SOP for Stability Studies of Active Pharmaceutical Ingredients

Objective

To provide Guidance on how stability studies are conducted under different environmental conditions such as temperature, light, and humidity and to assign retest/expiry date as per the stability data.

Scope

This standard operating procedure applies to all the drug substances manufactured at the Active pharmaceutical ingredients division of PharmaInfo Limited.

Responsibility

Quality Control Chemist.

Accountability

HOD - Quality Control.

Procedure

The procedure shall be as follows

Introduction

• To provide guidance on how to conduct stability studies under various environmental conditions such as temperature and humidity in container closure systems simulated to dispatch containers.

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Selection of Batches

• Stability studies shall be conducted on at least three primary batches of the drug substance. The batches shall be manufactured to a minimum of pilot scale by the same synthetic route or commercially produced batches.

• One commercial batch shall be added to the long term stability of every year [add on batch].
• Reprocessing or reworking batches shall be kept for stability studies.
• Materials that undergo physical modification such as micronization should be kept for stability studies.
• If the batch uses recovery solvents in the manufacturing process one batch should be kept for stability study in order to evaluate their effect on the stability of the drug substance.
• Enter the details of batches selected in the Stability Programme Register.

Container Closure System

• The stability studies shall be conducted on the drug substance packed in a container closure system that simulates the market containers.
• Label the container with details.

Testing Frequency

• Testing frequency shall be determined based on the condition at which stability is performed.
• Accelerated: Accelerated stability shall be conducted at 0,1,2,3 and 6 months.
• Long-term: Long-term stability studies shall be carried out at intervals of every three months in the first year and every six months on the second year and every year in the third year on words. E.g.: 0, 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.
• Intermediate: Intermediate stability studies shall be carried out at 0,3,6,9 and 12 months, or up to 60 months.
• The periods shall be determined before carrying out the long-term stability studies and preparing the stability schedule as per format.
• For add-on batch use long-term stability testing frequency and prepare a schedule as per the format.

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Storage Conditions

• Identify the storage conditions based on the pharmacopeial data or literature information or R&D information. For add-on batches use long-term storage conditions.

For General Case

Accelerated Stability: Temperature: 40°C ± 2°C. Humidity: 75% ± 5% RH

Long-term Stability: Temperature: 25°C ± 2°C. Humidity: 60% ± 5% RH

For Drug Substances Stored in Refrigerator

Accelerated Stability: Temperature: 25°C ± 2°C. Humidity: 60% ± 5% RH

Long-term Stability: Temperature: 5°C ± 3°C. Humidity: 60% ± 5% RH

For Drug Substances Stored in a Freezer

Long-term Stability: Temperature: -20°C ± 5°C

Test(s) to be Performed

• Identify the test(s) to be performed in the stability studies under accelerated and long-term stability based on the drug substance specification.
• Stability-indicating test procedures that are validated should be used for analysis of the stability samples.

Sampling Quantity, Sampling, and Analysis Time Window

• Identify the number of samples to be taken for stability study for both accelerated and long term and record in the stability register.
• Remove the samples from the stability chambers on the due date of analysis as given in the stability schedule. If this is not possible follow this procedure

1. Remove the accelerated samples within 2 days of the due date of analysis.
2. Remove the Long-term samples within 4 days of the due date of analysis.

• Store the samples below 25°C in a desiccator dedicated to stability samples in the refrigerator between 2-8°C until analysis of the samples is performed.
• Perform the sampling as per the standard operating procedure of quality control.
• Analysis of the sample shall be performed on the due date or if not possible, follow this procedure.

1. Analyze the accelerated samples within 3 days of the due date.
2. The Long-term samples which are having below 12 months of stability shall be analyzed within 2 weeks of the due date.
3. The Long-term samples which are having than 12 months of stability shall be analyzed within 4 weeks of the due date

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Stability Protocol

• Prepare stability protocol after entering the details in the Stability Programme- Register.
• Protocol numbering shall be given as per the following format.

PS/OM/FP-01

PS: Stability Protocol

OM: Two letter code for product (OM for Omeprazole)

FP: Finished Product

01: Procedure Number

Stability Summary

• Compile the stability report as per format at the end of the stability studies.
• The numbering for stability report shall be

RS/OM/FP01

RS: Stability Report

OM: Two letter code for product (OM for Omeprazole)

FP: Finished Product

01: Procedure Number

Storage Statement(s)

• Storage statements shall be concluded based on the evaluation of stability data.

Evaluation of Stability Data:

• Evaluate the stability data after analysis. Record the data in the stability data.
• Compile the data in the format at each time point and sign off this document.
• If there is any out-of-specification result or failure to meet specification (significant change) in stability analysis, follow OOS standard operating procedure.

Destruction of Leftover Samples

• Destroy the sample leftovers after analysis. Follow the written procedure from the quality control department.

In case of Changes in the manufacturing process or site

• If minor changes are made in the manufacturing process, Samples from batches produced under each change shall be added to the stability program (one batch).
• If major changes are made in the manufacturing process, collect the samples from the new batches (three batches) and perform the stability like a new product. In such a case the protocol and report procedure number shall be changed.

• In case of manufacturing site change, evaluate the affect on stability of the drug substance by keeping one batch for stability.

Documents

Stability Programme- Register

Stability Protocol

Stability Report

Stability schedule

Stability Data

Stability Label

Revision History

Nil

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