This document discusses process validation. It defines process validation as establishing documented evidence that a process will consistently produce a product meeting its predetermined specifications. The key aspects of process validation are to obtain consistent and reliable data, demonstrate that the process remains in control, and show the process works as intended. There are different types of process validation including prospective, retrospective, and concurrent validation. Process validation involves multiple phases from process design and qualification to process verification and monitoring. It is important for quality, safety, efficacy and compliance with global regulatory agencies.

1. Process validation
Guru Balaji.S
Global product development (R&D)
s.gurubalaji@gmail.com

2. Process

3. Process validation (PV)
Quality, safety, efficacy
Global regulatory agencies
History of validation
Definition
Why process validation
Overview of process validation
Importance of validation
Process validation team
PV: Types of documentation
PV documents and support documents
PV flowchart
PV team
PV – Types of documentation
Prospective validation
Retrospective validation
Concurrent validation
Revalidation
Phases of process validation

4. Process validation
is established
documented evidence
which give
high degree of assurance that a
specific process will
consistently produce a product
meeting its
quality characteristics
and
pre-determined specifications

5. API
Manufacturing
process
Excipients
Delivery
form
Quality
Safety
Efficacy

6. Global regulatory agencies

7.  Validation details are described in the current good manufacturing practice
(cGMP) for finished pharmaceuticals in 21 CFR parts 210 and 211 of USA
 Concept of validation - first proposed by two FDA officials,
Ted Byers and Bud Loftus, in the mid 1970’s in order to improve the
quality of pharmaceuticals
 It was proposed in direct response to several problems in the sterility of
LVP (.Large volume parentals)
 The first validation activities were focused on the processes involved in
making these products, but quickly spread to associated process of
pharmaceutical.
 U.S.F.D.A. was the pioneer in advocating the concept of process validation,
but till 29th September 1978 the definition did not appear any where.
History of validation

8.  US FDA Definition
“Process validation is establishing documented evidence which provides a high
degree of assurance that a specified process will consistently produce a product
meeting its pre-determined specifications and quality characteristics.”
 ICH Definition
“Process Validation is the means of ensuring and providing documentary
evidence that processes within their specified design parameters are capable of
repeatedly and reliably producing a finished product of the required quality.”
 WHO Definition
“The documented act of proving that any procedure, process, equipment,
material, activity or system actually leads to expected result.”
Definition

9. Why process validation
Why ?
Need of process validation:
• To obtain consistent, reliable and accurate data
• Act as proof in decision making
• To get assurance of quality product
• To demonstrate the process remains in control
• To demonstrate the process works as intended

10. 1
2
34
5
6Revalidate Planning
Process
monitoring
Installation
qualification
Process /product
qualification
Operational
qualification

11. Importance of Validation
 Assures the repeatability of the process
 Decreases the risk of manufacturing problems
 Minimal batch failures, improved efficiently and productivity
 Reduction in rejections
 Increased output
 Avoidance of capital expenditures
 Fewer complaints about process related failures
 Reduced testing in process and in finished goods
 More rapid and reliable start-up of new equipment's
 Easier scale-up form development work
 Improved employee awareness of processes
 More rapid automation
 Government regulation (compliance with validation requirements is necessary
for obtaining approval to manufacture and to introduce new products)

12. Quality
Assurance
Quality
control
(QC)
Production
Engineering
Formulation
R&D
Process
development
team
Technology
transfer
team
Process
validation
team

13. Process validation: Types of documentation

14. Change control
1. Process
understan
ding
2.
Process
design
3
qualification
3.
Process
qualification
4. Commercial
manufacture
5.Monitorin
g &
improvemen
t
Based on product
quality and patient
safety
Know the process Know the
variables
Have the
confidence
vigilance

15. Process
validation
documents
Miscellaneous
report
Development
report
Batch
records
Cleaning
validation
Operating
procedures
Analytical
methods
Schematic detailing how process validation documents reference other support documents

