- Delivery Method:
- VIA SIGNATURE CONFIRMED DELIVE
Recipient NameMr. Hong J. Shen
- Herbal Doctor Remedies
497 Cumbre Street
Monterey Park, CA 91754
- Issuing Office:
- Division of Pharmaceutical Quality Operations IV
Irvine, CA 92612-2506
October 4, 2019
Dear Mr. Shen:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Herbal Doctor Remedies, FEI 3003040962, at 497 Cumbre Street, Monterey Park, California, from April 15 to 19, 2019.
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 drug products were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, your drug products are adulterated within the meaning of section 501(a)(2)(A) of the Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(A).
Additionally, 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 FD&C Act, 21 U.S.C. 351(a)(2)(B).
FDA also reviewed your websites at www.herb-doc.com, www.theraherb.ecrater.com, and www.chinasecretremedy.com, in July 2019, and has determined that you take orders there for various products that are unapproved new drugs and misbranded drugs under sections 502(f)(1) and 505(a) of the FD&C Act, 21 U.S.C. 352(f)(1), and 355(a). The introduction of such products into interstate commerce is prohibited under 301(a) and (d) of the FD&C Act, 21 U.S.C. 331(a) and (d).
You have manufactured, prepared, propagated, compounded, or processed drugs that were being offered for commercial distribution in the United States while your drug manufacturing facility, Herbal Doctor Remedies at 497 Cumbre Street, Monterey Park, California, was not an FDA registered establishment. Section 510 of the FD&C Act and 21 CFR Part 207, subject to certain limited exceptions, require establishment owners and operators upon first engaging in the manufacture, preparation, propagation, compounding, or processing of drugs to register their establishments and submit listing information for all drugs in commercial distribution. Any drugs not included in the initial registration must be included with subsequent listing updates, either in June or December; whichever first occurs after the product has initially been marketed. Under section 502(o) of the FD&C Act (21 U.S.C. 352(o)), the failure to register an establishment as required by section 510, or failure to list a drug as required under section 510(j), renders a drug misbranded.
We reviewed your April 22, 2019, response in detail, and acknowledge receipt of your subsequent correspondence. Your response is inadequate because it did not provide sufficient detail or evidence of corrective actions to bring your operations into compliance with CGMP.
During our inspection, our investigators observed specific violations including, but not limited to, the following.
Insanitary Conditions Violations
You manufactured finished drug products intended to orally and topically treat conditions, such as autism, Alzheimer’s disease, herpes, and cancer. During the inspection, our investigator observed filthy conditions in your facility.
We observed layers of brown dust-like residue throughout the areas used for manufacturing your finished drug products, including on the processing tables, table covers, finished product label racks, finished product storage area, and your manufacturing equipment. Additionally, your main manufacturing area opens to the outside of your facility.
CGMP Drug Violations
1. Your firm failed to establish an adequate quality unit with adequate facilities and procedures to ensure that drugs are manufactured in compliance with CGMP regulations and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).
You lack fundamental elements of an adequate quality unit.
You did not have established procedures including, but not limited to, describing roles and responsibilities of the quality unit (21 CFR 211.22(d)); investigating deviations and laboratory out-of-specifications, and drug product complaints (21 CFR 211.100(b); 21 CFR 211.160(a); 21 CFR 211.192; 21 CFR 211.198(a)).
You lacked basic controls for ensuring that components used in your products are of acceptable quality, such as identity testing of components (21 CFR 211.84(d)(1)), testing components for conformity with appropriate written specifications, receiving Certificates of Analysis, or adequately qualifying your suppliers (21 CFR 211.84(d)(2).
You did not perform final release testing of your finished drug products (21 CFR 211.165(a)).
You lacked written procedures to assure that correct labels are used for your products and did not declare all ingredients on your finished product labels (21 CFR 211.130).
You confirmed the above violations in a signed affidavit during the inspection. 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 https://www.fda.gov/media/71023/download.
2. Your firm failed to establish a system by which the distribution of each lot of drug product can be readily determined to facilitate its recall if necessary (21 CFR 211.150(b))
Your firm lacked procedures describing your drug distribution system. You did not document the lot numbers of products distributed, and therefore your system cannot adequately trace products in the marketplace when a recall is necessary.
3. Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements and you failed to establish written procedures for cleaning and maintenance of equipment (21 CFR 211.67(a) & (b)).
Our investigators observed brown residue build-up on your equipment used to manufacture your drug products, as well as throughout your manufacturing area. Additionally, you have no written procedures for cleaning your non-dedicated equipment and utensils or any other drug product contact surfaces. You also lacked cleaning validation.
4. Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188).
You stated to the investigators that you lacked batch production records and had not established master production or control records for your drug products. Because of your lack of batch records, you do not have an accurate reproduction of the appropriate master production or control record, which is checked for accuracy, dated and signed. You also have no documentation that each significant step in the manufacture, processing, packing, or holding of the batch was accomplished.
