Teva Pharmaceutical Industries 1/31/11

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Silver Spring  MD  20993

Warning Letter

VIA UPS MAIL   

WL: 320-11-008

January 31, 2011

Mr. Shlomo Yanai
President and C.E.O.
Teva Pharmaceutical Industries, Ltd.
Petach-Tikva 5 Basel Street
P.O. Box 3190
Petach Tikva 49131 - Israel

Dear Mr. Yanai:

During our September 12-16, 2010 inspection of your pharmaceutical manufacturing facility, Teva Pharmaceutical Industries, Ltd., located at 24 Professor Hartum Street, Har Hozvim, Jerusalem, Israel, investigators 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 drug products 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 October 7, 2010, and note that it lacks sufficient corrective actions.  

Specific violations observed during the inspection include, but are not limited, to the following:

1. Your firm has not thoroughly investigated the failure of a batch or any of its components to meet its specifications whether or not the batch has already been distributed, and you failed to extend the investigation to other batches of the same drug product that may have been associated with the specific failure or discrepancy [21 C.F.R. § 211.192].  For example,

a. Your firm did not thoroughly investigate (b)(4)mg (b)(4) mg lot #(b)(4), when it failed to meet the established specification for both the single largest impurity and for total impurities amount. 

Specifically, the laboratory test results for lot #(b)(4) had a single impurity at RRT-(b)(4) minutes of (b)(4) (specification limit NMT (b)(4) %) and total impurity result of (b)(4)% (specification limit (b)(4)%). Your firm subsequently invalidated these results although your investigation was unable to confirm a root cause of the failure. Your firm selectively used passing results from a different analysis to approve the lot.

We reviewed your written response dated October 7, 2010. You do not provide adequate justification for invalidating the original results and utilizing retest results to release the batch. In your response you state the investigation results concluded that the original sample was contaminated during the processing of the test sample in the laboratory. However, you fail to describe how that conclusion was determined, or identify the root cause of the sample contamination, other than relying on the retest results being within specification.  In addition, you fail to provide corrective actions to prevent a recurrence.

We recommend you review the FDA guidance for industry entitled, "Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production," for some basic principles regarding conduct of OOS investigations. The guidance states that when laboratory errors are not convincingly identified in the initial test, there is a lack of scientific basis for invalidating initial OOS results in favor of passing retest results.  In addition, the guidance notes that all test results should be reported and considered in batch release decisions.

b. Your firm did not thoroughly investigate (b)(4) mg/(b)(4)mg lot #(b)(4) when black particles were found in the sample powder during laboratory analysis. 

Specifically, the investigation no. PRI-030 concludes that the original powder was probably contaminated by a weighing instrument in the laboratory. However, the black particles were not identified and source was not determined. In addition, there was no attempt to determine if the black particles originated from the manufacturing process, or if additional lots were affected.

Your response lacks an explanation and documentation to support your conclusion that the powder was contaminated in the laboratory. Provide in your response to this letter the corrective and preventive actions implemented to address this deficiency.  

c. Your firm did not thoroughly investigate (b)(4) tablets (b)(4) mg lot #(b)(4) when it failed to meet the finished product assay specification.

Specifically, the finished product assay specification result was (b)(4)% (specification of (b)(4)%). A reinjection of the sample obtained a value of (b)(4)%, confirming the original OOS results. Your firm decided to prepare a new working solution. This sample resulted in (b)(4)%, which is on the lower limit of the specification.

Your firm retested six new samples from the same original laboratory sample tested and obtained the following values: (b)(4)% (four of the six results were also close to the lower limit of the specification).

Your investigation lacks data to support its conclusion that the OOS results were probably related to samples not being properly extracted during the standard solution preparation stage. It also lacks a thorough evaluation of the manufacturing process and other lots that may have been affected prior to invalidating the OOS results.

In your response to this letter, please include your stability data for (b)(4) lot #(b)(4) to demonstrate that it remains within specification throughout its shelf life. In addition, include data to support that a laboratory error occurred, and provide corrective actions to prevent a recurrence. We also recommend that your firm evaluate trends for results that may indicate a lack of control over the manufacturing process, or may affect the safety and efficacy of the products that marginally meet the established specifications for release.

We are concerned that your firm has released and distributed finished drug batches to the U.S. market in which the OOS investigations were not scientifically sound. Specifically, we are concerned that laboratory results were invalidated without supporting data and the investigations did not extend to other batches that may have been associated with the failure.

Include in your response to this letter a complete list of all finished drug batches shipped to the United States within expiry (include lot number, date of shipment, customer name and address), in which there was an OOS investigation conducted. We request that you conduct a retrospective review of all opened and closed OOS investigations associated with these U.S. lots. Please supply supporting documentation for your evaluation and conclusions for each OOS investigation, as well as your corrective actions to prevent a recurrence, where appropriate. Inform this office of any additional action you plan to take to correct this violation and ensure that adulterated drug product have not been released to the U.S. market.

2. Your firm has not established separate or defined areas or such other control systems as necessary to prevent contamination or mix-ups during drug manufacturing [21 C.F.R. § 211.42(c)]. 

For example, your firm lacked an adequate assessment of the cross-contamination risks posed by the manufacture of several potentially hazardous compounds (e.g., (b)(4)) at your facility. Your facility contains shared manufacturing areas where you produce potentially hazardous compounds in multi-product equipment that are high powder generating operations, including (b)(4) drug products intended for the U.S. market. Your firm should ensure that a documented justification and well-designed contamination prevention strategy is in place to minimize the possibility of contamination. To achieve proper product protection, sound design and control approaches must be used.  Without proper separation, your firm lacks assurance that one drug does not contaminate another drug.

We recognize that your October 7, 2010 response states that you are in the process of developing a risk management program for control of cross-contamination of the products produced at the Jerusalem Oral Solid Dosage (OSD) plant. However, you did not submit that plan, or data to support the effectiveness of the plan, with your response. We also recognize your commitment to finish the risk assessment within four months. Please provide us with any update on your timeline, and the identification of resources allocated to address this issue.  Please also include in your risk analysis, procedures and data addressing the following potential routes for cross-contamination:  mix-up, retention, mechanical transfer, and airborne transfer.

