Inspections, Compliance, Enforcement, and Criminal Investigations
I Shay Cosmetics Inc 10/22/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
Los Angeles District Office
Irvine, CA 92612-2506
Telephone: (949) 608-2900
Fax: (949) 608-4415
VIA UNITED PARCEL SERVICE
October 22, 2012 WL 03-13
Mr. Mehdi Ehsan, President and CEO
I. Shay Cosmetics, Inc.
15627 New Century Drive
Gardena, CA 90248-2128
Dear Mehdi Ehsan:
During our February 1 to February 29, 2012 inspection of your pharmaceutical manufacturing facility, I. Shay Cosmetic, Inc., located at 15627 New Century Drive, Gardena, CA, an investigator from the Food and Drug Administration (FDA) identified significant violations of the Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations (C.F.R.), Parts 210 and 211. These violations cause your drug products to be adulterated within the meaning of the section 501 (a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351 (a)(2)(B)] in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
Specific violations observed during the inspection include, but are not limited to, the following:
- Your firm has not established scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components and drug products conform to appropriate standards of identity, strength, quality, and purity [21 C.F.R. § 211.160(b)].
For example, your water testing program is not based on scientifically sound methodology and has the potential for masking microbiological contamination. There is no assurance your water is of adequate quality for drug manufacturing. The microbiological testing methods used to determine microbial content in the water used to manufacture drug products are not validated. Additionally, the sample dilution and culture mediums are inappropriate for organisms typical of water systems because they could hinder detection if contamination was present.
In addition, your microbiological testing of drug products is inadequate because you do not use scientifically sound methods. You stated you follow USP <61> for microbial analysis. However, while USP <61> includes enumeration methods, it does not provide for all of the tests that may be required for your products. In addition, you are not performing growth promotion tests to determine the suitability of the media used in your testing. You are also not performing antimicrobial effectiveness studies to ensure suitability of the preservative, and you do not include preservative content in stability testing. In addition, you are not documenting colony counts and calculations of number of cfu/ml.
- Your firm does not have adequate written procedures for production and process controls designed to assure that the drug products you manufacture have the identity, strength, quality, and/or purity they purport or are represented to possess [21 C.F.R. § 211.100(a)].
For example, your firm has not established scientific evidence that your manufacturing processes are capable of consistently manufacturing quality products. In addition, your firm changed the manufacturing process of (b)(4) (Lot #(b)(4)) without the quality unit’s approval. An additional inactive ingredient, “(b)(4),” was added without change control (e.g., additional studies to determine its impact on product quality).
- Your firm has not cleaned and maintained equipment at appropriate intervals to prevent contamination that would alter the safety, identity, strength, or quality of the drug product [21 C.F.R. § 211.67(a)].
For example, your firm has not successfully validated the cleaning process used for cleaning non-dedicated manufacturing equipment. Your firm does not have assurance that the cleaning and sanitization processes effectively clean the equipment to prevent contamination of drug products with cleaning agents and carryovers from previously manufactured products. Please ensure your cleaning validation studies place special emphasis on “worst case/hardest to clean” drug products to assure cleaning is effective in all equipment used for manufacturing drug products. Also, take into account for attributes that may affect cleaning (e.g., solubility, viscosity, percent solids) and the cleaning parameters (e.g., wash times, temperature, and pH) intended to be used during routine cleaning.
In addition, your firm is not following your written procedures for cleaning equipment. Specifically, your cleaning procedure, QR 103, “Cleaning Procedure,” dated September 30, 2010, requires you to use “(b)(4)” for washing tanks and equipment; however, you are using (b)(4) oil soap. Your sanitization procedure, QA IS06, “Sanitization,” dated March 10, 2005, requires you to use “(b)(4)”; however, you are using “(b)(4).”
- Your firm does not have a written testing program designed to assess the stability characteristics of drug products in order to determine appropriate storage conditions and expirations dates [21 C.F.R. § 211.166(a)].
For example, your firm is not performing stability tests to determine expiration dates for the products you distribute. In addition, you failed to follow your procedure, QA 22, “Long Term Drug GMP Stability Testing Protocol,” effective July 7, 2011, which requires you to perform stability tests at “(b)(4) months” for samples stored at (b)(4)oC. Therefore, you have no assurance your Cough Syrup and Brush Rinse drug products are stable throughout expiry.
