detail about process validation strategy

1. Presented by
Prashik s shimpi
M.Pharm 2nd
year (Quality Assurance)
R.C. Patel Institute of pharmaceutical education and
research,shirpur

2.  The strategy selected for process validation
should be simple and straight forward.
 1.The use of different lots of raw materials
should be included.
 2. Batches should be run in succession and on
different days and shifts.
 3.Batches should be manufactured in the
equipment and facilities designed for eventual
commercial production.

3. 4.Critical process variables should be set within
their operating ranges and should not exceed
their upper and lower control limits during process
operation.
5. Failure to meet the requirements of the validation
protocol with respect to process input and output
control should be subjected to process
requalification and subsequent revalidation
following an thorough analysis of process data
and formal discussion by the validation team.

4. A. Prospective Process Validation- An
experimental plan called validation protocol is
executed before the process is put into commercial
use.
Most validation efforts require some degree of
prospective experimentation in order to process
validation support data.
This particular type of process validation is normally
carried out in connection with the introduction of new
drug products and their manufacturing processes.

5. 1. The facilities and equipment in which the process
validation is to be conducted meet CGMP
requirements(completion of installation qualification).
2. The supervising personnel should have understanding
of the process and its requirements
3. The design,selection and optimization of the formula
have been completed.

6. 4. The qualification trials using pilot laboratory
batches have been completed in which the
critical processing steps and process variables
have been identified.
5. Detailed technical information on the product and
manufacturing process have been provided.
6. At least one qualification trial of a pilot production
batch has been made and shows there were no
significant deviations from expected performance
of the process.
Validation of the process by this approach often
leads to transfer of the manufacturing process
from the development function to production

7. The retrospective validation option is chosen for
established products whose manufacturing processes
are considered stable.Prior to undertaking
retrospective validation the numerical in process and
or end product test data of historic production batches
are subjected to statistical analysis,the
equipment,facilities and subsystems used in
connection with the manufacturing process

8. Retrospective validation is achieving validation by
documenting all the historical information (e.g.
release data) for existing products and using that
data to support the position that the process is
under control.

9. 1. Gather the numerical values from the completed batch
record and includes assay values, end product test results
and in process data.
2. Organize these data in a chronological sequence, according
to batch manufacturing data.
3. Include data from at least the last 20-30 manufacturing
batches for analysis. If number of manufactured batches is
less than 20 then include all manufactured batches in
analysis.
4. Trim the data by eliminating test results from non critical
processing steps and delete all numerical information.

10. 5.Subject the resultant data to statistical analysis
and evaluation.
6. Draw a conclusion as to the state of control of the
manufacturing process based upon the analysis of
retrospective analysis validation data.
7.Issue a report of your findings (documented
evidence)

11. 1. Individual assay results from content uniformity test.
2. Individual tablet hardness values
3. Dissolution time.
The statistical methods like Basic statistics (mean, S.D.)
,regression analysis etc. may be employed to
analyze above data.

12. In process monitoring of critical processing steps and
end product testing of current production can provide
documented evidence to show that the manufacturing
process is in a state of control.
Such validation documentation can be provided from
the following test parameter and data sources.

13. Test parameter Data source
Content uniformity End product testing
Dissolution time End product testing
Particle size distribution In-process testing
Weight variation In-process testing
Tablet Hardness In-process testing
Disintegration Time In-process testing

14. Not all of the above in-process tests enumerated above
are
required to demonstrate that the process is in state of
control.
Selection should be made on the basis of the critical
Processing variables to be evaluated
The critical in process test parameters would be
particle or granule size distribution, Tablet hardness.

15. Conditions requiring revalidation study and
documentation are –
1.Change in a critical component(usually refers to raw
materials)
2.change or replacement in a critical piece of modular
equipment
3.Change in facility and or plant(usually location or site
4.Significant increase or decrease in batch size
5.Sequential batches that fail to meet product and
process specifications

16. Statistical process control is also called as statistical
quality control. It comprises various mathematical
tools (correlation chart, scatter diagram) used to
monitor a mfg. process.
Thus SPC represents the tools to be used, while
process validation represents the procedural
environment in which those tools are used.

17. 1. In- process and final product testing, which
normally depends upon sampling size.
2.Establishments of tighter specification limits that
hold product and mfg. process to a more
demanding standard will often reduce the need
for more extensive sampling requirements.
3. The modern approach is pursuit of “ZERO
DEFECT” by applying tighter control over
process variability.

18. There is no one way to establish evidence of
process validation .
If the manufacturer is certain that its products and
processes are under statistical control and in
compliance with CGMP regulations,it should be
a relatively simple matter to establish
documented evidence of process validation

19. REFERENCES
Nash RA ,Wachter AH , Pharmacutical Process Validation,An
International 3rd
Edition ,Revised &Expanded,Indian special
edition,Informa Healthcare, 2011 ,volume 129. p 607-609
ICH OFFICIAL WEB http://www.ich.org