Submitting a clinical trial application (CTA) is a pivotal part of early-phase clinical trials. It is often the first formal interaction with health authorities and a defining moment for your clinical development programme’s credibility, timelines and future investment potential.
The CTA must be carefully prepared to meet regulatory requirements, as approval is needed before any human trials can begin. If your application isn’t approved, you cannot proceed with your Phase 1 clinical study.
A clinical trial application typically includes:
- Pre-clinical data: evidence from laboratory and animal studies showing the safety and potential efficacy of the drug.
- Clinical protocol design: detailed plans for the study design, objectives, methods and data analysis, along with how patient safety will be ensured.
- Informed consent forms: documents explaining to participants the nature of the trial and their rights.
- Investigational medicinal product (IMP) information: details about the drug being tested, including manufacturing and quality control measures.
This blog explains how small to mid-sized biotech and pharma companies can prepare a robust, regulator-ready CTA, minimise risk and set their clinical development programme up for success.
Why your clinical trial application matters
There are many different types of regulatory submissions. The clinical trial application is one of the primary regulatory submission types in the UK and EU (followed by a marketing authorisation application).
In the EU, all interventional CTAs are submitted centrally via the Clinical Trials Information System (CTIS) following EU Clinical Trial Regulation #536/2014 . In the UK, CTAs are submitted to the Medicines and Healthcare products Regulatory Agency (MHRA) and Research Ethics Committees (REC) in parallel, via the Integrated Research Application System (IRAS) and in addition to the Health Research Authority (HRA) for trials involving NHS hospitals.
The CTA is more than a regulatory formality. It is a comprehensive demonstration that:
- The investigational product is supported by adequate quality, non-clinical and clinical data.
- The proposed clinical study is scientifically sound and ethically justified.
- Participant safety has been carefully considered and mitigated.
For early-stage biotech and pharma companies, the CTA also signals organisational maturity and regulatory competence — qualities that investors and partners closely scrutinise.
A well-prepared CTA submission can avoid delays to clinical study initiation and build regulator confidence. A poorly planned one can lead to delays, requests for further information or even rejection.
One of the most common pitfalls is treating CTA preparation as a documentation exercise rather than a strategic process. Before drafting begins, you should define:
- Target regions and authorities (e.g. MHRA, EMA member states).
- Submission pathway and timelines.
- Key risks and regulatory sensitivities for the product class or indication.
Early regulatory intelligence — such as precedent approvals, guidance documents and feedback from scientific advice — can significantly shape a successful submission strategy.
Here are four practical tips to help you prepare a high-quality clinical trial application and reduce the likelihood of regulatory questions and delays.
1. Align quality, non-clinical and clinical content early
A CTA is assessed holistically; misalignment between modules is a frequent cause of regulatory questions.
Before submitting a CTA, you must gather extensive pre-clinical data from laboratory and animal studies. Key areas to focus on include:
- Chemistry, manufacturing and controls (CMC) readiness: manufacturing process, specifications, stability data and good manufacturing practice (GMP) compliance must be appropriate for the clinical phase.
- Non-clinical justification: toxicology and pharmacology data should clearly support the proposed dose, route and duration.
- Clinical protocol coherence: endpoints, inclusion criteria and safety monitoring must be scientifically and ethically justified.
Cross-functional alignment between CMC, non-clinical, clinical and regulatory teams is essential well before submission.
2. Develop a regulator-friendly clinical protocol design
The clinical protocol design is often the focal point of CTA review. Best practices include:
- Clearly articulated objectives and rationale with detailed plans for study design.
- A dose selection strategy grounded in non-clinical and any available human data.
- Endpoints (primary and secondary) and methods for data collection.
- Proportionate safety monitoring and stopping rules.
- A realistic recruitment and operational plan with inclusion and exclusion criteria for participants.
The protocol must also align with international guidelines, such as good clinical practice (GCP), and demonstrate a clear pathway for patient safety.
Regulators value clarity, justification and proportionality — particularly for first-in-human and early-phase clinical trials.
3. Anticipate questions before regulators ask them
Regulatory authorities will review your clinical trial application and may request additional data or modifications to the clinical protocol design. Addressing their feedback promptly and thoroughly is key to obtaining approval and moving forward with your Phase 1 clinical study.
Ethical approval is also required before early-phase clinical trials can proceed. An independent ethics committee or institutional review board must review your clinical protocol design, the informed consent process and the safety precautions taken for participants.
A successful CTA submission proactively addresses potential concerns by:
- Justifying novel mechanisms of action or technologies.
- Explaining deviations from guideline expectations.
- Acknowledging data limitations and outlining mitigation strategies.
Including strong rationales and clear cross-references reduces the likelihood of requests for further information and review delays.
Rushed submissions often fail due to avoidable errors rather than scientific shortcomings. So, you should allow sufficient time for internal scientific and regulatory review, consistency checks across documents, formatting and country-specific requirements, and final quality assurance review.
Attention to detail reinforces credibility and professionalism in the eyes of regulators.
4. Leverage regulatory expertise early
The first CTA is a defining milestone in your clinical development programme. Success depends on strong science, strategic planning, cross-functional integration and regulatory insight and alignment.
Many small to mid-sized biotech and pharma companies reach the CTA stage with limited internal regulatory infrastructure. Engaging expert regulatory and clinical operations support can, therefore, help:
- Define the optimal submission strategy.
- Identify and mitigate risks early.
- Ensure alignment across disciplines.
- Improve submission quality and confidence.
Early expert input often saves time and cost downstream by preventing avoidable delays.
Once clinical trials have demonstrated that your drug is safe and effective, the next step is submitting your marketing authorisation application to the relevant regulatory authority. This application is a critical step toward drug commercialisation, as approval will allow you to market and sell the drug within the UK and EU.
Successfully submitting your clinical trial application and gaining marketing authorisation can be complex and challenging, particularly if you’re pressed for time or lack the necessary internal resources or regulatory expertise.
TMC Consulting delivers cross-functional integration across all stages of your product lifecycle — spanning regulatory, clinical, pharmacovigilance, medical and quality assurance support.
Our expert-led pharma consulting services guide you through complex decisions and help you mitigate risk, allowing you to complete your clinical trials — and reach market — faster.
TMC Consulting ensures you move from early-phase clinical development to drug commercialisation quickly, compliantly and cost-effectively with flexible support that scales with you. Contact our team today at connect@tmcpharma.com to find out more.