Unapproved New Drugs and Misbranded Drugs
On May 25, 2017, you received a warning letter notifying you that you marketed and distributed unapproved new drugs under sections 201(g)(1) and 201(p) of the FD&C Act, 21 U.S.C. 321(g)(1) and (p), and misbranded drugs within the meaning of section 502(f)(1) of the FD&C Act, 21 U.S.C. 352(f)(1). The FDA reviewed your May 30, 2017, response to the warning letter, where you stated that you “will investigate and determine the cause of violation by revise, edit and update the language of product description for the laymen.” Our review included evaluation of your websites at www.herb-doc.com, www.theraherb.ecrater.com, and www.chinasecretremedy.com, to determine if you made adequate corrections to the issues and violations described in the warning letter.
Based on our review of the current claims on your website in July 2019, you have not addressed the violations cited in the May 25, 2017, warning letter, and you continue to market and distribute unapproved new drugs and misbranded drugs. For example, some of your products are marketed for the treatment of conditions such as autism, Alzheimer’s disease, herpes, and cancer. Your continued marketing of unapproved new drugs and misbranded drugs, including products previously cited in the May 25, 2017, warning letter, violates sections 301(a), 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(a), 331(d) and 355(a).
We advise you to review all the information on your websites, products labels, and other labeling and promotional materials for your products to ensure the claims you make are not in violation of the FD&C Act. Your failure to promptly correct all violations may result in legal action against you without further notice, including, without limitation, seizure and injunction.
Your firm failed to register the manufacturing establishment and list all drugs manufactured at this establishment as required under the FD&C Act.
A review of the registration database reveals that although your firm manufactures drugs for U.S. commercial distribution, it failed to fulfill its registration obligations under section 510 of the FD&C Act, which is prohibited under Section 301(p), 21 U.S.C 360 and 331(p). As a result, all drugs you manufacture in this establishment are misbranded under Section 502(o) of the FD&C Act, 21 U.S.C. 352(o). In addition, drugs manufactured at this establishment are not listed with FDA as required by section 510 of the FD&C Act, (21 U.S.C. 360(j)), which is prohibited under section 301(p) of the FD&C Act, (21 U.S.C. 331(p)). Failure to properly list a drug with the FDA will also render it misbranded under section 502(o) of the FD&C Act, (21 U.S.C. 352(o)).
Production Ceased and Products Recalled
We acknowledge your commitment to cease production of drugs at this facility as of April 22, 2019. However, you also stated in your response that you “will ask outside GMP facility to do the compounding, filling the capsule and packaging the products if necessary.”
In response to this letter, clarify whether you intend to resume manufacturing any dietary supplements or drugs at this facility or at a contract manufacturer in the future. If you plan to resume manufacturing dietary supplements or drugs for U.S. distribution at this facility or at a contract manufacturer, notify this office prior to resuming your operations. If you plan to use a contract manufacturer, please note your obligations as the product owner. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/media/86193/download.
We also acknowledge you voluntarily recalled all your products within expiry after the FDA contacted you regarding your drug products being marketed without FDA approval and manufactured outside of the controls required by CGMP. On July 24, 2019, FDA issued a public notification regarding this voluntary recall. https://www.fda.gov/safety/recalls-marketwithdrawals-safety-alerts/herbal-doctor-remedies-issues-voluntary-nationwide-recall-alldrug-products
CGMP Consultant Recommended
If you intend to resume manufacturing drugs for the U.S. market in the future, we strongly recommend engaging a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. The consultant should address all above issues systemically and assist with comprehensive corrective actions and preventive actions prior to resumption of any drug product manufacturing.
In various communications with FDA over the past three years, you have made numerous inconsistent statements about what type of products you are intending to manufacture and distribute. During an inspection of your firm conducted in November 2016, you stated that your products are herbal products used for traditional Chinese medicine. In your May 30, 2017, letter to CDR Steven E. Porter, Jr., Director, Division of Pharmaceutical Operations IV, you stated that you have visited the FDA website and found that herbal formulas meet the Dietary Supplement category. During a May 2018 inspection of your firm, you referred to your products as drugs and said that your products are intended for your patients to deal with diseases such as herpes. During the April 2019 inspection, you again said that your products are dietary supplements, but you also referred to your products as Chinese medicines. In a July 12, 2019, email to FDA, you again referred to your products as Chinese medicines.
Irrespective of how you intend to market your product, an article intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease is a drug, subject to limited exceptions that do not appear relevant to your products (see section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B)). As noted previously, your products are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and therefore are drugs under section 201(g)(1)(B) of the FD&C Act.
Furthermore, even if your products did not bear claims that render them drugs, your products do not meet the definition of dietary supplements in section 201(ff) of the FD&C Act, 21 U.S.C. 321(ff). For example, under section 201(ff)(2)(C), a dietary supplement “means a product that… is labeled as a dietary supplement.” Your products are not labeled as dietary supplements. Additionally, under section 201(ff)(1), a dietary supplement “means a product…intended to supplement the diet.” It does not appear that your products are intended to supplement the diet.
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.
Because these violations are significant, contact Matthew R. Dionne, Pharm.D., Compliance Officer, at 303-236-3064 or via email at Matthew.Dionne@fda.hhs.gov within five days of receipt of this letter to schedule a regulatory meeting with the FDA to take place at our Irvine, CA office address.
Send your electronic reply to ORAPHARM4_RESPONSES@fda.hhs.gov or mail your written reply to:
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
19701 Fairchild Road
Irvine, CA 92612
Please identify your response with unique identifier 583205.
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV