OsteoSymbionics LLC

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Cincinnati District Office Central Region 6751 Steger Drive Cincinnati, OH 45237-3097 Telephone: (513) 679-2700 FAX: (513) 679·2771

November 30, 2010
 

WARNING LETTER
CIN-11-146792-02

VIA UPS

Cynthia M. Brogan
CEO
OsteoSymbionics, LLC.
1768 East 25th Street
Cleveland, OR 44114-4420

Dear Ms. Brogan:

During an inspection of your firm located in Cleveland, Ohio on October 13 through November 3, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is manufacturing cranial plate implants. Under section 201(h) of the Federal Food, Drug and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.

This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351 (h), in that the methods used in, or the facilities or controls used for, their manufacturing, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (C.F.R.), Part 820. These violations include, but are not limited to, the following:

1. Failure to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met, as required by 21 C.F.R. § 820.30(a). For example,

The following design controls were inadequate during the development of the design of the Cranial Plate Implant, which has been distributed since 2008:

a) Failure to establish a design and development plan, as required by 21 C.F.R. § 820.30(b).
b) Failure to establish design inputs, as required by 21 C.F.R. § 820.30(c).
c) Failure to implement your "Design Verification" procedure for verifying the device design, as required by 21 C.F.R. § 820.30(f). Specifically,

• Six of the eight design verification tests did not include a "Summation of the test outcome". Your procedure states a test report shall include the "Results of analysis compared to expected or predetermined outcome"; a "Summation and conclusion of the results compared to expected outcome"; and must be signed and dated by a designated individual.

d) Failure to validate the cranial implant design to ensure that devices conform to defined user/patient needs and intended uses, as required by 21 C.F.R. § 820.30(g).

2. Failure to establish procedures and to validate a process whose results can not be fully verified by subsequent inspection and test, as required by 21 C.F.R. § 820.75(a). Specifically,

a) The mixing, curing, casting, and cleaning processes used to manufacture the cranial plate implants have not been validated.
b) The implant's Instructions for Use states that "If re-sterilization is required the above instructions must be adhered to". Your sterilization validation did not include sterilizing the implant more than one cycle.
c) The implant's Instructions for Use states under the "Cleaning and Sterilization" section a sterilization parameter of "30-80% RH (relative humidity)". Your sterilization validation only included a 55% RH. The full range of 30-80% has not been validated.

3. Failure to establish corrective and preventive action procedures that include requirements for analyzing processes quality records and work operations to identify existing and potential causes of nonconforming product, or other quality problems, as required by 21 C.F.R. § 820.100(a)(1). For example,

Corrective and Preventive Action Procedure QSP4-02, dated 10/12/10 does not list manufacturing processes and nonconformances as data sources to be analyzed to identify existing and potential causes of nonconforming product, or other quality problems.

4. Failure to implement your procedures for the identification, documentation, validation or where appropriate verification, review and approval of all design changes before their implementation, as required by 21 C.F.R. § 820.30(i). Specifically,

Your "Engineering Change Notice Procedure No. QSP3-03" Rev C, dated 10/29/09, states in section 6.5 that "If a change does not require verification and/or validation, and associated risks are not affected, the reason is recorded on the ECN". All 11 ECN documents reviewed by the FDA investigator did not have the reason why no verification and/or validation were required completed on the form

5. Failure to maintain a device master record for the cranial plate implants, as required by 21 C.F.R. § 820.181.

You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action being initiated by FDA without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, no premarket submission to which the Quality System regulation deficiencies are reasonably related will be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.

Please notify this office in writing within fifteen (15) working days from the date you receive this letter as to the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrective actions you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, please state the reason for the delay and the time within which the corrections will be completed.

Your written response should be sent to Ms. Gina Brackett, Compliance Officer, Food and Drug Administration, 6751 Steger Drive, Cincinnati, Ohio, 45237. If you have any questions concerning the contents of this letter you may contact Ms. Brackett at (513) 679-2700, ext. 167, or you may forward a facsimile to her at (513) 679-2773.

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

Sincerely,

/S/
Teresa C. Thompson
District Director
Cincinnati District

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Optilasa SA 11/29/10

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

NOV 29 2010

WARNING LETTER

 
VIA United Parcel Service

 
Mr. Jose M. Bobes Lasa
President and Owner
Optilasa SA,
338 Arturo Soria Street
Madrid, Spain

 
Dear Mr. Bobes Lasa:

During an inspection of your firm located in Madrid, Spain on May 31, 2010, through June 2, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures tonometers.  Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.

This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (C.F.R.), Part 820.  We received a response from you dated June 24, 2010, concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you.  Your response will not be reviewed at this time for consideration, since the response was received after the 15 day time frame.  Your June 24 response will be reviewed at the time we receive your response to this letter.  These violations include, but are not limited to, the following:

1. Failure to establish and maintain adequate procedures to for the identification, documentation, validation, or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i).  For example, there is no design change procedure for the tonometer device.

2. Failure to establish and maintain a device history file (DHF) for each type of device.  The DHF shall contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the requirements of 21 CFR 820, as required by 21 CFR 820.30(j).  For example, there is no design history file for the Applanation Tonometer Models OP1H and OPIS.

3. Failure to develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications, specifically, failure to document standards for criteria of workmanship or by means of identified and approved representative samples, as required by 21 CFR 820.70(a)(5).  For example, the Work Instruction IT-20-01, Tonometer Verification, includes inconsistent specifications.  Section 5.3.1 includes a specification of (b)(4) as a tolerance for the tonometer device when the testing is done using a calibration bar.  Section 5.3.2 includes (b)(4 as a tolerance when the testing is done using electronic measuring equipment.  There is no documented rationale for the discrepancy.

4. Failure to establish and maintain adequate procedures for acceptance of incoming product; to inspect, test or otherwise verify incoming product conforms to specified requirements; and to document acceptance or rejection, as required by 21 CFR 820.80(b).  For example:

• Procedure PC-11, Verification of Purchased Product, defines requirements for incoming inspection of materials and components;

• Work Instruction IT-11-01, Quality Control Receipt of Materials and Components, defines the process for the inspection and acceptance of materials and components.

There was no documentation of incoming inspection and acceptance of components and materials used in the production of the tonometer devices.

5. Failure to establish and maintain procedures to control product that does not conform to specified requirements.  The procedures shall address the identification, documentation, evaluation, segregation, and disposition of nonconforming product.  The evaluation and any investigation shall be documented, as required by 21 CFR 820.90(a).  For example:

• Procedure, PC-22, Corrective and Preventative Actions requires that non-conformances be captured in the firm’s corrective and preventative actions system.  However, during a walk-through of the manufacturing area, manufacturing components were located on a shelf labeled as non-conforming material.  There was no documentation of the non-conformances being documented in the firm’s corrective and preventative action system.

• Procedure PC-21, Non-Conforming Product requires that non-conformances for finished product or components be documented on form RC-21-01.  There is no documentation of non-conformances for finished product or components for the tonometer devices.

6. Failure to document equipment identification, calibration dates, the individual performing each calibration, and the next calibration date, as required by 21 CFR 820.72(b)(2).  For example, there is no documentation to show that the calipers used for the production of the tonometers are calibrated.  There is no documentation of a calibration plan for the calipers used for the production of tonometers as called for by procedure PC-17, Equipment Calibration. 

7. Failure to maintain device history records (DHRs) and to establish and maintain procedures to ensure that DHRs for each batch, lot or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record (DMR) and the requirements of 21 CFR 820 as required by 21 CFR 820.184.  For example, the device history records for the tonometer devices lack documentation of the production of the devices, the packaging and labeling of the devices, and release of the devices for distribution.

