Clinical trials assess the efficacy and safety of therapeutic products; however, data gathering continues long after clinical trials end and the product is on the market. This process, known as postmarketing safety surveillance (PMS), remains an essential part of U.S. Food and Drug Administration (FDA) oversight and covers every step in the supply chain, from manufacturing and packaging organizations to companies marketing over-the-counter drugs and retailers who appear on the label.¹

Clinical trials are designed to identify potential adverse events associated with a specific investigational product (IP) on top of evaluating efficacy, but the number of patients involved at this stage is limited to only a few thousand at most, meaning some events may not emerge until an approved therapy reaches a larger pool of patients. If the new therapy sees slow adoption, it can take years to gather robust data, while therapies with more rapid uptake, such as the COVID-19 vaccine, can provide valuable data in a matter of months. Pharma, biotech and device companies must demonstrate to the FDA their readiness to process this data and respond as necessary, whether that means something as simple as revised product labeling or as significant as withdrawing the product from the market.²

However, beyond being a critical and ongoing part of product safety, the PMS process can also help consumers understand that clinical trials are not the last point of rigorous oversight for new treatments. Further, education around how the PMS process supports trials for future therapies sheds light on the industry’s dedication to research and reliance on a solid foundation of existing data. For example, the COVID-19 vaccines are new, but researchers went into product development and clinical trials with a wealth of clinical trial and postmarketing data from other vaccines, related formulations and experience with earlier viruses (including SARS-CoV-1). This is true across all therapeutic areas as PMS constantly informs future products by helping researchers further refine trials and better direct drug discovery efforts. Unfortunately, without intentional outreach efforts, much of this work goes largely unnoticed/unknown. Actively educating consumers on this ongoing process through both marketing and outreach campaigns lends transparency to research and development and helps sponsors build trust through education.

A Closer Look at Regulatory Guidelines

An approved PMS plan is required prior to reaching market approval from most regulatory agencies, including the FDA. As part of risk mitigation, the plan should be developed beginning in the earliest stages of trial design through analysis of existing trial data and identification of potential adverse events (AEs), plus any applicable mitigation strategies. The PMS plan is then further refined as clinical trials are conducted to better establish signals and trends to monitor after the product is on the market.

The FDA has prepared several guidances for industry clarifying its regulations on pre and postmarketing safety reporting. These guidances, however, do not provide step-by-step, product-specific strategies to ascertain FDA approval. Preparing a drug for market in multiple regions also means there may be multiple different requirements and guidelines to which sponsors must adhere. For example, for region-specific PMS plans, one must remain aware of the FDA Adverse Event Reporting System (FAERS) in the U.S., the Yellow Card Scheme in the UK and the Canada Vigilance Program when under Canadian jurisdiction. Though each of these regulations may dictate specific requirements, each product and the associated data are unique, meaning what each product needs to meet these requirements is unique, as well.

Independently gathering/providing excess data to meet PMS needs can be a tempting solution for sponsors trying to cover all their bases, but doing so can also unnecessarily waste valuable time and resources. This approach demands more of patients and healthcare workers and does not guarantee compliance. Experience is essential when determining what data to collect during PMS, how to analyze this data, and when and how to respond to the analysis. Furthermore, every step and consideration within a postmarketing plan requires a cost-benefit analysis and a watchful eye on constant regulatory changes and updates. Changes to guidance documents, sometimes even in the middle of a trial, can also affect PMS activities.

At the height of the COVID-19 pandemic in the United States, in May 2020, the FDA’s guidance document “Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During a Pandemic” offered some clarity surrounding event reporting during an unprecedented event. This document delineates steps for maintaining or delaying reporting and analysis when facing, primarily, significant absenteeism and/or increased event reporting. Further, the document notes that companies must not only resume normal procedures after the pandemic is resolved but also rapidly work through the reports that may have been delayed.³

Such unforeseen events leave even the most prepared companies making quick decisions, but a well-designed PMS plan helps ease the upheaval and demonstrates to consumers that safety efforts remain diligent. Similarly, an experienced research team that knows the importance of adaptability is better prepared to not only adjust plans but to execute with accuracy and ensure proper adherence to new guidelines. Though most consumers do not need the details surrounding every guidance document, they benefit from an understanding of what sponsors have set up to ensure continued safety. A robust PMS plan allows this information to be shared confidently.

Efficient Postmarketing Safety Supports a Strong Public-Facing Initiative

Designing an effective trial demands a comprehensive understanding of regulatory requirements across the entire product development process. Therefore, the most successful R&D requires strategy experts who have a thorough understanding of not only regulatory guidelines and clinical trial design, but also postmarketing data collection, organization and analysis.

The ability to properly collate the mass of postmarketing data is essential and enables rapid, effective response when adverse event trends arise. The data that arrives often comes from multiple sources rather than one centralized data capture module, making analysis less intuitive. Additionally, some sources, such as pharmacy databases and MedWatch, only offer limited exposure. Working with this data necessitates familiarity with where to look and what to look for or the entire process can quickly become burdensome, if not seemingly insurmountable.

However, postmarketing safety can become an efficient, effective process. Making your clinical trial team responsible for the collection and analysis of postmarketing safety data helps you anticipate all signals and trends well in advance of pursuing approval, providing you with a plan for not only gathering data, but also for ensuring an organized postmarketing response which helps you showcase your dedication to ongoing safety.

In addition to pharma, biotech, and device companies, postmarketing safety involves numerous groups: regulators, patients, healthcare providers, drug surveillance organizations and consumer advocacy organizations.² Consumers and patients in particular play a key role in the process but often know little about the extensive efforts clinical product development companies make to ensure continued product safety. Absent this knowledge, it is easy to understand why people may remain leery of recently approved products (or, in the case of COVID-19 vaccines, products granted emergency use authorization), but increased awareness can help counter these misconceptions.

Expounding upon your dedication to the PMS process, and providing education on the process itself, speaks directly to your commitment to ongoing safety. Additionally, postmarketing safety and surveillance require significant time and capital resources. Investing in both marketing and public outreach increases the value of this investment.

Rather than risk wasting resources or increasing your chances of overlooking an important piece of data, engaging with experienced safety and pharmacovigilance (SPV) and biometrics teams helps provide confidence in your processes, your products and the data itself while also improving your current and future drug development and trial design efforts. Working with SPV and biometrics experts over the course of a trial increases their understanding of the product, the adverse events observed during trials and the data to gather in support of postmarketing efforts. As a result, you benefit from a well-designed trial, expert analysis, rapid reporting and a strong market response while also having a clear plan you can use to support consumer-facing education and communication.

1. Center for Drug Evaluation and Research. (n.d.). Postmarketing adverse event reporting compliance program. U.S. Food and Drug Administration. https://www.fda.gov/drugs/surveillance/postmarketing-adverse-event-reporting-compliance-program.

2. Taylor, J. B., & Triggle, D. J. (2007). Comprehensive Medicinal Chemistry II. Elsevier Gezondheidszorg.

3. Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During an Influenza Pandemic_pdf | FDA. (2020, May). U.S. Food & Drug
Administration. www.fda.gov/media/72498