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.  If you wish to continue to ship your products to the United States, it is the responsibility of your firm to ensure compliance with all U.S. standards for CGMP and all applicable U.S. laws and regulations. 

Until all corrections have been completed and FDA has confirmed corrections of the violations and your firm’s compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer. In addition, failure to correct these violations may result in FDA refusing admission of articles manufactured at Teva Pharmaceutical Industries, Ltd. located at 24 Professor Hartum Street, Har Hozvim, Jerusalem, Israel into the United States. The articles are subject to refusal of admission pursuant to section 801(a)(3) of the Act [21 U.S.C. § 381(a)(3)], in that, the methods and controls used in their manufacture do not appear to conform to Current Good Manufacturing Practice within the meaning of section 501(a)(2)(B) of the Act [21 U.S.C. § 351(a)(2)(B)].  

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. Please identify your response with FEI #3005202697.

If you have questions or concerns regarding this letter, contact Denise M. DiGiulio, Compliance Officer, at the below address and telephone number.

U.S. Food and Drug Administration
Center for Drug Evaluation and Research
Division of Manufacturing and Product Quality
International Compliance Branch
White Oak, Building 51
10903 New Hampshire Ave
Silver Spring, MD  20993
Tel: (610) 430-7864
Fax: (301) 847-8741

Sincerely,

/s/

Richard L. Friedman 
Director
Division of Manufacturing and Product Quality
Office of Compliance
Center for Drug Evaluation and Research
 

-

Close Out Letter

• Teva Pharmaceutical Industries - Close Out Letter 9/9/11

-

-

Mom's Food Products, Inc. 1/31/11

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Dallas District 4040 North Central Expressway Dallas, Texas 75204-3128

January 31, 2011

2011·DAL-WL-07

WARNING LETTER

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

Leslie Charles "Charlie" Rankin, Co-Owner
Mom's Food Products, Inc.
4117 Garland Drive
Ft. Worth, Texas 76117-1706
 

Dear Mr. Rankin:

We inspected your seafood processing establishment, located at 4117 Garland Drive, Ft. Worth, Texas, on July 20-29, 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 (21 CFR Part 123), and the Current Good Manufacturing Practice regulation for foods, Title 21, Code of Federal Regulations, Part 110 (21 CFR Part 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 tuna salad sandwiches packed in a modified or reduced oxygen packaging material 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 conduct or have conducted for you a hazard analysis for each kind of fish and fishery product you produce to determine whether there are food safety hazards that are reasonably likely to occur and have a HACCP plan that, at a minimum, lists the food safety hazards that are reasonably likely to occur, to comply with 21 CFR §123.6(a) and (c)(1). A food safety hazard is defined in 21 CFR §123.3(f) as "any biological, chemical, or physical property that may cause a food to be unsafe for human consumption." However, your firm's HACCP plan entitled "HCCP PLAN TUNA FISH SANDWICH" which was collected during the inspection, does not list the food safety hazards of Clostridium botulinum growth and toxin formation, the hazard of undeclared allergens, and the hazard of histamines. We note that in your response to the FDA-483, you indicated that you have made corrections; however, you did not provide a copy of a revised HACCP Plan.

a. During the inspection your firm packaged Mom's Deli Style Tuna Salad Sandwich on Wheat Bread (5 oz.) and Mom's Deli Style Tuna Salad Sandwich on White Bread (5 oz.), in a polypropylene triangle wedge covered by a film with an oxygen transmission rate of (b)(4) cc/100in2 at 22°C. Approximately one half of the film was covered with a peel and stick label, further restricting oxygen permeability. The combination of packaging significantly limits the flow of oxygen and creates conditions that are conducive to Clostridium botulinum growth and toxin formation (i.e., a modified or reduced oxygen package). In your October 7,  2010 response, your firm provided specification for a new film to be used to continue manufacturing of tuna salad sandwiches. The new specification sheet indicates an oxygen permeability of (b)(4) cc/100in2 at 22°C. Based on the new specifications, the packaging continues to inhibit safe oxygen transmission. Clostridium botulinum continues to pose a reasonably likely food safety hazard for the tuna salad sandwiches manufactured by your firm. FDA considers a minimum oxygen transmission rate of 10,000 ccl m2/24 hrs to be oxygen permeable.

Chapter 13 of the Guide lists guidance for controlling C. botulinum growth and toxin formation that can help you choose a method of control most suited to your process.

b. The tuna salad your firm uses to manufacture Mom's Deli Style Tuna Salad Sandwich on Wheat Bread (5 oz.) and Mom's Deli Style Tuna Salad Sandwich on White Bread (5 oz.), includes the ingredients: tuna, eggs, soy, Wheat, and milk. Fish, wheat, soy, eggs, and milk are considered major food allergens. HACCP plans for fishery products that contain these ingredients should list and control the hazard of undeclared allergens. Chapter 19 of the Fish and Fisheries Products Hazards & Controls Guidance (the Guide) contains additional information regarding the control of this hazard.

2. You must take an appropriate corrective action when a deviation from a critical limit occurs, to comply with 21 CFR 123.7(a). However, during the inspection, your firm did not take a corrective action to control pathogen growth when your process for tuna sandwiches deviated from your critical limit at the storage temperature critical control point. Specifically, the temperature for Cooler # (b)(4) a cooler used to store bulk tuna salad and, on occasion, finished product tuna salad sandwiches, exceeded your critical limit of (b)(4)°F on May 5, 2010 at 1:03 PM. Your firm could not provide evidence that a corrective action was taken to correct the deviation or its cause and prevent interstate distribution of affected product. Your response did not address this issue.

3. You must monitor sanitation conditions and practices during processing with sufficient frequency to ensure compliance with current good manufacturing practice requirements in 21 CFR Part 110, to comply with 21 CFR §123.11(b). However, during the inspection it was observed that your firm did not monitor safety of water that comes into contact with food or food contact surfaces, condition and cleanliness of food contact surfaces, prevention of cross-contamination from insanitary objects, and the protection of food, and food contact surfaces from adulteration with sufficient frequency to ensure control as evidenced by these insanitary conditions that were not addressed in any of your firm's responses.

