Request 2082188 was opened four years ago with a similar request. In that time, the class has tripled in size to 30,000 lines and a single file over 1M.
The sheer size of the file, combined with the number of class properties, methods, and constants, poses problems even for the newest IDEs, and it's proven that large files are difficult for even the best programmers to maintain a handle on.
I have only begun to use TCPDF in a project, however my suggestion for splitting would be along the configuration/generation line. These are two distinctly different pieces of code that are currently intermixed, which makes it difficult for end-users to easily understand which pieces they should be using and which they (ostensibly) shouldn't (without a good deal of back-end knowledge).