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Thursday, December 30, 2010

Dr. Christopher's 12/30/10

  

Department of Health and Human Services' logoDepartment 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: 303-236-3100 

 

December 30, 2010


Ref: DEN-11-06 CIWL


WARNING LETTER

VIA UPS

Josh Scott
438 South 1680 West
Provo, Utah  84601

Dear Mr. Scott:                                                                                   

This is to advise you that the Food and Drug Administration (FDA) has reviewed your websites at the Internet addresses, www.drchristophers.com and www.herbshopconnection.com in December 2010 and has determined that the products “Bilberry Eye Capsule,” “Cayenne Pepper Extract,” “Hawthorn Berry Heart Syrup,”  “Blood Circulation Formula,”  “Chest Formula,” “Immune System Formula,” “Pancreas Formula,” “Cold Season Formula,” “Garlic Rosehips & Parsley Powder,”  and “Lung & Bronchial Capsule” are promoted for conditions that cause the products to be drugs under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 321(g)(1)(B)]. The therapeutic claims on your websites establish that the products are drugs because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.  The marketing of these products with these claims violates the Act.  You can find the Act and FDA’s regulations through links at FDA’s home page at http://www.fda.gov.

Examples of some of the claims observed on your website, www.drchristophers.com, include:

Bilberry Eye Capsule

• “[K]nown to prevent glaucoma ….”
• “[P]revent[s] myopia and slow[s] down or stop[s] progressive myopia….”
• “[A]pplied for the treatment of various types of myopia (including progressive myopia),  myopic chorioretinitis [sic] … retinal degeneration, diabetic retinopathy, various inflammatory reactions (retinitis, conjunctivitis, keratitis), macular degeneration … glaucoma ….”
• “[P]revents degenerative processes in the eye.”
• “Cayenne pepper [an ingredient in your product] … has anti-cancer properties and helps in the treatment of ovarian tumors.”
• “Eyebright Herb [an ingredient in your product] … produces a strong anti-inflammatory effect …”
• “Ailments traditionally used for: … Cataracts, Conjunctivitis … Glaucoma, Macular Degeneration …  Retinopathy ….”

Cayenne Pepper Extract

• “Ailments traditionally used for: … Arthritis, Atherosclerosis…Bursitis, Cancer …, Cold Sores, Colitis, Common Cold … Constipation, Coronary Artery Disease … Cystitis … Flu … Gout … Heart Disease … Herpes Simplex 1 … Hypercholsterolemia[sic], … Influenza … Irritable Bowel Syndrome … Measles … Mitral Valve Prolapse … Pleurisy … Stroke … Urinary Tract Infection …Yellow Fever.”

Hawthorn Berry Heart Syrup

• “Ailments traditionally used for:  Angina … Atherosclerosis … Congestive Heart Failure, Coronary Artery Disease … Glaucoma … Hypercholesterolemia, Hypertension, Macular Degeneration, Mitral Valve Prolapse … Retinopathy … Stroke …. ”

Blood Circulation Formula

• “It [Blood Circulation Formula] has freed many people of … tumors, [and] infections …”
• “Blood Circulation Capsule is irreplaceable in battling the consequences of diabetes.”
• “Ginger Root [an ingredient in your product] … is well known for bactericidal, anti-inflamatory [sic] … properties.”
• “Ginger root [an ingredient in your product] is also known to … treat atherosclerosis.”
• “Garlic Bulb extract [an ingredient in your product] is another excellent antiseptic and antibacterial element .…”
• “It [Garlic Bulb extract (an ingredient in your product)] treats disorders resulting from staphylococcal and streptococcal infections .…”
• “Garlic bulb [an ingredient in your product] … battles atherosclerosis and thrombophlebitis …”
• “Ailments traditionally used for: … Atherosclerosis … Blood Pressure … Congestive Heart Failure, Coronary Artery Disease … Glaucoma … Heart Disease … Hypercholesterolemia … Macular Degeneration, Mitral Valve Prolapse ….”

Chest Formula

• “Chest Formula Capsule is prescribed for the treatment of … viral infections … bronchial asthma, chronic obstructive pulmonary disease ….”
•  “The medicine [chest formula capsule] possesses, antiviral, bactericidal and antiseptic properties and is used effectively to treat … laryngitis, bronchitis, pneumonia, influenza, pleurisy, and asthma attacks.”
• “[I]t [chest formula capsule] has a strong antipyretic, anti-inflammatory … effect …”
•  “Chest Formula Capsule may be helpful in the treatment of … infections, colitis ….”
• Ginger Root … used in the treatment of cardiovascular diseases … prevent heart failure.”
• “Ailments traditionally used for: … Bronchitis … Chronic Obstructive Pulmonary Disease … Common Cold … Flu … Laryngitis … Periodontal Disease ….”    

Immune System Formula  

• “[D]esigned … to prevent and treat … cancer and tumors.”
• “Has anti-allergic and anti-inflammatory effect”
•  “May help prevent cancer”
• “[R]ecommended in the treatment and prevention of these diseases: …

o Bacterial and viral infections such as influenza or herpes …
o Atherosclerosis of coronary and cerebral arteries …
o Benign and malignant tumors
o Chronic leukemia
o Chronic form of hepatitis B ….”

• “Ailments traditionally used for:  Bacterial Infection, Herpes Zoster ….”

Pancreas Formula

•   “Prevents the development of diabetes”
• “[D]esigned to  … treat infectious and inflammatory diseases in the pancreas and the liver.”
• “Traditional Uses of the Formula:  Pancreatitis … Gastric ulcer … duodenitis … Tumors of the stomach and liver, Chronic hepatitis, Early stages of liver cirrhosis, Acute and chronic cholecystitis … Diabetes mellitus”
 
Examples of some of the claims observed on your website, www.herbshopconnection.com,  include:

Cold Season Formula

• “ The [Cold Season] Formula has antiviral and antibacterial properties.”
• “Ailments traditionally used for: … Candidiasis … Cold Sores, Common Cold, Congestive Heart Failure … Flu … Herpes Simplex 1 … Hypercholesterolemia … Laryngitis, Lupus, Mitral Valve Prolapse … Thrush, Ulcer ….”

Garlic Rosehips & Parsley Powder

• “Ailments traditionally used for:  … Common Cold, Congestive Heart Failure, Flu … Gastritis … Hypercholesterolemia, Influenza, Laryngitis, Lupus, Mitral Valve Prolapse … Stomach Ulcer ….”

Lung & Bronchial Capsule

• “[The Lung & Bronchial Capsule] has analgesic effect ,,,.”
• “Many people use Lung & Bronchial Capsule to … relieve inflammation in the genitourinary system.”
• “The formula may . . .

o Treat and prevent viral respiratory infections, influenza
o Treat and prevent infectious diseases”

• “Ailments traditionally used for:  Asthma, Bronchitis … Chronic Obstructive Pulmonary Disease, Cold … Pleurisy, Sinusitis, Tuberculosis, Whooping Cough.”

Your products are not generally recognized as safe and effective for the above referenced uses and therefore, the products are “new drugs” under section 201(p) of the Act [21 U.S.C. § 321(p)].  New drugs may not be legally marketed in the U.S. without prior approval from FDA as described in section 505(a) of the Act [21 U.S.C. § 355(a)].  FDA approves a new drug on the basis of scientific data submitted by a drug sponsor to demonstrate that the drug is safe and effective.

Furthermore, because your products, Bilberry Eye Capsule,” “Cayenne Pepper Extract,” “Hawthorn Berry Heart Syrup,”  “Blood Circulation Formula,”  “Chest Formula,” “Immune System Formula,” “Pancreas Formula,” “Cold Season Formula,” “Garlic Rosehips & Parsley Powder,”  and “Lung & Bronchial Capsule,”  are offered for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners, adequate directions cannot be written so that a layman can use the products safely for their intended uses.  Thus, their labeling fails to bear adequate directions for their intended uses, causing them to be misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)].

The above violations are not meant to be an all-inclusive list of deficiencies in your products and their labeling.  It is your responsibility to ensure that all of your products and labeling are in compliance with the laws and regulations enforced by FDA.  We advise you to review your website, product labels, and other labeling and promotional materials for your products to ensure that the claims you make for your products do not cause them to violate the Act.

