3TP LLC 05-Oct-04

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Center for Devices and Radiological Health 2098 Gaither Road Rockville, MD 20850

OCT 5 2004

WARNING LETTER

VIA FEDERAL EXPRESS
VIA FACSIMILE

Mr. Jordan Metzgar
3TP LLC
33 Flying Point Rd. Suite 217
Southampton, New York 11968

Re: 3TP Software, K031350

Dear Mr. Metzgar:

The Diagnostic Devices Branch (DDB), Office of Compliance (OC), Center for Devices and Radiological Health (CDRH), Food and Drug Administration (FDA) has reviewed your Internet website for 3TP Software. Based on our review of your website, it appears that your company is marketing 3TP Software for intended uses beyond the scope of your FDA clearance for the product.

3TP Software is a device as defined within the meaning of section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act) because it is intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or because it is intended to affect the structure or any function of the body.

FDA cleared 3TP Software for the following indications:

The 3TP Software Option is intended to be used as a post processing software package designed to provide a reliable means for visualizing the presence and pattern of contrast induced enhancement on MR datasets. 3TP supports the evaluation of dynamic MR data gathered during the injection of a bolus of contrast media. The resulting time course information can be displayed in a variety of formats, including a parametric image overlaid onto source MR images. In the hands of a trained physician the information provided by the 3TP Software Option could yield information that may assist in the interpretation of dynamic contrast enhanced studies.

Your website, http://vclassroom.hyperion.com, demonstrates that 3TP LLC is marketing the 3TP Software for intended uses that do not fall within the existing clearance. For instance, the website states that 3TP Software “facilitates rapid detection of breast cancer.”

Other items on the website that go beyond your FDA clearance include:

• “There are various methods of detecting cancer using MRI technology, however, the patented 3TP technique is the only one that provides an accurate, scientific based standardized system.”
• “3TP is an innovative software solution that facilitates detection of breast cancer through rapid interpretation of contrast enhanced MRI images.”

Marketing the 3TP Software for indications beyond the scope of your FDA clearance violates the law. Specifically, the device is adulterated under section 501(f)(1)(B) of the Act because you do not have an approved Premarket Approval Application (PMA) to demonstrate that the device is safe and effective for the new intended uses for which you are marketing it. In addition, your device is misbranded under section 502(o) of the Act because you have not submitted a section 510(k) premarket notification to notify the agency of your intent to introduce the device into commercial distribution for these new intended uses. For a product requiring premarket approval, the notification required by section 510(k) of the Act is deemed satisfied when a PMA is pending before the FDA. [21 CFR 807.81(b).]

This letter is not intended to be an all-inclusive list of deficiencies associated with your device. It is your responsibility to ensure adherence to each requirement of the Act and Federal regulations. You are responsible for investigating and reviewing these materials to assure compliance with applicable regulations.

You should take prompt action to correct these violations. Failure promptly to correct these deviations may result in regulatory action against your company being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil penalties. Also, federal agencies are informed about warning letters we issue, such as this one, so that they may consider this information when awarding government contracts.

Please notify this office, in writing, within 15 working days of receipt of this letter, outlining the specific steps you have taken to correct the cited violations. Your response should also include all steps being taken to address misleading information currently in the market place and actions to prevent similar violations in the future. 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 Mr. William C. Maloney, Physicist, Diagnostic Devices Branch (HFZ-322), at the letterhead address.

Sincerely yours,

/s/

Timothy A. Ulatowski
Director
Office of Compliance
Center for Devices and
Radiological Health

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Warning Letter Response

• 3TP, LLC Response Letter

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Aap Implantate AG 16-Jul-04

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Center for Devices and Radiological Health 2098 Gaither Road Rockville, MD 20850

WARNING LETTER

VIA FEDERAL EXPRESS

JUL 16 2004

Mr. Uwe Ahrens
CEO
Aap Implantate AG
Lorenzweg 5
12099 Berlin, Germany

Dear Mr. Ahrens:

During the inspection of your firm located in Berlin, Germany on January 26-29, 2004, United States Food and Drug Administration (FDA) investigator, James P. Mcreavey,
determined that your firm manufactures labeled non-sterile Class I and labeled non-sterile Class II orthopedic implants. Additionally, your firm has a current 510(k) under review for a labeled sterile Class II orthopedic implant. These products are devices within the meaning of Section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. 321(h)].

