With an increased demand for the repackaging of solid oral dosage form drugs into unit-dose containers, the US Food and Drug Administration (FDA) on Tuesday released revised draft guidance on the conditions under which it does not intend to take action regarding stability studies and the expiration date to assign.
This draft guidance revises an earlier draft guidance for industry from 2005, known as "Expiration Dating of Unit-Dose Repackaged Drugs: Compliance Policy Guide." According to the Federal Register notice, changes include:
- "Shortens the expiration date to be used under certain conditions for solid oral dosage forms repackaged in unit-dose containers from 12 months to 6 months or 25 percent of the time remaining until the expiration date on the container of the original manufacturer's product, whichever time period is shorter.
- Provides for an expiration date exceeding 6 months if supportive data from appropriate studies are available and other conditions are met. Excludes from the scope of the guidance products repackaged by State-licensed pharmacies, Federal facilities, and outsourcing facilities as defined under section 503B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 353b).
- Excludes from the scope of the guidance all dosage forms other than solid oral dosage forms.
- Provides for the use of containers meeting USP Class B standards if certain conditions are met."
FDA current good manufacturing practice regulations stipulate that for finished pharmaceuticals, each drug product is required to bear an expiration date determined by appropriate stability testing and that the date must be related to storage conditions stated on the label, the agency says.
For unit-dose repackaged products, USP General Chapter <1178> Good Repackaging Practices recommends that the expiration date "not exceed (1) 6 months from the date of repackaging; or (2) the manufacturer's expiration date; or (3) 25% of the time between the date of repackaging and the expiration date shown on the manufacturer's bulk article container of the drug being repackaged, whichever is earlier."
FDA notes that this guidance addresses repackaging of prescription and over-the-counter solid oral dosage form drugs into unit-dose containers by commercial pharmaceutical repackaging firms that are required to register with FDA.
In addition to replacing the draft guidance called "Expiration Dating of Unit-Dose Repackaged Drugs: Compliance Policy Guide" from 2005, this draft, once finalized, will also supersede the "Compliance Policy Guide 480.200 Expiration Dating of Unit-Dose Repackaged Drugs" from 1995.
Following USP, FDA says in the revised draft that for solid oral dosage form drugs repackaged into unit-dose containers, FDA "does not intend to take action regarding the requirements of §§ 211.137 and 211.166 (i.e., expiration dating determined by stability studies) if these products are assigned an expiration date that does not exceed (1) 6 months from the date of repackaging, or (2) 25 percent of the time between the date of repackaging and the expiration date on the container of the original manufacturer's product, whichever time period is shorter" if five conditions are met:
"(1) The unit-dose container complies with Class A or Class B standards as described in USP General Chapter <671> Containers—Performance Testing, 'Packaging System Classification for Single-Unit Containers and Unit-Dose Containers for Solid Oral Dosage Forms.' Under this condition, containers complying with the Class B standard are used only if (a) appropriate data on the moisture permeability of the Class B material and the moisture sensitivity of the drug product are available, and (b) a risk assessment of these data provides a high level of confidence that use of such containers will not compromise the quality of the product throughout the assigned expiration dating.
(2) If the drug product is sensitive to light as indicated by the manufacturer (e.g., 'Protect from light' on its labeling), the unit-dose repackaging container-closure system provides light protection equal to or greater than that of the drug product's original container- closure system.
(3) The drug product's original container has not been opened previously and the entire contents are repackaged in one operation.
(4) Repackaging and storage occur in an environment that is consistent with the conditions described in the original drug product's labeling. If temperature and humidity are not specified in the original labeling, the product should be maintained at 'controlled room temperature' and in a 'dry place' (as defined in USP <659> Packaging and Storage Requirements) during the repackaging process, including storage.
(5) The drug product's labeling does not caution against repackaging."
Expiration Dating of Unit-Dose Repackaged Solid Oral Dosage Form Drug Products: Guidance for Industry