Inspections, Compliance, Enforcement, and Criminal Investigations
Mushroom Wisdom, Inc. 10/18/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
Waterview Corporate Center
Telephone (973) 331-4904
October 18, 2012
Masaki (Michael) Shirota
Mushroom Wisdom, Inc.
1 Madison Street, Building F6
East Rutherford, New Jersey 07073
Dear Mr. Shirota:
The U.S. Food and Drug Administration (FDA) conducted an inspection of your dietary supplement manufacturing facility, located at 1 Madison Street, Building F6, East Rutherford, New Jersey, from April 2, 2012 through April 30, 2012. During the inspection, our investigators collected labeling for your products and evaluated the manufacturing of several of your products which you label as dietary supplements, including Amyloban 3399 From Lion’s Mane, Grifron Maitake, and Super Shiitake. Based on our review, we documented serious violations of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations. You may find the Act and its implementing regulations through links on FDA’s home page at http://www.fda.gov.
Unapproved New Drugs
Based on our review of the product labels for your products listed below, we have determined that these products are labeled for conditions that cause them to be drugs within the meaning of section 201(g)(1)(B) of the Act [21 U.S.C. § 321(g)(1)(B)]. The therapeutic claims on your labels establish that the products are drugs because they are intended for use in the cure, mitigation, treatment, or prevention of disease.
Examples of some of the therapeutic claims observed on your product labels include:
Amyloban 3399 From Lion’s Mane:
- “[W]e have successfully isolated a substance (amyloban) from a mushroom called Lion’s Mane (Hericium erinaceum) that has been shown to support the survival of nerve cells in the presence of toxic amyloid …”
- “It also displays hepato-protective and anti-fungal activities.”
Because these products are not generally recognized as safe and effective for the above referenced uses, they are “new drugs” under section 201(p) of the Act [21 U.S.C. § 321(p)]. New drugs may not be legally marketed in the United States without prior approval from FDA as described in section 505(a) of the Act [21 U.S.C. § 355(a)]. FDA approves a new drug on the basis of scientific data submitted by a drug sponsor to demonstrate that the drug is safe and effective.
Adulterated Dietary Supplements
In addition, even if your products, including those listed above, were not labeled for conditions that cause them to be unapproved new drugs, they would be adulterated dietary supplements within the meaning of section 402(g)(1) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 342(g)(1)], in that the dietary supplements have been prepared, packed, or held under conditions that do not meet the Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements regulation, Title 21, Code of Federal Regulations (CFR), Part 111 (21 CFR Part 111).
Your firm conducts a number of operations for products you label as dietary supplements and approves such products for release for distribution under your firm’s name. Based on our inspection, we note that you supply your contract manufacturers with raw materials, including the dietary ingredients, for use in the manufacture of your firm’s products. In addition, you develop the labels for your products and supply them to your contract manufacturers for use in the labeling of your products. All finished products made for you by other firms are then shipped back to your firm for approval for release and distribution.
In the dietary supplement CGMP final rule (72 Fed. Reg. 34752, 34790; June 25, 2007), FDA recognized it was not practical to list all possible contractual relationships that persons may enter into in the manufacture of a dietary supplement, or to list all businesses or practices that may be subject to the requirements of this final rule in order for persons to know whether they are subject to requirements of the final rule. Id. However, the agency did provide some examples. For example, a distributor may contract with one firm to manufacture a dietary supplement and another firm to package and label the dietary supplement that the distributor ultimately distributes under its own name. Such a distributor has an obligation to know what and how manufacturing activities are performed so that the distributor can make decisions related to whether the packaged and labeled product conforms to its established specifications and whether to approve and release the product for distribution. Id. Therefore, to the extent that Mushroom Wisdom, Inc. contracts with other firms to perform operations for its manufacturing, packaging and labeling for the dietary supplements it distributes under the firm’s name, Mushroom Wisdom, Inc. it is responsible for ensuring that such supplements are not adulterated under section 402(g) of the FD&C Act.
