The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Washington Homeopathic Products, Inc., FEI 3006489197, at 260 J R Hawvermale Way, Berkeley Springs, WV, from June 18 to July 2, 2019.
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).
In addition, the FDA reviewed your website at the Internet address www.homeopathyworks.com from October 2019 to May 2020, from which you take orders for your products “Apis Mellifica,” “Aceticum acidum,” “Colchicum,” “Natrum Sulphuricum,” “Sarsaparilla,” “Aconitum Napellus” and “Veratrum Album.” The FDA also reviewed your website at http://homeopathicremedysearch.com,which directs consumers to www.homeopathyworks.com to purchase your products. Based on our review, these products are unapproved new drugs under section 505 of the Federal FD&C Act, 21 U.S.C. 355. Introducing or delivering these products for introduction into interstate commerce violates section 301 of the FD&C Act, 21 U.S.C. 331.
These products are especially concerning from a public health perspective because they claim to cure, mitigate, treat, or prevent serious and/or life-threatening conditions such as cancer, diabetes, and hepatitis, and may cause consumers to forgo, delay, or discontinue medical treatments that have been found safe and effective for such conditions through the FDA review process. In addition, as described below, your firm has significant violations of CGMP regulations. Your firm’s poor manufacturing practices are particularly concerning because many of your products are labeled to contain potentially toxic ingredients, such as “Aconitum Napellus” and “Veratrum Album,” thereby presenting additional risk of serious harm to patients. In addition, your poor manufacturing practices are also concerning because many of your products are marketed for use in children or infants, who may be at greater risk for adverse reactions associated with certain drug products due to differences in their ability to absorb, metabolize, distribute, or excrete such drug products or their metabolites.
We reviewed your July 24, 2019, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.
During our inspection, our investigators observed specific violations including, but not limited to, the following.
1. Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products, including drug products manufactured, processed, packed or held under contract by another company. Your firm also failed to establish adequate written responsibilities and procedures applicable to the quality control unit (21 CFR 211.22(a) and (d)).
Your firm’s quality unit (QU) failed to have adequate oversight for homeopathic drug products and components you receive, manufacture, or distribute. Furthermore, you lacked adequate written procedures describing the responsibilities for the QU. During the inspection, you acknowledged the failure to define the manufacturing roles and responsibilities between you and your suppliers.
supplies you with homeopathic
and other components. On
, you became aware that (b)(4) had been placed on import alert 66-40 "Detention Without Physical Examination of Drugs From Firms Which Have Not Met Drug GMPs" and was issued
by FDA for egregious violations of CGMP.
The CGMP violations at (b)(4) included the following:
Despite you becoming aware of the violative conditions described at your supplier’s facility, your firm continued to distribute adulterated homeopathic drug products and components you received from
. Only after the FDA inspection at your firm did you propose a potential corrective and preventive action (CAPA) plan to address the poor quality of drugs you received from
In your response you stated that you removed
from your approved vendor list and quarantined all material received from
. You also performed a risk assessment and had a contract laboratory test these raw materials and finished products. Furthermore, you stated you were in the process of completing supplier quality agreements with your current suppliers of active homeopathic ingredients and tinctures. Additionally, you admitted in your response that you failed to implement an effective CAPA regarding vendor qualification as was discussed during the prior 2018 FDA inspection.
We acknowledge you recalled homeopathic drug products manufactured and labeled for you by (b)(4) and that you also recalled (b)(4) homeopathic product. You stated you would recall the tinctures your firm manufactured using (b)(4) “materials” that you deemed high risk and were distributed directly to consumers. However, for the other finished products your firm manufactured using (b)(4) “materials”, you stated in your risk assessment that you would contact your customers and “recommend that those lots of products are recalled. The final decision of a recall however, will be made by the customer”.
Your response is inadequate because you failed to demonstrate how oversight of your firm’s manufacturing practices would be improved to ensure your corrective actions are effective going forward. Also, you failed to ensure remediation of your supplier qualification program as discussed during a previous FDA inspection. It is your responsibility to ensure that drug products manufactured by you or received and further distributed are in accordance with 501(a)(2)(B) of the FD&C Act to ensure their safety, identity, strength, quality and purity.
In response to this letter, provide the following:
• A complete reconciliation of all drug products your QU released without adequate oversight of your suppliers.
• A comprehensive assessment and remediation plan to ensure you have implemented quality agreements with your suppliers and that all drug products are in accordance with 501(a)(2)(B) of the FD&C Act to ensure their safety, identity, strength, quality, and purity.
