Validation ( process validation, TT from R&D to pilot plant)

1. 1
Presented By:
Mr. Rushikesh palkar
First Year M.Pharm
(Dept. of Pharmaceutics)
Sub: Modern Pharmaceutics
Alard College Of Pharmacy, Pune.
Under the Guidance of:
Dr. Nalanda Borkar
Head of Department
(Dept. of Pharmaceutics)
Sub: Drug Delivery System
Alard College Of Pharmacy, Pune.

2. “Establishing documented evidence which provides
a high degree of assurance that a specific process
will consistently produce a product meeting its
pre-determined specifications and quality attributes. ’’
(Validation of the individual steps of the processes
is called the process validation.)
2

3. Process validation involves a series of activities taking
place over the lifecycle of the product and process.
This guidance describes process validation activities in
three stages.
Stage 1 – Process Design
Stage 2 – Process Qualification
Stage 3 – Continued Process Verification
3

4. Stage1– Process Design :
During this stage the commercial manufacturing process is defined based
on knowledge gained through development and scale-up activities.
Stage 2– Process Qualification:
During this stage, the process design is evaluated to determine if the process
is capable of reproducible commercial manufacturing.
Stage 3– Continued Process Verification:
Ongoing assurance is gained during routine production that the
process remains in a state of control.
4

5. A successful validation program depends upon information
and knowledge from product and process development.
So that manufacturers should.
Understand the sources of variation
Detect the presence and degree of variation
Understand the impact of variation on the process and
ultimately on product attributes.
Control the variation in a manner commensurate with the
risk it represents to the process and product.
5

6. An integrated team approach to process validation that includes
expertise from a variety of disciplines. Project plans, along with the full
support of senior management, are essential elements for success.
All studies should be planned and conducted according to sound
scientific principles, appropriately documented, and approved in
accordance with the established Procedure
Homogeneity within a batch and consistency between batches are
should be the goals of process validation activities.
6

7. To establish a record keeping system that considers all concept of
manufacturing process which includes controlled testing.
To evaluate all possible sources of variation in process.
To identify all sources of variation those are possible from the materials,
machines, methods and men.
To evaluate the requirement for in-process testing and evaluation.
To document everything that is done to follow establish procedures and
protocols as closely as possible.
Quality, safety and effectiveness must be designed and built in to the
product.
Quality must be assured.
7

8. Before introduction of a new method into routine use.
Whenever the conditions change for which a method has
been validated, e.g., instrument with different Characteristics.
Whenever the method is changed, and the change is outside
the original scope of the method.
8

9. an experimental plan called the validation protocols executed before
the process is put into commercial use.
Most validation efforts require some degree of prospective
experimentation to generate validation support data.
Its is normally carried out in connection with the introduction of new
drug products and their manufacturing processes.
9

10. Equipment / facilities should meet cGMP requirements.
Personnel have an awakeness about the requirements.
Critical processing stages and process variables are identified.
At least one qualification trial (size x 100) made which shows that there
is no significant deviation from expected performance of process.
Batches should be run at different days, shifts and different quantities.
10

11. It is chosen for established products whose manufacturing processes are
considered stable and when on the basis of economic considerations alone and
resource limitations, prospective validation programs cannot be justified.
Wherein the numerical in-process and/or end-product test data of historic
production batches are subjected to statistical analysis.
The equipment, facilities and sub systems used in connection with the manu-
facturing process must be qualified in conformance with CGMP requirements.
11

12. Gather all historical data of process/ product in chronological sequence
according to batch manufactured.
Data should consists of atleast last 20-30 manufactured batches for analysis.
Trim data by eliminating results of non-critical steps.
Subject the resultant data to statistical analysis and evaluation.
Draw the control charting & go for conclusion.
12

13. It is in-process monitoring of critical processing steps and end-
product testing of current production.
It can provide documented evidence to show that the manufacturing
process is in a state of control.
It provides validation documentation from the test parameter and data
sources disclosed in the section on retrospective validation.
13

