02.06.19
The US Food and Drug Administration (FDA) has sent a warning letter to Ji Hyun Min, CEO of Soleo of Korea. FDA conducted an inspection of the company’s drug manufacturing facility from August 6 to 9, 2018. The 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, as formulated and labeled, “Gen+Le Therapy Shampoo” is an unapproved new drug in violation of section 505(a) of the FD&C Act (21 U.S.C. 355(a)). Introduction of such a product into interstate commerce is prohibited under section 301(d) of the FD&C Act (21 U.S.C. 331(d)).
During the inspection, the FDA investigator observed specific violations.
For example, Sole failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and (2)).
According to FDA, the company lacked testing of incoming raw materials, including active pharmaceutical ingredients and components, used in manufacturing of your Gentle Therapy Shampoo over-the-counter (OTC) drug product, for their identity, strength, and other appropriate quality attributes. Instead, your firm relied solely on your suppliers’ certificates of analysis (COA) without establishing the reliability of the suppliers’ analyses through appropriate validation.
FDA said it reviewed the company’s August 23, 2018 response in detail, in which Soleo said it would “ try to proceed by purchasing the experimental equipment also so that we [Soleo] can directly analyze the ingredients contained in the raw material”.
FDA called the company’s response inadequate because it failed to provide a detailed procedure for conducting raw material testing, a target date for implementation, and a plan of action in the interim.
In response to this letter, FDA has asked the company to provide:
• Chemical and microbiological quality control specifications you will use to approve the release of each incoming lot of components for use in manufacturing.
• A description of how you will conduct at least one specific identity test for each incoming component lot, regardless of a COA validation program
• A description of how you will test each component lot for conformity with all appropriate specifications for strength, quality, and purity. If you intend to accept any testing results from your supplier’s COA in lieu of your testing of each component lot for purity, strength, and quality, specify how you plan to establish the reliability and consistency of your supplier’s test results for these attributes through initial validation (followed by periodic re-validation). Include your standard operating procedure that describes this COA validation program.
A summary of test results obtained from full testing of reserves samples of active pharmaceutical ingredient lots used in the manufacture of your drug product that were distributed to the U.S. market and within expiry.
• A comprehensive independent review of your material system to determine whether all containers, closures, and ingredients from each supplier are adequately qualified and are assigned appropriate expiration or retest dates. Also determine whether your controls for incoming material lots are adequate to prevent the use of unsuitable containers, closures, and components.
FDA said Soleo failed to establish and document the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)).
FDA also said Soleo failed to establish 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)).
FDA also contends Soleo failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).
Based upon the nature of the violations identified, FDA said it strongly recommends engaging a consultant, qualified as set forth in 21 CFR 211.34, to evaluate your operations and assist your firm in meeting CGMP requirements. “We also recommend that the qualified consultant perform a comprehensive audit of your entire operation for CGMP compliance and evaluate the completion and effectiveness of any corrective action and preventative action plan you have implemented,” FDA penned in its letter.
Examples of claims observed on Soleo’s product label, and on its labeling which includes your product website for “GEN+LE THERAPY Shampoo” that establish the intended uses of the product as defined in 21 CFR 201.128 include, but may not be limited to, the following:
· Label Claims:
“Prevents Hair Loss ... Hair Loss Prevention ... Anti-Dandruff”
· Website Claims:
“Is your dandruff out of control? The solution is GEN+LE THERAPY SHAMPOO & TREATEMENT ... Anti-Dandruff ... A inveterate Dandruff goes away in a short time ... Hair Loss Prevention ... Biotin helps your hair grow ...”
Based on the above claims, “GEN+LE THERAPY Shampoo” is a “drug” as defined by section 201(g)(1)(B) of the FD&C Act (21 U.S.C. 321(g)(1)(B)) because it is intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the FD&C Act (21 U.S.C. 321(g)(1)(C)) because it is intended to affect the structure or any function of the body. Specifically, this product is intended as a hair growth, hair loss prevention, and anti-dandruff drug product.
