UNITED STATES: FDA REGULATIONS

The U.S. Food and Drug Administration (FDA) oversees clinical trials under the Code of Federal Regulations (CFR), Title 21, Parts 50, 56, and 312. Key elements include:

Investigational New Drug (IND) Application

The Investigational New Drug (IND) application is performed before a new shortlisted drug can be taken for human clinical trials. The IND (Investigational New Drug application) is filed with the U.S. Food and Drug Administration (FDA) and must include, among other things, preclinical data (pharmacology and toxicology studies), manufacturing information, and a clinical trial protocol. The FDA has 30 days to review the IND to ensure a drug's safety during initial human exposure. If the FDA has not placed a Hold on Clinical, the coordinator must wait 30 days and can initiate clinical trials. 

Another important classification of IND is based on the purpose of the clinical trial: Commercial IND: The purpose is to market the product after approval. Research IND: The purpose is academic research. Emergency use IND: In certain situations, if a drug needs to be used in an emergency [2].

Institutional Review Board (IRB) Approval

The Institutional Review Board (IRB) must approve the study before a clinical trial can be conducted, to ensure that the study will be consistent with ethical principles and the federal regulations that protect human subjects. IRB is an independent board of scientists, ethicists, and people from the community who review the risk vs reward of the study to help ensure the benefit to society outweighs any risk to the participant, the latest risk of participating in the study, side effects, and the safety of participants continually. The IRBs function under 21 CFR Part 56 and are a part of Good Clinical Practice (GCP). One of the reasons clinical sites/investigators must have IRB approval before legally initiating a clinical trial.

ClinicalTrials.gov Registration

Under the FDA Amendments Act (FDAAA) of 2007, registering applicable clinical trials on ClinicalTrials.gov is mandatory. This database, managed by the National Library of Medicine (NLM), provides public access to Trial objectives, study design, eligibility criteria, Recruitment status, results, and adverse events data. Failure to register a trial or report results can lead to financial penalties and regulatory scrutiny [3].

EUROPEAN UNION: EMA AND CTR 536/2014

The clinical trials are regulated by the European Medicines Agency (EMA) in accordance with the Clinical Trials Regulation (CTR) 536/2014 that became applicable on 31 January 2022 [4]. This replaced the old Clinical Trials Directive (2001/20/EC). This regulation is designed to simplify trial concording, enhance information transparency, and create a competitive space to conduct research inside the EU. Key features include:

Centralized Submission Process

The Clinical Trials Information System (CTIS) is the cornerstone of the Centralized Submission Process introduced by the Clinical Trials Regulation (EU No 536/2014). It allows sponsors to submit a single application for clinical trial authorization across multiple EU member states, replacing the need for separate national submissions. The system ensures that the assessment of applications is conducted jointly by the concerned regulatory authorities, reducing redundancy and expediting the approval process. CTIS also facilitates seamless communication between sponsors, national competent authorities, and ethics committees, enhancing efficiency and consistency in trial evaluations. Additionally, the system promotes transparency by making key clinical trial data publicly accessible, enabling researchers, healthcare professionals, and patients to track trial progress and results.

Ethics Committees and other authorities

Ethics Committees (ECs) ensure that the trial is conducted to the best ethical standards, and participants in clinical trials (CTs) governed by law are also protected by ECs to protect the rights and welfare of the subjects. Every EU member state operates its own National Ethics Committees, which assess trial protocols, informed consent processes, and risk-benefit evaluations before providing approval. In addition to ECs, regulatory oversight is shared among National Competent Authorities (NCAs), who supervise compliance with regulations, monitoring of clinical trials, and adherence to Good Clinical Practice (GCP) guidelines. At the EU level, the European Medicines Agency (EMA) provides scientific guidance and has a regulatory agency responsible for ensuring harmonization and consistency across member states. This partnership intends to make sure clinical trials are both judicable and regulatory driven to support organizations with innovation in medical research.