14. Required when there is a change in
any of the critical process parameters,
formulation,
primary packaging components,
raw material ,
major equipment or premises.
Failure to meet product and process specifications in batches would
also require process re-validation.
14

15. the individual qualification steps alone do not constitute process
validation.
1. Installation Qualification (IQ)
2. Operational Qualification (OQ)
3. Performance Qualification (PQ)
15

16. “Installation qualification establishes that the instrument is
received as designed and specified, that it is properly
installed in the selected environment, and that this
environment is suitable for the operation and use of the
instrument.”
16

17. "Operational qualification (OQ) is the process of demonstrating that an
instrument will function according to its operational specification in the
selected environment.” The proper operation of equipment is verified by
performing the test functions specified in the protocol. A conclusion is
drawn regarding the operation of equipment after the test functions are
checked and all data has been analyzed.
17

18. "Performance Qualification (PQ) is the process of demonstrating that an instrument
consistently performs according to a specification appropriate for its routine use ".
PQ should always be performed under conditions that are similar to routine sample
analysis.
PQ should be performed on a daily basis or whenever the equipment is being used.
In practice, PQ can mean system suitability testing , where critical key system
performance characteristics are measured and compared with documented.
18

19. Improve the use of technology
Improve the business benefits
Improve operational efficiency
Improve compliance with regulations
Reduce the risk of failure
Reduce the cost
Process optimization
Increased customer satisfaction
19

20. 20

21. R&D provides technology transfer dossier (TTD) document to product development
laboratory, which contains all information of formulation and drug product as follows-
-Master Formula Card (MFC)– Includes product name along:-
with its strength, generic name, MFC number, page number, effective date, shelf life
and market.
-Master Packing Card– Gives information about packaging type:-
material used for packaging, stability profile and shelf life of packaging.
21

22. continued…
-Master Formula–:-
Describes formulation order and manufacturing instructions.
(Process order and environment conditions).
-Specifications and Standard Test Procedures (STP’S):-
Helps to know active ingredients and excipients profile, in-process
parameters, product release specifications and finished product Details.
22

23. GIVING SITE:-
Provide Latest Source documentation.
Latest Specifications (Internal or registered)
Provide process(technology)transfer.
Protocol/report (analytical report method)
RECEIVING SITE:-
Execute Protocol(analytical method)
Qualified Facility and equipment or instrument.
Setup system
Setup training program.
23

24. Communication
– Open communication between all team members
– Direct communication between technical members
– Effective and timely communication with regulators
Sending and Receiving Unit
– Technology transfer is not a “one way street”
– The sending unit and receiving unit must be equally involved in
the process to ensure success
Team work at all time
24

25. Production master formula.
Manufacturing and Dispensing instructions.
Analytical methods.
Cleaning instructions and previous cleaning validation.
Active specifications and source.
Primary packaging material specifications and source.
Packaging instructions.
Process deviations file, Analytical deviations file.
Specimen manufacturing batch record.
25

26. 26
Validation is one of the important steps in achieving and
maintaining the quality of the final product. If each step of
production process is validated we can assure that the final
product isof the best quality.
Finally it can be concluded that process validation is a key
element in the quality assurance of pharmaceutical product as
the end product testing is not sufficient to assure the quality of
finished product.

27. 27
Sharma sumeet, Singh gurpreet. process validation in pharmaceutical
industry: an overview . J Drug De & Therap; 2013, 3(4),184-
88,2021;2(4)
Fraderick J. Carleton, James P.Agalloco ; validation of
pharmaceutical processes; 2nd edition ,1999 New York ; page
No.257-59, 2021;2(4)
Berry IR, Nash RA. Pharmaceutical process validation.
2nd ed. 1993 Newyork: Marcel Dekker.Inc, 2021;2(4)

28. 28