IND-Enabling Studies

Key Considerations:

CMO/CDMO Selection Timing:

• Recommended Timeline: Identify a Contract Manufacturing Organization (CMO) or Contract Development and Manufacturing Organization (CDMO) approximately 18 months before entering preclinical development.
• Purpose: This allows time to determine whether your test material will be GMP-ready in time to start the toxicology program.
• Benefits: GMP-ready materials facilitate a smoother transition from preclinical to clinical trials, although they may take longer to manufacture.

Batch Documentation:

• Critical Requirement: Throughout the preclinical journey, document all batches of your test material.
• Ensuring Consistency: Documentation ensures consistency, purity, and potency of the material.

Test Article Stability:

• Proven Stability: Your test article should demonstrate proven stability before executing GLP toxicology and safety assessment evaluations.
• Storage and Sample Stability Plan: Alternatively, have a plan in place to support storage and maintain sample stability.

Key Considerations:

Clinical Strategy Alignment:

• Synthesis and Manufacturing: Aligning with synthesis, batch production, and scale-up of your test material is crucial.
• Clinical Understanding: Understand your clinical strategy to ensure adequate preparation.
• Dose Quantities and Regimens: Know your clinical dose quantities, dosing regimens, and administration methods.
• Nonclinical to Clinical Alignment: These parameters must align between the preclinical and clinical phases.
• Timing: Define this alignment at least 6 months prior to starting the toxicology program.
• Dose-Range Finding Studies: Conduct these studies as part of the preclinical package to support dosing plans.

Pre-IND Meeting:

• Regulatory Feedback: It is recommended to have a pre-IND meeting with regulatory agencies.
• Purpose: Gain feedback on the non-clinical approach.
• Strategic Insights: This meeting provides valuable insights to enhance your IND program.

Key Considerations:

Timelines for IND Submission and Clinical Trial Start Date:

1. IND Submission Targets:

   • To meet your IND submission targets and achieve your targeted first-in-human trial date, we need to know those specific dates.
   • As your partner, we can then collaboratively outline studies to align with these deadlines.

2. Clinician Identification:

   • Recommended Timing: Identify a clinician to support your clinical trials at least 18 months prior to starting your safety toxicology program.
   • Strategic Importance: Having a clinician on board early ensures seamless integration of preclinical and clinical phases.

3. Preclinical Data Impact:

   • Pharmacokinetics, Pharmacology, and Tolerability Data: Throughout your preclinical program, these data points play a crucial role in defining your clinical dose strategy.
   • Informed Decision-Making: They guide informed decisions for safe and effective dosing in human trials.

The purpose of IND-enabling studies is to secure approval to conduct the first-in-human clinical trials with a new drug. An IND application contains information on pharmacology and toxicology, manufacturing (e.g., composition, production, stability, etc.), human clinical study protocols, and investigator information. At Charles River, we focus primarily on the pharmacology and toxicology testing, which is designed to provide evidence that the drug has its intended effect and that the proposed human dose levels are safe.

The United States Food and Drug Administration (FDA) requires that an IND application be submitted in order to determine if the efficacy and safety profile, the proposed manufacturing process, and the clinical trial designs of a new drug are acceptable to allow for studies in humans. An IND program and application compiles all this information, which facilitates regulatory review. Once an IND application is submitted, the FDA has 30 calendar days to review the package. Unless the FDA indicates otherwise, the IND sponsor is free to initiate the proposed human studies once the 30 days have elapsed.

To support IND-enabling studies, nonclinical (i.e., “non-human”) studies are conducted to evaluate the efficacy and safety of the drug. The pharmacology studies most often consist of in vitro (cellular) and in vivo (whole animal) studies that demonstrate that the new drug binds to its intended target and has the desired effect. This is often done in animal models that mimic the human disease. Once proof-of-concept is demonstrated in the pharmacology studies, the nonclinical safety studies (i.e., the toxicology studies) evaluate the safety profile of the drug. This includes profiling the drug’s effect on DNA (genotoxicity), critical organ systems (i.e., cardiovascular, respiratory, and central nervous system effects through safety pharmacology), and general toxicity (through animal studies in rodent and nonrodent species). During the IND-enabling studies, the collected data will demonstrate systemic exposure to the drug, the exposures and nature of adverse effects at high dose levels, and the safety margin (i.e., the margin between doses/exposures associated with efficacy and doses/exposures associated with toxicity).

SEND stands for the Standard Exchange of Nonclinical Data and is an implementation of the CDISC Study Data Tabulation Model (SDTM) that provides a framework for the standardized, electronic representation of individual animal study data. SEND is intended to increase the effectiveness and efficiency of data review for regulatory submissions. These SEND datasets are required when submitting your IND program to agency.

The path towards investigational cellular and gene therapy products (IND-enabling) is very complex. Reduce risk and delays with best-in-class end-to-end support and insights needed for a successful first step towards first-in-human cell and gene therapeutics. We offer our clients "a single scientific partner" to accelerate cell and gene therapy work from discovery all the way to market. It’s critical to have an experienced partner to help you engage with regulators and design the study early on. Start outlining your nonclinical first-in-human (IND-enabling) program for cell and gene therapies with us.