Code of Federal Regulations

A Brief presentation on the Code of Federal Regulations in Pharmaceuticals (21 CFR), which covers the following aspects:
- Introduction to CFR
- Organization and structure of CFR
- History of CFR
- Table of Contents
- Title 21; CFR in Pharmaceuticals
- IND Application process regulations
- Research tools in CFR

1. CODE OF FEDERAL
REGULATIONS
Presented by:
Mohit Mahesh Angolkar
B.Pharm VIII Semester
KLE College of Pharmacy,
Belagavi
CODE OF
FEDERAL
REGULATIONS

2. Introduction to Code of Federal Regulations (CFR)
❖The Code of Federal Regulations (CFR) is the codification of the general
and permanent rules and regulations (sometimes called administrative
law) published in the Federal Register by the executive departments and
agencies of the federal government of the United States.
❖Federal Register is the part of the National Archives and Records
Administration.
❖The CFR annual edition is the general and permanent rules published
by the Office of the Federal Register and the Government Publishing
Office (GPO).
❖In addition to this annual edition, the CFR is published in an unofficial
format online on the Electronic CFR website, which is updated daily.
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3. How it is organized?
❖The CFR is divided into 50 titles that represents broad areas subject to
federal regulations.
❖Each title is divided into chapters, which usually bear the name of the
issuing agency.
❖Each chapter is further divided into parts that covers specific regulatory
areas.
❖Large parts may be subdivided into subparts.
❖All parts are organised in sections and most citations to the CFR refer to
material at the section level.
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4. Structure of a CFR citation
❖Title: The numeric value to the left of “CFR”
❖Part: The numeric value to the right of “CFR” and preceding the period
(“.”)
❖Section/subpart: The numeric value to the right of the period (“.”). A
subpart is a letter of the alphabet (A-Z) that is used to retrieve an entire
subpart of the CFR rather than many individual sections. For example:
Subpart E.
❖Revision year: It represents the year being cited.
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5. ❖Example : 21 CFR 310.502 Revised as of April 1, 1997
❖Title: 21
❖Part: 310
❖Section: 502
❖Year: 1997
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6. At the beginning, each
PART of the CFR
contains:
1. Table of contents for that part
2. Authority for the part
3. Source note
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7. ❖If an individual section has
separate authority or separate
source information, that will be
noted at the end of that section.
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8. History of CFR
❖The Federal Register Act originally provided for a complete compilation
of all existing regulations prior to the first publication of the Federal
Register, but was amended in 1937 to provide a codification of all
regulations every five years.
❖The first edition of the CFR was published in 1938 and included all
finalised regulations that were published in the Federal Register from
March 14, 1936 to June 1, 1938.
❖Beginning in 1963 for some titles and for all titles in 1967, the office of the
Federal Register began publishing yearly revisions.
❖Beginning in 1972- published revisions were conducted in staggered
quarters.
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9. ❖The 50 subject matter titles contain one or more individual volumes,
which are updated once each calendar year, on a staggered basis.
❖The annual update cycle is as follows:
•Titles 1-16 are revised as of January 1
•Titles 17-27 are revised as of April 1
•Titles 28-41 are revised as of July 1
•Titles 42-50 are revised as of October 1
❖The online CFR is a joint project authorized by the publisher, the
National Archives and Records Administration’s (NARA) office of the
Federal Register (OFR), and the Government Publishing Office (GPO) to
provide the public with enhanced access to Government information.
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10. ❖Each new set contains the text of all regulations in force as of the current
through date. New regulations are merged with, and revoked regulations
are deleted from, the previous set of regulations.
❖The Office of the Federal Register also keeps an unofficial, online version
of the CFR, the e-CFR, which is normally updated within two days after
changes that have been published in the Federal Register become
effective.
❖The Parallel Table of Authorities and Rules lists rule making authority
for regulations codified in the CFR.
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11. CFR- Table of Contents
❖Title 1 - General Provisions
❖Title 2 - Grants and Agreements
❖Title 3 - The President
❖Title 4 - Accounts
❖Title 5 - Administrative Personnel
❖Title 6 - Domestic Security
❖Title 7 - Agriculture
❖Title 8 - Aliens and Nationality
❖Title 9 - Animals and Animal Products
❖Title 10 - Energy
❖Title 11 - Federal Elections
❖Title 12 - Banks and Banking
❖Title 13 - Business Credit and Assistance
❖Title 14 - Aeronautics and Space
❖Title 15 - Commerce and Foreign Trade
❖Title 16 - Commercial Practices
❖Title 17 - Commodity and Securities Exchanges
❖Title 18 - Conservation of Power and Water Resources
❖Title 19 - Customs Duties
❖Title 20 - Employees' Benefits
❖Title 21 - Food and Drugs
❖Title 22 - Foreign Relations
❖Title 23 - Highways
❖Title 24 - Housing and Urban Development
❖Title 25 - Indians
❖Title 26 - Internal Revenue
❖Title 27 - Alcohol, Tobacco Products and Firearms
❖Title 28 - Judicial Administration
❖Title 29 - Labor
❖Title 30 - Mineral Resources
❖Title 31 - Money and Finance: Treasury
❖Title 32 - National Defense
❖Title 33 - Navigation and Navigable Waters
❖Title 34 - Education
❖Title 36 - Parks, Forests, and Public Property
❖Title 37 - Patents, Trademarks, and Copyrights
❖Title 38 - Pensions, Bonuses, and Veterans' Relief
❖Title 39 - Postal Service
❖Title 40 - Protection of Environment
❖Title 41 - Public Contracts and Property Management
❖Title 42 - Public Health
❖Title 43 - Public Lands: Interior
❖Title 44 - Emergency Management and Assistance
❖Title 45 - Public Welfare
❖Title 46 - Shipping
❖Title 47 - Telecommunication
❖Title 48 - Federal Acquisition Regulations System
❖Title 49 - Transportation
❖TItle 50 - Wildlife and Fisheries
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12. Title 21: Food and Drugs
Code of Federal
Regulations in
Pharmaceuticals
❖Title 21 is the portion of the Code of
Federal Regulations that governs food
and drugs within the United States for
the Food and Drug Administration
(FDA), the Drug Enforcement
Administration (DEA) and the Office of
National Drug Control Policy (ONDCP).
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❖It is divided into three chapters:
•Chapter I - Food and Drug Administration
•Chapter II - Drug Enforcement Administration
•Chapter III - Office of National Drug Control
Policy

