Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules.

October 2022 (Rev. 1)

We will now return to our series of looking at the growing list of FDA Guidance Documents related to the pharmaceutical industry and to compounding. This week, we will continue looking at the industry Guidance on Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules, a guidance document that applies only to manufacturing, but there may be some principles that we may want to be aware of in compounding.

The outline of the document is as follows:

1. INTRODUCTION
2. BACKGROUND
1. Differences in Size and Shape of Tablets and Capsules between a Reference Listed Drug and a Drug Product Subject to an Abbreviated New Drug Application
   1. Size
   2. Shape
   3. Patient Factors
2. Other Physical Attribute Considerations
3. RECOMMENDATIONS
   1. Size
   2. Shape
   3. Other Physical Attributes
   4. Biowaivers

INTRODUCTION

Tablets and capsules are widely manufactured and prescribed and may provide a number of advantages over other dosage forms, including ease of storage, portability, ease of administration, and accuracy in dosing. While generic formulations of these drug products are required to be both pharmaceutically and therapeutically equivalent to a reference listed drug (RLD), we are concerned that differences in physical characteristics (e.g., size and shape of the tablet or capsule) may affect patient compliance and acceptability of medication regimens or could lead to medication errors. We believe these patient safety concerns are important, and we are recommending that generic drug manufacturers consider physical attributes when they develop quality target product profiles (QTPPs) for their generic product candidates. The recommendations in this guidance apply to abbreviated new drug applications (ANDAs) and their supplements for additional strengths that are submitted to the Office of Generic Drugs (OGD). This guidance does not apply to approved ANDAs (generic drugs) already on the market. However, if the Agency determines that an approved product should be modified because the size or shape of a product poses a risk to public health, we will notify the holder of the ANDA. This guidance has been prepared by the Office of Generic Drugs and the Office of Pharmaceutical Quality in the Center for Drug Evaluation and Research. RLD means the listed drug identified by FDA as the drug product upon which an applicant relies in seeking approval of its ANDA. See 21 CFR 314.3(b). FDA publishes the identification of RLDs in the Approved Drug Products with Therapeutic Equivalence Evaluations (i.e., Orange Book). If the manufacturer of a RLD makes a postapproval change to the size or shape of a previously approved tablet or capsule, the generic versions generally will not need to be modified. However, the Agency could ask for modifications to the product if there are safety concerns because of the differences in physical characteristics.

Next week, we will continue looking at this specific Guidance Document, specifically the Background and Recommendations.

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition