Process validation

1.3 Process Analytical Technology (PAT)

Process Validation is the analysis of data gathered

throughout the design and manufacturing of a product in
order to conrm 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 nished-product inspection. Process validation can be broken down into 3 steps:
process design, process qualication, and continued process verication.

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 qualication.[3]

1.4 Critical Process Parameters (CPP)

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

1.5 Critical Quality Attributes (CQA)

Process Design

Critical Quality Attributes are attributes that are considIn this stage data from the development phase are gath- ered essential in determining product quality.
ered and analyzed to dene the commercial manufacturing process. By understanding the commercial process
1.6 Design Space Verication
a framework for quality specications can be established
and used as the foundation of a control strategy. Process
Design Space Verication conrms that quality can be
design is the rst of three stages of process validation.
guaranteed within an identied range of input and opData from the development phase is gathered and anaerating variables.[5]
lyzed to understand end-to-end system processes. These
data are used to establish benchmarks for quality and production control.

2 Process Qualication

In this stage the process design is assessed to conclude

if the process is able to meet determined manufacturing
Design of experiments is used to discover possible rela- targets. In this stage all production processes and mantionships and sources of variation as quickly as possible. ufacturing equipment is proofed to conrm quality and
A cost benet analysis should be conducted to determine output capabilities. Critical quality attributes are evaluated and critical process parameters taken into account
if such an operation is necessary.[2]
to conrm product quality. Once the process qualication stage has been successfully accomplished production
can begin. Process Qualication is the second phase of
1.2 Quality by Design (QBD)
process validation.

1.1

Design of Experiment (DOE)

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.

3 Continued Process Verication

Continued Process Verication 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
1

nal product irregularities are agged by a process analytics database system. The FDA requires production data
be recorded (FDA requirements ( 211.180(e)). Continued process verication is stage 3 of process validation.
The European Medicines Agency denes a similar process known as Continuous Process Verication. This alternative method of process validation is recommended
by the EMA for validating processes on a continuous
basis. Continuous Process Verication analyses Critical
Process Parameters and Critical Quality Attributes in real
time to conrm 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. Food and Drug Administration.
Retrieved 16 December 2014.
[2] A Case for Stage 3 Continued Process Verication.
Pharma Manufacturing. Retrieved 22 November 2014.
[3] PAT - A Framework for Innovative Pharmaceutical
Development, Manufacturing, and Quality Assurance.
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 Verication.
European Medicines Agency. Retrieved 17 December
2014.
[6] Continued Process Verication
[7] Continuous Process Verication. Atris Information
Systems. Retrieved 17 November 2014.

REFERENCES

Text and image sources, contributors, and licenses

6.1

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