In previous article we understood what is pharmaceutical validation study and scope (phase)of validation. We also saw the history
of validation concept.
In this article we are going to understand the definition
of process validation as per various regulatory agencies, type of process validation and objective
of process validation along with it’s advantages.
Definition
of Process validation:
ICH (International Conference on Harmonization): In
2000, ICH defines definition of process validation in cGMP Guidance document
ICH Q7 that “Process Validation (PV) is the documented evidence that the
process, operated within established parameters, can perform effectively and
reproducible to produce an intermediate or API meeting its predetermined
specifications and quality attributes.”
WHO (Word Health Organization): The
documented act of proving that any procedure, process, equipment, material,
activity or system actually leads to expected result.
USFDA: In 2011,
“The collection and assessment of data, from the process design stage all the
way through production, which establishes logical indication that a process is
capable of consistently delivering quality products.
European Commission: In 2000,
Documented
evidence that the process, operated within established Parameters, can perform
effectively and reproducible to produce a Medicinal product meeting its
predetermined specifications and quality attributes.
Stages
of process validation:
This
stage is the combination of all three phases of validation, i.e. Phase-I
(Process design), Phase-II (Process qualification) and Phase-III (Continuous
process verification).
Stage-I (Process Design):
When
we talk about Process design Part, it explains process / product development
activities. This is very important
stage, as without understanding the process / product to work on Qualification
of process would be worthless.
Hence,
it is important to understand the process / product right from development
stage. This stage gives knowledge gained during the process / product
development activities and scale-up activities. This is the stage where
acceptance criteria’s and its establishment are being taken, called as process
control strategy to get the desired product.
Stage-II
(Process Qualification):
This
is the execution phase of process validation, wherein execution of the process
is being done with the knowledge gained via stage-I (process design).
Establishment
of the process, acceptance criteria’s has been done in stage-I now to prove
consistency, accuracy and efficiency this stage is being applied to complete
the approach of process validation.
In
other words “Process qualification is the heart of the Process validation
concept”. Approaches being selected around the globe inline to regulatory
expectations are explained in this article. Sometimes it is also known as
Process Performance Qualification i.e. PPQ approach.
Stage-III
(Continuous process verification):
As
we have established a process and validated it, so maintenance of process is
also required to get the desired product with consistency of the quality.
This is the stage which is used for the
on-going assurance of the process taken during execution, to prove that process
remains in state of control.
“A
fruitful validation program lay on the leg of Knowledge, Understanding,
execution and approach to control the process”
and this all being obtained via execution of all above three stages of process
validation.
Type
of process validation (Process performance qualification)
of process validation (Process performance qualification)
Validation
is documented proof to prove that established parameters will perform effectively
and reproducible to supply a product meeting its established specifications and
quality attributes. There
are three types / approach of process validation;
1]
Prospective process validation:
This
is the approach / type of validation usually conducted prior to the
distribution of either a new product, or product made under amended
manufacturing process, where the revisions may affect the product’s
characteristics. (FDA) Validation carried out before routine production of
products intended for sale.
Basic concept of prospective validation is that batches those are considered under the validation study shall be released to market for the purpose of commercialization only after execution of all the validation batches and its quality inspection. Any exception in in this must be justified, reviewed and approved by Quality assurance.
2]
Concurrent process validation:
This
approach of validation is being carried out during routine production of
products intended for sale. It is identical to the prospective approach of
validation, except in this approach manufacturer can sell the product during
the execution of validation activity.
This
approach is being selected usually for recapitulation of the process which is
already validated under prospective approach of validation. Execution of this
approach is taken in condition when there is change in the already validated
equipment / plant or its site location.
3] Re-validation:
This
stage is the repetition of the process validation to provide an assurance that
changes in the process/equipment introduced in accordance with change control
procedures do not adversely affect process characteristics and product quality.
This
approach is also taken in the case of sequential batches that do not meet
established specifications. Various changes that may trigger the re-validation
likewise change in the key starting material / raw material and change in its
source of manufacturing, change in the process variables (drying temperature,
batch size etc.) or variation revealed by trend analysis.
In
simple word if we say this is all about the Confidence building and assurance
on established manufacturing process. To achieve main principal of cGMP
i.e. Manufacturing of Pharmaceutical product with high quality that meet global
standards, with consistency and with the principal of Quality, safety,
efficacy and reproduce-ability.
during the routine manufacturing. Execution of validation also provides a high degree of assurance of
quality of the product, consistency of the manufacturing process with reproduce-ability of the process.
Advantage of validation includes; enhancement of data evaluation capabilities for a product / process. process validation also gives an assurance that particular process will produce the desired product with the consistency of the quality as per predetermined specification.
In other words process validation helps to establish a process in such way, any process can be executed right first time and contributes in cost reduction as well. Process validation also helps to optimize the equipment, facility and system associated with the process. It also reduces failure cost.
I
hope this article helps you to refreshing your knowledge bucket; other useful
articles may uplift the information stock of the mind…..
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