You should take prompt action to correct the violations described above and prevent their future recurrence.  Failure to do so may result in regulatory action without further notice, such as seizure and/or injunction. The Act authorizes the seizure of illegal products and injunctions against manufacturers and distributors of those products [21 U.S.C. §§ 332 and 334]. 

Please notify this office in writing within fifteen (15) working days from your receipt of this letter as to the specific steps you have taken to correct the violations noted 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 before you respond, please explain the reason for the delay and the date by which the corrections will be completed.

Please send your reply to the attention of Thomas R. Berry, Compliance Officer, at the above letterhead address.

If you have any questions regarding any issues in this letter, please contact Thomas R. Berry, Compliance Officer, at 303-236-3028.

Sincerely,

/s/

Harry T. Warwick
Director, Denver District Office

 

 

 

cc:
Robert Scott, President
Wholistic Botanicals, L.L.C.
155 W. 2050 N.
Spanish Fork, Utah 84660

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Tuesday, December 28, 2010

Novacare, LLC 12/28/10

  

Department of Health and Human Services' logoDepartment 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: 303-236-3100

December 28, 2010

WARNING LETTER

Via UPS


Kelly D. Harvey, President
NovaCare, LLC (TSN Labs, Inc.)
330 West 6100 South
Salt Lake City, UT  84047

Ref: # DEN-11-06-WL

Dear Mr. Harvey:

The United States Food and Drug Administration (FDA) conducted an inspection of your facility at the address referenced above from March 8, 2010 through March 22, 2010.  During the inspection samples were collected of your firm’s (b)(4) an ingredient used by your firm in the manufacture of products marketed as dietary supplements, and of the Master Manufacturing Records for products manufactured by your firm, which show (b)(4) as a component in their production.  Laboratory analyses conducted by the FDA concluded that your firm’s (b)(4) contains sulfoaildenafil, an analogue of sildenafil, the active pharmaceutical ingredient in Viagra, an FDA-approved drug used to treat erectile dysfunction (ED).  Following this finding, FDA obtained samples of products manufactured by your firm and marketed as dietary supplement including, but not limited to, “Aziffa,” “MONSTER EXCYTE,” “Natural WOW! Ultra Perform for MEN,” “Natural WOW! Ultra Perform for WOMEN,” “OMG,” “ProLatis’,” “Stiff Nights,” “Verect,” “XaitriX,”  “Zilex,” and “Zotrex.”1   For the reasons stated below, these  products are unapproved drugs in violation of section 505(a) of the Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 355(a)] and misbranded drugs in violation of sections 502(f)(1) [21 U.S.C. § 352(f)(1)], 502(f)(2) [21 U.S.C. § 352(f)(2)] and 502(a) [21 U.S.C. § 352(a)].  In addition, [(b)(4) is a drug within the meaning of section 201(g)(1)(D) [21 U.S.C. § 321(g)(1)(D)] of the Act and is misbranded under section 502(f)(1) [21 U.S.C. § 352(f)(1)] of the Act.  

Your firm’s sexual enhancement products “Aziffa,” “MONSTER EXCYTE,” “Natural WOW! Ultra Perform for MEN,” “Natural WOW! Ultra Perform for WOMEN,” “OMG,” “ProLatis’,” “Stiff Nights,” “Verect,” “XaitriX,” “Zilex,” and “Zotrex” are labeled with claims such as the following:

“Aziffa”

• “Male Sexual Stimulant”
• “Sexual Stimulation Blend”

 “MONSTER EXCYTE”

• “INCREASED SEX DRIVE, STAMINA AND VIRILITY FOR MEN”
• “MALE SEXUAL VITALITY ENHANCER”
• “As a dietary supplement, take 1-2 capsules 45 minutes before sexual activity”

Natural WOW! Ultra Perform for MEN”

• “SEXUAL BOOSTER!”
• “INCREASES STAMINA”
• “BOOSTS SEXUAL APPETITE”
• “INCREASES SEXUAL VITALITY”
• “take one capsules 30-45 minutes before sexual activity”

“Natural WOW! Ultra Perform for WOMEN”

• “SEXUAL BOOSTER!”
•  “BOOSTS SEXUAL APPETITE”
• “INCREASES FEMALE SEXUAL VITALITY”
• “take one capsules 30-45 minutes before sexual activity”

“OMG”

• “As a dietary supplement, take 1-2 capsules 45 minutes before sexual activity”
• “OMG Vitality Formula”

ProLatis’

• “All-Natural Male Performance Pill”
• “Take 1-2 capsules 1-2 hours before sexual activity.”

Stiff Nights”

• “Male Sexual Stimulant”
• “Regain the Thunder”
• “Erection Booster BlendTM

“Verect”

• “Male Sexual Vitality”
• “As a dietary supplement, take 1-2 capsules 45 minutes before sexual activity.”
• “Zotrex Vitality Formula”

“XaitriX”

• “As a dietary supplement, take 1-2 capsules 45 minutes before sexual activity”

“Zilex”

• “Female Sexual Vitality”
• “Zilex Vitality Formula”
• “As a dietary supplement, take 1-2 capsules 45 minutes before sexual activity with a large glass of water.”

“Zotrex”

• “Male Sexual Vitality”
• “Zotrex Vitality Formula”
• “As a dietary supplement, take 1-2 capsules 45 minutes before sexual activity with a large glass of water”

These statements make clear that the above mentioned products are drugs under section 201(g)(1)(C) of the Act [21 U.S.C. § 321(g)(1)(C)] because they are intended to affect the structure or function of the human body.  Your firm’s “Aziffa,” “MONSTER EXCYTE,” “Natural WOW! Ultra Perform for MEN,” “Natural WOW! Ultra Perform for WOMEN,” “OMG,” “ProLatis’,” “Stiff Nights,” “Verect,” “XaitriX,” “Zilex,” and “Zotrex” sexual enhancement products are labeled as dietary supplements.  However, these products contain sulfoaildenafil, a phosphodiesterase type 5 (PDE5) inhibitor and an analogue of sildenafil, the active pharmaceutical ingredient in Viagra, an FDA-approved drug used to treat erectile dysfunction (ED).  Sulfoaildenafil is a synthetic active pharmaceutical ingredient and is not a dietary ingredient as defined in section 201(ff)(1) of the Act [21 U.S.C. § 321(ff)(1)].

Under section 201(g)(1) of the Act (last sentence), the structure/function claims made for a dietary supplement must be made in accordance with section 403(r)(6) of the Act [21 U.S.C. § 343(r)(6)] or the product is subject to regulation as a drug.  Section 403(r)(6) authorizes claims that describe the role of a nutrient or dietary ingredient intended to affect the structure or function of the body, or that characterize the way in which a nutrient or dietary ingredient maintains the structure or function of the body.  However, the structure/function claims quoted above do not describe the effects of nutrients or dietary ingredients in the products.  Rather, the claims are made for the products as a whole and relate to their sulfoaildenafil content.  Since sulfoaildenafil is not a nutrient or dietary ingredient, as defined in section 201(ff)(1) of the Act [21 U.S.C. § 321(ff)(1)], but a synthetic active pharmaceutical ingredient, claims about improvement of sexual function do not conform to section 403(r)(6) of the Act [21 U.S.C. § 343(r)(6)].  Accordingly, “Aziffa,” “MONSTER EXCYTE,” “Natural WOW! Ultra Perform for MEN,” “Natural WOW! Ultra Perform for WOMEN,” “OMG,” “ProLatis’,” “Stiff Nights,” “Verect,” “XaitriX,” “Zilex,” and “Zotrex” are drugs within the meaning of section 201(g)(1)(C) of the Act [21 U.S.C. § 321(g)(1)(C)].

Furthermore, under section 201(g)(1)(D) of the Act [21 U.S.C. § 321(g)(1)(D)], an article intended for use as a component of a drug is also a drug.  Component means any ingredient intended for use in the manufacture of a drug product, including those that may not appear in such drug product.  See Title 21 of the Code of Federal Regulations, Part 210.3(b)(3) [21 CFR 210.3(b)(3)].  Master Manufacturing Records obtained from your firm indicate that (b)(4) is an ingredient used in the manufacture of drugs, including, but not limited to “Zotrex.”  Accordingly, your firm’s (b)(4) is a drug within the meaning of section 201(g)(1)(D) of the Act [21 U.S.C. § 321(g)(1)(D)]. 