The investigator documented significant violations from the Quality System (QS) regulation Title 21, Code of Federal Regulations (CFR), Part 820. These violations cause the devices listed above to be 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 established by the QS regulation.

Your firm’s significant violations include, but are not limited to, the following:

1. Failure to establish and maintain adequate design input procedures, as required by 21 CFR 820.30(c), Design Input.

The QS regulation under 21 CFR 820.30(c) requires the Design Input procedures to include a mechanism for addressing incomplete, ambiguous, or conflicting requirements.

Your firm failed to comply with the requirements of 21 CFR 820.30(c). For example, your design control procedures for the knee endoprosthesis device lack a mechanism for addressing incomplete, ambiguous or conflicting design input requirements. FDA acknowledges receipt of your firm’s March 05, 2004 response to the FDA Form 483 observations. In the response, your firm promised to provide a revised procedure by March 2004. To date, we have not received any correspondence from your firm with the promised correction. Please supply the revised procedure.

2. Failure to adequately maintain device master records, as required by 21 CFR 820.181, Device Master Record (DMR).

The regulation under 21 CFR 820.181 requires that the DMR for each type of device shall include, or refer to the location of, the following information: device specifications, production process specifications, quality assurance procedures and specifications, packaging and labeling specifications and installation, maintenance and serving procedures and methods.

Your firm failed to comply with the requirements of 21 CFR 820.181. For example, the knee endoprosthesis DMR did not contain or reference (1) device drawings, (2) equipment specifications for the Roders machine used to manufacture the device, and (3) packaging and labeling specifications.

FDA acknowledges that these deficiencies were corrected by your firm and verified at the close-out of the inspection by the investigator. You appear to have adequately corrected this quality problem. Please explain how your firm intends to ensure that this kind of quality problem is not repeated.

3. Failure to validate, according to an established protocol, computer software for its intended use, when that software is used as part of the Quality System or part of production as required by 21 CFR 820.70(i), Automated Processes.

The regulation under 21 CFR 820.70(i) requires that when computers or automated data processing systems are used as part of production or the quality system, the manufacturer shall validate computer software for its intended use according to an established protocol. All software changes shall be validated before approval and issuance. These validation activities and results shall be documented.

Your firm failed to comply with the requirements of 21 CFR 820.70(i). For example:

(1) The [redacted] software used in the design and development process is not validated.
(2) The [redacted] program used by the [redacted] machine has not been validated for its intended use.
(3) The [redacted] software used for inventory and process control has not been validated for its intended use.

The March 05, 2004 response indicates that your firm would provide the missing validation information for the [redacted] software programs by July 2004. The response is not adequate. Please provide the software validation protocols for these three software programs and explain how your firm plans to prevent this error from recurring in the future.

4. Failure to establish and maintain a Design History File for each type of device as required by 21 CFR 820.30(j), Design History File (DHF).

The regulation under 21 CFR 820.30(j) requires that each manufacturer shall establish and maintain a DHF for each type of device.

You failed to comply with the requirements of 21 CFR 820.30(j). For example, there is no DHF for the knee endoprosthesis device. Your firm’s response dated March 05, 2004 promises correction by July 2004 and states your R&D manager has begun to provide the DHF and it should be completed and sent before the promised date. This is not an adequate response. Please provide a copy of the DHF for the knee endoprosthesis device, a copy of the procedure(s) your firm utilizes for assembling the DHF to fulfill the requirements of 820.30(j), and explain how your company plans to ensure this error is not repeated.

FDA also wishes to address a potential design verification violation. Although FDA acknowledges that your firm’s knee endoprosthesis has not yet been marketed in the USA and that all design control activities related to this device may not have been completed, at the time of the inspection your firm lacked documentation establishing that [redacted] sterilization of the [redacted] packaging did not impact on the performance of the [redacted] packaging. This observation was noted on the List of Inspectional Observations (Form FDA 483) issued at the closeout of the inspection.

FDA acknowledges that the investigator annotated this Form FDA 483 observation as Corrected and Verified. Additionally, your response, dated March 05, 2004, states that the certification from the supplier which assures that materials could be used for [redacted] sterilization has been integrated into the Device Master Record (DMR). The verification by the investigator and the response from your firm appear to be adequate. However, please take note that if your firm had not corrected this problem before marketing the device in the United States, it would have resulted in a failure to adequately document all design verification activities establishing that Design Outputs meet the Design Input requirements as required by 21 CFR 820.30(f), Design Verification.

