Types of FDA Drug Labeling and Their Requirements

Types of FDA Drug Labeling


FDA is charged with the duty of regulating the manufacture, sale and distribution of both prescription drugs and nonprescription drugs (aka over-the-counter or OTC medications).[1] A significant FDA role in the regulation of these medications is supporting sponsors in their efforts to ensure adequate drug product labeling. In this paper, we will describe the various types of drug “labeling” and their requirements. First, it is important to understand the regulatory distinction between “labels” and “labeling” which is illustrated as follows in Table 1:

Table 1[2]

As defined in section 201(k) of the FD&C Act (21 U.S.C. 321(k), the term label means a display of written, printed, or graphic matter upon the immediate container of any article, or is easily legible through the outside container or wrapper.
As defined in section 201(m) of the FD&C Act, the term labeling means “all labels and other written, printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2) accompanying such article.”

FDA’s Guidance for Industry entitled “Help-Seeking” and Other Disease Awareness Communications by or on Behalf of Drug and Device Firms (January 2004) describes two types of drug labeling: FDA-approved labeling, and promotional labeling.[3] An example of FDA-approved labeling is the Professional Package Insert (PPI). Promotional labeling generally includes all other prescription drug labeling e.g. a Dear Healthcare Professional Letter.[4] With the exception of Consumer Medical Information, this paper describes only FDA-approved labeling.

In addition to the PPI, FDA approved labeling includes FDA approved patient labeling and Medication Guides (though subsumed into PPIs) and in the case of nonprescription products, Drug Facts Labeling.[5] Another entity to be described is consumer medication information (CMI). See Table 2 for the basis of each.

Table 2

Professional Labeling
21 CFR 201.57
FDA Approved Patient Labeling
21 CFR 201.57(c)(18)
Medication Guide
21 CFR 208
Drug Facts Labeling
21 CFR 201.66
Consumer Medical Information
Guidance Useful Written Consumer Medication Information (CMI) July 2006

Professional Labeling/Professional Package Insert (PPI)

The PPI is “the official description of a drug product, which includes indication (what the drug is used for); who should take it; adverse events (side effects); instructions for use in pregnant women, children and other populations, and safety information for the patient.”[6] PPIs are considered the primary means of communicating information about drug products and serve as the basis for many other types of prescriber and patient materials including communications with healthcare providers (e.g. promotional labeling), pharmacists, and patients. It is important to note that it is the duty of the manufacturer to continually amend their package inserts,[7] and that oral communications, advertising and promotional labeling that are not consistent with the PPI have the potential of rendering a drug misbranded.[8]

FDA Approved Patient Labeling

FDA approved patient labeling (aka Patient Package Insert) should not be confused with patient counseling information, which is information for prescribers to share with patients. Nor should Medication Guides be considered the only type of approved patient labeling. Medication Guides only accompany drugs that are subject to a Risk Evaluation Mitigation Strategy (REMS; see discussion below). However, each of these components, as applicable, will be located at section 17 of PLR formatted labeling. FDA approved patient labeling should not be confused with CMI (materials commonly distributed by the pharmacy as discussed below). FDA approved patient labeling is included in the professional labeling and is specifically targeted to the patient.[9] Inclusion at section (17) allows the various forms of patient labeling to be more conveniently torn off and given to the patient and may also include instructions for use (IFU). Following are two illustrative examples:

  1. Cervarix® patient counseling information contains no medication guide but does include patient labeling:
    (17) PATIENT COUNSELING INFORMATION: “Advise the patient to read the FDA-approved patient labeling (Patient Information). Patient labeling is provided as a tear-off leaflet at the end of this Full Prescribing Information”.[10]
  2. Duragesic® does contain a medication guide but also points the patient to an IFU: (17) PATIENT COUNSELING INFORMATION: “Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use)”.[11]

As if this were not confusing enough, the CFR at subsection (c)(18) describes PLR labeling section 17. Emphasis added. This is illustrated in Table 3. Remember this anytime you review any labeling section in 21 CFR 201.57:

Table 3

21 CFR 201.57(c)(18)
(18) 17 Patient counseling information.
This section must contain information necessary for patients to use the drug safely and effectively (e.g., precautions concerning driving or the concomitant use of other substances that may have harmful additive effects). Any FDA-approved patient labeling must be referenced in this section and the full text of such patient labeling must be reprinted immediately following this section or, alternatively, accompany the prescription drug labeling. Any FDA-approved patient labeling printed immediately following this section or accompanying the labeling is subject to the type size requirements in paragraph (d)(6) of this section, except for a Medication Guide to be detached and distributed to patients in compliance with 208.24 of this chapter. Medication Guides for distribution to patients are subject to the type size requirements set forth in 208.20 of this chapter.

