Abbott Laboratories, Inc. 24-Sep-02

Departmentof Health and Human Services            PublicHealth Service

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Chicago District
550 West Jackson Blvd., 15^th Floor
Chicago, Illinois 60661
elephone: 312-353-5863

September 24, 2002

WARNING LETTER

CHI-25-02

CERTIFIED MAIL

RETURN RECEIPT REQUESTED

Mr. Miles D. White

Chairman & CEO

Abbott Laboratories, Inc.,

One Abbott Park Road, Bldg AP6

Abbott Park, IL 60064

Dear Mr. White:

An inspection of Abbott?s pharmaceutical manufacturing operations in BuildingAP- 16,located at Abbott Park, IL, was conducted from June 18 through July 24,2002,: Theinspection covered the production of [redacted]. During the inspection,our investigators documented significant violations of current Good ManufacturingPractice (cGMP) regulations listed Title 21, Code of Federal Regulations (CFR),in your firm?s production of [redacted]. These violations cause this productto be adulterated within the 501(a)(2)(B) of the Federal Food, Drug, and CosmeticAct (the Act).

1. Failure to conduct a thorough investigation when a batch or any of its components fail to meet specifications [21 CFR 211.192]. For example:

During the production of [redacted] lot#79298AF00, black, magnetic particulateswere observed in the granulation. The corrective action taken was to reconditionthe granulation by [redacted] that were expected to eliminate the particles.No validation study was performed to establish that this procedure would successfullyeliminate all of the particles.

During processing, lot #79298AF00 was stored in containers numbered from 1-153. After finding metal particulate contamination in tablets held in container #153, your firm?s investigation covered the tablets held in container# 152 only. No additional inspection of tablets held in containers #l-151 was conducted

During the production of Erythrocin Stearate Tablets, lot #81420AF00, a metalparticle was observed on the surface of one tablet held in container was heldin a total of nine containers numbered from 1 to 9. After the remaining tabletsheld in container #9 were destroyed, your firm visually the tablets held incontainer #8 and no re-examination of the tablets held in containers #1-7 wasperformed.

2. Failure to have adequate written procedures for procedures and process controlto assure that drug products have the identity, strength, quality and puritythey purport or are represented to possess [21 CFR 211.100(a)]. For example:

[redacted] tablet lot #79298AF00 was one of the batches included in the process validation study for this product. This lot was not produced using the manufacturing process discussed in the validation study protocol. Lot #79298AF00 was subjected to several reconditioning steps, due to particulate contamination, that were not listed in the master batch record. Some of the actions taken with respect to this lot, such as the hand pouring of the granules from a drum and [redacted] were steps that were performed for the production of the two additional [redacted] lots used in the validation study.

The master batch manufacturing instructions for the production of [redacted] differ from the procedures used in manufacturing the batches produced in the validation study. The drying process for the tablet granulation component used in the validation batches used a different type of dryer and different time and temperature parameters from the procedures directed in the master batch manufacturing.

3, Failure to clean, maintain and sanitize, at appropriate intervals, equipment and utensils used in the manufacture, processing, packing, or holding of a drug product [21 CFR 211.67(a)]. For example:

Your firm determined that black particles found in tablet granulations was due to the disintegration of the mill?s drive damper and grease seals. Your firm also determined that metal particles clinging to the surface of one tablet was due to the tablet press turret rubbing the upper guard, caused by a worn Neoprene mounting pad. In both examples, there was no established schedule for inspecting or replacing these parts.

At the conclusion of the inspection, our investigators issued the FDA 483, List of Inspectional Observations, to Kay E. Peel, Vice President, Quality Assurance, PPD. A copy of the FDA 483 is enclosed.

This letter and the FDA 483 are not intended to be an all-inclusive list ofdeficiencies at your facility. It is your responsibility to ensure that thedrug products you manufacture are in compliance with the Act and the regulationspromulgated under it. Federal agencies are routinely advised of Warning Lettersissued so that they may take this information into account when consideringthe award of government contracts.

You should take prompt action to correct deficiencies at your facility. Failureto implement corrective measures may result in further regulatory action withoutnotice. These actions may include seizure of your products or injunction.

You should notify this office in writing, within 15 working days of receipt of this letter, of the specific steps you have taken to correct the deficiencies at your firm and prevent their recurrence. Your reply should be directed to the attention of George F. Bailey.

We have received Ms. Peel?s written response, dated August 6, 2002, regarding inspectional observations on the FDA 483. We note that, in response to FDA 483 item #2, Abbott has committed to running three additional validation batches of [redacted] and that a target date for completion of this activity is scheduled for October 31, 2002. Please notify this office when you have completed the additional validation batches. With regard to that commitment and the other corrective steps Ms. Peel indict underway or have been completed, we will consider your FDA 483 response in conjunction with any response to p Warning Letter and will determine the acceptability of your responses during a subsequent follow-up inspection.

