1. Identify the Critical Quality Attributes
First, you must define what characteristics are critical for the product. Examples:
- Pharmaceuticals: potency, dissolution, appearance, sterility
- Food: microbiological safety, flavor, texture, nutrient content
- Cosmetics: consistency, microbial stability, color
2. Stability Studies
Shelf life is primarily determined by Stability Studies, which include:
a) Real-Time Stability Testing
- Store product in recommended storage conditions (e.g., 25 °C/60% RH).
- Periodically test samples over time (e.g., 0, 3, 6, 9, 12, 18, 24 months).
- This shows actual degradation over the intended shelf life.
b) Accelerated Stability Testing
- Store at higher stress conditions (e.g., 40 °C/75% RH).
- Helps predict degradation faster by simulating long-term conditions.
- Data from accelerated studies can be used to estimate shelf life using Arrhenius equations (rate of degradation vs. temperature).
c) Stress Testing
- Expose product to extreme conditions (light, heat, humidity) to understand degradation pathways and identify critical factors affecting stability.
3. Analytical Testing
At each time point, test samples to assess:
- Physical properties: appearance, phase separation, dissolution.
- Chemical properties: potency/assay, degradation products.
- Microbiological properties: microbial contamination.
- Packaging interaction: leachables or moisture ingress.
4. Data Analysis & Modeling
- Plot degradation data (e.g., % assay vs. time).
- Determine when the attribute crosses the acceptable specification limit.
- Apply statistical modeling to project the time when the product will fail criteria (this defines the shelf life).
Example:
- If potency must remain ≥90% and the trend line shows this will occur in 24 months, shelf life is set to 24 months.
5. Regulatory and Safety Considerations
- Regulatory agencies (e.g., FDA, EMA) have detailed guidance (ICH Q1A(R2)) for shelf life determination.
- Products may need multiple batches and different packaging configurations to be evaluated.
- Labels must reflect appropriate expiry dates.
6. Ongoing (Post-Market) Stability
- Even after launch, ongoing stability studies monitor products to ensure shelf life assignments remain valid.
- Reassessment may be needed if formulation or packaging changes.
Summary
Shelf life evaluation = Stability studies + Analytical testing + Modeling degradation + Regulatory compliance
Risk-Assessment-for-Shelf-Life-not-evaluated-on-the-Basis-of-Stability