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I assume that apart from having a large file size (frankly 50 Mb does not sound excessive), you are updating a large number of documents.
1) keep down the memory usage. if you are dealing with more than 100000 documents at a time try to avoid large arrays or lists of that size that track processed documents
2) release each NotesDocument once you are done
3) if you do view lookups and your views do not change during the agent run, make sure to set NotesView.Autoupdate = False
4) also make sure to cache any lookups and minimize their number, keep your lookup views global and do not release until done
5) do not update documents unnecessary - make sure that the doc is really changed before you save it
6) do not use NotesDocumentCollection.getNthDocument() unless you get collection from FTSearch
7) avoid using Search to obtain documents if you can build a view instead; though in some cases Search is pretty efficient way to get a few docs from a large db.
Feedback response number WEBB959T4C created by ~Gus Opfoolitnivu on 02/25/2013