8. Failure to establish and maintain the quality requirements, that must be met by suppliers, contractors, and consultants.  Each manufacturer shall evaluate and select potential suppliers, contractors, and consultants on the basis of their ability to meet specified requirements, including quality requirements.  The evaluation shall be documented, as required by 21 CFR 820.50(a)(1).  For example, Procedure PC-09, Evaluation of Suppliers, includes requirements for the evaluation of suppliers.  There was no documentation to show that suppliers of components and materials used in the tonometer devices were evaluated. 

9. Failure to establish and maintain adequate procedures to control all documents and designate an individual(s) to review for adequacy and approve  prior to issuance all documents established to meet the requirements of 21 CFR  820, as required by 21 CFR 820.40(a).  For example, procedure PC-20, Final Product Inspection, requires the use of form RC-20-02 for the inspection and testing of products prior to release.  There is no documentation to show that form RC-20-02 was used to document the inspection and testing of each device.  The firm’s records for its devices include the use of a different form for recording the inspection of a batch of devices instead of records for individual devices.

10. Failure to establish procedures for quality audits and conduct such audits to assure that  the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22.  For example, there is no documentation to show that internal quality audits were conducted since the last FDA inspection in May 2007.

11. Failure of management with executive responsibility to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure that the quality system satisfies the requirements of 21 CFR 820 and the manufacturer’s established quality policy and objectives, failure to document the dates and results of the quality system reviews, as required by 21 CFR 820.20(c).  For example, Procedure PC-04, Management Review, includes requirements for annual management reviews to be conducted. There is no documentation to show that management reviews were conducted since the last FDA inspection in May 2007.

12. Failure to establish a quality plan which defines the quality practices, resources, and activities relevant to devices that are designed and manufactured, as required by 21 CFR 820.20(d).  For example, quality planning activities have not been implemented for the tonometer device.

13. Failure to establish and maintain procedures to ensure that sampling methods are adequate for their intended use and to ensure that when changes occur the sampling plans are reviewed and documented, as required by 21 CFR 820.250(b). For example, Work Instruction IT-11-02, Quality Control Inspection Plans, defines the sampling plans to be used for the incoming inspection and acceptance of materials. However, there is no documentation to show that sampling plans were defined for materials and components used in the tonometer devices.

14. Failure to establish and maintain adequate procedures for identifying training needs and ensure that all personnel are trained to adequately perform their assigned responsibilities, to include documentation of the training, as required by 21 820.25(b).  For example, Procedure PC-05, Training, includes requirements for employee training. However, there is no documentation to show that employees were trained.

A follow up inspection will be required to assure that corrections are adequate.  We will contact the appropriate people and request an establishment re-inspection.  An FDA trip planner will be in touch with you to arrange a mutually convenient date for this inspection.

Given the serious nature of the violations of the Act, the tonometers  manufactured by your firm 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 "detention without physical examination," until these violations are corrected.  In order to remove the devices from detention, 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.

Also, 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 contracts.  Additionally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected.  Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.

Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again.  Include documentation of the corrective action you have taken.  If your planned corrections will occur over time, please include a timetable for implementation of those corrections.  If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.  Please provide a translation of documentation not in English to facilitate our review.

Your response should be sent to: Ronald L. Swann, Chief, Dental, Ear, Nose, Throat, and Ophthalmic Devices Branch, WO66-3534, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, U.S.A. If you have any questions about the content of this letter please contact: Debra Demeritt at 301-796-5472 or 301-847-8137.

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

/s/                            
                                                                         
Steven D. Silverman 
Director
Office of Compliance
Center for Devices and 
Radiological Health
 
 
 

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Sagami Rubber Industries Co., Ltd. 11/24/10

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

 

November 24, 2010

 

WARNING LETTER

 

 

Via United Parcel Service

 

Mr. Ichiro Oato

President

Sagami Rubber Industries Co., Ltd.

2-1, Moto-Cho

Atsugi City

Kanagawa-Prefecture 243-0002,

Japan

 

Dear Mr. Oato:

 

During an inspection of your firm, Sagami Manufacturers Sdn. Bhd., located in Perak, Malaysia on August 2 – 5, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Trojan Polyurethane Supra Condoms. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.

 

This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (C.F.R.), Part 820.  We received a response from you dated September 1, 2010, concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you.  Your response to the FDA 483 was not reviewed because it was not received within 15 business days. The response may be evaluated along with any other written material provided in response to this Warning Letter. These violations include, but are not limited to, the following:

  

1. Failure to adequately ensure that when the results of a process cannot be fully verified by subsequent inspection and test that the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a). For example:

 

a. Your process validation for Polyurethane Condom/Dipping process line (b)(4) which is used for the Supra brand product that goes to the US did not document or define the process condition for the rate of entry of the (b)(4) molds into the dipping tank, the time that the (b)(4) mold is held in the dipping tank and the rate at which the (b)(4) mold is removed from the tank.

 

b. As part of the Polyurethane Condom/Dipping process, your hot air drying steps for the (b)(4) molds using HEPA filters have not been adequately validated to determine the integrity of the filters and/or when the filters should be replaced.

 

2. Failure to establish and maintain adequate procedures for implementing corrective and preventive action to include requirements for analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems, as required by 21 CFR 820.100(a)(1). For example, the quality data associated with your (b)(4)% visual examination of condoms (PU: APPEARANCE CHECK SHEET, Form# PT-7-1 Ver.8, Processing Dated: August 29, 2009, (b)(4) Product: 38-35C-190) identifies (b)(4) however, this quality data is not used to identify potential causes of nonconforming product, or other quality problems.

 

3. Failure to establish and maintain adequate procedures for implementing corrective and preventive action to ensure activities required under this section, and their results, shall be documented, as required by 21 CFR 820.100(b).   For example, the corrective and preventive actions pertaining to higher rates of testing failure of (b)(4) micron thickness polyurethane condoms/38-28C-170 & 38-28C-190 (product type) based on (b)(4) abnormality reports from 2009 and 2010 have not been documented according to your Corrective and Preventive Action/SOP-08-01. Investigation and corrective actions pertaining to the (b)(4) mold (used in dipping process) replacement schedules have been made but there is no documentation of these activities in your CAPA system.

 

Given the serious nature of the violations of the Act, the Trojan Polyurethane Supra Condoms manufactured by your firm 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 "detention without physical examination," until these violations are corrected.  In order to remove the devices from detention, 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.

 

 

Also, 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 contracts.  Additionally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected.  Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.

 

Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again.  Include documentation of the corrective action you have taken.  If your planned corrections will occur over time, please include a timetable for implementation of those corrections.  If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.  Please provide a translation of documentation not in English to facilitate our review.

 

Your response should be sent to: Paul F. Tilton, Chief, Ob/Gyn, Gastroenterology, and Urology Devices Branch, WP66-3540, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, U.S.A. If you have any questions about the content of this letter please contact: Ronald T. Nowalk at (telephone) 301-796-5493 or (fax) 301-847-8137.

 

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

 

                                                                       

Sincerely yours, 

/S/                                                     

Steven D. Silverman

Director

Office of Compliance

Center for Devices and

Radiological Health

 

 

 

 

 

 

 

 

 

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Eagle Health Supplies, Inc. 11/24/10

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Los Angeles District 19701 Fairchild Irvine, California 92612-2506 Telephone (949) 608-2900 Fax (949) 608-4401

WARNING LETTER

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

November 24, 2010

W/L 14-11

Mr. Andy Chao
President
Eagle Health Supplies, Inc.
535 W Walnut Ave
Orange, CA 92868

Dear Mr. Chao:

During an inspection of your firm located in Orange, CA on July 14 through July 26, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is a specification developer, initial importer and distributor of disposable 4-O₂ CPR Mouth Barriers. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.

