FDA Publishes Draft Guidance for Evaluation and Labeling of Scored Tablets
On September 1, 2011, the U.S. Food and Drug Administration (FDA) released draft guidance for tablet scoring, see FDA Guidance for Industry Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation. This draft guidance provides recommendations regarding “guidelines to follow, data to provide, and criteria to meet and detail in an application to approve a scored tablet,” as well as nomenclature and labeling for approved scored tablets. This draft guidance applies only to sponsors of new drug applications (NDAs) and abbreviated new drug applications (ANDAs). These guidelines are optional for currently marketed drug products.
The FDA published this draft guidance in recognition of the need for consistent scoring between a generic drug product and its reference listed drug (RLD). Insurance companies and physician sometimes recommend that patients score drug tablets to allow patients to adjust a drug dose or as a cost-saving measure. This practice, however, carries possible safety issues. The FDAs concerns with splitting a tablet include “variations in the tablet content, weight, disintegration, or dissolution,” which may affect the concentration of a drug in a split tablet and its rate of absorption. The new draft guidance aims to achieve consistency and ensure the quality of NDA and ANDA scored tablet products.
In furtherance of those goals, the FDAs draft guidance recommends criteria by which scored tablets can be evaluated and labeled by:
- Providing a harmonized approach to chemistry, manufacturing, and controls reviews of scored tables;
- Ensuring consistency in nomenclature and labeling; and
- Providing information through product labeling or other means to healthcare professionals.
The FDA has outlined eight main guidelines and criteria by which a scored tablets characteristics will be evaluated during the review process:
- The dosage amount meant to be achieved after splitting the tablet should not be below 84 the minimum therapeutic dose indicated on the approved labeling.
- The scored dosage form should be safe to handle and not pose risk of unintended drug 87 exposure (e.g., teratogenic, chemotherapeutic, hormones).
- Modified release products for which the control of drug release can be compromised 90 by tablet splitting (e.g., tablets controlled by an osmotic pump system or an exterior 91 film coat) should not have a scoring feature.
- The split tablet, when stored in standard high-density polyethylene pharmacy bottles 94 and caps (no seal), should meet established stability requirements for a period of 90 95 days at 25º C, plus or minus 2º C/60 percent Relative Humidity (RH), plus or minus 5 96 percent RH.
- The split tablet portions should meet the same finished-product testing requirements 99 as for a whole-tablet product with equivalent strength. A risk assessment should be 100 provided to justify the tests and criteria for product with the proposed functional 101 score. The resulting data should be provided to the Agency for evaluation. The 102 assessment should be undertaken on both tablets that are split nonmechanically (by 103 hand) and tablets that are split mechanically (with a tablet splitter). Any 104 recommended dissolution test data must be generated on a minimum of 12 individual 105 split tablet portions.
- The scored tablet should be tested using the indicated patient population to ensure patients can split the tablet correctly, as labeled.
- Scoring configuration of generic drug products should be the same as the RLD
- New study data on tablet splitability should be provided during the postapproval period for an product changes at level 2 and Level 3 as defined in the Agencys Scale-up and Post-Approval changes (SUPAC) guidances.
In addition, the FDA will require new products that meet the above criteria to be labeled as having a functional score. The use of functional score is intended to indicate to healthcare professionals that the product has been evaluated against the FDAs newly established criteria. These product labels should reflect the following:
- “Dosage Forms and Strength” section of the Highlights
- “Dosage Forms and Strength” section of the Full Prescribing Information
- “How Supplied” section of the full prescribing information
The FDA will require newly approved products to include this information in the patient package insert or medication guide. Those products that do not meet the criteria set forth in the FDAs new draft guidance, should not make reference to scoring or indicate a scoring feature in its product labeling.
Fuerst Ittleman will continue to monitor developments in the FDAs regulation of medical drugs. For more information, please contact us at firstname.lastname@example.org.