Page 1 of 6 Home Inspections, Compliance, Enforcement, and Criminal Investigations Enforcement Actions Warning Letters Inspections, Compliance, Enforcement, and Criminal Investigations Keystone Laboratories Inc 3/18/13 Department of Health and Human Services Public Health Service Food and Drug Administration New Orleans District 404 BNA Drive Building 200, Suite 500 Nashville, TN 37217-1003 Telephone: 615-366-7801 Facsimile: 615-366-7802 March 18, 2013 WARNING LETTER NO. 2013-NOL-08 UNITED PARCEL SERVICE DELIVERY SIGNATURE REQUESTED Melinda Menke Burns, Owner Keystone Laboratories, Inc. 950 Martinez Springs Road Bozeman, Montana 59718 Dear Ms. Burns: During our August 15, 16, 20, 21, 23, and 29, 2012, inspection of your pharmaceutical manufacturing facility, Keystone Laboratories, Inc. located at 1103 Kansas Street, Memphis Tennessee, an investigator from the U.S. Food and Drug Administration (FDA) identified significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211 (21 CFR 210 & 211). These violations cause your drug products to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 United States Code (USC) 351(a)(2)(B)] as 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. In addition to the CGMP violations, your firm manufactures numerous products that are presented as cosmetics. Based on the labeling, such products are drugs as defined by Section 201(g)(1) of the Act [21 USC 321(g)(1)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body of man. As presently formulated, labeled, and promoted, these products are unapproved and/or misbranded drugs in violation of Sections 301(d), 505(a), 502(f)(2), 502(c), and 502(e)(1)(A)(ii) of the Act [21 USC 331(d), 355(a), 352(c), and 552(e)(1)(A)(ii)] as further described below. Please note this is not inclusive of all the products your firm manufactures and/or distributes and may not represent all product violations. Our inspection also revealed your firm failed to fulfill its registration obligations under Section
Page 2 of 6 510(i)(1) of the Act and its listing obligations under Section 510(i)(2) and 510(j) [21 USC 360 (i)(1), 360(i)(2), and 360(j)]. As a result, your drugs are misbranded under Section 502(o) of the Act [21 USC 352(o)]. You may find regulations through links on FDA s Internet home page at www.fda.gov 1. Our investigator observed specific violations during the inspection of your facility, which produces over-the-counter (OTC) topical drug products, including, but not limited to, the following: CGMP Violations 1. Your firm failed to maintain buildings used in the manufacture, processing, packing or holding of drug products in a good state of repair (21 CFR 211.58). For example, our investigator observed condensate leaking into a bucket that was secured to the ceiling over the production area, and peeling paint on the floors, walls and support beams in the production area. This is a repeat observation from our 2009 and 2011 inspections. 2. Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.63). For example, your firm utilizes wooden sticks in processing and cardboard covers on production equipment. These wooden sticks come into contact with your drug products and the cardboard is used on equipment to cover open product during processing. These materials (wood and cardboard) are not appropriate for drug manufacturing their construction makes them difficult or impossible to clean and can therefore become a source of microbial contaminants, dirt, and residues of other drugs that may alter your product s quality. 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 [21 CFR 211.67(a)]. Our investigator observed the following examples: a) Deep scratches and rust like stains in vessels used to measure and mix drug products. Equipment used in drug product manufacturing must have smooth surfaces which facilitate cleaning to prevent product contamination b) Equipment and utensils with visible build up and filth and lack of documentation to indicate that equipment was cleaned at appropriate intervals to prevent contamination This is a repeat observation from our 2009 and 2011 inspections. 4. Your firm failed to withhold from use each lot of components, drug product containers, and closures until the lot had been sampled, tested, or examined, as appropriate and released for use by the quality control unit [21 CFR 211.84(a) and 211.84(d)(6)]. For example, the water you use in your drug products is a component with the potential for microbiological contamination which is objectionable in view of the component s intended use. Notwithstanding this, your firm failed to subject the water to routine microbiological testing. Furthermore, your firm failed to validate the water system to ensure consistent water quality for drug production and implement procedures for maintaining or monitoring the quality of the water produced. You can determine the
