October 12, 2010

WARNING LETTER

CIN-11-108087-01

Via United Parcel Service

Gregory A. Neal
President and Owner
Advanced Testing Laboratory, Inc.
6954 Cornell Road, Suite 200
Cincinnati, Ohio 45242

Dear Mr. Neal:

During our February 18, 2010 to April 9, 2010 inspection of your pharmaceutical contract testing laboratory, Advanced Testing Laboratory, Inc., located at 6954 Cornell Road, Cincinnati, 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. These violations cause your client's drug product(s) 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 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 April 29, 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 failed to establish scientifically sound and appropriate test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity [21 C.F.R. §211.160(b)]. For example:

a. Your firm's microbiology laboratory processed 97 of 611 Agar plates on March 22, 2010, and 39 of 260 Agar plates on April 2, 2010, that were desiccated to a point where the medium was cracking or pulling away from the side of the plate. These Agar plates are used to test for objectionable microorganisms in your drug products and as such, it is unknown whether these defective plates can support microbial growth.

In your response, your firm states that you would assess the technique used to prepare the plates, incubator temperature, the incubation times, and the failure of management to document and address the issue. In addition, you state that you would conduct additional training and conduct process reviews to address procedures requiring five-day incubation times at temperatures that may cause desiccation.

Your response, however, is inadequate because you have not addressed the impact of the desiccated plates on the test results provided to your customers, nor have you performed any additional testing concerning test samples in desiccated plates observed during our inspection. Moreover, during the inspection your laboratory manager suggested that the problem with desiccated plates could be resolved by pouring additional media into the plates. Adding new media to a previously processed Agar plate may compromise both medium sterility and stability.

b. Your firm's microbiology laboratory did not record the presence of colonies in five plates because the colonies were considered contamination from laboratory personnel. According to Standard Operating Procedure (SOP) 300-M-0030, "Aerobic Plate Count and Enrichment Option," and SOP 300-M-0020, "Yeast and Mold Count," your analysts must record the number of colonies or each type of organism, respectively, as Colony Forming Units (CFU) in each countable plate. Your firm does not, however, define or have criteria to determine whether colonies present are due to personnel contamination.

In your response, your firm states that you will develop a new SOP to document the current peer review process regarding the counting and recording of microbial counts, including the identification of contamination and required documentation. However, your response does not include criteria to differentiate a false positive CFU without performing analytical identification of a colony observed on a plate.

In addition, please include your investigation methodology for false positive CFUs and the rationale for your approach in your response.

2. Your firm has failed to calibrate instruments and recording devices at suitable intervals in accordance with an established written program containing specific directions, schedules, limits for accuracy and precision, and provisions for remedial action in the event accuracy and/or precision limits are not met [21 C.F.R. § 211.160--Redacted--]. For example:

a. Several laboratory instruments (i.e., incubator #277, incubator #612, FT-IR spectrophotometer #597, ICP spectrometer #532, atomic absorption spectrophotometer #481, oven #112, and vacuum oven #113) used to analyze various drug components and drug products were either out of calibration, had not received proper maintenance according to your schedule, or a combination of both. Five of the seven instruments had no calibration records prior to the start of the inspection. Your SOP 600-G-0050, "General Calibration and Maintenance Procedure for Laboratory Equipment," states that laboratory equipment must be maintained and calibrated properly according to the calibration and maintenance schedule.

In your response, your firm states that all annual calibrations and scheduled maintenance will be current and documented, and that your analysts will be trained to comply with SOP 600-G-0050. However, your response only refers to those instruments listed above and does not include a review of all analytical instrumentation to ensure calibration and scheduled maintenance was performed. In addition, your response does not assess the validity of prior analytical test results using instruments that were not calibrated or lacked proper maintenance.

b. Incubators #277 and #9210-590 were not qualified properly for their intended use. Specifically, heat distribution studies were not conducted for these incubators prior to their use in performing stability studies for Over-the-Counter (OTC) drug products (e.g., --Redacted-- and --Redacted--).

In your response, your firm states that you will perform internal heat distribution studies for the incubators. However, your response is inadequate because you do not address extending these same studies to other incubators.