• On July 22, 2010, an employee was observed conducting the pre-operational sanitation inspection without first washing her hands after entering the production room. The inspector was observed touching food contact surfaces without gloves. Following the sanitation inspection, some, but not all, food contact surfaces were sprayed with a sanitizer bottle by a sanitation employee. However, the sanitizer within the bottle was found to only contain (b)(4) pm , rather then (b)(4) ppm (b)(4) per the sanitizer's instructions. Further, the inspection failed to include inspection of the hand washing sinks, and there were no records of checking hand sinks since June 24, 2010. Also, there were no records of checking the toilet facilities since June 11,2010.

• On July 20, 2010 two employees working on the cold line swept the floor and emptied the trash during the change out between turkey and swiss sandwiches and tuna salad sandwiches. When they finished cleaning, they washed their hands and changed their gloves, but did not change the plastic arms sleeves that extend down their arms to their wrists. They then proceeded to assemble Mom's Deli Fresh Tuna Salad Sandwiches lot 8/11/10.

• On July 20, 2010 the hand sink in the MAP room was blocked and inaccessible to all employees except those who were working along the backside of the roll stock packaging machine. Mom's Deli Style Tuna Salad Sandwiches lot 08/11/10 and Jumbo Turkey & Swiss lot 8/11/10 were being packaged in the room at the time.

• On July 21, 2010 water was dripping from the drain line of a ceiling cooling unit next to (b)(4) line #(b)(4) in the MAP room. Rolling racks containing empty bread trays on which sandwiches, including tuna salad sandwiches, are held were stored beneath this dripping line. These bread trays are used repeatedly throughout the week without washing, and when they are washed it is done using a power washer in the parking lot outside and without a sanitization step. Also, when this drip was pointed out to a production employee, that employee then obtained a broom that is used to sweep the floor and a rag and dabbed at the drip with the rag on the bristle end of the broom.

• Your firm uses (b)(4) sanitizer on equipment and in dip and utensil buckets during production. On July 20, 2010, while Mom's Deli Fresh Tuna Salad Sandwiches were being assembled (lot 8/11/10), a container was observed on a table next to the cold line that contained food contact utensils (knives, spatulas) soaking in sanitizer that was measured to be (b)(4) ppm (b)(4) instead of (b)(4) ppm.

4. You must maintain adequate 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 has not maintained adequate sanitation monitoring records for 1) checking hand sinks since June 24, 2010; and 2) checking toilet facilities required for the processing of tuna fish sandwich since June 11, 2010.

Your firm receives your raw material tuna salad manufactured and packaged in 30 pound bulk containers under refrigerated conditions. Pathogen growth, including potentially Clostridium botulinum growth and toxin formation, as well as histamine development are reasonably likely hazards that can occur during transit if the tuna is exposed to time and temperature abuse. We acknowledge your firm's response indicating that you have added a critical control point for receiving, however, because you did not provide a copy of the revised plan or fully explain the parameters listed in the revised plan, we are unable to assess its adequacy.

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 firm from operating.

You should respond in writing within fifteen (15) working days from your receipt of this letter. Your response should outline the progress of the specific things you are doing to correct these violations. Please send examples of any documentation showing that corrections have been achieved. If you cannot complete all the requested information before you respond, please explain the reason for your delay and the date that we can expect the requested documentation.

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: Sherrie L. Krolczyk, Compliance Officer, at the above letterhead address. If you have questions regarding any issues in this letter, please contact Sherrie L. Krolczyk at (214)253-5312.

Sincerely,
 

/s/

Reynado R. Rodriguez, Jr.
Dallas District Director

 

-

Teva Pharmaceutical Industries 1/31/11

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Silver Spring  MD  20993

Warning Letter

VIA UPS MAIL   

WL: 320-11-008

January 31, 2011

Mr. Shlomo Yanai
President and C.E.O.
Teva Pharmaceutical Industries, Ltd.
Petach-Tikva 5 Basel Street
P.O. Box 3190
Petach Tikva 49131 - Israel

Dear Mr. Yanai:

During our September 12-16, 2010 inspection of your pharmaceutical manufacturing facility, Teva Pharmaceutical Industries, Ltd., located at 24 Professor Hartum Street, Har Hozvim, Jerusalem, Israel, investigators 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 drug products 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 October 7, 2010, and note that it lacks sufficient corrective actions.  

Specific violations observed during the inspection include, but are not limited, to the following:

1. Your firm has not thoroughly investigated the failure of a batch or any of its components to meet its specifications whether or not the batch has already been distributed, and you failed to extend the investigation to other batches of the same drug product that may have been associated with the specific failure or discrepancy [21 C.F.R. § 211.192].  For example,

a. Your firm did not thoroughly investigate (b)(4)mg (b)(4) mg lot #(b)(4), when it failed to meet the established specification for both the single largest impurity and for total impurities amount. 

Specifically, the laboratory test results for lot #(b)(4) had a single impurity at RRT-(b)(4) minutes of (b)(4) (specification limit NMT (b)(4) %) and total impurity result of (b)(4)% (specification limit (b)(4)%). Your firm subsequently invalidated these results although your investigation was unable to confirm a root cause of the failure. Your firm selectively used passing results from a different analysis to approve the lot.

We reviewed your written response dated October 7, 2010. You do not provide adequate justification for invalidating the original results and utilizing retest results to release the batch. In your response you state the investigation results concluded that the original sample was contaminated during the processing of the test sample in the laboratory. However, you fail to describe how that conclusion was determined, or identify the root cause of the sample contamination, other than relying on the retest results being within specification.  In addition, you fail to provide corrective actions to prevent a recurrence.

We recommend you review the FDA guidance for industry entitled, "Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production," for some basic principles regarding conduct of OOS investigations. The guidance states that when laboratory errors are not convincingly identified in the initial test, there is a lack of scientific basis for invalidating initial OOS results in favor of passing retest results.  In addition, the guidance notes that all test results should be reported and considered in batch release decisions.

b. Your firm did not thoroughly investigate (b)(4) mg/(b)(4)mg lot #(b)(4) when black particles were found in the sample powder during laboratory analysis. 