This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (C.F.R.), Part 820. These violations include, but are not limited to, the following:

1. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a).

For example, according to your firm’s management, Corrective and Preventive Action (CAPA) procedures have not been established. Your firm’s management stated that they were not aware of the CAPA requirements of 21 CFR 820.100.

2. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a).
 

For example, your firm has not established complaint handling procedures for receiving, reviewing, and evaluating complaints by a formally designated unit.

3. Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50.

For example, your firm imports devices (including the 4-O₂ Disposable CPR Mouth Barrier) from contract manufacturers overseas. There are no procedures to ensure these suppliers are: (1) evaluated and selected based on their ability to meet specified requirements, including quality requirements; and, (2) controlled based on evaluation results. According to your firm’s Manager of Operations, your firm does not require its suppliers to provide finished device acceptance records or certifications of compliance to specified requirements.

4. Failure to establish and maintain procedures for acceptance activities, as required by 21 CFR 820.80(a).

For example:

A. Your firm does not have documented receiving acceptance procedures or document receiving acceptance activities for the 4-O₂ Disposable CPR Mouth Barrier (or any other device); and, B. Your firm has not established finished device acceptance procedures for the 4-O₂ Disposable CPR Mouth Barrier (or any other device).

5. Failure to establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i).

For example, your firm does not have an established procedure to control design changes for the 4- O₂ Disposable CPR Mouth Barrier (a Class II device).

6. Failure to maintain device master records (DMRs), as required by 21 CFR 820.181.

For example, during the inspection, you stated that your firm had drawing specifications which you provided to contract manufacturers, but during the inspection none of the cited drawings were presented to the investigator.

7. Failure to maintain Device History Records (DHRs), as required by 21 CFR 820.184.

For example, your firm does not maintain Device History Records (DHRs) for the 4-O₂ Disposable CPR Mouth Barrier (or any other device).

8. Failure to establish and maintain procedures to control all documents that are required by 21 CFR 820, as required by 21 CFR 820.40.

For example, your firm does not have any document control procedures.
 

9. Failure of management with executive responsibility to review the suitability of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure that the quality system satisfies the requirements of 21 CFR 820, as required by 21 CFR 820.20(c).

For example, according to your firm’s management, your firm does not conduct management reviews and has not established management review procedures.

10. Failure to establish quality system procedures and instructions, as required by 21 CFR 820.20(e).

For example, according to you, your firm does not have quality system procedures.

11. Failure of management with executive responsibility to establish its policy and objectives for, and commitment to, quality, as required by 21 CFR 820.20(a).

For example, according to you, your firm has not established a quality policy.

This inspection also revealed that these devices are misbranded within the meaning of section 502(t)(2), of the Act (21 U.S.C. § 352(t))(2), in that your firm failed or refused to furnish any material or information respecting the device that is required under section 519, 21 U.S.C. 360i, and 21 CFR Part 803 (Medical Device Reporting regulation).

12. Failure to develop, maintain, and implement written MDR procedures, as required by 21 CFR 803.17.

For example, according to your firm’s management, there are no written MDR procedures.

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

Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violation(s), or similar violation(s), from occurring again. Include documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.

Your response should be sent to:

Blake Bevill
Director, Compliance Branch
US Food & Drug Administration
19701 Fairchild, Irvine, CA 92612-2446

If you have any questions about the content of this letter please contact: Mei-Chen (Jessica) Mu at 949-608-4477.

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

Sincerely yours,

/S/
Alonza E. Cruse
District Director
 

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WalkMed Infusion, LLC 11/22/10

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Denver District Office Bldg. 20-Denver Federal Center P.O. Box 25087 6th Avenue & Kipling Street Denver, Colorado 80225-0087 Telephone: 303-236-3000 FAX: 303-236-3551

 

 

November 22, 2010

WARNING LETTER
  
   
VIA UPS

Mr. Lee Travis
Principal Owner
WalkMed Infusion, LLC
96 Inverness Dr. East, Suite J
Englewood, CO 80112

Ref # DEN-11-02

Dear Mr. Travis:

During an inspection of your firm located at 96 Inverness Drive East, Suite J, Englewood, Colorado, on September 7 – 16, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Class II electronic infusion pump systems (ambulatory and pole mount), including reservoir bags and administration sets.  Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), [21 U.S.C. § 321(h)], these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body. 

This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (C.F.R.), Part 820.  You can find these regulations on the FDA website at www.fda.gov
 
Significant deviations include, but are not limited to, the following:

1. You have failed to review, evaluate and investigate all complaints involving the possible failure of a device, 21 C.F.R. 820.198(c).  
Specifically: 

• (b)(4) complaints reviewed by our investigator related to severe under-delivery of infusion fluid.  However, you did not conduct investigations of these complaints to determine if medical intervention was required and the ultimate patient outcome in order to make appropriate MDR reportability determinations. 

• In addition, in (b)(4) complaints involving alarm failures, your Complaint Questionnaire was missing pertinent information.  However, it appears that no attempt was made to obtain this information in order to accurately assess the potential for patient injury.

We acknowledge receipt of your September 30, 2010 letter responding to our Inspectional Observations, Form FDA 483 dated September 16, 2010.  Your response is inadequate in that although you reported making changes to your Complaint Handling Procedure (b)(4), you did not provide a copy of this revised procedure for our evaluation.

2. You have failed to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met, 21 C.F.R. 820.30(a).

Specifically:

• Your Design Control Procedure (b)(4)  has not been implemented, in that the Triton Pump System Verification & Validation (b)(4) does not document that the design validation included testing of production units under actual or simulated use conditions, as required by 21 C.F.R. 820.30(g). 

• In addition, the Design Input for Triton Infusion Pump (b)(4) contains no inputs for the WalkMed Infusion administration sets which are to be used with the infusion pumps, as required by 21 C.F.R. 820.30(c).

• Because you did not include administration set inputs in your Triton Infusion Pump design verification/validation, your Triton Infusion Pump Risk Analysis/Failure Modes and Criticality Analysis, document (b)(4) is incomplete in that you failed to identify and evaluate potential hazards involved with use of the administration sets, such as, sub-component and connector failures and non-sterility, 21 C.F.R. 820.30(g).

• Your Triton Infusion Pump Risk Analysis/Failure Modes and Criticality, document (b)(4) is further inadequate in that it determined that over infusions would always be detected, when in fact the failure of the Door Open Alarm resulted in over infusions, causing your firm to conduct a product recall.

• Your Risk Management procedure, document (b)(4), requires that device risk analysis be revised to incorporate newly identified hazards.  However, you failed to revise the WalkMed Infusion Pump System risk Analysis, document (b)(4) after receiving at least (b)(4)  complaints of severe under-infusion when patients were using the pumps at home.

Your September 30, 2010 letter, responding to our Inspectional Observations Form FDA 483 and addressing these items, is further inadequate in that although you stated you had revised your Triton Pump design and risk assessment documents, and will conduct user testing; you did not provide the revised documents for our evaluation, and the user testing will not be completed for (b)(4).

You should take prompt action to correct the violations addressed in this letter.  Failure to promptly correct these violations may result in regulatory action being initiated by the Food and Drug Administration without further notice.  These actions include, but are not limited to, seizure, injunction, and/or civil money penalties.  Also, federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts.

Additionally, premarket approval applications for devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected.  Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.

As stated in your September 30, 2010 letter, we acknowledge that you submitted to this office documentation of the Triton Pole Mount Infusion Pump recall you initiated June 17, 2010, as required by 21 C.F.R. 806.10(a)(1).  We wish to remind you that reports of corrections or removals of this type are to be submitted to FDA within 10 days of initiating such correction or removal, 21 C.F.R. 806.10(b).  Your response regarding this issue is inadequate in that you did not provide a copy of your updated Field Action and Recall Procedure, document (b)(4), for our evaluation.

