# Presentation: 462029

## FDA PROCESS ANALYTICAL TECHNOLOGY SUB COMMITTEE

**MEETING 25****TH**** FEBRUARY 2002**

**PERSPECTIVE ON PROCESS AND ANALYTICAL**** ****VALIDATION**

- Robert S Chisholm

## THE TRADITIONAL APPROACH

- Processes Validated at Life cycle commencement
- Operated/Controlled by Standard Operating Procedures (SOPs)
- Quality Assurance based on off-line testing of a sample of product at the end of each batch
**THE PAT BASED APPROACH**
- On or at line Analysis for real time quality control of each unit operation process control throughout the batch
- Real time statistically based quality assurance throughout the batch
- Increased statistically based testing regimes provide the potential for release of product without further off-line testing

## QUOTATION 1

**THE NEED FOR STATISTICS**

- Statistical thinking will one day be as necessary
- for efficient citizenship as the ability to read and write

- H G WELLS 1925

## Implementation of the TQM Strategy

- In-Process Control & Monitoring
- Key Process Operations
- Identification / specification of all incoming raw materials in the dispensaries (& the warehouse)
- Fluid Bed Drier end point control
- Continuous in-line monitoring of blending & end point control
- In-line monitoring of Tablet Quality parameters against registered specifications
- 21CFR11 compliant data management system
- Real-time continuous quality assurance
- The platform for parametric release

## Solid Dosage Facility

**FB**
**Drier**

**Milling**

**Blender**

**Press**

**Coater**

**Sieve**

**Dispensary**

**Wet granulation**

**Direct Compression**

- Figure 1

## GENERALISED MODEL OF A PAT SYSTEM

- THE MODULES (Functionalities)
- Spectral (or other) data/model storage
- Analytical (or other) data storage
- Modelling
- Reporting (Batch and Validation Records and Storage)
- Statistical Process control (SPC) and Historic Trending
- THE MODES OF OPERATION
- Modelling
- Validation
- Manufacturing

## GENERALISED MODEL OF A PAT SYSTEM

- Figure 2

## CONSIDERATIONS FOR THE VALIDATION WG

- Regulatory status of Model source Data (Spectral analytical etc.) traceability and long term storage
- Traceability of spectral data, related, analytical data and model predictions for the model validation phase and its long term storage
- In manufacturing what form will the ‘PAT’ batch record and release data take,How can it be used by QA to release product and how would a regulatorybody inspector find an audit path from it for verification
- The MES/SPC Activities provide process understanding and knowledge –What regulatory status if any is associated with them

## FURTHER AREAS FOR DISCUSSION

- Registered processes (traditional) and statistically quality controlled processes
- Fundamental science and validation
- 21CFR11 and Computer validation complexity – Open and closed systems

## QUOTATION FOR THE DAY

**THE IMPACT OF INNOVATION**

- There is nothing		:	More difficult to plan
- 			:	More doubtful of success
- 			:	More dangerous to manage
- Than the creation of a new system
- For the initiator has
- 	The enmity of all who profit by preservation of the old institutions
- 				AND
-  	Merely lukewarm defenders in those who should gain by the new ones
- 						Machiavelli (1527)