SOP for Stability Study of Products

OBJECTIVE

To lay down the procedure for the Selection of batches, Sample Requirement, Initiation, Monitoring, Evaluation of Stability Study, and Preconditioning stability study of Drug Products.

SCOPE

This SOP shall be applicable for the Selection of batches, Sample Requirement, Initiation, Monitoring, and Evaluation of the Stability Study of Drug Products manufactured at PharmaInfo Limited.

RESPONSIBILITY

Initiation - Chemist & above-QA Department

Execution- Chemist & above-QC Department.

Checking- Asst. Manager & above-QC & QA Department.

PROCEDURE

Selection of batches:

For existing products:

• 1st optimization batch for LT and ACC,
• 1st validation batch for LT and ACC.
• 2nd and 3rd validation batches for ACC only.

For New products: 

• 1st optimization batch for LT and ACC,
• Three validation batches for LT and ACC.

For on-going stability study: 

• If the stability study of three batches has been completed for a particular product with an existing formulation that is found stable, a minimum one batch for every alternative year shall be kept for long-term stability study

ALSO READ: SOP for Stability Studies of Active Pharmaceutical Ingredients

Initiation

• QA shall initiate the stability study and the batches selected for the stability study through the stability study intimation sheet as per the format given in Annexure-3.
• A stability study protocol shall be prepared and approved for each product as per annexure-1.
• The numbering of the protocol shall be given as SP/X/YYY/ZZ Where, SP: Stability Protocol, X: Product Code, YYYY: Serial no starting from 001, ZZ: Serial no for same product starting from 00
• The chemist and above of the QC department shall review and receive the intimation slip along with stability samples and acknowledge the same.
• Chemists and above shall check the finished product release date. The initial finished product analysis result shall be considered as initial (0 month) stability data. If the stability study is initiated after more than 30 days of the initial analysis date, reanalysis must be done for “0” months (only instrumental tests that are listed in the stability protocol/stability information sheet).
• The chemist and above shall make an entry in the “MASTER STABILITY SCHEDULE” register as per Annexure No.-2 after receiving the stability samples.
• Prepare the “STABILTY SAMPLE LABEL” as per Annexure No.-4 and affix it on the sample container. Incubate the samples as per the required storage conditions mentioned in the intimation slip for stability study.
• Prepared the monthly schedule from the master schedule. According to the “MONTHLY STABILITY SCHEDULE,” concerned person shall schedule the analysis planning for the product being analyzed

Monitoring:

• The stability chemist shall arrange for the photocopy and issuance of the Stability Datasheet for the due product.
• Due dates are to be calculated according to the kept-on date e.g. for accelerated conditions if a sample is kept on the 21st of January then its 1st month due shall be 21st of February. For long-term conditions, if a sample is kept on 21st of January then its 3rd month due shall be 21st of April. The sample withdrawal date shall be 3 days before and after the due date. During closure periods (Holidays and factory closure) sampling will be performed after the due date. And if the sample analysis is not planned till then, then it should be stored in the refrigerator.
• The chemist shall withdraw the samples as required.
• QC chemist shall make entry of the sample withdrawn in “Stability Sample Reconciliation and Destruction Form as per Annexure No.-7.
• In case if any stability station is missed, Analysis for the next subsequent stability station or any other station shall be conducted and the actual date of analysis shall be mentioned in the Stability Summary Report as per Annexure No.-5. Missed stability station shall be mentioned as “Missed station” in the Stability Summary Report.
• The analysis shall be done as per the respective Standard Test Procedure and enter the raw data in the respective datasheet.
• The analysis must be completed within 15 days from the sample withdrawal dates for the accelerated study and within 21 days for long-term stability study. Analysis, which requires extended time, shall be justified.
• On completion of analysis of all tests, the chemist shall give the stability report for checking along with the raw data to the designated person.
• After checking and approval of stability reports the concerned person shall enter the results in the stability summary report and remarks shall be given by comparing the results obtained with the evaluation parameters and from the previous stability summary report. The actual date should be mentioned in the summary report in case of missed/delayed analysis.
• On completion of the stability schedule analysis (all stations) of a particular batch, the Head of the Quality Control Department or his Designee shall give remarks by evaluating all results generated against the remarks.

ALSO READ: SOP for Operation and Calibration Procedure for Stability Chamber

Temperature and humidity monitoring:

• The actual temperature and humidity should be monitored during stability storage to avoid any excursions.
• The excursions during the storage conditions should be reported & if it is more than 24 hours then suitable corrective & preventive action shall be taken. If instrument malfunction is observed then switch off the instrument and inform the engineering department for rectification if the instrument is not rectified within 48 hours then shift the samples to another location or chamber.
• If the temperature exceeds 10°C more than the set value for more than 24 hours because of malfunctioning of the equipment, then the study may be discontinued.

Evaluation - Handling of Significant Changes and Failure:

• Significant changes are defined as follows:

1. 5% potency loss from the initial assay value of the batch.
2. Any specified degradant exceeding its specification limit.
3. The product exceeds its pH limits.
4. Dissolution exceeding the specification limit of 12 capsules or tablets.
5. Failure to meet specifications for appearance and physical properties.

• In case any significant change occurs, the Head QC & QA or his Designee shall evaluate the data and confirm significant changes/failure, & shall suggest additional testing as follows.
• In case significant change occurs in accelerated conditions, samples from real-time shall be withdrawn in triplicate for analysis.
• If a sample does not meet the specifications, the Head QC or his Designee shall investigate the out-of-specification (OOS) results and a final conclusion shall be given by the Head of Quality Assurance.
• Head Quality Assurance shall discuss with the technical group comprising of the Plant Head, Head Production, and Head QC to take joint decision for recall/ revision of formulation/revision in product storage conditions

ABBREVIATION

SOP: Standard Operating Procedure

Asst.: Assistant

No.: Number

Qty.: Quantity

QA: Quality Assurance

QC: Quality Control

BOM: Bill of Material

BMR: Batch Manufacturing Record

Mfg.: Manufacturing

ACC: Accelerated

LT: Long term

ANNEXURE

Annexure No.-1: Stability study protocol

Annexure No.-2: Master stability schedule

Annexure No.-3: Sample Intimation slip

Annexure No.-4: Stability sample label

Annexure No.-5: Stability summary report

Annexure No.-6: Monthly stability schedule

Annexure No.-7: Stability sample reconciliation and destruction form

REVISION HISTORY

Nil

ALSO READ: Bracketing and Matrixing for Stability Testing in Pharmaceuticals