The information contained in this document is a compilation of data gathered from warning letters completed by the FDA in the year 2000 (www.fda.gov). The following is a list of the top twenty-two warnings awarded by the FDA in 2000.
1. Failure to assure that all products transfilled and distributed by facility conforms to appropriate final specifications prior to release. Failure to use an official test procedure for the assay of Oxygen, USP. (21 CFR 211.165)
2. Failure to calibrate equipment in accordance with an established written program. Failure to document or ensure that instruments are calibrated: transfilling pressure gauges, vacuum gauge, thermometer, Oxygen Analyzer. (21 CFR 211.160)
3. Failure to ensure that each person engaged in the manufacture, processing and transfilling of the drug product, and each person responsible for supervising these activities, has the education, training, and experience to enable that person to perform their assigned functions in such a manner as to provide assurance that drug product has the quality and purity that it purports or is represented to possess. (21 CFR 211.25)
4. A designated Quality Control Unit has not been established, or quality control unit is not performing duties. Duties such as approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and no review of production records to assure that no errors had occurred or, if errors had occurred, that they had been fully investigated. (21 CFR 211.22)
5. Failure to maintain appropriate batch production and control records for each batch of drug product produced, including documentation that each significant step in the manufacture, processing, packing, or holding of the batch was accomplished and the time of performance. (21 CFR 21.188)
6. Failure to establish written procedures designed to assure that correct labels and labeling are used for the product cylinders, including identification of the drug product with a lot or control number that permits determination of the history of the manufacture and control of the batch. (21 CFR 211.130)
7. Failure to perform adequate prefill operations on each product cylinder. (21 CFR 211.84)
8. Failure to test or verify the results of each lot of bulk oxygen to determine conformance with appropriate specification for identity and strength.
9. Failure to establish written procedures for the handling of any complaints regarding the drug product; and to adequately investigate complaints and document the findings of an investigation and follow-up. (21 CFR 211.198)
10. Failure to reconcile the quantities of medical gas labels issued and returned is not performed. (21 CFR 211.125(c))
11. Standard Operating Procedures do not contain information concerning the generation of tank lot numbers, or there are no Standard Operating Procedures.
12. Failure to establish detailed written procedures to cover the various aspects of transfilling operation. Batch production and control records for cryogenic vessels are not maintained to show that each significant step in the manufacturing operation was accomplished.
13. Failure to establish separate quarantine areas for the holding of empty and filled cylinders of Oxygen USP. Failure to have designated quarantine areas for empty cylinders, rejected cylinders, and finished medical gas product cylinders prior to release. (21 CFR 211.42)
14. Failure to establish written procedures with respect to the testing of Oxygen USP; the calibration of the oxygen analyzer; and the documentation of prefill and postfill inspections of product cylinder home units. (21 CFR 211.100(a))
15. Failure to store medical gas labels in an area limited to authorized personnel. (21 CFR 211.122(d))
16. Failure to complete employee training, or inadequate training, in GMP’s.
17. Failure to retain production, control or distribution records associated with Oxygen, USP for at least 1 year after the expiration date of the batch or, for products lacking expiration dating, a minimum of three years after distribution of the batch. Failure to take adequate action to correct deficiencies identified during internal audits. (21 CFR 211.180)
18. Failure to establish written procedures to determine the expiration date of a drug product. (21 CFR 211.137(a))
19. Failure to have a master label on file in the master production and control records. (21 CFR 211.186(b))
20. Failure to maintain records of the qualifications for consultants advising on the manufacture, processing, packing or holding of drug products. (21 CFR 211.34)
21. Failure to have a written record of maintenance for the oxygen analyzer. (21 CFR 211.182)
22. Failure to routinely calibrate in accordance with written procedures, vacuum gauges, pressure gauges, and thermometers. (21 CFR 211.68(a))