Purpose

The purpose of this Standard Operating Procedure (SOP) is to provide a step-by-step process for initiating a stability study, ensuring that all necessary preparations and documentation are completed to comply with regulatory requirements.

Scope

This SOP applies to all stability studies conducted on drug substances and drug products within the pharmaceutical company’s facilities.

Responsibilities

• Stability Manager: Approve and oversee the initiation of stability studies.
• Stability Technicians: Prepare samples, set up stability chambers, and ensure compliance with the stability protocol.
• Quality Assurance (QA) Team: Review and approve the stability protocol and ensure adherence to SOP.

Procedure

1. Preparation of Stability Protocol:
   • Develop a detailed stability protocol including objectives, scope, sample details, storage conditions, and testing intervals.
   • Ensure the protocol is reviewed and approved by the Stability Manager and QA Team.
2. Sample Preparation:
   • Collect samples from the designated batch(es) according to the protocol.
   • Label samples with identification codes, batch numbers, and storage conditions.
   • Document the sample collection process and initial conditions.
3. Setting Up Stability Chambers:
   • Place samples in the appropriate stability chambers set to the specified temperature and humidity conditions.
   • Ensure stability chambers are calibrated and validated before use.
4. Initiating the Study:
   • Record the start date of the stability study in the stability protocol.
   • Begin monitoring the storage conditions and ensure continuous recording of environmental parameters.
5. Documentation and Monitoring:
   • Maintain detailed records of storage conditions, sample handling, and any deviations from the protocol.
   • Review and verify data regularly to ensure compliance with the stability protocol.

Abbreviations Used

• QA: Quality Assurance
• SOP: Standard Operating Procedure

Documents

• Stability Protocol Template
• Sample Labeling Guidelines
• Stability Chamber Calibration Records
• Environmental Monitoring Logs

References

• ICH Q1A(R2) Stability Testing of New Drug Substances and Products
• FDA Guidance for Industry: Stability Testing of Drug Substances and Drug Products

SOP Version

Version 1.0 – Effective Date: [Insert Date]

Purpose

The purpose of this Standard Operating Procedure (SOP) is to outline the essential components and format required for a stability protocol to ensure comprehensive and consistent documentation for stability studies.

Scope

This SOP applies to all stability protocols prepared for stability studies on drug substances and drug products within the pharmaceutical company’s facilities.

Responsibilities

• Stability Manager: Ensure the stability protocol includes all required sections and is reviewed and approved.
• Stability Technicians: Prepare the stability protocol according to this SOP and submit for review.
• Quality Assurance (QA) Team: Review and approve the stability protocol for accuracy and completeness.

Procedure

1. Title Page:
   • Title of the stability study.
   • Protocol number and version.
   • Effective date and approval signatures.
2. Table of Contents:
   • List all sections and appendices with page numbers.
3. Introduction:
   • Purpose and objectives of the stability study.
   • Scope of the study, including drug substance or product name, batch numbers, and intended market.
4. Study Design:
   • Details of storage conditions (e.g., temperature, humidity) and duration for each stability condition (e.g., long-term, accelerated).
   • Number of batches and sample sizes to be tested.
5. Test Parameters:
   • List of physical, chemical, microbiological, and other relevant tests to be performed.
   • Specifications and acceptance criteria for each test.
6. Sample Handling:
   • Procedures for sample collection, labeling, and storage before testing.
   • Schedule for sample testing at defined intervals.
7. Data Collection and Reporting:
   • Methods for recording and reporting test results.
   • Criteria for evaluating data and determining stability conclusions.
8. Deviations:
   • Procedures for documenting and handling deviations from the protocol.
9. References:
   • Cite any guidelines, regulatory documents, or scientific literature referenced in the protocol.
10. Appendices:
    • Include any supplementary information such as detailed procedures, additional data, or supporting documents.

Abbreviations Used

• QA: Quality Assurance
• SOP: Standard Operating Procedure

Documents

• Stability Study Plan Template
• Test Method SOPs
• Sample Labeling Guidelines

References

• ICH Q1A(R2) Stability Testing of New Drug Substances and Products
• FDA Guidance for Industry: Stability Testing of Drug Substances and Drug Products

SOP Version

Version 1.0 – Effective Date: [Insert Date]

Purpose

The purpose of this Standard Operating Procedure (SOP) is to define the process for setting the ‘start date’ for a stability study to ensure consistency and compliance with regulatory requirements.

Scope

This SOP applies to all stability studies conducted on drug substances and drug products within the pharmaceutical company’s facilities.