16. Chemical process
research
Chemical process
development
Clinical API
manufacture
Continuous chemical
process
develolpment
API mfg.
Preformulation
Formulation
development
Clinical mfg.
Formulation
process
development
Drug
product mfg.
Pharmaceutical discovery
IND
Process
validation
NDA & preapproval
inspection
Analytical method
development
Analytical
method
validation

17.  The particular type of process validation is normally
carried out in connection with the introduction of new
drug products and their mfg. process
 Carried out prior to distribution of new product or
existing product made under a revised manufacturing
processes where such revision may affect product
specification or quality
 Also called as premarket validation
 An experimental plan called the validation protocol is
executed before the process is put into commercial use

18.  Conducted for a product already being marketed, and
is based on extensive historical data accumulated over
several lots and over time.
 Some essential elements of retrospective validation
- Batches mfg. for a defined period
- Batch size/strength/mfg./year
- Master manufacturing/packaging documents
- Current specifications for active
materials/finished products
- List of process deviations, corrective actions and
change to mfg. documents
- Data for stability testing for several batches
- Trend analysis including those for quality related
compliants

19. • 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.
• Study is carried out under a protocol during a course
of normal production
• This may be a practical approach under certain
circumstances
(a) When previously validated process is being
transferred to a third party contract
manufacturer or to another manufacturing site
(b) Where the product is a different strength of a
previously validated product with the same ratio of
active /inactive ingredients

20. It is repeating/ part of the original validation activity. It
is essential to maintain the validated status of the plant,
equipment, manufacturing processes and computer
systems.
Possible reasons for doing :
(1) The transfer of a product from one plant to another.
(2) Changes to the product, the plant, the manufacturing
process, the cleaning process, or other changes that
could affect product quality.
(3) Change - equipment (type,function,location,control
system,major repairs)
(4) Periodic revision
(5) Significant (usually order of magnitude) increase or
decrease in batch size.
(4) Sequential batches that fail to meet product and
process specifications.
It depends on the extent of the changes and the effect
upon the product.

21. Phases of process validation
Process design /process development1
Process qualification
a) Design of facility
b) Qualification of utilities & equipment
c) Process performance qualification(PPQ)
d) PPQ protocol
e) Process execution and report
2
Process verification3

22. Process development
Process development activities begin after the formulation has been
developed. It meets the following objectives
Develop a suitable process to produce a product which meets all
a) Product specification
b) Current good manufacturing practice's
Identify the key process parameter that affect the product attribute
Identify in process specification

23. Process Objective Variable (Monitor) Test (response)
Solution
preparation
To ensure a colorless/specified color
solution with specified pH and %
assay(specified % of labelled amount)
• Load
• Mixing time
• Mixing speed
Assay
Clarity
pH
Filtration To comply the sterility test
• Filtration rate
• Pressure
Sterility
Filling &
partial
stoppering
To ensure uniformity in filled volume
and % assay
• Filling rate
• pressure
Sterility
Lyophilisati
on &
stoppering
To ensure uniformity in appearance of
lyophilized cake and reconstitution time
• Load
• Vacuum
• time
• temperature
Water content
Scale formation
reconstitution time
pH
weight
Appearance
Sealing To ensure integrity of seal -
Leak test
seal integrated
Lyophilized formulation process with monitor and test

24. Process Objective Test (response)
Pre blending
To ensure uniformity % assay
(specified % of labeled amount)
Description
Assay
Dissolution
Water content
Weight variation
Related
substances
Granulation To comply the granulation parameters
Drying
To ensure the granules drying parameters
and PSD
Sizing
To ensure uniformity in appearance of
lyophilized cake and reconstitution time
Blending
To ensure uniformity % assay
(specified % of labeled amount)
Tableting Ensure tableting parameters
Film coating Ensure film coating parameters
Tablet formulation process with monitor and test

25. Knowledge……
is proud that he has learnt so much
Wisdom…
Is humble that he knows no more
William cowper

26. Guru Balaji.S
Global product development(R&D)
91-99 44 33 08 34
s.gurubalaji@gmail.com