We also acknowledge, as stated in your September 30, 2010 letter, that you faxed to FDA the MDR report for complaint (b)(4) dated January 13, 2009 on September 16, 2010.  However, 12 C.F.R. 803.50((a) requires that, if you are a manufacturer, you must report to FDA no later than 30 calendar days after the day that you receive or otherwise become aware of information, from any source, that reasonably suggests that a device that you market:  1.  May have caused or contributed to a death or serious injury; or 2.  Has malfunctioned and this device or a similar device that you market would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur.  Your response to this item is inadequate because you did not provide a copy of your revised Potential Hazard and Possible Resultant Harm section of your Risk Analysis WalkMed System, document (b)(4) for our evaluation.

Please notify this office in writing within fifteen (15) working days from the date you receive this letter of any additional steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violation(s), or similar violation(s), from occurring again.  Include documentation of the corrective action you have taken.  If your planned corrections will occur over time, please include a timetable for implementation of those corrections.  If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
 
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your facility.  It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA.  The specific violations noted in this letter and in the Inspectional Observations, Form FDA 483, issued at the closeout of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality assurance systems.  You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.

Your response should be sent to:  Food and Drug Administration, Denver District, P. O. Box 25087, Denver, CO 80225-0087, Attention: William H. Sherer, Compliance Officer.  If you have any questions, please contact Mr. Sherer at (303) 236-3051.

 

Sincerely,

/s/

 

H. Thomas Warwick
Denver District Director

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Close Out Letter

• WalkMed Infusion, LLC - Close Out Letter 1/25/11

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Fujino Enterprises, Inc. 11/19/10

Department of Health and Human Services	Public Health Service Food and Drug Administration
	San Francisco District 1431 Harbor Bay Parkway Alameda. CA 94502-7070 Telephone: 510/337-6700

VIA UNITED PARCEL SERVICE

Our Reference: FEI3004747039

November 19, 2010

Eriko Fujino, President
Fujino Enterprises, Inc.
Dba Blue Ocean Smokehouse
P.O. Box 370594
Montara, California 94037

WARNING LETTER

Dear Ms. Fujino:

We inspected your seafood processing facility, located at 205 Yale Avenue, Princeton-By-The Sea, California, on July 28,29, and August 3, 2010. We found that you have serious violations of the seafood Hazard Analysis and Critical Control Point (HACCP) regulation, Title 21, Code of Federal Regulations, Part 123, and the Current Good Manufacturing Practice regulation for foods, Title 21, Code of Federal Regulations, Part 110 (21 CFR 123 & 110). In accordance with 21 CFR 123.6(g), failure of a processor of fish or fishery products to have and implement a HACCP plan that complies with this section, or otherwise operate in accordance with the requirements of Part 123, renders the fish or fishery products adulterated within the meaning of Section 402(a)(4) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 342(a)(4). Accordingly, your refrigerated, vacuum packaged, ready-to-eat hot smoked and cold smoked salmon is adulterated, in that it has been prepared, packed, or held under insanitary conditions . whereby it 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 have a HACCP plan that, at a minimum, lists the critical limits that must be met, to comply with 21 CFR 123.6(c)(3). A critical limit is defined in 21 CFR Part 123.3(c) as "the maximum or minimum value to which a physical, biological, or chemical parameter must be controlled at a critical control point to prevent, eliminate, or reduce to an acceptable level the occurrence of the identified food safety hazard." However, your firm's HACCP plans for "HOT SMOKED SALMON" and "COLD SMOKED SALMON" list critical limits at the Brining critical control point that are not adequate to control pathogen growth and toxin formation. Your HACCP plans indicate that brining"is to occur for a (b)(4) Because certain pathogenic organisms, such as Staphylococcus aureus, are salt tolerant, FDA recommends that brining be conducted under refrigerated conditions (i.e., 40°F or below) and that you list brining temperature as a critical limit in your HACCP plans.

2. You must have a HACCP plan that, at a minimum, lists monitoring procedures and their frequency for each critical control point, to comply with 21 CFR 123.6(c)(4).

a. However, your firm's HACCP plans for "HOT SMOKED SALMON" and "COLD SMOKED SALMON" list a monitoring frequency (b)(4) at the Refrigerator Storage critical control point that is not adequate to control pathogen growth and Clostridium botulinum toxin formation. FDA recommends monitoring of the cooler temperature by a continuous temperature data recorder, with visual check of the monitoring instrument at least once per day.

b. However, your firm's HACCP plans for "COLD SMOKED SALMON" lists a monitoring frequency of (b)(4) at the Smoking critical control point that is not adequate to control pathogen growth and Clostridium botulinum toxin formation. FDA recommends continuous monitoring of every batch, by the instrument itself, with visual check of the monitoring instrument at least once per batch.

c. However, your firm's HACCP "HOT SMOKED SALMON" lists a monitoring frequency of (b)(4) at the Smoking critical control point that is not adequate to control pathogen growth and Clostridium botulinum toxin formation. In addition to continuous monitoring, FDA recommends a visual check of the monitoring instrument at least once per batch.

3. You must implement the monitoring procedures and frequencies that you have listed in your HACCP plan, to comply with 21 CFR 123.6(b) and (c)(4).

a. However, your firm did not follow the monitoring procedure of (b)(4) of (b)(4) at the Receiving critical control point to control "Pathogen growth" listed in your HACCP plan for "COLD SMOKED SALMON." Specifically, on July 22, 2010, you received (b)(4) Salmon but internal temperatures were not taken on any of the fish.

b. However our firm did not follow the monitoring procedures of (b)(4) at the Brining critical control point to control "Pathogen growth, C. Botulism" listed in your HACCP plan for "HOT SMOKED SALMON." Further your firm also did not follow the monitoring procedure of (b)(4) the (b)(4) of finished product listed in your HACCP plan for "HOT SMOKED SALMON." On July 29, 2010, our investigator observed that your employees made the brining solution. However, no measurements were taken of the brine strength, brining time specifically the end time, brine to fish ratio, and fish thickness. The percent water phase salt is not being tested on every batch of finished product as well.

c. However, your firm did not follow the monitoring procedure of (b)(4) at the Smoking critical control point to control "Pathogen growth, parasites, C. Botulism" listed in your HACCP plan for "HOT SMOKED SALMON." Specifically, on July 29, 2010, our investigator observed that only (b)(4) was used in the smoker (b)(4). In addition, your smoker for "Hot Smoke Sockeye," and "Hot Smoke King Salmon" dated July 24, 29, and 30, 2010, show that only (b)(4) for each production date was monitored at the smoking critical control point.

4. You must implement the record keeping system that you listed in your HACCP plan, to comply with 21 CFR 123.6(b) and (c)(7). However, your firm did not record monitoring observations at the Brining, Smoking and Cooler Storage critical control points to control pathogens and C. botulinum toxin formation listed in your HACCP plans for "COLD SMOKED SALMON" and "HOT SMOKED SALMON." For example, in July 2010, your firm acknowledged receiving (b)(4) pounds of frozen salmon in which (b)(4) of it was processed for ready-to-eat, refrigerated, hot and cold smoked salmon. Based on record review and discussion during the inspection, you did not monitor and maintain records such as receiving logs, salinity measurements, internal cook temperatures, or have records for other critical factors.

