Inspections, Compliance, Enforcement, and Criminal Investigations
Carib Supply of St. Croix, Inc. 04-Dec-08
Department of Health and Human Services
Public Health Service
San Juan District
Telephone: (787) 474-9500
December 4, 2008
Mr. Benson E. Straker
Carib Supply of St. Croix, Inc.
PO Box 22
BB 11000 Barbados W.I.
Dear Mr. Straker:
This letter is in reference to the inspection of your manufacturing facility Carib Supply of St. Croix, Inc., located at #3 Cassava Gardens (Hess Road), Christiansted, St. Croix, US Virgin Islands, 00822, conducted on June 26 and 27, 2008, by an investigator from the Food and Drug Administration (FDA). The inspection found that your firm's manufacture, processing, packing or holding of the human drug product medical grade oxygen deviates from the Current Good Manufacturing Practice (CGMP) Regulations as stated within 21 Code of Federal Regulations (CFR) Parts 210 and 211, rendering the drugs adulterated within the meaning of 21 U.S.C. § 351(a)(2)(B) [Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act)]. The manufacture and processing of the drugs do not conform to CGMP to ensure that the drug products meet the requirements of the Act as to safety, and have the identity and strength and meet the quality and purity characteristics that they purport or are represented to possess.
At the conclusion of the inspection a List of Inspectional Observations (Form FDA-483) was issued to and discussed with Mr. Maxwell C. Wilson, General Manager at the facility. The deviations observed during the inspection demonstrating your firm's failure to comply with 21 CFR parts 210 and 211 include, but are not limited to, the following:
1. Failure to establish a quality control unit having the responsibility and authority to approve and reject all components, drug product containers, closures, in-process materials, packaging materials, labeling and drug products and the authority to review production records to assure that no errors have occurred, as required by 21 CFR § 211.22(a). For example, your firm has not established a quality control unit. Personnel with quality control unit responsibility have not been designated. There are no written procedures defining its roles and functions, as required by 21 CFR § 211.22(d). There is also no documentation of quality control unit review of batch records to determine compliance with established, approved written procedures.
We acknowledge the corrective actions, including the new procedures describing the quality control unit and the designation of personnel, described in your response July 25, 2008 and sent September 8, 2008. However, this response is incomplete because it does not include the promised (by August 8, 2008) documentation showing quality control unit review of batch records. Batch records examined during the October 6, 2008, follow-up inspection still fail to show documentation of quality control unit review.
2. Failure to test each batch of drug product for conformance to final specifications including identity and strength prior to release, as required by 21 CFR § 211.165(a). For example, since at least January, 2008, your firm has failed to conduct identity and strength testing on either the commingled new batches of bulk liquid Oxygen USP created by deliveries to your storage tank or on the lots of compressed Oxygen USP finished product. In addition, your firm's batch record documentation indicates that the finished product odor test was not done on the Oxygen USP finished product.
We acknowledge the corrective actions outlined in your correspondence of July 14 and July 25, 2008, sent in response to the FDA-483, including the newly approved test procedures. However these responses did not include any of the promised documentation showing that the new test procedures have been implemented. In addition, no such documentation was presented during the follow-up inspection.
3. Failure to establish and follow scientifically sound and appropriate specifications, standards sampling plans, and test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality and purity, as required by 21 CFR § 211.160(b). Your firm's written procedures for testing have not been followed and also lack necessary detail. For example, there were no written procedures for operation of the (b)(4)(b)(4) oxygen analyzer. There was no written program for the calibration of this instrument and there were no calibration standards.
Your responses of July 14 and July 25, 2008, are incomplete because the new test procedures do not include any specific instructions for operation of the (b)(4)(b)(4) oxygen analyzer. In addition, the responses fail to include any documentation to show that calibration standards have been obtained for this instrument and the promised documentation of testing has not been included. Also, you failed to show any documentation of implementation of these procedures during the follow-up inspection.
