Stability testing requirements for Pharmaceuticals and Medical Devices

Development phase

Accelerated stability tests provide a means of comparing alternative formula-dons, packaging materials, and/or manufacturing processes in short-term experiments. As soon as the final formulation and manufacturing process have been established, the manufacturer carries out a series of accelerated stability tests which will enable the stability of the drug product or medical device to be predicted. From this, its shelf-life and storage conditions can be determined. Real-time studies must be started at the same time for confirmation purposes. Suitable measures should be taken to establish the utilization period for preparations in multi-dose containers, especially for topical use.

 

Registration dossier

The drug regulatory authority will require the manufacturer to submit information on the stability of the product derived from tests on the final dosage. The tests must be completed on the product while in its final container and packaging. The data submitted is obtained from both accelerated and real-time studies. Published and/or recently obtained experimental supporting stability data may also be submitted, e.g. on the stability of active ingredients and related formulations.

Where the product is to be diluted or reconstituted before being administered to the patient (e.g. a powder for injection or a concentrate for oral suspension), “in use” stability data must be submitted to support the recommended storage time and conditions for those dosage forms.

With the approval of the drug regulatory authority, a tentative (provisional) shelf-life is often established, provided that the manufacturer has undertaken, by virtue of a signed statement, to continue and complete the required studies and to submit the results to the registration authority.

 

Post-registration period

The manufacturer must carry out on-going real-time stability studies to substantiate the expiry date and the storage conditions previously projected. The data needed to confirm a tentative shelf-life must be submitted to the registration body. Other results of on-going stability studies are verified in the course of GMP inspections. To ensure the quality and safety of products with particular reference to degradation, national health authorities should monitor the stability and quality of preparations on the market by means of a follow-up inspection and testing programme.

Once the product has been registered, additional stability studies are required whenever major modifications are made to the formulation, manufacturing process, packaging or method of preparation. The results of these studies must be communicated to the competent drug regulatory authorities.

 

Table 1. Main objectives of stability testing

Objective Type of study Use
To select adequate (from the viewpoint of stability)

formulations and container-closure systems

Accelerated Development of the product
To determine shelf-life and storage conditions Accelerated and real-time Development of the product and of the registration dossier
To substantiate the claimed shelf-life Real-time Registration dossier
To verify that no changes have been introduced

in the formulation or manufacturing process

that can adversely affect the stability of the product

Accelerated and real-time Quality assurance in general, including quality control