Adverse Events & Drug Reactions: The Difference & Why It Matters

The FDA's oversight of drugs, medical devices and consumer products, such as OTC drugs, cosmetics and dietary supplements, relies heavily on post-marketing safety data collection and spontaneous adverse event reporting. This data is critically important given that potential safety issues may only emerge when a product is used by large populations. This is particularly relevant for drugs and medical devices that undergo initial safety testing in small groups.

Companies with FDA-regulated products, as well as manufacturers, packers and distributors listed on product labels, are required to submit post-marketing safety information to FDA, though the reporting requirements can differ based on the product category. Consult available guidance for reporting requirements for the appropriate product category, which may change from time to time. For instance, as described in a recent post, the Modernization of Cosmetics Regulation Act (MoCRA) introduced substantial changes in the regulatory landscape for U.S. cosmetic products, including a mandatory adverse event reporting requirement.

Given the importance of post-marketing safety data collection and spontaneous adverse event reporting, it is essential to understand the distinction between adverse events and adverse drug reactions, as this classification aids in the accurate identification, management and reporting of these events.

In the following sections, we describe the difference between adverse events and adverse drug reactions, examine the specific reporting responsibilities of manufacturers, applicants and distributors, explore the various spontaneous reporting systems, and outline the types of adverse events that must be reported to the FDA.

While safety reporting obligations can be challenging, especially to small and medium companies without a dedicated pharmacovigilance group, adopting a quality management system (QMS) can streamline the management of your safety reporting duties, helping to ensure patient and consumer safety as well as compliance with applicable regulations.

Contents

Adverse Drug Event (ADE) vs Adverse Drug Reaction (ADR)

Who must report?

Where are events reported?

Role of QMS in Adverse Event reporting

Conclusion

Adverse Drug Event (ADE) vs Adverse Drug Reaction (ADR)

An ADE is any unanticipated experience or side effect associated with the use of a drug in humans, whether or not it is considered related to the product. An adverse event could occur with use in professional practice, from overdose whether accidental or intentional, from abuse, from withdrawal and due to lack of expected effectiveness.

An ADR is a response to a drug which is noxious and unintended, and which occurs at doses normally used in humans for prophylaxis, diagnosis or therapy of disease or for modification of physiological function. An unexpected ADR is one, whose nature, severity, specificity or outcome is not consistent with the term or description used in the product labeling.

In short, an ADR is an adverse event with a causal connection to a drug. It is important to make this distinction to ensure effective drug monitoring and patient safety, as it helps in the process of identifying, managing and reporting these events accurately and the level of risk associated with these reports.

Who must report?

• Manufacturers are required to submit post marketing expedited safety reports to the FDA for device, prescription drug products marketed without an approved application (§ 310.305 and 803.3(l)(j) and (d)).

• Applicants (individual or corporate entities that hold an NDA or ANDA) are required to submit post marketing safety reports to the FDA for approved NDAs (§ 314.80) and ANDAs (§ 314.98).

• Any person whose name appears on the label of a marketed drug or device as its packer or distributor (§ 310.305(c)(1)(i)) or manufacturer, packer or distributor (§ 314.80(c)(1)(iii) and 803.3(j)) has post marketing safety reporting responsibilities.

• For dietary supplements manufacturers are responsible to submit any adverse events, including the events received as complaints from healthcare professionals or consumers to FDA.

Where are events reported?

MedWatch is a voluntary reporting program that allows consumers and healthcare professionals to report any unexpected adverse effects from skin rashes to serious adverse events with FDA-regulated products, including prescription and over the counter medicines, biologics, medical devices, combination products, special nutrition products, cosmetics and food.

MedWatch allows anyone to report adverse events, and submitting an online report is relatively simple. The system also provides comprehensive and current information on recalls and drug alerts, while offering a variety of delivery methods, including Really Simple Syndication (RSS) feed, Email and a News section on the FDA’s website. Below are the different databases where the adverse event data is stored and can be accessed for safety signaling assessments.

• FDA Adverse Event Reporting System (FAERS) is a database that receives reports from multiple sources, including healthcare professionals, consumers and drug manufacturers. FAERS is used to monitor the safety of therapies after they are approved by the FDA. The FAERS database not only includes adverse event reports, it also contains medication error reports and product quality complaints that resulted in adverse events. The structure of the database adheres to the international safety reporting guidance issued by the International Conference on Harmonization (ICH E2B).

• CFSAN Adverse Event Reporting System (CAERS) is a database that contains information on adverse event and product complaint reports submitted to FDA for foods, dietary supplements and cosmetics. The database contains data reported by consumers, healthcare practitioners, data that are voluntarily reported by industry and mandatory reporting. In addition, CAERS is not only limited to major medical events, but it can also include complaints about off-taste or color of a product, defective packaging and other non-medical issues.

• Manufacturer and User Facility Device Experience (MAUDE) database contains adverse events and reports related to medical devices. The database contains 10 years of medical device reports (MDR), and the database is updated every month. Although MDRs are a valuable source of information, this passive surveillance system has limitations, including the potential submission of incomplete, inaccurate, untimely, unverified or biased data. MAUDE data does not represent all known safety information for a reported medical device and should be interpreted in the context of other available information when making device-related or treatment decisions.

Role of QMS in Adverse Event reporting

In the complex and rapidly changing landscape of healthcare products, a robust Quality Management System (QMS) is indispensable for effective adverse event tracking. A well-implemented QMS standardizes procedures, ensuring consistent and accurate documentation and enabling effective tracking of adverse events.

An effectively organized QMS can help manufacturers track and then report AEs when necessary, ensuring regulatory compliance. A QMS also supports investigations and root cause analyses, leading to the development of corrective and preventive actions (CAPA). This systematic approach not only mitigates risks but also fosters continuous improvement, ultimately enhancing patient safety and regulatory compliance.

Through regular audits and clear communication channels, a QMS ensures that adverse event tracking and reporting remains effective and even evolves with industry standards.

Conclusion

Understanding the distinction between ADEs and ADRs is important for drug and medical device sponsors. With QT9 QMS, manufacturers can automate the collection, analysis and reporting of this information. This not only ensures timely submission to the FDA (as necessary), reducing the administrative burden and enhancing data accuracy, but also reinforces compliance with regulatory requirements and allows sponsors to reduce the risks associated with missing important safety information related to the use of their products.