Under 21 CFR 310.527, OTC drug products intended as an external hair grower, such as “GEN+LE THERAPY Shampoo”, that are labeled, represented, or promoted for external use as a hair grower or for hair loss prevention are regarded as new drugs within the meaning of section 201(p) of the FD&C Act and require an FDA-approved application prior to being marketed.
In addition, drug products intended for the treatment of dandruff, such as “GEN+LE THERAPY Shampoo” are subject to the Final Rule for Drug Products for the Control of Dandruff, Seborrheic Dermatitis, and Psoriasis (21 CFR 358, Subpart H). However, the formulation for “GEN+LE THERAPY Shampoo” is not consistent with the formulation requirements that describe acceptable active ingredients for drug products for the treatment of dandruff. Specifically, biotin, niacinamide, and dexpanthenol do not comply with the acceptable active ingredients in 21 CFR 358.710.
Thus, as formulated and labeled, “GEN+LE THERAPY Shampoo” does not comply with the final rules described above. Furthermore, we are not aware of sufficient evidence to show that “GEN+LE THERAPY Shampoo”, as formulated and labeled, is generally recognized as safe and effective. Therefore, this product is a new drug within the meaning of section 201(p) of the FD&C Act (21 U.S.C. 321(p)). As a new drug, “GEN+LE THERAPY Shampoo” may not be legally marketed in the United States absent approval of an application filed in accordance with section 505(a) of the FD&C Act (21 U.S.C. 355(a)). “GEN+LE THERAPY Shampoo” is not the subject of an FDA-approved application and therefore, the current marketing of this product violates section 505(a) of the FD&C Act (21 U.S.C. 355(a)). Introduction of such products into interstate commerce is prohibited under section 301(d) of the FD&C Act (21 U.S.C. 331(d)).
FDA placed the firm on Import Alert 66-40 on November 26, 2018, and indicated that until Soelo corrects all violations completely and FDA confirms compliance with CGMP, it 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 continuing to refuse admission of articles manufactured at Soleo at 24 Sandan-Ro, Pyeongtaek-Si, Gyeonggi-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)), said FDA.
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, as formulated and labeled, “Gen+Le Therapy Shampoo” is an unapproved new drug in violation of section 505(a) of the FD&C Act (21 U.S.C. 355(a)). Introduction of such a product into interstate commerce is prohibited under section 301(d) of the FD&C Act (21 U.S.C. 331(d)).
During the inspection, the FDA investigator observed specific violations.
For example, Sole failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and (2)).
According to FDA, the company lacked testing of incoming raw materials, including active pharmaceutical ingredients and components, used in manufacturing of your Gentle Therapy Shampoo over-the-counter (OTC) drug product, for their identity, strength, and other appropriate quality attributes. Instead, your firm relied solely on your suppliers’ certificates of analysis (COA) without establishing the reliability of the suppliers’ analyses through appropriate validation.
FDA said it reviewed the company’s August 23, 2018 response in detail, in which Soleo said it would “ try to proceed by purchasing the experimental equipment also so that we [Soleo] can directly analyze the ingredients contained in the raw material”.
FDA called the company’s response inadequate because it failed to provide a detailed procedure for conducting raw material testing, a target date for implementation, and a plan of action in the interim.
In response to this letter, FDA has asked the company to provide:
• Chemical and microbiological quality control specifications you will use to approve the release of each incoming lot of components for use in manufacturing.
• A description of how you will conduct at least one specific identity test for each incoming component lot, regardless of a COA validation program
• A description of how you will test each component lot for conformity with all appropriate specifications for strength, quality, and purity. If you intend to accept any testing results from your supplier’s COA in lieu of your testing of each component lot for purity, strength, and quality, specify how you plan to establish the reliability and consistency of your supplier’s test results for these attributes through initial validation (followed by periodic re-validation). Include your standard operating procedure that describes this COA validation program.
A summary of test results obtained from full testing of reserves samples of active pharmaceutical ingredient lots used in the manufacture of your drug product that were distributed to the U.S. market and within expiry.
