TL;DR
The company that initiates the clinical trial is the legal sponsor of the trial. Sponsorship means retaining ultimate legal and scientific accountability for the study, regardless of how much operational work is delegated to a Clinical Research Organization (CRO). The CRO executes on behalf of the sponsor. The data, the decisions, and the regulatory accountability remain with the sponsoring company.
ICH E6(R3) allows sponsors to transfer some or all trial-related activities to service providers, but the sponsor retains ultimate responsibility for participant protection, trial data reliability, and the transferred activities. Transferred activities should be documented in an agreement, while responsibilities that are not specifically transferred remain with the sponsor.
This distinction shapes every subsequent decision: how the CRO relationship is structured, where internal decision-making authority sits, and what the sponsor must be able to review and approve at each stage of the study.
Before a regulatory authority will allow human exposure to an investigational product, sponsors must demonstrate that the potential risks are scientifically justified and acceptable in the context of the proposed clinical trial. This requires an appropriate package of preclinical evidence to characterize the product’s pharmacological effects and potential toxicities, and support the proposed starting dose and duration of exposure.
The content requirements are largely harmonized internationally through ICH M3(R2) guidelines, which govern the nonclinical safety studies required to support human clinical trials.
It harmonizes the type, duration, and timing of nonclinical safety studies. The guideline covers pharmacology, general toxicity, toxicokinetic and nonclinical pharmacokinetic studies, reproductive toxicity, genotoxicity, and, where relevant, carcinogenicity and other specialized studies.
Both the FDA and EMA apply these guidelines, which means the core preclinical package is substantially the same for both jurisdictions. The primary differences lie in the submission format, the review process and the populations chosen for the study.
An initial strategy for the manufacture, characterization, and quality of the investigational product should be in place to inform clinical trial planning.
This includes sufficient understanding of the product and its manufacturing process to define a plan for producing clinical trial material in accordance with applicable Good Manufacturing Practice (GMP) requirements. The level of Chemistry, Manufacturing and Controls (CMC) development required depends greatly on the product type and stage of development. ICH Quality Guidelines provide a framework to help sponsors with this task.
For an FDA IND, the manufacturing section needs to provide information about the composition, manufacturer, stability, and controls used for the drug substance and drug product. The purpose is not to prove that the product is commercially ready. It is to demonstrate that the investigational product can be manufactured and controlled appropriately for the proposed clinical investigation.
Early-stage biotech companies do not need a complete clinical team in place before engaging a CRO. What is required is the scientific basis: the molecule, the preclinical data in its current state, and a working hypothesis about the indication.
The assumption that a company must first hire a Chief Medical Officer, regulatory affairs director, and clinical operations lead before approaching a CRO reflects a model built for large pharmaceutical organizations with established internal infrastructure. It does not apply to early-stage companies, and applying it causes delays that serve no regulatory or operational purpose under either the FDA or EMA system.
A full-service CRO partnership provides the clinical functions and expertise that the sponsor would otherwise need to staff internally. This includes medical oversight, regulatory strategy, protocol design, site selection and qualification, safety monitoring, data management, and operational execution. The sponsor retains scientific ownership and decision-making authority. The CRO provides clinical advice and manages execution.
Real life example
To illustrate what this looks like in practice, at Gouya Insights, we planned and managed the full scope of clinical operations for a US-based early-stage biotech conducting a first-in-human autoimmune study in the US. The sponsor conceived and developed the scientific rationale and the molecule. We provided strategic and scientific input into the clinical development plan and co-developed the study protocol. We then managed the operational execution end-to-end: from site identification across multiple states and investigator qualification, through data management and a 40-person investigator meeting coordinated across multiple time zones. That division of responsibility is often key in first studies, allowing the sponsor to retain ownership of the scientific strategy while leveraging the CRO’s operational infrastructure and expertise. In this case, the close collaboration between the sponsor and CRO enabled the study to progress to first-patient enrollment on schedule.
The example illustrates the core model: the sponsor owns the scientific strategy, while the CRO can provide the infrastructure and operational expertise required to execute it.
