Inspections, Compliance, Enforcement, and Criminal Investigations
Agropharma Laboratories, Inc.
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
466 Fernandez Juncos Avenue
May 30, 2000
Return Receipt Requested
Mr. Jose Gonzalez
Agropharma Laboratories, Inc.
P.O. Box 1150
Salinas, Puerto Rico 00751
Dear Mr. Gonzalez:
During an inspection of your drug manufacturing facility located at Road 701, Km. 0.4, Salinas Industrial Park Salinas, P.R. 00751 conducted on March 8 to 10, 2000, investigator Israel Santiago from this office of Food and Drug Administration, documented on an FDA-483, Inspectional Observations form, several deviations from the Good Manufacturing Practice Regulations (Title 21, Code of Federal Regulations, Part 211). These deviations are in connection to your firm's manufacture of OTC topical and oral drug products causing these to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act, as follows:
1. Failure to have written drug product specifications, standards, sampling plan and testing procedures, or other laboratory controls, to assure drug products conform to identity, strength, quality and purity standards, in accordance with 211.160. There are no establish laboratory testing in place to determine finish drug conformance to specifications, including identity and strength of each active ingredient, prior to release as required in 21 CFR 211.165(a). We refer you to FDA-483 Observation 3.
2. You failed to establish and implement written testing programs to assess the stability characteristics of "Miel Rosada con Borax" solution and the "Cicatrin" ointment in accordance with 21 CFR 211.166. These OTC products are either assigned a three (3) year expiration date, or bear no expiration date, but you do not have appropriate stability data to assure they meet applicable standards of identity, strength, quality, and purity at the time of use as required in 21 CFR 211.137, or meet the exemption specified in 21 CFR 211.137(g). We refer you to FDA-483 Observations 2.
3. Failure of the quality control unit to fully and adequately investigate production and process control deviations, and to record and justify deviations and corrective actions in accordance with 21 CFR 211.192 and 211.100(b), we refer you to FDA-483 Observations 1, 4 & 5. For example:
Miel Rosada W/Borax lot MR099J002 was overheated due to temperature control problems and resulted in about 4 gallons of product lost. The impact of high temperature on product quality and stability of the remaining 28 gallons was not evaluated. The lot was later reworked by adding additional raw materials to bring it up to a yield of over 40 gallons, however, this process was improvised and not based on approved reprocessing procedures. No additional precautions were taken to assure product quality.
4. Your procedures and controls for testing purified water that is used in the manufacturing of your drug products are inadequate in that:
a) There are no documented controls for quarantine of manufacturing water, nor sanitizing and maintenance of the water purifier system when out of specifications results are obtained, including follow-up testing in accordance with 21 CFR 211.67, 211.80 and 211.89. Refer to FDA-483 observation #8
b) The instrument used to conduct the total solids test has not been verified by appropriate testing to assure its accuracy and sensitivity within the operational range and parameter used as required in 21 CFR 211.165(e). Only a daily single-reading internal verification is done before use. Refer to FDA 483 observation #9.
c) There is no assurance that the test methods/parameters and acceptance criteria for the release testing of purified water are in accordance with USP XXIV requirements for Purified Water in accordance with 21 CFR 211.194(a)(2).
The above identification of violations is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to assure adherence with each requirement of the Good Manufacturing Practice Regulations. A copy of 21 CFR Part 211 is attached for your reference. 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.
You should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in regulatory action without further notice. These actions include seizure and/or injunction. The inspection also disclosed that you manufacture under contract sodium thiosulfate lotion, an OTC antifungal drug product under the name "Cabemar", and labeled these for treatment of tinea vericolor, a skin fungus. Our preliminary review has raised questions on this product's conformance to OTC Monograph and New Drug Application requirements. We have submitted this information to our FDA Center for Drug Evaluation and Research in Washington D.C. for their review and evaluation. Further communication on this matter will depend on that evaluation.
Please notify the San Juan District office in writing, within 15 working days of receipt of this letter, of the specific steps you have taken to correct the noted violations, including an explanation of each step being taken to prevent the recurrence of these or similar violations.
Your reply should be sent to the Food and Drug Administration, San Juan District Office, 466 Fernandez Juncos Ave., San Juan, Puerto Rico 00901-3223, Attention: Andres Toro, Compliance Officer.
Mildred R. Barber