GDPR Compliance in Clinical Trials

Compliance with the General Data Protection Regulation (GDPR) (EU 2016/679) is a critical aspect of conducting clinical trials in the EU, as it governs the processing and protection of personal data, including sensitive health information. Sponsors and investigators must implement strict data protection measures, ensuring that participants’ data is anonymized or pseudonymized wherever possible. Participants must provide explicit informed consent for their data to be collected and used, and they retain the right to access, correct, or withdraw their data at any time. Additionally, data transfers outside the EU must comply with GDPR provisions, requiring appropriate safeguards such as Standard Contractual Clauses (SCCs) or adequacy decisions. Regulatory bodies closely monitor compliance, and violations can lead to significant penalties. Balancing data privacy with research needs remains a challenge, but GDPR compliance ensures that patient rights and confidentiality are prioritized throughout the clinical trial process.

CHINA: NMPA REGULATIONS

They are subject to regulation by the National Medical Products Administration (NMPA) in China (previously known as China Food and Drug Administration [CFDA] and the Center for Drug Evaluation [CDE]). Clinical trial conduct in Taiwan is governed by the Drug Administration Law, as well as Good Clinical Practice (GCP) Guidelines. In 2017, China became a member of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), and since then has been working to align with global standards to help make the process of developing drugs more efficient and get them approved internationally. However, in China, clinical trial regulations are very pre-ye compared to USA regulations. Key aspects include:

IND Application and Approval in China

China's IND application process is governed by the National Medical Products Administration (NMPA) and reviewed by the Center for Drug Evaluation (CDE). For authorization, sponsors must provide detailed preclinical data, trial protocols, and ethics committee approval. The review process takes 60 working days, and the trial is automatically approved if there are no objections. China has a fast-track process for prioritizing drugs, including for rare diseases and medical needs with a clear sense of urgency. Also, accepting foreign clinical trial data can eliminate redundant early-phase studies. These reforms aim to make approvals more efficient and drive global pharmaceutical innovation into China.

Ethics Committee Review in China

Introduction Ethics Committees (ECs) are an essential component of the clinical trial process, ensuring the protection of the rights and welfare of research participants [1]. An IEC is responsible for approving each study and monitoring compliance with GCP and international ethical standards. Informed consent process, risk-benefit analysis, and concern for the subject are key review features. Ethics Committees provide continuing oversight, at which point study updates are regularly requested and amendments to the protocol to ameliorate safety issues are reviewed. This protects vulnerable populations and maintains ethical standards for clinical trials conducted in China.

Clinical Trial Listing in China

China has a public clinical trial registration database, the Chinese Clinical Trial Registry (ChiCTR) [5], which is the counterpart to the clinical trials in this country. Gov, which improves research transparency through information on study aims, sponsors, trial design,  eligibility criteria, and recruitment status. All interventional trials performed in China must be registered, adhering to the WHO International Clinical Trial Registry Platform (ICTRP) principles. Some pharmaceutical trials, for instance, are also maintained by the NMPA Drug Clinical Trial Registration and Information Disclosure Platform under regulatory review. These registries guarantee that ethics are addressed, publicly available trial data, and aid international cross-border cooperation.

INDIA: CDSCO AND NEW DRUGS AND CLINICAL TRIALS RULES (2019)

Clinical trials in India involve a structured regulatory pathway governed by the Central Drugs Standard Control Organization (CDSCO) under the Drugs and Cosmetics Act, 1940, and the New Drugs and Clinical Trials (NDCT) Rules, 2019 [6]. Key highlights include:

Regulatory Authority and Approval Process

CDSCO (Central Drugs Standard Control Organization) regulates clinical trials in India and operates under the DCGI (Drugs Controller General of India). The approvals are granted in compliance with the New Drugs and Clinical Trials (NDCT) Rules, 2019 under which, an application (Fom CT-04) must be submitted by the sponsors along with complete preclinical and clinical data, specifying the protocol of the trial,  investigator's brochure, informed consent documents, etc. It then forwards the application to the DCGI for final approval, after the SEC reviews the application for scientific and ethical validity. Upon its approval, the Form CT-06 will be issued by the DCGI, marking the start of the trial. It usually will take anywhere from 30 to 90 days, depending on the intricacy of the trial and if further clarifications are needed.