This letter is not intended to be an all-inclusive list of violations at your facility. It is your responsibility to ensure adherence to each requirement of the Act and applicable regulations. The specific violations noted in this letter and Form FDA 483 issued at the closeout of the inspection may be symptomatic of serious underlying problems in your firm’s manufacturing and quality assurance systems.

U.S. 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 government contracts.

Given the serious nature of these violations of the Act, the various orthopedic implants manufactured by your firm imported or offered for import are subject to refusal of admission under section 801 (a) of the Act, 21 U.S.C. 381 (a), in that they appear to be adulterated. As a result, FDA may take steps to refuse these products, known as “detained without physical examination,” until these violations are corrected. In order to prevent your devices from being detained without physical examination, you should provide a written response to this Warning Letter as described below and correct the violations described in this letter. We will notify you if your response is adequate, and we may need to re-inspect your facility to verify that the appropriate corrections have been made.

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. You should include all documentation of the corrective action you have already taken. If you plan to make any corrections in the future, include those plans with your response to this letter as well. If the documentation is not in English, please provide a translation to facilitate our review.

Your response should be sent to the Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Division of Enforcement B, Orthopedic, Physical Medicine and Anesthesiology Devices Branch, 2094 Gaither Road, Rockville, Maryland 20850 USA, to the attention of Ms. Christy Foreman.

If you need help in understanding the contents of this letter, please contact Ms. Christy Foreman at the above address, or at (301) 594-4659 (telephone) or (301) 594-4672 (telefax).

Sincerely yours,

/s/

Timothy A. Ulatowski
Director
Office of Compliance
Center for Devices and
Radiological Health

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Abbott Laboratories, Inc. 25-Mar-04

Departmentof Health and Human Services	Public Health Service Food and Drug Administration
	Chicago District 650 West Jackson Blvd., 15th Floor Chicago, Illinois 60561 Telephone:312-353-5863

March 25, 2004
WARNING LETTER
CHI-5-04

CERTIFIED MAIL

Mr. Miles D. White
Chairman& CEO
Abbott Laboratories, Inc.
One Abbott Park Road, Bldg AP6
Abbott Park, IL 60064

Dear Mr. White:

During inspections of your firm’s Hospital Products Division (Abbott HPD),located at 600 N. Field Drive, Lake Forest, IL, from April 22 to May 1, 2003,and from May 28 to September 2, 2003, United States Food and Drug Administration(FDA) investigators determined that your firm manufactures intravenous administrationsets. These products are devices as defined by Section 201 (h) of the FederalFood, Drug, and Cosmetic Act (the Act).

These inspections revealed that these devices are adulterated within the meaningof Section 501(h) of the Act, in that the methods used in, or the facilitiesor controls used for manufacturing, packing, storage, or installation are notin conformance with the Quality System Regulation (QSR), Title 21, Code of FederalRegulations (CFR), Part 820, as follows:

1. Your firm’s management with executive responsibility failed to ensurethat the quality policy was understood, implemented, and maintained at all levelsof the organization as required by 21 CFR 820.22. For example, from May 2 toMay 19, 2003, Abbott HPD continued to distribute the following products manufacturedwith [redacted] that Abbott HPD [redacted] (FDA 483 issued 09/02/2003, Item#1):

• Lifeshield Latex-Free Macrobore Ext. Set, 7 Inch with Clave and Option-Lok,List #120940402, Lot #021045H

• Lifeshield Latex-Free Secondary LV. Set, Convertible Pin, 32 inch Piggybackwith Option-Lok, List #1119530448, Lot #010804W
  

• Lifeshield Latex-Free Primary IV Set Convertible Pin, 100 inch, List #119620478. Lot # 910574W
  

• Lifeshield Latex-Fee Primary IV Set, Convertible Pin, 100 Inch, List #119650468, Lot # 010424W
  

• Latex-Free Primary IV Set, Convertible Pin, 80 Inch, List # 049680478,Lot # 921204W

• Lifeshield Latex Free Primary IV Plumset, Convertible Pin, 104 Inch, List# 120300412, Lot #941485H
  

• Lifeshield Latex Fm Primary IV Set, Convertible Pin, 100 Inch, List #I1196200478Lot # 900584W
  

• Lifeshield Latex Fret Secondary IV Set, Convertible Pin, 32 Inch, List#I 19540448, Lot # 860994W
  

• Lifeshield Latex Free Primary IV Set, Convertible Pin, 100 Inch, List #119620478, Lot # 911034W
  

