Implementation of Process Analytical Technology
Introduction
This document gives guidance on the implementation of Process Analytical Technology (PAT) applications at a GMP processing site. Implementation of PAT involves analytical measurement systems with associated methods that are integrated into a manufacturing process. PAT provides more direct information about control points of the manufacturing process and quality attributes of a product than that which is available by traditional analytical methods. Implementation of PAT applications should conform to current Good Manufacturing Practices (cGMPs).
PAT applications should be evaluated and documented according to the intended use and risk to quality and regulatory compliance. Guidance on the intended use and risk to quality is included in the following sections. The extent of verification testing (incorporating commissioning and qualification), method validation and approach to deviation investigation will depend on the outcome of the risk assessment and should be commensurate with the risk associated with the both the use of the PAT application and the data generated as result of application use.
Classification
Application classification should be based on both the intended use of data and the risk to quality.
1.0 Classification based on Intended Use
Classification should be based on the intended use of the data generated by the PAT application.
1.1 Development and evaluation of PAT technology:
- Includes measurement systems with associated methods under experimental development.
- Includes measurement systems with associated methods used to demonstrate feasibility for a specific use.
- Does not generate data to support acceptability decisions associated with a manufacturing process or product.
1.2 Monitoring and Control
- Includes measurement systems with associated methods used to support acceptability decisions associated with progression of material through a manufacturing process.
- Includes measurement systems with associated methods used to support process optimization.
- Includes measurement systems with associated methods used to used to support process validation.
- Includes measurement systems with associated methods where the data is used to make operational decisions based on non quality attributes (e.g. yield)
2.0 Classification based on Risk to Quality
Classification should be based on the intended use of the application, including the use of data
generated. Subsequent impact to product quality and regulatory compliance should be incorporated into the classification assessment.
2.1 Critical (Direct Impact) PAT System:
- A PAT system or application whose operation, data, control, alarm or failure is expected to have an effect on product quality or regulatory compliance.
- A PAT application that will produce, monitor, evaluate, store or report data used to accept or reject product or material, or data used to support regulatory compliance.
- A PAT application used to control or effect an identified critical product and/or quality attribute/parameter or specification
2.2 Key (Indirect Impact) PAT System:
- A PAT system or application whose operation, data, control, alarm or failure is not expected to have an effect on product quality or regulatory compliance and which links or interfaces with a direct impact system, application or test.
- A PAT application used to control or effect an identified key product and/or quality attribute/parameter specification.
2.3 Not Critical (No Impact) PAT System:
- A PAT system or application which will have no effect either directly or indirectly on product quality or regulatory compliance.
Implementation Requirements
1. General:
- Each Site PAT application should be approved for use at the site by the Site Quality Team, including a review of its potential impact upon the quality systems at the site.
- For PAT applications whose category of use is defined as Monitoring and Control, associated manufacturing and quality documentation should be revised in accordance with local change control policies in order to implement the PAT application at the site.
- When site-specific documents are generated to support PAT implementation, they should adhere to all central notification, review, and approval requirements.
2. Development and Evaluation of PAT technology:
- A PAT system whose category of use is defined as Development and Evaluation of PAT technology should be commissioned as per guidance 098.
- A PAT application method whose category of use is defined as Development and Evaluation of PAT technology does not need to be validated though appropriate demonstration of application suitability for intended use should be performed.
- Questionable results for PAT applications, whose category of use is defined as Development and Evaluation of PAT technology, can be investigated as part of the system or application development activity.
3. Monitoring and Control:
- A PAT system whose category of use is defined as Monitoring and Control and the risk to quality or regulatory compliance is considered critical (direct impact) or key (indirect impact) should be verified (incorporating commissioning and qualification) as per guidance 098.
- PAT systems whose risk to quality or regulatory compliance is considered not critical (noimpact) are commissioned only.
- For an existing process or product, all PAT applications whose category of use is defined as Monitoring and Control and the risk to quality or regulatory compliance is considered critical and key (direct and indirect impact), change control should be applied. The Site Quality Team, should coordinate appropriate changes including those where there is intent to register specifications or changes in specifications with regulatory agencies.
- A PAT application method whose category of use is defined as Monitoring and Control and critical (direct) or key (indirect) should be validated. The validation protocol(s) and report(s) should be approved by the relevant Quality Team, as per guidance 098.
- Questionable results for PAT applications whose category of use is defined as Monitoring and Control and that are considered critical (direct) impact should be investigated. Questionable results for PAT applications that are considered key (indirect impact) or non-critical (no impact) can be investigated as per the site RFT program.
Post-Implementation Requirements:
For critical (direct impact) and key (indirect) PAT methods, whose use is defined as Monitoring and Control, reliability of PAT applications should be periodically verified (based on risk) with a scientific and statistically-justified approach.
- For PAT methods that measure product or process characteristics that can be also measured by traditional analytical methods, samples should be taken at defined intervals based on risk, and analysed by the traditional analytical method(s) as well as the PAT method to evaluate PAT application performance.
- In cases where the above is not practical, then acceptable performance of the validated PATmethod should be demonstrated periodically, based on risk by measurement of a defined check sample or standard or by following a performance verification procedure applicable to the PAT application.
- For non-critical (no impact) PAT methods whose use is defined as Monitoring and Control, there should be an appropriate program in place to monitor the ongoing suitability of the application.