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. 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.

1 Process Design
o 1.1 Design of Experiment (DOE)
o 1.2 Quality by Design (QBD)
o 1.3 Process Analytical Technology (PAT)
o 1.4 Critical Process Parameters (CPP)
o 1.5 Critical Quality Attributes (CQA)
o 1.6 Design Space Verification

2 Process Qualification

3 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.

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.

Critical Process Parameters (CPP)

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

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.

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.
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 Continuous 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.