• A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:
o A determination of whether procedures used by your firm are robust and appropriate
o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices
o A complete and final review of each batch and its related information before the QU disposition decision
o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products
• Also describe how top management supports quality assurance and reliable operations, including, but not limited to, timely provision of resources to proactively address emerging manufacturing/quality issues and to ensure a continuing state of control.
2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product (21 CFR 211.84(d)(1)).
You purchase mother tinctures and other components such as
from outside suppliers, but you failed to test each lot of component received for identity before release for use in drug manufacturing.
You stated in your response that you were performing a risk assessment to address the manufacturing performed without appropriate raw material testing. You also stated you would revise your standard operating procedure (SOP) to include identity testing for all ingredients before use.
However, your response is inadequate because you failed to provide all test results for all components you currently have in inventory or retain samples that you released for production without establishing the identity of these components. It is unclear in your response how your risk assessment would address drugs manufactured “without appropriate raw materials testing”.
In response to this letter, provide the following:
• A comprehensive, independent review of your material system to determine whether all ingredients are tested for identity using appropriate methods before release for use in production. The review should also determine whether incoming material controls are adequate to prevent the use of unsuitable components.
• Your plan for performing at least one identity test for all incoming components used in your drug products labeled as homeopathic.
• The chemical and microbiological quality control specifications you use to test and release each incoming lot of component for use in manufacturing.
• A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s Certificates of Analysis (COA) instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.
• A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your SOP that describes this COA validation program.
• A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
3. Your firm failed to establish and document the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)).
Your firm failed to adequately validate the test method you used to analyze your raw materials and finished drug products for microbiological attributes. You attempted to validate your test method, but you failed to:
• Verify the suitability of your method under actual conditions of use
• Perform method suitability for all products manufactured by your firm to ensure your firm is capable of culturing organisms that may be present
• Establish a validated method for detecting objectionable microorganisms in your homeopathic drug products
In your response you stated that you are currently using a qualified laboratory for all testing and that you will “evaluate other validated microbiological tests performed to ensure that they represent actual product conditions”. You also stated you would perform a retrospective risk assessment.
However, it is unclear how you would ensure that your bioburden method is adequate for use while you evaluate other microbiological tests. You did not provide adequate supportive documentation of your proposed risk assessment or define how you would address other marketed products without a validated test method for bioburden. In addition you did not provide a CAPA that would ensure your firm can evaluate the effectiveness of your corrective actions.
In response to this letter, provide the following:
• Appropriate microbiological batch release specifications (i.e., total counts, identification of bioburden to detect objectionable microbes) for each of your drug products.
• All microbial test methods used to analyze each of your drug products.
• A summary of results from testing retain samples of all drug product batches within expiry. You should test microbiological quality (total counts and identification of bioburden to detect any objectionable microbes) of each batch. If testing yields an out-of-specification (OOS) result, indicate the corrective actions you will take, including notifying customers and initiating recalls.
• Your commitment to test all drug products you manufacture using a valid test method (e.g., USP method). These USP methods include USP <61>
Microbiological Enumeration of Nonsterile Products: Enumeration tests
and USP <62>
Microbiological Enumeration of Nonsterile Products: Tests for Specified Organisms
. In addition, it is essential that your firm also implements appropriate bioburden identification methods for your drug products.
Your firm’s quality systems are inadequate. See FDA’s guidance document
Quality Systems Approach to Pharmaceutical CGMP Regulations
for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at
CGMP Consultant Recommended
We acknowledge that you have hired a consultant, however, based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.
Unapproved New Drugs
Statements on your websites that establish the intended uses of your products include, but are not limited to, the following:
On your website at www.homeopathicremedysearch.com, on a page titled “Apis mellifica”
• “Apis mellifica . . . Get the Remedy at HomeopathyWorks.com GO >> . . . Apis cures diphtheria . . . Apis has proved [sic] a curative remedy, has often cured tumors, and has caused cystic formation to stop growing or to disappear.”
On your product page for “Apis Mellifica Pills” at www.homeopathyworks.com/apis-mellifica-pills/
• “Apis Mellifica Pills . . . Indicated for Stings, Allergy symptoms, Hives. . . . burning pains (feeling like the sting of a bee).”
On your website at www.homeopathicremedysearch.com, on a page titled “Aceticum acidum”
• “Aceticum acidum…Get the Remedy at HomeopathyWorks.com GO >>…Diabetes. . . . Narcotics, antidote to. . . . Stomach, cancer of. . . . It is suited to children and old people…Hemorrhage from bowels…Chronic diarrhoea[sic] of children…Convulsions. . . . typhous[sic] fevers.