3. Your firm has failed to establish and document the accuracy, sensitivity, specificity, and reproducibility of test methods [21 C.F.R. § 211. 165(e)].

For example, your firm performed analytical method transfers for 236 protocols without determining whether those methods had been properly validated by your clients.

In your response, your firm states that you will develop a new procedure to ascertain the validation status of your client's methods and to assure that all methods used for product release testing are properly validated. You also state that your firm will conduct and document employee training. However, your response does not include a plan for conducting a retrospective review of your client's methods to ensure that they are adequately validated and that the method transfer was sufficient to ensure accurate results.

4. Your firm has failed to follow written responsibilities and procedures applicable to the quality control unit [21 C.F.R. § 211.22(d)].

For example, your Quality Control Unit (QCU) does not fully document and evaluate internal defects. Between December 28, 2008, and December 31, 2009, 946 internal defects were recorded without laboratory codes as required by your SOP 700-G-0160, "Internal Defect Reporting & Tracking Procedure." Further, your firm was unable to provide either a Defect Report Form (DRF) or a Defect Summary Report (DSR) for any internal defects recorded or documentation of any actions taken to address these defect trends.

In your response, your firm states that additional training will be provided concerning SOP 700-G-0160. However, your response is inadequate because you do not address: (1) the omission of required information for internal defects; (2) your failure to provide internal defect reports, and; (3) the need for a more complete trending analysis. Further, you have not provided a detailed explanation of your corrective actions or a timeframe of completion.

In addition, your firm is currently not initiating DRFs for internal defects as required by your SOP 700G-0160. Since the internal defects are not addressed, your firm may be releasing and distributing defective drug products. It is your responsibility to review all defects for products within expiry and to determine and implement adequate corrective actions. You should inform all affected clients of your findings and your proposed corrective actions.

5. Your firm has failed to follow and document, at the time of performance, established test procedures and laboratory control mechanisms. Any deviation from the written test procedures and laboratory control mechanisms shall be recorded and justified [21 C.F.R. § 211.160(a)]. For example:

a. We observed 31 expired USP standards (i.e., --Redacted--) in a laboratory drawer next to a separate drawer containing unexpired standards. SOP 500-G-0330, "Qualification of Standards Used in the Analysis of a Drug Product," stated that expired material must be discarded.

In your response, your firm states that you have discarded the 31 expired standards and that you will conduct additional enforcement and training of SOP 500-G-0330 to assure that all future expired standards are discarded immediately upon their expiration. Your response, however, is inadequate because you do not include a review or documentation of past analytical tests to assure that samples were tested with valid standards.

In addition, please describe any steps to prevent inadvertent use of expired standards, especially when your procedure states, "When a reference standard has expired, consult the laboratory manager prior to disposal as some standards are client specific and may be difficult to replace."

b. We observed 8 of 9 worksheets where one or more tabs with formula cells were not locked. These worksheets were used for analyzing raw data from drug component and product samples, including --Redacted--. Your firm's SOP 100-G-0110, "Creation and Use of Templates," stated that cells, in which data is entered, must be locked within their electronic template.

In your response, your firm states that you will enforce the existing procedure by reviewing the current inventory of electronic data files and disposing of non-compliant spreadsheets. In addition, you will retrain analysts on the current procedure. Your response, however, is inadequate because you do not assess whether the raw data results, generated using unlocked templates, are valid.

c. Between May 10,2009, and March 23,2010, your firm obtained daily plate counts from the Coliform Bath #542 exceeding the action level 70 times (28 as being "too numerous to count") and the alert level 106 times. There was no documentation showing that an investigation was initiated or corrective action(s) implemented. Your firm's SOP 600-M-0260, "Cleaning and Plating of Media Water Baths and Coliform Bath," describes alert levels as having 2-10 CFUs and action levels as having greater than 11 CFUs.

6. 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, nor have you extended investigations to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy [21 C.F.R. § 211.192].

For example, your firm was unable to provide documentation of any investigation associated with two Out-of-Specification (OOS) events listed in the OOS Tracking Log and one OOS event associated with a drug component sample, --Redacted-- (lab code #0905-0824). Your Quality Assurance Manager stated that OOS investigations are not normally conducted unless they are requested by the client. However, your firm's SOP 700-M-0070, "Out of Specification (OOS) Policy for the Microbiology Laboratory," and SOP 700-C-0010, "Out of Specification Policy for the Chemistry Laboratory," both state that an OOS investigation must be performed whenever a client's sample results are outside of the stated specification.

