The guidance from April outlines the stability testing requirements for variations to a marketing authorization, noting specifically how much stability data is necessary for certain variations to manufacturing processes. For instance, if the quality characteristics or impurity profile of an active substance is changed in a way that may impact stability, six months stability data on at least two batches of at least pilot scale batch size are required.
Overall, EFPIA says that the proposed guideline “does not differentiate enough between stable/unstable products or conventional/critical dosage forms when defining specific stability requirements.”
But the EMA disagrees, stating simply and without further elaboration: “The guideline sufficiently differentiates between stable/unstable products or conventional/critical dosage forms.”
The EMA also rejected the association’s comment that the guidance should specifically state “that the assessment as to whether a change will have an impact on stability does not have to rely on formal stability studies, if science/risk-based approach is taken and enhanced product knowledge and process understanding is demonstrated.”
But the agency said that it agrees with EFPIA that there should not be an automatic expectation that six months data are required to support some changes. Six months’ data may not always be necessary, the agency and association agreed. The association and EMA also seemed to agree that if an active substance is known to be stable and there is no indication that stability is compromised, data from formal stability studies should not be needed for either the active substance or the resulting drug product.
The EMA also agreed with EFPIA’s suggestion that examples given relating to type II changes should be “carefully worded to avoid confusion.”
As far as the EGA is concerned, the EMA accepted the group’s proposal “to use the wording ‘of at least pilot scale’ batches” throughout the whole document to clarify that as the minimum size, especially for finished dosage forms.
But the EMA rejected the EGA’s call to include a glossary of terms “explaining some of the new terms used and, wherever possible, the terminology should be harmonised with that already in the variation guideline.”
For example, the EGA says, “it is not clear what the term ‘conventional dosage form’ encompasses.”