Specifically, the investigation no. PRI-030 concludes that the original powder was probably contaminated by a weighing instrument in the laboratory. However, the black particles were not identified and source was not determined. In addition, there was no attempt to determine if the black particles originated from the manufacturing process, or if additional lots were affected.

Your response lacks an explanation and documentation to support your conclusion that the powder was contaminated in the laboratory. Provide in your response to this letter the corrective and preventive actions implemented to address this deficiency.  

c. Your firm did not thoroughly investigate (b)(4) tablets (b)(4) mg lot #(b)(4) when it failed to meet the finished product assay specification.

Specifically, the finished product assay specification result was (b)(4)% (specification of (b)(4)%). A reinjection of the sample obtained a value of (b)(4)%, confirming the original OOS results. Your firm decided to prepare a new working solution. This sample resulted in (b)(4)%, which is on the lower limit of the specification.

Your firm retested six new samples from the same original laboratory sample tested and obtained the following values: (b)(4)% (four of the six results were also close to the lower limit of the specification).

Your investigation lacks data to support its conclusion that the OOS results were probably related to samples not being properly extracted during the standard solution preparation stage. It also lacks a thorough evaluation of the manufacturing process and other lots that may have been affected prior to invalidating the OOS results.

In your response to this letter, please include your stability data for (b)(4) lot #(b)(4) to demonstrate that it remains within specification throughout its shelf life. In addition, include data to support that a laboratory error occurred, and provide corrective actions to prevent a recurrence. We also recommend that your firm evaluate trends for results that may indicate a lack of control over the manufacturing process, or may affect the safety and efficacy of the products that marginally meet the established specifications for release.

We are concerned that your firm has released and distributed finished drug batches to the U.S. market in which the OOS investigations were not scientifically sound. Specifically, we are concerned that laboratory results were invalidated without supporting data and the investigations did not extend to other batches that may have been associated with the failure.

Include in your response to this letter a complete list of all finished drug batches shipped to the United States within expiry (include lot number, date of shipment, customer name and address), in which there was an OOS investigation conducted. We request that you conduct a retrospective review of all opened and closed OOS investigations associated with these U.S. lots. Please supply supporting documentation for your evaluation and conclusions for each OOS investigation, as well as your corrective actions to prevent a recurrence, where appropriate. Inform this office of any additional action you plan to take to correct this violation and ensure that adulterated drug product have not been released to the U.S. market.

2. Your firm has not established separate or defined areas or such other control systems as necessary to prevent contamination or mix-ups during drug manufacturing [21 C.F.R. § 211.42(c)]. 

For example, your firm lacked an adequate assessment of the cross-contamination risks posed by the manufacture of several potentially hazardous compounds (e.g., (b)(4)) at your facility. Your facility contains shared manufacturing areas where you produce potentially hazardous compounds in multi-product equipment that are high powder generating operations, including (b)(4) drug products intended for the U.S. market. Your firm should ensure that a documented justification and well-designed contamination prevention strategy is in place to minimize the possibility of contamination. To achieve proper product protection, sound design and control approaches must be used.  Without proper separation, your firm lacks assurance that one drug does not contaminate another drug.

We recognize that your October 7, 2010 response states that you are in the process of developing a risk management program for control of cross-contamination of the products produced at the Jerusalem Oral Solid Dosage (OSD) plant. However, you did not submit that plan, or data to support the effectiveness of the plan, with your response. We also recognize your commitment to finish the risk assessment within four months. Please provide us with any update on your timeline, and the identification of resources allocated to address this issue.  Please also include in your risk analysis, procedures and data addressing the following potential routes for cross-contamination:  mix-up, retention, mechanical transfer, and airborne transfer.

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.  If you wish to continue to ship your products to the United States, it is the responsibility of your firm to ensure compliance with all U.S. standards for CGMP and all applicable U.S. laws and regulations. 

Until all corrections have been completed and FDA has confirmed corrections of the violations and your firm’s compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer. In addition, failure to correct these violations may result in FDA refusing admission of articles manufactured at Teva Pharmaceutical Industries, Ltd. located at 24 Professor Hartum Street, Har Hozvim, Jerusalem, Israel into the United States. The articles are subject to refusal of admission pursuant to section 801(a)(3) of the Act [21 U.S.C. § 381(a)(3)], in that, the methods and controls used in their manufacture do not appear to conform to Current Good Manufacturing Practice within the meaning of section 501(a)(2)(B) of the Act [21 U.S.C. § 351(a)(2)(B)].  

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. Please identify your response with FEI #3005202697.

If you have questions or concerns regarding this letter, contact Denise M. DiGiulio, Compliance Officer, at the below address and telephone number.

U.S. Food and Drug Administration
Center for Drug Evaluation and Research
Division of Manufacturing and Product Quality
International Compliance Branch
White Oak, Building 51
10903 New Hampshire Ave
Silver Spring, MD  20993
Tel: (610) 430-7864
Fax: (301) 847-8741

Sincerely,

/s/

Richard L. Friedman 
Director
Division of Manufacturing and Product Quality
Office of Compliance
Center for Drug Evaluation and Research
 

-

Close Out Letter

• Teva Pharmaceutical Industries - Close Out Letter 9/9/11

-

-

Sanofi-Aventis U.S. LLC 1/28/11

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Waterview Corporate Center 10 Waterview Blvd., 3rd Floor Parsippany, NJ 07054 Telephone (973) 331.4900

 

January 28, 2011

 

WARNING LETTER

 

 

CERTIFIED MAIL

RETURN RECEIPT REQUESTED

 

Gregory Irace

President and Chief Executive Officer (CEO)

Sanofi-Aventis US LLC

55 Corporate Drive

Bridgewater, New Jersey 08807                                                                    

                                                                                                11-NWJ-06

Dear Mr. Irace:

 

The Food and Drug Administration (FDA or “Agency”) inspected Sanofi-Aventis (Sanofi) pharmaceutical facility located at the address above from April 16, 2010 through May 13, 2010. The inspection focused on Sanofi’s compliance with Postmarketing Adverse Drug Experience (PADE) reporting requirements.  FDA’s inspection found that your firm failed to comply with the postmarketing reporting requirements under 21 U.S.C. § 355(k) [Section 505(k) of the Federal Food, Drug, and Cosmetic Act (the Act)] and its corresponding regulations in Title 21 of the Code of Federal Regulations (21 C.F.R.) Section 314.80 and 314.81. Such failure to comply with Section 505(k) of the Act and its corresponding regulations is a prohibited act under Section 301(e) of the Act [21 U.S.C. § 331(e)]. Therefore, FDA concludes that Sanofi has engaged in prohibited acts in violation of Section 301(e) of the Act.