13. Chapter I - Food and Drug Administration
❖The regulations are derived from the Federal Food, Drug and Cosmetics Act.
❖21 CFR is generally known for 21 CFR part 11 which deals with rules concerning
digital signatures and electronic records maintenance.
❖This chapter has many sections dealing with various guidelines:
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Notable sections:
•11 Electronic records and electronic signature related
•50 Protection of human subjects in clinical trials
•54 financial disclosure by Clinical Investigators
•56 Institutional Review Boards that oversee clinical trials
•58 Good Laboratory Practices (GLP) for nonclinical studies

14. The 100 series - regulations pertaining to food
•101.9 Nutritional facts label related
- (c)(2)(ii) Requirement to include Trans-Fat Values
- (c)(8)(iv) Vitamin and Mineral values
•106-107 Requirements for infant formula
•110 et seq. cGMPs for Food Products
•111 et seq. cGMPs for Dietary Supplements
•170 Food Additives
•190 Dietary Supplements
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15. The 200 and 300 series - regulations pertaining to pharmaceuticals:
•202-203 Drug advertising and marketing
•210 et seq. cGMPs for pharmaceuticals
•310 et seq. Requirements for new drugs
•328 et seq. Specific requirements for over-the-counter (OTC) drugs.
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The 500 series - regulations for animal feeds and animal medications:
•510 et seq. New animal drugs
•556 Tolerances for residues of drugs in food animals
The 600 series - covers biological products (eg. vaccines, blood):
•601 Licensing under section 351 of the Public Health Service Act
•606 et seq. cGMPs for human blood and blood products

16. The 700 series - includes the limited regulations on cosmetics:
•701 Labelling requirements
The 800 series - for medical devices:
•803 Medical Device Reporting
•814 Premarket Approval of Medical Devices
•820 et seq. Quality system regulations (analogous to cGMP, but
structured like ISO)
•860 et seq. Listing of specific approved devices and how they are
classified
The 900 series - covers mammography quality requirements enforced by
CDRH.
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17. The 1000 series - covers radiation-emitting device:
•Example includes cell phones, lasers, x-ray generators
•Requirements enforced by the Centre for Devices and Radiological Health.
•It also talks about the FDA citizen petition.
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The 1100 series - includes:
•Updated rules deeming items that statutorily come under the definition
of “tobacco product” to be subject to the Federal Food, Drugs and
Cosmetics Act as amended by the Tobacco Control Act.
•The items affected include E-cigarettes, Hookah tobacco, and pipe
tobacco.

