Late last week, the FDA released a draft guidance providing manufacturers of chewable tablets with recommendations regarding critical quality attributes that should be assessed during the development of these products. The draft guidance, entitled “Quality Attribute Considerations for Chewable Tablets,” outlines the quality attributes that should be considered during the development of chewable tablets. In the document, FDA states that these criteria should be used as “appropriate and meaningful indicators of product performance throughout the shelf life of the product.”
In its draft guidance the FDA offers a number of recommendations, advising manufacturers to consider disintegrant(s) to facilitate release of the active ingredient, and sweeteners and flavoring agents for taste-masking when designing and developing potential products. In addition, FDA notes that “the possibility of the interaction of excipients with each other and/or the drug substance(s), and their likely impact on the manufacturing process, should be explored.”
When conducting pivotal clinical studies, manufacturers should take the following questions into consideration and the answers should be included in the subsequent new drug application (NDA):
“For ANDA applications, general information such as subject’s sensory experience (acceptability of taste, mouthfeel, and aftertaste) and ease of swallowing – in case of tablets swallowed intact – can be collected during the conduct of bioequivalence studies and reported in the subsequent ANDA submissions.”
FDA recommends establishing the hardness, dissolution, and disintegration of the chewable tablet early in the product’s development. The Agency recommends that manufacturers study multiple attributes in order to address the tablet’s overall performance and incorporate it into the product specification. As such, dependence on only one attribute should be avoided.
If the product requires the submission of an application to the FDA, all information pertaining to the product’s development should be provided in section 3.2.P.2 (Pharmaceutical Development) of a common technical document (CTD) formatted submission. “The information on tablet hardness and chewing difficulty index (see Appendix I) should be provided in section 3.2.P.3.4 (Control of Critical Steps and Intermediates) or section 3.2.P.5.1 (Specification) of a CTD formatted application.”
In the guidance, FDA offers a number of specific recommendations pertaining to the hardness, disintegration and dissolution, as well as other critical quality attributes to consider. For additional information, view the Agency’s full draft guidance.
The United States Pharmacopeia (USP) recognizes and distinguishes between the following types of chewable tablets:
In order to prevent patients from swallowing “[DRUG] Chewable Tablets” whole, FDA strongly advises manufacturers to include the following statement on the principle display panel of the container label as well as the carton labeling:
“Chew or crush tablets completely before swallowing.”
If space allows, the draft guidance also states that the labeling should include the following statement he with lesser prominence to reinforce the importance of chewing the tablets:
“Do not swallow tablets whole.”
Additionally, it is recommended that manufacturers include language similar to the above mentioned statements in the professional labeling as well as any accompanying patient information or Medication Guide (as necessary).
Are you in the process of developing an OTC or prescription drug product? We can help you obtain FDA approval. To learn more about our services and how we can help you achieve a successful interaction with FDA, contact us today.
June 22, 2016
On Thursday, June 17th the FDA issued a draft guidance entitled “Quality Attribute Considerations for Chewable Tablets.” The document “describes the critical quality attributes that should be...
December 16, 2015
The FDA publishes weekly enforcement reports highlighting drugs that have been recalled during the previous week. Over the past several months these reports have been littered with hundreds of...
July 17, 2018
On Wednesday, July 11th, FDA released six draft guidances to aid in the development of new gene therapies. Of the six guidances, three were disease specific and three were related to manufacturing....