Sincerely,

/s/

Arlyn H. Baumgarten

District Director

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21st Century Sports Nutritionals, Inc. 13-Jun-02

Departmentof Health and Human Services            PublicHealth Service

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Food and Drug Administration
Rockville, MD 20867

WARNING LETTER
June 13, 2002

President/Owner
21^st Century Sports Nutritionals, Inc
745 Hollywood Blvd., N.W.
Fort Walton Beach, Florida 32548

Ref: 02-HFD-312-05

Dear Sir or Madam

This letter is written in reference to your firm?s marketing of the products,Phenylkinetics, Libido Magic for Men, and Libido Magic for Women. Accordingto your Internet web site, http://www.2lcenturysports.com, Phenylkinetics contains,among other ingredients, norephedrine HCI, Libido Magic for Men contains, amongother ingmdiellts, 1R, 2s norephedrine HCI, and Libido Magic for Women contains,among other ingredients, 1R, 2s not-ephedrine HCI. Statements on your Internetweb site, indicate that these products are intended for stimulating sexual interestand function and/or for weight loss.

Although your web site represents these products as dietaty supplements, forexample by statements such as, " . . .Energy Supplements.. .?* and ".. .sports supplements.. . *?, they cannot be so considered because the norephedrineHCI used in your products appears to be a synthetic compound that is not derivedfrom any botanical source. Synthetic norephedrine HCI is not plant-derived andcannot, therefore, be considered a constituent or extract of a botanical source.Consequently, FDA has determined that synthetic ephedrine alkaloids am not ?dietaryingredients" as defined in the Federal Food, Drug and Cosmetic Act [theAct, Section 201(ff)(1)].

Therefore, products containing synthetic ephedrine alkaloids do not fall underthe dietary supplement regulatory scheme. Based on their intended uses, to affectthe structure or function of the body, these products are drugs within the meaningof Section 201(g) of the Act. Such products are considered drugs when theirintended use is established by structure injunction claims, such as those thatappear on your web site. Some of the claims on your Internet web site, http://www.21centurysports.com,from which these products may be ordered, state, for example, ". . Phenylkinetics..designed to promote weight loss through rapid metabolization of stored fat withoutcausing that bouncing off the walls? feeling?. , .?*, ". , . Libido Magicfor Men.. .increased sexual function by raising testosterone levels and enhancingblood circulation needed to support firmer, longer lasting erections...,? and" . . Libido Magic for Women.. . stimulate female sexual desire, intensifyorgasm strength and longevity while heightening sexual satisfaction.. .".

As drugs, the labeling claims made for these products subject them to the requirements for new drugs [Section 201(p) of the Act] because there is no evidence that these products are generally Page 2 - 21" Century Sports Nutritionals recognized as safe and effective for their claimed uses.

Under Section 505(a) of the Act, a "new drug" may not be introducedor delivered for introduction into interstate commerce unless an FDA-approvednew drug application is in effect for such drug. Because your products are notthe subjects of approved NDA?s, they may not be marketed in the United Statesand their continued distribution violates Section 505 of the Act.

This letter is not intended to be an all-inclusive review of your Internet web site nor all labeling and products your firm markets. The violation of the Act described above is not intended to be an all-inclusive list of violations concerning your firm and its products. It is your responsibility to ensure that all products marketed by your firm, including other synthetic ephedrine alkaloid products, are in compliance with the Act and its implementing regulations.

We request that you take prompt action to correct these violations. Failure to promptly correct violations may result in enforcement action being initiated by the FDA without further notice. The Act provides for the seizure of illegal products and for injunction against the manufacturer and/or distributor of illegal products.

Please notify this office within fifteen (15) working days of receipt of this letter as to the specific steps you have taken to correct the stated violations. You should also include an explanation of each step being taken to identify and make corrections to assure that similar violations will not recur. 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 implemented.

Your reply should be sent to the attention of Ms. Vesna Stanoyevitch, Compliance Officer, at the Food and Drug Administration, Center For Drug Evaluation and Research, Office of Compliance (HFD-310). Metropark North I, 7520 Standish Place, Rockville, MD 20855.

Sincerely yours,

/s/

David J. Horowitz, Esq.
Acting Director
Office of Compliance
Center for Drug Evaluation and Research
Food and Drug Administration

 

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A. Friscia Seafoods Inc 23-Apr-02

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration

San Francisco District

1431 Harbor Bay Parkway

Alameda, CA 94502-7070

Telephone: 510-337-6700

VIA FEDERAL EXPRESS

Our Reference: 2945025

April 23, 2002

WARNING LETTER

Anthony S. Friscia, President

A. Friscia Seafoods, Inc.

555 Francisco Street

San Francisco, California 94133

Dear Mr. Friscia:

On November 19-20 and December 3, 2001, we inspected your seafood processingfacility, located at 555 Francisco Street, San Francisco, CA. We found thatyou have serious deviations from the seafood HACCP regulations in Title 21,Code of Federal Regulations, Part 123 (21 CFR 123). These deviations cause yourAhi, Mahi, Tombo Tuna, and Cooked Crab to be adulterated within the meaningof Section 402(a)(4) of the Federal Food, Drug, and Cosmetic Act (the Act),in that the fishery products have been prepared, packed, and held under insanitaryconditions whereby they may be rendered injurious to health. You may find theAct and the seafood HACCP regulations through links in FDA? s home page at www.fda.gov.See attached handout, which gives information on how to obtain the Fish &Fisheries Products Hazards & Controls Guidance, 3ti edition, June 2001.

