OBJECTIVEDRUG SUBSTANCEDRUG PRODUCT

2.1.1. General

Stability of the drug substance is an integral part of the systematic approach to stability evaluation The design should be based on knowledge of the behavior and properties of the drug substance and from stability studies on the drug substance.

2.1.2. Stress Testing/

Photostability Testing

To be carried out on a single batch of the drug substance including the effect of temperatures; humidity; oxidation; hydrolysis and photolysis on the drug substance

To be conducted on at least one primary batch of the drug product.  (ICH Q1 B)

2.1.3. Selection of Batches3 primary batches – manufactured to a minimum of pilot scale by the same synthetic route as, and using a method of manufacture and procedure that simulates the final process3 primary batches – of the same formulation and packaged in the same CCS
2.1.4. Container Closure SystemTesting to  be conducted on the drug substance packaged in a container closure system that is the same as or simulates the packaging proposed for storage and distributionTesting to be conducted on the dosage form packaged in the container closure system proposed for marketing.
2.1.5. SpecificationIt include testing of those attributes of the drug substance that are susceptible to change during storage and are likely to influence Q, S, EIt include testing of those attributes of the drug product that are susceptible to change during storage and are likely to influence Q, S, E

2.1.6. Testing Frequency

LT – (0, 3, 6, 9, 12, 18, 24, 36)

Accelerated – 0, 3 and 6-months

LT – (0, 3, 6, 9, 12, 18, 24, 36)

Accelerated – 0, 3 and6-months

2.1.7. Storage Conditions
“Significant change” 

For a drug substance is defined as failure to meet its specification.

For a drug product is defined as:

1. A 5% change in assay from its initial value; or failure to meet the acceptance criteria for potency when using biological or immunological procedures;

2. Any degradation product’s exceeding its acceptance criterion;

3. Failure to meet the acceptance criteria for appearance, physical attributes, and functionality test; however, some changes in physical attributes may be expected under accelerated conditions; and, as appropriate for the dosage form:

4. Failure to meet the acceptance criterion for pH; or dissolution for 12 dosage units.

If significant change occurs:

– Within the first 3 months’ testing at the accelerated storage condition, a discussion should be provided.

– Between 3 and 6 months’ testing at the accelerated storage condition, the proposed re-test period should be based on the real time data

2.1.7.1 General case

STUDY CONDITIONTIME
LT25°C ± 2°C/60% RH ± 5% RH or

30°C ± 2°C/65% RH ± 5% RH

12 Months 
INTERMEDIATE30°C ± 2°C/65% RH ± 5% RH6 Months
ACCELARATED40°C ± 2°C/75% RH ± 5% RH6 Months

2.1.7.2. Intended for storage in refrigerator

STUDY CONDITIONTIME
LT5°C ± 3°C12 Months 
ACCELARATED25°C ± 2°C/60% RH ± 5% RH6 Months

2.1.7.3. Drug substances intended for storage in a freezer

STUDY CONDITIONTIME
LT– 20°C ± 5°C12 Months 
2.1.8. Stability Commitment 1. If the submission includes data from stability studies on at least three batches, a commitment should be made to continue these studies through the proposed re-test period.

2. If  the  submission  includes  data  from  stability  studies  on  fewer  than  three batches, a commitment should be made to continue these studies through the proposed re-test period and to place additional production batches, to a total of at least three, on long term stability studies through the proposed re- test period.

3. If  the  submission  does  not  include  stability  data  on batches,  a commitment should be made to place the first three production batches on long term stability studies through the proposed re-test period.

2.1.9. Evaluation

The purpose is to establish, based on testing a minimum of three batches of the drug substance and evaluating the stability information. The data may show so little degradation and so little variability The purpose is to establish, based on testing a minimum of three batches of the drug product, a shelf life and label storage instructions applicable to all future batches of the drug product manufactured and packaged under similar circumstances.

2.1.10. Statements/Labeling

The statement should be based on the stability evaluation of the drug substance. The statement should be based on the stability evaluation of the drug product. An expiration date should be displayed on the container label.

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