How USP is Tackling Split Dosages

January 1, 2013
Pharmaceutical Technology Editors

The US Pharmacopeia (USP) is examining the issue of uniformity of dosage units to address whether scoring yields consistent split doses. Anthony DeStefano, Ph.D., senior vice-president, general chapters and healthcare quality standards, provides an overview of the USP's work in this area.

It is our understanding that USP is examining the issue of uniformity of dosage units to address whether scoring yields consistent split doses, and how stability and friability of the splits can best be evaluated. What is the status of USP’s work on this issue? What are the key goals?

There is a draft FDA guidance that discusses tablet-scoring issues from a quality-by-design perspective, with a focus on what manufacturers need to do to demonstrate that a scored tablet can be labelled as “functionally scored”. USP is interested in developing a general chapter that would provide a test that at a minimum would define postmarket specifications, such as weight variation requirements, for demonstrating that a tablet is functionally scored.

Is USP considering harmonizing its potential new chapter on this topic with requirements proposed by the European Pharmacopoeia (Pharm.Eur.)?

USP is looking into the possibility of developing a guideline chapter that deals with large sample sizes. The USP statistics expert committee and dosage form expert committee are aware of the Pharm. Eur. general chapter and are certainly evaluating it as they consider this topic. Harmonization, to the extent possible, with general chapters from the Pharm.Eur.and other key pharmacopeias is a goal for any new general chapter under development by USP.

What current challenges is the USP aware of regarding tablet scoring for the drug development and manufacturing industry?

USP has published a stimulus article in Pharmacopeia Forum 35 (6) (2009), which received mixed comments with concerns from a wide audience including manufacturers, practitioner associations, and academic professionals. The prevalence of tablet splitting was recognized as a fact and the comments were in general supportive of USP efforts to establish standards for scored tablets and the advisability of tablet splitting. A common thread was that the ability to subdivide a tablet is implied by the score. The Pharm. Eur. standard on tablet scoring is seen as a good start with the possibility of improvement. Concerns were expressed that without evidence that the drug is uniformly distributed across a tablet, the use of weight to evaluate the quality of split tablet portions may not be adequate.