IND & CTA Enabling Studies
Advancing your compound into first-in-human clinical trials in the USA and Europe requires completion of an investigational new drug (IND) and clinical trial application (CTA), respectively. IND- and CTA-enabling studies comprise preclinical pharmacology, toxicology, metabolism and manufacturing studies that allow you to submit a formal application with either the FDA or EMA.
The specific IND/CTA-enabling GLP studies you need is unique to your drug candidate, its therapeutic indication, the study data and also the regulatory agency. The FDA and EMA have different regulatory requirements; therefore, it is vital to understand those differences so you can design and plan your IND/CTA-enabling studies accordingly. Because it’s common to file a drug application in both regions, strategically planning your IND/CTA-enabling GLP studies will help optimize your approach and spend.
Enjoy the benefit of our extensive experience in planning and executing the preclinical studies you need for a successful IND/CTA submission –getting you to FIH quickly and efficiently.
Where to start your IND/CTA journey?
The vision for your drug candidate defines the entire study program, which often requires customized services. Whether you choose to proceed step-by-step or programmatically, the aim is to streamline your transition from nonclinical development to clinical trials. This can be achieved with a dedicated team that’s with you for the entire journey. When preparing for the IND/CTA-enabling studies you should ensure your chosen partner is equipped, accredited and has the right expertise to conduct GLP studies.
What is the lifecycle of an IND and CTA?
The FDA reviews initial INDs in 30 days. Questions arising during the review are usually communicated during the last 2 weeks of the 30-day review. INDs are “cleared”, not “approved”. With INDs, there is no cost or time delay to amend or add new protocols.
In the EU, the CTA process has been harmonized for a more efficient and consistent supervision of clinical trials. Under the new Clinical Trial Regulation (CTR), CTAs are submitted based on a single dossier split into two modules, which leads to a single approval per member state. The average timeline for a national CTA is 60 days plus any additional time needed to respond to the questions from the health authority. Substantial protocol amendments require a CTA approval and new protocols require a separate CTA.
What happens after your IND is cleared or your CTA is approved?
While your drug candidate has reached an important milestone and moves into clinical trials, it is not the end of nonclinical studies. Later studies are aimed at supporting the clinical phases or marketing authorization, all of which should be planned and initiated in a timely manner. Continuity is vital to the success of your molecule development because nonclinical documentation is often required throughout the lifecycle of the drug candidate.
What is the difference between IND and CTA submissions?
Preclinical studies are essential for the development of all drug candidates. In general, CTAs contain fewer study documents than INDs, and hence require less preparation time.
Both IND and CTA submissions aim to enable clinical trials, but they have different requirements.
An IND can be opened with a study of any phase and it includes multiple forms specific to the FDA, all nonclinical study reports, nonclinical summaries, detailed CMC information, the protocol and Investigator’s Brochure (IB). Once an IND has been cleared by the FDA, multiple studies can be conducted under the same IND. For drugs that are in very early development, an exploratory IND, supported by limited nonclinical data, may be submitted to allow evaluation of up to five APIs simultaneously. Furthermore, some research studies may not require IND submission at all.
The EMA has set regulations differently as each interventional clinical study requires its own CTA. This, partly, helps explain why the documentation required for these submissions is not identical. For a CTA, the four main documents are the protocol, informed consent form, IB, and Investigational Medicinal Product Dossier (IMPD), which contains CMC data. In addition to these, other documents such as EU-specific forms, questionnaires and insurance certificates must be included.
What’s unique about biologic-development for IND/CTAs?
The type of preclinical studies depends on whether you have a small molecule or a biologic, which are sometimes exempt from some PK and safety studies. Instead, biologics often require additional case-by-case evaluations. For example, health authorities may request supplementing the omitted studies with data generated from transgenic study models. Also, immunogenicity testing for biologics can comprise a significant portion of the preclinical program as it can lead to unwanted PD or PK effects.
IND and CTA enabling studies
There are a range of possible studies that can be considered as IND- or CTA enabling.
Early Phase Development Solutions
Early Phase Development Solutions allow you to select a programmatic endpoint (for example, IND/CTA; FIH; PoC) and then proceed programmatically through your development journey.
Some clients shave off up to 30% on their development timelines, saving significant time and expense.
Learn more about early phase solutions.
SEND 3.1 (FDA Dataset Submissions)
Datasets from your general toxicology and carcinogenicity studies, cardiovascular or respiratory endpoint studies, and any non-GLP studies need to be in the SEND format for FDA submissions.
Options include core SEND services as well as automated data delivery.
Learn more about SEND services.