| Public Health Service Food and Drug Administration |
Los Angeles District |
Department of Health and Human ServicesWARNING LETTER
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
W/L 38-11
April 29, 2011
Mark S. Phillips, President
Standard Homeopathic Company
210 W 131st St
Los Angeles, CA 90061-1618
Dear Dr. Phillips:
During our September 8, 2010 to October 28, 2010 inspection of your pharmaceutical manufacturing facility, Standard Homeopathic Company, located at 210 W 131st Street, Los Angeles, California, investigators from the Food and Drug Administration (FDA or Agency) identified significant violations of Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations (C.F.R.), Parts 210 and 211. These violations cause your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 351(a)(2)(B)) in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
In addition, FDA reviewed your firm’s labeling submitted to the export certificate program for homeopathic drug products and labeling and marketing information found on your website at the internet address http://www.hylands.com. This review revealed that your firm is marketing drugs that are misbranded in violation of sections 502 and 503 of the Act (21 U.S.C. §§ 352 and 353).
We have reviewed your firm’s response of November 10, 2010, and note that it lacks sufficient corrective actions.
CGMP Deviations
Specific violations observed during the inspection include, but are not limited, to the following:
1. Your firm does not have adequate written procedures for production and process controls designed to assure that the drug products you manufacture have the identity, strength, quality, and/or purity they purport or are represented to possess [21 C.F.R. § 211.100(a)].
For example, your firm’s mixing times in the approved records for Belladonna, Chamomilla, Calcarea Phos., and Coffea Cruda 1X dilutions, and the approved record for Hyland's Teething Tablets, are not supported by adequate process validation.
We acknowledge your action to recall the Hyland’s Teething Tablets and your commitment to ensure that all (b)(4) tablet batch records will accurately reflect the times established in your mixing studies conducted with the 150 gallon (b)(4) and the 15 gallon (b)(4) mixers. However, we cannot consider your response adequate until you scientifically justify the use of surrogates, such as (b)(4) , in your validation study instead of the actual ingredients used in your products. There is no assurance that the surrogates have similar mixing characteristics, particle size distribution, or other potentially important characteristics to accurately simulate the (b)(4) mixing process.
2. Your firm failed to establish time limits for the completion of each phase of production to assure the quality of the drug product [21 C.F.R. § 211.111].
For example, your firm has failed to establish hold times for the 1X dilutions of Chamomilla and Belladonna. Hyland’s Teething Tablets (lot (b)(4)) were manufactured on May 26, 2010, using a Chamomilla 1X dilution (lot (b)(4)) and a Belladonna 1X dilution (lot (b)(4)) that were manufactured on January 27, 2010, and February 18, 2010, respectively. Your firm’s hold times of (b)(4) for the Belladonna 1X dilution and (b)(4) for the Chamomilla 1X dilution are not supported by any scientific evidence showing the lack of blend segregation.
3. Your firm failed to conduct testing on in-process materials for identity, strength, quality, and purity during the production process, at commencement or completion of significant phases, or after storage for long periods [21 C.F.R. § 211.110(c)].
For example, your firm failed to conduct in-process testing to ensure blend uniformity for Belladonna 1X dilution (lots (b)(4)). Your firm only conducted an examination for color, odor, and taste.
4. Your firm failed to test each lot of a component with a potential for microbiological contamination that is objectionable in view of its intended use [21 C.F.R. § 211.84(d)(6)].
For example, your firm fails to analyze and test your botanically derived components for the presence of likely objectionable organisms prior to the manufacture of drug products, including those intended for infants and toddlers. Although your firm commits to test components used in the Hyland’s Homeopathic Teething Tablets for total plate counts, Escherichia coli, Salmonella species, yeast, mold, and Clostridium botulinum, you have not committed to assess botanically derived components for other possible objectionable organisms such as Bacillus cereus. Furthermore, you response failed to address the other botanical components used to manufacture other marketed products, such as Hyland Colic Tablets, which are also intended for use in infants and toddler populations.
5. 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’s Quality Control Unit (QCU) failed to identify the root cause and assess the impact on other related lots when approximately 62 kilograms of Restful Legs Tablets (lot (b)(4) ) were rejected due to the presence of brown specs on April 8, 2010.
In your response, your firm states that you will train your QCU on Root Cause Analysis and Corrective Action Prevention. However, your response is inadequate because your firm has failed to extend the investigation to other lots and products that may be associated with this failure.
This is a repeat violation from the January 2010 inspection.
