Inspections, Compliance, Enforcement, and Criminal Investigations
Amerifit Brands, Inc 07-Nov-07
Department of Health and Human Services
Public Health Service
New England District
VIA FEDERAL EXPRESS
November 7, 2007
Cyrill Siewert, CEO
Amerifit Brands, Inc.
55 Sebethe Drive
Cromwell, Connecticut 06416
Dear Mr. Siewert:
An inspection of your drug manufacturing facility located at 11 State Street, Woburn, Massachusetts conducted by a Food and Drug Administration (FDA) investigator from April 10 to May 10, 2007, revealed significant deviations from FDA's current good manufacturing practice (CGMP) regulations, Title 21, Code of Federal Regulations (CFR) Parts 210 and 211. These CGMP deviations were listed on an Inspection Observations (FDA-483) form issued to your firm at the close of the inspection.
These CGMP deviations cause your human 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 test methods used in, and procedures and controls used for, the manufacture, processing, and holding of drugs do not conform with CGMP to assure that such drugs meet the requirements of the Act as to safety, and have the identity and strength, and meet the quality and purity characteristics, which they purport or are represented to possess.
Our investigator found the following significant deviations from the CGMPs for drug products:
1) Failure to confirm that each batch of drug product conforms to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release as required by 21 C.F.R. § 211.165(a). For example, your firm does not test for the active ingredient belladonna for your B & O Supprettes No. 15A and No. 16A Rectal Suppositories.
2) Failure to conduct at least one specific identity test and establish the reliability of the supplier's analyses through appropriate validation of the suppliers test results at appropriate intervals as required by 21 C.F.R. § 211.84(d)(2). For example, although you accept the certificate of analysis for the active ingredient belladonna, you do not perform at least one specific identity test and you have not established the reliability of the supplier's analyses. Belladonna is used in the manufacture of B & 0 Supprettes No. 15A and No. 16A Rectal Suppositories.
3) Failure to reject a component that did not meet the appropriate written specifications for strength, quality, and purity as required by 21 C.F.R. § 211.84(e). For example,
a) Your firm used [redacted] that failed the acceptance criteria of [redacted]. The assay results from [redacted] containers were [redacted] and [redacted], for an average of [redacted]. Your firm used this lot in manufacturing after applying a "correction factor for the [redacted] assay.
b) Your firm used [redacted] that failed the acceptance criteria for [redacted]. The assay results from [redacted] containers were [redacted] and [redacted] for an average of [redacted]. Your firm used this lot in manufacturing after applying a "correction factor" for the [redacted] assay.
4) Failure to establish scientifically sound and appropriate specifications and test procedures to assure that components and drug products conform to appropriate standards of identity, strength, quality, and purity as required by 21 C.F.R. § 211.160(b). For example,
a) Results for stability testing for the active ingredient powdered opium, which are used in B & O Supprettes No. 15A and 16A Rectal Suppositories, failed to meet your release specifications of [redacted]. The specifications were later changed to [redacted] and there is no evidence that these new specifications are scientifically sound and appropriate.
b) Urised Tablets stability specifications are [redacted] for each of the active ingredients: benzoic acid, methenamine, methyl blue, phenyl salicylate, atropine sulfate and hyoscamine. There is no evidence that the specifications are scientifically sound and appropriate.
5) Failure to test in-process materials for identity, strength, quality, and purity and approve or reject the materials by the quality control unit as required by 21 C.F.R. § 211.110(c). For example, material recovered from the filling machine at the end of production that is used in the manufacture of the next batch of B & O Supprettes is not tested for identity, strength, quality, and purity, and approved or rejected by the quality control unit.
6) Failure to have appropriate stability data to determine expiration dates for B & O Supprettes No. 15A and No. 16A Rectal Suppositories as required by 21 C.F.R. § 211.166(a). Your firm was unable to obtain consistent assay results in its testing for the active ingredient belladonna that would support a 3 year expiration dating period.
7) Failure to have separate areas or such other control systems as are necessary to prevent mix-ups of finished product, both before and after release, while in storage as required by 21 C.F.R. § 211.42(c)(7) and (8). For example,
a. Recalled product returned by customers was not identified as such or labeled as quarantined but was observed to be stored in close proximity to pallets of the same drug that was marked as acceptable.
b. Bulk tablets that had not yet been released by QC were stored next to approved bulk tablets awaiting packaging in the finished goods warehouse and were not identified as quarantined or unapproved.
8) Failure to store drug products under appropriate conditions of temperature, humidity, and light so that the identity, strength, quality, and purity of the drug products are not affected as required by 21 C.F.R. § 211.142(b). For example, your firm does not monitor the temperature or humidity in any warehouse areas where components and finished drug products are stored.
9) Failure to maintain records for all components for at least one year after the expiration date of the drug product as required by 21 C.F.R. § 211.180(b). For example, your firm destroyed records associated with Powdered Belladonna Extract, lot R01-21, based on the expiration of the lot of raw material, rather than the expiration date of the drug product in which it was used.
