Inspections, Compliance, Enforcement, and Criminal Investigations
Trusted Care 14-Dec-01
DEPARTMENT OF HEALTH & HUMAN SERVICES
Food and Drug Administration
New England District
One Montvale Avenue
Stoneham, Massachusetts 02180
December 14, 2001
RETURN RECEIPT REQUESTED
184 John Clarke Road
Middletown, RI 02842
Dear Mr. Cardinale:
An inspection of your firm, located at 184 John Clarke Road in Middletotin, RI, was
conducted from October 23 through November 8, 2001 by Investigator Daryl Dewoskin.
This inspection confirmed that you-repackage or relabel various over-the-counter (OTC)
drug products. These products are drugs, within the meaning of Section 201 (g)(l )(B) of
the Federal Food, Drug, and Cosmetic Act (the Act).
This inspection revealed that the drugs being repackaged at your firm are adulterated .
within the meaning of Section 501(a)(2)(B) of the Act, in that the methods used in, or the
facilities or controls used for, the manufacture, processing, packing, or holding of these
drug products do not conform to or are not operated or administered in conformity with
current good manufacturing practice (cGMP) regulations under Title 21, Code of -Federal
Regulations (CFR), Parts 210 and211.
The deviations noted during our inspection include, but are not limited to the following:
1) Employees have not been given training in the particular operations they perform as
part of their assigned functions and in current good manufacturing practice (including
written procedures required by the cGMP regulations). Your production supervisor
reported to our Investigator that she has not been trained in cGMP practices and
that employees performing repackaging and relabeling operations (under
hersupervision) are not able to complete records due to their limited fluency in
English. [21 CFR 211.25(a)-Form FDA 483 Observation 5]
2) Packaging and labeling controls for the usage and examination of materials are
deficient, in that:
a) There is a lack of written procedures describing in sufficient detail the receipt,
identification, storage, handling, sampling, and examination of labeling and
packaging materials. In addition, labeling and packaging materials are not
representatively sampled and examined upon receipt and before use in
packaging and labeling of drug products. [211.122(a)-Form FDA 483
Observations 15 and 16]
b) Labeling and other labeling materials are not stored separately with suitable
identification for each different drug product, strength, dosage form or quantity of
contents. In addition, access to the storage area for labeling and labeling
materials is not limited to authorized personnel. [211.122(d )-Form FDA 483
Observations 19 and 20]
3) Controls over labeling issuance are deficient, in that:
a) Personnel at your firm reported to our Investigator that procedures are not being
used to reconcile the quantities of labeling issued, used, and returned.
[21 1.125(c)-Form FDA 483 Observation 17]
b) Returned labeling is not stored in a manner to prevent mix-ups. There is no
documentation to demonstrate accountability for rolls of stored labels. No effort
has been made to physically segregate labeling for different products.
[211.125(e)-Form FDA 483 Observation 18]
4) Batch production and control records do not include complete information relating to
the production and control of each batch of drug product produced [21 CFR
211.188]. Examples of information missing from batch records include:
a) Dates of each significant step in the processing and packing of the batch.
[211.188(b)(l )-Form FDA Observation 13]
b) Results of the inspection of the packaging and labeling area before and after use.
[211.188(b)(6)-Form FDA 483 Observation 8]
c) Statements of the percentage of theoretical yield at appropriate stages of
production. [211.1 88(b)(7)-Form FDA 483 Observation 14]
d) Complete labeling control records, including specimens or copies of all labeling.
used. [211.188( b)(8)-Form FDA 483 Observation 11]
e) Description of drug product containers and closures used. [211.188(b)(9)-Form .
FDA 483 Observation 7]
f) Identification of the persons performing and directly supervising or checking each
significant step in the operation. [211.188(b)(l 1)-Form FDA 483 Observation
g) Results of examinations made of packaged and labeled products for correct
labeling, in accordance with 21 CFR 211.134. [211.188(b)(13)-Form FDA 483
Specific batches of products for which these deficiencies were noted include:
- Bisacodyl Tablets, 5 mg (Lot K-142-IS)
- Ibuprofen Caplets, 200 mg (Lot A-123-JT)
- Acetaminophen and Diphenhydramine Hydrochloride Tablets, 500 mg / 25 mg (Lot A-103-JK)
- Aspirin, Acetaminophen, and Caffeine Tablets, 250 mg / 250 mg./65 mg (Lot G-105-JK)
- "Non Aspirin Pain Relief" Tablets, 500 mg (Lot B-107-JT)
For one of these products, Ibuprofen Caplets, 200 mg (Lot A-123-JT), it would appear from your Work Order Forms (for orders 454 and 478), that you have applied an expiration date of 11/02 to the repackaged product. However, information supplied to you by the bulk manufacturer [redacted] in the form of a Quality Control Certificate of Analysis, clearly indicates that this product (Control # L930010, with a manufacturing date of 11/19/99) has an expiration date supported by stability data of 2 years. This would correspond to November 2001 (11/01), not November 2002 (11/02) as you have indicated on your Work Order Forms.