On your website at www.homeopathicremedysearch.com, on a page titled “Colchicum”
• “Colchicum…Get the Remedy at HomeopathyWorks.com GO>>… Appendicitis. . . . Asthma. . . . Cataract. . . . Cholera. . . . Diabetes. . . . Typhoid fever”
On your website at www.homeopathicremedysearch.com, on a page titled “Natrum sulphuricum”
• “Natrum sulphuricum . . . Get the Remedy at HomeopathyWorks.com GO>> . . . remedy for SPINAL MENINGITIS, head symptoms FROM INJURIES TO HEAD . . . Chronic gout. . . . Suicidal tendency . . . hepatitis . . . Diabetes. . . . Gonorrhea . . . Rheumatism”
On your product page for “Natrum Sulphuricum Pills” at https://www.homeopathyworks.com/natrum-sulphuricum-pills/
• “Other indications for its use include confusion after a blow to the head”
On your website at www.homeopathicremedysearch.com, on a page titled “Sarsaparilla”
• “Sarsaparilla… Get the Remedy at HomeopathyWorks.com GO>> . . . periosteal pains due to venereal disease. . . . Influenza. . . . cholera…SEVERE PAIN AT CONCLUSION OF URINATION. . . . CHILD SCREAMS BEFORE AND AFTER PASSING URINE. . . . PAIN FROM RIGHT KIDNEY DOWNWARD. . . . Intolerable stench on genitals. Herpetic eruption on genitals. . . . Syphilis. . . . Rheumatic pains after gonorrhea”
On your website at www.homeopathicremedysearch.com, on a page titled “Aconitum napellus”
• “Acotitum napellus… Get the Remedy at HomeopathyWorks.com GO>>”
• “Acon. Is a useful medicine in inflammation of the liver, when it comes suddenly . . . Violent inflammation of the liver, with violent tearing pains and much burning.”
• “Uterine hemorrhage with bright red blood and fear of death.”
• “New-born children, with difficulty of breathing, after the use of forceps, or from a tedious labor; the child is breathless, there is difficulty with the heart, and in a few hours fever comes on. Acon. is a very simple remedy.”
On your website at www.homeopathicremedysearch.com/, on a page titled “Veratrum album”
• “Veratrum album… Get the Remedy at HomeopathyWorks.com GO>>”
• “Profuse sweat, vomiting and diarrhea.”
• “Profuse watery discharges….In cholera or cholera morbus, it seems that the fluids run out of the body….Full of cramps; looks as if he would die….violent inflammations.”
• “Veratrum…remed[y] in the cure of cholera…”
On your product page for “Veratrum Album Pills” at https://www.homeopathyworks.com/veratrum-album-pills/
• “Veratrum album is a homeopathic remedy often used for individuals suffering with diarrhea and vomiting accompanied by a great coldness and weakness. Other indications for its use include cold sweat – particularly on the forehead, thirst, rice water stools, vomiting, and vomiting and diarrhea that can be virtually simultaneous.”
The above claims for “Apis Mellifica,” “Aceticum acidum,” “Colchicum,” “Natrum Sulphuricum,” “Sarsaparilla,” “Aconitum Napellus” and “Veratrum Album” demonstrate that they are drugs, as defined by the FD&C Act, 21 U.S.C. 321(g), because they are intended to cure, mitigate, treat, or prevent disease and/or intended to affect the structure or function of the body of man or other animals. Moreover, these products are “new drugs,” as defined by 201(p) of the FD&C 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 section 505(a) of the FD&C Act, 21 U.S.C. 355(a), new drugs may not be introduced or delivered for introduction into interstate commerce without prior approval from FDA. No approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for these products. Accordingly, the introduction or delivery for introduction into interstate commerce of these products violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a).
We recognize that “Apis Mellifica,” “Aceticum acidum,” “Colchicum,” “Natrum Sulphuricum,” “Sarsaparilla,” “Aconitum Napellus” and “Veratrum Album” are labeled as homeopathic drugs with active ingredients measured in homeopathic strengths. Under section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), the term “drug” includes articles recognized in the official Homeopathic Pharmacopeia of the United States (HPUS), or any supplement to it. Homeopathic drug products are subject to the same regulatory requirements as other drugs; nothing in the FD&C Act exempts homeopathic drugs from any of the requirements related to adulteration, misbranding, or approval.
The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of these violations and for preventing their recurrence or the occurrence of other violations.
Correct the violations cited in this letter promptly. Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction. Unresolved violations in this warning letter may also prevent other Federal agencies from awarding contracts.
FDA may also withhold approval of requests for export certificates and approval of pending new drug applications or supplements listing your facility as a supplier or manufacturer until the above violations are corrected. We may re-inspect to verify that you have completed your corrective actions.