Safety Labeling Changes (SLC) Overview

Section 505(o)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(o)(4)) authorizes FDA to require application holders for certain drugs¹ to make labeling changes based on new safety information² (including information related to reduced effectiveness) that becomes available after approval of the drug.   

SLC Procedures

Once FDA has determined that there is new safety information (NSI)² that should be included in labeling, FDA sends a Safety Labeling Change (SLC) notification letter to the application holder(s).  After receiving notification of the required SLC, the application holder(s) must either:³

• Submit a supplement with proposed labeling changes to reflect the NSI; or
• Notify FDA that it does not believe a labeling change is warranted and submit a statement detailing the reasons why such a change is not warranted (a rebuttal statement).

When the applicant submits a supplement with proposed labeling changes:

• If the proposed labeling can be approved without discussion with the application holder, FDA will approve the labeling supplement promptly and notify the application holder by sending a supplement approval letter. 
• If the labeling supplement proposes changes to the language or placement of the proposed labeling changes to what was provided in the SLC notification letter, the FDA may initiate a discussion period with the application holder to review and discuss the proposed revisions.⁴ The FDA will issue an action letter within 15 calendar days after the end of the discussion period. 

When the applicant submits a rebuttal:

• If the application holder submits a rebuttal statement and FDA accepts the reasons why labeling changes are not warranted, FDA intends to promptly notify the application holder.
• If the application holder submits a rebuttal statement and FDA does not accept the reasons why labeling changes are not warranted, FDA will initiate a discussion period with the application holder.⁴   

Within 15 calendar days of the conclusion of the 30-day discussion period (and any extension period, if applicable), FDA will proceed as follows:

• If FDA and the application holder reach consensus on the proposed labeling, FDA will notify the application holder by sending a supplement approval letter.
• If FDA does not agree with the application holder’s proposed labeling changes or rebuttal statement and FDA and the application holder cannot reach consensus, FDA can order the application holder to make the required labeling changes.⁵

SLC Order Issuance

If, at the conclusion of the 30-day discussion period (or extension, if applicable), FDA determines that the application holder’s proposed labeling changes do not adequately address the NSI or finds unacceptable the application holder’s reasons why the labeling changes are not warranted, FDA can issue an SLC order to change the product labeling.  FDA can also issue an SLC order if a labeling supplement or rebuttal statement is not submitted within 30 calendar days of the date of the SLC notification letter.⁶ SLC Order letters will be issued within 15 calendar days of the conclusion of the 30-day discussion period (or extension, if applicable).

All SLC Order letters issued by CDER will be posted on this FDA’s website.

For additional information, please refer to the guidance for industry “Safety Labeling Changes—Implementation of Section 505(o)(4) of the FD&C Act” .

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¹_{Drug products approved under section 505 of the FD&C Act (21 U.S.C. 355) and biological products licensed under section 351 of the Public Health Service Act (42 U.S.C. 262) that are regulated as drugs.}
²_{New safety information is defined as: “information derived from a clinical trial, an adverse event report, a postapproval study (including a study under section 505(o)(3) [of the FD&C Act]), or peer-reviewed biomedical literature; data derived from the postmarket risk identification and analysis system under section 505(k) [of the FD&C Act]; or other scientific data deemed appropriate by [FDA] about 1) a serious risk or an unexpected serious risk associated with use of the drug that [FDA] has become aware of (that may be based on a new analysis of existing information) since the drug was approved, since the risk evaluation and mitigation strategy (REMS) was required, or since the last assessment of the approved REMS for the drug, or 2) the effectiveness of the approved REMS for the drug obtained since the last assessment of such strategy.” (505-1(b) of the FD&C Act (21 U.S.C. 355-1(b))}
³_{Section 505(o)(4)(B)(i) and (ii) of the FD&C Act}
⁴_{Section 505(o)(4)(C) of the FD&C Act}
⁵_{Section 505(o)(4)(E) of the FD&C Act}
⁶_{Section 505(o)(4)(B) of the FD&C Act}

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