Sanofi’s deviations from FDA’s reporting requirements observed during the inspection include, but are not limited to, the following: inadequate written procedures for the surveillance, receipt, evaluation, and reporting of adverse events as required by 21 CFR 314.80(b), failure to submit serious and unexpected adverse drug experience (ADE) reports within 15 calendar days to FDA under 21 CFR 314.80, and failure to include all postmarketing studies in the Annual Report to FDA under 21 CFR 314. 81.

 

We acknowledge receipt of your June 3, 2010, July 28, 2010 and October 27, 2010 written responses to the FDA-483 Inspectional Observations issued to your firm on May 13, 2010. We have determined that your response and promised corrective actions are inadequate to address the deficiencies identified.

 

The specific violations observed during the inspection include, but are not limited, to the following:

 

1. Failure to review, evaluate, and submit adverse drug experience (ADE) reports that are both serious and unexpected to FDA within 15 calendar days of initial receipt of the information as required by 21 CFR 314.80(c)(1)(i).  For example, approximately 185 initial 15-day reports were submitted late for the time period of January 1, 2009 to March 31, 2010. The following are examples of initial 15-day reports that were submitted late to FDA.  

      

Product	Mfr. Control No.	Date Received By Mfr.	Date Sent to FDA	Days Late
Glyburide	200916879GDDC	1/18/2007	7/17/2009	896
Glibenclamide	200916952GDDC	4/3/2007	7/20/2009	824
Glibenclamide	200919278GDDC	5/25/2007	8/27/2009	810
Furosemide	200911209EU	2/4/2008	3/17/2009	392
Eligard	A03200803546	9/8/2008	2/4/2009	134
Allegra D	200914109US	2/20/2009	5/15/2009	69
Apidra	200918792GDDC	6/10/2009	8/19/2009	55
Multaq	A03200905040	11/05/2009	01/22/2010	63
Multaq	D01200903859	9/15/2009	1/20/2010	112
Multaq	A03200905053	10/28/2009	1/15/2010	64
Amaryl	2009SA011907	11/24/2009	1/8/2010	30
Plaquenil	2009SA006087	12/1/2009	2/3/2010	49
Lovenox	2009SA007588	12/4/2009	1/25/2010	37

 

2. Failure to submit follow-up PADE reports to FDA within 15 calendar days of receipt of new information concerning post marketing 15 day reports as required by 21 CFR 314.80(c)(1)(ii).  Specifically, approximately 127 follow-up reports were submitted late for the time period of January 1, 2009 to March 31, 2010.  The following are examples of 15-day follow-up reports which were submitted late to FDA:

 

Product	Mfr. Control No.	Date Received By Mfr.	Date Sent to FDA	Days Late
Furosemide	200910549FR	1/15/2009	6/30/2009	151
Ambien	A03200902916	7/10/2009	2/24/2010	214
Lantus	200917792US	10/23/2009	3/2/2010	115
Lantus	200915406US	10/28/2009	3/2/2010	110
Lovenox	200812498US	4/18/2008	12/21/2009	597

  

Sanofi’s responses to the violations described in numbered paragraphs 1 and 2 above state that Sanofi has committed efforts to ensure FDA compliance through improvements in infrastructure, training and internal processes. However, your corrective action plan does not adequately address procedural deficiencies critical to preventing late submission of 15-day alert and follow-up reports to FDA.  For example, your standard operating procedures (SOPs) for adverse drug experience (ADEs) US PV-002 v04 Handling Unsolicited Individual Case Safety Reports for registered/Marketed Products in the United States dated April 5, 2010, fails to provide written adverse drug experience definitions required to assess and evaluate adverse drug experiences for the submission of individual case safety reports including 15-day alert reports.  Also, the procedure lacks clear and concise work instructions for employees to promptly investigate and follow-up on reports not containing the minimum criteria (i.e., an identifiable patient, and identifiable reporter, a suspect drug, and a serious, unexpected adverse experience) for submission to FDA. 

 

The “Adverse Event Reporting Form,” used by your call center contractors for the receipt of adverse drug experience reports, fails to correctly identify the adverse outcomes required to determine the seriousness of an adverse drug experience.  Failure to correctly identify the outcomes of any serious adverse drug experience could lead to inaccurate data entry into your call center database, (b)(4), and on the MedWatch 3500A Form (Box 2). Indeed, it appears deficiencies in written procedures such as these may have contributed to the late reporting and non-reporting of 15-day reports that are identified in this warning letter. Yet, in your written responses, you also failed to identify all of the causes of late reporting. Your should conduct a thorough root-cause analysis of your  reporting systems and procedures in order to identify all potential deficiencies which led to the reporting violations and amend your procedures and implement any necessary changes accordingly to ensure that the violations are not repeated.

 

In addition, we remain concerned that your (b)(4) adverse drug experience reporting system has not been fully validated, and may have resulted in inaccurate assessment and untimely submission of 15-day alerts. The current application was released into production on November 9, 2009 using an Interim Validation report (IVR) that is still not final. Critical issues (deviations) identified in your interim validation report during the inspection included the following, but is not limited to: lack of training for your (b)(4)support team, incomplete SOPs and Work Instructions, and inaccurate data migration of legacy adverse experience cases from your previous adverse drug experience database, (b)(4). Currently, your (b)(4) system does not display accurate clock dates on MedWatch forms for cases which were initially entered in (b)(4) and later entered into (b)(4) due to the receipt of additional information (follow-up) for the same cases.  MedWatch forms printed out from (b)(4) for these migrated cases are documented as initial 15-day reports, instead of follow-up reports.  Also, the report date in Block B5 of the MedWatch form is the print date, not the actual date of submission. Shortcomings such as these affect the accuracy, reliability, consistency of the system and your firm’s ability to discern invalid or altered electronic records or make timely submissions to FDA as required. Your response states that you have hired a consultant, (b)(4), to assist with resolving these computer system issues. To date, however, we have not received any response from you indicating that you or your contractor has evaluated or determines the root cause of these issues, or taken steps to resolve them or re-validate your computer system to correct deficiencies.

