Investigational new drug: Meaning, Criticisms & Real-World Uses

What Is Investigational New Drug?

An Investigational New Drug (IND) refers to a new drug or biological product that is under investigation and has not yet been approved for general use by regulatory authorities. It falls under the broader category of Pharmaceutical Regulation, which governs the testing, approval, and marketing of pharmaceutical products. Before a new drug can be tested in humans through Clinical trials, its sponsor—typically a pharmaceutical company—must submit an Investigational New Drug application to the relevant regulatory body, such as the Food and Drug Administration (FDA) in the United States. This application seeks authorization to administer the experimental drug to human subjects and to ship it across state lines for investigational purposes. Th²²e primary objective of the Investigational New Drug program is to ensure the safety and rights of participants in Clinical research and to facilitate the scientific evaluation of the drug's effectiveness.

#²¹# History and Origin

The concept of regulatory oversight for new drugs evolved significantly over time, largely driven by public health concerns. A pivotal moment in U.S. drug regulation was the passage of the 1962 Kefauver-Harris Drug Amendments to the Federal Food, Drug, and Cosmetic (FD&C) Act. This legislation was spurred by public outcry following the thalidomide tragedy, where the drug, marketed as a sleeping pill, caused severe birth defects in thousands of babies in Western Europe. While thalidomide was kept off the U.S. market by FDA medical officer Dr. Frances Kelsey, the incident highlighted the need for stricter drug regulation. The 1962 amendments mandated that drug manufacturers not only prove the safety of a drug but also provide substantial evidence of its effectiveness before it could be marketed. Furthermore, these amendments instituted stricter agency control over drug trials, including a requirement for informed consent from study subjects and formalized good manufacturing practices. These legislative changes laid the groundwork for the modern Investigational New Drug application process, ensuring a more rigorous approach to Drug development and Patient safety.

#¹⁹, ²⁰# Key Takeaways

An Investigational New Drug (IND) is an experimental drug or biologic not yet approved for public sale.
An IND application is a formal request to a regulatory authority, like the FDA, to begin human Clinical trials.
The application includes data from Preclinical studies, manufacturing information, and proposed clinical protocols.
Regulatory authorities have a 30-day window to review an IND application; if no objection is raised, trials can commence.
There are different types of INDs, including commercial, research, emergency use, and treatment INDs, each serving distinct purposes in drug investigation.

Interpreting the Investigational New Drug

The submission and acceptance of an Investigational New Drug (IND) application represent a critical milestone in the journey of a potential new therapy from laboratory to market. It signifies that the sponsor has compiled sufficient preclinical data, typically from animal pharmacology and toxicology studies, to suggest that the drug is reasonably safe for initial human testing. The FDA's review of an IND primarily focuses on two objectives: ensuring the safety and rights of human subjects involved in the trials, and evaluating the scientific quality of the proposed studies to adequately assess the drug's effectiveness and continued safety.

S¹⁸uccessful navigation of the IND process allows for progression into various phases of Clinical research, which systematically evaluate the drug in human populations. This initial regulatory hurdle is crucial for any company in the Pharmaceutical industry or Biotechnology sector aiming to bring a new product to patients.

Hypothetical Example

Consider a hypothetical Biotechnology startup, "CureAll Pharma," which has developed a novel compound, CX-100, showing promise in treating a rare autoimmune disease during laboratory and animal testing. To proceed with human trials, CureAll Pharma must submit an Investigational New Drug (IND) application to the FDA.

Steps for CureAll Pharma's IND Application:

Preclinical Data Compilation: CureAll Pharma meticulously compiles all data from its extensive Preclinical studies. This includes detailed reports on how CX-100 affected various animal models, its toxicity profiles, and its pharmacological activity.
Manufacturing Information: The company provides comprehensive details about the composition of CX-100, its manufacturing process, quality control measures, and stability data to ensure consistent production.
Clinical Protocols: CureAll Pharma outlines its proposed Clinical trials in detail. This includes the study design, patient selection criteria, dosage regimens, duration of treatment, and planned safety monitoring procedures for Phase 1 studies, which typically involve a small number of healthy volunteers or patients to assess initial safety and dosage.
Investigator Information: Information on the qualified clinical investigators who will conduct the trials is included, along with their experience and the facilities where the trials will take place.

Once submitted, the FDA has 30 days to review the Investigational New Drug application. If the FDA does not raise any objections or place the study on clinical hold, CureAll Pharma can then proceed with its Phase 1 human trials, moving closer to potentially developing a new treatment. This initial regulatory clearance is a significant step, paving the way for larger and more complex studies that will ultimately determine the drug's efficacy and safety for Public health.

