Substantial Modifications and Amendments

CHANGES TO THE INVESTIGATIONAL MEDICINAL PRODUCT WITH A NEED TO REQUEST A SUBSTANTIAL AMENDMENT TO THE IMPD

The European Medicines Agency (EMEA) provides detailed guidance for notification to the competent authorities regarding changes to an IMP’s Product Specification File as the development of the product proceeds.

In this guidance, the EMEA lists examples of changes to IMP quality data that are to be be regarded as “substantial” where they are likely to have a significant impact on one or more of the following criteria:

•  the safety or physical or mental integrity of the patients;

•  the scientific values of the trial;

•  the conduct or management of the trial;

•  the quality or safety of any IMP used in the trial.

Although the following list is not exhaustive, substantial changes to the IMP’s quality data are likely to be caused by changes concerning one or more of the following:

•  Importation of the medicinal product

•  Change of name or code of IMPs

•  Immediate packaging material

•  Manufacturer(s) of drug substance

•  Manufacturing process of the drug substance

•  Specifications of active substance

•  Manufacture of the medicinal product

•  Specification (release or shelf-life) of the medicinal product

•  Specification of excipients where these may affect product performance

•  Shelf-life including after first opening and reconstitution

•  Major change to the formulation

•  Storage conditions

•  Test procedures of active substance

•  Test procedures of the medicinal product

•  Test procedures of non-pharmacopoeial excipients

Source: EMEA, For more information visit: