Purpose
To lay down the
procedure for conducting the hold time study of pharmaceutical products during
manufacturing at in-process stage(s).
Definition:
Hold time: Hold time is a time period in which
bulk awaiting for next stage may be held under specified condition and will
remain within predefined specification.
Hold Time Study:
Hold time study data shall give the assurance the maximum allowable hold times
for in-process products. One or more batches can be considered for validating
hold times. If any adverse results were observed, then some more batches can be
used for this study.
Hold time study
also define as it is the validation of hold time period of in-process products.
World Health
Organization recommended the hold time study during different stage of
pharmaceuticals manufacturing, their sampling and testing intervals. So hold
time study has more importance during manufacturing.
Samples need to
kept in the SS container or any container simulating to the original container
in which the in-process bulk is supposed to be kept for hold.
Hold samples
need to store at GMP conditions i.e. where the stage holds in the manufacturing
area.
Hold time study shall be
performed in following conditions:
Change in
storage condition.
Change in
formulation. For example, addition or deletion of ingredient.
Change in
manufacturing process.
For new
formulation.
Sampling Procedure for Hold
Time Study
Use cleaned
accessories during sampling.
Use PPEs during
sampling.
While sampling
in the area, ensure that all stainless steel containers are closed except from
which sample to be withdrawn.
After sampling
close the container taking proper precaution to avoid contamination.
For sampling of
microbiological test sample:
- Use sterile container/bottle for
sampling.
- Wear sterile hand gloves while
sampling.
- Remove Aluminum wrapper of
container/bottle.
- After sampling close the container
taking proper precaution to avoid contamination.
A written
protocol shall be prepared which includes the activities to be performed, test
parameters and acceptance criteria appropriate to the material or product under
test.
The Hold time
study protocol shall be Prepared by QA, reviewed by Head/ Designee Production,
Head/ Designee QC and Executive/ Designee - QA and then finally approved by
Head/ Designee-QA.
This product
dedicated protocol shall act as protocol and after completion of study, data
shall be compiled in it and act as report also. Thus it shall be protocol cum
report.
Protocol cum
report shall include the contents, but not limited to.
Approved hold
time shall be defined on the basis of period product complied with acceptance
criteria as defined in the hold time protocol.
Stages
to be studied for hold time study, shall be selected on the basis of following tree
 |
| Hold Time Study Chart |
Hold time study
shall be conducted on one batch and if not justified can be extended to other
batches.
The containers
used in which hold-time samples are stored should have the same MOC in which
the material is hold in production.
The sample
storage environmental conditions should be same as that of the manufacture
stage.
In case of
holiday the sample shall be sent to QC and analyzed on next working day.
Any deviation
occurred during handling of sample shall be handled through the SOP “Handling
of Deviation”.
Any out of
specification results shall be handled through the SOP of “Handling of OOS”.
Approved analytical
procedure shall be used for analysis of product.
After
compilation of results, recommendation of hold time study shall be shared to
production for incorporation the holding period of different steps in the BMR.
Hold Time Study
shall be performed with the following steps.
Selection of critical steps;
Hold Time Study points and tests;
Hold Time Study Protocol.
Hold Time Study Analysis
Hold Time Study results evaluation.
On the basis of
observations made during hold time study, a summary report shall be prepared by
QA, reviewed by other concerned departments and approved by QA Head/ Designee.
This report
shall include the observations made, summary, conclusion, and recommendations,
if any.
Hold time study
requirements for Aerosol dosage forms.
Hold study
required Hold study time points Tests required
Bulk As defined in protocol As defined in protocol
In case for any
product (batch), staging period exceeds approved holding time, it shall be
handled through deviation.
Sample shall be
sent to QC and Microbiology lab (as applicable), and batch shall proceed for
next stage, but the succeeding stage shall not be released for successive stage
till QC release obtained.
