CODE OF FEDERAL REGULATIONS {CFR}

NIPUN GUPTA M. PHARM 1ST YEARDEPTT. OF PHARMACEUTICS

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. The CFR is divided into 50 titles that represent

broad areas subject to federal regulation.

The CFR annual edition is the codification of the general and permanent rules

published by the Office of the Federal Register (part of the National Archives and

Records Administration) and the Government Publishing Office. In addition to this

annual edition, the CFR is published in an unofficial format online on the Electronic

CFR website, which is updated daily.

Code of Federal Regulations (CFR)

The regulations first published in the Federal Register on a daily basis are then codified in the Code

of Federal Regulations.

The regulations that are published chronologically in the Federal Register are codified and arranged

by title, then by chapter (one agency’s regulations) and finally by subject in the CFR.

The CFR is divided into 50 titles, just like the USCA

◦ Some titles covering the same subjects are numbered the same in the CFR and in the USCA;

others are not.

Each title is divided into chapters, subchapters, parts, and sections.

A regulation is cited by title, part, and section, e.g. 14 CFR 121.313 (Title 14, Part 121, Section 313).

The soft-cover volumes of the CFR are issued each year in sets on a staggered, quarterly basis:

◦ Titles 1 – 16 are updated as of January 1

◦ Titles 17 – 27 are updated as of April 1

◦ Titles 29 – 41 are updated as of July 1

◦ Titles 42 – 50 are updated as of October 1

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 color of each set of volumes is changed every year; a current full set may contain different

colored volumes, depending on the time of the year.

Title 3, which contains Presidential Proclamations and Executive Orders, is always white.

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 rulemaking authority for

regulations codified in the CFR.

CFR - Table of Contents

e - CFR

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 35 - Panama Canal [Reserved]

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

The following regulations apply to the IND application process:

21CFR Part 50 Protection of Human Subjects

21CFR Part 54 Financial Disclosure by Clinical Investigators

21CFR Part 56 Institutional Review Boards

21CFR Part 58 Good Lab Practice for Nonclinical Laboratory [Animal] Studies

21CFR Part 201 Drug Labeling

21CFR Part 312 Investigational New Drug Application

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

Approval)

21CFR Part 316 Orphan Drugs

In September 2010, the Food and Drug Administration issued final regulations addressing the safetyreporting requirements for investigational new drug applications (INDs) found in 21 CFR part 312 andfor 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 enhancingthe safety of patients in clinical trials. The final rule lays out clear definitions and standards so that criticalsafety information about investigational new drugs will be accurately and rapidly reported to the agency,minimizing uninformative reports and enhancing reporting of meaningful, interpretable information.

Research Tools in Each Volume of the CFR

Table of Contents listing all material within the book: titles, subtitles, chapters, subchapter(s), parts, andsections. 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 werepublished 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 sectionsof a regulation

List of CFR Sections Affected in the volume

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

Title 14

Chapter 1

Parts 60-139

Part 121

Subchapter D

121.313

CFR ti t les are broken down by chapter, subchapter, and par t .

Immediately preceding each par t is a table of contents for the individual

regulations contained within that par t .

TABLE OF CONTENTS

Title 14

Parts 60-139

Redesignation Table

Table of CFR Titles and Chapters

TABLE OF CFR TITLES AND CHAPTERS

REDESIGNATION TABLES TO HELP TRACE NEW LOCATION OF PARTS

AND SECTIONS OF A REGULATION

Title 14

Parts 60-139

List of CFR Sections Affected

List of CFR Sections Affected in Each Volume indicates the Type of

Change that was made.

Access to the CFR: Index and Finding Aids

CFR Index and Finding Aids is single volume

◦ Revised annually

◦ Index with subject entries and agency names in one listing

◦ Since 1980, a thesaurus has assured that all agencies use the same

terminology for subject headings

◦ Parallel Table of Authorities and Rules

◦ List of Agency-Prepared Indexes Appearing in Individual CFR Volumes

List of CFR Titles, Chapters,

Subchapters, and Parts

14 CFR 121 Index and Finding

Aids Volume

The List of CFR Titles, Chapters , Subchapters , and Parts Provides an

Outl ine of the CFR Organizat ion .

