Inspections, Compliance, Enforcement, and Criminal Investigations
Absolute Packaging, Inc. 9/9/10
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
555 Winderley Place, Suite 200
Maitland, Florida 32751
RETURN RECEIPT REQUESTED
September 9, 2010
Mr. Melvin C. Wilt
Absolute Packaging, Inc.
320 Stan Drive, Suite A
Melbourne, FL 32904-1091
Dear Mr. Wilt:
During our March 24, 2010 to April 9, 2010 inspection of your pharmaceutical manufacturing facility, Absolute Packaging, Inc., located at 320 Stan Drive, Melbourne, FL 32904, an investigator from the 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. 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 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. Your firm also manufactures drug products for over-the-counter (OTC) use that violate sections 502 and 505 of the Act (21 U.S.C. §§ 352 and 355).
We have reviewed your firm's response of April 15, 2010, and note that it lacks sufficient corrective actions.
Specific violations observed during the inspection include, but are not limited to, the following:
1. Your firm has not established or followed written procedures and responsibilities applicable to your quality control unit [21 C.F.R. § 211.22(d)].
For example, your firm manufactures over-the-counter (OTC) drug products without defining who has the responsibility to approve the master formulas used to manufacture the products and approve the product labeling your customers supply for the following products:
• Aloe Gel (master formulation (b)(4)) "Pain Relief. cc TM" (Pain Relief); and
• Aloe Gel (master formulation (b)(4) and (b)(4)) "Burn Relief' (Burn Relief).
Specifically, your firm used two different master formulas (b)(4) to manufacture Burn Relief, but could not provide documentation to show that your quality control unit (QCU) approved either formula. Furthermore, master formula (b)(4) does not include one of the labeled product ingredients, tocopheryl acetate (Vitamin E), but was used to manufacture at least four batches of Bum Relief.
You stated in your response that you are now providing a copy of your "Absolute Packaging Inc. 2010 Policies and Procedures" to all existing customers and including it as part of the new customer contracts. However, this response is not adequate because this procedure does not describe the quality control unit responsibilities to approve the master formulas used to manufacture the products or changes to the process. In addition, it lacks authorizing signatures and does not bear a date other than the year.
2. Your quality control unit has not approved or rejected all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product [21 C.F.R. § 211.22(c)].
For example, your QCU failed to approve specifications for the containers, closures, packaging materials, and labels used for the OTC drug products that you manufacture. Your firm does not maintain records of approval or rejection of these products. Moreover, your QCU did not date or approve two of your SOPs-(b)(4) and (b)(4) - which conflicts with (b)(4) "Document and Change Control SOP."
Your response failed to address this issue.
3. 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, you do not perform process validation for the filling, labeling, and packaging of OTC drug products you manufacture, including Pain Relief.
Your response failed to address this issue.
4. Your firm has not established scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity [21 C.F.R. § 211.160(b)].
For example, you have not developed adequate final product specifications for OTC drug products you manufacture that are released for distribution. Your firm conducts only pH, viscosity, specific gravity, and microbiological testing on the final drug product. However, these tests are not adequate because they do not verify the identity of the active ingredients used in your OTC drug products or that the products contain the correct amounts of the labeled ingredients. In addition, your firm has released at least four lots of Bum Relief that did not contain the labeled ingredient tocopheryl acetate (Vitamin E).
Your response did not address the issue of inadequate final product test procedures, except to state that you are implementing a double-check system to require a second person to verify the execution of the production order for the drug products you manufacture. This response is inadequate for the following reasons: (a) the double-check verification system would not necessarily prevent the release of drug products that lack a labeled ingredient when an incorrect formula is used to manufacture the product, and (b) you failed to address the lack of identity tests for ingredients used in your OTC drug products.
5. Your firm has not thoroughly investigated the failure of a batch or any of its components to meet its specifications whether or not the batch has already been distributed [21 C.F.R. §211.192].
Your firm's OTC drug products have been distributed prior to being released by your quality control unit. For example, Absolute Packaging, Inc. packing slip # 13402, dated November 5, 2009, documents that your firm shipped Aloe Gel lot # C1G01-09317 (4 oz. Solitary Solution), identified by your firm as Pain Relief, before your QCU released the lot on November 21, 2009. Our investigator noted that your firm's records indicated that you completed microbiological analysis on this lot on November 21, 2009, but your firm's documentation shows you shipped the lot on November 17, 2009.
