sop for stability management

1.0 OBJECTIVE:
To describe the procedure for performing the stability studies of finished dosage forms in the package in which they are marketed under recommended storage condition during their shelf life and confirm the conformance with specification. The studies are conducted to establish or to support the recommended storage condition and shelf life of the product.

2.0 SCOPE:

This procedure is applicable to all products manufactured at abc pharma

3.0 RESPONSIBILITIES:
3.1 QA Officer or Designee:
3.1.1 Collection of samples and handing over to QC for stability charging
3.1.2 Approval of stability protocol and summary report
3.2 QC Officer or Designee :
3.2.1 To prepare protocol & report.
3.2.2 Sample charging and withdrawal as per stability protocol and schedule.
3.2.3 To analyse the stability sample as per respective spec/STP.
3.2.4 To Inform the Section Head in case of Out of specification test results.
3.2.5 To prepare stability summary report and submit to section head for review.
3.3 Section Head or Designee:
3.3.1 Ensure timely withdrawal and charging of samples.
3.3.2 To initiate investigation in case of out of specification (OOS)/stability failure.

3.3.3 To inform any significant change and stability failure results to Head QC and Head QA.
3.3.4 To review and approve the stability report after analysis of sample.
3.3.5 To review the stability protocol and summary sheet

4.0 ACCONTABILITY
4.1 Head QC
Accountable for stability management.

5.0 DEFINITION:

5.1 Stability: The ability of a pharmaceutical product to retain its physical and chemical properties within specified limits throughout its shelf life.
5.2 Stability Tests: A series of tests designed to obtain information on the stability of a pharmaceutical product in order to define its shelf life and utilization period under specified packing and storage conditions.
5.3 Long Term or real time stability study: Experiments on the physical and chemical characteristics of a drug, during and beyond the expected shelf life and storage periods of samples under the storage conditions expected in the intended market.
5.4 Accelerated Stability study: Studies designed to increase the rate of chemical degradation and physical change of a drug by using exaggerated storage conditions as part of the formal stability- testing program.
5.5 Shelf Life: The period of time during which a drug product, if stored correctly, is expected to comply with the specifications determined by stability studies on a number of batches of the product. The shelf life is used to establish the expiry date of each product

6.0 PROCEDURE:
6.1 Stability protocol

6.1.1 A product specific stability protocol/Report shall be prepared to conduct the stability studies. The protocol/report shall be prepared as per SOP.
6.1.2 The stability protocol shall be prepared based on country specific guideline and current product specification.
6.1.3 In case of any additional test parameter/information which is only applicable to Stability shall be covered in the stability protocol.
6.1.4 The Stability protocol should specify a product expiry time point, e.g. Product expiry calculated from date of manufacturing and as per expiry on the label.
6.2 Selection of batches and stability study initiation:

6.2.1 First three commercial batches (other than regulatory market) shall be charged for accelerated, intermediate and long term stability study as per ICH guide line.
Note: For Regulated market stability sample shall be charged as per regulatory commitment/Regulatory requirement (As per the conditions mentioned in the stability protocol)
6.2.2 One batch of ongoing product shall be charged to real time stability study every year.
6.2.3 The samples shall be charged to stability study for following changes.

S.No. Changes – ACC – RT
1. Change in the formulation -3 batches – 3 batches
2. Change in manufacturing process -3 batches – 3 batches
3. Change in source of API – 1 batch – 1 batch
4. Change in batch size up to10 times – NA – 1 batch
5. Change in location – 1 batch – 1 batch
6. Change in primary packing closure system 3 batches 3 batches Change in manufacturing equipment (s)

Note: For regulated market, country specific guide line shall be followed for carrying out stability study in case of above changes.
6.2.4 The stability study shall be conducted whenever required to support any deviation evaluated by Head QA.
6.2.5 If required an additional stability studies may be carried out for market returned products, Complaint samples, samples collected from different sales depots.
6.3 Storage conditions
6.3.1 Following real time and accelerated storage conditions shall be followed according to current ICH and WHO guideline.

6.3.2 If 30°C ± 2°C /75% RH ± 5% RH is the real time condition, then sample shall not be charged for intermediate condition.

Sampling, Labeling and Charging
- Stability studies shall be performed as per the pre-approved protocol of the drug
- In-Process Quality Assurance (IPQA) personnel shall collect samples for stability studies during packing from start, middle and end of the packing
- Quality Assurance shall submit stability samples along with Stability charging Request Form as per Format
- After receiving the samples from Quality Assurance, samples shall be charged by QC
- Additional samples for one analysis shall be charged for each storage condition as per the respective stability
- Ensure that the Date in is within one month from the date of analysis. In case date of analysis is beyond the one month time “T0” analysis shall be performed for the batch and results shall be considered for stability study purpose.