Responsibilities

• Stability Manager: Approve the ‘start date’ and ensure it aligns with the study protocol and regulatory requirements.
• Stability Technicians: Document the ‘start date’ and ensure all preparatory activities are completed before this date.
• Quality Assurance (QA) Team: Verify that the ‘start date’ is documented correctly and all pre-study requirements are met.

Procedure

1. Review Stability Protocol:
   • Ensure the stability protocol is finalized and approved by the Stability Manager and QA Team.
   • Confirm the protocol includes clear guidelines for setting the ‘start date’.
2. Sample Preparation and Collection:
   • Collect samples from the designated batch(es) according to the protocol.
   • Ensure samples are labeled and documented as per the stability protocol.
3. Completion of Preparatory Activities:
   • Verify that all stability chambers and equipment are calibrated and ready for use.
   • Ensure that all initial testing (e.g., T0 analysis) is completed and documented.
4. Setting the ‘Start Date’:
   • The ‘start date’ should be the date when the samples are placed into the designated stability chambers under specified conditions.
   • Document the ‘start date’ in the stability protocol and all relevant logs.
   • Notify relevant stakeholders (e.g., Stability Manager, QA Team) of the ‘start date’.
5. Documentation:
   • Record the ‘start date’ in the stability protocol, sample logs, and any other relevant documents.
   • Ensure all documentation is reviewed and approved by the Stability Manager and QA Team.

Abbreviations Used

• QA: Quality Assurance
• SOP: Standard Operating Procedure

Documents

• Stability Protocol
• Sample Collection and Labeling Records
• Stability Chamber Calibration Records
• Initial Testing (T0) Results

References

• ICH Q1A(R2) Stability Testing of New Drug Substances and Products
• FDA Guidance for Industry: Stability Testing of Drug Substances and Drug Products

SOP Version

Version 1.0 – Effective Date: [Insert Date]

Purpose

The purpose of this Standard Operating Procedure (SOP) is to outline the process for determining the ‘due dates’ for various milestones in a stability study protocol to ensure timely completion and regulatory compliance.

Scope

This SOP applies to all stability studies conducted on drug substances and drug products within the pharmaceutical company’s facilities.

Responsibilities

• Stability Manager: Approve the ‘due dates’ for the stability study and ensure they align with the overall project timeline.
• Stability Technicians: Document the ‘due dates’ and adhere to the established timeline.
• Quality Assurance (QA) Team: Verify that the ‘due dates’ are realistic and ensure compliance with regulatory requirements.

Procedure

1. Review Stability Protocol:
   • Ensure the stability protocol includes a detailed schedule with predefined milestones and activities.
2. Identify Key Milestones:
   • List all critical milestones in the stability study, such as sample collection, testing intervals, data review, and final reporting.
3. Define Timeframes for Testing Intervals:
   • Establish testing intervals based on regulatory guidelines and the specific requirements of the stability study (e.g., 1 month, 3 months, 6 months, 12 months).
4. Calculate Due Dates:
   • Determine the ‘start date’ of the stability study as per SOP for setting the ‘start date’.
   • Calculate ‘due dates’ for each testing interval from the ‘start date’.
   • Ensure sufficient time for sample analysis, data review, and reporting at each interval.
5. Document Due Dates:
   • Record all ‘due dates’ in the stability protocol and associated logs.
   • Update any project management tools or calendars to reflect these ‘due dates’.
6. Review and Approval:
   • Submit the calculated ‘due dates’ to the Stability Manager and QA Team for review and approval.
   • Make any necessary adjustments based on feedback and finalize the ‘due dates’.
7. Communication:
   • Communicate the finalized ‘due dates’ to all relevant stakeholders, including Stability Technicians, QA Team, and project managers.
   • Ensure all team members are aware of their responsibilities and deadlines.

Abbreviations Used

• QA: Quality Assurance
• SOP: Standard Operating Procedure

Documents

• Stability Protocol
• Testing Interval Schedule
• Project Management Tools/Calendars

References

• ICH Q1A(R2) Stability Testing of New Drug Substances and Products
• FDA Guidance for Industry: Stability Testing of Drug Substances and Drug Products

SOP Version

Version 1.0 – Effective Date: [Insert Date]

Purpose

The purpose of this Standard Operating Procedure (SOP) is to define the process for generating the initial Certificate of Analysis (CoA) at time zero (T0) for a stability study to ensure accurate and comprehensive documentation of the initial condition of the drug substance or product.

Scope

This SOP applies to all stability studies conducted on drug substances and drug products within the pharmaceutical company’s facilities, specifically focusing on the generation and documentation of the T0 Certificate of Analysis.

