The therapeutic area is an attribute of the RPI, not the substance. An RPI can contain more than one substance, and two different RPIs containing the same substance may be aimed at different therapeutic area.
The RPI is used to track the product development across separate EMA procedures in the lifecycle, at present ITF, orphan designation and scientific advice, that have the same development product in common. Therefore, the RPI tracks all therapeutic areas in which the product has been, is being, or is likely to be developed. It does not apply to just a single procedure. For this reason, it is not possible to remove a therapeutic area once a request for a new RPI has been submitted, or in the course of a new submission for that RPI. Similar considerations apply for the enabling technologies associated to an RPI.
However, it is possible to add one or more enabling technologies or therapeutic areas, during the creation of a new Scientific Advice submission, if the product development now addresses them, and they need to be discussed in the new procedure. Addition is voluntary. The same feature will also be added, in future, to Orphan submissions.