In draft guidance published a year ago the US Food and Drug Administration (FDA) recommended an upper size limit of 2mm for beads delivered by sprinkling on soft food and swallowing. However, the industry called for a higher limit, more in line with Europe, and the FDA has accepted its thinking.
“The Agency recommends a target bead size up to 2.5mm with no more than 10 per cent variation over this size, to a maximum size of 2.8mm”, the FDA wrote in final guidance released this week.
Raising the maximum size moves the FDA guidance closer to European recommendations and fits with research into the size food is chewed to before swallowing. The revision should please some pharmaceutical companies that questioned the 2mm limit in the months following draft guidance.
“Novartis experience with an immediate release commercial product of a bead size somewhat greater than 2mm has been positive. In fact, the dosage form is being considered for global development of a paediatric dosage form, based upon its ease of use by the patient”, the Swiss firm wrote to the FDA.
In some cases the FDA may allow companies to exceed the 2.8mm maximum size. To justify use of a bigger bead the company should give the FDA data showing the product can be swallowed without chewing.
Chewing uniformity
Inadvertently chewing a bead could impact compliance by changing the taste, safety, or efficacy of the treatment. As such, the FDA is willing to use its regulatory powers to stop it happening.
Generics companies discovered this when submitting ANDAs (abbreviated new drug applications) for copies with fewer beads than the reference product, law firm Hyman, Phelps & McNamara reports. The FDA responded to the submissions by sending refuse-to-receive letters to the companies.