Bringing a new drug to market is a complex process that can take years with no guarantee of a successful outcome. The journey is highly regulated and includes numerous processes that require drug developers to have multiple levels of expertise within their teams. One such process is the Investigational New Drug (IND) application with the Food and Drug Administration (FDA).
The IND application must include information in three broad areas: animal pharmacology and toxicology studies, manufacturing information, and clinical protocols and investigator information. Any issues that occur during this process can result in the trial being put on hold by the FDA or sponsor company.
A clinical hold during the IND application process delays the opportunity for patients to receive potentially life-changing treatments, increases work for the drug developer, and can increase the expense of bringing a new drug to market.
IND application roadblocks
There were 777 IND applications and 24 Original Investigational Device Exemption (EDI) applications in FY2021. The number of actions taken on INDs and EDIs during this timeframe totaled 1,559. There are many reasons why the FDA or sponsors may half the approval process. The following are four top roadblocks and proven steps to prevent them.
- Incomplete preclinical data. Insufficient data is a significant issue that can slow the IND application approval process. The FDA cannot effectively evaluate that the product is reasonably safe without comprehensive, complete data from preclinical studies. This includes safety, efficacy, and pharmacokinetic profiles. While it can be an exhaustive effort, the most effective way to avoid this roadblock is to provide meticulously designed assays and thorough toxicology evaluations.
- Lack of CMC detail. Managing the manufacturing, quality, and regulatory side of the process takes a unique team with multiple areas of expertise. Smaller companies, especially, may find this challenging. However, it is critical to IND application success. The best way to avoid this roadblock is by ensuring the CMC information for both drug product and drug substance highlights every step of the manufacturing and quality control processes, including stability and proof of batch consistency.
- Inadequate trial design. Insufficient sample sizes, ambiguous endpoints, and poorly defined control groups are red flags for the FDA and sponsors. One of the best ways to avoid this roadblock is to involve the right stakeholders early in the design process. Including additional stakeholders can help teams identify issues so they can be proactively addressed before an application is submitted. The focus should be on crafting trials with clearly delineated endpoints, implementing rigorous statistical analysis plans and ensuring subjects will not be exposed to unnecessary risks.
- Poor documentation. Accurate and complete regulatory documentation is vital to IND application success. Poorly prepared investigator brochures, informed consent forms, and safety procedure reports can derail the entire process. The only way to avoid this roadblock is by taking the time necessary to prepare complete, comprehensive, and accurate documentation that follows all existing guidelines for each submission component.
The value of pre-IND meetings
Taking shortcuts to get an application submitted in a specific timeframe is an exercise in futility. This includes skipping pre-IND meetings. These meetings can prove invaluable in shaping a drug development program, especially when sponsor questions go beyond the scope of FDA guidelines. These meetings provide actionable insights that can facilitate and streamline more successful IND applications. Benefits of pre-IND meetings include:
- Reduces time to market
- Avoids unnecessary studies
- Ensures relevant studies are designed to yield meaningful data
- Drives FDA support
- Minimizes the potential for clinical holds
- Fosters creativity
- Helps define endpoints and objectives
- Facilitates discussion on eligibility for potential expedited programs (ex: fast track designation, breakthrough therapy designation, etc.)
Taking the time for pre-IND meetings can help ensure successful applications, especially for smaller drug development companies with limited CMC and regulatory expertise.
When to seek help
CMC and regulatory requirements for new products vary widely and are based on many factors, including the complexity of the molecule, formulation, indication, patient population, and more. For many drug developers, achieving an appropriate level of expertise in house can be challenging. Even for companies that have internal experts, they may have multiple initiatives underway and need additional help. Partnering with industry experts can help streamline the process, especially with IND submission preparation. Choosing the right partner can bring significant value, including faster, more successful IND applications. In our next blog, we will outline the capabilities to look for when choosing the best partnership for your organization.