Inspections, Compliance, Enforcement, and Criminal Investigations
Airgas, Inc. 12/1/10
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
New Orleans District
December 1, 2010
WARNING LETTER NO. 2011-NOL-04
UNITED PARCEL SERVICE
DELIVERY SIGNATURE REQUESTED
259 North Radnor-Chester Road
Radnor, Pennsylvania 19087-5283
Dear Mr. McCausland:
During our July 8, 9, 12, 13, 16, 19, 2010, inspection of your medical gas manufacturing facility, Airgas South, Inc., located at 4551 North Access Road, Chattanooga, Tennessee, investigators from the U. S. Food and Drug Administration (FDA) identified significant violations of Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211 (21 CFR 210 and 211). These violations cause your drug products to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [Title 21, United States Code 351(a)(2)(B)], as the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
We reviewed your firm's response of July 30, 2010, from Gregory P. Barnett, Director of Safety, and note it lacks sufficient corrective actions.
Specific violations observed during the inspection include, but are not limited to, the following:
1. Your firm has not thoroughly investigated the failure of a batch or any of its components to meet its specifications, whether or not the batch has already been distributed [21 CFR 211.192].
For example, your firm failed to extend your investigation of a contaminated Nitrogen NF cylinder (lot WC01X153A) to other lots. A hospital complaint received on June 17, 2010, resulted in the return of a Nitrogen NF cylinder. This cylinder was tested and found to contain several halogenated organics. You firm's investigation indicated these contaminants were soil fumigants. Based on these findings, Nitrogen NF cylinders (lot WC01X153A) were recalled. However, your investigation was isolated to this specific lot. As a direct result of discussions with our investigators, your Quality Control Unit extended the investigation to other batches of the same and other drug products. Due to this expanded investigation, all medical gas products within expiry were recalled.
2. Your firm failed to prepare batch production and control records for each batch of drug product produced, including documenting each significant step in the manufacture, processing, or holding of the batch [21 CFR 211. 188(b)].
For example, your firm filled batches of medical gas drug products without preparing or completing batch production records between April 9, 2009 and June 15, 2010. Specifically, your firm failed to document the performance of necessary cylinder pre- and post-fill checks, such as; dead ring test for corrosion; odor check; leak test; external cylinder examination; testing for residual gas removal, and the finished product assay test.
In your firm's response, your firm proposes training employees in "all applicable CGMP requirements" as a corrective action. Your response is inadequate because you have not defined what specific information will be included in your CGMP training.
Be advised all batch records must be generated and properly completed for each batch of drug product produced, including information relating to the production and control of each batch. It is essential to document each significant step (e.g., pre- and post-fill checks) in the manufacture of each batch of medical gases. If there is a need to determine possible causes for product defects or complaints at a later date, and determine the extent of impact on marketed products, complete batch records are a fundamental source of information.
Our inspection found your firm's quality unit failed to adequately review batch records. The above major batch record deficiencies underscore the importance of appropriate quality unit oversight at your firm.
3. Your firm has not established scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure drug products conform to appropriate standards of identity, strength, quality, and purity [21 CFR 211.160(b)].
For example, your firm failed to appropriately conduct the pre-fill odor test of high pressure medical gas cylinders. Our investigator observed employees painting Nitrogen NF cylinders (lot WC00X189A) immediately before conducting a pre-fill odor test on the same cylinders. The presence of paint fumes may interfere with the ability of employees to detect potential contamination.
In your firm's response, your firm commits to perform cylinder painting in a designated preparation area located away from the production area. However, the proposed corrective action in your response is inadequate because you have not identified the drying time requirement for the freshly painted cylinders and date of implementation. The adequacy of the implemented corrective action will be reviewed during our next inspection.
The violations cited in this letter are not intended to be an all inclusive list of violations which may exist at your facility. You are responsible for investigating and determining the causes of the violations identified and for preventing their recurrence and the occurrence of other violations. It is your responsibility to ensure your facility operates in compliance with all requirements of federal law and FDA regulations.
You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction. Other federal agencies may take this warning letter into account when considering the award of contracts. Additionally, FDA may withhold approval of requests for export certificates, or approval of new drug applications listing your facilities, until the above violations are corrected. FDA may re-inspect to verify corrective actions have been completed.
Within 15 working days of receipt of this letter, please notify this office in writing of the specific steps you have taken to correct violations. Include an explanation of each step taken to prevent the recurrence of violations and copies of supporting documentation. If you cannot complete corrective action within 15 working days, state the reason for the delay and the date by which you will have completed the correction.
Your written response should be sent to Rebecca A. Asente, Compliance Officer, at the address above. If you have questions regarding the contents of this letter, please contact Ms. Asente at (504) 219-8818, extension 104.
H. Tyler Thornburg
New Orleans District