21 CFR Food and Drugs
PART 211 Current Good Manufacturing Practice for Finished Pharmaceuticals
SUBPART A GENERAL PROVISIONS
211.1 The regulations in this part contain the minimum current good manufacturing practice for the preparation of
drug products for administration to humans or animals.
211.3 (Definitions) The scope of the regulations are explained for human prescription and OTC drug products including drugs used to produce medicated animal feed. Reference is made to Part 210.3 of the chapter that gives definitions for all significant terms used in the regulations.
SUBPART B ORGANIZATION AND PERSONNEL
211.22 (Responsibilities of Quality (QC) unit) The QC unit has total responsibility for ensuring that adequate
systems and procedures exist and are followed to ensure product quality.
211.25 (Personnel qualifications) Personnel, either supervisory or operational, must be qualified by training and
experience to perform their assigned tasks.
211.28 (Personnel responsibilities) The obligations of personnel engaged in the manufacture of drug products concerning their personal hygiene, clothing, and medical status are defined.
211.34 (Consultants) The qualifications (education, training, and experience, or any combination thereof) of consultants must be sufficient for the project to which they are assigned.
SUBPART C BUILDINGS AND FACILITIES
Buildings and facilities are considered acceptable only if they are suitable for their intended purpose and can be cleaned and otherwise maintained. Design and construction features for lighting, pest control, and maintenance are described below.
211.42 (Design and construction features)
211.46 (Ventilation, air filtration, air heating and cooling)
211.50 (Sewage and refuse)
211.52 (Washing and toilet facilities)
SUBPART D EQUIPMENT
Equipment must be designed, constructed, of adequate size, suitably located, and able to be maintained and cleaned to be considered suitable for its intended use. Regarding the use of automatic equipment, data processors, and computers, there is a need for input/output verification and for proper calibration of recorders, counters, and other electrical or mechanical devices.
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) Filters to be used liquid filtration shall not release fibres into products.
SUBPART E CONTROL OF COMPONENTS AND DRUG PRODUCT CONTAINERS AND CLOSURES
211.80 (General requirements) Written procedures must be available that describe the receipt, identification, storage, handling, sampling, testing, and approval or rejection of components (raw materials) and drug products.
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) Materials shall be rotated so that
the oldest approved stock is used first.
211.87 (Retesting of approved components, drug product containers, and closures) Materials shall be retested
or reexamined as necessary after storage for long periods or after exposure to air, heat or other conditions
that might adversely affect the component, drug product container, closure.
211.89 (Rejected components, drug product containers, and closures) These items shall be identified and controlled to prevent their use in manufacturing.
211.94 (Drug product containers and closures) Containers and closures (product contact materials) must protect the product and must be nonreactive with or additive to the product, suitable for their intended use, and controlled using written procedures.
SUBPART F PRODUCTION AND PROCESS CONTROLS
211.100 (Written procedures and deviations) Written standard operating procedures (SOPs) for each production process and control procedure are necessary. Any deviation from an SOP must be investigated, recorded, and approved prior to final product acceptance.
211.101 (Charge-in of components) The procedures used to formulate a batch shall be written and followed.
211.103 (Calculation of yield) Actual yields and theoretical yields shall be determined. All products are to
be formulated to provide not less than 100% of the required amount of active ingredients. The identity
and quantity of each component incorporated into a batch must be recorded.
211.105 (Equipment identification) Equipment shall be properly identified.
211.110 (Sampling and testing of in-process materials and drug products) Significant in-process steps are to be identified and appropriate sampling, testing, and approvals obtained before proceeding further in the production cycle. Rejected material must be controlled.
211.111 (Time limitations on production) If required, time limitations will be placed on in-process steps.
211.113 (Control of microbiological contamination) Appropriate procedures are to be prepared for the control and prevention of microbiological contamination. The sterilization process must be validated.
211.115 (Reprocessing) Reprocessing of product is allowed providing there are written procedures covering the methods and QC unit review to be used.
