FDA’s Tablet Scoring Final Guidance Requires Generics To Be Same As Brand

Generic industry concerns that scoring conventions could create barriers to entry did not win out in final tablet scoring guidance; FDA says to contact it if the scoring convention is patent protected.

FDA has not changed requirements that tablet scoring for generics should be identical to their reference products in its final guidance, despite industry concerns that it could be used by brands to prevent competition.

FDA has said it has enforcement discretion to deal with patent issues if they arise, but the agency chose to offer no specific instruction in the final guidance on “Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation,” which was released March 13. Instead, generic sponsors are asked to call FDA.

“Where the scoring configuration is protected by patent, contact the Office of Generic Drugs for guidance,” the guidance document states.

Industry officials worried when FDA released its draft guidance on tablet scoring in August 2011 that forcing generics to apply identical scoring features as the reference product could become another weapon for brands to block competition.

The language could invite citizen petitions requiring an ANDA to match the scoring convention before it can be approved (Also see "FDA Takes Its Tablet-Scoring Guidance To An Advisory Committee" - Pink Sheet, 13 Jul, 2012.).

FDA maintained its argument in the final guidance that “consistent scoring ensures that the patient is able to adjust the dose, by splitting the tablet, in the same manner as the [reference listed drug].”

“Consistent scoring ensures that neither the generic product nor the RLD has an advantage in the marketplace because one is scored and one is not,” the final guidance says. The language is identical to the draft.

FDA cannot regulate tablet splitting, but can oversee scoring because it can be a factor in equivalence with the brand product. The agency wrote the guidance because there were no existing rules for tablet scoring or markings.

But just like the draft, the final guidance also did not answer questions about determining scoring equivalence (Also see "FDA Tablet Scoring Guidance Advises Testing Patient Ability To Split Pills" - Pink Sheet, 5 Sep, 2011.).

The agency will allow products meeting all requirements in the guidance to add a “functional scoring” term to the “Dosage Forms and Strengths” and “How Supplied” sections of their labels. The new term is intended to communicate to practitioners that the product has been evaluated and meets established criteria.

Products already marketed will be able to obtain the added labeling, if they complete an assessment and provide data for evaluation, according to the guidance. That provision also was unchanged from the draft.

The agency did not allow for non-functional scoring in the final guidance, indicating that products not meeting the criteria “should not have a scoring feature or any reference to scoring” in the label, including language like “bisected.”

Patient Testing Dropped, Stability Specs Unchanged

Sponsors will not be forced to test their proposed scoring conventions on patients who would take the drug. The agency eliminated a requirement that scored tablets be tested using actual patients to ensure they can be split correctly.

While the criteria seemed to make sense on paper, it appeared marked for deletion after an August 2012 advisory committee meeting, when several committee members said the test had too many logistical, statistical and practical problems to be useful.

Committee members said patient behavior is not controllable enough for the type of test required (Also see "Tablet Scoring Guidance Could Drop Patient Testing Recommendation" - Pink Sheet, 10 Aug, 2012.).

Stability requirements also were largely unchanged in the final guidance, despite questions by the advisory committee about applicability in the real world.

FDA will require split tablets to show stability for 90 days at 25°C, plus or minus 2°, and at 60% relative humidity, plus or minus 5%, when stored in pharmacy dispensing containers with no seal or desiccant.

The language was nearly identical to the draft, except that desiccant was added to the storage conditions. The draft also described the containers as standard high-density polyethylene pharmacy bottles and caps.

Advisory committee members wondered whether the 90-day requirement was relevant because dispensing can occur more than 90 days after a tablet is manufactured, but still voted in favor of keeping it.

FDA said it recommended the stability requirement because some patients were receiving pre-split tablets at the pharmacy (Also see "Split Tablet Stability Testing Leaves Advisory Panel Uniformly Puzzled" - Pink Sheet, 20 Aug, 2012.).

Split tablets must meet the same testing requirements as the whole tablet and FDA wants a risk assessment provided to justify the tests, just as in the draft guidance. Testing should be done on tablets split mechanically as well as by hand, according to the final guidance. Dissolution tests must be done on at least 12 individual tablet portions.

FDA also expanded its description of the splitability requirement. The final guidance states that 15 tablets should be tested to determine whether the loss of mass is less than 3% between the individual segments, compared to the whole tablet.

The draft said only that the sponsor should ensure a loss of mass less than 3%.

The advisory committee recommended that loss-of-mass as well as friability standards for split sections of scored tablets remain requirements.

USP Expected To Weigh In This Summer

The [US Pharmacopeia] is also expected to publish a new general chapter on tablet scoring this summer.

The organization said March 14 that the new chapter is expected to go into its journal, Pharmacopeial Forum, on July 1 and will be accompanied by an article explaining the related issues. Comments likely will be allowed until Sept. 30, after which it could be finalized or revisions could be made.

A 2009 journal article recommended that USP adopt European tablet scoring guidelines that already were in place (Also see "FDA’s Top-Four Tablet Scoring Concerns To Get Advisory Committee Review" - Pink Sheet, 7 Aug, 2012.).

A USP official said at the 2012 advisory committee meeting no decisions had been made about its position on the tablet scoring issue, but it was leaning toward following FDA guidance.