Moreover, “Aziffa,” “MONSTER EXCYTE,” “Natural WOW! Ultra Perform for MEN,” “Natural WOW! Ultra Perform for WOMEN,” “OMG,” “ProLatis’,” “Stiff Nights,” “Verect,” “XaitriX,” “Zilex,” and “Zotrex” are new drugs, as defined by section 201(p) of the Act [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective for use under the conditions prescribed, recommended, or suggested in their labeling.  Under sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)], a new drug may not be introduced or delivered for introduction into interstate commerce unless an FDA-approved application is in effect for it.  Your distribution or sale of these products without an approved application violates these provisions of the Act.

“Aziffa,” “MONSTER EXCYTE,” “Natural WOW! Ultra Perform for MEN,” “Natural WOW! Ultra Perform for WOMEN,” “OMG,” “ProLatis’,” “Stiff Nights,” “Verect,” “XaitriX,” “Zilex,” and “Zotrex” are “prescription drugs” as defined at section 503(b)(1)(A) of the Act [21 U.S.C. § 353(b)(1)(A)] because, in light of their toxicity or other potentiality for harmful effect, the method of their use, or the collateral measures necessary to their use, they are not safe for use except under the supervision of a practitioner licensed by law to administer them.  Indeed, all FDA approvals of PDE5 inhibitors are limited to use under the professional supervision of a practitioner licensed by law to administer such drugs.

According to section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)] a drug is misbranded if, among other things, it fails to bear adequate directions for its intended use(s).  “Adequate directions for use” means directions under which a layman can use a drug safely and for the purposes for which it is intended [21 CFR § 201.5]. 

Prescription drugs can only be used safely at the direction, and under the supervision, of a licensed practitioner.  Therefore, it is impossible to write “adequate directions for use” for prescription drugs.  FDA-approved drugs that bear their FDA-approved labeling are exempt from the requirement that they bear adequate directions for use by a layperson [21 U.S.C. §§ 201.100(c)(2) and 201.115].  Because there is no FDA-approved application for “Aziffa,” “MONSTER EXCYTE,” “Natural WOW! Ultra Perform for MEN,” “Natural WOW! Ultra Perform for WOMEN,” “OMG,” “ProLatis’,” “Stiff Nights,” “Verect,” “XaitriX,” “Zilex,” and “Zotrex,” their labeling fails to bear adequate directions for their intended use, causing them to be misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)].

In addition, a drug in bulk package form intended for use in the manufacture of a new drug is only exempt from section 502(f)(1) of the Act [21 CFR § 352(f)(1)] if it satisfies the specific conditions set forth in 21 CFR § 201.122.  Your bulk package drug (b)(4) does not satisfy the conditions of the exemption. Thus, your firm’s (b)(4) is also misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)].

Under section 502(a) of the Act [21 U.S.C. § 352(a)], a drug is misbranded if its labeling is false or misleading in any particular.  Section 201(n) of the Act [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 . . . .”  The labeling of the above mentioned products does not declare that they contain sulfoaildenafil.  Sulfaoaildenafil is an analogue of sildenafil, and, like sildenafil, is a PDE5 inhibitor.  Because it is an analogue of sildenafil, sulfoaildenafil likely exhibits similar pharmacological action to sildenafil.  The use of PDE5 inhibitors, like sildenafil, can be associated with significant safety issues and the risk of serious adverse events.  The undeclared PDE5 inhibitor in the above mentioned products may pose a serious health risks because patients with underlying medical issues may take these products without knowing that they can cause serious harm or interact in dangerous ways with other drugs they may be taking.  For example, PDE5 inhibitors may interact with nitrates found in some prescription drugs (such as nitroglycerin), and can lower blood pressure to dangerous levels.  Consumers with diabetes, high blood pressure, high cholesterol, or heart disease often take nitrates.  Further, patients who have been advised against taking PDE5 inhibitors because of comorbidities or potential drug interactions may seek products like “Aziffa,” “MONSTER EXCYTE,” “Natural WOW! Ultra Perform for MEN,” “Natural WOW! Ultra Perform for WOMEN,” “OMG,” “ProLatis’,” “Stiff Nights,” “Verect,” “XaitriX,” “Zilex,” and “Zotrex” because they are marketed as not containing the active ingredients in approved ED drugs.  The failure to disclose the presence of sulfoaildenafil renders your products’ labeling false and misleading.  “Aziffa,” “MONSTER EXCYTE,” “Natural WOW! Ultra Perform for MEN,” “Natural WOW! Ultra Perform for WOMEN,” “OMG,” “ProLatis’,” “Stiff Nights,” “Verect,” “XaitriX,” “Zilex,” and “Zotrex” are therefore misbranded under Section 502(a) of the Act [21 U.S.C. § 352(a)]. 

“Aziffa,” “MONSTER EXCYTE,” “Natural WOW! Ultra Perform for MEN,” “Natural WOW! Ultra Perform for WOMEN,” “OMG,” “ProLatis’,” “Stiff Nights,” “Verect,” “XaitriX,” “Zilex,” and “Zotrex” are also misbranded under Section 502(f)(2) of the Act, [21 U.S.C. § 352(f)(2)] in that their labeling lacks adequate warnings for the protection of users.  As noted, there is potential for adverse events associated with the use of these products, particularly since someone who takes them would be unaware of the presence of sulfoaildenafil.  For example, because sulfoaildenafil is an analogue of sildenafil and is a PDE5 inhibitor, patients who take nitrates and consume “Aziffa,” “MONSTER EXCYTE,” “Natural WOW! Ultra Perform for MEN,” “Natural WOW! Ultra Perform for WOMEN,” “OMG,” “ProLatis’,” “Stiff Nights,” “Verect,” “XaitriX,” “Zilex,” and “Zotrex” may be at risk of life-threatening hypotension.

The introduction or delivery for introduction into interstate commerce of these misbranded products violates section 301(a) of the Act (21 U.S.C. § 331).

The issues and violations cited in this letter are not intended to be an all-inclusive statement of violations that exist in connection with your product.  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, injunction, and/or prosecution.

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 reply should be sent to the Food & Drug Administration, Denver District Office, Denver Federal Center – Building 20, 6th Avenue and Kipling Street, P.O. Box 25087, Denver, CO 80225-0087, to the attention of Thomas R. Berry, Compliance Officer.  If you have any questions regarding the content of this letter, please contact Mr. Berry at (303) 236 -3028.

 

Sincerely,

/s/

H. Thomas Warwick, Jr.
Denver District Director

 

 

________________________

1 In August 2010, your firm conducted a voluntary nationwide recall of all lots of certain products sold prior to June 17, 2010, including the products listed above, after FDA informed you that the products appeared to contain sulfoaildenafil.  FDA subsequently confirmed that the products above contain sulfoaildenafil.  
 

 


 

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McGuff Pharmaceuticals Inc. 12/28/10

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 
Los Angeles District
Compliance Branch
19701 Fairchild
Irvine, CA  92612-2506
 
Telephone: 949-608-4426
FAX: 949-608-4415 

      

Warning Letter
 
 
CERTIFIED MAIL                                                                        
RETURN RECEIPT REQUESTED
 
WL: 19-11
 
December 28, 2010
 
Ronald M. McGuff
President and CEO
McGuff Pharmaceuticals Inc.
2921 W Macarthur Blvd Ste 142
Santa Ana, CA 92704-7944
 
Dear Mr. McGuff:
 
During our May 18 to June 2, 2010 inspection of your pharmaceutical manufacturing facility, McGuff Pharmaceuticals, Inc., located at 2921 W Macarthur Blvd Ste 142, Santa Ana, California, investigators from the Food and Drug Administration (FDA) identified significant violations of Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug product(s) to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351(a)(2)(B)] in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP. 
 
In addition, you distribute unapproved new and misbranded drugs in violation of sections 505(a) and 502(f)(1) [21 U.S.C. §§ 355(a) and 352(f)(1)] of the Act.
 
We have reviewed your firm’s response of June 16, 2010, and note that it lacks sufficient corrective actions.   
 
