Real-time stability

  • Use of the most appropriate stability-indicating methods
  • Design of a deliberate long-term, real-time, real-condition stability program
  • Shelf-life recommendation

Did you know that a specific guideline for stability testing of biotechnological/biological products – ICH Q5C – was developed by the ICH Expert Working Group in 1995?

Why a specific guideline for biological products?

  • Biologicals have a complex 3-dimensional structure, from primary to quaternary, which is important because the function of a protein is closely tied to its 3-dimensional structure.
  • Biological characteristics and activity are dependent on covalent as well as non-covalent interactions, such as ionic bonds, hydrogen bonds, van der Waals forces, and hydrophobic interactions.
  • Biologicals are particularly sensitive to environmental factors such as temperature changes, oxidation, light, ionic strength and shear.
  • Stringent conditions for storage are necessary to ensure maintenance of biological activity and to avoid degradation.

Stability data should be provided for drug substances, drug products, reconstituted freeze-dried products, and for critical intermediates to assure their stability within the bounds of the developed process.

The real-time stability study simulates the life of the commercial product. The biopharmaceutical product is stored under the long-term storage conditions defined by the producer. The evaluation of stability requires appropriate and product-specific analytical methods that profile the stability characteristics of the biopharmaceutical product:

Tests for purity typically include more than one stability-indicating assay and should focus on methods for determining degradation products, such as deamidation, oxidation, aggregation, adsorption, and loss of 3-dimensional structure. The purity value derived from the different purity methods is method–dependent.

Storage conditions

  • Storage temperature for biopharmaceuticals is confined to the proposed storage temperature.
  • Biopharmaceuticals are generally distributed in containers protecting them against humidity; and therefore, stability tests at different relative humidities can usually be omitted.
  • The necessity for photostability testing should be evaluated on a case-by-case basis.
  • If interactions between a liquid product and the container/closure cannot be excluded, the effect should be determined including samples maintained in the inverted or horizontal position as well as in the upright position.
  • Additional stability data is required for multiple-dose vials, taking the repeated insertions and withdrawals into account.

Lack of capacity in your drug discovery and development program? We design and carry out a deliberate long-term, real-time, real-condition stability program for your product and advise you concerning shelf-life at intermediate intervals.