5. Because you chose to include a corrective action plan in your HACCP plan, your described corrective actions must be appropriate, to comply with 21 CFR 123.7(b).

a. However, your corrective action plan for "COLD SMOKED SALMON" at the Receiving critical control point (b)(4) to control pathogen growth is not appropriate. Your corrective action does not correct the cause of the deviation, e.g., discontinue use of supplier or carrier until evidence is obtained that transportation practices have changed.

b. However, your corrective action plans for "COLD SMOKED SALMON" and "HOT SMOKED SALMON" at the Smoking and Refrigerator Storage critical control point are not appropriate. Your corrective actions do not correct the cause of the deviation, e.g., make repairs or adjustments to the smoking chamber and the malfunctioning cooler.

6. 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, your firm did not monitor with sufficient frequency, the following areas of sanitation:

a. Safety of Water. On July 28, 2010, our investigator observed that your firm's water reservoir for your ice machine is corroded and contained a greenish, slimy substance. In addition, on July 29, 2010, our investigator observed that there is no back flow prevention device on a faucet used to attach a hose that is used in the production area.

b. Prevention of cross-contamination. On July 29, 2010, our investigator observed that plastic bins used to store fish and fishery products were cleaned on the floor of the production area. Our investigator also observed that the thermometer probe used to monitor the internal temperature in the smoker was not cleaned before and after its use. In addition, on the same day, our investigator observed that a hose used in the production area is stored on the floor. Employees picked up the hose to rinse off and/or remove ice from salmon fillets and immediately returned to handling the salmon without changing gloves or washing hands.

7. You must maintain sanitation control records that, at a minimum, document monitoring and corrections set out in 21 CFR 123.11 (b), to comply with 21 CFR 123.11(c). However, your firm did not maintain sanitation monitoring records for

a. Safety of water that comes into contact with food or food contact surfaces, or is used in the manufacture of ice;

b. Condition and cleanliness of food contact surfaces;

c. Prevention of cross-contamination from insanitary objects to food, food packaging material, and other food contact surfaces, including utensils, gloves, and outer garments and from raw product to cooked product;

d. Maintenance of hand washing, hand sanitizing, and toilet facilities;

e. Protection of food, food packaging material, and food contact surfaces from adulteration;

f. Proper labeling, storage, and use of toxic compounds;

g. Control of employee health conditions; and

h. Exclusion of pests from the food plant.

These records are required for the processing of vacuum packed, ready-to-eat cold smoked and hot smoked salmon.

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 in violation of Section 402(a)(4) of the Act [21 U.S.C. § 342(a)(4)] and the seafood HACCP regulation. We may also take further action to enjoin your firm from operating in violation of Section 415 of the Act (21 U.S.C. § 350d) and 21 CFR Part 1, Subpart H.

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

Please be advised that FDA noted a product label for Black Cod. Black Cod is not an acceptable market name for fish in the US. An acceptable market name for the species Anoplopoma fimbria, the fish you currently identify as Black Cod is "sablefish."

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), and is registered in accordance with the Food Facility Registration regulation (21 CFR Part 1, Subpart H). You also have a responsibility to use procedures to prevent further violations of the Federal Food, Drug, and Cosmetic Act and all applicable regulations.

Please send your reply to the U. S. Food and Drug Administration, Attention: Ms. Erlinda N. Figueroa, Compliance Officer, 1431 Harbor Bay Parkway, Alameda, CA 94502-7070. If you have questions regarding any issues in this letter, please contact Ms. Figueroa at (510) 337-6795.

Sincerely,

/S/
Barbara J. Cassens
District Director
San Francisco District

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VanderVeer Center 11/18/10

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Silver Spring, MD 20993-0002

WARNING LETTER

November 18, 2010

VIA FEDEX

Dr. Elizabeth VanderVeer
www.vanderveercenter.com
6650 S.W. Redwood Lane
Suite 150
Portland, OR 97224

Dear Dr. VanderVeer:

The United States Food and Drug Administration (FDA) has reviewed your website, www.vanderveercenter.com. As explained below, your website contains false or misleading claims related to your Lipodissolve products (which your website also refers to as mesotherapy and meso-lipotherapy), causing them to be misbranded in violation of the Federal Food, Drug, and Cosmetic Act (FDCA), 21 U.S.C. §§ 352(a), 352(n), and 321(n), and FDA’s implementing regulations. See 21 CFR 202.1(e)(5)(i) and (e)(6)(i).

Your Lipodissolve products are intended to cure, treat, mitigate, or prevent disease in humans or to affect the structure or function of the body. Statements on your website that document these intended uses include, but are not limited to, the following:

• “Mesotherapy has a variety of applications: spot fat reduction, cellulite reduction . . .scar revision . . . and the reduction of wrinkles.”

• “Meso-lipotherapy has also proven effective for the non-surgical treatment of lipomas.”

Because these Lipodissolve products are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans, or to affect the structure or any function of the body of man or other animals, they are drugs, as defined by section 201(g)(1) of the FDCA [21 U.S.C. § 321(g)(1)]. In addition, your firm’s injectable Lipodissolve products are prescription drugs, as defined in section 503(b)(1) of the FDCA [21 U.S.C. § 353(b)(1)], because the method of their use is not safe for use except under the supervision of a practitioner licensed by law to administer such drugs.

Under sections 502(a) and 502(n) of the FDCA and FDA’s implementing regulations, a prescription drug is misbranded if its labeling or advertising is false or misleading. Section 201(n) of the FDCA [21 U.S.C. § 321(n)] provides that, in determining whether a drug's labeling or advertising "is misleading, there shall be taken into account . . . not only representations made or suggested . . . but also the extent to which the labeling or advertising . . . fails to reveal facts material in light of such representations . . . . " Advertisements that contain a representation or suggestion that a drug is better, more effective, or safer than has been demonstrated by substantial evidence or substantial clinical experience are false or misleading.

VanderVeer Center’s website contains unsubstantiated efficacy and safety claims concerning Lipodissolve products for the following reasons:

1. Unsubstantiated Efficacy Claims

Your website contains unsubstantiated efficacy claims concerning Lipodissolve products, including:

• “Meso-lipotherapy has also proven effective for the non-surgical treatment of lipomas.”
• “Meso-Lipotherapy is revolutionizing facial rejuvenation by offering the only nonsurgical treatment available for treating facial fat deposits.”
• “Meso-lipotherapy is a cutting edge alternative to liposuction, plastic surgery and other invasive cosmetic procedures.”

FDA regards these claims as false or misleading. FDA is not aware of evidence that supports these claims.

2. Unsubstantiated Safety Claims

Your website contains unsubstantiated safety claims concerning Lipodissolve products, including:

• “Meso-lipotherapy bridges the gap between health and appearance by allowing us to safely shape bodies by eliminating unwanted fat and unsightly cellulite.”

• “We want you to know that Lipodissolve performed at VanderVeer Center is completely safe and effective and has been a consistently popular and successful procedure!”

These claims imply that these products have been proven safe. Although intravenous phosphatidylcholine has been approved in some countries for the treatment of a variety of conditions, it has not been approved in the U.S. FDA is unaware of evidence to support the safety claims for your Lipodissolve products.

As explained above, the claims made for your Lipodissolve products are false or misleading in that they are not supported by substantial evidence or substantial clinical experience. These claims cause your Lipodissolve products to be misbranded under the FDCA [21 U.S.C. §§ 352(a), 352(n), and 321(n)].

Conclusion

The issues and 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 or the occurrence of other violations. It is your responsibility to assure that your firm complies with all requirements of federal law and FDA regulations.

You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, seizure and injunction. Other federal agencies may take this Warning Letter into account when considering the award of contracts.

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, as well as copies of related documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction.

