Pharma and Health from Ingredients to Pills: What’s NEW on FDA Easy Labeling ?

Medicine labeling is important and affects individual health on a daily basis, for patients, and the effectiveness of prescriptions for healthcare professionals, as well as situations like drug interactions and potential side effects. Labels should present all the required information about a drug, the risks associated with its use, special considerations, and so on. It should present new, sound information and also discuss anything that the drug might affect. Finally, the label should be understandable. A clear presentation and limited jargon can make it more useful for both the practitioner and the patient.

According to the U.S. Food and Drug Administration (FDA), “labeling” is defined as “all labels and other written, printed, or graphic matters <1> upon any article or any of its containers or wrappers, or <2> accompanying such an article.” This may include packaging, instructions, product inserts, websites, and other promotional materials (1). Drug labeling is a process that might be underestimated by outsiders to the field, however, in practice, it is very important. FDA drug labeling fulfills several important functions and information. For many medications, it is the main source of information for the patient and allowing them to take the drug correctly. For professionals, it can allow them to be aware of side effects, correct usage, and drug interactions. FDA labels show drug efficacy, safety, and more. The drug labels are also reproduced online in the

FDALabel database which is a web-based database application of ~80000 drug labeling data.(2)

This information serves an important purpose, for instance, for preventing drug interactions. Furthermore, unanticipated, unrecognized, and mismanaged drug interactions contribute significantly to preventable morbidity and mortality, representing 3 to 5% of preventable in-hospital adverse drug reactions (ADRs). It is a contributor to emergency visits and hospital admissions, and 26% of total hospital admissions involved adverse reactions 52% of pharmacies, however, sold dangerous drugs without warning the patients. (3) Patients need to be more careful with what they take, but it is likely that they rely on their pharmacist or prescribing doctor to provide information if there is a risk involved or assume the medication is safe. While doctors might be aware of the effects of the medication they prescribe, they might not know every effect and potential interaction, especially if the patient has a rare condition or is taking an uncommon medication. This information should also be on the label.

The FDA has sought to change and improve labeling and has taken measures in this regard. In 2019, the institution issued two new draft guidances for the labeling requirements. The first one, Drug Abuse and Dependence Section of Labeling for Human Prescription Drug and Biological Products–Content and Format Guidance for Industry and applies for prescription drugs under the Controlled Substances Act (CSA) and those that are not covered under the CSA, but those that might be related to dependence and abuse. This guidance includes the following principles, which requires descriptions about the potential the drug has for abuse, misuse, addiction, dependence, and tolerance, as well as abuse-deterrent properties, withdrawal symptoms, and other related information for the safe use of the drug. The information should be included succinctly in the Warning section, and the information should be accurate and updated. This guidance is tied primarily to the abuse and dependence potential. (3)

The second guidance is “Instructions for Use–Patient Labeling for Human Prescription Drug and Biological Products and Drug-Device and Biologic-Device Combination Products–Content and Format”. It provides recommendations guidelines for content and format of Instructions for Use for the products that are included. It recommends describing the use of the drug, its dosage and administration, the way it is supplied, storage and handling, and patient counseling information. It recommends writing in nontechnical language, using an active voice and command  language, as well as using action verbs whenever possible. It is important to avoid abbreviations, to use clear and proper formatting, use of fonts and sizes, capitalization and other means of emphasis for organizing information, and the use of step-by-step instructions, as well as visuals to support the information presented. (4)

So, what are the current practices for easy labeling? Effective labeling needs to have essential scientific information for the safe use of the product. It should be accurate and not promotional. It should be updated with new information that needs to be revised at the very least every year and include all relevant information about the biological pharma products interactions with other drugs or foods, both observed and predicted. The label should include information about the interference of the drug with laboratory tests, metabolic pathways, transporter systems, the mechanism for drug interactions, and others. (3)

Some common problems that these FDA regulations seek to address involve the following problems such as a bad or confusing structure, excessive or insufficient information, wrong information, lack of guidance, and a lack of information about risk are the key problematic elements of a drug label. Presenting a clear structure, useful and pertinent information, and a clear understanding of the risk associated with the medication are essential elements of the new guidelines. (3)

At the moment, there are specific challenges for labeling that are not easily addressed even by these guidelines. Pharmaceutical manufacturers might have different understanding of the underlying pathways, and this information quickly evolves, however, labels cannot be updated in real-time. As information becomes updated, old labels might still be around. Additionally, labels might not reflect the drug interaction potential between older drugs and new ones. (3) These challenges are not easily addressed and logistically difficult, requiring additional sources of information that the providers and patients need to know about and be able to access. For a database like FDALabel, how many patients would know about it and be able to use it when required?

Overall, labeling presents significant issues that the FDA has tried to address. New approaches to drug labels have made it easier for patients and providers to understand risks and prevent drug interactions, but a label is not always up-to-date because of logistics. (3) Finding ways to minimize these problems and provide accurate and relevant information is essential. In the future, some issues might be resolved using current technologies, but at the moment the labeling for the physical packages still are somewhat limited. The current guidelines make the labels easier to use and understand and represent a good step forward in regards to this issue.

About the Author:

Lin Zhang, M.D., senior director of a health care industry company in the United States. With the experience in clinical medicine, biotechnology, health industry and other fields, he is responsible for the research and development of plant medicine, functional food and health products. He was a clinician and worked for the National Cancer Institute, FDA and the National Cancer Center of Japan for many years.