FDA Proposes More Restrictive Expiration Dating For Repackaged Solid Oral Drugs

FDA has proposed to tighten proposed limits on the use of oral solid drugs from one year to just six months after they're repackaged into unit doses, except under certain circumstances, in line with USP standards on expiration dating.

FDA has revised longstanding draft guidance on expiration dating for unit-dose-repackaged non-sterile solid oral drugs, shortening the proposed period these drugs can be used from one year to six months after they're repackaged. Periods exceeding six months would be allowed if certain conditions are met. The revisions conform to USP standards on dating non-sterile, unit-dose repackaged drugs.

This proposal was announced Aug. 8 in FDA’s revised draft guidance for industry, “Expiration Dating of Unit-Dose Repackaged Solid Oral Dosage Form Drug Products.” The guidance does not cover sterile, liquid or topical products, or any products repackaged by state-licensed pharmacies, federal facilities and outsourcing facilities. The revised guidance describes the conditions under which FDA will not enforce certain stability study requirements for repackaged drug products.

This action was taken in response to increasing demand for solid oral dosage form drug products repackaged into unit-dose containers in various health care settings, which hold a quantity of drug for administration as a single dose. The guidance states that “the increase in unit-dose repackaging has led to questions regarding stability studies and appropriate expiration dates for these repackaged products.”

FDA’s current good manufacturing practice regulations require that each drug product bear an expiration date determined by appropriate stability testing and that the date must be related to storage conditions stated on the labeling under section 211.137 of Title 21 of the Code of Federal Regulations. Samples used for stability testing must be in the same container-closure system as the marketed drug under 21 CFR 211.166 to ensure the drug product’s safety and efficacy over its intended shelf life.

The guidance puts the agency's enforcement stance on these GMP requirements in line with USP standards for expiration dating. USP General Chapter <1178> on good repackaging practices recommends that repackagers affix an expiration date not to exceed six months from the date of repackaging, or carry the manufacturer’s expiration date, or to cut the expiration date for repackaged doses to 25% of their remaining expiration, whichever is earlier.

FDA is proposing to shorten the expiration date from 12 months under the current policy to six months or 25% of the time remaining until the expiration date on the container of the original manufacturer’s product, whichever is shorter, and if the following conditions are met:

• The unit dose container complies with Class A or Class B standards as described in USP General Chapter <671> Containers – Performance Testing;
• The unit-dose repacking container provides light protection equal to or greater than that of the drug product’s original container closure system if the drug product is sensitive to light;
• The drug product’s original container has not been opened before and the entire contents are repackaged in one operation;
• Repackaging and storage occur in an environment that is consistent with the conditions described in the original drug product’s labeling; and
• The drug product’s labeling does not caution against repackaging.

In the earlier guidance on expiration dating issued in May 2005, the agency had proposed to set the expiration date for nonsterile, unit-dose repackaged drugs to one year, which also aligned with USP standards at the time for beyond use dating for unit-dose repackaging by dispensers. (Also see "FDA Extends Expiration Dating Of Repackaged Drugs To One Year" - Pink Sheet, 31 May, 2005.)

FDA also proposes to permit the expiration date to exceed six months if the above-listed conditions are met and if repackagers have supportive data from appropriate studies using an adequate number of samples to demonstrate that the container closure system used for repackaging is at least as protective of the drug product as the original packaging.

Once the revised draft guidance is final, it will supersede Compliance Policy Guide 480.200 “Expiration Dating of Unit-Dose Repackaged Drugs” issued Feb. 1, 1984, and revised in March 1995.

FDA will consider comments received by Oct. 10 when crafting the guidance's final version. Submit comments online to Docket No. FDA-2017-D-0829 at regulations.gov.

From the editors of the Gold Sheet.