Practical Applications

The Investigational New Drug (IND) application is a foundational element in the lifecycle of new drug development within the highly regulated Pharmaceutical industry. Its practical applications are multifaceted:

Enabling Human Trials: The core purpose of an Investigational New Drug is to permit the administration of an unapproved drug or biologic to human subjects. This is the gateway to collecting essential Clinical research data on safety and efficacy.
¹⁷ Regulatory Oversight: It provides the Food and Drug Administration with an opportunity to review the preclinical data, manufacturing information, and proposed clinical protocols before human exposure, ensuring appropriate Risk assessment and Patient safety.
¹⁶ Facilitating Interstate Commerce: From a logistical and legal standpoint, an Investigational New Drug application allows sponsors to legally ship unapproved investigational drugs across state lines to clinical investigators, which would otherwise be prohibited.
Investment and Valuation: For investors and analysts, the filing and acceptance of an Investigational New Drug application by a company marks a significant de-risking event in the Drug development pipeline. It often triggers increased investor interest and can influence Investment decisions as it signals progress towards potential Market entry.
Expedited Pathways: Different types of Investigational New Drug applications exist, such as Emergency Use INDs or Treatment INDs, which allow for accelerated access to promising experimental drugs for patients with serious or immediately life-threatening conditions who lack alternative therapies.

M¹⁴, ¹⁵ore information on the Investigational New Drug application process can be found on the U.S. Food and Drug Administration's website. https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-application

Limitations and Criticisms

While the Investigational New Drug (IND) process is crucial for patient safety and scientific rigor in Drug development, it is not without its limitations and criticisms. One significant aspect is the substantial financial burden and time commitment associated with the extensive Preclinical studies and the preparation of the IND application itself. This process often requires considerable Capital expenditure for pharmaceutical and biotechnology companies.

There is ongoing debate regarding the true Costs of Drug Development, with industry estimates often reaching into the billions of dollars for a new drug to gain approval, while some academic studies suggest lower figures. Su¹⁰, ¹¹, ¹², ¹³ch high costs can disproportionately impact smaller companies, potentially limiting innovation or discouraging research into less common diseases that may not offer high returns.

Another criticism sometimes leveled at the regulatory process, of which the Investigational New Drug application is the initial step, is the potential for delays in bringing life-saving drugs to market. The 30-day review period and potential for clinical holds by the Food and Drug Administration (FDA) can extend the development timeline. Balancing the need for thoroughness and Patient safety with the urgency of getting new treatments to patients remains a persistent challenge in Pharmaceutical regulation.

Investigational New Drug vs. New Drug Application (NDA)

The terms Investigational New Drug (IND) and New Drug Application (NDA) represent distinct, sequential stages in the drug approval process, often leading to confusion.

An Investigational New Drug (IND) is the initial application filed with a regulatory body (like the FDA) by a sponsor to gain authorization to administer an unapproved drug or biological product to humans in Clinical trials. The IND essentially permits the interstate shipment of the experimental drug and the initiation of human studies. It focuses on demonstrating that the proposed human trials are reasonably safe and scientifically sound based on preclinical data and proposed protocols.

In contrast, a New Drug Application (NDA) is a comprehensive submission filed much later in the Drug development process, after all three phases of human Clinical research have been completed successfully. The NDA contains all the scientific data and information about the drug, including safety and efficacy results from the pivotal Phase 3 trials, manufacturing methods, and proposed labeling. The purpose of an NDA is to formally request marketing approval from the regulatory agency, allowing the drug to be sold to the public. If approved, the NDA signifies that the drug is considered safe and effective for its intended use, paving the way for Market entry.

Essentially, the IND is permission to investigate a new drug in humans, while the New Drug Application is the request to market it.

FAQs

What information is included in an Investigational New Drug application?

An Investigational New Drug application typically includes data from animal pharmacology and toxicology studies (Preclinical studies) to assess safety, manufacturing information (composition, controls, stability), and detailed clinical protocols for the proposed human studies, along with information about the investigators.

How long does the FDA take to review an IND application?

After an Investigational New Drug application is submitted, the Food and Drug Administration generally has 30 calendar days to review it. If the FDA does not object within this period, the clinical trials may begin.

#⁹## What happens if the FDA places an IND on clinical hold?
If the FDA finds issues with an Investigational New Drug application that raise concerns about patient safety or the scientific integrity of the proposed trials, it can place the IND on a "clinical hold." This halts the initiation or continuation of the clinical study until the identified problems are resolved.

#⁸## Are all Investigational New Drugs intended for commercial marketing?
No, not all Investigational New Drugs are intended for commercial marketing. There are "Research INDs" (also called investigator INDs) filed by researchers to study unapproved drugs or to investigate approved drugs for new indications or in different patient populations, often for non-commercial purposes.

#⁶, ⁷## What are the phases of clinical trials that follow an IND?
Once an Investigational New Drug application is cleared, the drug typically progresses through three main phases of Clinical trials: Phase 1 (safety, dosage in small groups), Phase 2 (effectiveness, side effects in larger groups), and Phase 3 (comparative effectiveness, monitoring adverse reactions in large patient populations). A ³, ⁴, ⁵Phase 4 occurs after Regulatory approval, monitoring long-term effects.¹, ²