Specific violations observed during the inspection include, but are not limited to, the following: 
 
CGMP Violations
                                    
1. Your firm has not established appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes [21 C.F.R. § 211.113(b)].  For example:
 
a. Your firm has failed to conduct a media fill representative of the different packaging configurations of your drug products for the past two years. Your firm has been using a volume of (b)(4) for media fills; however, commercial products are available in (b)(4) and (b)(4). In addition, you have not established maximum aseptic fill duration.
 
In your response, your firm states that you have amended your Standard Operating Procedure (SOP) (b)(4) to “bracket” the container sizes by utilizing both the (b)(4) and (b)(4) volumes. Your response, however, is inadequate because you have not provided a risk assessment that examines the effects of differences between product fill sizes (i.e., fill speed, operating methods, container opening size, mass) to determine if bracketing is appropriate.  
 
b. Your firm’s qualifications of the Getinge Model 4300 autoclave and the Grieve CLE-500 oven are inadequate in that you have not qualified this equipment with representative loads. Your firm’s practice is to qualify the equipment using minimum loads as opposed to actual loads during routine operation (e.g., Grieve CLE-500 oven was qualified to depyrogenate glass vials using (b)(4) tray when the actual load is a maximum of 60 trays).
 
In addition, your use of biological indicators and penetration thermocouples in the qualification studies are inadequate. Your firm has not used any penetration thermocouples during the qualification of Getinge Model 4300 since February (b)(4), nor have you incorporated the use of biological indicators. During the maximum load configuration study, your firm only used a (b)(4) penetration thermocouple and failed to use any biological indicators. 
 
In your response, your firm commits to evaluate the adequacy of your current procedure, to qualify your minimum and maximum load on each of your manufacturing operations, and to include penetration thermocouples and biological indicators in appropriate areas and in appropriate quantities. However, your response is inadequate because you did not explain how you will determine the appropriate locations and quantities for the thermocouples and the biological indicators. Since your firm is currently manufacturing sterile drug products using unqualified equipment, your response fails to include any additional controls to assure the quality of your drug products while you are evaluating your current procedures.
 
2. Your firm has not conducted at least one specific identity test and has not established the reliability of the supplier’s analyses through appropriate validation of the supplier’s test results at appropriate intervals [21 C.F.R. § 211.84(d)(2)]. 
 
For example, your firm accepts and relies upon the Certificate of Analysis (COA) from your active pharmaceutical ingredient (API) suppliers without conducting appropriate validation of the supplier’s test results. This is of heightened concern since you have not established endotoxin specifications, nor have you performed endotoxin testing on APIs intended to be used in the manufacture of sterile drugs.
 
In your response, your firm commits to test any APIs with amended specifications in an attempt to correct this deficiency.  However, your response fails to explain which specifications are to be amended or which APIs are to be tested. In addition, you do not describe corrective actions regarding products currently in the market manufactured with APIs of questionable quality.
 
Please note that adequate qualification of suppliers is critical in assuring that your sterile drug products are of the quality intended.
 
3. Your firm has not thoroughly investigated the failure of a batch or any of its components to meet its specifications whether or not the batch has already been distributed [21 C.F.R. § 211.192]
 
For example, your firm failed to conduct adequate investigations into action level excursions. Your investigations (e.g., (b)(4)) of growth in a media fill did not include a review of the batch records, equipment logs, or HVAC system by the most responsible personnel (e.g., a microbiologist reviewed a batch record). Further, the Quality Assurance Unit did not review and approve the investigation. Finally, your firm failed to implement the corrective/preventative action identified in the investigation. 
 
In your response, your firm states that: 1) your SOP will be revised to require a formal investigation by the Quality Assurance Unit when environmental monitoring action levels are exceeded and 2) retrospective investigations into previous excursions were conducted. You also commit to re-investigate (b)(4) and that any impact on aseptic operations will be assessed by the Quality Assurance Unit. Your response, however, is inadequate because you have not described how you will assess the potential impact on products that have already been distributed.
 
Unapproved New Drug and Misbranding Violations
 
In addition to violating CGMPs, you manufacture and market unapproved new drugs in violation of sections 505(a) and 502(f)(1) [21 U.S.C. §§ 355(a) and 352(f)(1)] of the Act.  Based on the information your firm submitted to FDA’s Drug Registration and Listing System and the information collected during the inspection of your facility, you manufacture the following prescription drugs, including, but not limited to: 
  • Ascor L 500, Ascorbic Acid Injection, USP, 500 mg/mL in 50 mL vial (McGuff Pharmaceuticals)
  • Ascorbic Acid Injection, USP, 500 mg/mL in a 50 mL vial ((b)(6))
  • Ascor L NC, Ascorbic Acid Injection, USP, Non-Corn Source (500 mg/mL in 50 mL vial) (McGuff Pharmaceuticals)
  • Magnesium Chloride Injection, 200 mg/mL, in 50 mL Multi-Dose vial (McGuff Pharmaceuticals)
  • Magnesium Chloride Injection, 200 mg/mL, in 50 mL Multi-Dose vial ((b)(6))
  • Vitamin B-Complex 100 Injection, 30 mL Multi-Dose vial (McGuff Pharmaceuticals) 
These products are drugs within the meaning of section 201(g) of the Act, [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases. Further, they are “new drugs” within the meaning of section 201(p) of the Act [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective for their labeled uses. Under sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)] a new drug may not be introduced into or delivered for introduction into interstate commerce unless an application approved by FDA under either section 505(b) or (j) of the Act [21 U.S.C. § 355(b) or (j)] is in effect for the drug. Based on our information, you do not have any FDA-approved applications on file for these drug products. The marketing of these products, or other applicable products, without an approved application constitutes a violation of these provisions of the Act.
 
Additionally, because the above products are intended for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners, adequate directions cannot be written for them so that a layman can use this product safely for its intended uses. Consequently, their labeling fails to bear adequate directions for their intended uses, causing it to be misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)] Because your products lack required approved applications, they are not exempt under 21 C.F.R. § 201.115 from the requirements of section 502(f)(1) of the Act. The introduction or delivery for introduction into interstate commerce of these products therefore violates sections 301(a) of the Act [21 U.S.C § 331(a)].  
 
You should discontinue manufacturing and distributing all of your unapproved drugs at all facilities immediately. For questions about the regulatory status of your drugs, contact Kathleen Joyce, at 301-796-3329. For assistance in communicating with the FDA concerning the application process for your unapproved drug(s), contact FDA's unapproved drugs coordinator, Dr. Sally Loewke, at 301-796-0710. 

To ensure that all drugs marketed in the U.S., prescription and over-the-counter, have been shown to be safe and effective, FDA published a Compliance Policy Guide (CPG) Section 440.100, Marketed Unapproved Drugs, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070290.pdf. FDA expects manufacturers of products requiring approval to submit applications to the agency showing that their products are safe and effective. The CPG describes the very strict criteria under which the Act permits drugs to be marketed without approval. The CPG also outlines the Agency’s enforcement policies aimed at efficiently and rationally bringing all drugs requiring approved applications into the approval process.  

 
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence and the occurrence of other violations.  It is your responsibility to assure compliance with all requirements of federal law and FDA regulations.

You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction. Other federal agencies may take this Warning Letter into account when considering the award of contracts. Additionally, FDA may withhold approval of requests for export certificates, or approval of pending drug applications listing your facility, until the above violations are corrected. FDA may re-inspect to verify corrective actions have been completed.

Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations and copies of supporting documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the date by which you will have completed the correction. Additionally, your response should state if you no longer manufacture or distribute the drug products manufactured at this facility, and provide the date(s) and reason(s) you ceased production. For discontinued products, you must update the Drug Listing files in accordance with 21 C.F.R. § 207.30(a)(2).
 
Your reply should be sent to the following address: Food and Drug Administration, Attention: Blake Bevill, Director Compliance Branch, 19701 Fairchild, Irvine, California 92612-2445.
 