In your response, your firm states that you will revise both OOS procedures to require that all OOS events will be completed regardless of client specific directives. However, your response does not address a review of current and recent OOS events to ensure that adequate investigations are performed. It is your responsibility to conduct adequate and complete investigations into OOS results to include the evaluation of all data associated with the lot.

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.

We are concerned that your extended autoclave sterilization cycle time may affect the liquid media to an extent whereby it is no longer viable and thus, possibly resulting in release of contaminated samples (i.e., false negative results). The manufacturer of the liquid media states that the media should not be overheated. We are concerned that the media may be denatured due to excessive sterilization time. Please provide your scientific rationale (and any supporting data) for the extended cycle time or a corrective action(s).

Your firm acts as a contract laboratory testing for various drug components and products including: Active Pharmaceutical Ingredients (APIs), excipients, and finished drug products (e.g., antimicrobial ointments and soaps, and hand sterilizers). It is essential that you understand your responsibility to operate in full compliance with CGMPs and to inform all of your customers of significant problems encountered during the testing of these products.

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 test drug product(s) at this facility, and provide the date(s) and reason(s) you ceased testing.

Your reply should be sent to the following address:

U.S. Food and Drug Administration
c/o Mark E. Parmon, Compliance Officer
6751 Steger Drive
Cincinnati, Ohio 45237.

Sincerely,

/s/

Teresa C. Thompson
District Director
Cincinnati District

September 21, 2010

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

WARNING LETTER

Richard A. Curran
President
Perma Pure LLC
8 Executive Drive
Toms River, NJ 08755

10-NWJ-16

Dear Mr. Curran:

During an inspection of your firm located at 8 Executive Drive, Toms River, NJ, conducted between August 11-23, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures moisture exchange gas dryers. These products are medical devices according to section 201(h) of the Federal Food, Drug and Cosmetic Act (the Act) because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.

The inspection revealed that your devices are adulterated within the meaning of section 501(h) of the Act (21 U.S.C. 351(h)) in that the methods used in, or the facilities or controls used for their manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation, Title 21 Code of Federal Regulations, Part 820 (21 CFR 820). We received a response from Mr. Robert Rozek, Quality System Leader, dated September 3, 2010, concerning our investigator's observations listed on the FDA-483, List of Inspectional Observations, which was issued to Mr. Richard A. Curran, President. We address this response below in relation to each of the noted violations; however, overall we do not consider the response to be adequate. These violations include, but are not limited to the following:

1. Management with executive responsibility has not reviewed the suitability and effectiveness of the quality system at defined intervals to ensure that the quality system satisfies the requirements of 21 CFR, Part 820 and your firm's established quality policy and objectives as delineated in 21 CFR 820.20(c). For example, although management reviews were conducted, they failed to detect that seven of eight quality system deficiencies cited during the previous inspection in July 2006 had not been corrected even though a written commitment for corrective actions, dated August 31, 2006, was submitted.

Your September 3, 2010 response is not considered to be adequate. No revised procedure was provided. Corrective actions for subsequent observations list the increased number of management review meetings and agenda items as a means of preventing "recurrence of incomplete follow-through of non-conforming conditions." There is no assurance that the proposed actions for management reviews will result in a satisfactory review of the quality system regarding overall compliance with the Quality System regulations and your internal quality policy and objectives.

2. A validated process was not revalidated when changes or process deviations occurred, as required by 21 CFR 820.75(c). Specifically, your firm changed the size of tanks and method of tubing placement used in the conversion process for creating the Nafion tubing used for the ME dryers. Although you notified your customers of this process change in April 2006, a validation study including an approved protocol, acceptance criteria, final report, etc., was not conducted. Furthermore, this same observation was made during the previous inspection of July 2006.

Your response indicates that you intend to implement a pending process and equipment validation protocol as a "Systems Level" procedure. We cannot determine the adequacy of this response as no document was submitted. Also, as stated above, we do not consider your response regarding management reviews to be adequate. We also note that the retrospective validation review conducted during the recent inspection, does not appear to have been conducted per an approved protocol or documented predetermined acceptance criteria.

