In America, the FDA (Food and Drug Administration) was established as a federal agency in 1906 with the Pure Food and Drug Act. Since then, they have protected the health of Americans by ensuring the safety and efficacy of medication, medical devices and biological products. 

Regarding clinical trials, the FDA evaluates the data on an investigational drug and decides whether it is safe enough to become available to the public. To do that, they need to be sure that the medication works and that the benefits outweigh any possible risks. 

Drug Development and FDA Approval 

The clinical trial and approval process of a new drug can be a complex, long process. Most drugs that go through early-stage testing in animals don’t even make it through to the human testing stage and review by the FDA. 

Discovery and Preclinical Testing 

Scientists discover a new molecule that has the potential to become an effective medication. The drug is tested on animals. They provide an Investigational New Drug (IND) application to the FDA which includes the chemical makeup of the drug, animal testing results and plans for clinical trials. The FDA then decides whether it should be put on the public market. The FDA reviews the proposed clinical trials and once they approve it, the clinical trial can begin. 

Clinical Trial Phases and Outcomes 

Clinical trials usually take place in three phases which allow clinical trial staff to collect enough information. 

All clinical trials have endpoints that measure the desired outcomes of the trial. They include: 

  • Clinical endpoints: Measure the ability of a drug to make someone feel better, function longer and live longer. 
  • Surrogate endpoints: Biomarkers including genetic characteristics are measured. 

The FDA Approval Process 

  1. New Drug Application or Biologics License Application: The company submits a New Drug Application (NDA) or a Biologics License Application (BLA) which includes the in-depth analysis of the clinical trial, as a well as manufacturing and label information. 
  1. Acceptance and Review: 
    • It takes 60 days for the FDA to decide if it will accept the NDA or BLA applications. 
    • After 10 months, the drugs that offer major advancements in treatment are approved. 
    • It takes 6 months for drugs that offer small improvements to be approved. 

3) Facility Inspection: The FDA visits the facility where the drug will be manufactured and thoroughly inspects it to make sure it is up to standard. 

4) Approval: The FDA makes one final review and approves the label for the new drug to ensure that it includes all the important information that patients and healthcare professionals need to know. 

The approval process can be fastracked by the FDA if the drug is for a serious or rare disease. These steps include: 

  • Fast track: Designed to help shorten the development time of drugs that treat serious conditions. There needs to be fequent communication between the FDA and the drug company. 
  • Breakthrough therapy: If evidence from clinical trials shows that the drug  provides a noticeable improvement compared to other available treatments, the development and review can be sped up by the FDA. 
  • Priority review: The FDA reviews the New Drug Application (NDA) within 6 months, compared to the normal 10 months. 
  • Accelerated approval: An FDA regulation that allows for early approval of drugs that meet a medical need or treat serious diseases. 

Clinical Trial Guidance 

The FDA has updated their guide for clinical trials in 2022. It includes updated suggestions for how clinical trial sponsors and pharmaceutical companies should design and carry out clinical trials. The updated guide includes: 

Investigational Drugs (IND FDA) 

This consists of a unique clinical trial protocol design. Sub-studies can have their own goals and requires collaboration across the data science team to analyse various investigational drugs. 

The FDA describes the benefits of a master protocol across the clinical trial design. This provides the clinical trial sponsor with flexibility through new technologies and practices, including Electronic Data Capture (EDC). 

Clinical Trial Design 

Provides insights into any potential challenges that may arise when using master protocols. 

Any lack of adverse event reporting clarity can impact the safety profile of a study drug. This has a negative impact on the clinical analysis and the FDA approval needed for the regulatory body. 

Control Arm 

The FDA recommends a clinical trial sponsor use a common control arm in cases where multiple drugs are evaluated in a single illness. Changes in the Standard of Care (SOC) can also be adapted during the trial when it has been approved by the FDA. 

Novel Drugs 

When a clinical trial uses sub-studies to assess multiple drugs. The FDA advocates for providing a thorough reasoning for the combination of drugs.

Data Monitoring 

The FDA recommends an independent radiologic review committee which includes a blind assessment that provides a charter for the Independent Data Monitoring Committee (IDMC). 

The IDMC provides guidance for drug effectiveness and patient efficacy They can also recommend clinical trial protocol actions (changes in sample size, etc). 

 

Clinical Trial Regulations & the FDA 

Informed Consent 

Effective since 1981. The FDA believes that every participant needs to have adequate information about the clinical trial, including the potential risks before giving their informed consent to take part in the clinical trial. All participants must give written and legally effective informed consent that meets all the requirements before being allowed to participate in clinical trials. 

Institutional Review Boards (IRB) 

Effective since 1981. An Institutional Review Board (IRB) has the responsibility to review clinical trials that have been regulated by the FDA. This ensures that the rights and welfare of the participants are always protected and put first. 

Electronic Records; Electronic Signatures 

Effective since 1997. Outlines the criteria for which the FDA considers electronic signatures, and records to be reliable, trustworthy and equal to handwritten and paper records with handwritten signatures. 

Investigational New Drug Application 

Established in 1987. Contains the requirements that are needed for governing the use of investigational new drugs, including the submission to and review by the FDA. 

Bioavailability and Bioequivalence Requirements 

Established in 1977. States that anyone submitting a new drug application to the FDA, should include evidence measuring the bioavailability (the rate at which the drug enters systemic circulation) of the drug product or evidence that the investigational drug is bioequivalent (a similar drug) to the reference listed drug. A complete report needs to be submitted for the bioequivalence study. 

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