 
Sincerely,
/S/ 
Alonza E. Cruse
District Director

 

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Thursday, December 23, 2010

Syneron, Inc 12/23/10

  

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 

Los Angeles District
Pacific Region
19701 Fairchild
Irvine, CA 92612-2506
Telephone: 949-608-2900
FAX:   949-608-4415

 

WARNING LETTER

W/L 17-11


CERTIFIED MAIL 
RETURN RECEIPT REQUESTED


December 23, 2010

Mr. Louis P. Scafuri, CEO
Syneron Inc.
3 Goodyear, Suite A
Irvine, California 92618

Dear Mr. Scafuri:
 
During an inspection of your firm located in Irvine, California on August 3, 2010, through August 6, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the eMax System device.  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 the eMax System device is adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. 351(f)(1)(B), because you do not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. 360j(g).  The device is also misbranded under section 502(o) of the Act, 21 U.S.C. 352(o), because you did not notify the agency of your intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. 360(k).  For a device requiring premarket approval, the notification required by section 510(k) of the Act, 21 U.S.C. 360(k), is deemed satisfied when a PMA is pending before the agency, 21 CFR 807.81(b).  The kind of information you need to submit in order to obtain approval or clearance for your device is described on the Internet at http://www.fda.gov/cdrh/devadvice/3122.html.  The FDA will evaluate the information you submit and decide whether your product may be legally marketed.
 
Additionally, the device is misbranded under section 502(o) of the Act, 21 U.S.C. 352(o), in that the device was manufactured, prepared, propagated, compounded, or processed in an establishment not duly registered under 21 U.S.C. 360; was not included in a list required by 21 U.S.C. 360(j); or a notice or other information respecting the device was not provided to the FDA as required by 21 U.S.C. 360(k).

Our inspection also revealed that your eMax System device is misbranded under section 502(a) of the Act, 21 U.S.C. 352(a), in that the labeling for your device, namely the eMax User Manual and eMax product brochure, contain statements which represent or suggest that your device is adequate and effective for skin tightening, which representations or suggestions are false or misleading or otherwise contrary to fact because your device is not adequate or effective for such purposes.

Our inspection also revealed your eMax System device is misbranded under section 502(f)(1), 21 U.S.C. 352(f)(1), in that the labeling for the device fails to bear adequate directions for use for the purposes for which it is intended, because adequate directions cannot be written for skin tightening as stated in the eMax User Manual and product brochure since skin tightening is not an approved indication and there are no such devices cleared for this indication.

Given the serious nature of the violations of the Act, the eMax System device manufactured by your firm is subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that it appears 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.

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 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.
 
In addition, FDA has noted nonconformances with the following Current Good manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at 21 CFR Part 820.  These nonconformities include, but are not limited to, the following:

1. Failure to establish and maintain adequate procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meet acceptance criteria until: (1) the activities required by the Device Master Record (DMR) are completed; (2) the associated data and documentation is reviewed; (3) the release is authorized by the signature of a designated individual(s); and (4) the authorization is dated, as required by 21 CFR 820.80(d).  For example, your firm’s Acceptance Test Procedure (ATP) and “Final Test” form used in the inspection of imported devices (e.g. eMax System) to ensure conformance with specifications, do not explain how to perform the testing or describe which tests are required. 

We have reviewed your response dated August 18, 2010, and have concluded that the adequacy of your response cannot be determined at this time.  Your response stated that you would establish a fully documented procedure for finished goods testing including training, process validation, and an internal audit to verify implementation within 60 days.  Your response also stated that ATP forms on file would be reviewed for compliance by technical team leaders.  Your firm, however, has not provided evidence of implementation of the corrective actions.

2. Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a).  For example, Clinical Complaints form QA70001 states that “ALL FIELDS MUST BE COMPLETE BEFORE YOUR REQUEST WILL BE PROCESSED.”  A review of complaints  (b)(6)   found all fields were not filled out.  There was no documentation on the form stating a reason why the fields were not completed.

We have reviewed your response dated August 18, 2010, and have concluded that the adequacy of your response cannot be determined at this time. Your response stated that QA7001 form was updated to include a statement saying in the case that the information field in the form is not applicable, to add “NA” in the form.  Your response also stated that employees who conduct and/or review clinical investigations would be trained on the revised form no later than September 1, 2010.  Your firm also stated your corrective action involved reviewing previous investigations reported on form QA7001 to determine: (1) if they were completed properly and met all the firm’s requirements by September 15, 2010, and (2) to verify that any “missing data” did not affect the investigation results.  Your firm, however, has not provided evidence of implementation of the corrective actions.

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

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

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

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,
                                                           
                       
Alonza E. Cruse, Director
Los Angeles District                                             

 


 

-

Wednesday, December 22, 2010

Vistar Corporation 12/22/10

  

Department of Health and Human Services' logoDepartment 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-11-12

December 22, 2010

Mr. Wayne L. Entsminger
President
Vistar Corporation
3595 Nw 125th St,
Miami, FI 33167-2413

Dear Mr. Entsminger:

We inspected your seafood processing facility, located at 3595 Nw 125th St. Miami, FL from October 18, 2010 to October 21,2010. 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 frozen cooked ready to eat Snow Crab, your canned pasteurized crabmeat and your frozen cooked lobster are adulterated, in that they have been prepared, packed, or held under insanitary conditions whereby they may have been rendered injurious to health. You may find the Act, the seafood HACCP regulation and the Fish and Fisheries Products Hazards & Controls Guidance through links in FDA's home page at www.fda.gov.

Your significant violations were as follows:

1. You must 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 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 plan for frozen cooked lobster lists a critical limit that does not ensure control over one or more hazards. The HACCP plan does not include the length of the cook cycle, the temperature of the steam, and the minimum or maximum size of the lobster. FDA recommends that you establish these parameters through scientific studies.

• Your firm's HACCP plan for "Crab Product" lists a critical limit of, "Product NTE 40°F at time of receipt" which is not adequate to control for the hazard of pathogen growth during transit. FDA recommends continuous monitoring of product or ambient temperature during transit.

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

• Your firm's HACCP plan for cooked lobster entitled "Frozen or Fresh Spiny Lobster" does not include the monitoring procedure for the length of the cooling cycle, the type of thermometer used to monitor the internal temperature of the product, the method used to monitor the length of the cooling cycle, and the frequency for monitoring the critical factors in the cooling cycle.

• Your firm's HACCP plan for frozen cooked lobster entitled "Frozen or Fresh Spiny Lobster" does not include monitoring for the declaration of presence of sulfiting agents on cartons and labeling, the method and the frequency of monitoring at the "Addition/Labeling of Sulfites CP.

3. You must adequately monitor sanitation conditions and practices during processing to comply with 21 CFR 123.11 (b). However, your firm did not monitor the cleanliness of food contact surfaces, prevention of cross-contamination from insanitary objects, and maintenance of hand washing, hand sanitizing, and toilet facilities with sufficient frequency to ensure control as evidenced by: 

•The employee that received the cooked ready to eat stone crab claws on 10/19/2010 did not wash/sanitize his hands. Our investigator observed the employee handling shipping cartons and mesh bags with exposed stone crab claws while checking the temperature of the product.

•Your firm was splitting frozen, cooked snow crabs and packaging the product into cartons that had liners that were in direct contact with old chemical containers that were not properly cleaned and sanitized. At the end of the packaging process, the plastic liners were folded inside the carton and came into direct contact with the ready to eat frozen stone crabs.

•On 10/19/2010 our investigator observed that two employees conducting the cleaning operation of the electric band saws in processing room (b)(4) did not use any sanitizing solution.

•There was no hot water available at the hand wash station outside of the processing rooms (b)(4) and (b)(4)

•There was no hand soap available at the hand wash station in the ladies' restroom.

•On 10/19/2010 our investigator observed during the cleaning operation of the processing rooms (b)(4) and (b)(4) three hoses ends in direct contact with the floor of the processing rooms.

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

You should respond in writing within fifteen (15) working  days from your receipts  of this letter. Your response should outline the specific things you are doing to correct these violation.  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.

We acknowledge your response to the FDA 483 received on December 7,2010. We will review that submission together with your response to this letter once we have received it. Because your response to the FDA 483 was not received within 15 working days of the end of the inspection we were not able to respond to your submission in this letter.

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

Please send your reply to the Food and Drug Administration, Attention: Emma Singleton, District Director, 555 Winderley Place, Suite 200, Maitland Florida 32751. If you have questions regarding any issues in this letter, please contact Carla Norris at 407-475-4730.