Page 3 of 6 frequency of water testing based upon the intended use of the product and other considerations. This is a repeat observation from our 2011 inspection. 5. Your firm failed to follow 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 to document same at the time of performance, and to record and justify any deviations from them [21 CFR 211.100(b)]. Specifically, records for released product routinely required, but lacked the secondary verification of significant steps in the operation, such as verification of component weights dispensed. Violative Over-the-Counter (OTC) Drug Products Long Aid Medicated Hair Revitalizer Anti-Itch Formula The package labeling for the Long Aid Medicated Hair Revitalizer Anti-Itch Formula identifies Salicylic Acid as the active ingredient and based on information on its label the product is intended for the control of dandruff and microbial growth. The dandruff indication is addressed under 21 CFR 358 Subpart H Drug Products for the Control of Dandruff, Seborrheic Dermatitis, and Psoriasis. Therefore, this product is a drug as defined by Section 20l(g)(l) of the Act [21 USC 321(g)(l)] because it is intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body of man. However, Long Aid Medicated Hair Revitalizer Anti-Itch Formula is not labeled in conformance with the final monograph. In particular, the antibacterial indication for Long Aid Medicated Hair Revitalizer Anti-Itch Formula is not included as an indication for use in the OTC Final Monograph for Drug Products for the Control of Dandruff, Seborrheic Dermatitis, and Psoriasis. For this reason, Long Aid Medicated Hair Revitalizer Anti-Itch Formula is a new drug under Section 201(p) of the Act [21 USC 321(p)] and may not be legally marketed in the United States without approved applications under Section 505(a) of the Act [21 USC 355(a)]. Since the product is not the subject of an approved new drug application, its marketing in the United States violates Sections 301(d) and 505(a) of the Act [21 USC 331(d) and 355(a)]. Furthermore, Long Aid Medicated Hair Revitalizer Anti-Itch Formula products are misbranded under Section 502(c) of the Act [21 USC 352(c)], because the product is not labeled in accordance with the Drug Facts labeling requirements described in 21 CFR 201.66. Long Aid Medicated Hair Revitalizer Anti-Itch Formula is also misbranded under Section 502(f) (2) of the Act [21 USC 352(f)(2)] because the product fails to bear required warnings per 21 CFR 358.750(c). For instance, its labeling must include the statement: For external use only. ULTRA GLOW Fade Creams The package labeling for your ULTRA GLOW Fade Creams identifies Hydroquinone 2% and Padimate O 1.5%as active ingredients. The labeled uses for these products include fades skin discolorations by lightening dark spots such as freckles, age spots, and blemishes. Based on the labeling described above, your ULTRA GLOW Fade Creams are drugs as defined by Section 20l(g)(l) of the Act [21 USC 321(g)(l)] because they are intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body of man. Based on the product s labeled indications for use, the products intended use is addressed under the Proposed Rule for Miscellaneous External Drug Products for Over-the- Counter Human Use Subpart A Skin Bleaching Drug Products (71 FR 39108, September 3, 1982). As a skin bleaching OTC drug, your product must either be addressed by the ongoing OTC rulemaking for skin bleaching products, be eligible for inclusion in the OTC rulemaking, or have an FDA approved application in order to be legally marketed. Furthermore, such marketing
Page 4 of 6 under ongoing rulemaking is subject to the rulemaking becoming final and may result in you having to reformulate your product. Furthermore, as OTC drugs your products must also meet general OTC drug labeling requirements. However, your ULTRA GLOW Fade Creams are misbranded under Section 502(c) of the Act [21 USC 352(c)], because the products are not labeled in accordance with the Drug Facts labeling requirements described in 21 CFR 201.66. Your ULTRA GLOW skin care products are also misbranded under Section 502(c) of the Act [21 USC 352(c)] because their labeling includes both English and French but some of the information required under authority of the Act appears only in English and not in French. For example, the labels include a list of inactive ingredients in the English language as required under Section 502(e)(1)(A)(iii) of the Act [352 USC (e)(1)(a)(iii) ] but lacks a complete list of inactive ingredients in the French language. Under 21 CFR 201.15(c)(2) and 201.15(c)(3) if a product s label or labeling contains any representation in a foreign language, all words, statements, and other information required by or under authority of the Act to appear on the label shall appear thereon in the foreign language. BETTER BRAIDS Hair Care Products medicated BETTER BRAIDS Shampoo medicated BETTER BRAIDS Leave-in-Conditioner medicated BETTER BRAIDS Un-Braid medicated BETTER BRAIDS Spray The package labeling for the products mentioned above identifies Salicylic Acid as the active ingredient and based on information on their labels or their labeling at www.keystone-labs.com these products are medicated and