SUBPART G PACKAGING AND LABELING CONTROL
211.122 (Materials examination and usage criteria) Labeling and packaging materials are to be received, identified, stored, sampled, and tested following detailed written procedures.
211.125 (Labeling issuance) Strict control shall be exercised over labelling for use in drug product labelling operations.
211.130 (Packaging and labelling operations) There shall be written procedures designed to ensure that correct labels, labelling, and packaging materials are used for drug products. Special controls must be exercised over labelling to ensure that only the correct labels are issued to packaging for a specific product and that the quantities used are reconciled with the quantity issued.
211.132 (Tamper-resistant packaging requirements for over-the-counter (OTC) human drug products) Provides details of tamper-resistant packaging.
211.134 (Drug product inspection) Packaged and labelled products shall be inspected for correct labels.
211.137 (Expiration dating) As supported by appropriate stability studies, products on the market shall bear an expiration date.
SUBPART H HOLDING AND DISTRIBUTION
211.142 (Warehousing procedures) Describes the requirements for warehousing holding products under appropriate conditions of light, temperature, and humidity.
211.150 (Distribution procedures) Written procedures describing product distribution shall be prepared.
SUBPART I LABORATORY CONTROLS
211.160 (General requirements) The general requirements for laboratory control mechanisms are described.
211.165 (Testing and release for distribution) There shall be written procedures in the form of specifications, standards, sampling plans, and test procedures that are used in a laboratory for controlling components and finished drug products. Acceptance criteria for sampling and approval shall be adequate to support the release of the product for distribution.
211.166 (Stability testing) There shall be a written testing program designed to assess the stability characteristics of drug products. The results of this testing shall be used in assigning appropriate storage conditions and expiration dates.
211.167 (Special testing requirements) There are special testing requirements for sterile and/or pyrogen-free ophthalmic ointment and controlled-release dosage form products.
211.170 (Reserve samples) Reserve sample quantity and retention times are described.
211.173 (Laboratory animals) Animals used in any testing shall be maintained and controlled in a manner suitable for use.
211.176 (Penicillin contamination) Drug products cannot be marketed if, when tested by a prescribed procedure, found to contain any detectable levels of penicillin.
SUBPART J RECORDS AND REPORTS
211.180 (General requirements) Describes record retention time and availability for inspection.
211.182 (Equipment cleaning and use log) A written record of major equipment cleaning, maintenance, and use shall be included in major equipment logs.
211.184 (Component, drug product container, closure, and labelling records) Deals with the issues of the receipt, testing, and storage of components, drug product containers, and closures. Details the various records and documents that should be generated during the manufacture of drug products and that are to be available for review.
211.186 (Master production and control records) A master production record must be prepared for each drug product, describing all aspects of its manufacture, packaging, and control. Individual batch records are derived from this approved master.
211.188 (Batch production and control records) Batch production and control records with information about the production and control of each batch are prepared.
211.192 (Production record review) All drug product batch records shall be reviewed and approved by the QC unit (QA/QC) before the batch is released.
211.194 (Laboratory records) Complete records of any laboratory testing shall be maintained to include raw data, test procedures and results, initials or signatures of personnel performing the test or reviewing the results of tests, periodic equipment calibration, and stability test results.
211.196 (Distribution records) Distribution records include warehouse shipping logs, invoices, bills of lading, and all documents associated with distribution. These records should provide all the information necessary to trace lot distribution to facilitate product retrieval if necessary.
211.198 (Complaint files) Written records of complaints received from consumers and professionals are to be maintained along with the report of investigations and responses.
SUBPART K RETURNED AND SALVAGED DRUG PRODUCTS
211.204 (Returned drug products) Records are to be maintained of drug products returned from distribution channels and the reason for their return. These data can be used as part of the total lot accountability, should the need arise, to trace its distribution and/ or for its recall.
211.208 (Drug product salvaging) Drug products that have been stored improperly are not to be salvaged.