Process validation

Process Validation is the analysis of data gathered throughout the design and manufacturing of a product in order to confirm that the process can reliably output products of a determined standard. Regulatory authorities like EMA and FDA have published guidelines relating to process validation.^[1] The purpose of process validation is to ensure varied inputs lead to consistent and high quality outputs. Process validation is an ongoing process that must be frequently adapted as manufacturing feedback is gathered. End-to-end validation of production processes is essential in determining product quality because quality cannot always be determined by finished-product inspection. Process validation can be broken down into 3 steps: process design, process qualification, and continued process verification.

Process Design

In this stage data from the development phase are gathered and analyzed to define the commercial manufacturing process. By understanding the commercial process a framework for quality specifications can be established and used as the foundation of a control strategy. Process design is the first of three stages of process validation. Data from the development phase is gathered and analyzed to understand end-to-end system processes. These data are used to establish benchmarks for quality and production control.

Design of Experiment (DOE)

Design of experiments is used to discover possible relationships and sources of variation as quickly as possible. A cost benefit analysis should be conducted to determine if such an operation is necessary.^[2]

Quality by Design (QBD)

Quality by Design is an approach to pharmaceutical manufacturing that stresses quality should be built into products rather than tested into products; that product quality should be considered at the earliest possible stage rather than at the end of the manufacturing process. Input variables are isolated in order to identify the root cause of potential quality issues and the manufacturing process is adapted accordingly.

Process Analytical Technology (PAT)

Process Analytical Technology is used to measure critical process parameters (CPP) and critical quality attributes (CQA). PAT facilitates measurement of quantitative production variables in real time and allows access to relevant manufacturing feedback. PAT can also be used in the design process to generate a process qualification.^[3]

Critical Process Parameters (CPP)

Critical Process Parameters Operating parameters that are considered essential to maintaining product output within specified quality target guidelines.^[4]

Critical Quality Attributes (CQA)

Critical Quality Attributes are attributes that are considered essential in determining product quality.

Design Space Verification

Design Space Verification confirms that quality can be guaranteed within an identified range of input and operating variables.^[5]

Process Qualification

In this stage the process design is assessed to conclude if the process is able to meet determined manufacturing targets. In this stage all production processes and manufacturing equipment is proofed to confirm quality and output capabilities. Critical quality attributes are evaluated and critical process parameters taken into account to confirm product quality. Once the process qualification stage has been successfully accomplished production can begin. Process Qualification is the second phase of process validation.

Continued Process Verification

Continued Process Verification is the ongoing monitoring of all aspects of the production cycle.^[6] It aims to ensure that all levels of production are controlled and regulated. Deviations from prescribed output methods and final product irregularities are flagged by a process analytics database system. The FDA requires production data be recorded (FDA requirements (§ 211.180(e)). Continued process verification is stage 3 of process validation.

The European Medicines Agency defines a similar process known as Ongoing Process Verification. This alternative method of process validation is recommended by the EMA for validating processes on a continuous basis. Continuous Process Verification analyses Critical Process Parameters and Critical Quality Attributes in real time to confirm production remain within acceptable levels and meet standards set by ICH Q8, Pharmaceutical Quality Systems, and Good manufacturing practice.^[7]

External links

• FDA – U.S. Food and Drug Administration
• EMA – European Medicines Agency
• Parental Drug Association
• Process Validation according FDA Guidances

References

1. "Guidance for Industry Process Validation: General Principles and Practices" (PDF). Food and Drug Administration. Retrieved 16 December 2014.
2. "A Case for Stage 3 Continued Process Verification". Pharma Manufacturing. Retrieved 22 November 2014.
3. "PAT - A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance" (PDF). Food and Drug Administration. Retrieved 10 December 2014.
4. "PROCESS VALIDATION (P2V)". Validation Online. Retrieved 22 November 2014.
5. "Questions and Answers on Design Space Verification" (PDF). European Medicines Agency. Retrieved 17 December 2014.
6. Continued Process Verification
7. "Continuous Process Verification". Atris Information Systems. Retrieved 17 November 2014.