Ethics Committee (EC) Oversight

Every clinical trial in India must be reviewed and approved by an Ethics Committee (EC) that is registered with CDSCO. The EC ensures that the trial adheres to Good Clinical Practice (GCP) guidelines, protecting the rights, safety, and well-being of trial participants. It evaluates the study protocol, informed consent documents, and risk-benefit ratio before granting approval. The EC also plays a crucial role in monitoring the study’s progress, reviewing Serious Adverse Events (SAEs), and ensuring that participants receive adequate compensation in case of trial-related injuries or harm. Without EC approval, a clinical trial cannot proceed.

Final Safety and Regulatory Compliance

Clinical trials in India are subject to strict safety monitoring and regulatory compliance measures enforced by CDSCO. Sponsors must report all Serious Adverse Events (SAEs) to the DCGI, Ethics Committee, and Data Safety Monitoring Board (DSMB) within 14 days of occurrence. Post-marketing surveillance (Phase IV trials) is required to assess long-term safety and effectiveness. Regular inspections and audits by CDSCO ensure adherence to Good Clinical Practice (GCP) and regulatory guidelines. Any non-compliance may lead to penalties, suspension, or termination of the trial, ensuring patient safety remains the top priority.

JAPAN: PMDA AND GCP REGULATORY AND KEY REGULATIONS

Clinical trials in Japan are regulated by the Pharmaceuticals and Medical Devices Agency (PMDA) and the Ministry of Health, Labor and Welfare (MHLW) under the Pharmaceutical and Medical Device Act (PMD Act). Trials must comply with Good Clinical Practice (GCP) guidelines, which align with ICH-GCP but include Japan-specific requirements. Ethical considerations are guided by the Ethical Guidelines for Medical and Health Research Involving Human Subjects. PMDA plays a crucial role in reviewing trial applications, providing scientific advice, and ensuring compliance through inspections [7].

Clinical Trial Notification (CTN), Approval (CTA), and Process

Early-phase trials, particularly exploratory Phase I studies, require a Clinical Trial Notification (CTN), where sponsors submit trial details to PMDA without formal approval. However, confirmatory Phase II and III trials intended for regulatory submission require Clinical Trial Approval (CTA), where PMDA reviews and approves the study before initiation. The process includes pre-consultation with PMDA, Institutional Review Board (IRB) approval, submission of the CTN or CTA, adherence to GCP during trial conduct, safety reporting, and submission of a New Drug Application (NDA) upon successful Phase III completion.

Ethics Committee

Ethical oversight of clinical trials is conducted by Institutional Review Boards (IRBs) at each study site, ensuring that trials meet ethical and regulatory standards. IRB approval is mandatory before trial initiation, and ongoing ethical review is required throughout the study. Japan’s GCP mandates that IRBs include independent members, ensuring unbiased assessments. In addition to IRB approval, trials involving human subjects must comply with Japan’s Ethical Guidelines for Medical and Health Research Involving Human Subjects, which emphasize patient rights, informed consent, and data protection.

Country-Specific Requirements

Japan has unique regulatory expectations, including a preference for local clinical data, meaning a substantial portion of study participants must be Japanese. Bridging studies are often required when sponsors rely on foreign clinical data to ensure drug efficacy and safety in Japanese patients. First-in-Human (FIH) Phase I trials can be conducted in Japan under specific conditions, but foreign data is sometimes accepted with additional justification. PMDA strongly encourages early regulatory consultation to streamline approvals, and compliance with Japan’s rigorous adverse event reporting requirements is essential throughout the trial.

