Scientists continue to uncover the mysteries behind various diseases and conditions. Surmounting evidence shows a need for new drugs and therapeutic developments to combat these ailments with minimal risks. But, have you ever wondered how new drug approvals go from discovery to the pharmacy? There are rigorous processes to ensure that new drug approvals don’t put people at risk.
Regulatory bodies in North America
The U.S. Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) is responsible for approving new drugs in the U.S. In contrast, the Center for Biologics Evaluation and Research (CBER) handles approvals for vaccines and other biological products such as blood-based treatments.
For each application, the CDER always considers the rationale behind the new treatment, the way the new treatment is tested and produced, as well as the ailment(s) that the new treatment has been tested against.1 The Health Products and Food Branch (HPFB) in Canada is responsible for ensuring the safety of new and existing drugs and medical products.2
New drugs may be brand-new products, biosimilars, or “next-generation” products like existing ones. Canada follows a similar model ottohe FDA. The FDA labels treatments as new molecular entities (NMEs) if they contain new, unapproved ingredients. The designation NME should not be confused with the designation new chemical entity (NCE) that falls under the Federal Food, Drug, and Cosmetic Act.1
New drugs in North America
The drug approval process consists of a pre-clinical phase, three main clinical phases, and a fourth post-market clinical phase. The pre-clinical phase involves laboratory studies and animal studies.
First, scientists create the drug in the lab, removing impurities and preparing for basic testing. Then once purified, scientists test the drug in cells and tissues in the laboratory setting. At this point, they are studying how the drug works.
If the drug has promising effects in the lab, the scientists then develop animal studies. In these studies, the scientists are trying to determine how the drug affects a living system, the optimal dose of the drug, and, importantly, whether the drug causes dangerous effects.
Once the drug is deemed effective and safe after several laboratory and animal studies, the drug’s sponsor can submit an application to the regulatory authority. This application requests approval for a clinical trial to be conducted.
The four phases of a clinical trial
The purpose of clinical trials for new drug approvals is to determine the following:
- whether the drug is safe for humans,
- what the optimal dose is,
- whether the drug is effective as a treatment in humans,
- and what the risks are of the drug.
Clinical trials occur in the following four phases:
Phase I is often known as the “first in human” phase. Phase I aims to ensure optimal safety dosing of the new drug in humans. These studies are smaller and consist of around 20 to 100 healthy participants. There are exceptions for certain conditions, i.e., cancer where, the participants are not considered healthy and must have the disease to participate. Phase I typically requires 3 to 6 months.3
This phase of the clinical trials is known as the proof of concept and safety stage. During this phase, it is determined how effective the drug is in humans and the adverse events or reactions. This phase typically includes a few hundred participants with a condition that the drug is being tested for. Phase II can require up to two years to be completed.3
The purpose of this phase is to continue monitoring for efficacy and side effects. These studies can have a few thousand study participants with a condition for which the drug is being tested for. This phase may take up to four years to complete.3
This phase is known as the post-market(ing) phase when the drug has been approved for sale. This phase is when the drug’s short and long-term effects are monitored in public health settings, clinics, or real-life scenarios where adverse events are reported. Phase IV continues for several.3
New drugs are typically approved for sale after successful phase III studies.4 However, depending on the country and the situation, approval may be granted earlier. In a global emergency, such as the case of COVID-19, steps can be taken to expedite the process without jeopardizing work’s safety or quality.5
What happens after the clinical trials?
If clinical trials prove that the drug is effective and safe in humans, a New Drug Submission or New Drug Application can be submitted to the appropriate regulatory authority; in Canada, this is Health Canada, and in the United States, this is the Food and Drug Administration Centre for Drug Evaluation and Research (CDER). This report contains all of the trial’s details including pre-clinical animal or lab data to the three phases of clinical research.2
Once the report is submitted, the reviews begin, and its details are analyzed extensively. Ultimately, if the regulatory body and stakeholders determine the drug is safe and that its medical benefits outweigh its potential risks, approval will be granted.
At this point, the regulatory body will issue a Notice of Compliance (NOC) and assign the drug a new Drug Identification Number (DIN). Researchers may do additional laboratory testing before the drug reaches the market.2
Patient health and safety always come first with clinical trials and new drug approvals. When reviewing a submission, authorities evaluate an array of potential and probable risks and determine if the benefits for those needing the drug outweigh those risks.2
Suppose the drug is found to be harmful during any phase of the clinical trials. In that case, those studies will be stopped immediately. If the drug is found to be dangerous after it reaches the market, it will be pulled from the shelf, in the case of over-the-counter medicines. It will be prohibited from being prescribed by healthcare providers. Efforts are always ongoing to ensure patient and public safety.
2023 is off to a great start
We are well into the second month of 2023, and already seven new drug drug approvals by the CDER that have undergone the first three phases of a clinical trial. Among these new products include treatments for type 2 diabetes, mantle cell lymphoma, and even Alzheimer’s disease.1 It will be exciting to see what new treatments continue to emerge throughout the rest of the year from all regulatory authorities.
1. Drug USF. Novel Drug Approvals for 2023. Accessed February 17, 2022. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2023
2. Canada H. How Drugs are Reviewed in Canada. Government of Canada. Accessed February 1, 2023. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/fact-sheets/drugs-reviewed-canada.html
3. Administration USFD. Step 3: Clinical Research. Accessed February 4, 2023. https://www.fda.gov/patients/drug-development-process/step-3-clinical-research
4.Health A. Phases of a Clinical Trial. Accessed February 4, 2023. https://myhealth.alberta.ca/Health/Pages/conditions.aspx?hwid=abo5220
5. Medicine N. Were the COVID-19 Vaccines Rushed? Here’s How the Vaccines were Developed so Fast. Accessed February 4, 2023. https://www.nebraskamed.com/COVID/were-the-covid-19-vaccines-rushed