“21 CFR” is shorthand for Title 21 of the Code of Federal Regulations — the body of federal regulations that the U.S. Food and Drug Administration (FDA) uses to govern food, drugs, biologics, medical devices, cosmetics, and human-subjects research it oversees. Anyone who works on an FDA-regulated study eventually runs into a specific Part or section citation (21 CFR Part 11, 21 CFR 312.23(a)(6), 21 CFR Part 56) without ever having been shown the map of how Title 21 is organized or which Part governs which activity. This page is that map: what Title 21 actually is, how to read a CFR citation, and a routing table showing which Part governs what, who it binds, and where to read CASRAI’s dedicated coverage of it.
What Title 21 of the CFR Actually Is
The Code of Federal Regulations (CFR) is the official, annually updated codification of the general and permanent rules published by federal agencies in the Federal Register. It is organized into 50 numbered Titles, each covering a broad subject area administered by one or more federal agencies. Title 21, “Food and Drugs,” is the Title assigned to FDA’s rulemaking (it also contains the Drug Enforcement Administration’s controlled-substances regulations in a separate chapter). When someone says “21 CFR,” they mean “a regulation FDA issued, codified in Title 21.”
Practically, this matters because 21 CFR is not one rule — it is the entire regulatory output of an agency that oversees everything from food labeling to drug manufacturing to human-subjects protections. A research administrator, investigator, or sponsor typically only needs a handful of the hundreds of Parts within it. The routing table below is organized around the Parts that actually come up in research administration and clinical/nonclinical research operations.
The authoritative, continuously updated version of the CFR is the electronic CFR (eCFR), maintained jointly by the National Archives’ Office of the Federal Register and the Government Publishing Office. The eCFR is updated close to daily and is the version to cite or rely on for current text; the print CFR is republished only once a year.
How to Read a CFR Citation
CFR citations follow a consistent hierarchy: Title → Chapter → Part → Subpart → Section → Paragraph. Once you know the pattern, any citation becomes readable without looking anything up.
Take 21 CFR 312.23(a)(6) as a worked example:
- 21 — the Title (Food and Drugs, i.e., FDA’s regulatory domain)
- CFR — signals this is a codified regulation, not a statute (statutes are cited to the U.S. Code, “U.S.C.”)
- 312 — the Part (here, Investigational New Drug Application)
- .23 — the Section within that Part (here, IND content and format)
- (a)(6) — the paragraph and subparagraph within that section (here, the pharmacology-and-toxicology section of the IND)
A Part is sometimes broken into lettered Subparts (for example, 21 CFR Part 50 has Subpart B, “Informed Consent of Human Subjects,” and Subpart D, additional protections for children) that group related Sections together before the individual Section numbers. Citations you will see written as “21 CFR Part 56” (referring to an entire Part) versus “21 CFR 56.108” (referring to one specific Section, here IRB written procedures) both follow the same underlying structure — the difference is just how far down the hierarchy the citation drills.
Which Part Governs What: The 21 CFR Routing Table
The table below covers the Parts of Title 21 that most often come up in research administration, clinical trial operations, and regulated laboratory work. It is not exhaustive of all ~1,400 Parts of Title 21 (most concern food additives, cosmetics, and other subject matter outside CASRAI’s scope) — it is the practical subset a research administrator, investigator, IRB member, or QA professional actually needs.
| Part | Subject | Who it binds | CASRAI coverage |
|---|---|---|---|
| Part 11 | Electronic Records; Electronic Signatures — criteria for when an electronic record/signature is considered trustworthy and equivalent to a paper record/handwritten signature | Any FDA-regulated entity maintaining records or obtaining signatures electronically (EDC systems, eTMF, eConsent platforms) | 21 CFR Part 11: Electronic Records & Signatures |
| Part 50 | Protection of Human Subjects — general informed consent requirements and the required elements of consent | Investigators and sponsors of FDA-regulated clinical investigations | 21 CFR Part 50 (Protection of Human Subjects) |
| Part 54 | Financial Disclosure by Clinical Investigators — disclosure of financial interests/arrangements that could bias study results | Clinical investigators and sponsors submitting marketing applications | 21 CFR Part 54 (Financial Disclosure by Clinical Investigators) |
| Part 56 | Institutional Review Boards — IRB composition, function, operating procedures, and review authority | IRBs reviewing FDA-regulated research | 21 CFR Part 56 (Institutional Review Boards) |
| Part 58 | Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies — facility, personnel, and data-integrity requirements for nonclinical safety studies submitted to FDA | Nonclinical (animal/in vitro) safety-testing facilities and sponsors | Good Laboratory Practice (GLP) · see also GCP vs. GLP |
| Part 312 | Investigational New Drug Application (IND) — the pathway and ongoing obligations for testing an unapproved drug or biologic in humans | Drug/biologic sponsors and investigators conducting IND-governed trials | Investigational New Drug (IND) · 21 CFR 312.60 (General Responsibilities of Investigators) · FDA Form 1571 |
