21 CFR Part 211: Current Good Manufacturing Practice for Finished Pharmaceuticals

Exactly 100 vocabulary flashcards covering the definitions and specific requirements of 21 CFR Part 211 for current good manufacturing practice.

21 CFR Part 211

The authoritative federal regulation governing current good manufacturing practice for finished pharmaceuticals.

Subpart A

The section of 21 CFR Part 211 covering General Provisions, including scope and definitions.

§ 211.1 Scope

Specifies the minimum current good manufacturing practice for the preparation of drug products for administration to humans or animals.

§ 211.3 Definitions

States that the definitions set forth in § 210.3 apply to Part 211.

Quality control unit

The organizational unit responsible for approving or rejecting all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products.

§ 211.22(c)

Mandates that the quality control unit has responsibility for approving or rejecting all procedures or specifications impacting identity, strength, quality, and purity.

Personnel Qualifications (§ 211.25)

Requires each person engaged in manufacture, processing, packing, or holding to have education, training, and experience to perform assigned functions.

CGMP Training

Must be conducted by qualified individuals on a continuing basis to ensure employees remain familiar with CGMP requirements.

Protective apparel

Clean clothing and coverings (head, face, hand, arm) worn to protect drug products from contamination.

Limited-access areas

Building areas designated by supervisory personnel where only authorized personnel may enter.

Exclusion from direct contact

Required for any person with an apparent illness or open lesions that may adversely affect the safety or quality of drug products.

Consultants

Individuals advising on manufacturing who must have sufficient education, training, and experience, with records maintained of their qualifications.

Suitable size, construction, and location

Building requirements under § 211.42 intended to facilitate cleaning, maintenance, and proper operations.

Orderly placement

The requirement for adequate building space to prevent mixups and contamination between components, containers, and products.

Aseptic processing surfaces

Floors, walls, and ceilings that must be smooth, hard, and easily cleanable.

HEPA filters

High-efficiency particulate air filters used to provide filtered air under positive pressure for aseptic processing.

Penicillin manufacturing

Must be performed in facilities separate from those used for other drug products for human use.

§ 211.44 Lighting

Mandates that adequate lighting shall be provided in all areas.

Air filtration systems

Must include prefilters and particulate matter air filters when appropriate for production areas.

Potable water

Water meeting EPA Primary Drinking Water Regulations ($40 CFR part 141$) supplied under continuous positive pressure.

Air break

A mechanical device required on drains connected directly to a sewer to prevent back-siphonage.

Sewage and refuse disposal

Must be handled in a safe and sanitary manner from the building and immediate premises.

Sanitation procedures (§ 211.56)

Written procedures describing cleaning schedules, methods, equipment, and agents designed to prevent contamination.

FIFRA

The Federal Insecticide, Fungicide, and Rodenticide Act ($7 U.S.C. 135$), which governs the registration and use of rodenticides.

Equipment Construction (§ 211.65)

Requirements that surfaces contacting components or drug products must not be reactive, additive, or absorptive.

Lubricants or coolants

Substances used in equipment operation that must not contact components or drug products to alter their safety or purity.

Equipment cleaning intervals

Cleaning, maintenance, and sterilization at appropriate intervals to prevent malfunctions or contamination.

§ 211.67(b) procedures

Written steps for cleaning equipment, including disassembly, removal of previous batch identification, and protection from contamination.

Equipment Log

Records of maintenance, cleaning, sanitizing, and inspection that must be maintained.

Automatic equipment calibration

Electronic or mechanical equipment, including computers, must be routinely calibrated and checked according to a written program.

Input/output verification

Accuracy checks for computer systems based on complexity and reliability to ensure master production and control records are correct.

Backup file

An exact, complete, and secure duplicate of computer data maintained on hard copy, tapes, or microfilm.

Fiber-releasing filters

May be used in injectable drug manufacture only if impossible to manufacture without them, and MUST be followed by a nonfiber-releasing filter.

$$0.2\,micron$$

The maximum nominal pore size rating for a nonfiber-releasing filter used to reduce particles after a fiber-releasing filter.

Asbestos-containing filter

An equipment component whose use is prohibited in the manufacture of injectable drug products.

Off the floor storage

Required for bagged or boxed components and closures to permit cleaning and inspection.

Distinctive code

A code assigned to each lot in each shipment of components, containers, or closures to record its disposition.

Quarantine

The status of components, drug product containers, and closures until they have been tested or examined and released.

Representative samples

Material collected based on statistical criteria, supplier history, and quantity needed for analysis.

Aseptic sampling techniques

Procedures and sterile equipment used when necessary to collect samples without introducing contaminants.

Specific identity test

A test conducted on at least one component of a drug product to verify its identity.

Report of analysis

A document from a supplier that may be accepted in lieu of certain tests if the manufacturer validates the supplier's results.

Rotation of stock

The practice of using the oldest approved stock of components, containers, and closures first.

Retesting criteria (§ 211.87)

Conditions such as long storage or exposure to air/heat that necessitate re-evaluating approved components.

Reactive, additive, or absorptive containers

Prohibited characteristics for drug product containers and closures to ensure drug safety and purity.

Depyrogenation

The process of removing pyrogenic properties from containers or closures, which must be validated.

§ 211.100 Written procedures

Requirements for production and process control designed to ensure drug products have their purported identity and purity.

Justified deviation

Any departure from written procedures that must be recorded and defended at the time of performance.

Charge-in of components

The formulation of a batch intended to provide not less than $100\,\%$ of the labeled amount of active ingredient.

Yield calculation (§ 211.103)

The determination of actual yields and percentages of theoretical yield at the conclusion of manufacturing phases.

Theoretical yield

The quantity that would be produced at any appropriate phase based upon the quantity of components to be used.

Major equipment identification

The use of a distinctive number or code to record specific equipment used in the batch production record.

In-process controls (§ 211.110)

Written procedures to monitor output and validate performance of manufacturing processes that cause variability.

Bioburden testing

Testing for microbiological loads during in-process sampling and testing.

Time limitations on production

Limits established for the completion of each phase of production to ensure drug quality.

Objectionable microorganisms

Contaminants that must be prevented by written procedures in drug products not required to be sterile.

Reprocessing batch

A system for treating batches that do not conform to standards so that they meet established specifications.

Gang-printed labeling

Labeling from sheets containing different drug products, prohibited unless differentiated by size, shape, or color.

Cut labeling

Individual container labels that require special control procedures like dedication of lines or $100\,\%$ electronic examination.

Labeling reconciliation

An evaluation of discrepancies between the quantity of drug product finished and the quantity of labeling issued.

Lot or control number

A distinctive identification that permits determination of the history of manufacture and control of a batch.

Tamper-evident package

A package having one or more indicators or barriers to entry which provide visible evidence of breaching.

Distinctive by design

Packaging that cannot be duplicated with commonly available materials or processes.

Citizen petition (§ 10.30)

The form required to request an exemption from tamper-evident packaging and labeling rules.

Special packaging

Packaging defined under § 310.3(l) required under the Poison Prevention Packaging Act of 1970.

Expiration dating (§ 211.137)

A date on a drug product label determined by stability testing to ensure it meets standards at the time of use.

Stability testing (§ 211.166)

A written program assessing stability characteristics to determine storage conditions and expiration dates.

Homeopathic drug products

A class of drug products exempt from the expiration dating requirements of § 211.137.

Allergenic extracts

Products labeled 'No U.S. Standard of Potency' which are exempt from stability testing requirements.

Warehousing procedures

Written steps including quarantine before release and storage under appropriate temperature, humidity, and light.

Oldest approved stock (Distribution)

The requirement to distribute the earliest approved drug products first.

Subpart I Laboratory Controls

Regulatory section covering general requirements, testing, stability, and reserve samples.

Calibration (§ 211.160)

The checking of instruments at suitable intervals against limits for accuracy and precision.

Short-lived radiopharmaceuticals

Drug products that may be released prior to complete sterility testing if testing is finished ASAP.

Sensitivity and reproducibility

Attributes of test methods that must be established and documented by the firm.

Accelerated studies

Studies used with basic stability info to support tentative expiration dates when full shelf life studies are absent.

Sterile and pyrogen-free testing

Mandatory laboratory testing for each batch of drug product purporting to have these characteristics.

Ophthalmic ointment testing

Testing to determine conformance to specifications regarding foreign particles and harsh substances.

Controlled-release dosage form testing

Laboratory tests to determine the rate of release for each active ingredient.

Reserve Sample (Active ingredient)

A representative sample retained from each lot, consisting of at least twice the quantity for all required tests.

Retention time (Active ingredient)

Usually $1\,year$ after the expiration date of the last lot of drug product containing the ingredient.

Reserve Sample (Drug product)

A sample in its marketed container-closure system stored under labeled conditions and examined visually annually.

Laboratory animals

Animals used in testing whose health and history must be documented to ensure suitability for intended use.

Penicillin contamination testing

Testing required for non-penicillin drugs when cross-contamination is possible; must have no detectable levels.

Record retention (Subpart J)

The requirement to keep batch records for at least $1\,year$ after the expiration date of the batch.

Individual equipment logs

Chronological records of major equipment cleaning, maintenance (except routine lubrication), and use.

Master production and control records

Standardized documents for each drug product and batch size, requiring two signatures (prepared and checked).

Theoretical yield percentage

Limits established in master records beyond which an investigation under § 211.192 is required.

Batch production and control records

Records for each batch that include dates, equipment used, components, weights, and in-process results.

Production record review (§ 211.192)

The quality control unit examination of all records to determine compliance before a batch is released.

Unexplained discrepancy

A failure or yield variation that must be thoroughly investigated, including extension to other associated batches.

United States Pharmacopeia

A recognized standard reference for testing methods mentioned in § 211.194.

Distribution records (§ 211.196)

Records containing product name, dosage form, consignee address, date, quantity shipped, and lot number.

Complaint files (§ 211.198)

Written records of oral or written complaints maintained at the manufacturing establishment or accessible through inspection.

Serious and unexpected adverse drug experience

A type of complaint that must be identified and reported to the Food and Drug Administration.

Returned drug products (§ 211.204)

Products that must be identified and held; must be destroyed if storage/shipping conditions cast doubt on quality.

Drug product salvaging (§ 211.208)

Prohibits returning products to the marketplace if subjected to improper conditions (fire, disaster) unless proven safe by tests.

Organoleptic examinations

Sensory evaluations (e.g., smell, appearance) allowed only as supplemental evidence in salvaging operations.

$(s)$, $(l)$, $(g)$, $(aq)$

The standard LaTeX state symbols for solid, liquid, gas, and aqueous, used in scientific notations for CGMP documents.

43 FR 45077

The Federal Register source code for the original 1978 Current Good Manufacturing Practice regulations.