and/or standardizing operations…
Regulations 21 CFR Part 210 & 211 as below apply to laboratory equipment and cover areas such as cleaning and use log, routine check, maintenance, production and process control, laboratory control, deviations, records and reports, and batch records.
- 21 CFR Part 210& 211, Current Good Manufacturing Practice for the Manufacture, Packing or Holding of Drugs, September 1978
- 211.68 Automatic, mechanical, and electronic equipment.
- 211.100 Written procedures; deviations
- 211.180 General Requirements
- 211.182 Equipment cleaning and use log
- 211.186 Master production and control records
- 211.188 Batch production and control records
- 211.194 Laboratory Records
In regard to electronic records / signatures, laboratory equipment must be assessed to determine whether or not 21 CFR Part 11 is applicable. Generally,Good—clinical or documentation or laboratory or manufacturing—Practices (i.e.,GxP) and 21 CFR Part 11 assessments must be conducted prior to validation.Assessments can be used to categorize equipment and define compliance risk and how to manage these risks. Title 21 CFR Part 11 requirements as follows must be considered:
- 21 CFR Part 11, Current Good Manufacturing Practice, Electronic Records, Electronic Signature, August 1997 (if applicable)
- 11.10 Controls for closed systems
- 11.30 Controls for open systems
- 11.50 Signature manifestations
- 11.70 Signature/record linking
- 11.100 General requirements
- 11.200 Electronic signature components and controls
- 11.300 Controls for identification codes/passwords
The International Organization for Standardization (ISO) can be in considerationto set up analytical laboratories:
- ISO9000 Quality Standard
- ISO17025 Accreditation Standard
- ISO/IEC 12207 International Standard- Information Technology-Software
- Lifecycle Processes, 1995
Guidelines
To set up qualification and validation processes for laboratory equipment, follow these guidelines:
-
GAMP 4, Good Automated Manufacturing Practice (GAMP) guide for validation of automated systems, December 2001.
-
ISO/IEC 17025, General Requirements for the Competence of Testing and Calibration Laboratories, November 2005.
-
GALP, Good Automated Laboratory Practice (GALP), EPA, 1995
A proper understanding of validation terminology is the key to successful setup of the validation process.
“Process validation is establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality characteristics.”
Validation of Laboratory Equipment
Validation of laboratory equipment follows categorization of equipment as computerized or non-computerized
Validation of laboratory equipment is an approved process to demonstrate that predefined requirements for intended use of equipment are consistent, satisfied,confirmed, and documented. Validation testing includes but is not limited to Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ).
Depending upon equipment categorization, the validation process for laboratory equipment may include these phases: user requirements; validation planning and risk assessment; design and installation and operational qualification; performance qualification and user acceptance tests; maintenance; and replacement/retirement phases. For each of these phases, a corresponding set of documents provides evidence of validation and compliance with applicable regulations. Whereas computer-run laboratory equipment is assessed as a computerized system, validation of such equipment follows the pattern for validation of computerized systems.
A computerized Chromatography Data-acquisition System (CDS), such as Empower that interactively controls HPLC and GC instruments, is an example of laboratory equipment that would be validated as a computerized system. HPLCs and GCs connected to a CDS such as Empower for example, can be qualified when the Empower software is qualified. Validation of computerized systems in the laboratory can follow the GAMP 5 guideline. Nevertheless, any laboratory equipment that is not operated under computer software must also be qualified.
Equipment Categorization
Conduct inventory of laboratory equipment and classify it as equipment, instrument or computerized system.
The equipment categorization is an important task to define the level of qualification or validation to be applied. The equipment categorization starts from the inventory of all laboratory equipment, including instruments and computerized systems. For computerized systems the risk assessment should be conducted to define the level of compliance with regulations and the level of validation to be applied. Prioritization of validation activities is necessary to establish in order to mitigate critical systems with the high risk first.
The Qualification and Validation of Laboratory Equipment Model
The qualification and validation methodology for laboratory systems must be established.