• Lifeshield Latex Free Primary IV Set, Convertible Pin, 100 ID&, List#I 19650468, Lot # 020984W
  

2. Your firm failed to revalidate the manufacturing and sterilization processwhere appropriate as required by 21 CFR 820.75(c). For example, on December19, 2001, Abbott HPD began using [redacted] to manufacture drip chambers for[redacted] IV set products. Abbott HPD's specifications required [redacted]to be used in manufacturing IV set products [redacted] Abbott HPD had no documentationof validation for this new process change. (FDA 483 issued 05/01/2003, Item#1)

3. Your firm failed to maintain procedures for implementing corrective andpreventive action as required by 21 CFR 820.100(a). [redacted] Abbott had nodocumentation that shows they tool follow-up action in response to the [redacted](FDA 483 issued 05/01/2003, Items #4-6)

4. Your firm failed to maintain procedures to ensure all purchased, or otherwisereceived, product conforms to specifications as required by 21 CFR 820.50, Forexample, Abbott’s specifications require [redacted] to be used to manufacture[redacted] drip chambers. [redacted] entitled, [redacted] requires, "Verificationthat material meets specifications, and was produced in accordance with indicatedmaterial and process specifications.” After December 19, 2001, Abbott receivedcertificates of analysis (labeled as Certification Records) for [redacted].Despite receipt of the [redacted] certificates of analysis, Abbott used the[redacted] to manufacture [redacted] drip chambers. (FDA 483 issued 05/01/2003,Item #2)

5. Your firm failed to ensure that all personnel are adequately trained toperform their assigned responsibilities as required by 21 CFR 820.25(b). Forexample, the Supplier Quality Assurance Engineering Project Specialist &Supervisor (performs audits of Abbott HPD's suppliers) had not been trainedon the following required procedures for Abbott supplier auditors: [redacted](FDA 483 issued 05/01/2003, Item #7)

6. Your firm failed to establish adequate procedures for quality audits asrequired by 21 CFR 820.22. For example, the [redacted] include specific timeframes for conducting internal audits. Both these procedures stated that qualityaudits be conducted at defined intervals and at a sufficient frequency. However,the procedures did not define the interval or frequency. ( FDA 483 issued 05/01/2003,Item #8)

This letter is not intended to be an all-inclusive list of deficiencies atyour facility. It is your responsibility to ensure adherence to each requirementof the Act and regulations. Federal agencies are advised of the issuance ofall Warning Letters about devices so that they may take this information intoaccount when considering the award of contracts.

You should take prompt action to correct these deviations and to establishprocedures to prevent their recurrence. Failure to promptly correct these deviationsmay result in regulatory action being initiated by FDA without further notice.These actions include, but are not limited to, seizure, injunction, and/or civilpenalties. Additionally, no premarket submissions for Class III devices to whichthe QS regulation deficiencies are reasonably related,will be cleared or approveduntil the violations have been corrected. Also, no requests for Certificatesfor Products for Export will be approved until the violations related to thesubject devices have been corrected and verified.

We acknowledge receipt of your firm’s responses to the Forms FDA-483,dated September 2 and May 1, 2003. Your firm’s responses include lettersdated September 18, August 4, June 10, July 28, May 29, May 23, and May 21,2003; a teleconference dated May 12, 2003; and meetings dated July 23 and May2, 2003. Although it appears from your responses that you are working towardcorrecting the deviations noted at your firm, you must adequately implementand maintain each corrective action to ensure its effectiveness. We will verifythe adequacy of your corrective actions during a subsequent inspection.

Please notify this office, in writing, within fifteen (15) working days ofreceipt of this letter of the specific steps you have taken to correct the notedviolations, including (1) the time frames within which the corrections willbe completed (2) any documentation indicating that the corrections have beenachieved, and (3) an explanation of each step being taken to identify and makecorrections to any underlying systems problems necessary to assure that similarviolations will not occur.

Your response should be sent to Michael Lang, Compliance Officer, Food andDrug Administration, at 550 West Jackson Blvd., 15th Floor, Chicago, lL, 60661-5716.If you have any questions regarding this letter, please contact Mr. Lang at(312) 596-4225.

