Investigational New Drug (IND)

An Investigational New Drug (IND) is a critical regulatory designation within the pharmaceutical and biotechnology industries. It represents the permission given by the U.S. Food and Drug Administration (FDA) to a sponsor to initiate clinical trials on human subjects with an unapproved drug or biological product. The IND is a pivotal step in the drug development process, marking the transition from preclinical research to clinical investigations.

Background

The development of new drugs undergoes multiple stages, which typically include discovery, preclinical testing, clinical trials, and post-marketing surveillance. An IND is required after preclinical testing and before clinical trials can begin. The primary purpose of an IND is to ensure the safety and rights of human subjects are protected during these trials.

Types of INDs

There are three primary types of INDs:

  1. Commercial IND: Submitted by companies intending to market the drug upon approval.
  2. Research or Investigator IND: Filed by individual investigators, often academic researchers, who initiate and conduct the investigation.
  3. Emergency Use IND: Allows the FDA to authorize the use of an experimental drug in an emergency situation that does not allow time for submission of a full IND.

IND Application

An IND application includes critical information that the FDA needs to evaluate the safety and feasibility of the proposed clinical trials. The application generally comprises:

  1. Animal Pharmacology and Toxicology Studies: Data from preclinical studies that support the rationale for testing the drug in humans.
  2. Manufacturing Information: Details on the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product.
  3. Clinical Protocols and Investigator Information: Protocols for proposed clinical studies, along with information on the qualifications of the clinical investigators.

FDA Review Process

Upon submission, the FDA reviews the IND application to ensure that the human subjects involved in the clinical trials will not be exposed to unreasonable risks. The review process includes:

  1. Administrative Review: Ensures the application is complete.
  2. Scientific Review: Involves evaluation by experts in the fields of pharmacology, toxicology, chemistry, and clinical practice. The expert review assesses the risk-to-benefit ratio of the proposed studies.

If the FDA does not place a clinical hold within 30 days, the sponsor may proceed with the clinical trials.

Clinical Trials Phases

Once the IND is approved, the drug enters the clinical trial phases, which are categorized into:

  1. Phase I: Tests the drug on a small group (20-80) of healthy volunteers to assess its safety, determine safe dosage ranges, and identify side effects.
  2. Phase II: Involves a larger group (100-300) of patients to evaluate the drug’s effectiveness and further assess its safety.
  3. Phase III: Conducted on large groups (1,000-3,000) of patients to confirm effectiveness, monitor side effects, and compare it to commonly used treatments.

Responsibilities of IND Sponsors

IND sponsors are responsible for:

  1. Reporting Adverse Events: Sponsors must inform the FDA of any serious and unexpected adverse events during the trial.
  2. Ensuring Compliance: Adhering to Good Clinical Practice (GCP) guidelines and ensuring that clinical trials are ethically conducted.
  3. Record Keeping: Maintaining accurate records of all clinical trial-related activities and results.
  4. Annual Reports: Submitting annual progress reports to the FDA.

Case Studies and Examples

Moderna

Moderna, a biotechnology company, became globally known for its mRNA-based COVID-19 vaccine. They filed an IND in early 2020 https://investors.modernatx.com for their vaccine candidate, which rapidly progressed through clinical trials and received Emergency Use Authorization (EUA) later the same year.

Pfizer

Pfizer, in collaboration with BioNTech, also filed an IND for their mRNA-based COVID-19 vaccine https://www.pfizer.com/science/clinical-trials. The vaccine went through the necessary clinical phases quickly, demonstrating the streamlined process during a public health emergency.

Ethical Considerations

Conducting clinical trials under an IND involves several ethical considerations:

  1. Informed Consent: Participants must provide informed consent, being fully aware of potential risks and benefits.
  2. Patient Safety: Monitoring safety through data and safety monitoring boards (DSMBs).
  3. Transparency: Publishing trial results irrespective of the outcome to contribute to scientific knowledge.

Global Perspective

While the IND process is specific to the United States, other countries have equivalent systems:

  1. Clinical Trial Application (CTA) in the European Union.
  2. Clinical Trial Notification (CTN) in Australia.
  3. New Drug Submission (NDS) in Canada.

These international equivalents also aim to ensure the safety and rights of human subjects in clinical trials.

The landscape of INDs and clinical trials is continually evolving, with ongoing advancements in technology and regulatory practices:

  1. Decentralized Clinical Trials: Utilization of technology to conduct remote or virtual trials.
  2. Real-World Evidence (RWE): Integration of RWE from electronic health records and other sources to complement clinical trial data.
  3. Adaptive Trial Designs: Flexible designs that allow modifications to the trial or statistical procedures after trial initiation without undermining the validity and integrity of the study.

Conclusion

The IND process is a cornerstone of drug development, underpinning the transition from laboratory research to human clinical testing. It ensures that new drugs are evaluated rigorously for safety and efficacy before becoming available to the public. Companies like Moderna and Pfizer exemplify the successful navigation of this complex regulatory landscape, contributing to significant medical advancements and addressing global health challenges.