10) Failure to evaluate, at least annually, the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures as required by 21 C.F.R. § 211.180(e).
11) Failure to follow your written procedure to update your firm drug listing information on Form FDA-2657 as required by 21 C.F.R. § 207.30. For example, you have not listed Anestacon Jelly, Cystospaz Tablets, Urised Tablets, Aquachloral Supprettes 5 gr, B & O No. 15A and 16A Supprettes and AZO Standard since you acquired these products in October 2005.
Moreover, you market unapproved new drugs in violation of the Act. B & O No. 15A Rectal Suppositories, B & O No. 16A Rectal Suppositories, Urised 100 Tablets, Aquachloral 5 gr Suppositories, and Cystospaz are drugs within the meaning of Section 201(g) of the Act, 21 U.S.C. § 321(g), because they are intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease. Further, they are "new drugs" within the meaning of Section 201(p) of the Act, 21 U.S.C. § 321(p), because they are not generally recognized as safe and effective for their labeled uses. Under Sections 301(d) and 505(a) of the Act, 21 U.S.C. §§ 331(d) and 355(a), a new drug may not be introduced into or delivered for introduction into interstate commerce unless an FDA-approved application is in effect for the drug. Your sale of B & O No. 15A Rectal Suppositories, B & O No. 16A Rectal Suppositories, Urised 100 Tablets, Aquachloral 5 gr Suppositories, and Cystospaz without such approved applications violates the Act. We acknowledge your response, dated July 26, 2007, to the inspectional observations that address violations of the CGMP requirements. However, until an FDA-approved application is in effect for B & O No. 15A Rectal Suppositories, B & O No. 16A Rectal Suppositories, Urised 100 Tablets, Aquachloral 5 gr Suppositories, and Cystospaz, we will defer our comments on corrective actions for the CGMP violations provided in your response that relate to these products or any other unapproved new drugs that you manufacture.
Additionally, the above products are misbranded because, as prescription drugs, adequate directions cannot be written for them so that a layman can use these products safely for their intended uses. Consequently, their labeling fails to bear adequate directions for use as required under Sections 502(f)(1) of the Act, 21 U.S.C. § 352(f)(1), and because they lack required approved applications, they are not exempt from this requirement under 21 C.F.R. § 201.115.
Although there were numerous drug products marketed before the enactment of the Act in 1938 and its amendment in 1962, FDA believes that it is unlikely that currently marketed products such as yours are grandfathered or otherwise not a new drug. The grandfather clauses have been construed very narrowly by the courts and drug products on the market would not be entitled to grandfather status if they differed from the previous versions in some respect, such as formulation, dosage or strength, dosage form, route of administration, indications, or intended patient population. (See the appendix of our marketed unapproved drugs CPG, http://www.fda.gov/cder/guidance/6911fnl.htm, lines 323-329.)
Further, it is FDA's view that companies claiming that their products are grandfathered bear responsibility to fully document their products' grandfathered status. Any company marketing products on this basis should have available documentation to demonstrate the market presence of the product prior to the enactment of the new drug requirements that were established in 1938 and 1962.
The issues and violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility or include all drugs that are marketed in violation of the drug approval requirements. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence or the occurrence of other violations. It is your responsibility to assure that your firm complies with all requirements of federal law and FDA regulations.
You should discontinue manufacturing and distributing your B & O No. 15A Rectal Suppositories, B & O No. 16A Rectal Suppositories, Urised 100 Tablets, Aquachioral 5 gr Suppositories, and Cystospaz drug products, and any other new drugs, until an FDA-approved application is in effect. You should take prompt action to correct the CGMP deviations cited for any of your other products that may be legally marketed without anapproved application. Failure to promptly correct violations may result in regulatory 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 my withhold approval of requests for export certificates, or approval of pending new drug applications listing your facility as a manufacturer until the above violation are corrected. A reinspection may be necessary.
Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct the violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well ascopies of related documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will completethe correction. Provide us also with a list of all drugs that you manufacture or market, along with, for each drug, the NDA or ANDA number under which you manufacture or market the drug or a statement describing the basis on which you claim for the drug an exemption from the drug approval requirements. With the exception of B & O No. 15A Rectal Suppositories, B & O No. 16A Rectal Suppositories, Urised 100 Tablets, Aquachloral 5 gr Suppositories, and Cystospaz, please provide the labeling for each drug marketed without an approved application. If you no longer manufacture or market any of your drug products, your response should so indicate, including the reasons for, and the date on which, you ceased production.
Your reply should be directed to Food and Drug Administration, Attention: Bruce R. Ota, Compliance Officer, One Montvale Avenue, Fourth Floor, Stoneham, Massachusetts 02180.
Gail T. Costello
New England District
Attachment: Form FDA-483, List of Observations
cc: Craig Larson, VP Legal & Regulatory Affairs
Amerifit Pharma, Inc.
11 State Street
Woburn, Massachusetts 01801