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The following message was posted to: PharmPK
Kindly forward my question to relevent group
I have a query on Understanding of Proportionally Similar Formulations
as per FDA
Guideline 5356fnl. The guideline says :
Scope 1 : All active and inactive ingredients are in exactly the
same proportion between different strengths (e.g., a tablet of 50-mg
strength has all the inactive ingredients, exactly half that of a
tablet of 100-mg strength, and twice that of a tablet of 25-mg
Scope 2 : Active and inactive ingredients are not in exactly the
same proportion between different strengths as stated above, but the
ratios of inactive ingredients to total weight of the dosage form are
within the limits defined by the SUPAC-IR and SUPAC-MR guidances (up
to Level II).
Scope 3 : For high potency drug substances, where the amount of the
active drug substance in the dosage form is relatively low, the total
weight of the dosage form remains nearly the same for all strengths
(within + 10 % of the total weight of the strength on which a biostudy
was performed), the same inactive ingredients are used for all
strengths, and the change in any strength is obtained by altering the
amount of the active ingredients and one or more of the inactive
ingredients. The changes in the inactive ingredients are within the
limits defined by the SUPAC-IR and SUPAC-MR guidances (up to Level
Exceptions : Exceptions to the above definitions may be possible, if
adequate justification is provided.
My Query is related to Scope 2/3 (Innovator capsule formulation data
is as below)
Strength Inactive/Total weight(%w/w) %> Difference to RLD
RLD (60mg) 77.7 % NA
Lower St 1 (25mg) 87.5% 9.8%
Lower St 2 (10mg) 95.0 % 17.3%
I intend to formulate formulations similar to Innovator in all respects.
If I prove BE of generic against Innovator RLD
I understand Biowaiver may be requested for Lower St 1 (40mg) under
Supac IR but what about Lower St 2 (10mg) where the diff is more than
10% as allowed by Supac Level -II.
F2 for all strengths against RLD is within 50-100
Therapeutic Linearity is claimed by Innovator.
Fill weights for innovator are 60mg -310mg, 25mg - 230mg, 10mg- 230mg
and only one inactive is present in the formulation.
May I go ahead with the formulations similar to Innovator or I need to
change Lower strength 2 (10mg) inactive to meet Supac Level - II.
If it is possible to get a waiver as per innovator formulation for
lower st 2 (10mg) what kind of supporting data may be required.
I am looking for suggested readings to know the basis of FDA guideline
development for further understanding.
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