This depends on the country where you are submitting the documentation. In the US, sponsors submit an Investigational New Drug application (IND) to the FDA. An IND is cleared by default 30 days after submission if there are no holds, but that does not include IRB approval or site activation, which run separately and add their own weeks and even months.
In the EU, sponsors submit a Clinical Trial Application (CTA) through CTIS, the Clinical Trials Information System established in the European Union. A CTA requires between 35 to 110 days to be approved, depending on the country. For example, Austria offers a clear example of the fast end of that range.
The key to speeding up the process is to present a submission that will not trigger formal questions. Sponsors with prior experience plan three to six months of preparation before their submission date, and still find small gaps during internal review.
When a preclinical package is “regulatory ready”, it means the package supports human exposure at a proposed dose, in a specific population, via a route of administration, for a treatment duration. Each of those parameters requires specific supporting evidence under both FDA and EMA frameworks.
Recurring preclinical gaps documented in early-phase clinical development include: animal studies that do not support the intended treatment duration or route of administration in humans, or preclinical models that lack translational relevance to the proposed indication. Regarding pharmaceutical quality, while initial data may demonstrate biological activity, the quality package often lacks key elements required to support clinical development, including evidence of manufacturing consistency, robust stability data, predefined release specifications, and established (qualified or validated) analytical methods.
These gaps are completely preventable and can be identified earlier through structured review of the preclinical package and development strategy.. This white paper walks through the questions that catch these gaps to avoid mistakes in your preclinical package.
From our experience, the most expensive mistake an early-stage biotech company can make is waiting until the preclinical package is complete before seeking clinical and regulatory input.
A CRO engaged early contributes to building a package that will hold up under regulatory scrutiny, whether that scrutiny comes from the FDA, the EMA, or both. Early engagement allows the CRO to provide strategic input on the decisions with the highest downstream impact: indication selection, study design, endpoint choice, regulatory pathway decision, and the questions brought to the regulatory agency before submission.
Some of the most predictable and preventable problems in first clinical trials share a common root: decisions made in isolation, without regulatory or clinical operations input, that prove difficult to reverse once the program is further along. For example, patient recruitment assumptions prove incorrect, inclusion criteria that are too restrictive for the available patient population, or site feasibility that was not adequately assessed before contracting.
A clinical advisor or clinical operations consultant engaged before these decisions are locked can surface and address each of these problems.
The minimum useful starting point is a defined indication, a molecule with some preclinical evidence behind it, and a hypothesis about the patient population. Arriving without these means the CRO cannot scope the study or identify the regulatory gaps in the current package.
A subtler version of the same problem occurs when sponsors arrive with a scientifically complete protocol that has not been tested against regulatory expectations. The protocol describes what the study will do. It does not yet establish why a regulator, whether the FDA or an EMA Member State authority, will accept the design, the endpoints, or the patient population as defined. That gap, between scientific soundness and regulatory acceptability, is where early CRO involvement adds the most value before any document is formally submitted.
The most productive clinical development partnerships begin before any regulatory submission is filed.
Regulatory strategy, pre-submission meeting preparation, site feasibility analysis, protocol design, and endpoint selection all benefit from clinical advisors’ input well before patient enrollment begins.
Standard practice for well-structured early-phase programs includes approaching regulatory agencies with the full development plan before filing, that is, not only the immediate next study, but the entire intended development path. Under the FDA framework, this takes the form of a pre-IND meeting. Under the EMA framework, it is the scientific advice procedure, available through the EMA or national competent authorities.
For companies at an even earlier stage, particularly those still determining whether their product fits the EU regulatory framework or which pathway applies, the EMA’s Innovation Task Force (ITF) offers informal briefing sessions at no cost and without initiating any formal regulatory procedure. The ITF is also available to US-based companies and is relevant for both drug and device developers facing genuine classification or pathway uncertainty.
