The US Food and Drug Administration (FDA) is recommending drugs made by generic manufacturers closely mimic the physical attributes, including the size, shape and color, of the drugs they reference.
When FDA approves an abbreviated new drug application (ANDA), it does so primarily on the basis of a drug's bioequivalence to the Reference Listed Drug (RLD), the drug to which the generic is compared. Data must show a drug contains the same active ingredient, in the same dose, in the same physical form, and is administered through the same route of administration.
One of the few areas in which a generic drug may differ from the RLD is in its use of inactive ingredients, such as excipients, which also affect the look, texture, size and shape of a generic drug tablet.
But even so, FDA explained in a 2013 draft guidance document, Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules, there are limits to how physically different it will permit two bioequivalence drugs to be.
According to FDA, the problem is that consumers are affected when tablets and capsules have substantial physical differences relative to the RLD. A drug may be more difficult to swallow if it is much larger, has a different shape (e.g. sharp edges), or a different coating. Even the smell or appearance (e.g. color) of the drug tablet might affect patient adherence, FDA said.
"[We] are concerned that differences in physical characteristics (e.g., size and shape of the tablet or capsule) may affect patient compliance and acceptability of medication regimens or could lead to medication errors," FDA wrote in its guidance. "We believe these patient safety concerns are important, and we are recommending that generic drug manufacturers consider physical attributes when they develop quality target product profiles (QTPPs) for their generic product candidates," FDA added.
FDA has now issued final guidance regarding the size, shape and other physical characteristics of generic drugs. The final guidance is largely the same as the original draft guidance with the exception of a few editorial differences.
The guidance recommends tablets closely approximate the products they reference in size. For example, FDA recommends generic drugs not be larger than any drug already equal to or greater than 17 mm in its largest dimension. For drugs smaller than 17 mm, FDA recommends drugs be "no more than 20% larger than the RLD in any single dimension," and that no single dimension exceed 17 mm.
"Efforts should be made to develop tablets and capsules that are of a similar size 160 and shape to the RLD," FDA wrote. And in any event, no drug should exceed 22 mm in any dimension, the guidance adds.
Products should also be of "a similar shape" to the RLD, and have other physical similarities which make it as easy to swallow as the original. For example, a product's weight, surface area, tablet coating and disintegration time should all be similar.
Critically, the guidance only applies to new generic drug products submitted via an abbreviated new drug application (ANDA).
Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules (FR)