Figure 1
The qualification and validation of laboratory equipment follows the above model displayed in Figure 1. Start from the plan, continue through the build and qualify, then maintain, and if any changes occurred, plan again under the change control. The red arrow represents verification. All qualification protocols must be verified and traceable to the planning.
Validation of Laboratory Systems
The typical schema for validation of laboratory systems is the following:
| Plan | ||
| User Requirements | Outline the regulatory, user and business needs. | |
| Vendor Audit | Specify vendor documentation and level of testing. | |
| Risk Assessment | Determine the compliance risk with regulations. | |
|
Design and Functional Requirements |
Outline the design, functional and operational needs. | |
|
Validation Plan |
Outline the validation approach and all validation tasks and deliverables during validation process, define the acceptance criteria. | |
| Build and Qualify | ||
|
Design Qualification |
Confirm the design parameters met acceptance criteria. | |
| Installation Qualification | Confirm the installation parameters met acceptance criteria. | |
| Operational Qualification | Confirm the configuration of the system and operational functions met acceptance criteria. | |
| Performance Qualification | Confirm the user requirements met acceptance criteria. | |
| Traceability Matrix | Verify all requirements are tested. | |
| SOP | Procedural control of operations and maintenance of equipment. | |
| Change Control | Change control process for equipment and documentation changes. | |
| Periodic Audit | Internal and external audit. | |
| Training | Training program for equipment use. | |
| Summary Reports | Summarize the DQ, IQ, OQ, PQ and overall validation | |
| Maintain | ||
| SOPs | Operate and Maintain according to SOPs | |
| Periodic Audit | Conduct the internal and external audit. | |
| Change Control | Change control process for equipment and documentation changes. | |
User Requirements
User Requirements is the first step
in the validation process.
To gather user requirements is a very important step in the validation process. The user requirements should include high level of functions to be used for the system, business, regulatory and user needs. All requirements must be clearly defined and be testable one way or another, procedurally or technically.
Risk Assessment and Risk Analysis
Risk assessment and risk analysis is a tool to define level of validation to be conducted with laboratory equipment
The Risk Assessment and Risk Analysis is a tool to calculate a risk related to regulatory requirements for system use. It is a tool to define if the full validation or partial testing is necessary. For the critical requirements with a high risk usually full testing is necessary. For the non-critical requirements with low risk usually partial testing or just the configuration check is necessary.
The process for Risk Assessment and Risk Analysis of laboratory systems is fully defined with SDLC methodology.
Vendor Audit
Vendor Audit is necessary to define level of validation to be conducted in house.
The Vendor Audit is an important task in validation effort. The vendor documentation can be considered to support the validation activities.
Usually the vendor documentation covers the design, and functional testing of equipment. If the vendor provides documentation testing for IQ, OQ and PQ, those tests must be traceable to the design and functional requirements.
In some cases it is not necessary to repeat those testing in house, as long as the testing satisfies established acceptance criteria. In some cases, the system purchased from the vendor has more functions as required. Those functions needs to be defined, and procedural or technical control must be established around it.
Design and Functional Requirements
Vendor Audit is necessary to define level of validation to be conducted in house.
The Vendor Audit is an important task in validation effort. The vendor documentation can be considered to support the validation activities.
Usually the vendor documentation covers the design, and functional testing of equipment. If the vendor provides documentation testing for IQ, OQ and PQ, those tests must be traceable to the design and functional requirements. In some cases it is not necessary to repeat those testing in house, as long as the testing satisfies established acceptance criteria. In some cases, the system purchased from the vendor has more functions as required. Those functions needs to be defined, and procedural or technical control must be established around it.
Design and Functional Requirements
Vendor Audit is necessary to define level of validation to be conducted in house.
The Vendor Audit is an important task in validation effort. The vendor documentation can be considered to support the validation activities.
Usually the vendor documentation covers the design, and functional testing of equipment. If the vendor provides documentation testing for IQ, OQ and PQ, those tests must be traceable to the design and functional requirements. In some cases it is not necessary to repeat those testing in house, as long as the testing satisfies established acceptance criteria. In some cases, the system purchased from the vendor has more functions as required. Those functions needs to be defined, and procedural or technical control must be established around it.