One of FDA?s major concerns with regard to repackaging operations is the use of
expiration dates that are supported by sound scientific data (stability studies). It
appears from this inspection that your practice is to apply the original manufacturer?s
expiration date (for bulk quantities of incoming finished drug products) to your
repackaged product, without conducting stability studies. FDA?s Draft Guideline on
Repackaging of Solid Oral Dosage Form Drug Products allows this practice, but only
under certain conditions, examples of which are:
A. The original bulk container of the drug product was not opened previously and the
entire contents are repackaged in one operation;
B. Where the original bulk drug manufacturer?s container was other than glass, the "
repackaging container was demonstrated to be equivalent to or exceed the original
bulk manufacturer?s container in terms of water vapor permeation and compatibility
with the drug product, or where the original bulk manufacturer?s container is
polyethylene, the repackaging container meets current USP (United States -Pharmacopoeia) standards for high density polyethylene containers;
C. The repackaging container meets or exceeds the original bulk manufacturer?s "
container specification for light transmission or meets the current USP standard for
D. The repackaging container meets or exceeds the special protective feature(s) of the
original" bulk manufacturer?s container, e.g., for the prevention leaching of container
material into the drug product or for maintaining low moisture; and
E. The repackaging container-closure system meets the current USP standards for a
"tight container" or a "well-closed container."
A copy of this guideline, with a complete set of conditions, is enclosed for your review. If
your firm fails to meet or chooses not to meet these conditions, you will be required to
conduct adequate stability studies to support the expirations dates of your repackaged
This inspection also revealed that your firm is not currently registered with the Food and
Drug Administration (FDA). Section 510(c) of the Act requires every firm engaged in the manufacture, preparation, propagation, compounding, or processing of drug products to
register with FDA. Under 21 CFR 210.3(b)(l 2), packaging and labeling operations are
included in the definition of the manufacture, processing, packing or holding of drug
products. In addition, Section 510(j) of the Act requires that your firm?s repackaged
drug products be listed with FDA. Failure to either register or list, in accordance with
Section 510, causes your firm?s products to be misbranded under Section 502(0) of the
The violations identified in this letter are not intended to be an all-inclusive list of
deficiencies at your facility. As a manufacturer of human drugs, you are responsible for
ensuring that your overall operations and the products you manufacture and distribute
conform to each requirement of the Act and the regulations.
Other 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. They may elect to defer or discontinue payment for any health care product
in violation of federal law.
You should take prompt action to correct these deviations. Failure to promptly correct
these deviations may result in regulatory. action being initiated by the FDA without
further notice. These actions include, but are not limited to, seizure, and/or injunction.
Please notify this office in writing, within fifteen (15) working days of the receipt of this letter, of the specific steps you have taken to correct the noted violations. Your response should include:
- an explanation of each step that has or will be taken to correct the current violations, violations and to identify and make corrections to any underlying system problems necessary to assure that similar violations will not recur;
- any reason for a delay, if corrective action cannot be completed within 15 working days and the time within which these corrections will be completed;
- any documentation demonstrating that corrections have been achieved.
In your written response, please provide any plan of action you intend to take, as a
result of this letter, with regard to products that are already in commercial-distribution as
well as those finished products in your control that were produced under these violative
Furthermore, we request that you update this office in writing as full corrective actions
are completed and ultimately when you believe that your facility is in compliance with
cGMP regulations, so that a verification inspection can be scheduled. Only when
corrections have been verified will this office withdraw our. advisory to Federal agencies
concerning the award of government contracts. Any delays in implementing a full
corrective action plan may result in an inspection by FDA and contemplation of further
If you have any questions concerning this matter, please contact Mark Lookabaugh,
Compliance Officer at 781-596-7757.
Gail A. Costello
New England District