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U.S. Department of Health and Human Services

CFR - Code of Federal Regulations Title 21

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The information on this page is current as of April 1 2020.

For the most up-to-date version of CFR Title 21, go to the Electronic Code of Federal Regulations (eCFR).

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Help | More About 21CFR
[Code of Federal Regulations]
[Title 21, Volume 4]
[Revised as of April 1, 2020]
[CITE: 21CFR212.50]



Subpart F - Production and Process Controls

Sec. 212.50 What production and process controls must I have?

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.

(a) Written control procedures. 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.

(b) Master production and control records. 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 production;

(5) An accurate statement of the weight or measurement of each component, using the same weight system (metric, avoirdupois, or apothecary) for each component. Reasonable variations are permitted in the amount of component necessary if they are specified in the master production and control records;

(6) A statement of action limits on radiochemical yield, i.e., the minimum percentage of yield beyond which investigation and corrective action are required;

(7) Complete production and control instructions, sampling and testing procedures, specifications, special notations, and precautions to be followed; and

(8) A description of the PET drug product containers, closures, and packaging materials, including a specimen or copy of each label and all other labeling.

(c) Batch production and control records. Each time a batch of a PET drug is produced, a unique batch production and control record must be created. The batch production record must include the following information:

(1) Name and strength of the PET drug;

(2) Identification number or other unique identifier of the specific batch that was produced;

(3) The name and radioactivity or other measure of each active pharmaceutical ingredient and each inactive ingredient per batch or per unit of radioactivity or other measurement of the drug product;

(4) Each major production step (obtained from the approved appropriate master production and control record);

(5) Weights (or other measure of quantity) and identification codes of components;

(6) Dates of production steps and times of critical production steps;

(7) Identification of major pieces of equipment used in production of the batch;

(8) Testing results;

(9) Labeling;

(10) Initials or signatures of persons performing or checking each significant step in the operation; and

(11) Results of any investigations conducted.

(d) Area and equipment checks. The production area and all equipment in the production area must be checked to ensure cleanliness and suitability immediately before use. A record of these checks must be kept.

(e) In-process materials controls. Process controls must include control of in-process materials to ensure that the materials are controlled until required tests or other verification activities have been completed or necessary approvals are received and documented.

(f) Process verification. (1) For a PET drug for which each entire batch undergoes full finished-product testing to ensure that the product meets all specifications, process verification, as described in paragraph (f)(2) of this section, is not required.

(2) When the results of the production of an entire batch of a PET drug are not fully verified through finished-product testing or when only the initial sub-batch in a series is tested, the PET drug producer must demonstrate that the process for producing the PET drug is reproducible and is capable of producing a drug product that meets the predetermined acceptance criteria. Process verification activities and results must be documented. Documentation must include the date and signature of the individual(s) performing the verification, the monitoring and control methods and data, and the major equipment qualified.