Title 21 CFR reference

The following definitions apply to words and phrases as they are used in this part. Other definitions of these words may apply when they are used in other parts of this chapter. Acceptance criteria means numerical limits, ranges, or other criteria for tests that are used for or in making a decision to accept or reject a unit, lot, or batch of a PET drug product. Actet seq. means the Federal Food, Drug, and Cosmetic Act, as amended (21 U.S.C. 321 ). Active pharmaceutical ingredient means a substance that is intended for incorporation into a finished PET drug product and is intended to furnish pharmacological activity or other direct effect in the diagnosis or monitoring of a disease or a manifestation of a disease in humans, but does not include intermediates used in the synthesis of such substance. Batch means a specific quantity of PET drug intended to have uniform character and quality, within specified limits, that is produced according to a single production order during the same cycle of production. Batch production and control record means a unique record that references an accepted master production and control record and documents specific details on production,…

You must have a sufficient number of personnel with the necessary education, background, training, and experience to perform their assigned functions. You must have adequate resources, including facilities and equipment, to enable your personnel to perform their functions.

Written complaint procedures.(a) You must develop and follow written procedures for the receipt and handling of all complaints concerning the quality or purity of, or possible adverse reactions to, a PET drug product. Complaint review.(b) The procedures must include review by a designated person of any complaint involving the possible failure of a PET drug product to meet any of its specifications and an investigation to determine the cause of the failure. Complaint records.(c) A written record of each complaint must be maintained in a file designated for PET drug product complaints. The record must include the name and strength of the PET drug product, the batch number, the name of the complainant, the date the complaint was received, the nature of the complaint, and the response to the complaint. It must also include the findings of any investigation and followup. Returned products.(d) A PET drug product that is returned because of a complaint or for any other reason may not be reprocessed and must be destroyed in accordance with applicable Federal and State law.

Record availability.(a) Records must be maintained at the PET drug production facility or another location that is reasonably accessible to responsible officials of the production facility and to employees of FDA designated to perform inspections. Record quality.(b) All records, including those not stored at the inspected establishment, must be legible, stored to prevent deterioration or loss, and readily available for review and copying by FDA employees. Record retention period.(c) You must maintain all records and documentation referenced in this part for a period of at least 1 year from the date of final release, including conditional final release, of a PET drug product.

Current good manufacturing practice for PET drugs is the minimum requirements for the methods to be used in, and the facilities and controls used for, the production, quality assurance, holding, or distribution of PET drugs intended for human use. Current good manufacturing practice is intended to ensure that each PET drug meets the requirements of the act as to safety and has the identity and strength, and meets the quality and purity characteristics, that it is supposed to have.

Production operations.(a) You must oversee production operations to ensure that each PET drug meets the requirements of the act as to safety and has the identity and strength, and meets the quality and purity characteristics, that it is supposed to have. Materials.(b) You must examine and approve or reject components, containers, closures, in-process materials, packaging materials, labeling, and finished dosage forms to ensure compliance with procedures and specifications affecting the identity, strength, quality, or purity of a PET drug. Specifications and processes.(c) You must approve or reject, before implementation, any initial specifications, methods, processes, or procedures, and any proposed changes to existing specifications, methods, processes, or procedures, to ensure that they maintain the identity, strength, quality, and purity of a PET drug. You must demonstrate that any change does not adversely affect the identity, strength, quality, or purity of any PET drug. Production records.(d) You must review production records to determine whether errors have occurred. If errors have occurred, or a production batch or any component of the batch fails to meet any of its…

Facilities.(a) You must provide adequate facilities to ensure the orderly handling of materials and equipment, the prevention of mix-ups, and the prevention of contamination of equipment or product by substances, personnel, or environmental conditions that could reasonably be expected to have an adverse effect on product quality. Equipment procedures.(b) You must implement procedures to ensure that all equipment that could reasonably be expected to adversely affect the identity, strength, quality, or purity of a PET drug, or give erroneous or invalid test results when improperly used or maintained, is clean, suitable for its intended purposes, properly installed, maintained, and capable of repeatedly producing valid results. You must document your activities in accordance with these procedures. Equipment construction and maintenance.(c) Equipment must be constructed and maintained so that surfaces that contact components, in-process materials, or PET drugs are not reactive, additive, or absorptive so as to alter the quality of PET drugs.

Written procedures.(a) You must establish, maintain, and follow written procedures describing the receipt, login, identification, storage, handling, testing, and acceptance and/or rejection of components and drug product containers and closures. The procedures must be adequate to ensure that the components, containers, and closures are suitable for their intended use. Written specifications.(b) You must establish appropriate written specifications for the identity, quality, and purity of components and for the identity and quality of drug product containers and closures. Examination and testing.(c) Upon receipt, each lot of components and containers and closures must be uniquely identified and tested or examined to determine whether the lot complies with your specifications. You must not use in PET drug production any lot that does not meet its specifications, including any expiration date if applicable, or that has not yet received its material release. Any incoming lot must be appropriately designated as quarantined, accepted, or rejected. You must use a reliable supplier as a source of each lot of each component, container, and closure. (1)(i) If you conduct finished-product…

