FDA’s Drug Approval Process How it Fits into the US Health Delivery System

The U.S. Food and Drug Administration has a rigorous drug approval method, but recent years have shown that even this thorough process undergoes certain trends. Each year more new drug applications (NDA) are submitted and approved, including specialty drugs. The annual increase in the approval rates of novel and specialty drugs may signal a general advancement in technology or an increasingly competitive drug market.

The Approval Process

The FDA’s Center for Drug Evaluation and Research (CDER) is responsible for reviewing and approving NDAs. Initially, pharmaceutical companies develop and test their new products to determine efficacy and safety. Manufacturers are in close discussions with the FDA during this time. Following the initial findings, a sponsor for the drug sends an investigational new drug application (IND) to the FDA, and then the administration helps the sponsor develop human trials. After these are completed, the evidence regarding a drug’s human benefit and risk of harm is sent to CDER in an NDA.

Drugs created for life-threatening and rare illnesses may be approved through an accelerated process where the FDA looks closely at scientific findings instead of proven human outcomes from trials to determine if there will likely be a benefit to patients.

The FDA reviews the scientific results, determines if the drug is safe and inspects the manufacturing facilities. While teams of scientific professionals review NDAs, sometimes the FDA asks independent advisory committees to review the applications as well.

The efficacy of a drug is determined by seeing if it has the intended effect on people with a certain condition or disease. The FDA, and possibly an advisory committee, reviews the percentage of people positively affected by the drug during human trials as well as how likely it is to work in larger populations. The administration also asks how the medication brings about positive results, as it may be an entirely new mechanism for treating a particular condition.

A drug is deemed safe if the benefit for its intended use appears to outweigh the known risks. Phase 1 human trials emphasize safety issues by looking at types of side effects exhibit by patients, the frequency of side effects, and how the medication is metabolized and excreted from the body. Later trials also gauge the safety of the drug in various populations and with different dosages.

In addition to the safety of the drug itself, the FDA reviews the safety of the manufacturing process. Drug manufacturers must abide by Current Good Manufacturing Practices, which are in place to ensure the facility has the necessary monitoring and control to produce safe, quality products. CGMP prevents contamination and manufacturing errors.

The FDA must also decide the appropriate labelling for the medication. A label should convey important information to health care professionals and often contains warnings regarding dangerous side effects. The FDA updates individual drugs and class labels over time if it discovers new information. For instance, the administration now requires a boxed warning regarding the risk of abuse, addiction, overdose and death associated with immediate-release opioid medications. This is the strictest warning the FDA has for prescription drug labels.

Monitoring the Benefit of New Drugs

While the approval of new drugs is a boon for the health system and for patients who are waiting for better management of their conditions or cures for their ailments, the approval rate is only one important measurement of many. New drugs increase the potential for patient benefit, but actual benefit remains to be seen through long-term monitoring of the drug, including its safety and effectiveness.

“FDA approvals should not be looked at in isolation but must be coupled with the long-term patient outcome data,” according to Dr. Louisine Alpern, AMR's Medical Director. “We need to look at whether or not this will actually increase the quality of care for the patient and we include these types of questions as part of our review workflow.”

Specialty Drugs Gaining Approval

Last year, the FDA approved 45 novel drugs, which was the largest rate of new approvals since 1996. Sixteen (36 percent) of the novel drugs were labeled First-in-Class, which means they bring entirely new treatment mechanisms to the market. For example, "ibrance" was approved last year and creates a new method for treating advanced breast cancer.

Additionally, a larger percentage of these new drugs were considered specialty medications, meaning they treat rare or life-threatening illnesses. Twenty-one (47 percent) of the drugs approved in 2015 were for rare diseases. Orkambi is a new medication to treat cystic fibrosis, for instance, and Unituxin treats pediatric patients with high-risk brain tumors.

While new drugs mean additional treatment options for patients, many people are worried that they signal a continuance in rising drug prices. Some of the newly approved drugs could cost hundreds of thousands of dollars for one year of treatment, which means pharmacy benefit management companies have their work cut out for them tracking specialty drug data and negotiating reduced prices for their clients.