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 The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

have published guidelines relating to process validation. 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 In chemical engineering, process design is the choice and sequencing of units for desired physical and/or chemical transformation of materials. Process design is central to chemical engineering, and it can be considered to be the summit of that ...

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.

Quality by design (QBD)

Quality by design is an approach to pharmaceutical manufacturing that stresses quality should be built into products rather than tested in 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 Process analytical technology (PAT) has been defined by the United States Food and Drug Administration (FDA) as a mechanism to design, analyze, and control pharmaceutical manufacturing processes through the measurement of critical process paramete ...

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.

Critical process parameters (CPP)

Critical process parameters Critical process parameters (CPP) in pharmaceutical manufacturing are key variables affecting the production process. CPPs are attributes that are monitored to detect deviations in standardized production operations and product output quality or cha ...

are operating parameters that are considered essential to maintaining product output within specified quality target guidelines.

Critical quality attributes (CQA)

Critical quality attributes (CQA) are chemical, physical, biological, and microbiological attributes that can be defined, measured, and continually monitored to ensure final product outputs remain within acceptable quality limits. CQA are an essential aspect of a manufacturing control strategy and should be identified in stage 1 of process validation:

process design In chemical engineering, process design is the choice and sequencing of units for desired physical and/or chemical transformation of materials. Process design is central to chemical engineering, and it can be considered to be the summit of that ...

. During this stage, acceptable limits, baselines, and data collection and measurement protocols should be established. Data from the design process and data collected during production should be kept by the manufacturer and used to evaluate

product quality In business, engineering, and manufacturing, quality – or high quality – has a pragmatic interpretation as the non-inferiority or superiority of something (goods or services); it is also defined as being suitable for the intended purpose (f ...

and

process control An industrial process control in continuous production processes is a discipline that uses industrial control systems to achieve a production level of consistency, economy and safety which could not be achieved purely by human manual control. I ...

. Historical data can also help manufacturers better understand operational process and input variables as well as better identify true deviations from quality standards compared to false positives. Should a serious product quality issue arise, historical data would be essential in identifying the sources of errors and implementing corrective measures.

Process qualification

In this stage, the process design is assessed to conclude if the process is able to meet determined manufacturing criteria. 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 Continued process verification (CPV) is the collection and analysis of end-to-end production components and processes data to ensure product outputs are within predetermined quality limits. In 2011 the Food and Drug Administration published a report ...

is the ongoing monitoring of all aspects of the production cycle. 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 The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

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 Critical process parameters (CPP) in pharmaceutical manufacturing are key variables affecting the production process. CPPs are attributes that are monitored to detect deviations in standardized production operations and product output quality or cha ...

and critical quality attributes in real time to confirm production remains within acceptable levels and meets standards set by ICH Q8, Pharmaceutical Quality Systems, and

Good manufacturing practice Current good manufacturing practices (cGMP) are those conforming to the guidelines recommended by relevant agencies. Those agencies control the authorization and licensing of the manufacture and sale of food and beverages, cosmetics, pharmaceutica ...

References

External links

FDA – U.S. Food and Drug Administration

EMA – European Medicines Agency

Parental Drug Association

{{Webarchive, url=https://web.archive.org/web/20141023233151/http://www.atris-systems.com/210.0.html , date=2014-10-23 Software testing Formal methods Software quality Enterprise modelling Business process management