Case B: Low permeability, high solubility drugs if multipoint dissolution profile should be performed in the

application/compendial medium at 15, 30, 45, 60 and

120 minutes or until an asymptote is reached.

Case C: High permeability, low solubility drugs if multipoint dissolution profiles should be performed in water,

0.1 N HCl, and USP buffer media at pH 4.5, 6.5, and 7.5

(five separate profiles) for the proposed and currently

accepted formulations. Adequate sampling should be

performed at 15, 30, 45, 60, and 120 minutes until either

90% of drug from the drug product is dissolved or an

asymptote is reached.

3. In vivo bioequivalence None (if the drug product does not belong to any of the

documentation above-mentioned cases, then refer to level 3 changes)

Filing Documentation

i. Prior approval supplement (all information including accelerated stability data)

ii. Annual report (that includes long-term stability data and all other information)

Note: The test and filing documentation of level 2 depends upon three factors:

Solubility, permeability and therapeutic range of drug product.

SUPAC Guidelines and Platform Technology 31

c. Level 3

Definition: These are the changes that are likely to have a significant impact on the

quality or performance of formulations.

Examples:

i. Change in the technical grade of an excipients

ii. All changes in which drug is not meeting dissolution criteria of level 2 changes.

iii. Changes in the excipients as per the following per cent ranges (based on an

assumption that the drug substance in the formulation is 100% of as mentioned

on label/potency) are given in Table 3.5.

Table 3.5: Change in excipients (in %) as per SUPAC guidelines level 3

Name of excipients Percentage excipient of total target dosage form

weight (± n %)

Filler Beyond 10

Disintegrant

Starch Beyond 6

Other Beyond 2

Binder Beyond 1

Lubricant

Calcium or magnesium stearate Beyond 0.5

Other Beyond 2

Glidant

Talc Beyond 2