This is a new Compliance Policy Guide (CPG) concerning the requirements for stability studies for in vitro diagnostic products (IVDs) licensed by the Center for Biologics Evaluation and Research (CBER). It is an update to the Compliance Policy Guides Manual (August 1996), and will be included in the next printing of the manual. It is intended for FDA personnel and will be added to the electronic version of the CPG manual available on the Internet.
This document represents the Agency's current thinking on the stability requirements for licensed in vitro diagnostic products. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both.
In vitro diagnostic products may be approved or cleared through the medical device authorities of the Federal Food, Drug, and Cosmetic Act or licensed under the Public Health Service Act, depending on their intended use and active substances. Licensed IVDs must meet the requirements in the Quality System Regulation at 21 CFR Part 820, the provisions for in vitro diagnostic products in 21 CFR Part 809, the requirements of 21 CFR Part 211.166, the requirements in the biologics regulations at 21 CFR Part 600, and the requirements in the biologics license for the particular product.
Biological IVDs are subject to a number of different provisions that pertain to stability testing prior to product approval. The regulations for biologics licenses require that data establishing the stability of the product through the dating period be included in the license application (21 CFR 601.2 (a). The IVD regulations, at 21 CFR 809.10(b)(5)(iv), require that the product label include appropriate storage instructions to protect the stability of the product.
CBER requires, as a condition of licensure, that stability studies must be conducted before the application for a new IVD product is approved to ensure it will meet the expiration dating and storage conditions stated on the label. Post-approval stability studies generally are not required for licensed IVDs. Exceptions to this include:
- Stability studies that are required as a condition of approval of the license;
- Stability studies for products that have undergone changes or deviations in the manufacturing process or formulation changes; and
- Stability studies that are indicated as part of a corrective and preventative action plan developed in response to a failure investigation that would then support a previously cited expiration date.
REGULATORY ACTION GUIDANCE:
Investigators may cite a licensed IVD manufacturer for failing to perform post-approval stability studies when (1) the manufacturer is required to perform the post-approval studies as a condition of their license; (2) the manufacturer has made a formulation or manufacturing change; or (3) the manufacturer has committed to perform post-approval stability studies as part of a corrective and preventative action plan. Investigators should refer any questions regarding a firm's need to perform stability studies post-approval to CBER's Office of Compliance and Biologics Quality, Division of Case Management (HFM-610).