Your serious HACCP deviations are as follows:

1. You must have a HACCP plan that lists the critical limits that must be metto comply with 21 CFR 123.6(c)(3). However, your firm? s HACCP plans for Ahi,Mahi, and Tombo Tuna list critical limits, "Cooler temp not to exceed [redacted]degrees F for more than 4 hours in a 24 hour period. Cooler temp not to exceed[redacted] degrees F control cumulative," at the receiving critical controlpoint that is not adequate to control histamine formation.

FDA recommends that either:

All lots received are accompanied by transportation records (e.g., temperaturerecording chart) that show the fish were held at or below 40?F throughout transit

OR

For fish held under ice or other cooling media at the time of delivery--thereis an adequate quantity of ice or other cooling media to completely surroundthe product

OR

For fish delivered with a total transit time of 4 hours or less, the internaltemperature of a representative number of fish in the lot at the time of deliveryis not more than 40?F.

2. You must have a HACCP plan that lists the critical control points to complywith 21 CFR 123.6(c)(2). However,

1. Your firm?s HACCP plans for Ahi, Mahi, and Tombo Tuna do not list the critical control point of storage for controlling the food safety hazard of scombrotoxin formation. FDA recommends that refrigerated seafood products be held at 40?F or less and that the temperature be monitored continuously by means of a temperature data recorder or by using an alarm system.


2. Your firm?s HACCP plan for Cooked Crab does not list the critical control point of storage for controlling the food safety hazard of bacterial pathogen growth. FDA recommends that refrigerated seafood products be held at 40?F or less and that the temperature be monitored continuously by means of a temperature data recorder or by using an alarm system.

3. Since you chose to include corrective actions in your HACCP plan, your describedcorrective actions must be appropriate to comply with 21 CFR 123.7(b). However,your corrective action plan for Cooked Crab at the cooking critical controlpoint is not appropriate. Your corrective action plan does not address the correctiveaction to be taken when your time-temperature critical limit is not met (i.e.,[redacted]minutes at [redacted] degrees F). Your corrective action plan should also addresscorrecting the cause of the deviation and ensuring that unsafe product (i.e.,under-processed product) does not reach consumers.

4. You must maintain sanitation control records that document the monitoringand corrections applied to the following to comply with 21 CFR 123.1l(c):

• Safety of water


• Condition and cleanliness of food-contact surfaces


• Prevention of cross-contamination


• Maintenance of hand-washing, hand-sanitizing, and toilet facilities


• Protection from adulterants


• Labeling, storage, and use of toxic compounds


• Employee health conditions


• Exclusion of pests

5. You must have a HACCP plan that lists the food safety hazards that are reasonablylikely to occur, to comply with 2 1 CFR 123.6(c)( 1). However, your firm?s HACCPplan for Cooked Crab does not list the food safety hazard of natural toxins.

6. You must adequately monitor sanitation conditions and practices during processing,to comply with 21 CFR 123.1 l(b). However, your firm did not monitor the followingareas of sanitation with sufficient frequency to ensure control:

a. Your firm failed to monitor the condition and cleanliness of food contactsurfaces as evidenced by our investigator observing an employee using a telephonewhile wearing latex gloves and subsequently handling ready-to-eat crabmeat withoutwashing and sanitizing the gloves.

b. Your firm failed to prevent cross-contamination from insanitary object tofood or food-packaging material as evidenced by our investigator observing employeesroutinely packing ready-to-eat crabs into recycled boxes that were previouslyused to package fresh and frozen crabs.

At the conclusion of the inspection, the deviations were listed on Form FDA483 and discussed with you. A copy of this form is enclosed for your ready reference.This list is not meant to be an all-inclusive list of violations. You are responsiblefor ensuring that your processing facility operates in compliance with the Act,the seafood HACCP regulations, and the Good Manufacturing Practice regulations(21 CFR 110).

We may take further action if you do not promptly correct these violations.For instance, we may take further action to seize your products and/or enjoinyour firm from operating.

Please respond in writing within fifteen (15) working days of receipt of thisletter. More than four months have elapsed since FDA inspection. Please providethis office with information on what progress you have made in achieving FDAcompliance with the seafood HACCP regulations. You may wish to include in yourresponse documentation that would assist us in evaluating your corrections.If you cannot complete all corrections before you respond, we expect that youwill explain the reason for your delay, and state when you will correct anyremaining deviations.

Your response should be directed to: Ms. Harumi Kishida, Compliance Officer,U.S. Food and Drug Administration, 143 1 Harbor Bay Parkway, Alameda, CA 94502-7070.

If you have any questions regarding any issue in this letter, please contactMs. Kishida at (510) 337-6824.

Sincerely,

Dennis K. Linsley

District Director

San Francisco District

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