Research synthesis only; not medical advice. The regulations and guidelines described here govern clinical research involving human subjects. They apply to studies conducted under an Investigational New Drug (IND) application, Clinical Trial Authorisation (CTA), or equivalent. Unapproved or investigational products should only be used in the context of a formal, ethics-approved clinical trial.
Foundational documents
| Document | Year | Scope | Key provisions |
|---|---|---|---|
| Nuremberg Code | 1947 | Foundational | Voluntary consent, benefit must outweigh risk, qualified investigators |
| Declaration of Helsinki | 1964 (revised often, latest 2024) | International | Respect for persons, beneficence, justice; independent ethics committee review; special protections for vulnerable populations |
| Belmont Report | 1979 | US | Three principles: respect for persons (autonomy, informed consent), beneficence (risk--benefit analysis), justice (fair selection of subjects) |
| CIOMS International Ethical Guidelines | 2016 | International | Detailed guidance on informed consent, community engagement, and research in resource-limited settings |
| ICH E6 Good Clinical Practice (GCP) | 1996 (R3: 2025) | International | Unified standard for design, conduct, recording, and reporting of clinical trials; E6(R2) withdrawn by FDA April 2026 |
Regulatory frameworks
United States
FDA regulations: 21 CFR Part 50 (Informed Consent), Part 56 (IRBs), Part 312 (IND), Part 812 (IDE for devices)
HHS regulations: 45 CFR Part 46 (Common Rule) — Subpart A (basic), B (pregnant women/fetuses/nconates), C (prisoners), D (children)
ClinicalTrials.gov registration: Required for all applicable clinical trials per FDAAA 2007
IND requirements: Any clinical investigation of an unapproved drug, or a new indication/route/dose of an approved drug, requires an IND unless exempted (21 CFR 312.2)
European Union
Clinical Trial Regulation (EU) 536/2014: Replaced the Clinical Trials Directive (2001/20/EC) as of 2022. Single authorisation via the Clinical Trials Information System (CTIS).
Informed consent: Detailed requirements in Article 29; includes right to withdraw, compensation for damage, and data protection.
EU Clinical Trials Register (https://www.clinicaltrialsregister.eu): Public registry.
United Kingdom
Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031): As amended post-Brexit.
Health Research Authority (HRA): Approves research in the NHS.
ISRCTN registry: One of the WHO-recognized primary registries.
Other jurisdictions
Japan: Pharmaceutical and Medical Device Act (PMD Act); Clinical Trials Notification system; MHLW GCP Ministerial Ordinance.
Canada: Food and Drugs Act and Regulations (Division 5 — Clinical Trials); Health Canada authorization required.
Australia: Therapeutic Goods Act 1989; Clinical Trial Notification (CTN) or Clinical Trial Exemption (CTX) scheme.
WHO: International Clinical Trials Registry Platform (ICTRP); Good Clinical Practice guidelines.
Institutional Review Board / Ethics Committee
An IRB (US) or Research Ethics Committee (REC, UK; IEC, EU) is an independent body that reviews, approves, and monitors research involving human subjects.
Composition (21 CFR 56.107)
An IRB must have at least five members with:
Varying backgrounds to promote complete and adequate review
At least one member whose primary concerns are in scientific areas
At least one member whose primary concerns are in nonscientific areas
At least one member unaffiliated with the institution
Review categories
| Category | Criteria | Examples |
|---|---|---|
| Full board review | Greater than minimal risk; involves vulnerable populations | Phase I peptide study in healthy volunteers |
| Expedited review | Minimal risk; fits one of nine expedited categories | Blood draw from consenting adults for PK study |
| Exempt | Minimal risk and fits exempt categories | De-identified sample analysis; certain survey research |
Key considerations for peptide studies
An IRB reviewing a peptide research protocol evaluates:
Scientific rationale: Is there sufficient preclinical data (pharmacology, toxicology) to support human testing?
Risk--benefit analysis: Are the potential benefits proportionate to the risks?
Informed consent process: Is the consent form clear, complete, and non-coercive? Does it disclose the investigational status?
Subject selection: Are the inclusion/exclusion criteria justified? Is the recruitment process fair?
Safety monitoring: Is there a Data Safety Monitoring Board (DSMB) or Safety Monitoring Committee (SMC) for higher-risk studies?
Adverse-event reporting: Are there clear procedures for SAE reporting?
Privacy and data security: Are subject data adequately protected?
Informed consent
Informed consent is the process of providing a potential subject with all relevant information about a study so they can make a voluntary decision about participation.
Required elements (21 CFR 50.25, ICH E6 4.8.10):
Statement that the study involves research
Purpose of the research
Duration of participation and procedures
Foreseeable risks or discomforts
Expected benefits, if any
Alternative procedures or treatments available
Confidentiality of records
Compensation and treatment for injury (for more than minimal risk)
Contact information for questions, concerns, and injuries
Voluntary participation and right to withdraw without penalty
Additional elements (when applicable):
Risk of fetal harm if pregnant
Circumstances for termination of participation by the investigator
Additional costs to the subject
Consequences of withdrawal
Significant new findings that may affect willingness to continue
Approximate number of subjects involved
Research-use-only products and the ethical boundary
Products sold or labeled "for research use only" (RUO), "not for human use," or "for laboratory use" are explicitly not intended for human administration (21 CFR 812.3; 21 CFR 312.160). Using such products in a human subject:
Violates the terms of the product's labeling
Circumvents the IND/CTA process
Lacks the quality assurance (sterility, endotoxin, assay verification) required for human use
Exposes subjects to unknown risks without oversight
An IRB cannot approve a protocol using such products because the product's safety and quality cannot be assured.
Sources
US Department of Health and Human Services. Protection of Human Subjects (Common Rule). 45 CFR Part 46. 2018 revision. https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html
FDA. Protection of Human Subjects. 21 CFR Parts 50 and 56. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=50
FDA. Investigational New Drug Application. 21 CFR Part 312. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=312
ICH Harmonised Guideline. Good Clinical Practice (E6(R3)). Final version, adopted 6 January 2025. https://database.ich.org/sites/default/files/ICH_E6%28R3%29_Step4_FinalGuideline_2025_0106.pdf
World Medical Association. Declaration of Helsinki — Ethical Principles for Medical Research Involving Human Subjects. 2024. https://www.wma.net/hb-e-version-2024-2/
CIOMS. International Ethical Guidelines for Health-Related Research Involving Humans. 2016. https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf
Regulation (EU) No 536/2014 of the European Parliament and of the Council on Clinical Trials on Medicinal Products for Human Use. 2014. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32014R0536
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report. 1979. https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html