Medication Guide

To understand what distinguishes a Medication Guide from other FDA approved patient labeling, one must understand FDA’s Risk Evaluation and Mitigation Strategies, or “REMS”.[12] REMS are “required risk management plans that use risk minimization strategies beyond the professional labeling to ensure that the benefits of certain prescription drugs outweigh their risks”.[13] The REMS program came about as a result of a new law passed in 2007 known as the Food and Drug Administration Amendments Act (aka FDAAA). FDAAA gave FDA many new authorities and responsibilities to enhance drug safety.[14]

One of the components of a REMS that might be assigned by FDA is the Medication Guide. Medication Guides contain “prescription drug information for certain medications that pose a serious and significant public health concern, developed by the manufacturer, approved by FDA, and required to be distributed to consumers each time the medication is dispensed”.[15]

Any drug that requires a new Medication Guide is considered to have a REMS.[16] However, because many Medication Guides predate FDAAA/REMS, there are drugs with Medication Guides that are not part of the REMS program.[17]

Consumer Medication Information (CMI)

You have probably noticed something that resembles drug product labeling stapled to the bag containing prescriptions dispensed by your pharmacist. This is CMI aka PMI (Patient Medication Information), which is developed by third party vendors such as First Databank or Wolters Kluwer Health. CMI is not part of FDA-approved labeling, nor is it approved by FDA.[18] The history of CMI is fascinating and the effectiveness questionable. The Guidance describes the history in fairly minute detail[19] and FDA’s Consumer Medication Information: Expert and Consumer Evaluation of Consumer Medication Information describes various effectiveness metrics.[20] The purpose of such labeling has been to provide consumers with easy access to information regarding their prescription medications and is intended to be “clear, current, accurate, actionable, and accessible”.[21]

Drugs Facts Labeling

The “Drug Facts Rule” was finalized on March 17, 1999, standardized format and content requirements for nonprescription labeling,[22] and is codified at 21 CFR 201.66. When the rule was finalized, it was summarized as follows:

SUMMARY: “The Food and Drug Administration (FDA) is issuing a final rule establishing a standardized format and standardized content requirements for the labeling of over-the-counter (OTC) drug products. This final rule is intended to assist consumers in reading and understanding OTC drug product labeling so that consumers may use these products safely and effectively. This final rule will require all OTC drug products to carry the new, easy-to-read format and the revised content requirements within prescribed implementation periods.”

Drug Facts Labels are those easily recognizable labels on most of the nonprescription drug products on pharmacy shelves. Drug Facts labeling is required whether the drug is marketed through the monograph system or via an approved NDA. It should be noted that there are certain nonprescription drugs that also have professional labeling.[23]

If you have questions or concerns regarding your drug product’s labeling, feel free to click here to contact us.

Charles Jaap is Vice-President of Operations and Business Development for PDG, a global pharmaceutical and medical device consultant with extensive experience in the strategic development of drug products and medical devices. Please feel free to contact us for more information.

The opinions and statements in this paper are solely those of Charles Jaap and do not necessarily reflect those of PDG.

[1] Guidance for Industry: “Help-Seeking” and Other Disease Awareness Communications by or on Behalf of Drug and Device Firms. January 2004.
[2] Guidance for Industry: Safety Considerations for Container and Carton Labeling Design to Minimize Medication Errors. April 2013.
[3] Ibid @ 1.
[4] CDER Manual of Policies and Procedures (MAPP): NDAs: “Dear Health Care Professional” Letters. MAPP 6020.10. Effective Date: 07/02/03. As accessed at www.fda.gov on August 8, 2016.
[5] Technically, drug facts labeling for certain monograph products may not be considered “FDA approved labeling” while drug facts labeling for nonprescription products approved via the NDA or ANDA pathway would be. For the purposes of this paper it will remain a distinction that does not make a difference.
[6] Drugs@FDA Instructions: Health Information. As accessed at www.fda.gov on August 8, 2016.
[7] Supreme Court of the United States; Wyeth, PETITIONER v. Diana Levine 2009.
[8] Warning Letters and Notice of Violation Letters to Pharmaceutical Companies; Office of Prescription Drug Promotion. As accessed at www.fda.gov on August 8, 2016.
[9] Ibid @ 6.
[10] Cervarix® (Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant) Full Prescribing Information. As accessed at www.fda.gov on August 8, 2016.
[11]Duragesic (Fentanyl Transdermal System) for transdermal administration Prescribing Information revised: 04/2014. As accessed at www.fda.gov on August 8, 2016.
[12]Guidance: Medication Guides — Distribution Requirements and Inclusion in Risk Evaluation and Mitigation Strategies (REMS). November 2011. As accessed at www.fda.gov on August 8, 2016.
[13]A Brief Overview of Risk Evaluation & Mitigation Strategies (REMS). As accessed at www.fda.gov on August 8, 2016.
[14]FDA Basics Webinar: A Brief Overview of Risk Evaluation and Mitigation Strategies (REMS). As accessed at www.fda.gov on August 8, 2016.
[15]Patient Labeling 101. As accessed at www.fda.gov on August 8, 2016.
[16]Ibid @ 15
[17]Approved Risk Evaluation and Mitigation Strategies (REMS). As accessed at www.fda.gov on August 8, 2016.
[18]Ibid @ 15
[19]Guidance: Useful Written Consumer Medication Information (CMI). July 2006. As accessed at www.fda.gov on August 8, 2016.
[20]Consumer Medication Information: Expert and Consumer Evaluation of Consumer Medication Information‐2008.12/15/2014. As accessed at www.fda.gov on August 8, 2016.
[21]Ibid @ 15.
[22]64 FR 13254.
[23]63 FR 56802.