To lay down the procedure for performing the drying process validation in the manufacturing of Intermediates and Active Pharmaceutical Ingredients.
1.0 PURPOSE
1.1 To lay down the procedure for performing the drying process validation in the manufacturing of Intermediates and Active Pharmaceutical Ingredients.
2.0 SCOPE
2.1 This procedure is applicable to the Drying process validation of Intermediates and Active Pharmaceutical Ingredients manufactured
3.0 RESPONSIBILITY
3.1 Head – Production
3.2 Head – Quality control
4.0 ACCOUNTABILITY
4.1 Head - Quality Assurance
5.0 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 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
5.2.2 Drying parameters
5.2.3 Sampling interval
5.2.4 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 The batches taken for prospective process validation shall be considered for drying process validation.
6.0 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).
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).
7.0 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.
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Drying process, validation, quality assurance