3. The --Redacted-- Calibration Management software has not been validated as required by 21 CFR 820.70(i). This software is used to maintain equipment calibration records and calibration procedures. This same observation was made during the previous inspection of July 2006.

Your response to this observation was not substantively different than your response to observation #2 above regarding process validation. We continue to find your response to be insufficient. Specifically, we cannot determine the adequacy of this response as no document was submitted; we do not consider your response regarding management reviews to be adequate; and the software validation conducted during the recent inspection does not appear to have been conducted per an approved protocol or documented predetermined acceptance criteria.

4. Procedures to ensure that equipment is routinely calibrated have not been established as required by 21 CFR 820.72(a). Specifically, out of sixteen calibration records reviewed by our investigator, seven calibrations were completed past the due date. For example, leak/flow test V2 was calibrated on 3/28/10, four months past the due date of 11/5/09. Five of the seven late calibrations failed to include any documentation to confirm that the equipment had been removed from use until calibrated.

Your response indicates that procedure SLP-12, Control of Inspection, Measuring, and Test Equipment, will be revised. The response cannot be considered as adequate as no revised procedure was provided.

5. Schedules for the adjustment, cleaning, and other maintenance of equipment were not adequately established, per 21 CFR 820.70(g)(1). For example, your Preventative Maintenance Program procedure, PMP-WI001, requires maintenance records to be maintained for five years; however, your firm was only able to produce records for two years, and those records were incomplete. Furthermore, maintenance activities were not performed in accordance with your Preventative Maintenance Control Plan, PMP-CP-001.

Your response indicates that the preventative maintenance program procedure and preventative maintenance control plan, along with corresponding forms, will be reviewed and revised as necessary. This response cannot be considered as adequate as no revised procedures were provided. Furthermore, your response refers to the corrective actions specified for the management review of the quality system. As stated above, we do not consider that response to be satisfactory.

6. Your firm failed to adequately document acceptance activities for finished devices as required by 21 CFR 820.80(e). For example, the device history records for lots 704, 840, and 977 list a single date on the Quality Assurance Inspection Form; however, according to your personnel, device lots are tested in batches over several days.

We do not consider your response to be adequate as the revised Quality Assurance Inspection form was not provided.

7. The device history record does not demonstrate that the device was manufactured in accordance with 21 CFR 820. Specifically, your device history records for the ME dryers do not include records of the packaging or labeling of the devices as required by 21 CFR 820.184. Packaging and labeling are part of the manufacturing process and all dates of these activities need to be recorded. Furthermore, a copy of the device label, including lot number, must be kept in the device history record.

Your response states that the "ME Packaging Overview" document will be revised. We cannot make any assessment regarding the corrective actions because no revised document was submitted.

8. Procedures for corrective and preventive actions have not been adequately established per 21 CFR 820.100(a). Specifically, your Corrective and Preventive Action procedure, SLP-15, Revision 2, fails to include several of the provisions listed in 21 CFR 820.100(a) such as:

i. Analyzing quality data sources and employing appropriate statistical methodology where necessary to detect recurring quality problems;
ii. Verifying or validating the corrective action to ensure the corrective action does not adversely affect the finished device;
iii. Submitting relevant information on identified quality problems as well as corrective and preventive actions for management review.

A similar observation was made during the previous inspection of July 2006.

Your response included a revised CAPA procedure, prepared during the inspection. Although the procedure appears to include most of the
provisions of 21 CFR 820.100(a), it still does not include all the provisions and we cannot deem it satisfactory. Furthermore, your response also cites the corrective actions regarding management reviews as a corrective and preventive measure for this observation; however, as stated above, we do not consider your response to be satisfactory regarding that observation.