Both pre-submission mechanisms serve the same purpose: obtaining the agency’s view on whether the proposed approach is acceptable before the sponsor commits budget to executing it. While the agency’s advice is not binding, it offers important insight into the regulators’ interpretation of the available data and their expectations for future development, making it a valuable basis for strategic decision-making.
Clinical trial submissions to both the FDA and EMA require a defined set of documents. The specific format differs by jurisdiction, but the underlying content requirements are largely aligned under ICH M3(R2) for the nonclinical package and ICH E6(R3) for GCP-compliant trial conduct.
These five document groups typically account for the vast majority of scientific and regulatory review comments in both CTIS and FDA IND submissions.
| Document Group | Purpose |
|---|---|
| Protocol | Defines the study objectives, design, endpoints, statistics, eligibility criteria, and operational conduct of the trial. |
| Investigator's Brochure (IB) | Summarizes the available nonclinical and clinical data supporting the use of the investigational product. |
| Quality / CMC / IMPD-Q | Demonstrates how the investigational product is manufactured, controlled, released, stored, and tested for quality. |
| Informed Consent Form (ICF) | Ensures participants are appropriately informed about risks, benefits, procedures, and their rights before participation. |
The cost depends on the product, indication, protocol complexity, number of sites, geography, patient population, manufacturing requirements, laboratory strategy, and amount of work retained internally versus outsourced.
The 2024 ASPE analysis estimated average out-of-pocket drug development cost at $172.7 million, with clinical trials accounting for $117.4 million, or approximately 68% of out-of-pocket R&D expenditure.
Clinical trials become more expensive as protocols become more complex, sites increase, recruitment takes longer, and additional operational requirements accumulate, causing clinical trial costs increase of 5-7% annually
Most recurring trial expenses come from investigator and site costs, patient visits, monitoring, data management, laboratory work, technology, and other operational activities.
Complexity adds cost through operational load. Sample management, diagnostics, and data cleaning expand as protocols add more assessments per visit and more data points per patient. A trial with three biomarker panels and centralized lab logistics carries a different cost structure than one with a single endpoint measured locally.
Trials might take longer to complete than sponsors originally planned. Long follow-up periods and delays resulting from slow patient recruitment extend the calendar timeline, and every additional month before the last patient completes the study adds cost across site fees, data management, and project oversight.
We dive deeper into this question in our Clinical Trial Costs in Europe vs the US article.
What do you need before starting a first-in-human clinical trial?
A biotech should have a defined product or candidate, a clear indication and development hypothesis, appropriate preclinical evidence, and an initial manufacturing and quality strategy. The exact requirements depend on the product, proposed population, route of administration, treatment duration, and regulatory jurisdiction.
Do the FDA and EMA require the same preclinical data package?
The core nonclinical framework is substantially harmonized through ICH M3(R2), but sponsors should not assume that the two regulatory pathways are identical. The differences can include submission format, review process, jurisdiction-specific requirements, and questions around the proposed clinical population and development strategy.
How long does an FDA IND take?
FDA’s initial IND review period is 30 days from receipt. The sponsor may proceed after 30 days if the IND has not been placed on clinical hold, or earlier if FDA notifies the sponsor that the investigation may begin. Read FDA’s IND procedures. This does not include IRB review, site activation, contracting, or other operational activities required before first-patient enrollment.
How does CTIS work for an EU clinical trial?
CTIS is the EU’s single entry point for clinical trial authorization and supervision, allowing sponsors to submit an application for authorization in multiple European countries through one system. Read EMA’s CTIS overview. The process includes validation, scientific and regulatory assessment, requests for information where applicable, and an authorization decision.
What is the difference between an IND and a CTA?
An IND is the regulatory submission used to initiate certain drug investigations in the US and is filed with the FDA. A Clinical Trial Application is used to obtain authorization for a clinical trial in the EU through CTIS under the Clinical Trials Regulation. The two systems have different procedures and timelines, so sponsors planning development in both jurisdictions should account for both from the beginning.
Can a biotech company run a clinical trial without a Clinical Research Organization (CRO)?