intended for the control of dandruff or psoriasis. Such indications are addressed under 21 CFR 358 Subpart H Drug Products for the Control of Dandruff, Seborrheic Dermatitis, and Psoriasis. In accordance with this Final Rule, your products mentioned above are drugs, as defined by Section 20l(g)(l) of the Act [21 USC 321(g) (l)] because they are intended to affect the structure or function of the body of man. In addition, in order to be legally marketed for control of dandruff or psoriasis without an FDA approved application, your products must conform to the requirements set forth under the final monograph noted above. Absent conforming to the conditions of the final monograph your products would be considered new drugs under Section 201(p) of the Act [21 USC 321 (p)] and without an approved application, unapproved new drugs under Sections 301(d) and 505(a) of the Act [21 USC 331(d) and 355(a)], may not be introduced or delivered for introduction into interstate commerce. Furthermore, as OTC drugs your products must meet general OTC drug labeling requirements. However, BETTER BRAIDS products are misbranded under Section 502(f)(2) of the Act [21 USC 352(f)(2)] because they fail to bear required warnings per 21 CFR 358.750 (c). For instance, their labeling must include the statement: For external use only. Further, your BETTER BRAIDS products are misbranded under Section 502(e)(1)(A)(ii) of the Act [21 USC 352(e)(1)(A)(ii)] because their labeling fails include the percentage of Salicylic Acid. The acceptable range, listed in 21 CFR 358.710(a), is 1.8 to 3 percent. Your BETTER BRAIDS products are also misbranded under Section 502(c) of the Act [21 USC 352(c)], because the products are not labeled in accordance with the Drug Facts labeling requirements described in 21 CFR 201.66. Your BETTER BRAIDS products are also misbranded under Section 502(c) of the Act [21 USC 352(c)] because their labeling includes both English and French but some of the information required under authority of the Act appears only in English and not in French. As an example, the labels include a list of inactive ingredients in the English language as required under Section 502(e)(1)(A)(iii) of the Act [352 USC (e)(1)(a)(iii) ] but lacks a complete list of all inactive ingredients in the French language. Under 21 CFR 201.15(c)(2) and (3) if a product s label or
Page 5 of 6 labeling contains any representation in a foreign language, all words, statements, and other information required by or under authority of the Act to appear on the label shall appear thereon in the foreign language. Drug Registration and Listing Violations Additionally, under Section 510 of the Act [21 USC 360], manufacturers of drug products are required to annually register with the FDA. Our records indicate your firm has failed to fulfill its registration obligations. Because of this, all drug products you prepare are misbranded as they were manufactured, prepared, propagated, compounded, or processed in an establishment not duly registered under Section 510 of the Act [21 USC 360], and the products have not been listed, as required by Section 510(j) of the Act [21 USC 360(j)]. You were given prior notice of this by letter dated November 2, 2011, after our inspection during June 2011, during which your firm committed to update your registration with the FDA. The violations cited in this letter are not intended to be an all-inclusive list of violations existing 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. Repeat citations from prior inspections indicate your quality control unit is not exercising its responsibilities, and may not have the appropriate authority to carry out its responsibilities. Due to continuing CGMP issues at your firm, we recommend you engage a third party consultant with appropriate CGMP expertise to assess your firm s facility, procedures, processes, and systems to ensure the drugs you manufacture have their appropriate identity, strength, quality, and purity. 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 (15) working days of receipt of this letter, please notify this office in writing of the specific steps you have taken to correct and prevent the recurrence of violations, and provide copies of supporting documentation. If you cannot complete corrective actions within 15 working days, state the reason for the delay and the date by which you will have completed the corrections. Additionally, if you no longer manufacture or distribute the drug products at issue, provide the date(s) and reason(s) you ceased production. Please address all correspondence to Rebecca A. Asente, Compliance Officer, at the address above. If you have questions regarding the contents of this letter, please contact Ms. Asente at (504) 832-1290, extension 1104. Sincerely, /S/ Patricia K. Schafer District Director New Orleans District cc: Bonnie L. Culp General Manager and Comptroller Keystone Laboratories, Inc. 1103 Kansas Street Memphis, Tennessee 38106-1913 Page Last Updated: 03/21/2013
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