You are here: Home Lifecycle Management
Lifecycle Management

All eCTDs will require amendments or supplements, for example:

  • Submission of additional information requested by regulatory authorities during their review;
  • Changes to product information e.g. indications, dosing recommendations, precautions, warnings and other information relating to product safety;
  • Changes in manufacturing and quality control.

These activities are referred to as "lifecycle management". As mentioned previously, eCTDs are submitted as a series of discrete sequences.  The initial submission is sequence 0000, and each subsequent amendment or supplement is sequentially numbered e.g. 0001, 0002, 0003, 0004.  Each sequence only contains the new or changed information - existing information submitted in previous sequences is never resubmitted.

Each eCTD sequence is a collection of documents with an XML index file (sometimes referred to as a "backbone") that is essentially a "catalogue" or "inventory" of the contents of the sequence.  The XML index file contains inventory information on each document provided in the sequence, including its location (folder and filename) and its relationship (if any) to a corresponding document submitted in a previous sequence i.e. "new", "replace" or "append" (these are referred to as "operations").  In addition, the XML index can also include references to documents in earlier sequences that are no longer relevant and need to be marked as deleted (operation = "delete" ).

 Operation  Description  Example of usage
NEW Identifies the document as a brand new document, unrelated to any document submitted in any previous sequence Adding a new active substance manufacturer e.g. a set of documents for a new Section 3.2.S
REPLACE Identifies the document as a replacement for a document submitted in a previous sequence - the XML index refers back to the relevant index file for the previous sequence, in order to identify the document that is being replaced. Replacing the drug substance specification in Section 3.2.S.4.1 with an updated version
APPEND Identifies the document as an appendix to a document submitted in a previous sequence - the XML index refers back to the relevant index file for the previous sequence, in order to identify the document that is gaining the appendix Adding stability data tables for an additional time point to Section 3.2.P.8.3
DELETE Identifies a document in a previous sequence as being no longer relevant. Removing documents relating to an excipient in Module 3.2.P.4 that has been removed from the product during a reformulation.

 

A useful analogy: In January, a catalogue retailer sends out a new 200 page catalogue for its entire range, including price, description and stockroom location of every item. In June, the retailer sends a 1 page supplement as follows: "The electric drill on page 7 of our previous catalogue (cat no 2356) has been replaced with a new model (cat no 2367). The cuddly toy on page 50 (cat no 2367) has been discontinued. We have an exciting new range of Garden Gnomes (cat no 2225-7) pictured below."

The original catalogue is analogous to sequence 0000 in the eCTD - it is completely new and does not refer to any earlier catalogue. The supplementary catalogue is analogous to sequence 0001 - it just details the changes and refers back to the entries in the previous catalogue so that the customer knows exactly what has changed.