Marketed drugs will not need to be tested under final guidelines on 'tablet scoring' for branded and generic medicines issued by the US Food and Drug Administration (FDA) this week.
In the new guidance the FDA calls for modified release products for which the control of drug release can be compromised by tablet splitting to not have a scoring feature.
Otherwise, delayed and modified release products should meet all of the same requirements as immediate release products, though they should also ensure dissolution is demonstrated at both ends of the hardness range and that the dissolution on whole versus split tablet portions should meet the similarity factor (f2) criteria.
The difference between the draft guidance and final version “isn’t terribly remarkable,” but it clarifies "what the FDA is expecting on delayed or modified released and coating,” Geoff Green, VP of business development at tablet scoring tech firm Accu-Break Pharmaceuticals, Inc., told In-Pharmatechnologist.com.
Green added that the big question going into the final guidance was whether companies would have to retroactively apply the scoring tests to products already on the market, but he noted that the FDA is “not asking companies to do that.”
He said that the point of the guidance is mainly to “prevent generic copies of drugs from having score marks that are non-functional” if the score marks were functional on their brand-name counterparts. “Patients relying on that score mark in the brand suddenly would switch over to the generic and the FDA couldn’t reliably say they were getting the same dose if [the generic tablet] was split.”
One of the challenges for manufacturers will be “to identify a robust formula that creates correct hardness and satisfies quality requirements for splitting,” Green added. “Being able to screen rapidly is key in order to test many formula, formats and options. The challenge here is to perform tests quickly.”
The final guidance also calls for scored tablets’ characteristics to meet the following criteria:
- The dosage amount meant to be achieved after splitting should not be below the minimum therapeutic dose indicated on the approved labelling;
- Split tablets should not pose any risk of unintended drug exposure;
- When stored in pharmacy dispensing containers, the split tablet should demonstrate adequate stability for a period of 90 days at 25º C, plus or minus 2ºC/60 percent Relative Humidity (RH), plus or minus 5 percent RH; and
- Split tablet portions should meet the same finished-product testing requirements as for a whole-tablet product with equivalent strength.
“As you get into coating, modified release and more than one score, the hurdle gets much higher [for a manufacturer] to prove [the score is] functional,” Green noted.
But perhaps a more prescient issue is whether patients will be able to actually use the functional scoring to split tablets effectively. Green notes that both the FDA and EMA (European Medicines Agency) considered whether representative patients, such as the elderly, should be the ones to test the efficacy of a tablet’s score.
Ultimately, the EMA, European Pharmacopeia FDA and USP (US Pharmacopeia) rejected the idea because it would be too onerous for manufacturers, and the final guidance remains “somewhat silent on who would do the testing” of the tablet scores, Green added.
Green noted that the final FDA guidance comes about a decade after the EMA issued its guidance and there are only “subtle differences” between the two documents.