Design and Functional Requirements
Gather design and functional
requirements from the vendor documentation.
Usually the design and functional requirements can be found in the design specifications of the vendor documentations. All design and functional requirements must be traceable to the user requirements.
Validation Plan
Validation Plan defines all validation activities.
Validation plan defines the validation process. It outlines all validation activities and defines the acceptance criteria for each validation phase. Validation Plan explains all definitions and terms used for validation activities, and defines how validation be conducted.
Design, Installation, Operational and Performance Qualification
The design, installation and operational qualification must be traceable to the design and functional requirements. The performance qualification must be traceable to the user requirements.
Common terms for qualification and validation of laboratory equipment are DQ, IQ, and OQ, PQ.
DQ is a design qualification of laboratory equipment where all design and configuration parameters define.
IQ is an installation qualification that records and proves the hardware and software installation.
OQ is an operational qualification that tests the operational functions of equipment.
PQ is a performance qualification that tests the intend use of equipment. Design, Installation, Operational testing must be traceable to the design and functional requirements. Performance Qualification testing must be traceable to the user requirements.
Qualification Methodology for Laboratory Equipment
The qualification methodology for laboratory equipment must be established.
The typical schema for qualification of laboratory equipment is the following:
|
Plan |
|
|
Requirements Specifications |
Outline the design, operational and business needs. |
| Qualification Plan | Outlines the design, installation, operational and performance approach, as well as acceptance criteria. |
|
Build and Qualify |
|
|
Design Qualification |
Confirm the design parameters met acceptance criteria. |
|
Installation Qualification |
Confirm the installation parameters met acceptance criteria. |
|
Operational Qualification |
Confirm the operational functions met acceptance criteria. |
|
Performance Qualification |
Confirm the user requirements met acceptance criteria. |
| Training | Conduct Training for equipment use. |
| SOP | Outline operation and Maintenance |
| Summary Report | Summarize the qualification activities. |
|
Maintain |
|
|
SOPs |
Operate and maintain according to SOPs. |
| Change Control | Change control process for equipment and documentation changes. |
The qualification of laboratory equipment is comparable to the validation of laboratory equipment, with the difference that the CFR Part 11 requirements usually do not apply, and equipment does not require full validation.
How SDLC Inc. Can Help You
SDLC Inc. has been a leader in validation and qualification of laboratory equipment and can provide a broad range of services across the validation lifecycle.
SDLC Inc. has been a premier provider of auditing, assessment and validation and qualification services for laboratory equipment used by pharmaceutical clients since 1996. Our expertise is recognized in the industry and our personnel have worked with the majority of equipment and computerized systems used in the laboratory including:
-
Millennium
-
Empower
-
HPLC
-
GC
-
AA
-
FTIR
Our services encompass the full system lifecycle, covering everything from requirements gathering through to post implementation validation gap analysis. Internally, SDLC Inc. has developed a set of generic protocols that can be used to accelerate the process of validation and qualification. This tool is utilized as a foundation for ensuring that a set of user requirements can be generated that is completely compliant with regulatory expectations. It can also be used for an assessment of existing requirements or for a compliance gap analysis at any point in the lifecycle.
In addition, SDLC Inc. also has the ability to leverage the knowledge and expertise of its client company, Integrated Pharma Technologies, a leading provider of sample management and sample accountability programs. This includes provision of combined audits team that can assess an operation for validation compliance.
About the Author
Lana Cherny is a Senior Validation Scientist who has been with SDLC, Inc. since 2006. While at SDLC, she has specialized in the compliance of computerized systems and laboratory equipment, and worked with the major clients in pharmaceutical industry providing validation expertise on Computer Validation Systems methodology. Lana Cherny has an excessive experience in pharmaceutical industry providing validation services for analytical laboratories, as well as clinical, development and medical devices. She has a broad knowledge of FDA regulations. Lana conducted audits, regulatory assessments, and gap analysis. She was involved in setting up validation processes, and conduct validation activities, writing Validation Plan, IQ, OQ, PQ protocols and summary reports.
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