Sincerely,
/s/

Richard Harrison

Acting District Director

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Shanghai Medical Ltd 10-Feb-04

Departmentof Health and Human Services	Public Health Service Food and Drug Administration
	Rockville, MD 20857

WarningLetter

Via Certified andRegistered Mail

WL:320-04-03

FEB 10, 2004

Ding You Xin
Factory Director
Shanghai Medical Ltd.,
No. 15 Pharmaceutical Factory
1440 Bei Di Road
Shanghai, China

Dear Mr. Ding:

We have completed our reviewof the inspection of your pharmaceutical manufacturing facility in Shanghai,China, by Investigator Robert C. Horan, Ph.D. and Chemist Susan W. Ting, duringthe period of 27-31 October 2003. The inspection revealed significant deviationsfrom U.S. current Good Manufacturing Practice (cGMP) in the manufacture of activepharmaceutical ingredients (APIs). The deviations were presented to you on anInspectional Observations (FDA-483) Form, at the close of the inspection. ThesecGMP deviations cause your APls to be adulterated within the meaning of section501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act.

We have reviewed your November7, 20 and December 22, 2003, responses to the FDA 483 Inspectional Observationssent through [redacted] Group Vice President, of [redacted] These responsesdo not sufficiently address the deviations observed during the aforementionedinspection.

Specific areas of concerninclude, but are not limited to:

1. Qualifications ofthose working in the Quality Assurance (QA) and Quality Control (QC) unitshave not been demonstrated to be adequate.

In your response datedNovember 20,2003, you state that, “Our parent company has transferredtwo qualified QC supervisors” and that, “The interim head of QChas been replaced with a qualified individual.” In the organization chartthat you provided as Appendix 3, two of these individuals are identified ashaving Bachelor of Science degrees in engineering and one as being a LicensedPharmacist having graduated from a Secondary Technical School. Further, no oneon the organizational chart, including supervisors in QA and QC, are identifiedas having academic or other suitable training in chemistry or microbiology.This is of particular concern because all of the items listed on the FDA 483related to the chemistry and microbiology deviations in the quality controlunit. The investigative team also stated that analysts could not always answertheir questions about testing. For example, a supervisor and QC manager couldnot explain how the calculation was done for the [redacted] assay determinationfor [redacted] and [redacted] In addition, the analyst performing this assaywas unaware that it is necessary to enter the [redacted] in order for the resultto be calculated properly. Lastly, the two microbiologists interviewed wereunable to accurately answer questions about growth promotion and the identificationof microorganisms.

In your recent correspondenceyou offered to provide our office a copy of the internal audit that resultedfrom this inspection. We would like to see your audit findings.

2. One of the discussionpoints with management concerned missing data for the analysis of [redacted]and [redacted] by [redacted] There were six entries in the [redacted] logbookthat could not be found in the correlating computer files.

In your response, you statethat these were samples tested for training purposes and their [redacted] weresubsequently discarded. We fail to see how this could be accurate since theanalyst conducting the test on 2/13/03 conducted 24 other acceptable tests beforethis. In addition, the analyst conducting the tests on 2/21/03, 2/23/03, 2/25/03,2/27/03, and 3/01/03 conducted analyses on 2/20/03, 2/24/03, 2/26/03, and 2/28/03.These test results were entered as acceptable prior to completion of what youare telling us is training. We are concerned about this discrepancy.

3. The microbiologicaltest records all appear to be recently written in spite of the fact that somedate back as far as two years.

You state that the documentsmay appear new because they are kept in plastic folders away from heat and light.The investigative team says they never observed any of the documents they requestedfrom the microbiological laboratory being removed from plastic folders, nordid they observe this practice anywhere else in the firm. In addition, the investigativeteam expressed concerns that the records having one entry per day appeared tohave multiple entries in the same handwriting written at a single time. Also,entries identified as being performed by a single person appeared to be writtenin more than one person’s handwriting. They observed this with virtuallyall of the documents they reviewed in the microbiological laboratory, includingsuch documents as equipment usage logs, logs for record receipt of materials,and for transfer of cultures. You failed to address this in your responses.