 

Please provide the status of your corrective action regarding any revised written procedures related to ADE reporting and updated computer system validation in your response to this letter.

 

3. Failure to include all other postmarketing studies in Annual Reports as required by 21 CFR 314.81(b)(2)(viii).  Specifically, NDA Annual Reports submitted to FDA for marketed drug products were incomplete and did not include all other postmarketing studies for studies such as:

 

1. Apidra (study APIDR_L_02012)
2. Eloxatin (studies OXALI_L_00737 and OXALI_L_00869)
3. Ketek (study TELIT_L_05072)

 

In addition, your firm did not include summaries of completed, unpublished clinical trials conducted by, or otherwise obtained by, the applicant as required by 21 CFR 314.81(b)(2)(vi)(b). Examples of completed clinical trials reported late include:

 

a.       Ambien (zolipidem tartate)

b.      Apidra (insulin glulisine injection)

c.       Eloxatin (oxaliplatin injection)

 

Information obtained from FDA’s inspection revealed that your firm failed to report the status of the studies associated with the marketed drugs mentioned above.  Your firm stated during the inspection, that in March 2008, Sanofi made the decision to start including foreign clinical trials that were conducted by, or on behalf of your firm in the company’s database for NDA Annual Reports. Yet, information obtained during the inspection, as described above, indicates that your firm has still failed to report on the status of certain foreign postmarketing clinical trials or studies.  Moreover, we are troubled that your firm did not disclose to FDA, until the 2010 inspection, that it did not report on foreign trial or studies prior to 2008.

 

During the inspection, a review of your (b)(4) noted that it instructed your employees or designee that studies filed to a Sanofi-Aventis IND should not be included in the NDA Annual Reports.  FDA regulations, 21 CFR 314.81(b)(2), require that all IND and NDA clinical trial studies associated with an approved drug be reported in the NDA Annual Reports.

 

We have reviewed your corrective and preventive action plan and the revised NDA Annual Reports, (b)(4), effective date June 7, 2010, and have determined that they are still inadequate. The deficiencies noted in the procedure include: lack of definition of terms used in the reporting postmarketing studies (i.e., postmarketing study, postmarketing study requirement, and postmarketing study commitment); the procedure eliminates trials and studies that should be included in the “Status of other postmarketing studies” section of the NDA Annual Report; (b)(4) suggests that only the status of “ongoing” clinical trials that were conducted should be included under (b)(4). The procedure should include current status (i.e., cancelled, delayed, or terminated) of all postmarketing studies since the last annual report.  Your response only addresses studies identified since 2008.  Your response to the Warning Letter should include a retrospective analysis of all clinical studies that were conducted by, or on behalf of your firm for all NDA products held by Sanofi to ensure that they have been properly identified and reported, and describe the specific steps you have taken to prevent future violations.

 

The issues and violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility. It is your responsibility to ensure 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 injunction.  Federal agencies are advised of the issuance of all Warning Letters about drugs and devices so that they may take this information into account when considering the award of contracts.  FDA may re-inspect to verify corrective actions have been completed.

 

Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step 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.

 

We also recommend that you contact, Andrew Ciaccia at Andrew.Ciaccia@fda.hhs.gov, or 973-331-4904, within five days of receipt of this letter. Your reply should be sent to the following address: U.S. Food & Drug Administration, 10 Waterview Boulevard, 3^rd Floor, Parsippany, New Jersey 07054.

 

Sincerely,

/S/

Diana Amador-Toro
District Director
New Jersey District

-

Close Out Letter

• Sanofi - Aventis U.S. LLC - Close Out Letter 7/5/11

-

-

Fresenius Se 1/28/11

Department of Health and Human Services	Public Health Service Food and Drug Administration
	10903 New Hampshire Avenue Silver Spring, MD 20993

JAN 28 2011
 

VIA United Parcel Service

Warning Letter

 

Dr. Ulf M. Schneider
Chairman of the Management Board
Fresenius SE
61346 Bad Homburg v.d.H.
Germany

RE: Red Blood Cell Set, AS104
Refer to GEN1 001508 when replying to this letter

Dear Dr. Schneider:

The Food and Drug Administration (FDA) has learned that your firm is marketing the Red Blood Cell (RBC) Set, and the AS104 Blood Cell Separator (AS104) in conjunction with the RBC Set, in the United States (U.S.) without marketing clearance or approval, in violation of the Federal Food, Drug, and Cosmetic Act (the Act).

Under Section 201 (h) of 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 intended to affect the structure or function of the body. The Office of Compliance (OC) in the Center for Devices and Radiological Health (CRDH) reviewed documents provided by your firm to the FDA Seattle office, for the RBC Set and the AS104 Blood Cell Separator.

Review of our records indicates that a premarket notification (510(k)) for the AS104 Blood Cell Separator and bloodlines for therapeutic plasma exchange (TPE) was cleared November 2, 1990 (K895435). We cleared the AS104 solely to perform therapeutic plasma exchange (TPE) and bloodlines used to perform TPE were cleared. No labeling claims for therapeutic RBC exchange were cleared for the AS104 system. Further, the tubing sets necessary to perform the RBC exchange treatments were not cleared for marketing. We note that your submission K895435 initially included a range of plasma and cell separation modalities, including RBC exchange; however, during the course of its review, the labeling was restricted to only indicate TPE and that you provided that the only disposable tubing set to be marketed with the AS104 through this 510(k) application was the PL-1 tubing set for therapeutic plasma separation. We also note that the Com.Tec system, K060734, cleared September 5, 2006, was cleared solely to perform TPE. We note that, during the September 11, 2008, inspection of Fresenius Kabi, LLC, you informed our investigator that the AS104 cell separator is no longer being manufactured but that users continue to operate it within the United States and that you provide service and repairs for this device.

