FDA Draft Guidance on Critical Quality Attributes for Chewable Tablets

On June 16, 2016, the US Food and Drug Administration, FDA, published a draft guidance on "Quality attribute considerations for chewable tablets". Comments and suggestions regarding this draft document should be submitted within 60 days of publication.

The United States Pharmacopeia (USP) differentiates between two types of chewable tablets:

  • 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.

The concepts of the draft guidance are applicable to both types of chewable tablets.

The draft states that a review of numerous approved drug product applications for chewable tablets revealed that in certain cases critical quality attributes (CQAs) such as hardness, disintegration, and dissolution were not given as much consideration as may have been warranted.
The draft describes the CQAs that should be considered when developing chewable tablets and recommends that the selected acceptance criteria be appropriate and meaningful indicators of product performance throughout the shelf life of the product.

An ideal chewable tablet should be:

  • Easy to chew (incompletely chewed tablets can result in gastrointestinal (GI) obstruction),
  • Palatable (taste masked or of acceptable taste),
  • Of appropriate size and shape,
  • Able to disintegrate readily to minimize aspiration and facilitate dissolution.

CQAs for chewable tablets should include:

  • Hardness,
  • Disintegration,
  • Dissolution,
  • All factors that may influence bioavailability and bioequivalence.

Additionally, tablet size, thickness, friability and taste should be considered.
The following information should be collected either during the conduct of pivotal clinical studies:

  • Were the tablets swallowed intact or after being thoroughly chewed?
  • If swallowed intact, does the shape and size of chewable tablet pose shoking or bowel obstruction risk?
  • If water was used to aid swallowing, what was the volume?
  • What was the subject´s sensory experience?

The development information should be provided in section 3.2.P.2 (Pharmaceutical Development) of the common technical document (CTD). Information on tablet hardness and chewing difficulty index (calculated according to Appendix I of the draft guidance) should be provided in section 3.2.P.3.4 (Control of critical steps and intermediates) or section 3.2.P.5.1 (Specification).

FDA encourages manufacturers of currently approved chewable tablets and non-application chewable tablets to reeavluate the CQAs and ensure appropriate specifications are in place. "Should the agency have reason to determine that marketed chewable tablet poses a particular risk to public health because it is difficult to chew (e.g. causes damage to teeth or dental prosthetics, or GI obstruction), appropriate action will be taken to alleviate the risk to public health."

More information can be found in the draft guidance for industry on  "Quality attribute considerations for chewable tablets".

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