To market a prescription drug in the United States, all new human drugs and biological products must have FDA approval. To get approval, you must demonstrate that the drug is safe and effective by conducting lab, animal and human clinical testing for the intended use. The FDA reviews and determines if the drug provides benefits that outweigh its potential risks for the patients. The Agency can approve the drug, request more testing, or deny approval.

The responsibilities of the Food and Drug Administration (FDA) is to protect the public health by ensuring the safety, efficacy, and security of drugs, biological products, and medical devices. FDA also supports the acceleration of medical innovations with the potential to improve public health. For a promising new drug, this means that it encounters several regulatory landmarks as it navigates from the lab to the market in the US.

Safety and efficacy data from preclinical research determines the selection of which drug candidate should entry into clinical trials. The first step of the regulatory approval journey is when the developing company intend to test the diagnostic or therapeutic potential of a candidate in humans and file an IND application. This application should include information in three main areas:

• Animal Pharmacology and Toxicology Studies - Robust data must be generated in order to determine whether the product is reasonably safe for initial testing in humans.
• Manufacturing Information - During the preclinical phase, the CMC documentation should accurately describe the composition, manufacture and control of the drug to demonstrate a thorough understanding of the molecule and the consistency of every batch.
• Clinical Protocols and Investigator Information - Early developmental protocols should specify in detail all the elements of the study that are critical to safety. Also, the qualifications and obligations of the clinical investigators should be confirmed.

The principle of an IND review is that an interactive process with the regulators facilitates efficient and thorough development that increases the chances of a complete marketing application submission, or alternatively, prompts early termination of a development program for an unsafe or ineffective drug.

Once the clinical trials, from first-in-human to the pivotal study, are completed, a new drug application (NDA) should be submitted to FDA’s Center for Drug Evaluation and Research (CDER).

The NDA must contain the following for the FDA review team to be able to make a decision:

• Analysis of the target disease and available treatments. The benefits versus the risks may be differently considered depending on the medical need in a certain indication.
• Assessment of benefits and risks from clinical data. Different factors of uncertainties, such as incomplete data, or settings where randomised controlled trials have not been feasible, must be taken into account by the assessors.  
• Risk management strategies. Labelling clearly describing the drug’s benefits and risks, and how the risks can be detected and managed.

The FDA provides guidance documents presenting the Agency’s current thinking on different topics in relation to filing an NDA.

During the NDA review, CDER officials evaluate the full story of the drug. If the review team consider the NDA to not be complete, they can refuse to file it. The review team has six to ten months to review a filed NDA and representatives from each technical discipline reviews their section of expertise. FDA inspectors travel to clinical study sites to conduct a routine inspection. Finally, the review team issues a recommendation, and a senior FDA official makes a decision.

Once the FDA approves the drug, it can be marketed in the U.S. However, the FDA will continue to monitor the drug after its approval. FDA maintains a system of post-marketing surveillance and risk assessment programs to identify adverse events that did not appear during the approval process. FDA also oversees issues that may occur with the manufacturing, distribution, or availability of a drug.

Normally, any changes in formulation, labelling, or dosage strength as well as any kind of significant change must be approved by the FDA first.

A major change is a change that has a substantial potential to have an adverse effect on the identity, strength, quality, purity, or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product. A major change requires the submission of a supplement and approval by FDA prior to distribution of the drug product made using the change.

A moderate change is a change that has a moderate potential to have an adverse effect related to the safety or effectiveness of the drug product. There are two types of moderate change which requires different handling.

A minor change is a change that has minimal potential to have an adverse effect related to the safety or effectiveness of the drug product. The applicant must describe minor changes in its next Annual Report.

It is only when your product reaches the market that it starts to deliver on its promise. At NDA, we have a team committed to ensuring that the best possible medicines reach the market without unnecessary delay and making sure that they remain there for as long as they benefit the patients. Find out how we can help by using the form below.