Your written response should be addressed to:

Edisa L. Gozun, PharmD
Consumer Safety Officer
FDA/CDER/Office of Compliance
10903 New Hampshire Avenue, WO51-5199
Silver Spring, MD 20993-0002

Sincerely,

/S/
Michael M. Levy, Jr., Esq.
Director
Division of New Drugs and Labeling Compliance
Office of Compliance
Center for Drug Evaluation and Research

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Close Out Letter

• VanderVeer Center - Close Out Letter 7/26/11

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AES Optics 11/18/10

Department of Health and Human Services	Public Health Service Food and Drug Administration
	New Orleans District 404 BNA Drive Building 200 - Suite 500 Nashville, TN 37217 Telephone: (615) 366-7801 Fax: (615)366-7802

November 18, 2010

WARNING LETTER NO. 2011-NOL-03

UNITED PARCEL SERVICE
Delivery Signature Requested

Wade H. Whitley, President
AES Optics
201 Corporate Court
Senatobia, Mississippi 38668

Dear Mr. Whitley:

During an inspection of your firm, located in Senatobia, Mississippi, on May 13, 18, and 20, 2010, an investigator from the United States Food and Drug Administration (FDA) determined your firm to be the specifications developer, thus manufacturer, of UVA and UVB protection sunglasses. Under Section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), [21 United States Code (USC) 351(h)], these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.

This inspection revealed these devices are adulterated within the meaning of Section 501(h) of the Act [21 USC 351(h)], because 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 requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations, Part 820 (21 CFR 820).

The investigator's observations were noted on a Form FDA 483, Inspectional Observations, issued to you on May 20, 2010. These violations include, but are not limited to, the following:

1. Failure to establish a quality plan [21 CFR 820.20(d)]. There is no agreement with the contract manufacturer to follow specifications or to interact with the owner of the device. There is no procedure or evidence the contract manufacturer contacts AES Optical when non-conformances occur.

2. Failure to establish written procedures for a third party to conduct quality audits (21 CFR 820.22). A third party is performing quality testing on the protective lens, but no procedures have been established for the third party firm.

3. Failure to establish written procedures to cover Corrective and Preventive Action (CAPA) [21 CFR 820.100(b)]. There is no CAPA in place to cover product failure.

4. Failure to establish and identify valid statistical techniques needed for UV testing of UV protective sunglasses [21 CFR 820.250(a)]. There is no agreement with the contract manufacturer or written procedures for testing finished devices.

5. Failure to establish and implement Medical Device Reporting procedures (21 CFR 803.17).

6. Failure to establish written criteria for workmanship expressed in documented standards or by means of identified and approved representative samples [21 CFR 820.70(a)(5)]. There are no specifications or directions to test the UV protective sunglasses for effectiveness.

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

Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violation, from occurring again. Include documentation of the corrective action you have taken. 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.

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

Your response should be addressed to Karl L. Batey, Compliance Officer, US Food and Drug Administration, at the above address. If you have any questions about the content of this letter please contact Ms. Batey at (615) 366-7808.

Sincerely,
/S/
Patricia K. Schafer

Acting District Director
New Orleans District
 

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YeYa Products Corp 11/17/10

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Florida District 555 Winderley Place, Suite 200 Maitland, Florida 32751 Telephone: 407-475-4700 FAX: 407-475-4770

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

WARNING LETTER

FLA-11-08

November 17, 2010

Mr. Roberto D. Sanchez
Owner
YeYa Products Corp.
3820 NW 32nd Avenue
Miami, FL 33142

Dear Mr. Sanchez:

The Food and Drug Administration (FDA) conducted an inspection of your food processing facility, located at 3820 NW 32nd Avenue, Miami, FL 33142, from July 22, 2010, to July 26, 2010. The inspection revealed serious violations of Title 21 of the Code of Federal Regulations (CFR) Part 110 - Current Good Manufacturing Practice in Manufacturing, Packing, or Holding Human Food (CGMP). At the close of the inspection, you were issued a form FDA 483, List of Inspectional Observations, which included a number of insanitary conditions observed in your manufacturing facility. These conditions cause your products, YeYa Plain, Butter and Garlic crackers, to be adulterated within the meaning of section 402(a)(4) [21 U.S.C. § 342(a)(4)] of the Federal Food, Drug and Cosmetic Act (the Act) in that they had been prepared under insanitary conditions whereby they may have become contaminated with filth or may have been rendered injurious to health. You can find the Act through links on the FDA's homepage http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/default.htm.

The inspection revealed the following violations:

1. Your firm failed to maintain its equipment, containers, and utensils, used to convey, hold, or store raw materials, work-in-process, or food in a manner that protects against contamination during manufacturing or storage, as required by 21 CFR 110.80(b)(7).Specifically, our investigator observed:

• The ceiling of the proofers, where the cracker dough is placed to rise, had a moldlike substance on it. The raw crackers could become contaminated from the drops of steam, which form on the moldy ceiling.
 

• Uncovered barrels of cracker dough stored in the cooler were exposed to mold, which was growing on the wall above the door and on the ceiling.

2. Your firm failed to store raw materials in a manner that protects against contamination and minimizes deterioration, as required by 21 CFR 110.80(a)(1). Specifically, our investigator observed:

• Stored in the cooler were six (6) buckets of uncovered dough.

• Wooden tops that had accumulated dirt and organic material covered eight (8) buckets of dough in the cooler.

3. Your firm failed to clean and sanitize your equipment to protect against contamination of food or food-contact surfaces, as required by 21 CFR 110.35(a). Specifically, our investigator observed:

• Your cleaning process for the mixers includes a step where undiluted bleach is poured in the mixer and wiped around inside with a cloth. Undiluted bleach cannot be used as a sanitizing agent because it is toxic and there is a risk that food which comes into contact with surfaces cleaned with undiluted bleach will be contaminated.

4. Your firm failed to design, construct, and use its equipment and utensils to preclude the adulteration of food with contaminants, as required by 21 CFR 110.40(a). Specifically, our investigator observed the following:

• A wooden box, made from splintered wood, collected dough scraps at the end of the depositor conveyor. These dough scraps were recycled back into the roller and were used to shape additional crackers.

• The conveyor belt, which transports dough and ready-to-eat crackers, was made of frayed cloth and was held together in some places with ties, leaving gaps in between sections of the belt.

5. Your firm's facility was not constructed in such a manner that floors, walls, and ceilings may be adequately cleaned and kept clean and in good repair to prevent condensate from fixtures or pipes from contaminating food, food-contact surfaces, or food packaging materials, as required by 21 CFR 110.20(b)(4). Specifically, our investigator observed the following:

• The walls and ceiling of the proofer room are constructed of material that is not smooth and contains uneven surfaces. Such material cannot be adequately cleaned and kept clean and in good repair because the grooves of the uneven surfaces collect dirt, dust, and other contaminants.

• The floor has many holes and depressions where standing water and dirt collect For example, steam, which condensed and mixed with dirt on the floor, formed a muddy puddle in front of stowed carts with trays of in-process crackers. The puddle's proximity to the lower trays of these carts risks these crackers could become contaminated. Additionally, the wheels of these carts routinely pass through this puddle, tracking muddy water throughout the processing area.

6. Your firm failed to maintain your building and fixtures of the plant in a sanitary condition, as required by 21 CFR 110.35(a). Specifically, our investigator observed:

• A mold-like substance was on the ceiling of the proofer.

This letter is not intended to be an all-inclusive list of the violations at your facility. You are responsible for ensuring that your processing facility operates in compliance with the Act and the CGMP regulation for foods (21 CFR Part 110). You also have a responsibility to use procedures to prevent further violations of the Act and all applicable regulations.

We may take further action if you do not correct these violations. Failure to implement corrective action may result in regulatory action being initiated by FDA without further notice. Such action may include seizing your products and/or enjoining your firm from operating.

