Dear Commissioner Sharpless:
On behalf of the Pharmaceutical Printed Literature Association (PPLA) I am pleased to submit these
comments to the Food and Drug Administration (“FDA” or “Agency”) on the draft guidance published in
the Federal Register of July 2, 2019.1
Background
PPLA is a trade group representing printers of regulated pharmaceutical information, including Package
Inserts (PIs), Medication Guides (MedGuides), Patient Package Inserts (PPIs), Instructions For Use
(IFUs) as well as other label packaging such as folding cartons and pressure-sensitive labels. Material and
technology suppliers are also part of PPLA. PPLA member companies are proud to be leaders in an
industry that facilitates communication of critical clinical information regarding the use and safety
precautions for pharmaceutical products worldwide. PPLA appreciates FDA seeking comments on
requirements for content and format of labeling for human prescription drug and biological products.
Labeling for Human Prescription Drug and Biological Products Serves Public Health
All drug and biological products distributed in the United States, regardless of country of origin, must
comply with the United States Food Drug and Cosmetic Act and the rules promulgated by FDA. Labeling
for Human Prescription Drug and Biological Products includes FDA approved information contained on
the container label, carton, prescribing information (PI), and/or, when applicable, Medication Guides
(MedGuides), Patient Package Inserts (PPIs), and Instructions, Instructions For Use (IFUs) Labeling for
Human Prescription Drug and Biological Products is mandated by the Food Drug and Cosmetic Act, 21
USC § 321;
k) The term “label” means a display of written, printed, or graphic matter upon the
immediate container of any article; and a requirement made by or under authority of this chapter
that any word, statement, or other information appear on the label shall not be considered to be
complied with unless such word, statement, or other information also appears on the outside
container or wrapper, if any there be, of the retail package of such article, or is easily legible
through the outside container or wrapper.
(l) The term “immediate container” does not include package liners.
(m) 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.
(n) If an article is alleged to be misbranded because the labeling or advertising is misleading,
then in determining whether the labeling or advertising is misleading there shall be taken into
account (among other things) not only representations made or suggested by statement, word,
design, device, or any combination thereof, but also the extent to which the labeling or advertising
fails to reveal facts material in the light of such representations or material with respect to
consequences which may result from the use of the article to which the labeling or advertising
relates under the conditions of use prescribed in the labeling or advertising thereof or under such
conditions of use as are customary or usual.
All required labeling must be printed on paper, be FDA approved, manufacturer produced and distributed. The Instructions For Use (IFU) is no exception. PPLA applauds FDA for issuing guidance for IFU intended to help develop consistent content and format across IFUs to help ensure that patients receive clear, concise information that is easily understood for the safe and effective use of such prescription products. The draft guidance obligates the applicant (manufacturer) to develop the IFU content and format, FDA to review and approve the IFU, and mandates the IFU be provide to patients when the drug product is dispensed. The guidance falls short of specifically mandating the manufacture procure the printed, approved IFU, and distribute the printed IFU accompanying the product through the supply chain. This proven PI distribution methodology must be adhered to for all Labeling required by the Food Drug and Cosmetic Act, including Medication Guides, Patient Package Inserts, and the much-anticipated FDA mandated and approved Patient Medication Information (PMI).
Language, Readability, Format, and Design Impacts Cognition by Patients
Pharmacists currently dispense greater than four and one half billion prescriptions per year. Each of the
prescriptions are for dangerous drugs which require a prescription issued by a licensed medical
practitioner. Patient safety concerns remain a significant challenge with pharmaceutical use; poor
adherence to medication regimens accounts for substantial worsening of disease, death, and increased
health costs in the United States,2 4.5 million ambulatory visits related to adverse drug events occur each
year,3 and adherence with medication therapy is generally low, approximately 50% to 65% on average for
common chronic conditions such as hypertension and diabetes. 4 ‘ 5 U.S. patient medical information
leaflets printed in pharmacies adhere to required criteria on less than 68% of prescription dispensed and
less than 50% for information on contraindications and precautions.6
Research on patient comprehension of drug information often finds limited understanding and sometimes misunderstandings that can lead to medication errors. Modification of factors such as legibility, readability, and format can improve performance somewhat, but the improvement is generally modest at best. Research has shown patient medication information produced based on various cognitive
accessibility principles such as clustering, chunking, coding, visual distinctiveness, overall spatial layout,
and use of spatial displays for key information result in substantial increased amount and depth of
information people grasp from the patient medication information.7
As FDA considers guidance for IFU, cognitive principles must be implemented to increase the amount
and depth of the intended message sought to conveyed to patients. The IFU Draft Guidance properly
identifies the importance of visuals, spacing, and color, yet does not standardize the application of these
layout and design elements.
Conclusion
PPLA members currently print the majority of current IFU and look forward to working with FDA and
industry as FDA issues IFU guidance to improve IFU based on current science of medical cognition.
Enhanced designs for printed IFU will result in greater patient cognition of the IFU to support the
universal goal of improved patient understanding of how to properly utilize their pharmaceuticals and
manage their overall health.
Thank you for the opportunity to submit comments.
Sincerely,
Dave Joesten
Chairman
Pharmaceutical Printed Literature Association
______________________________________________________________________________________________________
1 See 84 Fed. Reg. 127.
2 Office of Disease Prevention and Health Promotions in the U.S. Department of Health and Human Services, Health
People 2000 National Goals
3 Sarkar, U, Lopez, A, Maselli, J, Gonzales, R, Adverse Drug Events in U.S. Adult Ambulatory Medical Care: Health
Serv Res. 2011 October; 46(5): 1517-1533.o]doi:10.111/j.1475-6773.2011.01269.x.
4 Nichol MB, Venturini F, Sung JCY. A critical evaluation of the metholdology of the literature on medication
compliance. Ann Pharmacotherapy, 1999;33:531-540
5 Schlenk Ea, Burke LE, Rand C., Behavioral strategies to improve medication-taking compliance. In: Burke LE, Ockene
IS, eds. Compliance in Healthcare and Research, Armonk, NY; Futura Publishing Co: 2001:57-70.
6 Svarstad, BL, Bultman, DC, Mount, JK, Tabak, ER. Evaluation of Written Prescription Information in Community Pharmacies: A Study in Eight States J Am Pharm Assoc. 2003;43:383-93.
7 Day, Ruth S. Enhanced Designs for Patient Medication Information: Effects on Cognition