Inspections, Compliance, Enforcement, and Criminal Investigations
Reese Pharmaceutical Company 5/18/11
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|Cincinnati District Office|
6751 Steger Drive
Cincinnati, OH 45237-3097
Telephone: (513) 679-2700
FAX: (513) 679-2761
May 18, 2011
Via United Parcel Service
Mr. George W. Reese, President
Reese Pharmaceutical Company
10617 Frank Avenue
Cleveland, OH 44106-4218
Dear Mr. Reese:
During our November 3-24, 2010 inspection of your pharmaceutical manufacturing facility, Reese Pharmaceutical Company, located at 10617 Frank Avenue, Cleveland, Ohio, an investigator from the 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. 1 These violations cause your drug product(s) to be adulterated within the meaning of the 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 manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
We have reviewed your firm’s response of December 10, 2010, and note that 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 C.F.R. § 211.192].
For example, your firm failed to thoroughly investigate the mislabeling of cold decongestant tablets containing acetaminophen, phenylephrine HCL and chlorpheniramine maleate as a cough expectorant product containing guaifenesin. Your investigation determined that only one lot of cold decongestant (lot 091612) was involved in the mislabeling, while failing to identify a root cause. This lot was recalled.
In your response, your firm states the investigation of the cough expectorant at the retail level resulted in a total of 15 mislabeled bottles and led to the conclusion that only lot 091612 was mislabeled. However, your response is inadequate because your firm fails: (1) to provide a root cause as part of the conclusion to the investigation; (2) to provide your rationale as to why the expectorant product was not at risk for being mislabeled, and; (3) to define the “unaccounted” category associated with the reconciliation of lot 091612. In addition, your firm has failed to address the employee training regarding the two revised Standard Operating Procedures entitled, “A11-Inspection of Finished Product,” and, “A16-Custom Imprint Tracking Form.”
2. Your firm failed to exercise strict control over labeling issued for use in drug product labeling operations [21 C.F.R. § 211.125(a)].
For example, your firm issues various labels for different drug products for production weeks in advance of the labeling operation. These labels are stored in uncontrolled open boxes increasing the risk for packaging employees to select the wrong labels.
In your response, your firm states that you will increase the control of the label using a tracking form by the labeling department. Your response, however, is inadequate because your firm fails to provide a comprehensive corrective action plan describing how your firm will exercise strict control over label issuance, use, and return procedures to prevent label mix-ups and recalls.
3. Your firm has not established procedures to reconcile the quantities of labeling issued, used, returned, and failed to evaluate the discrepancies found between the quantity of drug product finished and the quantity of labeling issued when such discrepancies are outside narrow preset limits based on historical operating data. [21 C.F.R. § 211.125(c)].
For example, your firm failed to reconcile the number of unlabeled drug product bottles issued to production with the number of labels used for batch records A74859 and A86926.
In your response, your firm states that you will carefully compare and control the product and packaging in the future. Your response, however, is inadequate because you fail to provide an adequate and specific corrective action plan regarding how your firm will reconcile the labeling.
4. Your firm failed to establish written procedures to identify the drug product with a lot or control number that permits determination of the history of the manufacture and control of the batch [21 C.F.R. § 211.130(c)].
For example, your firm attached identical labels (i.e., lot 10H572) to two different batch records (A86616 packaged on 9/21/2010 and A65626 packaged on 10/18/2010) without using a unique identifier on the actual label or bottled product to distinguish the two separate label operations.
In your response, your firm states that you are currently considering different options to apply a control number during your different labeling operations. This response is inadequate. Your firm is required to implement a unique lot or control numbers for each batch of drug products packaged.
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 and the occurrence of other violations. It is your responsibility to assure 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 pending drug applications listing your facility, until the above violations are corrected. FDA may re-inspect to verify corrective actions have been completed.
Within fifteen 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 and copies of supporting documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the date by which you will have completed the correction. Additionally, your response should state if you no longer manufacture or distribute products, and provide the date(s) and reason(s) you ceased production.
Your reply should be sent to the attention of: Allison C. Hunter, Compliance Officer, U.S. Food and Drug Administration, 6751 Steger Drive, Cincinnati, OH 45237. If you have any questions about this letter, please contact Compliance Officer Hunter at (513) 679-2700, Ext. 2134.
Teresa C. Thompson
1 Reese Pharmaceutical Company is a repacker, relabeler, and an own-label distributor of Over-the-Counter drug products.