We request that you notify this office in writing within fifteen (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. Your response should include documentation on how you plan to protect food products from possible contamination, photographs of structural repairs that have been made since the inspection, and/or any other useful information that would assist us in evaluating your corrections. If you cannot complete all corrections before you respond, we expect that you will explain the reason for your delay and state when you will correct any remaining violations.

Please send your response to the U.S. Food and Drug Administration, Attention: Carla A. Norris, Compliance Officer, 555 Winderley Place, Suite 200, Maitland, Florida 32751. If you have questions regarding any issue in this letter, please contact Ms. Norris at (407) 475-4730.

Sincerely,

/S/
Emma Singleton
Director, Florida District
 

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United Brands Company Inc 11/17/10

Department of Health and Human Services	Public Health Service Food and Drug Administration
	College Park, MD 20740

 

NOV. 17,2010

WARNING LETTER

Via FAX and OVERNIGHT MAIL via UPS

Mr. Michael Michail
United Brands Company, Inc.
5360 Jackson Drive, Suite 208
La Mesa, CA 91942

Re: 134070

Dear Mr. Michail:
 

The Food and Drug Administration (FDA) has reviewed the regulatory status of the ingredients  declared on the label of your products, "Joose" and "Max,"¹ each of which contains caffeine that has been directly added to an alcoholic beverage and packaged in combined caffeine and alcohol form. As it is used in your products, caffeine is an unsafe food additive, and therefore your products are adulterated under section 402(a)(2)(C) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 342(a)(2)(C)]. Regulations on the general provisions for food additives are located in Title 21, Code of Federal Regulations, Part 170 (21 CFR 170). You may find copies of the Act and these regulations through links in FDA's Internet home page at http://www.fda.gov.

As defined in section 201(s) of the Act [21 U.S.C. § 321(s)], the term "food additive" refers to any substance the intended use of which results in its becoming a component of any food, unless the substance is the subject of a prior sanction or is generally recognized as safe (GRAS) among qualified experts under the conditions of its intended use. Under section 409 of the Act [21 U.S.C. § 348], a food additive is unsafe unless a regulation is in effect that prescribes the conditions under which the additive may be safely used, and the additive and its use or intended use are in conformity with that regulation. There is no food additive regulation authorizing the use of caffeine as a direct addition to alcoholic beverages, and we are not aware of any information to establish that caffeine added directly to alcoholic beverages is the subject of a prior sanction. Likewise, we are not aware of any basis to conclude that caffeine is GRAS under these conditions of use.

FDA's regulations in 21 CFR Part 170 describe the eligibility criteria for classification of a substance added to food as GRAS. Under 21 CFR 170.30(a)-(c), general recognition of safety must be based on the views of qualified experts. The basis of such views may be either (1) scientific procedures or (2) in the case of a substance used in food prior to January 1, 1958, through experience based on common use in food. Further, general recognition of safety requires common knowledge about the substance throughout the scientific community knowledgeable about the safety of substances directly added to food.

FDA's regulations in 21 CFR Part 170 define "common use in food" and establish eligibility criteria for classification as GRAS through experience based on common use in food. Under 21 CFR 170.3(f), common use in food means "a substantial history of consumption of a substance for food use by a significant number of consumers." Under 21 CFR 170.30(c)(1), "[g]eneral recognition of safety through experience based on common use in food prior to January 1, 1958, shall be based solely on food use of the substance prior to January 1, 1958, and shall ordinarily be based upon generally available data and information." Importantly, however, the fact that a substance was added to food before 1958 does not, in itself, demonstrate that such use is safe, unless the pre-1958 use is sufficient to demonstrate to qualified experts that the substance is safe when added to food. See section 201(s) of the Act [21 U.S.C. § 321(s)]; see also Fmali Herb, Inc. v. Heckler, 715 F.2d 1385, 1389-90 (9th Cir. 1983) ("Under the statute, 'common use in food' of an ingredient does not automatically exempt the substance from pretesting requirements. Instead, 'common use in food' merely describes one form of evidence that may be introduced by a proponent for the purpose of meeting the ultimate standard... ").

Similarly, FDA's regulations in 21 CFR Part 170 define "scientific procedures" and establish eligibility criteria for classification as GRAS through scientific procedures. Under 21 CFR 170.3(h), scientific procedures "include those human, animal, analytical, and other scientific studies, whether published or unpublished, appropriate to establish the safety of a substance." Under 21 CFR 170.30(b), general recognition of safety based upon scientific procedures "shall require the same quantity and quality of scientific evidence as is required to obtain approval of a food additive regulation for the ingredient." Section 170.30(b) further states that general recognition of safety through scientific procedures is ordinarily based upon published studies, which may be corroborated by unpublished studies and other data and information.

FDA's regulations in 21 CFR Part 170 also define "safe" and "safety." Under 21 CFR 170.3(i), "[s]afe or safety means that there is a reasonable certainty in the minds of competent scientists that the substance is not harmful under the intended conditions of use." The regulations identify factors to be considered in determining the safety of a substance added to food. 21 CFR 170.3(i).

By letter dated November 12, 2009, FDA requested that, within 30 days, your company provide evidence of the rationale, along with supporting data and information, for concluding that the use of caffeine in your products is GRAS or prior sanctioned. The letter informed your company that if FDA determined that the use of caffeine in your alcoholic beverages is neither GRAS nor the subject of a prior sanction, the agency would take appropriate action to ensure that these products are removed from the marketplace. FDA's letter also reiterated that it is the continuing responsibility of your company to ensure that the foods it markets are safe and in compliance with all applicable legal and regulatory requirements.

FDA acknowledges that, by letter dated December 11, 2009, United Brands responded through counsel to the agency's November letter. But, as discussed in more detail below, FDA has reviewed that response and continues to have safety concerns about your caffeinated alcoholic beverage products. Accordingly, the agency is issuing this warning letter.

To establish that the use of a substance in food is GRAS under its specific conditions of use (for example, the GRAS status of caffeine when directly added to an alcoholic beverage), there must be consensus among qualified experts that the substance is safe under its conditions of use, based on publicly available data and information. FDA is aware that, based on the publicly available literature, a number of qualified experts have concerns about the safety of caffeinated alcoholic beverages. Moreover, the agency is not aware of data or other information to establish the safety of the relevant conditions of use for your products. Therefore, the criteria for GRAS status have not been met for the caffeine in your beverages.

Based upon the publicly available literature, FDA has the following specific concerns about the safety of caffeine when used in the presence of alcohol:²

• Reports in the scientific literature have described behavioral effects that may occur in young adults when energy drinks are consumed along with alcoholic beverages (O'Brien et al., 2008; Thombs et al., 2010; Miller, 2008).
• Studies suggest that the combined ingestion of caffeine and alcohol may lead to hazardous and life-threatening situations because caffeine counteracts some, but not all, of alcohol's adverse effects. In one study, a mixture of an energy drink and alcohol reduced subjects' subjective perception of intoxication but did not improve diminished motor coordination or slower visual reaction times using objective measures (Ferreira et al., 2006). In a dual-task model, subjects co-administered caffeine and alcohol reported reduced perception of intoxication but no reduction of alcohol-induced impairment of task accuracy (Marczinski and Fillmore, 2006).
• Because caffeine alters the perception of alcohol intoxication, the consumption of pre-mixed products containing added caffeine and alcohol may result in higher amounts of alcohol consumed per drinking occasion, a situation that is particularly dangerous for naive drinkers (Oteri et al., 2007).

