Introduction

Last week, we covered the final step of the drug development process before the drug is approved and sold in the market. We went over a general recap of the pipeline stages and the regulatory checkpoints for each stage. This entire process is operated by an FDA review team of experts in various fields to ensure the drug is safe for the public. After the FDA team approves the drug and decides it is safe to enter the market the company can create a patent for their drug. The existing data can be used for repurposed drugs or other development processes, but until the patent expires the drug belongs to the manufacturer. This week we head into the post-market surveillance for the approved drugs to ensure that all issues related to the drug medically are solved. Even with the various testing that occurred during the trials and research, it is impossible to have all the information about the drug during this stage of the process, therefore post-market surveillance is conducted to improve on the issues that arise from the general public using the drug, Some of these problems include allergies, incorrect prescriptions, addictiveness, and more.

Information about Post Market Surveillance

Post-market surveillance is the fifth and final stage in the drug development pipeline. After approval from the FDA, the drug enters the market and becomes mass-distributed through various channels. Even with the data from the previous stage, there can still be unexpected reactions due to the limited sample size, time, and controlled environment the trials took place. Therefore, this stage of overseeing the approved drugs to resolve any issues that arise. The FDA uses a system called Sentinel Initiative to scan for all the approved drugs. MedWatch is used to report problems with medical products accessible to both doctors and consumers. Other companies have various systems such as Adverse Event Reporting System (AERS) that collect and analyze data from healthcare providers, patients, and manufacturers about adverse events from drugs. The manufacturer must also implement a Risk Management Plan after submitting a New Drug Application (NDA) to minimize the risk associated with the drug and possible actions the company will take for patients if there are unknown side effects. In addition to checking the efficacy and safety of the drug to the general public, the FDA also ensures the company keeps legal conditions for the workers in the manufacturing process with Good Laboratory Practices (GLP).  The company must also submit regular reports to the FDA and other regulatory authorities detailing any changes, adverse event reports, and post-market studies they privately conducted. In the case of too many adverse effects, the FDA can send the drug back into the drug development process for more data to be discovered to counter the side effects that are harming people. The FDA also checks if the labeling on ads and containers matches the description of the drug and its effects and logs this data in the system. The Sentinel Initiative (SI) is a program created by the FDA in 2008 created as a result of the FDA Amendments Act of 2007. There are two main parts of the SI: the Sentinel System and the FDA-Catalyst. “The Sentinel System helps to answer the FDA’s questions on approved medical products. It does this by creating computer programs that analyze electronic healthcare data. These computer programs use statistical methods to study relationships and patterns in medical billing information and electronic health records.” (Sentinel).

Adopted from FDA 2016. The graph shows the split between manufacturer given data and FDA MedWatch data for the FAERS database. Most the data is given from the manufacturer and any unknown data that is discovered after release is sent by MedWatch.

The Sentinel System contained Active Post Market Risk Identification and Analysis (ARIA) and Electronic Health Records Complementary Data Sources. ARIA has two components, the Sentinel Common Data Model and computer programs that allow the FDA to analyze the data. ARIA observes the current market and gathers data from EHR, adverse event reports, feedback, literature reviews, etc to provide risk analysis and plan risk management. The FDA-Catalyst provides the data to the Sentinel System and uses the Sentinel Infrastructure to answer more questions than the Sentinel System can do alone. The FDA-Catalyst and Sentinel System complement each other making the SI reliable and trustworthy for the FDA to rely on to analyze the market. The Sentinel Initiative is also supported by the CBER Biologics Effectiveness and Safety (BEST) Initiative.  The CBER BEST conducts its post-market analysis outside of the FDA and shares the data. In the future, this entire process could become automated with the help of ML and AI. Using ML and AI algorithms, surveillance systems could detect signs of adverse effects sooner and more accurately decreasing the number of drugs removed off shelves and back into the pipeline.

Written and Constructed by Joshua Minami, Christopher Korban, Christian Chung

Works Cited:

About the Food and Drug Administration (FDA) sentinel initiative. Sentinel Initiative. (n.d.). https://www.sentinelinitiative.org/about

Center for Drug Evaluation and Research. (n.d.). Drug safety priorities 2016: Initiatives and Innovation. U.S. Food and Drug Administration. https://www.fda.gov/drugs/drug-safety-and-availability/drug-safety-priorities-2016-initiatives-and-innovation

Commissioner, O. of the. (n.d.). Step 5: FDA Post-Market Drug Safety Monitoring. U.S. Food and Drug Administration. https://www.fda.gov/patients/drug-development-process/step-5-fda-post-market-drug-safety-monitoring