9. Procedures for receiving, reviewing, and evaluating complaints by a formally designated unit have not been adequately established as required by 21 CPR 820.198(a). The Customer Complaint and Return Authorization Instructions, RA-WI-001 Revision 00, was insufficient. For example:

i. The procedure did not ensure that complaints were evaluated to determine whether the complaint constituted an event required to be reported under 21 CFR 803, Medical Device Reporting;
ii. The procedure did not require that all complaints were evaluated to determine if an investigation was necessary;
iii. The procedure did not require that when no investigation was conducted, the reason and name of individual responsible for the decision not to investigate was recorded;
iv. The procedure did not require that when a complaint represented an MDR reportable event, that the complaint was promptly reviewed and evaluated by a designated individual and that the subsequent investigation include a determination of whether the device failed to meet specifications, was being used for treatment or diagnosis, and the relationship of the device to the reported event.

The same observation was made during the previous inspection of July 2006.

Your response included a revised Customer Complaint and Return Authorization Instructions procedure, RA-WI-001, Rev. 01, dated 8/15/10. We cannot determine whether or not the revised procedure and customer complaint form will be satisfactory under actual conditions of use, nor have you provided any evidence that appropriate training has been conducted for all groups listed (quality, sales, customer service, and management) on the revised procedure, and associated requirements and procedures, such as MDR reporting. Furthermore, the response again cites the promised corrective actions regarding management reviews, and as stated previously, we do not consider that response to be sufficient.

10. Document control procedures have not been adequately established in accordance with the requirements of 21 CFR 820.40. Specifically, the Control of Documents procedure, SLP-06 Revision 04, does not include a requirement that forms used to document quality system related activities be reviewed and approved prior to issuance and/or change. During the inspection, our investigator observed two different CAPA forms, Q-F-011, with the same issue date.

We do not consider your response to be adequate. A revised procedure was not provided, nor did you provide any assurance that all existing forms related to quality system activities will be reviewed and approved, and that obsolete forms will be removed from use.

Our inspection also revealed that the device is misbranded within the meaning of section 502(t)(2) of the Act [21 U.S.C. § 352(t)(2)] in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act [21 U.S.C. § 360i] and 21 CFR § 803 - Medical Device Reporting (MDR) regulation. These violations include, but are not limited to, the following:

1. Failure to develop, maintain, and implement written MDR procedures for internal systems and the documentation and recording of required information, as required by 21 CFR § 803.17. Specifically, your firm has not developed, maintained, and implemented written MDR procedures for internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements.

The revised procedure included with your response does not clearly identify a person or group responsible for identification and evaluation of events that may be subject to MDR requirements. Neither the revised customer complaint procedure, RA-WI-001, nor the MDR procedure, MDR-WI-001, completely explain how an event is evaluated to determine if it is MDR reportable. Additionally, the number of groups listed as able to record complaints, including the MDR determination, includes quality, sales, customer service and management. You have not provided any evidence that all personnel who may record a complaint have been properly trained to evaluate events for MDR filing.

You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action being initiated by FDA without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are advised of the issuance of all warning letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices, to which the Quality System regulation deviations are reasonably related, will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.

Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrective actions you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. 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 sent to the following address: U.S. Food and Drug Administration, 10 Waterview Boulevard, 3rd Floor, Parsippany, New Jersey 07054, Attn: Sarah A. Della Fave, Compliance Officer. If you have any questions about the content of this letter, you may contact Ms. Della Fave at 973-331-4910.

Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and on the FDA-483 issued at the close of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality assurance systems. You should investigate and determine the causes of the violations and take prompt actions to correct the violations and to bring your products into compliance.

Sincerely,

/s/

Diana Amador-Toro
District Director
New Jersey District

WARNING LETTER

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

W/L 37-10August 16, 2010

Mr. Romel E. Perez
Owner/President
R&P Seafood Corp.
P.O. Box 336
Bell, CA 90201

Dear Mr. Perez:

We inspected your seafood processing facility, located at 649 Ceres Ave., Los Angeles, California on April 9, 12 and 14, 2010. We found that you have serious violations of the seafood Hazard Analysis and Critical Control Point (HACCP) regulation, Title 21, Code of Federal Regulations, Part 123, and the Current Good Manufacturing Practice regulation for foods, Title 21, Code of Federal Regulations, Part 110 (21 CFR 123 & 110). In accordance with 21 CFR 123.6(g), failure of a processor of fish or fishery products to have and implement a HACCP plan that complies with this section or otherwise operate in accordance with the requirements of Part 123, renders the fish or fishery products adulterated within the meaning of Section 402(a)(4) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 342(a)(4). Accordingly, your histamine forming species including Tuna and Mahi-Mahi are adulterated, in that they have been prepared, packed, or held under insanitary conditions whereby they may have been rendered injurious to health. You may find the Act, the seafood HACCP regulation and the Fish and Fisheries Products Hazards & Controls Guidance through links in FDA's home page at www.fda.gov.