• A comprehensive independent review of your material system to determine whether all containers, closures, and ingredients from each supplier are adequately qualified and are assigned appropriate expiration or retest dates. Also determine whether your controls for incoming material lots are adequate to prevent the use of unsuitable containers, closures, and components.
FDA said Soleo failed to establish and document the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)).
FDA also said Soleo failed to establish 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)).
FDA also contends Soleo failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).
Based upon the nature of the violations identified, FDA said it strongly recommends engaging a consultant, qualified as set forth in 21 CFR 211.34, to evaluate your operations and assist your firm in meeting CGMP requirements. “We also recommend that the qualified consultant perform a comprehensive audit of your entire operation for CGMP compliance and evaluate the completion and effectiveness of any corrective action and preventative action plan you have implemented,” FDA penned in its letter.
Examples of claims observed on Soleo’s product label, and on its labeling which includes your product website for “GEN+LE THERAPY Shampoo” that establish the intended uses of the product as defined in 21 CFR 201.128 include, but may not be limited to, the following:
· Label Claims:
“Prevents Hair Loss ... Hair Loss Prevention ... Anti-Dandruff”
· Website Claims:
“Is your dandruff out of control? The solution is GEN+LE THERAPY SHAMPOO & TREATEMENT ... Anti-Dandruff ... A inveterate Dandruff goes away in a short time ... Hair Loss Prevention ... Biotin helps your hair grow ...”
Based on the above claims, “GEN+LE THERAPY Shampoo” is a “drug” as defined by section 201(g)(1)(B) of the FD&C Act (21 U.S.C. 321(g)(1)(B)) because it is intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the FD&C Act (21 U.S.C. 321(g)(1)(C)) because it is intended to affect the structure or any function of the body. Specifically, this product is intended as a hair growth, hair loss prevention, and anti-dandruff drug product.
Under 21 CFR 310.527, OTC drug products intended as an external hair grower, such as “GEN+LE THERAPY Shampoo”, that are labeled, represented, or promoted for external use as a hair grower or for hair loss prevention are regarded as new drugs within the meaning of section 201(p) of the FD&C Act and require an FDA-approved application prior to being marketed.
In addition, drug products intended for the treatment of dandruff, such as “GEN+LE THERAPY Shampoo” are subject to the Final Rule for Drug Products for the Control of Dandruff, Seborrheic Dermatitis, and Psoriasis (21 CFR 358, Subpart H). However, the formulation for “GEN+LE THERAPY Shampoo” is not consistent with the formulation requirements that describe acceptable active ingredients for drug products for the treatment of dandruff. Specifically, biotin, niacinamide, and dexpanthenol do not comply with the acceptable active ingredients in 21 CFR 358.710.
Thus, as formulated and labeled, “GEN+LE THERAPY Shampoo” does not comply with the final rules described above. Furthermore, we are not aware of sufficient evidence to show that “GEN+LE THERAPY Shampoo”, as formulated and labeled, is generally recognized as safe and effective. Therefore, this product is a new drug within the meaning of section 201(p) of the FD&C Act (21 U.S.C. 321(p)). As a new drug, “GEN+LE THERAPY Shampoo” may not be legally marketed in the United States absent approval of an application filed in accordance with section 505(a) of the FD&C Act (21 U.S.C. 355(a)). “GEN+LE THERAPY Shampoo” is not the subject of an FDA-approved application and therefore, the current marketing of this product violates section 505(a) of the FD&C Act (21 U.S.C. 355(a)). Introduction of such products into interstate commerce is prohibited under section 301(d) of the FD&C Act (21 U.S.C. 331(d)).
FDA placed the firm on Import Alert 66-40 on November 26, 2018, and indicated that until Soelo corrects all violations completely and FDA confirms compliance with CGMP, it 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 continuing to refuse admission of articles manufactured at Soleo at 24 Sandan-Ro, Pyeongtaek-Si, Gyeonggi-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)), said FDA.
