Understanding the Drug Approval Process
The Need for New Therapeutics
Scientists are diligently working to unravel the complexities of various diseases and conditions. Growing evidence highlights the urgent need for innovative drugs and therapeutic solutions that minimize risks. This raises an essential question: how do new drug approvals transition from initial discovery to availability at pharmacies?
Regulatory Bodies in North America
In the United States, the U.S. Food and Drug Administration (FDA) plays a crucial role in drug approvals through its Center for Drug Evaluation and Research (CDER). Meanwhile, the Center for Biologics Evaluation and Research (CBER) is responsible for approving vaccines and biological products, including blood-based treatments. For each application, CDER evaluates the rationale behind the treatment, the testing and production methods, and the diseases it targets. In Canada, the Health Products and Food Branch (HPFB) oversees the safety of both new and existing drugs.
Types of New Drugs
New drugs can be entirely novel, biosimilars, or advancements of existing products. The FDA identifies new molecular entities (NMEs) for drugs containing unapproved ingredients, a designation distinct from new chemical entities (NCEs) defined by the Federal Food, Drug, and Cosmetic Act.
The Drug Approval Process
Phases of Drug Development
The drug approval process is comprehensive, encompassing a pre-clinical phase, three main clinical phases, and a post-market phase.
Pre-Clinical Phase
The pre-clinical phase begins with laboratory studies, where scientists synthesize the drug, eliminate impurities, and prepare for basic testing. After purification, the drug undergoes testing in cell and tissue cultures to understand its mechanisms. If results are promising, researchers proceed with animal studies to evaluate the drug’s impact on living systems, determine optimal dosing, and assess potential harmful effects. Upon demonstrating safety and efficacy through these studies, the drug’s sponsor submits an application for clinical trial approval.
Clinical Trial Phases
The clinical trial process is crucial for evaluating the following aspects of new drugs:
1. Safety for human use
2. Optimal dosing
3. Effectiveness as a treatment
4. Associated risks
Clinical trials are conducted in four phases:
Phase I
Phase I is often referred to as the “first in human” stage, focusing on determining optimal safety dosing. This phase involves a small group of 20 to 100 healthy participants, although exceptions exist for conditions like cancer, where participants must have the disease. Phase I typically lasts 3 to 6 months.
Phase II
Known as the proof of concept and safety phase, Phase II assesses the drug’s effectiveness and the occurrence of adverse reactions. This stage generally includes a few hundred participants with the relevant condition and can take up to two years to complete.
Phase III
In Phase III, the drug’s efficacy and side effects are further monitored, involving several thousand participants with the condition being treated. This phase may take up to four years.
Phase IV
Phase IV, or the post-marketing phase, occurs after the drug has been approved for sale. During this phase, the drug’s short- and long-term effects are monitored in real-world settings. This phase continues for several years.
Post-Trial Procedures
If clinical trials demonstrate that a drug is safe and effective, a New Drug Submission (NDS) or New Drug Application (NDA) is submitted to the relevant regulatory authority—Health Canada in Canada and the FDA’s CDER in the United States. This submission includes comprehensive trial details and data from pre-clinical and clinical phases.
Upon receiving the submission, regulatory bodies conduct extensive reviews. If the drug is deemed safe and its benefits outweigh potential risks, approval is granted, resulting in a Notice of Compliance (NOC) and the assignment of a Drug Identification Number (DIN). Researchers may conduct additional laboratory testing before the drug is available to the public.
Prioritizing Safety
The safety of patients is paramount throughout clinical trials and drug approvals. Regulatory authorities rigorously assess potential risks to ensure that the benefits of a drug justify any associated dangers. If a drug is found to pose harm at any trial stage, studies are halted immediately. Should adverse effects arise post-approval, the drug may be withdrawn from the market or prohibited from being prescribed.
Looking Ahead to 2023
As of early February 2023, seven new drug approvals have been processed by the CDER, following successful completion of the initial clinical trial phases. These include treatments for conditions such as type 2 diabetes, mantle cell lymphoma, and Alzheimer’s disease. The year promises further advancements in drug development from various regulatory authorities.