A sponsor can manage clinical operations internally, but for an early-stage company without established clinical infrastructure, full internal management may not be practical. The more relevant question is how to structure the division of responsibilities between the sponsor and the CRO based on internal capacity, therapeutic area, and long-term organizational strategy.
Who is legally responsible when a CRO runs the clinical trial?
The sponsor remains ultimately responsible for sponsor trial-related activities even when those activities are transferred to a CRO or another service provider. Read ICH E6(R3) on sponsor responsibility. The transferred responsibilities should be documented, and the sponsor should maintain appropriate oversight of the service provider.
What is the most common reason first clinical trials get delayed at the preclinical stage?
Recurring gaps include animal studies that do not support the intended treatment duration or route of administration in humans, preclinical models with limited relevance to the proposed indication, and manufacturing data that shows activity without yet demonstrating consistency. These gaps can often be identified before the preclinical package is locked by reviewing the proposed clinical exposure, manufacturing strategy, and regulatory pathway together.
How much does it cost to prepare for a first clinical trial?
There is no single reliable figure because costs depend heavily on the product, protocol, geography, sites, patient population, manufacturing requirements, and amount of work outsourced. ASPE’s 2024 analysis estimated average out-of-pocket drug development cost at $172.7 million, but that figure covers overall drug development and should not be treated as a first-patient-in budget. Read the ASPE analysis
References
1. International Council for Harmonisation (ICH). ICH E6(R3): Guideline for Good Clinical Practice. Final Consolidated Guideline, 2026. https://database.ich.org/sites/default/files/ICH%20E6%28R3%29_Step4_FinalConsolidatedGuideline_2026_0616_.pdf
2. International Council for Harmonisation (ICH). ICH M3(R2): Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals. 2009. https://database.ich.org/sites/default/files/M3_R2__Guideline.pdf
3. U.S. Food and Drug Administration (FDA). Investigational New Drug (IND) Application. FDA. https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-application
4. U.S. Food and Drug Administration (FDA). IND Application Procedures: Overview. FDA. https://www.fda.gov/drugs/investigational-new-drug-ind-application/ind-application-procedures-overview
5. U.S. Food and Drug Administration (FDA). IND Applications for Clinical Investigations: Chemistry, Manufacturing, and Control (CMC) Information. FDA. https://www.fda.gov/drugs/investigational-new-drug-ind-application/ind-applications-clinical-investigations-chemistry-manufacturing-and-control-cmc-information
6. U.S. Food and Drug Administration (FDA). Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products. Guidance for Industry, August 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/formal-meetings-between-fda-and-sponsors-or-applicants-pdufa-products
7. European Medicines Agency (EMA). Scientific advice and protocol assistance. EMA. https://www.ema.europa.eu/en/human-regulatory-overview/research-development/scientific-advice-protocol-assistance
8. European Medicines Agency (EMA). Clinical Trials Information System (CTIS). EMA. https://www.ema.europa.eu/en/human-regulatory-overview/research-development/clinical-trials-human-medicines/clinical-trials-information-system
9. European Medicines Agency (EMA). Clinical Trials Regulation becomes fully applicable. EMA, 31 January 2025. https://www.ema.europa.eu/en/news/clinical-trials-regulation-becomes-fully-applicable
10. U.S. Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation (ASPE). The Cost of Drug Development. 2024. https://aspe.hhs.gov/reports/drug-development
About the Author
PD Dr. Ghazaleh Gouya-Lechner is the founder of Gouya Insights and a cardiologist with over 20 years of hands-on clinical practice. She has worked across clinical development, regulatory strategy, and pharmacovigilance for both pharmaceutical and medical device companies. In 2017 she founded Gouya Insights, a CRO supporting early-stage biotech and medtech companies through clinical trials and drug development.
Nora holds degrees in law from Janus Pannonius University and in pharmacy from Semmelweis University, combining legal and scientific expertise. She is a certified Data Protection Officer with hands-on experience supporting GDPR compliance and contractual safeguards for biotech and pharma clients. With over 20 years in clinical research, she brings a pragmatic, risk-aware approach to data protection in global trials
