Process validation is defined as collecting data throughout production to establish that a process can consistently deliver quality products. It involves three stages: process design, process qualification, and continued process verification. Process design uses development data to define the commercial process. Process qualification assesses if the process meets manufacturing targets. Continued process verification monitors all production aspects to ensure control. There are four types of validation: prospective, retrospective, concurrent, and revalidation. Prospective validation establishes a process can meet requirements before use. Retrospective uses historical data to validate existing processes. Concurrent monitors current production. Revalidation repeats validation due to changes.

1. Process Validation
Definition of process validation: Process validation is defined as the collection and evaluation
of data, from the process design stage throughout production, which establishes scientific
evidence that a process is capable of consistently delivering quality products.
The Process validation activities can be described in three stages:
Stage 1 – 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.
Designof 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.

2. Critical Quality Attributes (CQA)
Critical Quality Attributes are attributes that are considered essential in determining product
quality.
DesignSpace Verification
Design Space Verification confirms that quality can be guaranteed within an identified range of
input and operating variables.
Stage 2 – 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.
Stage 3 – 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 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.
Types of Process Validation:
The guidelines on general principles of process validation mentions four types of validation:
A) Prospective validation (or premarket validation)
B) Retrospective validation
C) Concurrent validation
D) Revalidation

3. A) Prospective validation: Establishing documented evidence prior to process implementation
that a system does what it proposed to do based on preplanned protocols. This approach to
validation is normally undertaken whenever the process for a new formula (or within a new
facility) must be validated before routine pharmaceutical production commences. In fact,
validation of a process by this approach often leads to transfer of the manufacturing process from
the development function to production.
B) Retrospective validation: Retrospective validation is used for facilities, processes, and
process controls in operation use that have not undergone a formally documented validation
process. Validation of these facilities, processes, and process controls is possible using historical
data to provide the necessary documentary evidence that the process is doing what it is believed
to do. Therefore, this type of validation is only acceptable for well-established processes and will
be inappropriate where there have been recent changes in the composition of product, operating
processes, or equipment. This approach is rarely been used today because it’s very unlikely that
any existing product hasn’t been subjected to the Prospective validation process. It is used only
for the audit of a validated process.
C) Concurrent validation: Concurrent validation is used for establishing documented evidence
that a facility and processes do what they purport to do, based on information generated during
actual imputation of the process. This approach involves monitoring of critical processing steps
and end product testing of current production, to show that the manufacturing process is in a
state of control.
D) Revalidation: Revalidation means repeating the original validation effort or any part of it,
and includes investigative review of existing performance data. This approach is essential to
maintain the validated status of the plant, equipment, manufacturing processes and computer
systems. Possible reasons for starting the revalidation process include:
 The transfer of a product from one plant to another.
 Changes to the product, the plant, the manufacturing process, the cleaning process, or
other changes that could affect product quality.
 The necessity of periodic checking of the validation results.
 Significant (usually order of magnitude) increase or decrease in batch size.
 Sequential batches that fail to meet product and process specifications.
 The scope of revalidation procedures depends on the extent of the changes and the effect
upon the product.