Post Authorization Safety Studies! (PASS)
Post-authorization safety studies are the term used by the European Medicines Agency (EMA), the nodal clinical research regulator in Europe, to define those studies that are performed on the effects of a drug after it has gained regulatory approval and is being widely marketed and consumed.
The US regulatory agency, the Food and Drugs Administration (FDA) terms post-marketing pharmacovigilance as post-marketing requirements and post-marketing commitments. PMR and PMC address different aspects of drug safety studies, but they fall under the broad category of post-approval studies. While the terms differ, both define the safety studies and practices to be followed by sponsors and companies once approval is given to a drug to sell it in the market to the public. This is important because pharmacovigilance is the prime concern of regulatory agencies. Ensuring drug safety during trials and monitoring its safety after trials are paramount for regulators.
The EMA doesn’t completely differentiate between a trial and a study and uses both interchangeably whereas the FDA considers a trial to be different from a study. Hence, the FDA has evolved into different mechanisms to address post-marketing pharmacovigilance. This distinction is provided in the 2011 document on post-marketing studies and clinical trials – implementation of section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act.
The FDA in 2011 released a guidance document which described the processes to be followed by companies and sponsors on after the approval to market a drug. It distinguishes between PMR and PMC. This distinction between PMR and PMC denotes the formal shift in US FDA strategy and policy to address post-marketing pharmacovigilance.
PMR is used to describe all those studies or clinical trials which occur after a drug has been approved by the FDA to be marketed. Under PMR, sponsors of clinical trials are required by law to conduct certain studies and trials after FDA approval for a drug. In other words, PMR makes it mandatory to perform post-marketing surveillance of the approved drugs.
Some PMRs that are often used include:
- observational studies that help in obtaining long-term clinical data, compare drug responses, identify risk factors like patient characteristics, patient registries, etc
- meta-analyses which help evaluate a safety end point
- animal studies since the FDA recognizes that it may have given accelerated approval to drugs that actually needed more trials or studies before approval
Since the terms commitments and requirements are treated differently by the law, the concept of PMC evolved in the FDA regulations. It refers to those trials or a study that a sponsor has agreed to conduct, but is not required to do so by the law. In other words, it’s a voluntary effort on the part of the sponsors to conduct post-marketing surveillance of the approved drugs.
Examples of PMCs include:
- drug and biologic quality studies that don’t have drug safety as the primary endpoint and rather focus on manufacturing, stability, and immunogenicity of the drugs
- studies and trials conducted with vaccines when available data doesn’t point to serious risk or a potential for risk
- pharmacoepidemiological studies that are designed to examine the natural history of a disease
