The development of any new drug or biologic requires extensive research and rigorous testing at every stage of the process. After the preliminary development and in vitro or in vivo testing, a proof of concept is finalized prior to clinical testing.
If the product contains any amount of heretofore unapproved drug or biologic, however, the FDA requires it first be submitted to their Investigational New Drug (IND) program. Any new product must meet the approval of this program before human trials can begin. Furthermore, new drugs or biologics cannot even be legally shipped across state lines until this hurdle is cleared.
Fortunately, while the IND application process is rigorous, it should not present any issues so long as the proper studies are conducted. Maintaining best practice protocols throughout these IND-enabling studies allows new products to come to market as quickly and safely as possible.
Unless the FDA finds some cause to require further testing or documentation, IND applications are automatically approved one month after submission
Investigational New Drug (IND) enabling studies must provide the FDA with detailed data in a number of different areas.
Preclinical studies are understandably the cornerstone of any IND application. Without extensive animal pharmacology and toxicology testing, no product will pass the FDA’s approval. These are necessary to demonstrate that a new drug is safe for human trials.
The FDA also requires detailed information on every stage of the proposed manufacturing of the drug. Information on the clinical investigators overseeing the trials must be submitted, along with the proposed protocols of any clinical trials. Commitments to secure informed consent from participants are also required, as is an investigator’s brochure outlining best practices.
With proper foresight, IND-enabling studies will provide all the necessary data under demonstrable and consistently repeatable clinical conditions. This holds true for developing cellular therapies as well as both small and large molecule drugs.
Due diligence and an adherence to best practice principles maximizes the potential of Investigational New Drug (IND) Enabling programs.
Pre-formulation studies to determine physicochemical properties are part of the early stages of any drug development. These may include physicochemical characterization and screening for polymorphism, as well as excipient and salt selection. All of these enable the drug to be fast-tracked for formulation development.
Yet while it is standard GLP (good laboratory practices) to have one’s pre-formulation studies and formulation development secure from the beginning, too often in the rush to market certain formulation developments will prove inadequate during the mandatory IND-enabling pharmacology and toxicology trials.
Before launching any IND-enabling studies, it is best practice to have already fully developed and mapped out the clinical trials that will take place once the IND receives FDA approval. These proposed clinical trial protocols will help determine what exact IND-enabling animal pharmacology and toxicology testing to conduct in order to directly move to human trials.
A major factor in animal studies is which species to employ, which can vary a great deal depending on the IND. It may be beneficial to conduct trials using multiple species, as working with the wrong species or using the wrong dose can lead to inaccurate ADME/PK (absorption, distribution, metabolism, excretion, and pharmacokinetics) data.
Be it is toxicological or pharmacological, identifying a definitive exposure-response relationship and clinically translating the data is crucial. Inadequate or inaccurate data collection can be every bit as damaging as a poorly designed study, hence the need for GLP throughout every stage of IND-enabling studies.
Potential Chemistry, Manufacturing, and Controls (CMC) complications also need to be kept in mind throughout IND-enabling studies. Unless the formulation is thoroughly identified and characterized, is will be impossible to get accurate results. There may also be potential issues with scaling up any drug.
Investigational New Drug (IND) Enabling studies are far more than just an FDA requirement.
Human dose prediction is heavily based on these animal trials. Of course, even when the FDA approves an IND, that is no guarantee that a drug will prove safe in clinical trials. Animal models are just that, and to maximize the safety of human trials it is essential that IND-enabling tests provide detailed, accurate information.
The clinical investigators will also be operating on the data provided, and even a minor error or oversight in preclinical trials can increase the risk for human volunteers. With this in mind, stridently maintaining GLP throughout the IND-enabling studies does far more than simply hasten a drug to market or fulfill a bureaucratic requirement. It helps ensure the well-being of clinical trial participants, allowing a new drug to transition from viable possibility to major commercial success.
