Inspections, Compliance, Enforcement, and Criminal Investigations
The Service Center 17-Aug-06
Department of Health and Human Services
Public Health Service
August 17, 2006
RETURN RECEIPT REOUESTED
Messrs. Roger Miller & Jeffery Adante
The Service Center
2000 South 25th Avenue, Suite S
Broadview, IL 60155-2818
The Food and Drug Administration (FDA) inspected your firm, which performs both medical oxygen gas transfilling and the refurbishment of used medical oxygen cylinders, on April 5, 10 and 14, 2006, and performed a follow-up inspection on May 30, June 1 and 6, 2006. Our inspections found significant deviations from the current Good Manufacturing Practice (cGMP) regulations for drug products, as set forth in Title 21, Code of Federal Regulations (21 CFR), Part 210 and 211. These deviations cause your medical gas to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (The Act) [21 U.S.C. § 351(a)(2)(B)], in that the methods used in, or the facilities or controls used for, their manufacturing, processing, packing, storage and holding, are not in compliance with cGMP. Medical gases are drugs as defined by Section 201(g) of the Act.
At the conclusion of the April inspection, investigator Russell Riley issued and discussed with Dale Koenick, General Manager, the Form FDA 483, Inspectional Observations, which identifies the objectionable practices found during the inspection. A copy of the FDA-483 issued to Mr. Koenick is attached. The inspection revealed deviations from the cGMP regulations as follows:
1. Failure to establish and follow written procedures describing the receipt, identification, storage, handling, sampling, testing and approval or rejection of components and drug product containers and closures [21 CFR § 211.80(a)]. For example, your firm has not established procedures for the examination, acceptance, or rejection of new or previously used cylinders prior to their first use in your firm's own Oxygen, USP production.
2. Failure to maintain records of the identity and quantity of each shipment of each lot of components, drug product containers, closures and labeling, and of the name of the supplier [21 CFR § 211.184(a)]. For example, your firm does not maintain records of the origins of the used cylinders used in your Oxygen, USP manufacture that would allow identification of the original supplier of a cylinder.
3. Failure to maintain records of the results of any tests or examinations performed on drug product components, and the conclusions derived therefrom [21 CFR § 211.184(b)]. For example, your firm has no documentation of any repairs, reconditioning, or tests performed to show that used high-pressure cylinders are suitable for medical use prior to their use in your manufacture of Oxygen, USP.
4. Failure of the quality control unit to conduct an adequate investigation of any unexplained discrepancy whether or not the batch has been distributed as required by 21 CFR 211.192. The current inspection revealed that your firm received three complaints: one of a burning sensation from the gas (received November 30, 2004); one that the oxygen in the tanks gave the consumer headaches (received February 2004); and, one complaint of a diesel smell in four oxygen tanks received (received January 2004). The inspection revealed that in all three cases your firm reportedly conducted USP testing on the cylinders, but failed to perform testing for impurities.
We have received your written response to the FDA-483, dated April 27, 2006. This response will be added to our official files. For several reasons we do not find this response to be satisfactory. For example, your response to FDA 483 item # 1 states that in your capacity as a "cylinder broker," you do not have to maintain drug product container and component records that would be required by cGMP regulations for finished pharmaceuticals. This is not the case, however, with the cylinders undergoing the same reconditioning procedures that are later used in your own Oxygen, USP manufacturing. In addition, the response to FDA 483 item # 2 is inadequate in that it indicates that it is not your firm's policy to attempt to identify a chemical contaminant or its source when a complaint indicates the presence of one. The documentation of the referenced complaint investigations, which involve the detection of chemical odors by the end users, fails to include any conclusions as to the cause of the discrepancies. Also, please note that United States Pharmacopeia, in its "General Notices" states that adulterants "...may arise from a change in the source of the material or from a change in the processing, or may be introduced from extraneous sources." It further states that, "Tests suitable for detecting such occurrences, the presence of which is inconsistent with applicable good manufacturing practice or good pharmaceutical practice should be employed in addition to the tests provided in the individual monograph." Thus, given the concerns of contamination raised by the consumer complaints, your firm's tests of the returned product did not constitute "full USP testing" according to USP's definitions.
This letter is not intended to be an all-inclusive list of deficiencies at your firm. It is your responsibility to ensure adherence to each requirement of the law and relevant FDA regulations. Federal agencies are advised of the issuance of all Warning Letters about drugs so that they may take this information into account when considering the award of contracts. Until FDA can confirm correction of the deficiencies observed during the most recent inspection, this office can recommend disapproval of any new applications listing this site as a manufacturer of drugs.
You should take prompt action to correct these deviations. Failure to do so may result in regulatory action being initiated by FDA without further notice to you. These actions include, but are not limited to, seizure and injunction.
Please notify this office in writing within 15 working days of receipt of this letter, of the specific steps you have taken to correct the noted violations and to prevent their recurrence. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
Your response should be submitted to the attention of Compliance Officer George F. Bailey, at the above listed address.
Scott J. MacIntire