The present invention provides for pharmaceutical compositions comprising pancreatic enzyme preparations (PEPs) with viral infectivity reduced below significant levels and having high enzymatic activity. The PEPs can comprise lipases, proteases, amylases, non-enveloped viruses (e.g., porcine parvovirus (PPV), porcine circovirus type 2 (PCV-2), porcine encephalomyocarditis virus (EMCV)), and enveloped viruses (., vesicular stomatitis virus (VSV), and influenza A (IF A)). The present invention also includes methods of treating pancreatic insufficiency by administering these pharmaceutical compositions and methods of making the same by treating the PEP with beta-propiolactone (BPL) to reduce viral infectivity.