Division of Pharmaceutical Quality Operations IV
VIA UNITED PARCEL SERVICE
September 1, 2017 CMS# 514129
Dr. Charles L. Bernaert
Owner / President
Nova Homeopathic Therapeutics, Inc.
5600 McLeod Rd NE, Suite F
Albuquerque, NM, 87109
Dear Dr. Bernaert:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Nova Homeopathic Therapeutics at 5600 McLeod Rd NE, Suite F, Albuquerque from October 3 to 12, 2016.
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 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, based on our review your products Depression Complex, Circulation Complex, and Liver Complex are misbranded drugs under sections 503(b) and 502(f)(1) of the FD&C Act, 21 U.S.C. 353(b) and 352(f)(1).
We reviewed your October 24, 2016, response in detail.
During our inspection, our investigator 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 material, labeling, and drug products (21 CFR 211.22(a)).
You lack quality oversight for the manufacture of finished drugs, including those manufactured from ingredients that pose potentially toxic effects. For example, you manufacture an oral liquid drug, Teething Complex, that contains, among other things, the potentially toxic substance belladonna. This Teething Complex oral liquid is intended for administration to infants and children to relieve pain associated with teething.
Your firm lacks adequate written procedures, including, but not limited to, procedures governing the responsibilities and functions of the quality control unit (QCU), complaint handling, annual product review, stability studies, and quality review of incoming materials and finished product batch release.
During our inspection, you stated in an affidavit signed on October 12, 2016, that, prior to the beginning of this inspection you were “unaware” that homeopathic drugs are subject to current good manufacturing practice. You also affirmed in the same affidavit that you have made homeopathic products in your drug manufacturing establishment since 1983, and currently manufacture and market (b)(4) homeopathic drug products.
In your response, you committed to “draft a QCU” and other procedures to “aid…in complying” with CGMP requirements. During the inspection you also stated to our investigator that your current procedures were created in response to the last FDA inspection and had not been followed.
Your response is not adequate. You failed to provide documentation to show that you have drafted and implemented such procedures, nor have you offered scientific justification that the procedures are adequate to assure product quality control. You also failed to address the potential effects of your lack of quality oversight on the quality of drugs that you manufactured without such oversight and which remain within expiry.
In response to this letter, provide your plan for establishing an adequate quality unit, and include any procedures you have drafted and implemented that address the responsibilities and functions of your quality unit.
See FDA’s guidance document, Quality Systems Approach to Pharmaceutical CGMP Regulations, for help implementing modern quality systems and risk management approaches to meet the requirements of CGMP regulations (2l CFR parts 210 and 211), at
2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to test each component for conformity with all appropriate written specifications for purity, strength, and quality (21 CFR 211.84(d)(1) & (2)).
You did not test any of the components you use to manufacture your drugs to verify their identities before using them. For example, you performed no identity tests on components such as belladonna mother tincture and ethyl alcohol.
Furthermore, you failed to determine whether each component conformed with all appropriate written specifications for purity, strength, and quality before using them. You asserted in your signed affidavit that all of your products are (b)(4) over-the-counter products and each of your products contains (b)(4). Although the Certificate of Analysis for the (b)(4) you use in all of your drugs explicitly states, “Disclaimer: For Industrial/Lab use only. Not intended as a Drug Substance…” you could not provide any scientific evidence that this component was compliant with USP specifications for use in human drugs, and did not perform any testing to determine whether this component conformed with specifications.
In your response, you committed to draft procedures for handling drug product containers, closures, and packaging. However, you failed to address your critical failure to test all components for identity prior to use. Your response was also inadequate because you failed to provide evidence that your components met appropriate written specifications of identity, strength, quality, and purity. You did not address potential risks to patients. Finally, you did not address how failure to conduct required testing on components to verify identity and determine conformance with specifications for purity, strength, and quality may have compromised the quality of the products you have previously manufactured.
In response to this letter, provide a risk assessment for any drug products manufactured using components which were not adequately tested and controlled. Include all products within expiry and distributed within the United States. Describe any specific additional risks posed to infants and children, for whom many of your products are intended.
3. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).
You failed to validate your drug manufacturing processes, and your firm lacked adequate written procedures for production control records. Each significant step of a manufacturing process must be controlled to assure that in-process materials and finished drugs meet their quality attributes and specifications. Unvalidated production processes increase the probability that your products will vary in strength, quality, and purity. Your failure to validate your drug manufacturing processes means that you cannot assure consistency in, and may result in variable levels of potentially toxic ingredients in, both your in-process materials and in finished drug products, such as Teething Complex and Colic Complex, which are marketed for infants and children.
We acknowledge your commitment to begin drafting validation protocols in accordance with FDA’s Guidance for Industry, Process Validation: General Principles and Practices. However, you failed to provide scientific justification that assures uniformity and integrity of your drug products. You also failed to address the potential effects of your failure to validate your manufacturing processes on the quality of products that you have already released for distribution in the United States remaining within expiry.
In response to this letter, provide:
- A data-driven and scientifically sound validation protocol to ensure that you will identify and control all sources of variability in your drug manufacturing processes to ensure that all of your drugs consistently meet appropriate quality attributes.
- A plan to implement adequate in-process controls, including any appropriate in-process and finished product testing and examination, to ensure batch uniformity and integrity of your drugs.
- A risk assessment for distributed drug products you manufactured using an unvalidated process. Address the potential effects of your lack of validation on all products intended for vulnerable populations, such as infants and children, distributed within the United States, and still within expiry.
CGMP consultant recommended
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 fully resolving all deficiencies and ensuring ongoing CGMP compliance.
Your firm’s products Depression Complex, Circulation Complex, and Liver Complex are drugs under section 201(g)(1) of the FD&C Act (21 U.S.C. 321(g)(1)), because they are intended to diagnose, cure, mitigate, treat, or prevent disease, and/or intended to affect the structure or any
function of the body.
Examples of claims that establish the intended uses for Depression Complex, Circulation Complex, and Liver Complex include, but may not be limited to, the following:
- “Grief, anxiety, despair and melancholy.”
- “Poor circulation, cold hands and feet and hardening of the arteries.”
- “Liver congestion and dysfunction due to toxic overload from alcohol and pharmaceutical drugs.”
Because of their toxicity or other potential for harmful effect, or the method of use, or the collateral measures necessary to their use, Depression Complex, Circulation Complex, and Liver Complex are not safe for use except under the supervision of a practitioner licensed by law to administer such drugs. Therefore, these products are subject to section 503(b)(1) of the FD&C Act (21 U.S.C. 353(b)(1)) and are misbranded under section 503(b)(4) of the FD&C Act (21 U.S.C. 353(b)(4)) in that their labels fail to bear the symbol, “Rx only.”
Depression Complex, Circulation Complex, and Liver Complex are intended for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners. “Adequate directions for use” is defined in 21 CFR 201.5 as “directions under which the layman can use a drug safely and for the purposes for which it is intended.” Because these conditions require the supervision of a practitioner licensed to prescribe drugs, adequate directions cannot be written so that a layperson can use your products safely for these indications. Thus, your products’ labeling fails to bear adequate directions for use for these indications, which causes the products to also be misbranded under section 502(f)(1) of the FD&C Act (21 U.S.C. 352(f)(1)). It is a prohibited act to introduce or deliver for introduction into interstate commerce a misbranded drug under section 301(a) of the FD&C Act (21 U.S.C. 331(a)).
We recognize that Depression Complex, Circulation Complex, and Liver Complex 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 drugs 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, labeling, misbranding, or approval. We acknowledge that many homeopathic drugs are manufactured and distributed without FDA approval under enforcement policies set out in the FDA’s Compliance Policy Guide entitled, Conditions Under Which Homeopathic Drugs May be Marketed (CPG 400.400) (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 FD&C Act. The CPG states that 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.
Violations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing 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.
Until these violations are corrected, we may withhold approval of pending drug applications listing your facility. We may re-inspect to verify that you have completed your corrective actions. We may also refuse your requests for export certificates.
After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your violations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.
Your written notification should refer to the Warning Letter Number above (CMS# 514129) and should be sent to:
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
United States Food and Drug Administration
Irvine, California 92612
If you have any questions about the content of this letter, please contact CDR Matthew Dionne, Compliance Officer, via email at Matthew.Dionne@fda.hhs.gov or by phone at 303-236-3064 and reference unique identifier 514129.
Acting for CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
 FDA’s Compliance Policy Guide, “Conditions Under Which Homeopathic Drugs May be Marketed (CPG 400.400),” states that, in accordance with 503(b)(1) of the FD&C Act, homeopathic drug products offered for conditions that require diagnosis or treatment by a licensed practitioner must bear the prescription legend, “Caution: Federal law prohibits dispensing without prescription.” This CPG was issued by the agency in 1988. In 1997, Congress enacted the Food and Drug Administration Modernization Act (FDAMA); section 126 of FDAMA amended 503(b)(4) of the FD&C Act to require that the label of a prescription drug must bear, at a minimum, the symbol “Rx only.”
This page was posted on January 1, 2018.