1.0
PURPOSE
1.1
2.0
To lay down the procedure for performing the drying process validation in the
manufacturing of Intermediates and Active Pharmaceutical Ingredients.
SCOPE
2.1
This procedure is applicable to the Drying process validation of Intermediates and
Active Pharmaceutical Ingredients manufactured
3.0
RESPONSIBILITY
3.1
3.2
4.0
ACCOUNTABILITY
4.1
5.0
Head – Production
Head – Quality control
Head - Quality Assurance
PROCEDURE :
5.1
Drying process validation shall be carried out in equipment that are qualified for
operation. (for the tray driers / Vacuum tray driers temperature mapping study
shall be conducted).
5.2
Drying Process shall be studied during execution of trial batches for the following
parameters as minimum requirement.
5.2.1
5.2.2
5.2.3
5.2.4
Drying Time versus specification
5.2.1.1
Water content / Loss on drying for intermediates
5.2.1.2
Water Content / Loss on Drying and Residual Solvents &
Organic Volatile Impurities for API
Drying parameters
Sampling interval
De-lumping if required during drying
5.3
The wet material obtained after centrifuging shall be weighed and recorded.
5.4
Divide the wet material quantity with number of trays available in dryer which
will give the material quantity to be loaded in each tray. (applicable in the case of
vacuum tray dryer or tray dryers)
Example :
Wet weight of Product X
= 96 Kg
No of trays in Tray drier
= 48
Material to be loaded in each tray = 96 / 48 = 2 Kg (Approximately)
5.5
Uniformly load the wet material in all the trays as per the above calculation.
5.6
Sampling Procedure and data to be collected during trial batches for
Intermediates :
5.6.1
Draw the wet samples as per locations mentioned in Appendix - I to IV
(whichever applicable) and send a composite sample to QC for analysis as
per the drying specification given in BPCR.
5.6.1.1
Preparation of Composite Sample : Draw the samples from
the locations mentioned in Appendix – I to IV (whichever
applicable) into a 5 kg capacity polythene bag and shake
thoroughly for uniformity for 1 minute. Take the required
quantity of sample from the polythene bag for analysis.
5.6.2
Dry the material for the time intervals mentioned in the BPCR. (i.e., for 2
hours, 4 hours etc.,)
5.6.3
Stop the dryer and draw the samples as per locations mentioned in
Appendix – I to IV (whichever applicable) and send a composite sample to
QC for analysis as per the drying specification given in BPCR.
5.6.4
Record the observations (de-lumping, vacuum, hot water and steam
applied and sampling times etc,.), results in the table given in BPCR.
5.6.5
When the composite sample result is below 60% of drying specification
(target), stop drying, draw and identify the samples as per the diagrams
mentioned in Appendix – I to IV (whichever applicable) and send all the
individual samples for individual analysis.
5.6.6
When all the individual samples are meeting the target drying
specification unload the material.
5.6.7
If any one of the samples is showing out of target drying specification
result, dry the material for another interval and send individual samples to
QC till all the individual samples meet the specification.
5.6.8
Tabulate all the data in Trial batch report on drying process (Annexure –
I).
5.7
Sampling Procedure and data to be collected during trial batches for APIs:
5.7.1
Draw the wet samples as per locations mentioned in Appendix - I to IV
(whichever applicable) and send a composite sample to QC for analysis as
per the drying specification given in BPCR.
5.7.2
Dry the material as per the time intervals mentioned in the BPCR.
5.7.3
Stop the dryer and draw the samples as per locations mentioned in
Appendix – I to IV (whichever applicable) and send a composite sample to
QC for analysis as per the drying specification given in BPCR.
5.7.4
Record the observations (de-lumping, vacuum, hot water and steam
applied and sampling times etc,.), results in the table given in BPCR.
5.7.5
When the composite sample result is below 60% of drying specification
(target), stop drying, draw and identify the samples as per the diagrams
mentioned in Appendix – I to IV (whichever applicable) and send all the
individual samples for individual analysis for Water content and/or Loss
on Drying, Residual Solvents and Organic Volatile Impurities (OVI).
5.7.6
When all the individual samples are meeting the Water Content, Loss on
Drying, Residual Solvents and OVI target drying specification unload the
material.
5.7.7
If any one of the samples is showing out of target drying specification
result, dry the material for another interval and send individual samples to
QC till all the individual samples meet the specification.
5.7.8
Tabulate all the data in Trial batch report on drying process (Annexure –
I).
5.8
If any mechanical mode of de-lumping is adopted, after de-lumping, the same
procedure for data collection and sampling shall be adopted.
5.9
Production department shall prepare a trial batch report as per the evaluation of
data collected during trial batches on drying process (as per Annexure – I).
5.10
Drying validation protocol shall contain the following as minimum requirement:
5.10.1 Justification for drying time fixation versus drying specification.
5.10.2 Drying process for validation batches.
5.11
6.0
The batches taken for prospective process validation shall be considered for
drying process validation.
Drying and sampling procedure and data collection during validation batches:
6.1
Based on the trial batch report on drying process, during validation batches the
material shall be dried for the specific interval (as per trial batch report).
7.0
6.2
Draw and identify samples in penultimate interval from different locations as
shown in Appendix – I to IV (whichever is applicable).
6.3
Send the individual samples to QC for Water content and/or LOD, Residual
Solvents, OVI analysis.
6.4
Continue the drying and follow the procedure mentioned in 6.2 to 6.3 for next two
intervals.
6.5
Stop drying and unload the material when all samples are below target drying
specification.
6.6
Tabulate all the data in the “Validation Report on Drying Process” (Annexure –
II).
Drying and sampling procedure and data collection during routine batches:
7.1
During routine batches execution, drying shall be carried out for the fixed time
interval (Evaluated in the drying process validation report) and dryer shall be
stopped.
7.2
Send a composite sample to QC as per the procedure mentioned in Appendix – I
to IV (whichever is applicable).
7.3
After obtaining the analysis result, the material can be unloaded.
7.4
If the sample does not conforms to specification, raise a deviation, and re-dry the
material.
END OF DOCUMENT