| Part 314 | Applications for FDA Approval to Market a New Drug — New Drug Application (NDA) and Abbreviated NDA (ANDA) requirements | Drug sponsors seeking marketing approval | 21 CFR Part 314 (Applications for FDA Approval to Market a New Drug) · 21 CFR 314.70 (Changes to an Approved NDA/ANDA) · 21 CFR 314.80 (Postmarketing Reporting of Adverse Drug Experiences) |
| Part 601 | Licensing — the Biologics License Application (BLA) pathway for biological products, under the Public Health Service Act | Biologic sponsors seeking marketing authorization | No dedicated CASRAI page yet |
| Part 812 | Investigational Device Exemptions (IDE) — the device analog to Part 312, governing clinical study of unapproved medical devices | Device sponsors and investigators conducting IDE-governed studies | Investigational Device |
| Part 820 | Quality System Regulation (QSR) — being replaced by the Quality Management System Regulation (QMSR), effective February 2, 2026 (see below) | Medical device manufacturers | ISO 13485: Medical Device Quality Management Systems Explained |
| Parts 210/211 | Current Good Manufacturing Practice (cGMP) for drugs and biologics | Drug/biologic manufacturers | GLP vs. GMP · GCP vs. GLP vs. GMP |
Two cross-cutting pages are worth knowing about even though they are not tied to a single Part: FDA Form 483, the form FDA investigators use to document objectionable conditions found during an inspection under any of the Parts above, and ICH GCP, the international standard (codified for FDA purposes primarily through Parts 50, 56, and 312) that Part 50/56/312 compliance is generally understood to implement.
The QSR-to-QMSR Transition Changes Part 820
Part 820, historically FDA’s standalone Quality System Regulation for device manufacturers, has been replaced by the Quality Management System Regulation (QMSR), effective February 2, 2026. Rather than maintaining a separate FDA-specific quality standard, the QMSR incorporates ISO 13485:2016 by reference as the base quality management system requirement for device manufacturers, with a small number of FDA-specific additions layered on top. This is a harmonization move: a device manufacturer that is already ISO 13485-certified for other markets no longer has to run a functionally separate U.S.-specific quality system in parallel. See CASRAI’s ISO 13485 guide for what the incorporated standard actually requires. Anything still referring to “21 CFR Part 820” or “the QSR” as a standalone FDA-only regulation is describing the pre-February-2026 state; current device-manufacturer obligations should be read through the QMSR.
How 21 CFR Relates to the Common Rule (45 CFR 46)
Researchers frequently need to know whether a study is governed by FDA’s Part 50/56 or by the Department of Health and Human Services’ Common Rule at 45 CFR 46 (or both). In short: FDA-regulated studies of a drug, biologic, or device follow 21 CFR Parts 50/56; federally funded human-subjects research more broadly follows 45 CFR 46; a single study testing an investigational product with federal funding can be subject to both, and the two rules are not identical (for example, in their expedited-review categories and continuing-review triggers). See CASRAI’s 45 CFR 46 vs. 21 CFR 50 comparison and the Common Rule entry for the detailed differences.
Frequently Asked Questions
What does “21 CFR” stand for?
It stands for Title 21 of the Code of Federal Regulations — the codified body of FDA regulations covering food, drugs, biologics, medical devices, and related human-subjects protections.
Is 21 CFR the same as an FDA guidance document?
No. 21 CFR contains binding regulations that carry the force of law once finalized through notice-and-comment rulemaking. FDA guidance documents describe the agency’s current thinking on how to comply with those regulations (or with statutes) but are explicitly non-binding on FDA and industry alike.
How often does 21 CFR change?
The eCFR (electronic CFR) is updated close to daily as individual final rules take effect; the bound, print edition of Title 21 is republished once a year (Title 21 is updated annually as of each April 1). Always check the eCFR for the current text of a specific Part rather than relying on a downloaded or cached copy.
What’s the difference between a “Part” and a “Section” in 21 CFR?
A Part is a broad regulatory subject (e.g., Part 312 covers the entire IND pathway). A Section is one specific numbered provision within that Part (e.g., 312.23 covers IND content and format specifically). Parts are sometimes subdivided into lettered Subparts that group related Sections before the individual Section numbers appear.
Which Part of 21 CFR governs informed consent?
21 CFR Part 50, specifically Subpart B, governs informed consent for FDA-regulated human-subjects research. See CASRAI’s 21 CFR Part 50 entry.
Does 21 CFR apply outside the United States?
21 CFR is U.S. federal law and applies to research and manufacturing that falls within FDA’s jurisdiction, which generally means products intended for the U.S. market or studies intended to support a U.S. marketing application, regardless of where the study is physically conducted. Non-U.S. sites participating in an FDA-regulated trial are still expected to meet the relevant 21 CFR requirements (or an FDA-recognized equivalent, such as ICH GCP) for that data to support a U.S. submission.