18. The 1200 series - consists of rules primarily based in laws other than
the Food, Drug and Cosmetics Act.
•1240 rules promulgated under 361 of the Public Health Services Act
on interstate control of communicable disease, such as:
- Requirements for pasteurisation of milk
- Interstate shipment of turtles as pets.
- Interstate shipment of African rodents that may carry
monkeypox.
- Sanitation on interstate conveyances ( i.e. airplanes and ships)
•1271 Requirements for human cells, tissues, and cellular and tissue-
based products (i.e. the cGTPs).
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19. Chapter II - Drug Enforcement Administration
Notable sections:
❖1308 - schedules of controlled substances
•1308.03(a) Administrative Controlled Substances Code Number
•1308.11 List of Schedule I drugs
•1308.12 List of Schedule II drugs
•1308.13 List of Schedule III drugs
•1308.14 List of Schedule IV drugs
•1308.15 List of Schedule V drugs
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20. Chapter III - Office of National Drug Control Policy
❖It deals with rules concerning the implementation of a drug-free
environment in government workplaces.
Notable section
•1405 Government-Wide requirements for Drug-Free workplaces
❖Programs of the ONDCP:
•The High Intensity Drug Trafficking Areas (HIDTA) program
•National Youth Anti-Drug Media Campaign
•World Anti-Doping Agency (WADA)
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21. IND Application Process Regulations
❖21 CFR Part 50 Protection of Human Subjects

❖21 CFR Part 54 Financial Disclosure by Clinical Investigators
❖21 CFR Part 56 Institutional Review Boards

❖21 CFR Part 58 Good Lab Practices for Nonclinical Laboratory (animal) studies

❖21 CFR Part 201 Drug Labelling
❖21 CFR Part 312 Investigational New Drug Application

❖21 CFR Part 314 INDA and NDA Applications for FDA Approval to Market a
New Drug (New Drug Approval)

❖21 CFR Part 316 Orphan Drugs
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22. ❖In September 2010, the Food and Drug Administration issued final
regulations addressing the safety reporting requirements for
investigational new drug applications (INDs) found in 21 CFR Part 312
and for Bioavailability and Bioequivalence studies found in 21 CFR Part
320.
❖This final rule is expected to improve the quality of safety reports
submitted to FDA, thereby enhancing the safety of patients in clinical
trials.
❖The final rule lays out clear definitions and standards so that critical
safety information about Investigational New Drugs will be accurately
and rapidly reported to the agency, minimising uninformative reports
and enhancing reporting of meaningful, interpretable information.
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23. Research tools in each volume of the CFR
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❖Table of contents listing all material within the book: titles, subtitles, chapters,
subchapters, parts and sections.
•Subtitles are referenced to page numbers.
❖Material approved for incorporation by Reference, which is regulatory material
not published in the Federal Register or CFR;
•Has force of law as if it were published in the Federal Register and CFR
•Mostly technical standards, state law and regulations
❖Table of CFR titles and chapters; Redesignation tables to help trace new location
of parts and sections of a regulation.
❖List of CFR sections affected in each volume.

24. Table of Contents:
At the beginning of each print issue:
❖Documents are listed by agencies in alphabetical order
•Cross-referenced from Cabinet departments to subordinate agencies
•Each agency document is arranged by category
- Rules
- Proposed rules
- Notices
❖Presidential documents are arranged as follows;
•Executive orders
•Proclamations
•Determinations/Memoranda
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25. ❖CFR titles are broken down by chapter, subchapter and part.
❖Immediately preceding each part is a table of contents for the individual
regulations contained within that part.
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26. ❖Material approved for incorporation by Reference, which is regulatory material not
published in the Federal Register or CFR;
•Has force of law as if it were published in the Federal Register and CFR
•Mostly technical standards, state law and regulations
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27. ❖Table of CFR titles and chapters;
•Redesignation tables to help trace new location of parts and sections of a
regulation.
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28. ❖List of CFR sections affected in each volume indicates the type of change
that was made.
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29. Conclusion
❖The Federal Register and the Code of Federal Regulations replaced the
existing system of dual set of regulations and legislations that were in
place.
❖Although not perfect, the Federal Register and the CFR appear to have
met their original purpose of providing the public with a comprehensive
publication vehicle for all the regulations issued by Federal agencies and
the President.
❖The CFR provided a codified form of the regulations, based on title,
chapters and subjects, that streamlined the process of finding the
required regulations and laws for the Pharmaceutical industry and
public in general, thereby making these guidelines easily accessible.
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30. REFERENCES
❖CFR- Code of Federal Regulations Title 21. Available form: https://
www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm
❖CFR Table of Contents https://www.law.cornell.edu/cfr/text
❖https://www.govinfo.gov/app/details/CFR-2011-title21-vol7/CFR-2011-title21-vol7-
part740-toc-id346/context
❖Introduction to Code of Federal Regulations. Slideshare: https://www.slideshare.net/
AnkitMalik60/cfr-ankit
❖https://www.slideshare.net/SwapnilFernandes1/code-of-federal-regulations
❖https://www.slideshare.net/ArabindaChangmai/code-of-federal-regulations-cfr-in-
pharmaceutical-88513524
❖https://slideplayer.com/amp/2488561/
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31. THANK YOU