You also failed to determine that your OTC drug product, Burn Relief (labeled as "(b)(4)"), conformed to the specifications for the identity and strength of each active ingredient. For example, your firm released for distribution four lots of this product that did not contain the labeled ingredient tocopheryl acetate (Vitamin E).
Additionally, your QCU released lot # CL-G01-09317 of Pain Relief for distribution even though the results for viscosity testing were outside the target specification range. Your QCU also failed to record the results for specific gravity testing for this lot in either the batch record or the Specific Gravity Measurements Log Book dated January 7, 2008 - March 10, 2010. Similarly, your QCU released lot # CL-G01-09139 of Pain Relief for distribution even though the results for viscosity testing were outside the target specification range and pH test results were not recorded in the pH Measurements Log Book dated November 8, 2008 - March 10, 2010. Your QCU did not investigate any of these failures and did not evaluate the adequacy of the product already distributed and available to consumers.
Your response is inadequate because the only corrective action your firm took was to notify your customer of the Burn Relief formulation error and of your subsequent correction to the master formula on March 31, 2010. Additionally, in your response, you stated that your firm implemented a double-check system requiring verification signature by a second person, but you failed to supply documentation that your firm has actually implemented this system. Also, your response did not address the failure of your QCU to review and approve manufacturing batch records before product is released for distribution.
6. 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, you did not perform a specific identity test on the menthol and camphor active ingredients used in Pain Relief. In addition, you failed to appropriately validate your suppliers' test results (as furnished to you on the suppliers' certificates of analysis) at appropriate intervals. We have concerns regarding your lack of compliance with CGMP regulations. Several of the CGMP deficiencies observed during this inspection were also observed during our 2007 and 2008 inspections. We recommend that you hire a qualified consultant to help you establish an adequate quality system that will clearly define your QCU's responsibilities and procedures regarding CGMP requirements. The consultant should also conduct appropriate CGMP training. In addition, you, with the assistance of your consultant, should conduct a comprehensive evaluation of all of your written procedures to ensure that they are adequate, complete, and in compliance with the CGMP regulations. In your response to this letter, please include an explanation of how you intend to implement, support, and sustain a comprehensive quality system at your firm that is consistent with CGMP.
In addition to the CGMP violations, your firm also manufactures drug products for over-the-counter (OTC) use that violate sections 502 and 505 of the Act (21 U.S.C. §§ 352 and 355).
Based on a review of the product labeling collected during the inspection of your facility, including each product's website that appears on its pre-printed label that you affix to it before shipping into interstate commerce, your products are drugs, as defined in section 201(g) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 321(g)], because they are intended for the use in the 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 they are intended to affect the structure or any function of the body of man.
Objectionable claims and the products for which these claims are being made, as well as statements of ingredients, include, but are not limited to, the following:
Statements found on the label:
• "Active ingredients ... Menthol, USP 2.0% ...Camphor, USP .53% ...."
• '"Inactive ingredients: Water, Aloe Vera Gel, Carbomer 940, Triethanolamine, Eucalyptus Oil, Methyl Salicylate, Peppermint Oil, Methylparaben, Propylparaben, EDTA ...."
Statements found on distributor's website, (b)(4)
• '"I suffered significant knee and ankle injuries while playing for the Miami Dolphins. The Pain Relief.cc reduced the pain and helped me recover and continue my career ...."
• "I have found miraculous results with the pain relief gel. All my adult life I've been plagued with degenerative discs and arthritis problems. I received instant pain relief from this gel ...."
• '"I use the Pain Relief.cc gel as a pretreatment for Ultrasound with tremendous results .."
• "We have started to apply the Gel to Horses with some remarkable results ...."
• '"Phil discovered the Pain relief.cc Gel and advised the owner to try some. We video taped the results. Tom, "I wouldn't believe it if I didn't see it." Shortly after the farriers applied the (b)(4) Then she was able to put her head down to the ground, lift and keep her forelegs up as they cleaned her hooves. After a few minutes she trotted back into the pasture for the first time in years ...."
