(a) The establishment of any specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms required by this subpart, including any change in such specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, shall be drafted by the appropriate organizational unit and reviewed and approved by the quality unit. The requirements in this subpart shall be followed and shall be documented at the time of performance. Any deviation from the written specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms shall be recorded and justified.
(b) Laboratory controls shall include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, medical gas containers and closures, in-process materials, labeling, and medical gases conform to appropriate standards of identity, strength, quality, and purity. Laboratory controls shall include:
(1) Determination of conformity to applicable written specifications for the acceptance of each lot within each shipment of components, medical gas containers and closures, and labeling used in the manufacture, processing, packing, or holding of a medical gas. The specifications shall include a description of the sampling and testing procedures used. Samples shall be representative and adequately identified. Such procedures shall also require appropriate retesting of any component, container, or closure that is subject to deterioration.
(2) Determination of conformance to written specifications and a description of sampling and testing procedures for in-process materials. Such samples shall be representative and properly identified.
(3) Determination of conformance to written descriptions of sampling procedures and appropriate specifications for medical gases. Such samples shall be representative and properly identified.
(4) The calibration or verification of calibration for instruments, apparatus, gauges, and recording devices at suitable intervals in accordance with an established written program containing specific directions, schedules, limits for accuracy and precision, and provisions for remedial action in the event accuracy and/or precision limits are not met. Instruments, apparatus, gauges, and recording devices not meeting established specifications shall not be used.
(a) For each batch of medical gas, there shall be appropriate laboratory determination of satisfactory conformance to final specifications for the medical gas, including the identity and strength, prior to release.
(b) Any sampling and testing plans shall be described in written procedures that shall include the method of sampling, the number of units per batch to be tested, and acceptance criteria. Such written procedures shall be followed.
(c) The accuracy, sensitivity, specificity, and reproducibility of test methods employed by the firm shall be established and documented. Such validation and documentation may be accomplished in accordance with § 213.194(a)(2). The suitability of all testing methods shall be verified under actual conditions of use.
(d) Medical gases failing to meet established standards or specifications and any other relevant quality criteria shall be rejected.
(e) This section does not apply to the filling of a designated medical gas or medically appropriate combination of designated medical gases via liquid to liquid into a container at a delivery site.
(a) For medical gases marketed under applications submitted under section 505 or section 512 of the Federal Food, Drug, and Cosmetic Act, any stability testing performed and any expiration date established shall be in accordance with paragraph (b) of this section, subject to the conditions established in their approved applications, if any.
(b) To assure that the medical gas described in paragraph (a) of this section meets applicable standards of identity, strength, quality, and purity at the time of use:
(1) The stability testing program shall be designed to assess the stability characteristics of the medical gas and its container closure system. The results of stability testing shall be used in determining appropriate storage conditions and any expiration date included on the label. The stability program shall include the appropriate sample size, test intervals, container closure systems, and storage conditions for samples retained for testing.
(2) Any expiration dates included on the label shall appear in accordance with the requirements of § 201.17 of this chapter.
(3) Stability shall be evaluated periodically to ensure that the medical gas continues to meet the standards for identity, strength, quality, and purity stated on the labeling to support the expiration date.