In cases where a manufacturing change(s) results in a product with structural and/or bioactivity differences, and/or differences in pharmacokinetics patterns, and those differences are meaningful with respect to potential impact on the product's safety, purity, or potency (efficacy) -

Additional clinical study(ies) may be needed

The manufacturing change will not be approved by FDA

An animal study comparing PKPD may suffice

None of the above