- Your firm has not conducted at least one specific identity test and has not established the reliability of the supplier’s analyses through appropriate validation of the supplier’s test results at appropriate intervals [21 C.F.R. § 211.84(d)(2)].
For example, your firm is not performing at least one identity test on incoming materials prior to use and your firm has failed to perform full testing to qualify your suppliers. Your firm tests the component, Eucalyptus oil, but does not compare it to a known standard. The Laboratory Technician could not find the Eucalyptus oil standard in the libraries available. The technician shows the results of the IR test to you for approval rather than comparing the results to a known standard.
You stated during the inspection that you do not qualify suppliers because you perform identity tests on incoming ingredients. Please note that both testing incoming ingredients and ongoing supplier evaluation are part of basic CGMP conformance.
Unapproved and Misbranded Over-the-Counter (OTC) Drugs
In addition to the cGMP violations, your firm manufactures and distributes drug products for over-the-counter (OTC) use. During the inspection noted above, the investigators collected labeling for some of these products. As presently formulated, labeled, and promoted, these products are unapproved and/or misbranded drugs in violation of Sections 301(d), 505(a) and 502 of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. §§ 331(d), 355(a), and 352]. These violations are described in more detail below. Please note that this is not inclusive of all the products your firm manufactures and/or distributes and may not represent all product violations.
Product Name: INK-EEZE Black Label Numbing Spray
Ingredients Listed on Label: “Active Ingredients: Lidocaine HCL 5.00%”
Statements Found on Label: “Uses: External Use Only: Temporarily relieves pain, itching, or swelling due to tattooing or on open skin associated with other pain sensitive procedures.”
Statements Found on Distributor’s Website “www.inkeeze.com: “Use INK-EEZE during tattooing, piercing or other broken skin procedures.”
Based on the above labeling claims, INK-EEZE Black Label Numbing Spray is a “drug” as defined by section 201(g)(1)(B) of the 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 Act [21 U.S.C. § 321(g)(1)(C) because it is intended to affect the structure or any function of the body of man.
Drug products intended for external analgesic indications such as the temporary relief of pain, itching or swelling are covered under the Tentative Final Monograph (TFM) for OTC External Analgesics (48 FR 5852, February 8, 1983). While lidocaine HCL, the labeled active ingredient in INK-EEZE Black Label Numbing Spray, is included in the External Analgesic TFM, the concentration of lidocaine HCL at 5.00%, exceeds the concentration proposed in the TFM for this ingredient. The TFM includes lidocaine hydrochloride in a dosage range of “ 0.5 to 4 percent” (48 FR 5852, 5867) for the temporary relief of pain and/or itching, which can be followed by “associated with” minor burns, sunburn, minor cuts, scrapes, insect bites, and/or minor skin irritations. However, neither INK-EEZE Black Label Numbing Spray’s concentration of lidocaine hydrochloride nor the indications related to tattooing, piercing, and pain sensitive procedures are proposed under the TFM. Nor are we aware that this concentration of lidocaine HCL for indications related to tattooing, piercing, and pain sensitive procedures having been commercially available in the United States on or before the inception of the OTC Drug Review or otherwise eligible for inclusion in the ongoing rulemaking, in accordance with existing regulations (21 C.F.R. §§ 330.10(a)(12) and 330.14).
Thus, INK- EEZE Black Label Numbing Spray is a “new drug” under section 201(p) of the Act [21 U.S.C. § 321(p)], because it is offered for uses not covered by FDA’s OTC Drug Review, and we are not aware of any data establishing that this product is generally recognized as safe and effective for its labeled uses. “New drugs” may not be legally marketed in the United States without an approved application under section 505(a) of the Act (21 U.S.C. § 355(a)]. Since INK-EEZE Black Label Numbing Spray is not so approved, its marketing in the United States violates sections 301(d) and 505(a) of the Act (21 U.S.C. § 331(d) and 355(a)].
INK-EEZE Black Label Numbing Spray is also misbranded under section 502(c) of the Act [21 U.S.C. § 352(c)] because it does not contain the required labeling information in an OTC Drug Facts Panel in accordance with 21 C.F.R. § 201.66.
