Package Inserts

When Congress passed the United States Federal Food, Drug, and Cosmetic Act, it required that every drug product must have labeling consisting of “written, printed, or graphic matter” that is placed “upon the immediate container of any article” and that “bears adequate directions for use” and “adequate warnings.”

In the ensuing decades, the labeling information became the package insert (PIs) or labeling content. Pharmaceutical manufacturing companies evolved to requiring that qualified, audited and approved specialty printers produce PIs utilizing the same current Good Manufacturing Practices (cGMPs) required by the FDA of the drug manufacturers themselves.

In 2006, the FDA issued a major new regulation on package inserts. Below are all 18 elements of content listed in that 2006 regulation:

  1. Boxed Warnings
  2. Indications and Usage
  3. Dosage and Administration
  4. Dosage Forms and Strengths
  5. Contraindications
  6. Warnings and Precautions
  7. Adverse Reactions
  8. Drug Interactions
  9. Use in Specific Populations (pregnancy, pediatrics, geriatrics)
  10. Drug Use and Dependence
  11. Overdosage
  12. Description
  13. Clinical Pharmacology (how it works)
  14. Nonclinical Toxicology (other long term effects such as carcinogenesis or reducing fertility)
  15. Clinical Studies
  16. References
  17. How Supplied / Storage / Handling
  18. Patient Counseling Information (“information necessary for patients to use the drug safely and effectively)
    • Any FDA-approved labeling such as Medication Guides or Patient Package Inserts must be reprinted with the PI or accompany the labeling contents.

The PI is written for healthcare providers, so-called “learned intermediaries” in legal language. Looking at the FDA’s requirements for useful consumer medication information (CMI), as well as the criteria used in the studies by the University of Wisconsin and the University of Florida, shows that items 1 through 9, and 18, are all extremely relevant to patients. It is no surprise that many patients and caregivers do ask for and read the official PI.


Regulated by the FDA

The Food and Drug Administration’s criteria for drug information is based on scientific accuracy presented without bias. Drug manufacturers are held to a high standard when the FDA reviews their labeling content, the written contents of the PI. The FDA has provided manufacturers clear directions not only on the content required, but also on format, including legibility, readability, and limits on type size.

When the FDA approves a drug for “launch,” the labeling copy is usually the last element approved. The FDA is not a rubber stamp in these negotiations, which are private. Many launches have been delayed because the FDA and the manufacturer could not agree on the wording of warnings, precautions, or claims.

Reliable and Readily Available

The existing system of printed PIs thus offers unbiased scientific information throughout the entire drug supply chain. The PI is the primary source of reliable, scientific information for healthcare professionals as “learned intermediaries” to patients, or for the involved patient or caregiver who reads the PI for their own benefit.

Benefiting Healthcare Professionals

The printed literature designs that developed and evolved in response to the 1938 Food, Drug and Cosmetic Act were effectively delivering essential medication information to patients and health care providers when, following a six-year period of study, the FDA published a set of new requirements for PI in 2006.

As the FDA noted, “In recent years, there has been an increase in the length, detail, and complexity of prescription drug labeling, making it harder for health care practitioners to find specific information.”

The FDA’s cost / benefit analysis of the net savings was compelling: almost half a billion dollars saved from avoiding adverse drug events and saving practitioners’ time, balanced against minor costs for printing and designing to the new format.

One of the key elements of the final rule was to require a highlights section. The FDA also specified how small type could be, particularly for information intended for patients such as Medication Guides or Patient Package Inserts (PPIs).

As a result of this action, printed packaging suppliers to the pharmaceutical industry made substantial investments in order to achieve full compliance in a timely manner. Those printers, while not regulated directly by the FDA, practice the same current Good Manufacturing Practices (cGMPs) that the FDA requires of drug producers.