Sincerely,

/s/


Emma R. Singleton
Director, Florida District

 


 

-

Heritage Labs International LLC 12/22/10

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 Kansas City District
Southwest Region
11630 West 80 Street
Lenexa, Kansas 66214-3340
Telephone: (913) 752-2100 

December 22, 2010
 

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

WARNING LETTER
Ref. KAN 2011-03

Mark S. Patterson, President
Heritage Labs International LLC
560 N. Rogers Road
Olathe, Kansas 66062

Dear Mr. Patterson:

During an inspection of your firm located in Olathe, Kansas on June 15 through June 23, 2010, Investigator(s) from the United States Food and Drug Administration (FDA) determined that your firm manufactures In-Vitro Diagnostic Devices (IVD's) including the Appraise® Biometric Collection Tests for Hemoglobin Ale, Microalbumin, Prostate Specific Antigen, Thyroid Stimulating Hormone and Lipids. 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 the Appraise® Biometric Collection Tests for Hemoglobin A1c, Microalbumin, PSA and TSH are misbranded under section 502(o) of the Act, [21 U.S.C.352(o)], because you did not notify the agency of your intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. 360(k). For a device requiring premarket approval, the notification required by section 510(k) of the Act, [21 U.S.C. 360(k)], is deemed satisfied when a PMA is pending before the agency, 21 Code of Federal Regulations (CFR) 807.81(b). The kind of information you need to submit in order to obtain approval or clearance for your device is described on the Internet at http://www.fda.gov/cdrh/devadvice/3122.html. The FDA will evaluate the information you submit and decide whether your product may be legally marketed.

This inspection also revealed that the Appraise® Biometric Collection Tests for Hemoglobin A1c, Microalbumin, PSA and TSH are adulterated within the meaning of section 501 (f)(1)(B) [21 U.S.C. 351(f)(1)(B)] because you do not have in effect an approved application for premarket approval. Our inspection also revealed that the Appraise® Biometric Collection Tests for Prostate Specific Antigen (PSA), Thyroid Stimulating Hormone (TSH), Microalbumin and Lipids are misbranded under section 502(0) of the Act [21 U.S.C. 352(o)] because at the time of registration you did not include these devices in the listing of all devices manufactured by your firm.

Our inspection also revealed that your devices are misbranded under Section 502(a) of the Act [21 U.S.C. 352(a)] and within the meaning of 21 CFR 807.39. Your website (b)(4) displays a large banner which states "FDA Registered" which creates an impression of official approval of your establishment or its products.

We acknowledge the receipt of your July 15, 2010, response to the FDA 483 issued during the June 2010 inspection. These responses were related to the quality system deficiencies noted during the inspection and are not related to the contents of this warning letter. Your letter will be made part of our official permanent records for your firm. You must adequately implement and maintain each corrective action to ensure its effectiveness. Your corrective actions will be assessed during a further inspection. This acknowledgement is not an endorsement of the current operating conditions within your firm.

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.

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: Matthew A. Walburger, Compliance Officer, at the address above. If there are questions regarding the content of this letter please contact Mr. Walburger at (913)752-2104.

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

Sincerely,
/S/
John W. Thorsky
District Director
Kansas City District
 

-

Bauer & Hasselbarth Gmbh 12/22/10

  

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 

10903 New Hampshire Avenue
Silver Spring, MD 20993

December 22, 2010

WARNING LETTER
 

Via United Parcel Service

Mr. Stefan Lenz
General Manager
Bauer & Haselbarth - Chirurg - Gmbh
Sauerbruchstr 7
25479 Ellerau, Germany
 
Dear Mr. Lenz:
 
During an inspection of your firm located in Ellerau, Germany on September 13–16, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Tracheal Tubes, and Vaginal & Rectal Specula.  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 (CFR), Part 820. We received a response from Manfred Salamon, Director R&D & QA dated September 29, 2010 concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address this response below, in relation to each of the noted violations. 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 is validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR 820.75(a). For example, the processes used in the induction welding process have not been validated. There is no documentation to support the parameters used in the (b)(4) welding processes are validated.

Your firm provided no response to this QS regulation violation identified in the review of your Establishment Inspection Report.

2. Failure to establish and maintain adequate procedures for implementing corrective and preventive action to include 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, your firm has not been analyzing non-conformance (internal complaint) information to identify existing or potential causes of the nonconforming product.  Not all non-conformances identified during finished product inspections (e.g. product associated with rework orders) are handled under the non conformance (internal complaint) procedure.

We reviewed your response and concluded the adequacy cannot be determined at this time. Your firm provided a revision of “Instructions for Procedure – VA.832 Managing Defective Products Decision Request/Complaint”, QMM Revision D, dated September 28, 2010. This procedure discussed error/fault findings and information transfer (internal complaint). However, your firm did not provide evidence of implementation of the corrective action to ensure internal complaints are used to identify existing and potential causes of nonconforming products.

3. Failure to establish and maintain adequate procedures for implementing corrective and preventive action that include identifying the action(s) needed to correct and prevent recurrence of nonconforming product and other quality problems, as required by 21 CFR 820.100(a)(3).  For example:

•18 rework orders observed since January 2010 for the Weitlaner retractors identified non conformance due to the presence of rust on the devices.  However, there was no documentation of an investigation to identify appropriate corrective actions.
•Corrective and preventive actions that have been made pertaining to external and internal complaints have not had documented investigations and have not included verification of corrective actions.

We reviewed your response and concluded that it is not adequate.  Your firm revised “Instructions for Procedure VA.832 Managing Defective Products Decision Request/ Complaints”, Revision D, Dated September 28, 2010” for the handling of internal and external complaints.  Your firm stated this procedure is currently being followed and will be reviewed for its effectiveness and compliance.  However, your firm did not provide evidence that the 18 Weitlaner retractor rework orders were adequately investigated to identify appropriate corrective actions.

4. Failure to develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications.  Where deviations from device specifications could occur as a result of the manufacturing process, the manufacturer shall establish and maintain process control procedures that describe any process controls necessary to ensure conformance to specifications, as required by 21 CFR 820.70(a). Specifically, the (b)(4) (welding process used for (b)(4) (welding) of components for various assemblies is not consistently using the recommended settings that are maintained in (b)(4).  For example: 

• The  (b)(4) indicates the time setting as (b)(4) minutes and the Power setting as (b)(4). However, the production staff is using (b)(4) minutes for the elapsed time with a power of (b)(4).

• The Power (b)(4) was changed from (b)(4) to (b)(4) (used for article (b)(4)).

• There is no procedure to provide guidance for the permissible adjustment of the process parameters and to establish acceptable working ranges specific to the (b)(4) welding process.

We reviewed your response and concluded that it is not adequate. Your firm provided procedure “QS – SOP – QSA 04-04, “((b)(4) (b)(4))” Dated September 20, 2010”. However, this procedure did not provide adequate guidance for the permissible adjustment of the process parameters or acceptable working ranges specific to the (b)(4) welding process. Additionally, your firm provided no evidence of implementation for the corrective actions to ensure the production staff is currently using the correct time and power settings for the (b)(4) welding process.

5. Failure to establish and maintain adequate 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 of nonconformance shall include a determination of the need for an investigation and notification of the persons or organizations responsible for the nonconformance. The evaluation and any investigation shall be documented, as required by 21 CFR 820.90(a). Specifically, rework orders made as a result of non conformance for sharp or rough surfaces of vaginal or rectal specula have not been investigated to identify the cause of the nonconformities. For example:

• Rework Order (b)(4) documents that on final inspection, (b)(4) pieces of Vaginal Specula were identified that were not adequately deburred. There was no investigation to determine why the processes to adequately prepare the surface were not effective.

• Rework order (b)(4) documents that on June 28, 2010 final inspection identified (b)(4) pieces of Beckman rectal specula had prongs that were too sharp.There was no investigation to determine why the product had not been finished correctly.

We reviewed your response and concluded that it is not adequate. Your firm revised “Instructions for Procedure VA.832 Managing Defective Products Decision Request/ Complaints”, Revision D, Dated September 28, 2010” for the handling of internal and external complaints. Your firm stated this procedure is currently being followed and will be reviewed for its effectiveness and compliance. However, your firm did not provide evidence that the Rework Orders for (b)(4) and (b)(4) were adequately investigated to identify cause of the nonconformities. 

