EMA Ups Stability Data Required for Changes to Active Substances

The EMA is tightening stability testing requirements for drugmakers submitting applications for significant post-approval manufacturing changes that involve active substances.

The new requirements, published Apr. 10, apply to any change that could affect the quality, safety or efficacy of active substances used in a drug.

For substances known to be stable, drugmakers must submit three months of stability data on at least one pilot scale batch size. For substances known to be unstable, the requirements increase to six months of data on at least three pilot scale batch sizes, according to the new EMA guidelines.

If the quality characteristics of the active substance are altered in a way that may change the stability of the finished product, the agency asks for additional stability data on the finished product, in long-term and accelerated testing conditions, as well as six months of data on at least two batches of pilot scale batch size.

The guidelines also require six months of stability data for changes in:

• Immediate packaging of sterile and non-frozen biological/immunological active substances, as well as finished products with changes in storage conditions and shelf life, type, shape or dimension of the container;

• Manufacturers of starting materials, intermediate materials and reagents used to manufacture active substances;

• Excipients in finished products that may impact safety, quality or efficacy;

• Coating weight of oral dosage forms or capsule shells when coating is critical for the release mechanism of gastro-resistant, modified or prolonged-release pharmaceuticals;

• Concentration of a single-dose, total use parenteral product with the same amount of active substance per dose;

• Conventional and critical dosage forms for replacements or additions of manufacturing sites of finished products;

• Batch size of conventional and critical dosage forms relating to all other pharmaceutical forms manufactured via complex processes;

• Fill weight and volume of sterile single- or multi-dose parenteral products, including biological/immunological products.

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