We want to use transaction VK12 to add a lot of material records to the system and then use VA42  to update several fields for these materials. What is the best solution to do this with InputAssistant? To create an EXCEL-file and import the file in VA42 (any limits in number of items?) or to create hundreds of variables to save the material number in VK12 and pick them up in VA42?

A good approach is to use a file (CSV format = comma delimited variables) to save and then read the material numbers. You can use the Windows temp directory "&%[temp]"  (=environment variable temp) as file location. Variables are possible. However, if you want to avoid files, I would prefer CopyText to add the material numbers to a long text (kept in memory). But files are better, since in case of system failures the file can be read again, but variables or long texts are lost. It might be necessary to write a second file while reading the material numbers in order to  be able to restart the process without redoing everything all over again.