6. Failure to establish and maintain adequate procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 CFR 820.80(d).  Specifically, the finished device inspection of Vaginal and Rectal Specula do not fully document inspection of devices for sharp or rough edges on the surface. For example:

• Work Order (b)(4) for the Brinkerhoff Rectal Specula only includes documentation of the dimension characteristics of the device.

• Work Order (b)(4) for the Auvard Vaginal Specula has a notation that devices should be free from sharp edges but does not document that each piece is inspected.

• Work Order (b)(4) for the Trelatt Vaginal Specula does not document that the devices have been inspected for sharp or incorrect surfaces or edges.

We reviewed your response and concluded that it is not adequate. Your firm provided corrections using CAPA plan No. (b)(4). This CAPA states your firm will use a computer system to store inspection results and to monitor data processing for corrective action  planning. However, your firm did not provide evidence of implementation for the corrective actions to ensure Work Orders (b)(4)(b)(4), and (b)(4) met acceptance criteria as finished devices. 

7. Failure to establish and maintain adequate procedures to ensure that device history records for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record, as required by 21 CFR 820.184. Specifically, not all device history records are complete and demonstrate that all processing steps have been completed. For example, device history records for work order numbers (b)(4)(b)(4), and (b)(4) for Brinkerhoff Rectal Specula were released for distribution with largely incomplete documentation of the completion of specified processing steps.

We reviewed your response and concluded that the adequacy cannot be determined at this time. Your firm provided an instruction document to identify documents belonging to the devices and to ensure manufacturing steps are properly fill-in and signed. Additionally, your staff was trained on the instructions for handling shop orders (manufacturing papers) on September 21, 2010. However, your firm did not submit any documentation specific to the implementation of the corrective action.

8. Failure to establish adequate 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. Quality audits shall be conducted by individuals who do not have direct responsibility for the matters being audited, as required by 21 CFR 820.22. For example, the Director R&D and QA is performing the internal audits for the Design areas, Non Conformance, Quality Monitoring and CAPA. However, the Director of R&D and QA is directly responsible for each of these audited areas.

Your response to this observation appears to be adequate. Your firm has rewritten the 2010 audit plan and assigned a new medical engineer to conduct the audits who does not have direct responsibility for the matters being audited.

Our inspection also revealed that your Tracheal Tubes, and Vaginal & Rectal Specula devices are misbranded under section 502(t)(2) of the Act 21 USC 352 (t)(2), in that your firm failed or refused to furnish material or information respecting the devices that is required by under section 519 of the Act, 21 USC 360i, and 21 CFR Part 803 – Medical Device Reporting (MDR) Regulation.  Significant deviations include, but are not limited to:

Failure to develop, maintain and implement written MDR procedures as required by 21 CFR Part 803.17.  As a manufacturer, you must develop, maintain, and implement written MDR procedures for the following:

(a) Internal systems that provide for:

(1) Timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements;

(2) A standardized review process or procedure for determining when an event meets the criteria for reporting under this part; and

(3) Timely transmission of complete medical device reports to manufacturers or to us, or to both if required.

(b) Documentation and recordkeeping requirements for:

(1) Information that was evaluated to determine if an event was reportable;

(2) All medical device reports and information submitted to manufacturers and/or us.

We reviewed your response dated September 29, 2010, and concluded that it is not adequate because procedure “VA 830 Observation and Reporting System Harmonized with MPS and FDA-MDR” does not address the above requirements.

Please note that your procedure contains reporting requirements for other regulatory or competent authorities. To insure that your firm can meet its regulatory obligations for 21 CFR Part 803, we highly recommend that you develop your MDR procedure as a separate document.

If your firm wishes to submit MDR reports via electronic submission you can follow the directions stated at the following URL:

http://www.fda.gov/MedicalDevices/deviceregulationandguidance/guidancedocuments/ucm094529.htm#where

If you wish to discuss MDR reportability criteria, you may contact Sharon Kapsch, Branch Chief; Reporting Systems Monitoring Branch, to schedule further communications, at 301-796-6104 or by email at Sharon.Kapsch@fda.hhs.gov.

Given the serious nature of the violations of the Act, the Tracheal Tubes, and Vaginal & Rectal Specula 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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Aqueduct Medical, Inc. 12/22/10

  

Department of Health and Human Services logoDepartment 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 


WARNING LETTER


VIA UPS EXPRESS


December 22, 2010


Benjamin Krempel
Chief Executive Officer
Aqueduct Medical, Inc.
665 Third Street, Suite 20
San Francisco, CA 94107


Dear Mr. Krempel:


During an inspection of your firm located in San Francisco, California on April 22, 2010, through May 17, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the AqueCool™ Rapid Recovery System, AqueVest™ device, and the AqueCool™ Masque device. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(b), 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.


Our inspection revealed that the AqueCool™ Rapid Recovery System, AqueVest™ device and AqueCool™ Masque devices are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. 351(f)(1)(B), because you do not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. 360j(g). The device is also misbranded under section 502(o) the Act, 21 U.S.C. 352(o), because you did not notify the agency of your intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. 360(k). Specifically, you are marketing the device with claims of rapid recovery and/or accelerated healing, which exceeds the limitations of 21 CFR 890.9 for devices classified under 21 CFR 890.5720 as Water circulating hot or cold packs. For a device requiring premarket approval, the notification required by section 510(k) of the Act, 21 U.S.C. 360(k), is deemed satisfied when a PMA is pending before the agency. 21 C.F.R. 807.81(b). The kind of information you need to submit in order to obtain approval or clearance for your device is described on the Internet at http://www.fda.gov/cdrh/devadvice/3122.html. The FDA will evaluate the information you submit and decide whether your product may be legally marketed.
 

This inspection also 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 13, 2010, concerning our investigator's observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:


1. Failure to establish and maintain adequate procedures to ensure that where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR 820.75(a). Specifically, there is no process validation study for the radio frequency welding process that is used to weld flanges onto the bladder that is a component of the AqueCool masques and AqueVests.


We reviewed your response and conclude that it is inadequate because you have not provided any evidence of a corrective action or systemic corrective action. You provided your product specifications list for the face mask with a list of quality control tests you use. You also included a letter from (b)(4) that indicates no formal validation is required because you use 100% static inflation testing and visual inspection. It is unclear what this testing entails and how it absolves your firm from completing the required process validation for a welding process.


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


a. Complaint Investigation Reports (CIR) for Customer Service Reports (CSR) # (b)(4) do not include investigations into the cause of non-conformities related to leaking vests and masques.


b. There were two different Customer Service Reports (CSR) with the number (b)(4) and two different CSRs with the number (b)(4). These reports represented different complaints but were given duplicate CSR numbers.


c. Twenty-eight of twenty-eight Customer Service Reports were not adequately completed to include: name of the device, date the complaint was received, or customer address and phone number.
 

We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or a systemic corrective action. You provided training records for two employees, although it is not clear which procedures these documents cover. You also provided a blank "CSR Log Sheet" and a "Weekly Status Report" dated July 26 - July 30, 2010. It is not clear how these documents address the above deficiency.


3. Failure to ensure that any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications shall be reviewed, evaluated, and investigated, unless such investigation has already been performed for a similar complaint and another investigation is not necessary, as required by 21 CFR 820.198(c). For example:


a. The documents: "Quality Records Policy/Procedure," (b)(4)."Customer Service Report," (b)(4) (CSR);and "Customer Investigation Report-CIR," (b)(4) serve as the complaint handling procedure and lack instructions or guidance on how to review, evaluate, and investigate any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications.


b. CSR#(b)(4)outlined a complaint that reported a ''patient had a very bad reaction to the product." There was no investigation. The CSR indicates that the action or investigation required was a ''refund.''


c. No investigation was conducted for the following complaints that reported leaking masques: CSR#(b)(4)(no date), (b)(4)


d. No investigation was conducted for the following complaints that reported missing device components: CSR#(b)(4)


We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You provided training records for two employees, a blank "CSR Log Sheet," and a "Weekly Status Report," dated July 26 - July 30, 2010. You also provided Engineering Change Order Form No.(b)(4) The specific change is not outlined on this form.


