Lyophilization, or freeze-drying, is a process by which a drug formulation is first frozen and then the ice is removed by
sublimation under a vacuum. For a lyophilized drug product, the residual moisture specification is a crucial component of
the data package for regulatory filing. A defined acceptable range of water content also provides flexibility in the manufacturing
process. Such data are usually generated by assessing product stability at various moisture levels.
Richard Bunnell, PhD
The moisture content of the product vial in stability studies is usually inferred from that determined for sister vials. Such
an approach raises two concerns. First, the moisture content of the vial in the stability study potentially may not be identical
to the reference sister vials due to vial-to-vial variability, and therefore, may be imprecise for resolving stability issues.
Second, moisture levels in the product being analyzed are usually generated by sorption of water (via exposure or equilibration) onto a previously highly dried sample, whereas the moisture in an actual product results from
incomplete desorption (during freeze-drying). Further data must be obtained to justify that each individual product stability
is the same no matter which method is used to introduce moisture, due to the unique properties of each product being evaluated.