Application solely to PET drugs.(a) The regulations in this part apply only to the production, quality assurance, holding, and distribution of PET drugs. Any human drug that does not meet the definition of a PET drug must be manufactured in accordance with the current good manufacturing practice requirements in parts 210 and 211 of this chapter. Investigational and research PET drugs.gt@usp.org,http://www.usp.org/USPNF/notices.http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html.(b) For investigational PET drugs for human use produced under an investigational new drug application in accordance with part 312 of this chapter, and PET drugs produced with the approval of a Radioactive Drug Research Committee in accordance with part 361 of this chapter, the requirement under the act to follow current good manufacturing practice is met by complying with the regulations in this part or by producing PET drugs in accordance with Chapter 823, “Radiopharmaceuticals for Positron Emission Tomography—Compounding,” May 1, 2009, pp. 365-369, 32d ed. of the United States Pharmacopeia (USP) National Formulary (NF) (USP 32/NF 27) (2009). The Director of the…

You must have adequate production and process controls to ensure the consistent production of a PET drug that meets the applicable standards of identity, strength, quality, and purity. Written control procedures.(a) You must have written production and process control procedures to ensure and document that all key process parameters are controlled and that any deviations from the procedures are justified. Master production and control records.(b) You must have master production and control records that document all steps in the PET drug production process. The master production and control records must include the following information: (1) The name and strength of the PET drug; (2) If applicable, the name and radioactivity or other measurement of each active pharmaceutical ingredient and each inactive ingredient per batch or per unit of radioactivity or other measurement of the drug product, and a statement of the total radioactivity or other measurement of any dosage unit; (3) A complete list of components designated by names and codes sufficiently specific to indicate any special quality characteristic; (4) Identification of all major pieces of equipment used in…

Testing procedures.(a) Each laboratory used to conduct testing of components, in-process materials, and finished PET drug products must have and follow written procedures for the conduct of each test and for the documentation of the results. Specifications and standards.(b) Each laboratory must have sampling and testing procedures designed to ensure that components, in-process materials, and PET drug products conform to appropriate standards, including established standards of identity, strength, quality, and purity. Analytical methods.(c) Laboratory analytical methods must be suitable for their intended use and must be sufficiently sensitive, specific, accurate, and reproducible. Materials.(d) The identity, purity, and quality of reagents, solutions, and supplies used in testing procedures must be adequately controlled. All solutions that you prepare must be properly labeled to show their identity and expiration date. Equipment.(e) All equipment used to perform the testing must be suitable for its intended purposes and capable of producing valid results. Equipment maintenance.(f) Each laboratory must have and follow written procedures to ensure that equipment is routinely…

Stability testing program.(a) You must establish, follow, and maintain a written testing program to assess the stability characteristics of your PET drug products. The test methods must be reliable, meaningful, and specific. The samples tested for stability must be representative of the lot or batch from which they were obtained and must be stored under suitable conditions. Storage conditions and expiration dates.(b) The results of such stability testing must be documented and used in determining appropriate storage conditions and expiration dates and times for each PET drug product you produce.

Specifications.(a) You must establish specifications for each PET drug product, including criteria for determining identity, strength, quality, purity, and, if appropriate, sterility and pyrogens. Test procedures.(b) Before you implement a new test procedure in a specification, you must establish and document the accuracy, sensitivity, specificity, and reproducibility of the procedure. If you use an established compendial test procedure in a specification, you must first verify and document that the test works under the conditions of actual use. Conformance to specifications.(c) Before final release, you must conduct an appropriate laboratory determination to ensure that each batch of a PET drug product conforms to specifications, except for sterility. For a PET drug product produced in sub-batches, before final release, you must conduct an appropriate laboratory determination to ensure that each sub-batch conforms to specifications, except for sterility. Final release procedures.(d) Except as conditional final release is permitted in accordance with paragraph (f) of this section, you must establish and follow procedures to ensure that each batch of a PET drug product is not…

Rejection of nonconforming product.(a) You must reject a batch of a PET drug product that does not conform to specifications. You must have and follow procedures to identify and segregate the product to avoid mix-ups. You must have and follow procedures to investigate the cause(s) of the nonconforming product. The investigation must include, but is not limited to, examination of processes, operations, records, complaints, and any other relevant sources of information concerning the nonconforming product. Investigation.(b) You must document the investigation of a PET drug product that does not meet specifications, including the results of the investigation and what happened to the rejected PET drug product. Correction of problems.(c) You must take action to correct any identified problems to prevent recurrence of a nonconforming product or other quality problem. Reprocessing.(d) If appropriate, you may reprocess a batch of a PET drug product that does not conform to specifications. If material that does not meet acceptance criteria is reprocessed, you must follow procedures stated in the product's approved application and the finished product must conform to specifications,…

(a) A PET drug product must be suitably labeled and packaged to protect the product from alteration, contamination, and damage during the established conditions of shipping, distribution, handling, and use. (b) Labels must be legible and applied so as to remain legible and affixed during the established conditions of processing, storage, handling, distribution, and use. (c) All information stated on each label must also be contained in each batch production record. (d) Labeling and packaging operations must be controlled to prevent labeling and product mix-ups.

Written distribution procedures.(a) You must establish, maintain, and follow written procedures for the control of distribution of PET drug products shipped from the PET drug production facility to ensure that the method of shipping chosen will not adversely affect the identity, purity, or quality of the PET drug product. Distribution records.(b) You must maintain distribution records for each PET drug product that include or refer to the following: (1) The name, address, and telephone number of the receiving facility that received each batch of a PET drug product; (2) The name and quantity of the PET drug product shipped; (3) The lot number, control number, or batch number for the PET drug product shipped; and (4) The date and time you shipped the PET drug product.