4. Failure to ensure that any complaint that represents an event which must be reported to FDA under part 803 of this chapter shall be promptly reviewed, evaluated, and investigated by a designated individual(s) and shall be maintained in a separate portion of the complaint files or otherwise clearly identified, as required by 21 CFR 820. 198(d). For example:


a. Customer Service Report#(b)(4) reported a leaking AqueCool Masque, but the leaking masque was not identified as a device failure per the answer to the first question in the Post-Service Questionnaire on the Customer Service Report.


b. Customer Service Report#(b)(4) reported the, ''patient had a very bad reaction to the product," but problem was not identified as a device failure, nor was it identified as an "MDD adverse event, Vigilance reporting event," on the Post-Service Questionnaire section of the Customer Service Report.


We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You provided training records for two employees, a blank "CSR Log Sheet," and a "Weekly Status Report," dated July 26 - July 30, 2010. You also provided Engineering Change Order Form No. (b)(4) The specific change is not outlined on this form.


5. Failure to establish and maintain documented instructions, standard operating procedures (SOPs), and methods that define and control the manner of production, as required by 21 CFR 820.70(a)(1). Specifically, according to the Operations Manager, there is no documented instruction for the life test for flow rate and temperature. The life test is performed on newly produced and repaired AqueCool Rapid Recovery Systems to ensure each system meets specified requirements.


We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You explain that document (b)(4)(AqueCool service manual) was updated to include a life test check for each unit. The flow chart located in (b)(4) is not prescriptive in the tests required for each type of failure.


6. Failure to establish and maintain procedures for changes to a specification, method, process, or procedure, as required by 21 CFR 820.70(b). Such changes shall be verified or where appropriate validated according to 21 CFR 820.75, before implementation and these activities shall be documented. For example:


a. "Production and Process Control Policy / Procedure," (b)(4) states, " ... changes to specifications, equipment, assembly procedures or related manufacturing processes will be reviewed and approved before usage." However, it lacks the requirement of verification or validation of such changes before implementation.


b. The "Production and Process Control Policy / Procedure" was not implemented when the continuity test was discontinued for the AqueCool Rapid Recovery System. This change was not reviewed and approved prior to implementation.
 

c. The "Production and Process Control Policy / Procedure" was not implemented when the (b)(4) thermocouple temperature recorder, digital multimeter, and flow rate meter were replaced by the AqueCool Service Tool. This change was not reviewed and approved prior to implementation.


We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. The document you provided, (b)(4) is the AqueCool service manual, and not a manufacturing process procedure. This document does not appear to include procedures for changes to a specification, method, process, or procedure, as required by 21 CFR 820.70(b). It also does not appear to include validation or verification of the AqueCool Service Tool. You explain that verification is completed by showing consistency between the original test set-up and AqueCool Service Tool, but this is not adequate to address the requirements of this part.


7. Failure to establish and maintain adequate procedures to ensure that all inspection, measuring, and test equipment, including mechanical, automated, or electronic inspection and test equipment, is suitable for its intended purpose and is capable of producing valid results, as required by 21 CFR 820.72(a). For example, the "Production and Process Control Policy / Procedure", (b)(4) states test equipment is to be inspected on a (b)(4) basis for maintenance and calibration. The calibration equipment inspection was conducted (b)(4) only from January 8, 2007, to October 4, 2007. The last calibration equipment inspection was conducted on April 2, 2008. The AqueCool Service Tool required a calibration on October 26, 2008, and was used until April 22, 2010, despite requiring calibration.


We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You explain that all equipment requiring calibration has been brought up to date and you provided the calibration certificates along with a calibration log that is reviewed at the monthly manager meeting. You did not provide a procedure or evidence of any corrective actions.


8. Failure to establish and maintain adequate procedures to control all documents, as required by 21 CFR 820.40. For example, the "Document and Data Control Policy / Procedure," (b)(4) states documents released to the electronic vault are password protected as a read-only document to prevent unwanted or uncontrolled changes and the physical document vault is locked. However, the electronic vault is not currently password protected nor is the physical document vault locked.


We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action, or systemic corrective action. You indicate that controlled documents are now stored in a locked cabinet where the Operations Manager holds the only key. In addition, the electronic vault users have unique user names and passwords to track who makes changes to controlled documents. There was no procedure or other evidence provided to support these changes were made.


9. Failure to retain all records required by this part for a period of time equivalent to the design and expected life of the device, but in no case less than two years from the date of release for commercial distribution by the manufacturer, as required by 21 CFR 820.180(b). Specifically, the Device History Records for the AqueCool Rapid Recovery Systems serial number (b)(4) and serial number (b)(4) could not be located.


We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or a systemic corrective action. You indicate that you created replacement Device History Files for #(b)(4) and #(b)(4) however it is unclear what you have done to prevent this type of problem from recurring.


10. Failure to establish and maintain adequate procedures for identifying training needs and ensuring that all personnel are trained to adequately perform their assigned responsibilities and to ensure the training shall be documented, as required by 21 CFR 820.25(b). Specifically, the Operations Manager is responsible for document control, purchasing/supplier evaluation, control of monitoring and measuring devices, disposition of non-conforming products, and work environment control, yet the Operations Manager has not been trained to the respective policies/procedures.


We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You provided training records for two employees indicating retraining on several procedures. It is not clear what revision of each of the procedures was part of the training, or what the procedures include.


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 this part and the manufacturer's established quality policy and objectives, as required by 21 CFR 820.20(c). For example, the last management review was conducted on August 6, 2007. The meeting agenda for the August 6, 2007, meeting has the next meeting scheduled for February 25, 2008. There is no evidence that this February meeting occurred or that any subsequent meeting occurred. According to the Chief Executive Officer, there is currently no schedule for management reviews.


We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You provided, "Management Review Policy/Procedure," (b)(4) The revision date of this procedure dates back to 2004, so it is unclear how providing this procedure for review addresses the above deficiency since it does not appear the procedure was being followed at the time of inspection. You also provided "Internal Audits Policy/Procedure," (b)(4) which appears to be an audit record. This record states that an audit was conducted from July 7, 2010, through July 12, 2010, and that all procedures were audited except design and development. The procedure/record does not appear to correspond directly to all the procedures within the scope of the audit. There is no procedure dictating how the audit is to be conducted.


12. Failure to establish and maintain procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements. These quality audits shall be conducted by individuals who do not have direct responsibility for the matters being audited, as required by 21 CFR 820.22. For example, the "Aqueduct Medical Responsibility Assignments" document, updated April 20, 2010, indicates the Chief Executive Officer has the responsibility of conducting quality audits. The Chief Executive Officer also has direct responsibility over the matters being audited such as design and development, control of non-conforming product, corrective and preventive action, infrastructure management, and work environment control.

 

We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You provided an organizational chart and a list of responsibilities as they pertain to the CEO, Engineering, and the Operations Manager. It is indicated that the CEO has responsibility for conducting quality audits. It appears the CEO also has direct responsibility over design and development and work environment control. The quality audits are to be completed by those who do not have direct responsibility over the matters being audited.


Our inspection also revealed that your AqueCool Rapid Recovery System and associated masks and vests used as accessories with the system are misbranded under section 502(t)(2) of the Act, 21 U.S.C. 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. 360i, and 21 C.FR Part 803 - Medical Device Reporting (MDR) regulation.


Significant deviations include, but are not limited to, the following:


1. Failure to develop, implement, and maintain complete MDR procedures for the documentation and record keeping requirements for all medical device reports and information submitted to manufacturers and/or FDA, as required by 21 CFR 803.17(b)(2).


2. Failure to maintain written MDR procedures as evidenced by the use of an out-of-date FDA guidance document for MDR reporting that is part of "Quality Records Policy / Procedure," (b)(4) The out-of-date guidance is part of a table on page 7 of the procedure.


We reviewed your response and conclude that its adequacy cannot be determined because you have not submitted your written MDR procedure (b)(4), that contains the table, "FDA in icedence [sic] Reporting Guideline." Therefore, the adequacy of this procedure cannot be determined.


A follow up inspection will be required to assure that corrections are adequate.


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 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.


Your response should be sent to: Mr. Russell A. Campbell, Compliance Officer, 1431 Harbor Bay Parkway, Alameda, CA 94052. If you have any questions about the content of this letter please contact: Mr. Campbell at (501)337-6861.


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/
Barbara J. Cassens
District Director
San Francisco District
U.S. Food and Drug Administration

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