SOP: Shelf-life Extension of Pharmaceutical Products

 

1. Purpose

To define the procedure for generating stability data, evaluating results, and submitting applications to regulatory authorities for the extension of product shelf-life.

2. Scope

Applicable to all commercial drug products manufactured at [Company Name] intended for global markets (EU, US, WHO, ROW).

3. Responsibility

  • Quality Assurance (QA): Approval of stability protocol, review of data, preparation of regulatory package.

  • Quality Control (QC): Execution of stability testing and data compilation.

  • Regulatory Affairs (RA): Preparation and submission of variation application to authorities.

  • Production & Warehouse: Ensure correct labeling and stock control after approval.

4. Procedure

Step 1 – Stability Study Design

  • Follow ICH Q1A (R2), WHO TRS 953, EMA/FDA guidelines.

  • Include:

    • Long-term: 25°C ± 2°C / 60% RH ± 5% RH (or climatic zone specific).

    • Accelerated: 40°C ± 2°C / 75% RH ± 5% RH.

    • Intermediate: 30°C ± 2°C / 65% RH ± 5% RH (if required).

  • Use 3 commercial-scale batches in market packaging.

Step 2 – Data Generation

  • Continue testing beyond currently approved shelf-life (e.g., 36M → test up to 48M).

  • Analyze: assay, degradation products, dissolution, pH, appearance, microbiological quality (if applicable).

  • Maintain records in stability logbook and electronic database.

Step 3 – Statistical Evaluation

  • Perform regression analysis as per ICH Q1E.

  • Confirm that all batches remain within specifications through proposed new expiry.

  • Document any out-of-trend (OOT) or out-of-specification (OOS) results.

Step 4 – Justification of Shelf-life

  • Prepare summary report including:

    • Product description (formulation, strength, pack).

    • Current approved shelf-life.

    • Stability data beyond expiry.

    • Statistical justification.

    • Risk assessment (no safety/efficacy impact).

Step 5 – Regulatory Filing

  • EU: Submit as Type IB or Type II variation depending on extension period.

  • US FDA: Submit as Prior Approval Supplement (PAS) if >6 months extension, or include in Annual Report if minor.

  • WHO / Local DRA: Submit as variation application with complete stability package.

Step 6 – Approval & Implementation

  • Await regulatory approval before updating packaging/label artwork.

  • QA to update expiry date in ERP system, batch records, and labeling SOPs.

  • Warehouse to relabel stock only after approval.

Step 7 – Exceptional Situations

  • In shortage/emergency, temporary extension may be granted by DRA upon request.

  • Requires at least real-time stability data supporting quality at new proposed expiry.

5. Records / Documents

  • Stability protocol & study plan.

  • Raw data & trend charts.

  • Stability summary report.

  • Regulatory submission package.

  • Approved variation letter from DRA.

6. References

  • ICH Q1A (R2), ICH Q1E

  • WHO TRS 953, Annex 2

  • EMA Guideline on Stability Testing

  • FDA Guidance for Industry: Stability Testing of Drug Substances and Products

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