FDA today issued a draft guidance on factors relating to physical equivalence of generic products to the corresponding RLD (see here).
This promised draft guidance addresses Size, Shape, Other Physical Attributes, and Biowaivers for generics relative to the corresponding Reference product (the RLD) for orally administered Tablets and Capsules. A summary of the guidance recommendations follows.
Size
Where the RLD is less than of equal to 17 mm in the largest dimension, the generic should be no more than 20% larger than the RLD in any dimension and no larger than 17 mm in any dimension, and no greater than 40% in volume compared to the RLD.
Where the RLD is greater than 17 mm in its largest dimension, the generic should be no larger than the RLD in any single dimension or in volume.
The largest dimension of a tablet should not exceed 22 mm and the largest capsule should not exceed a standard 00 (indicated to be 23.3 mm long and 8.53 mm in diameter when locked).
Note that the above recommendations allow an increase in capsule shell size of one when the RLD is size 3 or less, and no increase without additional justification when the RLD is size 2 or greater.
Shape
In general, generics should be a similar shape or a shape that has been found easier to swallow when compared to the RLD shape. Tablets with larger cross sectional area are generally considered harder to swallow.
In making measurements to determine RLD volume and cross sectional areas, the guidance recommends using "spatial imaging or .. computer models".
The size and presumably the shape of a tablet or capsule should be provided at section 3.2.P.1 of the Common Technical Document.
Other Physical Attributes
Other physical attributes in this context includes things like tablet coatings, weight, surface area, disintegration time and propensity for swelling. These should be included in the QTPP and described in section 3.2.P.2 of the CTD. Although not stated as a recommendation, the effect of coating on ease of swallowing and preventing premature swelling and disintegration would presumably be considerations in this section.
Biowaivers
This part discusses proportional similarity in the context of biowaivers and "suggests" that "other" methods of proportional similarity may be more amenable to maintaining appropriate tablet sizes. This part also refers to the (now) old General Considerations Guidance which has just been superseded (for ANDAs at least) by the new "Bioequivalence Studies with Pharmacokinetic Endpoints" draft guidance. This new draft guidance has a slightly different section on similarity and biowaivers. We will have to wait to see if this is a case of "ships passing in the night" or whether they really mean to reference the General Considerations guidance.
In summary, the message here is clear - copy the brand!