You have provided information to the FDA Seattle District Office, on November 15, 2010, December 6, 2010, and December 9, 2010, that

1. The Fresenius RBC red blood cell set is used for depletion or exchange of red blood cells during therapeutic apheresis procedures on the Fresenius AS104 Blood Cell Separator Device. This set is used with a single stage separation chamber.

2. The Fresenius RBC set is marketed as Catalog Number 9007601.

3. The RBC sets, article no 9007601, are used in conjunction with the AS104 cell separator, for therapeutic red cell exchange in patients suffering from sickle cell disease.

4. You have marketed and distributed RBC Sets in the United States.

The RBC Set, and the AS104 when promoted for use for RBC exchange, are adulterated under Section 501 (f)(1)(B) of the Act, 21 U.S.C. 351 (f)(1)(8), because you do not have approved applications for premarket approval (PMA) in effect pursuant to Section 515(a) of the Act, 21 U.S.C. 360(a), or approved applications for investigational device exemptions (IDE) under Section 520(g) of the Act, 21 U.S.C. 360j(g), for the new intended uses. The RBC Set is also misbranded under Section 502(o) of the Act, 21 U.S.C. 352(o), because you did not notify the agency of your intent to introduce the device into commercial distribution, as required by Section 510(k) of the Act, 21 U.S.C. 360(k). For a device requiring premarket approval, the notification required by Section 510(k) of the Act is deemed satisfied when a PMA is pending before the agency (21 U.S.C. 807.81 (b)).

The kind of information you need to submit in order to obtain approval or clearance for your device is described on the Internet at http://www.fda.gov/cdrh/devadvice/3122.html. The FDA will evaluate the information you submit and decide whether your product may be legally marketed.

The Office of Compliance requests that Fresenius immediately cease the dissemination of promotional materials for the RBC Set and for the AS104 when promoted for use for RBC exchange, the same as or similar to those described above. You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action, which may include detaining your devices without physical examination upon entry into the United States until the corrections are completed.

Please submit a written response to this letter within 15 working days from the date you receive this letter, describing your intent to comply with this request, listing all promotional materials for Red Blood Cell Set and the AS104 the same as or similar to those described above, and explaining your plan for discontinuing use of such materials.

Please direct your response to Paul F. Tilton at the Food and Drug Administration, 10903 New Hampshire Ave., W066-3540, Silver Spring, MD 20993, facsimile at (301) 847-8137. We remind you that only written communications are considered official. 

The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for Red Blood Cell Set and the AS104 comply with each applicable requirement of the Act and FDA implementing regulations.
 

Sincerely yours,
/S/
Steven D. Silverman
Director
Office of Compliance
Center for Devices and
Radiological Health
 

cc:
Dr. Thomas Graf
President
Fresenius HemoCare Netherlands B.V.
Runde zz 41
NL-7881 HM Emmer-Compascuum, NL-DR
The Netherlands
 

Ms. Katherine J. Sivertson
Director of Transfusion Technology North America
Fresenius Kabi, LLC
8653 154th Ave. NE
Redmond, WA 98052

-

A.G.S. Wholesalers, Inc. 1/26/11

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Los Angeles District Pacific Region 19701 Fairchild Irvine, CA 92612-2506 Telephone: 949-608-2900 FAX: 949-608-4415

WARNING LETTER

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

January 26, 2011

W/L 22-11

Anastasios Sotiropoulos, Owner
A.G.S. Wholesalers, Inc.
1419 S Alameda St.
Compton, CA, 90220-4901

Dear Mr. Sotiropoulos:

The U.S. Food and Drug Administration (FDA) conducted an inspection of your facility located at 1419 S Alameda St, Compton, CA, 90220 on September 10-21, 2010. During the inspection, it was determined that your facility repackages acidified, fermented, and acid foods, and distributes other food products. The inspection revealed that your repacked cascabella pepper, sliced pepperocini pepper, sliced pickle, and whole pickle products are not labeled, and are therefore misbranded under section 403 of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. 343]. Regulations implementing the food labeling requirements of the Act are found in Title 21, Code of Federal Regulations, Part 101 (21 CFR Part 101). Additionally, your cascabella pepper, sliced pickle, and whole pickle products are adulterated within the meaning of section 402(c) of the Act [21 U.S.C. 342(c)] because they bear or contain an unsafe color additive. The inspection also revealed significant violations of the Current Good Manufacturing Practice (CGMP) regulation for foods, at 21 CFR Part 110. Failure to manufacture foods in accordance with the CGMP requirements in 21 CFR Part 110 renders your firm's food products adulterated within the meaning of Section 402(a)(4) of the Act [21 U.S.C. 342(a)(4))], in that they have been prepared, packed, or held under unsanitary conditions whereby they may have become contaminated with filth, or whereby they may have been rendered injurious to heath. The Act and FDA regulations can be found through links on FDA's webpage at www.FDA.gov.

Your significant violations were as follows:

Your cascabella pepper, sliced pickle, and whole pickle products are adulterated within the meaning of section 402(c) of the Act [21 U.S.C. 342(c)] because the products bear or contain a color additive which is unsafe within the meaning of section 721 (a) of the Act [21 USC 379(a)] Section 721(a) deems a color additive to be unsafe if its use is not in conformity with the color additive's listing regulation. Your cascabella pepper, sliced pickle and whole pickle products contain FD&C Yellow No.5. The listing regulation for FD&C Yellow No.5 requires that the color additive be listed by that name in the ingredient list in the labeling of foods for human use [21 CFR 74.705(d)(2)]. However, the labels for your cascabella pepper, sliced pickle and whole pickle products fail to declare the presence of FD&C Yellow No.5 in the ingredient statements.

