What controls and acceptance criteria must I have for my finished PET drug products?
(a) Specifications. You must establish specifications for each PET drug product, including criteria for determining identity, strength, quality, purity, and, if appropriate, sterility and pyrogens.
(b) Test procedures. 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.
(c) Conformance to specifications. 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.
(d) Final release procedures. 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 given final release until the following are done:
(1) An appropriate laboratory determination under paragraph (c) of this section is completed;
(2) Associated laboratory data and documentation are reviewed and they demonstrate that the PET drug product meets specifications, except for sterility; and
(3) A designated qualified individual authorizes final release by dated signature.
(e) Sterility testing. Sterility testing need not be completed before final release but must be started within 30 hours after completion of production. The 30-hour requirement may be exceeded due to a weekend or holiday. If the sample for sterility testing is held longer than 30 hours, you must demonstrate that the longer period does not adversely affect the sample and the test results obtained will be equivalent to test results that would have been obtained if the test had been started within the 30-hour time period. Tested samples must be from individual batches and not pooled. If the product fails to meet a criterion for sterility, you must immediately notify all facilities that received the product of the test results and provide any appropriate recommendations. The notification must be documented. Upon completion of an investigation into the failure to meet a criterion for sterility, you must notify all facilities that received the product of the findings from the investigation.
(f) Conditional final release.(1) If you cannot complete one of the required finished-product tests for a batch of a PET drug product because of a malfunction involving analytical equipment, you may approve the conditional final release of the product if you meet the following conditions:
(i) You have data documenting that preceding consecutive batches, produced using the same methods used for the conditionally released batch, demonstrate that the conditionally released batch will likely meet the established specifications;
(ii) You determine that all other acceptance criteria are met;
(iii) You retain a reserve sample of the conditionally released batch of drug product;
(iv) You promptly correct the malfunction of analytical equipment, complete the omitted test using the reserve sample after the malfunction is corrected, and document that reasonable efforts have been made to prevent recurrence of the malfunction;
(v) If you obtain an out-of-specification result when testing the reserve sample, you immediately notify the receiving facility; and
(vi) You document all actions regarding the conditional final release of the drug product, including the justification for the release, all followup actions, results of completed testing, all notifications, and corrective actions to prevent recurrence of the malfunction involving analytical equipment.
(2) Even if the criteria in paragraph (f)(1) of this section are met, you may not approve the conditional final release of the product if the malfunction involving analytical equipment prevents the performance of a radiochemical identity/purity test or prevents the determination of the product's specific activity.
(3) You may not release another batch of the PET drug product until you have corrected the problem concerning the malfunction of analytical equipment and completed the omitted finished-product test.
Title 21 published on 2012-04-01
no entries appear in the Federal Register after this date.
This is a list of United States Code sections, Statutes at Large, Public Laws, and Presidential Documents, which provide rulemaking authority for this CFR Part.