Responsibilities

• Stability Manager: Approve the initial CoA and ensure it aligns with regulatory requirements and study protocols.
• Analytical Chemists: Conduct the initial testing and generate the CoA for T0.
• Quality Assurance (QA) Team: Review and approve the initial CoA for accuracy and completeness.

Procedure

1. Review Stability Protocol:
   • Ensure the stability protocol specifies the tests and acceptance criteria for the initial analysis at T0.
2. Sample Collection:
   • Collect samples from the designated batch(es) according to the protocol.
   • Ensure samples are labeled and documented properly.
3. Conduct Initial Testing:
   • Perform all specified tests on the collected samples according to validated analytical methods.
   • Record all raw data and observations during testing.
4. Generate Certificate of Analysis:
   • Compile the results of the initial tests into a Certificate of Analysis.
   • Include the following information in the CoA:
     • Product name and batch number
     • Testing parameters and methods used
     • Results for each test
     • Acceptance criteria
     • Date of testing
     • Signature of the responsible analyst
5. Review and Approval:
   • Submit the CoA to the QA Team for review and approval.
   • Ensure the CoA is signed and dated by the QA representative.
6. Documentation:
   • Store the approved CoA in the stability study file and any relevant databases.
   • Ensure that copies of the CoA are available for regulatory inspections and internal audits.
7. Communication:
   • Distribute the approved CoA to relevant stakeholders, including the Stability Manager and project team.

Abbreviations Used

• CoA: Certificate of Analysis
• QA: Quality Assurance
• SOP: Standard Operating Procedure
• T0: Time Zero

Documents

• Stability Protocol
• Analytical Method SOPs
• Sample Collection and Labeling Records
• Initial Testing Raw Data

References

• ICH Q1A(R2) Stability Testing of New Drug Substances and Products
• FDA Guidance for Industry: Stability Testing of Drug Substances and Drug Products

SOP Version

Version 1.0 – Effective Date: [Insert Date]

Purpose

The purpose of this Standard Operating Procedure (SOP) is to define and document the study parameters for stability studies, ensuring consistency, accuracy, and regulatory compliance throughout the testing process.

Scope

This SOP applies to all stability studies conducted on drug substances and drug products within the pharmaceutical company’s facilities.

Responsibilities

• Stability Manager: Approve the study parameters and ensure they align with regulatory guidelines and study objectives.
• Stability Technicians: Implement and document the study parameters as specified in the stability protocol.
• Quality Assurance (QA) Team: Review and approve the study parameters for accuracy and completeness.

Procedure

1. Review Stability Protocol:
   • Ensure the stability protocol outlines the required study parameters and acceptance criteria.
2. Define Study Parameters:
   • List the physical, chemical, microbiological, and other relevant parameters to be tested.
   • Specify the methods and procedures for each parameter.
3. Temperature and Humidity Conditions:
   • Identify the storage conditions (e.g., 25°C/60% RH, 30°C/65% RH, 40°C/75% RH).
   • Define the duration for each storage condition (e.g., 1 month, 3 months, 6 months, 12 months).
4. Sampling Plan:
   • Detail the frequency and number of samples to be tested at each interval.
   • Specify the procedures for sample collection and labeling.
5. Test Methods:
   • Describe the analytical methods to be used for each parameter.
   • Ensure all methods are validated and documented.
6. Acceptance Criteria:
   • Define the acceptance criteria for each parameter based on regulatory guidelines and product specifications.
7. Documentation:
   • Record all study parameters in the stability protocol and associated logs.
   • Ensure all data is reviewed and approved by the Stability Manager and QA Team.
8. Review and Approval:
   • Submit the defined study parameters to the Stability Manager and QA Team for review and approval.
   • Make any necessary adjustments based on feedback and finalize the study parameters.
9. Communication:
   • Communicate the finalized study parameters to all relevant stakeholders, including Stability Technicians, QA Team, and project managers.

Abbreviations Used

• QA: Quality Assurance
• RH: Relative Humidity
• SOP: Standard Operating Procedure

Documents

• Stability Protocol
• Analytical Method SOPs
• Sample Collection and Labeling Records
• Validation Reports

References

• ICH Q1A(R2) Stability Testing of New Drug Substances and Products
• FDA Guidance for Industry: Stability Testing of Drug Substances and Drug Products

SOP Version

Version 1.0 – Effective Date: [Insert Date]

Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish the process for setting limits for check specifications in a stability study to ensure consistency, accuracy, and compliance with regulatory requirements.