SINGAPORE: HSA

Clinical Trials Regulation in Singapore is with the Health Sciences Authority (HSA) under the Ministry of Health (MOH), Singapore, to ensure the safety, efficacy, and ethical integrity of investigational medicinal products. HSA CTB is formally responsible for reviewing and approving clinical trial applications, ensuring adherence to Good Clinical Practice (GCP) guidelines, and overseeing ongoing studies. HSA mandates clinical trials to follow Singapore’s Medicines Act, Health Products Act, and ICH-GCP (International Council for Harmonization – Good Clinical Practice) standards. The applications need to be made via the Pharmaceutical Regulatory Information System (PRISM) portal by sponsors and investigators, where HSA will review study protocols, safety data, and ethical considerations before approval is granted. The HSA also performs inspections and audits to verify compliance with regulatory requirements and participant safety throughout the lifecycle of the trial.

Regulatory Pathway

Singapore has a well-defined regulatory framework for clinical trials comprising two different routes of approval: Clinical Trial Authorization (CTA) and Clinical Trial Notification (CTN). However, for unregistered medicinal products, first-in-human (FIH) and high-risk investigational drugs, the clinical trial authorization (CTA) pathway is necessary as HSA carries out a detailed risk-based assessment that must be granted before proceeding. For lower-risk studies, such as those involving registered medicinal products used within their approved indications,  the CTN pathway applies, enabling a more streamlined path to approval. Sponsors must furnish extensive documentation, including the clinical trial protocol, the investigator’s brochure, chemistry, manufacturing, and control (CMC) data, informed consent forms from patients, and Institutional Review Board (IRB) approval. HSA reviews CTA applications in 30–60 days, whereas CTN applications can be processed within 5–7 working days, facilitating faster kick-off for low-risk trials. Compliance with HSA guidelines must be adhered to throughout the study, with deviations potentially resulting in regulatory actions, including, but not limited to, suspension or termination of the trial [8].

Ethics Review and Compliance

In Singapore, ethical oversight has long been considered an integral part of clinical trials, protecting participants' rights, safety, and well-being. All clinical trials must be reviewed and approved by an MOH-accredited Institutional Review Board (IRB). Some examples of well-known IRBs are Singapore General Hospital (SGH), National University Hospital (NUH), Tan Tock Seng Hospital (TTSH), and independent ethics committees. The IRB reviews trial protocols, informed consent processes, risk-benefit assessments, and investigator qualifications. Trials must adhere to ICH-GCP (International Council for Harmonization – Good Clinical Practice),  and Singapore's regulatory guidelines, to ensure data integrity and participant welfare. It is up to sponsors and investigators to keep accurate records, report adverse events, and follow proper informed consent procedures. Through random or for-cause inspections, HSA can verify compliance, with violations leading to regulatory warning, suspension, or trial termination.

Post-Trial Obligations

After completing a clinical trial, sponsors have post-trial responsibilities, including transparency, compliance with regulatory requirements, and ensuring the ongoing safety of participants. Upon completion of the trial, a final clinical study report must be submitted to HSA, comprising the results of the trial as well as safety and efficacy data. HSA must be informed of any Serious Adverse Events (SAEs) or unexpected safety issues identified during or after the clinical trial within 7 to 15 days, depending on the severity. Sponsors can seek product registration and marketing authorization (as appropriate) in Singapore if the investigational drug shows clinical benefit (including safety and efficacy). Depending on the scenario, participants and their proxies must be informed of any new safety data or findings that may affect their health, and sponsors may also offer continued access to investigational products if they are of benefit. HSA may also require further post-market studies or ongoing surveillance to assess the product's long-term safety.

CONCLUSION

Understanding and navigating the regulatory landscape for clinical trials is essential for global pharmaceutical companies. While regional differences persist, ongoing harmonization efforts seek to streamline processes, ensuring patient safety and accelerating medical innovation worldwide.