Guidance 097 – Use of Process Analytical Technology Pharmaceuticals quality assurance & validation procedures GMPSOP

Use of Process Analytical Technology in Process Validation

Introduction

This document provides examples of the possible use of Process Analytical Technology (PAT) systems during traditional process validation to demonstrate that a manufacturing process is in a validated state. This guidance is supplemental to guidance ‘Process Validation for Drug Products and Medical Devices’ and ‘Process Validation for Active Pharmaceutical Ingredients (API)’.

PAT systems can be used to:

Collect data in parallel with the collection of traditional process validation data
Reduce the traditional validation testing or
Replace a traditional test (regulatory or an in-process release test) during process validation.

Whatever type of use, PAT testing can provide an opportunity to increase data analysis and process knowledge compared to traditional tests. This guidance includes examples of PAT applications for each of the three scenarios listed above. Modification of registration documentation to support the replacement of a registered method by a PAT application must comply with local and international regulatory requirements.

Recommendations and Rationale

PAT system application in process validation offers the opportunity to leverage experience with scientific inquiry and innovation. If possible, it is recommended to utilize PAT to evaluate a process before validation begins. This will establish a baseline for comparisons in later studies and provide an opportunity to evaluate the PAT approach itself.

This guidance provides an example of approaches for applying PAT in support of process validation activities. PAT may be applied in three primary forms;

1. Parallel PAT activity – traditional validation occurs without change while PAT activity is added and performed concurrently to traditional validation. The PAT provides additional information about the process, quality attributes and/or parameters. If the traditional process validation criteria are met but the PAT data suggest that the process might need further evaluation, an investigation should be initiated. If the PAT results are related to product quality, lot release should be held until the PAT investigation is completed.

2. QC reductive PAT activity – the PAT activity is integrated into the validation approach to provide information that will assist in the conclusion of the validation exercise. Alternatively, the PAT activity could be applied to reduce the volume or frequency of traditional validation testing. Integration into traditional validation documentation and potential alteration to traditional validation testing can mean that the PAT testing may come under regulatory scrutiny.

3. Alternate PAT activity – the PAT activity is integrated into the validation approach and traditional testing is replaced by alternate PAT methods. PAT data directly affects the outcome of the validation exercise and would come under regulatory scrutiny.

Some reasons for selecting the different approaches are as follows:

Limited past experience of applying the PAT for a particular product may suggest initial Parallel Approach
Where timelines for PAT method inclusion as an alternate method in the regulatory filing are limited, Parallel or QC reductive approach may be suggested.
Where the validation testing is considered laborious or has safety concerns, QC reductive or Alternate PAT may be suggested
Where there is no regulatory requirement to perform particular validation testing, QC reductive approach may be suggested

The qualification requirements for a PAT system should be defined based on how the data obtained from the PAT application will be used. If the data obtained from the PAT system will be used for parallel information to the validation tests only, the PAT application maybe considered an indirect or no impact system (Ref 1). Complementary validation data with the

intent of reduced testing would be a direct-impact system. If the PAT data will replace a regulatory or an in-process release test that is not verified by another established quality test then the PAT application will be considered a direct impact system. Generally, if quality decisions are to be made based on the output of the PAT application, even if implemented with the parallel approach, the PAT application would be considered direct impact depending on the controls in place.

Revisit of the qualification of the PAT application is necessary if the PAT application purpose is changed, e.g. was used initially for information only or in parallel and is later planned to be used to replace an established validation test.

Figure:

*Fit for purpose validation- the extent of PAT method validation is governed by the intended use of the method. Depending on the use of the PAT method, some parameters typically validated in laboratory analytical methods may not be applicable. Refer to Appendices I-IV for examples of how PAT has been applied to support process validation within Site and how various PAT techniques can be applied using the three described approaches.