During the inspection of your firm, it was observed that you fail to label your cascabella pepper, sliced pepperocini pepper, sliced pickle and whole pickle products that are repacked into fifteen gallon barrels. These products have the following labeling violations:

• Your cascabella pepper, sliced pickle, and whole pickle products are misbranded within the meaning of section 403(k) of the Act [21 U.S.C. 343(k)], because the products bear or contain artificial coloring, but fail to bear labeling stating such fact. In accordance with 21 CFR 101.22(k) the label of a food to which any coloring has been added shall declare the coloring in the statement of ingredients. According to the ingredient statement of the products that you receive and repackage, your cascabella pepper, sliced pickle and whole pickle products contain certified color additives FD&C Yellow No.5. Under 21 CFR 101.22(k)(1), certified colors must be declared by the name of the color additive listed in the applicable regulation. The common or usual name may be abbreviated to omit the "FD&C" prefix and the term ''No.'' (e.g., Yellow 5).

• Your cascabella pepper, sliced pepperocini pepper, sliced pickle, and whole pickle products are misbranded within the meaning of section 403(i)(I) of the Act [21 U.S.C. § 343(i)(1)] because these products fail to bear a label with a statement of identity as required by 21 CFR 101.3.

Your cascabella pepper, sliced pickle, and whole pickle products are misbranded within the meaning of section 403(i)(2) of the Act [21 U.S.C. § 343(i)(2)] because they are all fabricated from two or more ingredients and their labels fail to list the common or usual name of each ingredient.

• Your cascabella pepper, sliced pepperocini pepper, sliced pickle, and whole pickle products are misbranded within the meaning of section 403(e) of the Act [21 U.S.C. § 343(e)] in that the labels for these products do not bear the name and place of business of the manufacturer, packer, or distributor in accordance with 21 CFR 101.5; and fail to bear an accurate statement of the net quantity of contents in terms of weight, measure, or numerical count in accordance with 21 CFR 101.105.

Current Good Manufacturing Practices


Our investigator documented a number of significant objectionable conditions relating to your facility's compliance with the CGMP regulations. Significant CGMP violations observed during the inspection include:

1. Your firm failed to perform packaging operations in a manner that protects food against contamination, including using food packaging materials that are safe and suitable as defined in 21 CFR 130.3(d), as required by 21 CFR 110.80(b)(13)(iii). Specifically, your cascabella pepper, pepperocini pepper, and sliced dill pickle products are packaged into can liners that are not suitable food packaging materials. According to the can liner manufacturer, the can liners you use to repackage these foods should not be used for storing food.
2. Your firm failed to take effective measures to exclude pests from the processing areas and protect against the contamination of food on the premises by pests, as required by 21 CFR 110.35(c). Specifically, our investigator found the following:
   • Flying insects inside your food storage area.
   • Ants on a box of lettuce and on a head of lettuce.
   • Spider webs were observed in the immediate area where bags of onions were stored outside.
3. Your firm failed to provide adequate and convenient hand washing facilities as required by 21 CFR 110.37(e). Specifically, there is no hand washing sink in the area where you repackage foods that enables employees to wash their hands as necessary to protect against contamination.

Furthermore, the FDA has determined that your facility is subject to the registration requirement in section 415 of the Act, 21 U.S.C. § 350d, and our implementing regulation at 21 CFR Part 1, Subpart H. During our inspection of your facility located at 1419 S Alameda St, Compton, CA, 90220 on September 10-21, 2010 you were advised of this requirement. The failure to register a facility as required is a prohibited act under § 301(dd) of the Act, 21 U.S.C. § 331(dd). Our records indicate that, to date, this facility has not been registered with FDA.

As a responsible official of a facility that manufactures/processes, packs, or holds food for human or animal consumption in the United States, you are responsible for ensuring that your overall operation and the products you distribute are in compliance with the law.

We request that the owner, operator, or agent in charge of this facility, or an individual authorized by this facility's owner, operator, or agent in charge, register the facility with FDA within 30 working days of the date of this letter. Registration may be accomplished on-line at http://www.access.fda.gov. We strongly encourage the use of electronic registration because it will result in an automatic confirmation of registration and automatic issuance of a registration number.

Alternatively, the owner, operator, or agent in charge of this facility, or an individual authorized by the facility's owner, operator, or agent in charge, may register the facility by mail or fax (e.g., if you do not have reasonable access to the Internet) using FDA's food facility registration form, Form 3537. This form may be obtained by calling the FDA Industry Systems Help Desk at 1-800-216-7331 or 301-575-0156, or by writing to the agency at the following address:

U.S. Food and Drug Administration, HFS-681
5600 Fishers Lane
Rockville, MD 20857

When completed, the form may be faxed to (301) 210-0247 or mailed to the address above. FDA will process registrations submitted by mail or fax and provide a facility's registration number using the same method used to submit the registration to FDA.

The above violations are not meant to be an all-inclusive list of deficiencies in your products and their labeling. It is your responsibility to ensure that all of your products are in compliance with applicable laws and regulations. You should take prompt action to correct all of the violations noted in this letter. Failure to promptly correct these violations may result in regulatory action without further notice, such as seizure and/or injunction.

In addition to the violations described above, we have the following additional comment regarding your repackaged acidified cascabella peppers. Please be advised that FDA has issued draft guidance that states that repackers of acidified foods are subject to the applicable requirements in 21 CFR Part 108.25 and 114. You may submit comments on this draft guidance to the agency as outlined in the document. The draft guidance is available online at:

http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/AcidifiedandLow-AcidCannedFoods/ucm222618.htm

We request that you notify this office in writing within 15 working days from your receipt of this letter of the current status of your corrective actions and the specific steps you have taken to correct the noted violations. In your response, include documentation of your corrective actions. If you cannot complete all corrections before you respond, we expect that you will explain the reason for your delay and include a timetable for the implementation of any remaining corrections.

Please send your reply to:

U.S. Food and Drug Administration
Attention: Blake Bevill
Director Compliance Branch
Los Angeles District
19701 Fairchild
Irvine, CA, 92612-2506

If you have questions regarding any issues in this letter, please contact David Whitman, Compliance Officer at 858-550-3850 x106.

Sincerely,
/S/
Alonza E. Cruse District
Director
Los Angeles District

-