Misbranding [§§ 503(b)(4) and 301(a)]
FDA reviewed your labeling submission to the Export Certificate Program dated August 5, 2010 and your website at the internet address http://www.hylands.com in January 2011. FDA reviewed your firm’s labeling and website information for homeopathic drug products, including but not limited to: “Leg Cramps with Quinine Tablets,” “Nighttime Cold ‘n Cough 4 Kids,” and “Bedwetting Tablets.”
Your product labeling and website document the intended uses of your products including, but not limited to the following:
Leg Cramps with Quinine Tablets: “Viscum Album 3X HPUS – for symptoms of . . . sciatica” “Rhus Toxicodendron 6X HPUS – for . . . Sciatica with pains in tendons and ligaments.”
Nighttime Cold ‘n Cough 4 Kids: “Pulsatilla 6X HPUS - spasmodic cough . . . ” “Sulphur 12X HPUS
. . . burning runny nose”
Bedwetting Tablets: “Rhus Aromatica 3X HPUS - for incontinence with constant dribbling in children.” “Belladonna 3X HPUS (0.0003% Alkaloids) – for frequent and profuse urination with sensation of motion in bladder. For incontinence and continuous dropping.”
Based on the above labeling and claims, these products are drugs under section 201(g)(1)(B) of the Act (21 U.S.C. § 321(g)(1)(B)), because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man, and 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 body.
Section 503(b)(1) of the Act (21 U.S.C. 353(b)(1)) identifies criteria for determining the prescription status of a product. The products listed above are prescription drugs within the meaning of Section 503(b)(1) of the Act because they are intended to treat diseases that require diagnosis and treatment by a physician or are intended to provide treatment for symptoms usually caused by an underlying disease process that requires diagnosis and treatment by a physician. Because they may be dispensed only by prescription of a licensed practitioner, these products are misbranded under Section 503(b)(4) of the Act (21 U.S.C. § 353(b)(4)) in that their labels fail to bear the symbol, "Rx only." 1 Your marketing of these misbranded products violates Section 301(a) of the Act (21 U.S.C. § 331(a)).
We recognize that these products are labeled as homeopathic drugs with active ingredients measured in homeopathic strengths.2 The definition of "drug" in section 201(g)(1) of the Act (21 U.S.C. § 321(g)(1)) includes articles recognized in the official Homeopathic Pharmacopeia of the United States (HPUS), or any supplement to it. Homeopathic drugs are subject to the same regulatory requirements as other drugs; nothing in the Act exempts homeopathic drugs from any of the requirements related to adulteration, labeling, misbranding, or approval. We acknowledge that many homeopathic drugs are manufactured and distributed without FDA approval under enforcement policies set out in the Agency’s Compliance Policy Guide entitled, “Conditions Under Which Homeopathic Drugs May be Marketed (CPG 7132.15)” (the CPG). As its title suggests, the CPG identifies specific conditions under which homeopathic drugs may ordinarily be marketed; thus, in order to fall under the enforcement policies set forth in the CPG, a homeopathic product must meet the conditions set forth in the CPG. One of those conditions is compliance with Section 503(b) of the Act. Under the CPG, only homeopathic products intended solely for self-limiting disease conditions amenable to self-diagnosis (of symptoms) and treatment may be marketed OTC. Homeopathic products offered for conditions not amenable to OTC use must be marketed as prescription products.
Misbranding [§§ 502(a) and 301(a)]
Your firm’s products “Leg Cramps with Quinine” and “Leg Cramps PM with Quinine” are misbranded under Section 502(a) of the Act because the labeling is false and misleading. The labeling of “Leg Cramps with Quinine” and “Leg Cramps PM with Quinine” prominently displays the ingredient “Quinine” on the front of the package and in the name of the product. The labeling is false and misleading because it suggests that quinine is the active ingredient when in fact the active ingredient is “Cinchona Officinalis.”
Further, the label indentifies this active ingredient as “Cinchona Officinalis 3X HPUS (Quinine).” According to the HPUS, although Cinchona bark contains quinine, it also contains other related alkaloids. Your selective identification of only one of the alkaloids in Cinchona bark is false and misleading because it incorrectly suggests that there is only one alkaloid in Cinchona bark.
Your marketing of these misbranded products violates Section 301(a) of the Act (21 U.S.C. § 331(a)).
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 any of the products that are the subject of this letter, including Hyland Teething Tablets, and provide the date(s) and reason(s) you ceased production and if or when you plan to resume production.
Your reply should be sent to: Blake Bevill, Compliance Branch Director, U.S. Food and Drug Administration, 19701 Fairchild, Irvine, CA 92612-2445. If you have question a regarding any issue in this letter, please contact Marco Esteves, Compliance Officer at (949) 608-4439.
Sincerely,
/s/
Alonza E. Cruse
District Director
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