Scope

This SOP applies to all stability studies conducted on drug substances and drug products within the pharmaceutical company’s facilities.

Responsibilities

• Stability Manager: Approve the limits for check specifications and ensure they align with regulatory guidelines and product specifications.
• Analytical Chemists: Implement and document the check specifications as specified in the stability protocol.
• Quality Assurance (QA) Team: Review and approve the check specifications for accuracy and completeness.

Procedure

1. Review Regulatory Guidelines:
   • Ensure compliance with relevant regulatory guidelines such as ICH Q1A(R2) and FDA guidelines.
2. Identify Critical Quality Attributes (CQAs):
   • Determine the key quality attributes of the drug substance or product that need to be monitored during stability testing.
3. Set Initial Specifications:
   • Define initial specifications based on product development data, historical data, and regulatory requirements.
   • Include specifications for physical, chemical, microbiological, and other relevant attributes.
4. Establish Acceptance Criteria:
   • Set acceptable limits for each identified CQA based on stability data and regulatory guidelines.
   • Ensure the acceptance criteria are stringent enough to detect any significant changes in the product quality over time.
5. Review and Approval:
   • Submit the proposed specifications and acceptance criteria to the Stability Manager and QA Team for review and approval.
   • Make any necessary adjustments based on feedback and finalize the specifications.
6. Document Specifications:
   • Record the final approved specifications in the stability protocol and associated logs.
   • Ensure all documentation is reviewed and approved by the Stability Manager and QA Team.
7. Monitoring and Re-evaluation:
   • Regularly review stability data to ensure the specifications remain appropriate and effective.
   • Re-evaluate and adjust the specifications as necessary based on new data or changes in regulatory guidelines.
8. Communication:
   • Communicate the finalized specifications and any subsequent changes to all relevant stakeholders, including Stability Technicians, QA Team, and project managers.

Abbreviations Used

• CQA: Critical Quality Attribute
• QA: Quality Assurance
• SOP: Standard Operating Procedure

Documents

• Stability Protocol
• Product Development Reports
• Historical Data Records
• Regulatory Guidelines

References

• ICH Q1A(R2) Stability Testing of New Drug Substances and Products
• FDA Guidance for Industry: Stability Testing of Drug Substances and Drug Products

SOP Version

Version 1.0 – Effective Date: [Insert Date]

Preparing a Schedule for Withdrawal of Stability Samples Completing Storage Period

Purpose

The purpose of this SOP is to outline the procedure for preparing a schedule for the withdrawal of stability samples that have completed their designated storage period.

Scope

This SOP applies to all stability studies conducted within the pharmaceutical company where samples are withdrawn at specific intervals for testing.

Responsibilities

• Stability Coordinator: Responsible for creating and maintaining the withdrawal schedule.
• Quality Control (QC) Department: Responsible for withdrawing the samples as per the schedule and performing the necessary tests.
• Quality Assurance (QA) Department: Responsible for reviewing and approving the withdrawal schedule and ensuring compliance with the SOP.

Procedure

1. Review Stability Study Protocol

• Obtain the stability study protocol for each product under stability testing.
• Identify the specified storage conditions and test intervals for each product.

2. Prepare Withdrawal Schedule

• Create a master schedule in a tabular format that includes:
  • Product Name
  • Batch Number
  • Storage Condition
  • Start Date of Stability Study
  • Scheduled Withdrawal Dates (e.g., T0, 1 month, 3 months, 6 months, etc.)
• Ensure that the schedule covers all required intervals as per the stability study protocol.
• Use software or a spreadsheet to track and update the schedule as needed.

3. Schedule Review and Approval

• Submit the prepared schedule to the QA department for review and approval.
• Ensure that any changes or updates to the schedule are communicated to all relevant departments.

4. Sample Withdrawal

• QC department withdraws samples on the scheduled dates.
• Ensure samples are labeled correctly and stored under appropriate conditions until testing.

5. Record Keeping

• Document each withdrawal in the stability study logbook.
• Record the date, time, and initials of the person performing the withdrawal.
• Note any deviations or issues encountered during the withdrawal process.

Abbreviations

• QC: Quality Control
• QA: Quality Assurance

Documents

• Stability Study Protocol
• Stability Study Logbook
• Withdrawal Schedule

References

• ICH Q1A(R2): Stability Testing of New Drug Substances and Products
• Company SOP on Stability Testing

SOP Version

Version: 1.0

Effective Date: [Insert Date]

Purpose

The purpose of this Standard Operating Procedure (SOP) is to outline the process for determining the number and size of batches required for stability testing to ensure representativeness, consistency, and regulatory compliance.