Updating Regulations in Print

LSA: List of CFR Sections Affected

Issued monthly

Indicates final and proposed changes made since the last publication of the CFR set

CFR Parts Affected

◦ In each volume of the Code of Federal Regulations

◦ Incorporated in the cumulative list in the Reader Aids section

CFR Parts Affected in this Issue

◦ In each daily issue of the Federal

Register

The Code of Federal Regulations Database (CFR) on Westlaw

The CFR database includes all 50 titles.

The database incorporates all but the most recent changes to the Code of Federal Regulations.

There is an approximately two-week lag between publication of the Final Rule in the Federal

Register and incorporation into the CFR database.

Historical CFR databases date back to 1984.

◦ Database identifiers are CFR01, CFR00, CFR99, etc.

Westlaw CFR Searches

If you know the citation of a CFR section

◦ Access the Find service

◦ Enter: 14 CFR 121.313

THE CFR ON WESTLAW

Useful fields :

The prelim field (PR) contains the CFR title and other headings that precede the caption

The caption field (CA) contains the CFR section number and heading

The notes field (NO) contains editorial and effective date notes

The credit field (CR) contains USCA authority and Federal Register source notes

21 CFR PART 210-CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING,

PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL

§210.1 Status of current good manufacturing practice regulations

§210.2 Applicability of current good manufacturing practice regulations

§210.3 Definitions

Definitions :

(a) The definitions and interpretations contained in section 201 of the act shall be applicable to such

terms when used in this part and in parts 211 through 226 of this chapter.

(b) The following definitions of terms apply to this part and to parts 211 through 226 of this chapter.

Act means the Federal Food, Drug, and Cosmetic Act, as amended (21 U.S.C.)

Batch means a specific quantity of a drug or other material that is in-tended to have uniform character

and qua1ity, within specified limits, and is produced according to a single manufacturing order during

the same cycle of manufacture.

Component means any ingredient intended for use in the manufacture of drug product, including

those that may not appear in such drug product.

Product means a finished dosage form, for example, tablet, capsule, solution, etc., that contains an

active drug ingredient generally, but not necessarily, in association with inactive ingredients. That

product does not contain an active ingredient but is intended to be used as a placebo.

Lot number, control number, or batch number means any distinctive combination of letters, numbers,

or symbols, or any combination of them, from which the complete history of the manufacture,

processing, packing, holding, and distribution of a batch or lot of drug product or other material can be

determined.

Manufacture, processing, packing, or holding of a drug product includes packaging and labeling

operations, testing, and quality control of drug products.

The term medicated feed means any Type B or Type C medicated feed defined as the feed contains

one or more drugs.

Quality control unit means any person or organizational element designated by the firm to be

responsible for the duties relating to quality control.

Strength means the concentration of the drug substance (for example, weight/weight, weight/volume,

or unit dose/volume basis)

Fiber means any particulate contaminant with a length at least three times greater than its width.

Non-fiber-releasing filter means any filter, which after any appropriate pre treatment such as washing or

flushing, will not release fibers into the component or drug product that is being filtered. All filters

composed of asbestos are deemed to be fiber-releasing filters.

Active ingredient means any component that is intended to furnish pharmacological activity or other direct

effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any

function of the body of man or other animals.

Inactive ingredient means any component other than an active ingredient.

In-process material means any material fabricated, compounded, blended, or derived by chemical reaction

that is produced for, and used in, the preparation of the drug product.

Lot means a batch, or a specific identified portion of a batch, having uniform character and quality within

specified limits; or, in the case of a drug product produced by continuous process, it is a specific identified

amount produced in a unit of time or quantity in a manner that assures it.

