FDA Issues Draft Guidance on Critical Quality Attributes for Chewable Tablets

Regulatory News

The US Food and Drug Administration (FDA) on Thursday issued new draft guidance covering the quality attributes drugmakers should consider when developing chewable tablets.

The guidance also includes recommendations for what information drugmakers should include when submitting developmental, manufacturing and labeling information to FDA.

FDA says the new guidance is needed, as "numerous approved drug product applications for chewable tablets revealed that in certain cases critical quality attributes such as hardness, disintegration, and dissolution were not given as much consideration as may have been warranted."

Specifically, the agency says that some applications contained insufficient data on quality attributes or used "widely ranging values that were not justified as acceptance criteria."

While the guidance is mostly targeted at new drug applications (NDAs), abbreviated new drug applications (ANDAs) and some chemistry, manufacturing and controls (CMC) supplements, FDA says some of its recommendations also apply to investigational new drug applications (INDs) as well.

FDA says the quality attributes and information discussed in the draft guidance apply to both types of chewable tablets recognized by the United States Pharmacopoeia (USP): "those that may be chewed for ease of administration, and those that must be chewed or crushed before swallowing to avoid choking and/or to ensure the release of the active ingredient."

According to FDA, a chewable tablet should have the following four characteristics:

• Easy to chew
• Palatable (taste masked or of acceptable taste)
• Of appropriate size and shape
• Able to disintegrate readily to maximize aspiration and facilitation of dissolution

"Critical quality attributes for chewable tablets should include hardness, disintegration, and dissolution, as well as all factors that may influence drug bioavailability and bioequivalence. In addition, careful attention should be given to tablet size, thickness, and friability, as well as taste, which may impact the ability or willingness of a patient to chew the chewable tablet," FDA writes.

As such, FDA says that reliance on a single quality characteristic is insufficient, and calls on companies to ensure they have a proper balance of quality attributes.

For NDAs specifically, FDA says that sponsors should be able to answer the following questions:

1. Were the chewable tablets swallowed intact (i.e., without breaking) or after being thoroughly chewed?
2. If swallowed intact, does the shape and size of the chewable table pose a choking or bowel obstruction risk?
3. If water was used to aid swallowing, what was the volume?
4. What was the subject's sensory experience (e.g., taste, mouth feel, and aftertaste?

And for ANDAs, the agency says sponsors should focus on sensory experience, such as taste and mouthfeel, and ease of swallowing when conducting bioequivalence studies.

Additionally, FDA says that companies with already-approved products in chewable tablet form should reevaluate their products' critical quality attributes, and warns that the agency will take "appropriate action … to alleviate the risk to public health" posed by any tablets that do not meet FDA's quality expectations.