Your significant violations were as follows:

1. You must implement the monitoring procedures and frequency that you have listed in your HACCP plan, to comply with 21 CFR 123.6(b) and (c)(4). However, your firm did not follow the monitoring procedures and frequency for histamine forming fish critical limit of "product shall be covered with ice" and "monitoring the presence of ice at the beginning and end of each shift and on a hourly basis" and "Cooler temperature maintained at 40°F or below" at the Cooler Step critical control point to control the hazard of "histamine formation during cooler storage". On 4/09/10, multiple tuna fillets were observed in the cooler that were not covered in ice. In addition, according to your February 2010 Cooler Log, the temperature of the cooler was not recorded at the end of the shift on 2/27/10.

2. You must maintain sanitation control records that, at a minimum, document monitoring and corrections set out in 21 CFR 123.11(b), to comply with 21 CFR 123.11(c). However, your firm did not maintain sanitation monitoring records for (1) the safety of water that comes into contact with food or food contact surfaces including water used to manufacture ice; (2) condition and cleanliness of food contact surfaces; (3) prevention of cross-contamination from insanitary objects; (4) maintenance of hand washing, hand sanitizing, and toilet facilities; (5) protection of food, food packaging material and food contact surfaces from adulteration; (6) proper labeling, storage and use of toxic chemicals; (7) control of employee health conditions, and (8) exclusion of pests required for the processing of fresh tuna intended to be consumed raw. You did not document any monitoring on your firm's "Daily Sanitation Control Record" sheet, except for the dates 11/20/09, 11/21/09 and 11/23/09. In addition, there is not a specific area on your "Daily Sanitation Control Record" sheet to document corrections.

3. You must verify that your HACCP plan is adequate to control food safety hazards that are reasonably likely to occur, to comply with 21 CFR 123.8(a)(2)(ii). However, your firm did not verify the calibration of process monitoring instruments, specifically the thermometer(s) used at the Storage critical control point to control histamine formation.

4. You must have a HACCP plan that, at a minimum, lists monitoring procedures and their frequency for each critical control point, to comply with 21 CFR 123.6(c)(4). However, your firm's HACCP plan for Histamine Formers lists a monitoring frequency of Each Delivery -Each Badge [sic] at the Receiving Step critical control point that is not adequate to control Histamine Presence Formation During Transit. Your monitoring frequency does not specify how many cartons or fish will be monitored per delivery.

5. Because you chose to include a corrective action plan in your HACCP plan, your described corrective actions must be appropriate, to comply with 21 CFR 123.7(b). However, your corrective action plan for scombrotoxin producing fish at the Receiving critical control point to control to control histamine formation is not appropriate.

When the critical limit is exceeded, in that the ice is not adequate, a corrective action that involves taking the temperature of only one fish is not adequate to prevent the distribution of potentially unsafe fish. We recommend taking the temperatures of fish at various locations throughout the truck.

We may take further action if you do not promptly correct these violations. For instance, we may take further action to seize your product(s) and/or enjoin your film from operating.

You should respond in writing within fifteen (15) working days from your receipt of this letter. Your response should outline the specific things you are doing to correct these violations. You should include in your response documentation such as HACCP and verification records, or other useful information that would assist us in evaluating your corrections. If you cannot complete all corrections before you respond, you should explain the reason for your delay and state when you will Correct any remaining violations.

This letter may not list all the violations at your facility. You are responsible for ensuring that your processing plant operates in compliance with the Act, the seafood HACCP regulation (21 CFR Part 123) and the Current Good Manufacturing Practice regulation (21 CFR Part 110). You also have a responsibility to use procedures to prevent further violations of the Act and all applicable regulations.

Please send your reply to the Food and Drug Administration, Attention:

Blake Bevill
Compliance Director
Los Angeles District
19701 Fairchild
Irvine, CA 92612-2506

If you have questions regarding any issues in this letter, please contact Marco Esteves, Compliance Officer at 949-608-4439.