GRAS status is not an inherent property sofa substance, but must be assessed in the context of the intended conditions of use of the substance (section 201(s) of the Act [21 U.S.C. § 321(s)]). The assessment includes a consideration of the population that will consume the substance (21 CFR 170.30(b); section 409(b) of the Act [21 U.S.C. § 348(b)]). Therefore, the scientific data and information that support a GRAS determination must consider the conditions under which the substance is safe for the use for which it is marketed. Reports in the scientific literature have raised concerns regarding the formulation and packaging of pre-mixed products containing added caffeine and alcohol. For example, these products, presented as fruity soft drinks in colorful single-serving packages, seemingly target the young adult user. Furthermore, the marketing of the caffeinated versions of this class of alcoholic beverage appears to be specifically directed to young adults (Bonnie and O'Connell, 2004). FDA is concerned that the young adults to whom these pre-mixed, added caffeine and alcohol products are marketed are especially vulnerable to the adverse behavioral effects associated with consuming caffeine added to alcohol, a concern reflected in the publicly available literature (O'Brien et al., 2008; Simon and Mosher, 2007).

It is FDA's view that the caffeine content of your beverages could result in central nervous system effects if a consumer drank one or more containers of your product. Therefore, FDA believes that the consumption of your products, "Joose" and "Max," may result in adverse behavioral outcomes because the caffeine is likely to counteract some, but not all, of the adverse effects of alcohol. The agency is unaware of any data that address the complex, potentially hazardous behaviors that have been identified in the scientific literature as associated with these beverages or that otherwise alleviate our concerns about the effects of consuming these pre-mixed caffeine and alcohol beverages. Moreover, FDA is not aware of any publicly available data to establish affirmatively safe conditions of use for caffeine added directly to alcoholic beverages and packaged in a combined form.

The agency is aware that your company received a Certification/Exemption of Label/Bottle Approval (COLA) from the Alcohol and Tobacco Tax and Trade Bureau (TTB) and that, as part of your application for the COLA, you informed TTB that your product would contain caffeine. A COLA does not constitute a food additive petition approval, a statement regarding GRAS status, or a prior sanction, and you are obligated to abide by the provisions of the Federal Food, Drug, and Cosmetic Act.

Your company's December 11, 2009, response discussed two human clinical studies in the peer reviewed literature that address the safety of the co-consumption of caffeine and alcohol (Ferreira et al., 2006; O'Brien et al., 2008), and purported to identify shortcomings in the design and interpretation of these studies. FDA notes that these alleged deficiencies were included in a letter from your counsel and were not endorsed, supported, or otherwise accompanied by the opinion of a qualified expert as to their significance. Even if certain studies in the scientific literature have limitations due to their design or the interpretation of their results, the peer-reviewed literature as a whole is sufficient to raise, among qualified experts, safety concerns about alcoholic beverages to which caffeine has been directly added. Similarly, even if the results from no single study are sufficiently comprehensive to characterize fully the potential responses to beverages containing caffeine added to alcohol, these studies are collectively sufficient to raise concerns about consumption of this combination and to support the conclusion that more research is required. Furthermore, FDA is not aware of any reports in the literature that refute the association between the co-consumption of alcohol and caffeine and adverse behavioral results or that otherwise affirmatively establish the safety of these beverages. Indeed, our review of this literature, as well as certain related studies in animals, shows that there are currently no studies or other information that refute the safety concerns or otherwise affirmatively establish the safety of caffeine directly added to alcoholic beverages. Therefore, we are not aware of a sufficient basis to support a conclusion that caffeine, when directly added to alcohol to form a single beverage, is generally recognized as safe.

In light of the safety concerns identified above, the use of added caffeine in the alcoholic beverage products "Joose" and "Max" does not satisfy the criteria for GRAS status outlined above. Further, FDA is aware of no other exemption from the food additive definition that would apply to caffeine when used as an ingredient in an alcoholic beverage product. Therefore, caffeine as used in your products is a food additive under section 201(s) of the Act [21 U.S.C. § 321(s)] and is subject to the provisions of section 409 of the Act [21 U.S.C. § 348]. Under the latter, a food additive is required to be approved by FDA for its proposed conditions of use prior to marketing. Because caffeine is not an approved food additive for its use in your products, "Joose" and "Max," those products are adulterated within the meaning of section 402(a)(2)(C) of the Act [21 U.S.C. § 342 (a)(2)(C)].

You should take prompt action to correct this violation and prevent its recurrence. Failure to do so may result in enforcement action without further notice. The Act authorizes the seizure of illegal products and injunctions and prosecutions against manufacturers and distributors of those products. Also, we want you to be aware that FDA did not conduct an all-inclusive review of your products, "Joose" and "Max" or any other products that you may manufacture or distribute. Under the applicable law, it is your responsibility, as a manufacturer of these products, to ensure that the foods your firm markets are safe and otherwise in compliance with all applicable legal requirements.

Please advise this office in writing within fifteen (15) days from your receipt of this letter as to the specific steps you have taken to correct the violation identified above and to assure that similar violations do not occur. Your response should include any documentation necessary to show that correction has been achieved. If you cannot complete all corrections within the 15 days, please explain the reason for your delay and the date by which each such item will be corrected and documented.

Please send your reply to Seyra Hammond, Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Compliance (HFS-605), 5100 Paint Branch Parkway, College Park, MD 20740.

 

Sincerely,

/s/

Joann M. Given
Acting Director
Office of Compliance
Center for Food Safety
and Applied Nutrition

 

cc: Food and Drug Administration
Los Angeles District Office

 

References

Bonnie, R. and O'Connell, M., Editors, Reducing underage drinking: a collective responsibility. The National Academies Press, 2004.

Ferreira SE, de Mello MT, Pompeia S, and de Souza-Formigoni ML. Effects of energy drink ingestion on alcohol intoxication. Alcohol Clin Exp Res 30, 598-605, 2006.

Heckman, MA, Sherry, K., and Gonzalez de Mejia, E. Energy drinks: an assessment of their market size, consumer demographics, ingredient profile, functionality, and regulations in the United States. Compr Rev Food Sci Food Saf, 9, 303-317, 2010.

Marczinski, CA and Fillmore, MT. Clubgoers and their trendy cocktails: implications of mixing caffeine into alcohol on information processing and subjective reports of intoxication. Exp Clin Psychopharmacol,14,450-458,2006.

Miller, KE. Wired: energy drinks, jock identity, masculine norms, and risk taking. J Am College Health, 56, 481-489, 2008.

O'Brien, MC, McCoy, TP, Rhodes, SO, Wagoner, A, and Wolfson, M. Caffeinated cocktails: energy drink consumption, high-risk drinking, and alcohol-related consequences among college students. Acad Emerg Med 15, 453-460, 2008.

Oteri A, Salvo F, Caputi AP, and Calapai G. Intake of energy drinks in association with alcoholic beverages in a cohort of students of the School of Medicine of the University of Messina. Alcohol Clin Exp Res 31,1677-1680,2007.

Simon M. and Mosher J. Alcohol, energy drinks, and youth: a dangerous mix. Marin Institute, 2007. Thombs, OL, O'Mara, RJ, Tsukamoto, M, Rossheim, ME, Weiler, RM, Merves, ML, and Goldberger, BA. Event-level analysis of energy drink consumption and alcohol intoxication in bar
patrons. Addict Behav 35, 325-330, 2010.

 

__________ 

¹ This letter addresses the following flavors of "Joose": green apple, raspberry lemonade, red, blue, orange, dragon, jungle, mamba, panther, watermelon, and lemon tea. This letter addresses the following flavors of "Max": green apple, watermelon, and vibe.
 

² As used in the discussion below, the term "energy drink" identifies beverages that contain a significant amount of calories and caffeine as well as other ingredients, such as taurine, herbal extracts, or vitamins (Heckman et al., 2010).

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