Abstract: The present invention provides improved methods to lyophilize (freeze-dry) active ingredients such as proteins, nucleic acids and viruses. The present methods improve the degree of excipient crystallization during lyophilization over prior methods. The improvement in excipient crystallization is based, in part, on a high-temperature annealing step is conducted prior to or at the same time as secondary drying. Importantly, the high-temperature annealing step does not destabilize active ingredients. Further, the high-temperature annealing step does not require sub-zero annealing steps prior to its enactment in order to provide complete excipient crystallization.