• "We have DVDs showing several trainers applying the gel and the reaction of the horses. These DVDs show the application techniques that are working and provide an excellent visual demonstration. These DVDs cover Laminitis, injuries, and stress ...."
(b)(4) for Sunburn Relief
Statements found on the label:
• "INGREDIENTS: Aloe Extract, Tea Tree Oil, Eucalyptus, Potassium Sorbate, Tocopheryl Acetate (Vitamin E), Scelorium Gum ...."
• '"This pure Aloe Gel and Eucalyptus combines the healing effect of the aloe and the soothing properties of eucalyptus to help relieve sunburn pain ...."
• "Also excellent for skin rashes, shaving irritation, insect bite and jellyfish stings ...."
Statements found on distributor's website, www. (b)(4)
• "Our Aloe gel is excellent for sunburn but also knocks out irritation and itching from insect bites, eczema and rosacea ...."
• "I have rosacea, and my skin can have flare-ups especially around my nose. I had one about two weeks ago, my husband had just used the gel, and it was still out. I decided to try it, thinking it might bring the inflimation [sic] down, and therefore the redness . . . Wow!! It not only helped my redness, but actually helped with the breakouts that the rosacia [sic] causes ...."
• "I have large pores on my nose, have since I was a teenager, and I have tried EVERYTHING on the market (Neutragina(sp?) had a pore reducer a few years ago that worked, but you can't find it anymore). Your recovery gel, not even the stuff you sell for this purpose, worked better than anything I have ever used. My pores thank you ...."
Unapproved Drug Charges
Drug products intended for some of the indications as those promoted for Pain Relief.cc and (b)(4) for Sunburn Relief are being evaluated under the Tentative Final Monograph (TFM) for OTC External Analgesics in the Over-the-Counter (OTC) Drug Review (48 FR 5852 (February 8, 1983)).
Pain Relief.cc contains camphor, USP .53%, which is below the proposed dosage range of this ingredient for counterirritant uses. Camphor is proposed as a generally recognized safe and effective ingredient for use in a counterirritant product; however, the acceptable dosage range in the TFM is between 3% and 11%. Furthermore, indications such as significant knee and ankle injuries, degenerative discs, and the treatment of pain in horses are not included in any part of the OTC Drug Review. Additionally, we are not aware of a product with this formulation, for topical application, to treat pain associated with significant knee and ankle injuries, degenerative discs, or pain in animals, having been available in the U.S. market as an OTC drug at the inception of the OTC Drug Review. Therefore, this product is not eligible for the OTC Drug Review. Thus, the current marketing of Pain Relief.cc violates section 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)] because it is a new drug and it is not the subject of an approved new drug application.
The External Analgesics TFM also does not propose Tea Tree Oil, Eucalyptus, Potassium Sorbate, Tocopheryl Acetate (Vitamin E), and Scelorium Gum-the individual ingredients declared on the label for (b)(4) for Sunburn Relief-as generally recognized safe and effective active ingredients for analgesic, anesthetic, and antipruritic use. Further, the TFM does not include this particular combination of ingredients, nor was the combination evaluated in the developing monograph.
Moreover, the External Analgesics TFM does not provide for the treatment of jellyfish stings, for which (b)(4) for Sunburn Relief is labeled. In addition, your product is labeled for the treatment of eczema. The TFM does provide for the temporary relief of itching from minor skin irritations, inflammation, and rashes due to eczema, insect bites, poison ivy, poison oak, or poison sumac, soaps, detergents, cosmetics, jewelry, and/or for external genital, feminine and/or anal itching. However, the TFM lists hydrocortisone as the only acceptable active ingredient for this indication, and your product does not contain hydrocortisone.
In addition, OTC topical products intended for the treatment of eczema are subject to the Final Rule for Skin Protectant Drug Products under Title 21 CFR 347. This regulation lists the acceptable active ingredients and their concentration for products labeled for the treatment of minor cuts, scrapes, burns, chapped skin and lips, poison ivy, poison oak, poison sumac, and minor skin irritation and itching, including that caused by rashes, eczema, poison ivy, oak or sumac or insect bites. (b)(4) for Sunburn Relief is labeled to contain Aloe Extract, Tea Tree Oil, Eucalyptus, Potassium Sorbate, Tocopheryl Acetate (Vitamin E), and Scelorium Gum as the active ingredients. This regulation does not permit any of these ingredients as active ingredients when used for this indication (eczema). Further, this regulation does not provide for the treatment of rosacea for which (b)(4) for Sunburn Relief is labeled.
