Procedure For Stability Study

1.0     PURPOSE
1.1     To lay down the procedure for stability study. 

2.0     SCOPE
2.1     This procedure is applicable in Quality Control.

3.0     RESPONSIBILITY
3.1     Head – Quality control.
    
4.0     ACCOUNTABILITY

4.1    Manager – Quality Assurance 
    
5.0    PROCEDURE

5.1    Criteria for Initiation of Stability Study

5.1.1  Stability study shall be conducted for the following reasons,

5.1.1.1    To evaluate new product or new manufacturing process.

5.1.1.2    To evaluate the reprocessed/rework batches.

5.1.1.3    To approve the changes as per change control procedure.

5.1.1.4    Routine evaluation of existing product.
 
5.2         Procedure of Stability Study

5.2.1    Stability study protocol shall be prepared and approved for each product. A template protocol is attached as per the format given in Annexure–I.

5.2.2    Numbering of the stability study Protocol:
Stability study protocol shall have 8 digit alphanumeric, which contain as follows:

5.2.3    Category shall be given as follows:

5.2.3.1    API        - A
5.2.3.2    Intermediates    - M
    
5.3        Storage Conditions

5.3.1    Storage condition shall be based on the International climatic zone or as per specific country guidelines and storage temperature as instructed on product label. The specific requirement is described in the following matrix.
For products storage condition Labeled as ‘Store below 25°C’

For products storage condition Labeled as ‘Store in refrigerator’

5.3.2    Other storage condition shall be applicable only for specific requirement of any regulatory market.

5.3.3    Where significant change occurs during storage under accelerated condition at temperature 40°C ± 2°C and RH 75±5%, discontinue the accelerated study and continue for Intermediate and long term storage condition.

5.3.4    Significant change for API and Intermediate shall be as failure to meet its specification.

5.4         Test Station:
Stability study shall be carried out as per the following test station 

5.5        Test Specification:

5.5.1    If subjected product is specified in the Pharmacopoeia, compendial specification shall be set as stability test specifications for stability study along with in house test parameters. During storage condition, change in compendial specification will trigger the change in stability test specification and the same will be added as amendment to protocol.

5.5.2    If subjected product is not specified in Pharmacopoeia, stability specification shall be prepared based on the stability report of R&D lab batches or Innovator specification.

5.5.3    Stability specification shall contain the quality parameters which may be affected on storage.

5.6        Test Method:

5.6.1    Test of assay of the product under stability study shall be carried out with the validated analytical method established as stability indicating through forced degradation study or as per respective compendial method.
5.7         Selection of the Batches and number of Batches:

5.7.1    Selection Criteria:

5.7.1.1    Batches shall meet the release specification.

5.7.2    Number of batches:

5.7.2.1    For introduction of a new product or manufacturing process, three consecutive batches of established manufacturing process shall be kept for stability study at long term, intermediate and accelerated storage condition.

5.7.2.2    For routine study: Yearly add one batch for stability study at long term storage condition. Normally 1st batch shall be considered for routine stability study. In case of batch of particular product exceed more than 100, follow minimum with 0.1 % sampling level.

5.7.2.3    For change control, number of batches shall be selected based on the decision in change control.

5.7.3    Sample Preparation:

5.7.3.1    Stability sample shall be collected in simulated container closures system, which represents the market pack.

5.7.3.2     Separate sample pack shall be prepared for each station of testing and if require separate pack for different test parameters shall be kept e.g. Microbiological testing.

5.7.3.3    Collect sufficient quantity of sample as calculated in test matrix of stability protocol required for testing.

5.7.3.4    Excess quantity of sample sufficient to conduct two complete tests shall be collected for any additional tests.

5.7.3.5    Sample packs shall be labeled as per Annexure-II / III / IV which ever is applicable.

5.8        Analysis of stability study samples:

5.8.1    Prepare the samples as per the approved protocol as per the format given in Annexure - I. 

5.8.2    Batches shall be kept for stability study within 15 days after the batch release.

5.8.3    If it is delayed for more than 15 days, then sample shall be re tested for initial results.  
    
5.8.4    The release/retest results shall be used as initial data for test parameter in stability specification.

5.8.5    Enter the sample details in the register as per format given in Annexure-V.

5.8.6    Keep the samples in the respective Environmental Chamber and record the IN-OUT (charging and unloading) of stability samples in Environmental Chamber logbook as per the format given in Annexure-VI.

5.8.7    Samples are taken out from chambers as per schedule and enter the details in register for analytical reference number allocation as per the format given in Annexure VII

5.8.8    After withdrawal of samples from stability chambers the samples are taken up for analysis.

5.8.9    Carry out the sample analysis with in 7 days for Accelerated study samples and within 15 days in case of Long term and Intermediate stability studies respectively.
 
5.8.10     If the samples are not tested within the above mentioned period, keep the samples in refrigerator. If the label claims is to store in refrigerator, samples to be tested within seven days from the due date for testing as in the storage condition.

5.8.11    Incase of any deviation take approval from quality assurance and plan the activity accordingly.

5.8.12    Record the analytical findings in approved analytical protocol/ data sheet and maintained all raw data along with data sheet.

5.8.13    Summarize the test report of each station in Stability Report as per the format given in Annexure-VIII, IX, & X.

5.8.14    If any failure observed during stability studies, investigation shall be carried out on analytical parameters only.

5.8.15    Prepare the final stability report as per the format given in Annexure - VIII, IX, & X.

5.9    Evaluation of Result

5.9.1    Based on 6 month’s accelerated or 12 months long term stability study data, a 2 year shelf life may be assigned for an API or Intermediate.

5.9.2    Final shelf life shall be assigned to a product supported by long term stability data.  

                                                        END OF DOCUMENT

Procedure, stability study, quality assurance