4. Individuals responsiblefor overseeing testing, other management, [redacted] technical managers, andthe individual hired by [redacted] as a cGMP consultant were not forthcomingwith testing documents for [redacted] testing by [redacted]

The investigative teamwas together during the interaction with the above mentioned individuals regardingthe test records for [redacted] testing. Both give the same account of whathappened. They have documented a detailed description of who they spoke withand what responses they received. None of the responses from the above mentionedindividuals was accurate until the investigative team found the test resultson the [redacted]computer. All of the above mentioned individuals initiallydenied that the firm has ever tested [redacted] for [redacted] by [redacted]Then, the QC manager said that they had done the test once a long time ago,but did not have record of the test. Later, when the investigative team lookedat the [redacted] computer files, they found that [redacted] testing for [redacted]was routinely performed. In addition, the QC Manager denied having a writtentest method for [redacted] testing for [redacted] by [redacted] but the writtentest method was later found locked in her office desk. Lastly, when asked whythe testing was performed, both the QC Manager and the Assistant Plant Managerboth stated that the test was done for no reason. When the investigative teamspoke with you and your management team the following day (10/30/2003) theysay that you told them the testing was done at a customer’s request. Theinvestigative team also said that you admitted that your firm had been untruthfulabout the testing. As the investigative team expressed to you that they didnot have confidence in the integrity of your test data as a result of this incident,so we also express our concern that your test records may be unreliable.

Another related observation statedthat one [redacted] test result represented as many as five and eight lots offinished [redacted] and [redacted] API, respectively. Although you have respondedto this observation, it nonetheless adds to our concerns about the reliabilityof the records at your firm.

5. Compendial and secondaryreference standards were not properly stored.

The investigative team found thecompendial and secondary reference standards stored in the controlled room temperaturestability room. We do not have assurance that these reference standards usedto test the finished APIs have not degraded as a result of being subjected tothe temperature and humidity conditions in the stability room. In your response,before installing a ceiling fan, you state that the temperature was [redacted]at the outlet of the heater. The observation indicates that this air was blowingdirectly on the reference standards. Reference standards that are not storedunder appropriate conditions could result in false test values. Product thatis out of specification could test within specification. This draws into questionyour test results for product shipped to the United States.

6. Microbiological testingwas inadequate in that the [redacted] samples was not neutralized prior toperforming the [redacted] testing.

In your response you expressed concernthat if the [redacted] in the sample was neutralized, you would not be testingthe [redacted] "as is". It is necessary to neutralize the [redacted] becauseit interferes with microbiological testing. Without the neutralization step,the [redacted] test will likely show a lower number of bacteria than is actuallypresent in the sample.

The procedure you submitted withyour response indicates that you will add a neutralizing agent, [redacted] tothe sampling container prior to [redacted] Please submit to data or scientificrational that the [redacted] does not alter the effectiveness of the neutralizingagent. In addition, the procedure should require swabbing the sample port andrunning [redacted] for five minutes if this is how you draw the [redacted] beforeadding it in the manufacturing process.

The cGMP deviations identifiedabove or on the FDA-483 issued to your firm are not to be considered an all-inclusivelist of the deficiencies at your facility. FDA inspections are audits, whichare not intended to determine all deviations from cGMP that exist at a film.It is the responsibility of your firm to assure compliance with all U.S. standardsfor current Good Manufacturing Practice.

Due to the significance of thesedeficiencies the FDA will deny entry of drugs manufactured by your firm intothe United States. The articles will be subject to refusal of admission pursuantto Section 801(a)(3) of the Act in that the methods and controls used in theirmanufacture do not appear to conform to current Good Manufacturing Practicewithin the meaning of Section 501(a)(2)(b) of the Act.

Until FDA can confirm compliancewith cGMP and correction to the most recent inspection deficiencies, this officewill recommend disapproval of any new applications listing your firm as themanufacturer of active pharmaceutical ingredients.

Please contact Karen K. Moksnes,Compliance Officer, at the address and telephone number shown below if you haveany questions related to human drugs.

U.S. Food & Drug Administration
Center for Drug Evaluation and Research
Foreign Inspection Team, HFD-325
11919 Rockville Pike, 4th Floor
Rockville, MD 20852
Tel: (301) 827-9008; FAX (301) 827-8909

Or, contact Jorge F. Christian,Compliance Officer at the address and telephone number shown below if you haveany questions related to veterinary drugs.

U.S. Food & Drug Administration
Center for Veterinary Medicine
Division of Compliance, HFV-232
7500 Standish Place
Rockville, MD 20855
Tel: (301) 827-0152; FAX (301) 827-1498

Sincerely,

/s/

Nicholas Buhay for

Joseph C. Famulare Director
Division of Manufacturing and Product Quality
Center for Drug Evaluation and Research

/s/

Gloria Dunnavan
Director
Division of Compliance
Office of Surveillance and Compliance
Center for Veterinary Medicine

cc: [redacted]
Group Vice-President
[redacted]

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