SPLITTING THE DIFFERENCE. At Shamrock Medical, we have some past experience with tablet splitting.

To give you some background, in March 2013, the FDA issued a Guidance for Industry that provides recommendations to sponsors of new drug applications (NDAs) and abbreviated new drug applications (ANDAs). It outlines what criteria should be met when evaluating and labeling tablets that have been scored. Scoring facilitates the practice of tablet splitting. (Just a reminder: Previously, the FDA considered tablet scoring as an issue when determining whether a generic drug product is the same as the reference listed drug [RLD]. One characteristic of a tablet dosage form is that it may be manufactured with a score or scores.) As of this writing, the guidance does not establish legally enforceable responsibilities, but it details current thinking on the topic.

According to the FDA, this characteristic is useful because the score can be used to facilitate the splitting of the tablet into fractions when less than a full tablet is desired for a dose, although, presently, there are no standards or regulatory requirements that specifically address scoring of generic vs. RLD tablets.

The FDA goes on to say that, "Consistent scoring ensures that the patient is able to adjust the dose, by splitting the tablet, in the same manner as the RLD. This enables the patient to switch between products made by different manufacturers without encountering problems related to the dose. In addition, 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.

This, folks, is a considerable issue to consider.

A SHORT HISTORY CONTEMPLATING DRUG SPLITTINGThe Center for Drug Evaluation and Research (CDER) Drug Safety Oversight Board considered the practice of tablet splitting at its October 2009 and November 2010 meetings. During those meetings, they discussed how insurance companies and doctors are increasingly recommending that patients split tablets, either to adjust the patients’ dose or as a cost-saving measure. Because of this, the Agency conducted internal research on tablet splitting and concluded that in some cases, there are possible safety issues, especially when tablets are not scored or evaluated for splitting. The Agency’s concerns with splitting a tablet included variations in the tablet content, weight, disintegration, or dissolution,
which can affect how much drug is present in a split tablet and available for absorption. In addition, there may be stability issues with splitting tablets.

WHERE SHAMROCK MEDICAL STANDS ON THIS ISSUEIf you remember, drug repackagers used to split tabs for the customers, but the FDA said a split tab was a new drug, and required a new drug application, stability studies, etc. So we no longer split tabs. This guidance document may lay the groundwork for allowing drug repackagers to once again split tabs; but there are other outcomes to consider before the drug repackaging industry can feel comfortable with this concept.

These FDA recommendations on are not simply a matter of splitting a tablet. In my next post on this topic, I'll discuss the criteria that the industry would have to follow, and the pros and cons of this proposal by the FDA.

Here's to better solutions,　
Dave Bystrom