4. Failure to follow written production and process control procedures, as required by 21 CFR § 211.100(b). For example, written procedures on the premises requiring testing on new bulk shipments of Oxygen USP to the storage tank, testing of filled containers of liquid Oxygen USP for identity and purity, and recording of all prefill and postfill test results on the batch record were not followed. Your firm's management admitted that written production and process control procedures were not being followed.
We acknowledge the new procedures presented as corrective action in your response of July 25, 2008, and your promise to provide documentation showing that the new procedures were being followed. However, the promised documentation to show implementation of these new procedures was not included. Your firm also failed to provide this documentation during the follow-up inspection.
5. Failure to document each significant step in the manufacture of the drug product, as required by 21 CFR § 211.188(b). For example, your "Daily Production Report -Oxygen" batch records do not consistently document that necessary cylinder prefill checks and procedures were performed, such as a visual examination, dead ring test for corrosion, prefill odor check, and vacuum evacuation. Many also fail to document the performance of valve-open and valve-closed leak checks, post fill.
We acknowledge the corrective actions, including the new batch record forms, presented in your response of July 25, 2008. However, the promised batch record documentation showing its use was not included. In addition, batch records examined during the follow-up inspection showed that the new batch record forms were not in use and the records still do not consistently record prefill and postfill procedures such as label checks and post fill leak checks.
6. Failure to establish and follow adequate written procedures for the handling of all written and oral complaints involving a drug product, as required by 21 CFR § 211.198(a). Your firm lacked written procedures for the handling of complaints and did not maintain a complaint file.
We acknowledge the corrective actions, including the new complaint file and new written complaint handling procedures, described in your response of July 25, 2008. However this response is unsatisfactory because the new complaint procedures do not require extension of complaint investigations to other lots that may be impacted.
7. Failure to ensure that strict control is exercised over labeling issued for use in drug product labeling operations as required by 21 CFR § 211.125(a). Your firm does not exercise adequate controls over the labeling issuance and labeling operation of the drug products being handled at your facility. Your firm personnel were not aware of the labeling requirements set forth by the above mentioned regulation.
We acknowledge the corrective actions described in your July 25, 2008, response, including the revised SOPs and label control forms. However, the promised documentation of the first ten days of production showing the implementation of the new procedures was not included. Your firm also failed to provide this documentation during the follow-up inspection.
8. Failure to ensure that written procedures are designed and followed to assure that correct labels, labeling, and packaging materials are used for drug products as required by 21 CFR § 211.130. Your firm had not established or implemented procedures to assure that correct labels were applied to your medical Oxygen products.
We acknowledge the corrective actions, including the revised SOPs and label control forms, described in your July 25, 2008, response. However the promised documentation of the first ten days of production showing the implementation of the new procedures was not included. Your firm also failed to provide this documentation during the follow-up inspection.
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence or the occurrence of other violations. It is your responsibility to assure that your firm complies 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 pending new drug applications listing your facility as a supplier or manufacturer until the above violations are corrected. A reinspection may be necessary.
Within 15 working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will complete the correction. If you no longer manufacture or market drug products, your response should so indicate, including the reasons that, and the date on which, you ceased production. You may find the Act, the current Good Manufacturing Practice Regulations for finished pharmaceuticals through links in FDA's home page at www.fda.gov. You can find guidance and information regarding compliance for medical gas manufacture through FDA's internet page for the regulated industry at http://www.fda.gov/cder.
Your reply should be sent to the Food & Drug Administration, San Juan District Office, 466 Fernandez Juncos Ave., San Juan, PR 00901-3223, to the attention of Carlos A. Medina, Compliance Officer. If you have any questions concerning the violations noted please contact Mr. Medina at (787) 474-9538 or by electronic mail at email@example.com.
San Juan District
Cc: Mr. Maxwell C. Wilson
Site General Manager
Carib Supply of St. Croix, Inc.
#3 Cassava Gardens (Hess Road)
Christiansted, St. Croix, Virgin Islands, 00822