Scope

This SOP applies to all stability studies conducted on drug substances and drug products within the pharmaceutical company’s facilities.

Responsibilities

• Stability Manager: Approve the number and size of batches for stability testing and ensure they align with regulatory guidelines and study objectives.
• Production Manager: Coordinate the production of batches as per the stability study requirements.
• Quality Assurance (QA) Team: Review and approve the batch selection for accuracy and completeness.

Procedure

1. Review Regulatory Guidelines:
   • Ensure compliance with relevant regulatory guidelines such as ICH Q1A(R2) and FDA guidelines for stability testing.
2. Determine Batch Size:
   • Identify the intended market batch size and scale down proportionally for stability testing if necessary.
   • Ensure that the batch size is sufficient to provide samples for all testing intervals.
3. Select Number of Batches:
   • For new drug substances and products, typically select a minimum of three production batches.
   • For established drug substances and products, use at least one production batch unless otherwise justified.
4. Produce Batches:
   • Coordinate with the production team to manufacture the required number of batches.
   • Ensure that each batch is produced under consistent conditions to ensure comparability.
5. Sample Collection:
   • Collect samples from each batch according to the stability protocol.
   • Ensure samples are labeled and documented properly.
6. Document Batch Information:
   • Record the batch number, size, and production date for each batch in the stability protocol.
   • Include information on any deviations or special conditions during production.
7. Review and Approval:
   • Submit the batch information to the Stability Manager and QA Team for review and approval.
   • Make any necessary adjustments based on feedback and finalize the batch selection.
8. Storage and Monitoring:
   • Store the batches under the specified stability conditions.
   • Monitor the storage conditions and ensure compliance with the stability protocol.

Abbreviations Used

• QA: Quality Assurance
• SOP: Standard Operating Procedure

Documents

• Stability Protocol
• Batch Production Records
• Sample Collection and Labeling Records
• Regulatory Guidelines

References

• ICH Q1A(R2) Stability Testing of New Drug Substances and Products
• FDA Guidance for Industry: Stability Testing of Drug Substances and Drug Products

SOP Version

Version 1.0 – Effective Date: [Insert Date]

Purpose

The purpose of this Standard Operating Procedure (SOP) is to define the process for determining the number of samples required for performing stability tests to ensure adequate and representative sampling throughout the study duration.

Scope

This SOP applies to all stability studies conducted on drug substances and drug products within the pharmaceutical company’s facilities.

Responsibilities

• Stability Manager: Approve the number of samples required for stability testing and ensure they align with regulatory guidelines and study objectives.
• Stability Technicians: Implement and document the sampling process as specified in the stability protocol.
• Quality Assurance (QA) Team: Review and approve the sampling plan for accuracy and completeness.

Procedure

1. Review Stability Protocol:
   • Ensure the stability protocol specifies the number of samples required for each test interval and storage condition.
2. Determine Sampling Points:
   • Identify the time points for stability testing (e.g., 0, 3, 6, 9, 12, 18, 24 months).
   • Ensure sampling points align with regulatory guidelines and product stability profile.
3. Calculate Sample Quantity:
   • Determine the number of samples needed per time point for each batch and storage condition.
   • Consider additional samples for reserve, repeat tests, and potential OOS (Out of Specification) investigations.
4. Sample Collection:
   • Collect samples from each batch at the specified time points according to the stability protocol.
   • Ensure samples are labeled and documented properly.
5. Storage of Samples:
   • Store collected samples under the specified stability conditions until testing.
   • Ensure that storage conditions are monitored and documented.
6. Documentation:
   • Record the number of samples collected for each time point and storage condition in the stability protocol and associated logs.
   • Ensure all documentation is reviewed and approved by the Stability Manager and QA Team.
7. Review and Approval:
   • Submit the sampling plan to the Stability Manager and QA Team for review and approval.
   • Make any necessary adjustments based on feedback and finalize the sampling plan.
8. Communication:
   • Communicate the finalized sampling plan to all relevant stakeholders, including Stability Technicians, QA Team, and project managers.

Abbreviations Used

• QA: Quality Assurance
• OOS: Out of Specification
• SOP: Standard Operating Procedure

Documents

• Stability Protocol
• Sample Collection and Labeling Records
• Storage Condition Logs
• Regulatory Guidelines

References

• ICH Q1A(R2) Stability Testing of New Drug Substances and Products
• FDA Guidance for Industry: Stability Testing of Drug Substances and Drug Products

SOP Version

Version 1.0 – Effective Date: [Insert Date]