Therefore, (b)(4) for Sunburn Relief's combination of Aloe Extract, Tea Tree Oil, Eucalyptus, Potassium Sorbate, Tocopheryl Acetate (Vitamin E), and Scelorium Gum does not comply with the Final Rule for Skin Protectant Drug Products nor are they covered by the External Analgesics TFM. Further, we are unaware of any evidence that such a product formulated and labeled as (b)(4) for
Sunburn Relief was available in the U.S. market as an OTC drug at the inception of the OTC Drug Review. Thus, the current marketing of (b)(4) for Sunburn Relief violates section 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)] because it is a new drug and it is not the subject of an approved new drug application.
Since the adequacy of the indications for the labeled uses have not been established for Pain Relief.cc and (b)(4) for Sunburn Relief, these products are misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)].
In addition, these products are sold OTC as drugs, and as required by 21 U.S.C. § 352(e)(1)(A)(ii) and (iii), OTC drugs must list the active and inactive ingredients separately. The labeling for (b)(4) for Sunburn Relief does not differentiate between active and inactive ingredients, as required, and, therefore, this product is misbranded under section 502(e)(1)(A) of the Act [21 U.S.C. § 352(e)(1)(A)].
(b)(4) for Sunburn Relief is further misbranded under section 502(c) of the Act [21 U.S.C. § 352(c)] because it does not follow the drug labeling format requirements under 21 C.F.R. § 201.66.
In addition, Pain Relief.cc and (b)(4) for Sunburn Relief are misbranded under section 502(a) of the Act [21 U.S.C. § 352(a)] because they are false or misleading in that the products lack adequate labeling for their intended uses that are found on the distributor's website, (b)(4), and (b)(4), respectively. Under regulation 21 C.F.R.§ 201.128, intended uses for a product manufactured by you include those uses for which you are aware. Specifically, the objective intent: may be shown by the circumstances that the article is, with the knowledge of such persons or their representatives, offered and used for a purpose for which it is neither labeled nor advertised ... if a manufacturer knows, or has knowledge of facts that would give him notice that a drug introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than the ones for which he offers it, he is required to provide adequate labeling for such a drug which accords with such other uses to which the article is to be put.
In this case, your firm manufactures the product Pain Relief.cc for the distributor (b)(4)" and (b)(4) for Sunburn Relief for the distributor "(b)(4)" and includes the names of these distributors on each respective product label, and, therefore, would have access to the distributor's websites, making the drug claims listed above. The labels of your products are misleading because they "fail to reveal facts material in the light of such representations or material with respect to consequences which may result from the use of the article to which the labeling or advertising relates under the conditions of use prescribed in the labeling or advertising thereof or under such conditions of use as are customary or usual." Section 201(n) of the Act [21 U.S.C. § 321(n)]. Specifically, you do not include information about the treatment of pain for significant knee and ankle injuries, degenerative discs, and the treatment of pain in horses on the label of Pain Relief.cc or the treatment of eczema and rosacea on the label of (b)(4) for Sunburn Relief. Therefore, both of these products are misbranded under § 502(a) of the Act [21 U.S.C. § 352(a)]. In addition, the products are misbranded under section § 502(f)(1) of the Act, [21 U.S.C. § 352(f)(1)] because the products' labels fail to provide adequate directions for use.
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. Additionally, your response should state if you no longer manufacture or distribute the OTC drug products manufactured at this facility, including, but not limited to, Burn Relief (labeled for sale as (b)(4) for Sunburn Relief') and Pain Relief, and provide the date(s) and reason(s) you ceased production.
Please send your reply to the Food and Drug Administration, Attention: Carla A. Norris, Compliance Officer, 555 Winderley Place, Suite 200, Maitland, Florida, 32751. If you have questions regarding any issues in this letter, please contact Ms. Norris at (407) 475-4730.
Emma R. Singleton
Director, Florida District