Sincerely,

/S/

Alonza E. Cruse
District Director
Los Angeles District
Sacramento, CA 95899-7413

WARNING LETTER

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

August 9, 2010

Monica F. Abelas, President
Diasol, Inc.
1110 Arroyo Street
San Femando, CA 91340

Dear Ms. Abelas:

The Food and Drug Administration (FDA) recently performed inspections at both of your Diasol, Inc. manufacturing sites located at 1110 Arroyo Street, San Fernando, California and 310 S. 43rd Avenue Phoenix, Arizona. The inspections were performed at Diasol Inc. San Femando, CA from May 19 through May 28, 2010 and at Diasol Inc. Phoenix, AZ from January 1 through February 3, 2010. These inspections determined that your firms manufacture liquid and dry hemodialysis concentrates. These products are indicated for use in acute and chronic hemodialysis. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.

The inspections revealed that these devices are adulterated within the meaning of section 501(h) of the Act (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (C.F.R.), Part 820. Similar violations were observed during an inspection of your facility located at 310 S. 43rd Avenue, Phoenix, Arizona from January 1 through February 3, 2010. We received your responses dated February 14 and June 9, 2010 concerning our investigator's observations noted on the Form FDA 483. We address these responses below, in relation to each of the noted violations. Unless otherwise noted, the violations below pertain to the May 28, 2010 San Fernando, CA inspection. These violations include, but are not limited to, the following:

1. Failure to validate to a high degree of assurance and approve according to established procedures a process, where the results of the process cannot be fully verified by subsequent inspection and test as required by 21 CFR 820.75(a). Specifically, the the liquid dialysis concentrate is filled into --Redacted-- and then delivered to customers --Redacted--. The validation for the process of cleaning --Redacted-- has not been completed.

This violation was identified during the February 3, 2010 Phoenix inspection and the May 28, 2010 San Fernando inspection. We reviewed your FDA 483 response letter dated February 14, 2010, and determined it was inadequate because your cleaning validation was incomplete and insufficient data was provided to support your acceptance criteria. Your FDA 483 response letter dated June 9, 2010 to the San Femando, CA inspection indicates you are in the process of performing a larger scale --Redacted-- validation at both of your manufacturing sites.

Your Validation Protocol --Redacted-- and data that was provided with your June 9, 2010 response does not take into account the microbial condition of the --Redacted-- prior to washing. This protocol states --Redacted--. This procedure would require validation to insure that --Redacted-- contaminants will be detected and --Redacted-- are properly identified.

Your validation procedure describes your acceptance criteria and states --Redacted--. However, your validation report does not address --Redacted--. In addition, your testing described in your Validation Protocol --Redacted-- does not account for detection of --Redacted--. Your validation data and results should ensure that all your acceptance criteria are met.

In addition, your microbiological results provided with your response do not indicate whether the results reflect --Redacted--. Your procedure that appears on your --Redacted-- worksheet indicates --Redacted--.

2. Failure to establish and maintain acceptance procedures to ensure that specified requirements for in-process products are met as required by 21 CFR 820.80(c). Specifically, your procedure --Redacted-- states that when processing --Redacted-- water for production samples that --Redacted-- will be delivered to --Redacted-- for incubation and reading. However, it was observed that the delivered volume is not measured and --Redacted-- are used. In --Redacted-- and therefore a measured volume is required.

Your response is not adequate. You stated in your June 9, 2010 response that you have updated your procedure to state that --Redacted--.  You have not indicated how this volume is being measured and a written procedure was not provided. Please provide your water testing  procedures for both the Phoenix and San Fernando sites.

3. Failure to document all activities and results required under 21 CFR 820.100 Corrective and Preventative Action (CAPA). Specifically, your CAPA procedure --Redacted-- indicates a corrective action log is maintained. However, a CAPA log is not being maintained.

Your response is not adequate. You indicated in your response that the CAPA log has been created and all incidents and actions taken were logged. However, you did not provide evidence of your corrective action.