Product Name: (b)(4) Cough & Chest Congestion Relief
Ingredients Listed on Label: “Active Ingredient: Eucalyptus Oil 0.775%
Statements Found on Label: “Cough & Chest Congestion Relief” “Temporarily helps to sooth irritation due to coughing.”
In order for OTC cough, cold, allergy, bronchodilator, and antiasthmatic drug products, which includes products for cough and chest congestion relief, to be generally recognized as safe and effective and not misbranded, and thus be marketed without an approved NDA, they must meet the requirements of the final monograph for Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for OTC use, 21 CFR Part 341. (b)(4) Cough & Chest Congestion Relief is an unapproved new drug because it does not meet this final monograph. Specifically, the product contains eucalyptus oil as an active ingredient, which is not included in the final monograph as an acceptable oral active ingredient for these indications. Therefore, as formulated and labeled, (b)(4) Cough & Chest Congestion Relief is not generally recognized as safe and effective, and is a new drug under section 201(p) of the Act [21 U.S.C. § 321(p)]. Under section 505(a) of the Act [21 U.S.C. § 355(a)], a new drug may not be introduced or delivered for introduction into interstate commerce unless it is the subject of an FDA-approved application.
(b)(4) Cough & Chest Congestion Relief is also misbranded under section 502(c) of the Act [21 U.S.C. § 352(c)] because it is not labeled in accordance with the “Drug Facts” labeling requirements as described in 21 C.F.R. § 201.66.
Product Name: Permanent Hair Removal System
Statement Found on Label: “FDA Compliant”
In accordance with section 502(a) of the Act [21 U.S.C. § 352(a) of the Act), (b)(4) System is misbranded because the statement, “FDA Compliant” is both false and misleading. Such a statement connotes FDA approval or at the least that FDA has reviewed the product for compliance. OTC drug products are approved only if they are the subject of a FDA approved application while OTC drug products covered by FDA’s OTC Drug Review are not approved by the agency nor does the Agency certify compliance. Therefore, the inclusion of “FDA Compliant” on your product’s label is false and misleading and renders your product misbranded under 502(a) of the Act.
It should be noted that a convenience kit (i.e., a kit comprised of one or more drugs) must be fully labeled regarding the drugs in that kit and must comply with any labeling requirements relevant to each individual product within the kit. If the drug is covered by an OTC drug monograph, the kit must include all of the labeling specified by that monograph. If the drug in the kit is the subject of an approved NDA, the kit must include all of the labeling specified by that NDA. If the drug is deferred to the OTC Drug Review, but not yet the subject of a final monograph or rule, the kit must include all of the labeling needed for the OTC drug to remain covered by the OTC Drug Review.
Kits containing one or more OTC drugs must comply with section 502(c) of the Act [21 U.S.C. § 352(c)] so that all required information is visible at the time of purchase and use. In addition, section 502(c) of the Act [21 U.S.C. § 352(c)] requires that the kit complies with the “Drug Facts” labeling requirements under 21 C.F.R. § 201.66.
It appears that you have not implemented a robust quality system at your firm. Several of the CGMP deficiencies observed during this inspection were also observed in previous inspections. Because of your failure to correct these repeat violations, we recommend that you engage a third party consultant having appropriate CGMP expertise to assess your firm’s facility.
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence and the occurrence of other violations. It is your responsibility to assure compliance with all requirements of federal law and FDA regulations.
You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction. Other federal agencies may take this warning letter into account when considering the award of contracts. Additionally, FDA may withhold approval of requests for export certificates, or approval of pending drug applications listing your facility, until the above violations are corrected. FDA may re-inspect to verify corrective actions have been completed.
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations and copies of supporting documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the date by which you will have completed the correction.
Your reply should be directed to the U.S. Food and Drug Administration, Los Angles District Office, Pacific Region, Attention: Dr. Raymond W. Brullo, Compliance Officer, 19701 Fairchild, Irvine, CA 92612-2506. If you have questions regarding any issues in this letter, please contact Dr. Brullo at (949) 608-2918.
Alonza E. Cruse
Los Angles District
Los Angles District