10903 New Hampshire Avenue
Silver Spring, MD 20993
Via UPS Warning Letter 320-18-10
November 20, 2017
Mr. JongWoo Kim
Chief Executive Officer
Dae Young Foods Company, Ltd.
7F. KTIS Sungin Bldg. 390
Jong-ro, Jongno-gu, Seoul 110-825 Korea
Dear Mr. Kim:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Dae Young Foods at 32 Gumgul-4-gil Boeun-eup, Boeun-gun, Chungchongbuk-do, from March 13 to 17, 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, the FDA reviewed your product label for Smoker’s Appetite Relief and determined that your product is a misbranded drug under section 502(a) of the FD&C Act, 21 U.S.C. 352(a).
We reviewed your April 9, 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 visually examine each container of components for appropriate labeling as to contents upon receipt and before acceptance (21 CFR 211.82(a)).
Your firm accepted at least one shipment of a drug component without ensuring it was properly labeled. For example, the label on drums of an in-process (b)(4) #(b)(4) containing multiple active ingredients indicated “(b)(4)” only and failed to identify any of the active ingredients in the component or list their concentrations. Furthermore, the batch number on the drums did not match the batch number in the documents you provided to support the use of this component.
This in-process (b)(4) was manufactured from ingredients that pose potentially toxic effects, such as Nux vomica, which contains strychnine. Strychnine, a highly toxic, well-studied poison, is also used as a rodenticide. You manufactured a homeopathic drug product, (b)(4), using a portion of the component that you accepted without examining for appropriate labeling.
You cannot accept drug components unless the containers are appropriately labeled as to contents. In response to this letter provide your detailed plan for ensuring that incoming drug components you receive from your suppliers are appropriately labeled as to contents, for example, accurately labeled with the identity and strength of all ingredients.
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)).
Your firm failed to test incoming drug components, the in-process (b)(4) received from (b)(4), for identity or any quality criteria prior to use in your drug manufacturing process. By not adequately analyzing these in-process (b)(4) for identity, purity, strength, and quality, you failed to ensure the suitability of incoming raw materials for processing.
Your firm also has not established the reliability of your in-process (b)(4) supplier’s certificates of analysis. Your use of supplier questionnaires, without appropriate validation of your supplier’s test results, is inadequate to ensure the certificates of analysis you receive can be used in lieu of testing your drug components for quality attributes.
In your response, you stated that you will begin testing your incoming in-process (b)(4) for the presence of (b)(4), but not the active ingredients in this (b)(4). The active ingredients you purport to use are potentially toxic and could pose a significant safety hazard if present in levels higher than the labeled content.
In response to this letter, provide your scientific justification for how you will assure that all of your components, including those containing ingredients that pose potentially toxic effects, will meet appropriate specifications before use in manufacturing. Also describe how you will correct your supplier qualification procedure with steps such as clearly predefined specifications and periodic revalidation of supplier test results.
Also provide a risk assessment for any drug product lots manufactured using components that were not adequately tested and qualified. Your risk assessment should address all products within expiry and distributed within the United States.
3. Your firm failed to establish an adequate quality control unit and procedures applicable to the 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 (21 CFR 211.22(a) and (d)).
Your firm lacks an adequate quality control unit.
You failed to establish written procedures for numerous functions. For example, there were no procedures addressing the quality control unit, complaints, deviations, investigations, and various other basic drug manufacturing operations.
Further, your quality unit lacked documentation to demonstrate acceptability of batch manufacturing and quality. For instance, you lacked records relating to:
- change control;
- annual product reviews;
- batch record review to assure that any errors were discovered and fully investigated; and
- approval or rejection of your drug products.
During our inspection one of your employees confirmed that that your quality unit does not review the complete batch records for your finished drug products prior to release. In response to this letter, provide your corrective actions to ensure that:
- you establish an adequate quality control unit with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality;
- you establish adequate procedures in accord with CGMP covering all aspects of your facility and operations that may compromise the identity, strength, quality, and purity of your drug products; and
- you create and maintain full documentation to demonstrate acceptability of all operations.
Misbranded drug charge
Your firm’s product, Smoker’s Appetite Relief is a drug under section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), because it is 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 Smoker’s Appetite Relief include, but may not be limited to, the following:
- Temporarily relieves and calms
o Excessive Appetite
o Food Cravings
- The purposes of the ingredients are listed as
o Nicotine cleansing
o Excessive appetite, overeating
o Food cravings
o Liver support
o Digestion / metabolism support
o Mental withdrawal
o Physical withdrawal
Under section 502(a) of the FD&C Act, 21 U.S.C. 352(a), a drug is misbranded if its labeling is false or misleading in any particular. Section 201(n) of the FD&C Act, 21 U.S.C. 321(n), provides that, “in determining whether [an article’s] labeling or advertising is misleading there shall be taken into account . . . not only representations made or suggested . . . but also the extent to which the labeling or advertising fails to reveal facts material in the light of such representations.” According to your batch record for Smoker’s Appetite Relief, there are numerous ingredients that were included in the product but were not declared on the finished product label, such as (b)(4), and (b)(4). In addition, there are ingredients listed on the finished product label that do not appear in the batch record, such as Carduus marianus, Hypericum, Kreosotum, and Lobelia. The failure to declare ingredients on the label and the inclusion of ingredients on the label that were not included in the product is false or misleading, and therefore such product is misbranded under section 502(a) of the FD&C Act.
We recognize that Smoker’s Appetite Relief is labeled as a homeopathic drug 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.
The introduction or delivery for introduction into interstate commerce of a drug that is misbranded or adulterated violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).
Responsibilities as a contractor
Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors, such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.
You and your customer, (b)(4), have a quality agreement regarding the manufacture of (b)(4). You are responsible for the quality of drugs you produce as a contract facility, regardless of the quality agreements in place. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act.
Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified under 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.
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.
Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.
Failure to correct these violations may also result in FDA refusing admission of articles manufactured at Dae Young Foods, Ltd. at 32 Gumgul-4-gil Boeun-eup, at Boeun-gun, Chungchongbuk-do, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Under the same authority, articles may be subject to refusal of admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).
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 violationsand to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.
U.S. Food and Drug Administration
White Oak Building 51, Room 4359
10903 New Hampshire Avenue
Silver Spring, MD 20993
Please identify your response with FEI 3009719616.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
This page was posted on January 1, 2018.