Division of Pharmaceutical Quality Operations I
10 Waterview Blvd, 3rd FL
Parsippany, NJ 07054
Telephone: (973) 331-4900
FAX: (973) 331-4969
RETURN RECIPT REQUESTED
September 7, 2017
Mrs. Edith Scheiner
President and Owner
HomeoCare Laboratories, Inc.
7 Odell Plaza, Suite 142-146
Yonkers, NY 10701
Dear Mrs. Scheiner:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, HomeoCare Laboratories, Inc. (HomeoCare) at 7 Odell Plaza, Suite 142-146, Yonkers, NY from January 4 to 11, 2017.
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 HBP Relief, Cholestop, and IBS Relief 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 February 2, 2017, response in detail and acknowledge receipt of your subsequent correspondence.
During our inspection, our investigator observed specific violations including, but not limited to, the following.
1. 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, and your firm’s quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)).
You manufacture various homeopathic drugs from ingredients that pose potentially toxic effects. For example, some of your drugs include the ingredient Nux vomica, which contains strychnine. Strychnine is a highly toxic, well-studied poison that is used as a rodenticide.
You released numerous lots of homeopathic drugs without validating your manufacturing process. Before any batch is commercially distributed for use by consumers, a manufacturer should have gained a high degree of assurance in the performance of the manufacturing process such that it will consistently produce drug products meeting those attributes relating to identity, strength, quality, purity, and potency. Information and data should demonstrate that the commercial manufacturing process is capable of consistently producing acceptable quality products within commercial manufacturing conditions. Especially for drugs that contain ingredients with potentially toxic effects, failure to validate manufacturing processes could expose patients to unnecessary risks due to the lack of knowledge about and control over sources of variation.
In your response, you stated that you have written more than 100 standard operating procedures (SOP) and are working on reviewing and approving them by September 30, 2017. However, you did not address your failure to validate your manufacturing processes. You also failed to assess the effects of your lack of validation on the quality, safety, efficacy, and other characteristics of drugs that you have already distributed in the United States and that remain within expiry. These effects include patients’ potential exposure to risks due to lack of control over your manufacturing processes.
In response to this letter, provide:
- A data-driven and scientifically sound program that identifies and controls sources of variation, such that your drugs will consistently meet appropriate quality attributes. This includes, but is not limited to, assuring quality of input materials and determining the capability of each manufacturing process step and control.
- A risk assessment for all distributed drug products you manufactured using un-validated processes. Address any such products distributed within the United States and still within expiry.
2. Your firm failed to establish and follow adequate written procedures designed to assure batch uniformity and integrity of drug products that describe the in-process controls, and tests, or examinations to be conducted on appropriate samples of in-process materials of each batch (21 CFR 211.110(a)).
You failed to establish adequate in-process controls for drug products manufactured from active ingredients (e.g., Nux vomica, Atropa belladonna, Aconitum napellus, and Gelsemium sempervirens) that pose potentially toxic effects.
Your Testing and Control of In-Process Products SOP states, “In process testing is performed only if necessary since testing is done for finished products.” Your finished product testing is limited to microbiological testing only, and does not include testing for content uniformity. Although you perform some in-process testing, your control criteria are insufficient to comply with CGMP because they are highly subjective, requiring human manipulation and visual assessment.
For example, as your senior management explained, you determine tablet hardness using a (b)(4). You deem tablets acceptable (b)(4). Similarly, you use a (b)(4) for powder dryness—(b)(4). Procedural steps for your batch records state, “(b)(4).” Also, you check powder blends (b)(4) for uniformity.
(b)(4) by different operators does not account for inherent individual differences and capabilities in performing these tests, and cannot ensure uniform quality of your in-process components. Your failure to ensure the quality of in-process components may contribute to variability in the characteristics of both in-process components and, ultimately, in the quality of finished drug products.
In your response, you included an updated procedure with some additional requirements, such as tablet disintegration and friability. However, your revised in-process controls do not sufficiently ensure homogeneity, or the uniform character and quality of each batch. For example, a powder blend that contains Nux vomica has no in-process controls to ensure adequate mixing for uniformity and homogeneity prior to release and shipment. You failed to provide adequate scientific justification that your production and process controls ensure that your drugs meet appropriate specifications of identity, strength, quality, and purity. You also failed to address potential effects on products already distributed in the United States within expiry.
In response to this letter, provide your plan to implement adequate in-process controls such as adequacy of mixing and homogeneity.
3. 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 establish the reliability of component supplier analyses on which you rely in lieu of certain tests through appropriate validation of the supplier’s test results at appropriate intervals (21 CFR 211.84(d)(1) & (2)).
You do not test each component of your homeopathic drug products for identity prior to using components in your drug manufacturing process. You also failed to establish the reliability of your suppliers’ analyses, and to test each component for conformity with all appropriate written specifications for purity, strength, and quality.
For example, Nux vomica contains strychnine, a highly toxic poison. Our inspection findings indicate that you did not conduct strychnine assay testing of the Nux vomica mother tincture lot #CH91 as required by the Homeopathic Pharmacopeia of the United States.
Although you state that you require vendor surveys to qualify your suppliers, your management indicated that you had only one survey available out of the ten supplier surveys the investigator requested during the inspection. In addition, you accepted some components, such as homeopathic attenuations, without a certificate of analysis (COA) and did not conduct identity testing. As a result, you lack assurance that your components meet all appropriate specifications.
In your response, you stated that you conduct “[o]rganoleptic and visual tests … on raw materials (inactive ingredients) against the manufacturer’s COA…” and that you now “routinely” perform “identification tests of raw materials.” You also stated that homeopathic attenuations “do not come with a certificate of analysis” and that testing is not possible for homeopathic attenuations.
Your response is inadequate. You must test each component to verify its identity. You must also test all components, including active ingredients, homeopathic attenuations, and inactive ingredients, for conformity with all appropriate written specifications for purity, strength, and quality. If you intend to rely on your suppliers’ COA in lieu of such testing, you must still conduct at least an identity test on each component. You must also periodically validate the supplier's test results.
In your response, you did not clearly indicate that you will conduct an identity test on each component, nor have you shown how you will validate the test results of each supplier for which you intend to rely on COA. Finally, you did not address the potential effects of your failure to conduct incoming component testing on the quality of products you have distributed in the United States that remain within expiry.
In response to this letter, provide a detailed description of how you plan to test each component for conformity with all appropriate written specifications for identity, purity, strength and quality. For example, describe how you intend to meet compendial or other written requirements for assay testing of toxic substances such as strychnine. If you accept your suppliers’ COA in lieu of testing components, describe in detail how you plan to establish the reliability of your suppliers’ test results through periodic validation. Lastly, provide a risk assessment for any drugs within expiry and distributed within the United States that were manufactured from inadequately tested and controlled components. Include your plan to test your retain samples to ensure that drugs do not contain any active ingredient levels that may increase the risks of patient exposure to toxic effects.
4. Your firm failed to maintain written records so that data therein could be used for evaluating, at least annually, the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures (21 CFR 211.180(e)).
You failed to follow your Product Quality Review SOP requirement to evaluate quality standards for each drug product at least annually, including products manufactured from ingredients with potentially toxic effects. You have never conducted an annual product review for any of your own products. Failure to perform annual product reviews limits your ability to identify variability in your manufacturing processes, to make appropriate manufacturing process improvements, and ultimately, to advance the quality of your products.
In your response, you committed to conducting annual product reviews if you manufacture at least three batches of product during your review period. However, your response contradicts your own SOP requirements: it does not require annual evaluation of the quality standards for each of your drug products.
In response to this letter, provide your plan or procedure to ensure that you will complete product quality reviews at least annually for all drug products that you manufacture and distribute within the United States. Provide your procedures for investigating, responding to, and correcting any deviations from product quality and safety standards identified as a part of your product quality review findings and risk assessments.
Your firm does not have an adequate ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality. See FDA’s guidance document, Process Validation: General Principles and Practices
, for general principles and approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf
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, HBP Relief, Cholestop, and IBS Relief, 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 HBP Relief, Cholestop, and IBS Relief include, but may not be limited to, the following:
- “Temporarily relieves symptoms associated with high blood pressure (hypertension).”
- “HomeoCare® HBP Relief was created as a safe alternative to conventional drugs which may cause unwanted side-effects.”
- “Your doctor may have told you that you have high cholesterol…enter CHOLESTOP™ by HomeoCare®.”
- “CHOLESTOP™ is a natural homeopathic formula composed of ingredients clinically proven to stimulate and regulate hepatic functions to help reduce cholesterol levels.”
- “For the temporary relief of diarrhea; constipation; abdominal cramps and bloating associated with Irritable Bowel Syndrome.”
- “If you suffer from bloating, cramps, diarrhea, and constipation you may have IBS (Irritable Bowel Syndrome). . . . HomeoCare IBS Relief gently helps correct a dysfunctional digestive system and relieve stress causing symptoms.”
Because of their toxicity or other potential for harmful effect, or the method of their use, or the collateral measures necessary to their use, HBP Relief, Cholestop, and IBS Relief 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.”
HBP Relief, Cholestop, and IBS Relief 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 product safely for these indications. Thus, your products’ labeling fails to bear adequate directions for use for this indication, 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 prohibited 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 HBP Relief, Cholestop, and IBS Relief 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 our Compliance Policy Guide, 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 in all your facilities.
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.
Food and Drug Administration
200 Chestnut Street/ Room 900
Philadelphia, PA 19106
Please identify your response with reference number #
Diana Amador Toro
Division Director/OPQ Division I
New Jersey District Office
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 FDA 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.