Samples for stability shall be charged in its actual or proposed marketing pack and shall be labeled with respective condition label before charging. Each conditions label are printed in different colors as follows;

40°C ± 2°C / 75% RH ± 5% RH : Yellow

30°C ± 2°C / 65% RH ± 5% RH : Red

25°C ± 2°C / 60% RH ± 5% RH : Green

30°C ± 2°C / 75% RH ± 5% RH : Light blue

Labeled samples shall be charged in respective stability
Stability charging register shall be maintained as per

Specification
- The protocols of stability studies shall include all Stability including tests which are likely to influence quality, safety, efficacy of the
- Each product shall be tested for the tests mentioned in the product specific stability
Testing Frequency

Test stations:

Accelerated

Real time

Intermediate

Initial, 1 month, 2

months, 3 months

and 6 months.

Initial, 3, 6, 9, 12, 18 , 24 M or expiry and 36M or expiry and thereafter up to one station beyond shelf life . Beyond shelf life, if required

sample will be charged as per stability protocol.

Initial, 3, 6, 9

& 12 months.

6.6.2 The samples shall be withdrawn within +7 days of the due date and the analysis shall be initiated within 3 days form the removal of the sample from the stability chambers. Store the withdrawn samples at storage condition mentioned in the protocol and if not mentioned in the protocol then store the samples at NMT 25°C till the analysis is complete. The analysis shall be completed within 30 days from the date of initiation of analysis.
Any deviation from above mentioned procedure shall be handled through deviation report.
Note: If intermediate study has to be initiated as a result of significant change in accelerated condition then, the tolerance limit for product shall be calculated from the date of confirmed significant change in accelerated condition
6.6.3 Samples shall be tested up to one year after expiry for commercial pack and no further stability to be performed for the same. Samples shall be pulled within +7 calendar days of the defined expiration date
6.6.4 The “Start Date” of stability study is the date on which the samples are charged for stability according to the storage conditions, since the format itself indicate charging date then not required.
6.6.5 The “Due Date “at each testing interval (testing station) is the date that the samples are to be removed from the storage chamber and submitted for analysis.
6.6.6 The study shall be conducted beyond the expiry, in case of requirement from regulatory.
6.6.7 Bracketing/Matrixing of samples shall be carried out wherever possible with prior authorization from Quality Assurance.
6.7 Evaluation of Reports
6.7.1 If “Significant change” occurs at any time during 6 months testing at the accelerated stability condition; additional testing at the intermediate storage condition should be conducted and

evaluated against significant change criteria. When testing at the intermediate storage condition is called for a result of significant change at the accelerated storage condition, a minimum of four time points, including the initial and final time points (e.g., 0, 6, 9, 12 months), from a 12-months study is recommended.

6.7.2 The “Significant Change” criteria for a drug product is defined as
6.7.2.1 A 5% change in assay from its initial value; or failure to meet the acceptance criteria for potency.
6.7.2.2 Any degradation product’s exceeding its acceptance criterion:
6.7.2.3 Failure to meet the acceptance criteria for appearance, physical attributes, and functionality test (e.g., color), however, some changes in physical attributes may be expected under accelerated conditions as appropriate for the dosage form.
6.7.2.4 Failure to meet the acceptance criteria for pH
6.7.3 Any significant change/OOS shall be investigated as per SOP.
6.7.4 Any Out of Trends result shall be investigated as per SOP.
6.8 Stability data review and documentation.
6.8.1 On completion of testing, stability result shall be reported in stability summary report as per format no.SOP.
6.8.2 The stability study data shall be reviewed by QC head/designee and approved by Quality Assurance Head or designee.
6.8.3 Any result outside the finished product specification shall be immediately reported to all concern departments/regulatory dept.
6.8.4 Any results outside the specification shall be informed to manufacturing contract givers.
6.8.5 The stability study shall be discontinued in case of failure to comply the specification with approval of QA. This shall be communicated to Research and Development Head, Regulatory department,

and Production Head.

The OOS investigation shall be conducted. The investigation shall be extended to other batches manufactured under similar condition and / or other batches, which are likely to be affected. The recall shall be initiated whenever required and shall be communicated to Regulatory department, Production Head and contract givers.

In case of discontinues the study; the remaining sample shall be destroyed as per
The extra kept sample shall be withdraw along with the last time point of the stability study of particular condition

The allowable tolerance in variation of temperature and humidity and Excursions :
- The allowable tolerance in variation of temperature and humidity is ± 2°C and ±5% RH respectively from the set values. Short term variations due to opening of doors of the stability chamber shall be Excursions in the range

(i.e. ± 2°C and 5%) if exceeds 24 hours, the impact on ongoing study shall be evaluated by calculating the mean kinetic temperature. If MKT falls below the acceptance criteria then the withdrawal date samples shall be increased by the no. days under the excursions.

Note: Backup services such as for power failure are provided through on-line UPS system.

7.0 ABBREVIATION:

OOS : Out of specification

ICH : International Committee on Harmonization RH : Relative humidity

ANDA: Abbreviated new drug application

PLC : Program logic control

WHO : World health organization.