PLR Recent Major Changes

What are ‘Recent Major Changes’ (§201.57(a)(5))?

When substantive labeling changes are made to any of the following sections of the FPI the heading(s) of the changed section(s) must be listed in Highlights under the heading Recent Major Changes:

  • Boxed Warning
  • Indications and Usage
  • Dosage and Administration
  • Contraindications
  • Warnings and Precautions

Note: Minor corrections, such as typographical errors or grammatical changes, are not considered substantive labeling changes.

References:
Labeling for Human Prescription Drug and Biological Products --- Implementing New Content and Format Requirements (draft) Jan 2006 Labeling
http://www.fda.gov/cder/guidance/6005dft.pdf
See http://www.fda.gov/cder/regulatory/physLabel/default.htm for any updates to the guidance.
See http://www.fda.gov/OHRMS/DOCKETS/98fr/06-545.pdf for the Final Rule: Requirements on the Content and Format of Labeling for Human Prescription Drug and Biological Products,
January 24, 2006. Effective June 30, 2006



What do I include in a ‘Recent Major Change’ (§201.57(a)(5))?

At a minimum, the section heading, identifying number, and the date on which the change was incorporated in the labeling in month/year format (e.g., 6/2005 or June 2005). And, if appropriate, the section subheading (e.g., when there are multiple sub heading listings for a section).
(i.e, Indications and Usage, Coronary Senting (1.2) 2/200X)heading, subheading, numerical identifier, date
Note: the numerical identifier should be created as a cross-reference to the appropriate secion in the FPI.
If there are no recent major changes to the label, then the RMC should be omitted from the highlights.

References:
Labeling for Human Prescription Drug and Biological Products --- Implementing New Content and Format Requirements (draft) Jan 2006 Labeling http://www.fda.gov/cder/guidance/6005dft.pdf
See http://www.fda.gov/cder/regulatory/physLabel/default.htm for any updates to the guidance.
See http://www.fda.gov/OHRMS/DOCKETS/98fr/06-545.pdf for the Final Rule: Requirements on the Content and Format of Labeling for Human Prescription Drug and Biological Products, January 24, 2006. Effective June 30, 2006




If I have more than one ‘Recent Major Change’ (§201.57(a)(5)), what order do I write them in?

There are 3 possible scenarios:

  1. If there are changes in more than one section of the labeling, the sections in Recent Major Changes should be listed in the same order as they appear in the FPI.
  2. If there is more than one change in the same labeling section during the 1-year period listed and the change is to the content under the same subheading, the date that supersedes the previous one should be listed.
    For example, if a new indication (hypertension) was added to the labeling in March 2005, and a limitation to the hypertension indication was added in June 2005, the change under the Recent Major Changes heading should be listed as:

    Indications and Usage, Hypertension (1.2) 6/2005
  3. If there is more than one change in the same labeling section during the 1-year period listed, but the change is to the content under different subheadings, each section heading, subheading, identifying number, and date should be listed separately. For example:

    Indications and Usage, Hypertension (1.2) 6/2005
    Indications and Usage, Heart Failure (1.3) 9/2005

References:
Labeling for Human Prescription Drug and Biological Products --- Implementing New Content and Format Requirements (draft) Jan 2006 Labeling http://www.fda.gov/cder/guidance/6005dft.pdf
See http://www.fda.gov/cder/regulatory/physLabel/default.htm for any updates to the guidance.
See http://www.fda.gov/OHRMS/DOCKETS/98fr/06-545.pdf for the Final Rule: Requirements on the Content and Format of Labeling for Human Prescription Drug and Biological Products, January 24, 2006. Effective June 30, 2006