USP Chapter <1049.1> Stability Studies for Biotechnological and Biological Products

USP Chapter <1049.1> is divided into several core areas that address the stability assessment of biologics - both in drug substance (DS) and drug product (DP) form - across all development phases.

1. Stability strategy and design

This chapter describes how stability programmes are designed based on storage conditions, product type (e.g. recombinant proteins, mAbs), product formulation and container. Long-term storage is usually at 5 °C or below, supplemented by accelerated (25 °C or 30 °C) and stress conditions (37 °C or 40 °C).

2. Life cycle-related application

Preclinical phase: Use of simple but meaningful studies, often with only one batch.

Early clinical phases: Real-time data is necessary, e.g. to support clinical shelf life claims and ensure patient safety.

Late clinical phases: Requires at least three batches from a commercially representative process.

Approval and market application: Includes comprehensive stability testing, including temperature cycles, agitation, light stability, cumulative studies and in-use scenarios.

3. Containers, storage conditions and material representativeness

This chapter emphasises the importance of representative primary packaging (e.g. glass vials, syringes) and its storage orientation (e.g. upright vs. inverted) which may affect product stability. Humidity control is important for certain types of packaging, such as semi-permeable bags.

4. Extended stability studies

Additional studies are recommended, such as: 

  • Temperature changes (e.g. transport conditions)
  • Agitation
  • Light stability
  • In-use stability (e.g. after reconstitution or application)
  • Studies on combination products (e.g. autoinjectors, on-body injectors)

5. Statistics and evaluation

Stability data are analysed using statistical models (e.g. linear, non-linear) to derive expiry dates with statistically justified confidence intervals. The chapter also distinguishes between shelf life estimation and stability trending and describes the procedure for out-of-trend (OOT) results.

6. Application for post-approval changes

Stability data support regulatory changes after market approval. This chapter provides approaches for risk-based reductions in the number, duration, or conditions of stability studies.

7. Validation and selection of test methods

Only stability-indicating methods that can detect changes are permitted. Special requirements apply to potency tests, e.g. in biological assays. Methods must be tailored to specific degradation pathways.

USP chapter <1049.1> from draft USP PF 51.4 provides comprehensive, practical guidance on conducting stability studies of biotechnology products. For full context and regulatory compliance, refer to the complete draft available on the official USP website. Public comments are accepted until 30 September 2025

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