4. Failure to investigate certain indicators of nonconformities to determine the cause of the nonconformity as required by 21 CFR 820.100(a)(2). Specifically, on 9/15/2009 the pyrogen test on the --Redacted-- process water was reported by an outside laboratory to have greatly exceeded the limit of --Redacted--. There was no documented investigation of this non-conformity until one was prepared during the inspection.

Your response is not adequate. You indicated that the high pyrogen test results for the --Redacted-- water were a result of in house contamination. However, you have not provided a detailed investigation determining the root cause of the contamination and have not provided evidence of a corrective and preventative action.

5. The device history record fails to include or refer to the location of the dates of manufacture as required by 21 CFR 820.184(a). Specifically, the device history record for liquid acid concentrate did not record the date when key components --Redacted-- did not record the date when  key components --Redacted-- were weighed.

Your response is not adequate. Your response states that you have changed your procedure, however a copy of your revised procedure(s) was not provided. In addition, the corrective and preventative action to prevent re-occurrence was not provided with your response.

6. Failure to maintain device history record as required by 21 CFR 820.184. Specifically, the device history record for of Diasol Liquid Bicarbonate shows that this lot was mixed --Redacted-- and filled into --Redacted-- on 4/07/2010. However, a sticky note and interviews with plant personnel indicates the lot was mixed and filled on 4/21/2010.

Your response is not adequate. You have indicated that you have made changes to your operating procedure, however a copy of your revised procedure was not provided. In addition, the preventative action to prevent re-occurrence was not provided with your response.

7. Failure to establish and maintain procedures to ensure that equipment is routinely calibrated, inspected, checked and maintained as required by 21 CFR 820.72(a). Specifically, your calibration program procedure, --Redacted-- requires a calibration schedule for measuring equipment. However, there is no calibration schedule for measuring equipment.

Your response is not adequate. You have indicated that you have made changes to your calibration procedure, however a copy of your revised procedure was not provided. In addition, the preventative action to prevent re-occurrence was not provided with your response.

8. Failure to document activities with respect to inspection, measuring, and test equipment as required by 21 CFR 820.72(a). Specifically,

a. The --Redacted-- scale used to weigh the --Redacted-- for formulation of --Redacted-- on 5/25/2010 had a calibration sticker which expired on 8/05/2009. There was no documentation that this scale had been calibrated after 8/05/2009.
b.The --Redacted-- thermometer --Redacted-- used to record the daily temperature in the counter top incubation oven was put into service on 4/28/2008. The manufacturer recommends that it be calibrated once a year. There is no documentation that this thermometer has been calibrated once a year. There is no documentation that this thermometer has been calibrated since 4/28/2008.

Your response is not adequate. You have indicated that your scale had been calibrated twice in-house since 8/05/2009 and that your thermometer was checked against a NIST traceable thermometer. However, you did not provide evidence of past or current calibration of your --Redacted-- scale or the --Redacted----Redacted--. Please provide evidence that you have implemented your corrective actions and provide calibration documentation. In addition, the preventative action to prevent re-occurrence was not provided with your response. thermometer

You should take prompt action to correct the violation(s) addressed in this letter. Failure to promptly correct these violation(s) may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.

You should take prompt action to correct the violation(s) addressed in this letter. Failure to promptly Collect these violation(s) may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.

Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to Correct the noted violations, including an explanation of how you plan to prevent these violation(s), or similar violation(s), from occurring again. Include documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. 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 written response should be sent to:

Blake Bevill
Director, Compliance Branch
Food and Drug Administration
19701 Fairchild
Irvine, CA 92612-2506

If you have any questions about the content of this letter please contact Marco Esteves, Compliance Officer at 949-608-4439.

Finally, you should know that this letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violation(s) noted in this letter and in the Inspectional Observations, Form FDA 483 (FDA 483), issued at the closeout of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality assurance systems. You should investigate and determine the causes of the violation(s), and take prompt actions to correct the violation(s) and to bring your products into compliance.

Sincerely,

/s/

Alonza E. Cruse
District Director
Los Angeles District

Cc: Monica F. Abelas, President
Diasol, Inc.
310 S. 43rd Avenue, Bldg. B
Phoenix, AZ 85009

Cc: Branch Chief
Food and Drug Branch
California Department of Public Health
1500 Capitol Avenue - MS 7602
P.O. Box 997413
Sacramento, CA 95899-7413