Theoretical yield means the quantity that would be produced at any appropriate phase of manufacture,

processing, or packing of a particular drug product, based upon the quantity of components to be used, in

the absence of any loss or error in actual production.

Actual yield means the quantity that is actually produced at any appropriate phase of manufacture,

processing, or packaging of a particular drug product.

Percentage of theoretical yield means the ration of the actual yield (at any appropriate phase of

manufacture, processing or packing of a particular drug product) to the theoretical yield (at the same

phase), stated as a percentage.

Acceptance criteria means the product specifications and acceptance/rejection criteria, such as

acceptable quality level and unacceptable quality level, with an associated sampling plan, that are

necessary for making a decision to accept or reject a lot or batch (or any other convenient sub groups of

manufactured units).

21 CFR PART 211 CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED

PHARMACEUTICALS.

SUBPART A GENERAL PROVISIONS

§ 211.1 Scope

§ 211.2 Definitions

SUBPART B ORGANIZATION AND PERSONNEL

§ 211.22 Responsibilities of quality control unit.

§ 211.25 Personnel qualifications

§ 211.28 Personnel responsibilities.

§ 211.34 Consultants

SUBPART C BUILDINGS AND FACILITIES

§ 211.42 Design and construction features

§ 211.44 Lighting

§ 211.46 Ventilation, air filtration, air heating and cooling

§ 211.48 Plumbing

§ 211.50 Sewage and refuse

§ 211.52 Washing and toilet facilities

§ 211.56 Sanitation

§ 211.58 Maintenance

SUBPART D EQUIPMENT

§ 211.63 Equipment design, size, and location

§ 211.65 Equipment construction

§ 211.67 Equipment cleaning and maintenance

§ 211.68 Automatic, mechanical, and electronic equipment

§ 211.72 Filters

SUBPART E CONTROL OF COMPONENTS AND DRUG PRODUCT CONTAINERS AND

CLOSURES

§ 211.80 General requirements

§ 211.82 Receipt and storage of untested components, drug product containers, and closures.

§ 211.84 Testing and approval or rejection of components, drug product containers, and closures

§ 211.86 Use of approved components, drug product containers, and closures

§ 211.87 Retesting of approved components, drug product containers, and closures

§ 211.89 Rejected components, drug product containers, and closures

§ 211.94 Drug product containers and closures

SUBPART F PRODUCTION AND PROCESS CONTROLS

§ 211.100 Written procedures; deviations

§ 211.101 Charge-in of components

§ 211.103 Calculation of yield

§ 211.105 Equipment identification

§ 211.110 Sampling and testing of in-process materials and drug products

§ 211.111 Time limitations on production

§ 211.113 Control of microbiological contamination

SUBPART G PACKAGING AND LABELING CONTROL

§ 211.122 Materials examination and usage criteria

§ 211.125 Labeling issuance

§ 211.130 Packaging and labeling operations

§ 211.132 Tamper-resistant packaging requirements for over-the-counter (OTC) human drug products

§ 211.134 Drug product inspection

§ 211.137 Expiration dating

SUBPART H HOLDING AND DISTRIBUTION

§ 211.142 Warehousing procedures

§ 211.150 Distribution procedures

SUBPART I LABORATORY CONTROLS

§ 211.160 General requirements

§ 211.165 Testing and release for distribution

§ 211.166 Stability testing

§ 211.167 Special testing requirements

§ 211.170 Reserve samples

§ 211.173 Laboratory animals

§ 211.176 Penicillin contamination

SUBPART J RECORDS AND REPORTS

§ 211.180 General requirements

§ 211.182 Equipment cleaning and use log

§ 211.184 Component, drug product container, closure, and labeling records

§ 211.186 Master production and control records

§ 211.188 Batch production and control records

§ 211.192 Production record review

§ 211.194 Laboratory records

§ 211.196 Distribution records

§ 211.198 Complaint files

SUBPART K RETURNED AND SALVAGED DRUG PRODUCTS

§ 211.204 Returned drug products

§ 211.208 Drug product salvaging

THANK YOU