Although such other firms must comply with the CGMP requirements that apply to their operations related to the manufacture, packaging, labeling, and holding of dietary supplement, Mushroom Wisdom, Inc., is responsible for ensuring that the dietary supplements manufactured, packaged, and labeled under its direction, are not adulterated for failure to comply with dietary supplement CGMP requirements. Thus, Mushroom Wisdom, Inc. is ultimately responsible for the manufacturing, packaging and labeling operations, even though it has hired another person to perform those job tasks (72 Fed. Reg. 34752 at 34790). As such, we would expect Mushroom Wisdom, Inc., under such circumstances, to have records related to dietary supplement CGMP requirements (e.g., specifications, master manufacturing record) readily available during the retention period for inspection and copying by FDA when requested (see 21 CFR 111.610).
Our investigators noted a number of violations on the form FDA 483, Inspectional Observations, based on dietary supplement CGMP requirements related to the operations that your firm conducts, which was issued to you on April 30, 2012. Specifically, our investigators observed the following violations:
- Your firm did not verify that a subset of the finished batches of dietary supplements, identified through a sound statistical sampling plan, or every finished batch, meets product specifications for identity, purity, strength, and composition, and for the limits on those types of contamination that may adulterate or that may lead to adulteration of the dietary supplement as required by 21 CFR 111.75(c). Specifically, you did not verify that the following finished dietary supplements met product specifications for identity, purity, strength and composition: Breast Mate with Vitamin D3, Heart Mate with CoQ10, and Prost Mate with Saw Palmetto.
Although your firm sent out samples of these finished product lots to outside laboratories for testing, the laboratories only tested for heavy metals (mercury, lead, arsenic, and cadmium) and food chemistry (ash, total calories, total carbohydrates, fat, moisture, and protein); instead of conducting assay tests to determine that the components were consistent with your firm’s established specifications. Heavy metals and food chemistry are not included in your finished product specifications.
- Your firm did not conduct at least one appropriate test or examination to verify the identity of a component that is a dietary ingredient, prior to its use, as required by 21 CFR 111.75(a)(1)(i). Your firm supplies its contract manufacturers with raw materials, including dietary ingredients, that such other manufacturers use in the manufacture of your firm’s dietary supplements; however, our investigators found that you did not conduct at least one test or examination to verify the identity of such dietary ingredients, as required by 21 CFR 111.75(a)(1). Instead, your firm relied on Certificates of Analysis (COA) from your suppliers. A COA from a supplier may not be used to verify the identity of any component that is a dietary ingredient [see 21 CFR 111.75(a)]. Specifically:
- Your firm received the dietary ingredient, Maitake PSX-Fraction Lot #100625, from (b)(4). with a COA and did not verify the identity of the dietary ingredient prior to sending the product to the contract manufacturer for use in the manufacture of your dietary supplement. In addition, your firm’s specification sheet for the Maitake PSX-Fraction declares 18% active glycoproteins for your mushroom ingredients used in products such as Maitake PSX-Fraction, Heart Mate, and Joint Mate; however, you have no records to support that you verified this claim.
- Your firm did not conduct tests to verify the identity of eight out of approximately (b)(4) released for use in manufacture of your firm’s dietary supplements since September 2010 in accordance with the regulation; instead, your firm randomly performs heavy metal analysis on these dietary ingredients.
Before using a component that is a dietary ingredient, you must conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient, unless you have petitioned FDA for an exemption from such testing, consistent with the requirements in 21 CFR 111.75(a)(1)(ii), and FDA has granted such petition. Your firm has not petitioned FDA for such an exemption.
Furthermore, if you would like to rely on a certificate of analysis from the supplier of the components (other than dietary ingredients) you receive for use in your firm’s dietary supplements to confirm the identity of such components, you must first qualify your suppliers by establishing the reliability of the suppliers’ certificates of analysis through confirmation of the results of the supplier's tests or examinations [21 CFR 111.75(a)(2)(ii)(A)].
- A qualified person from your firm did not investigate any product complaint that involves a possible failure of a dietary supplement to meet any of its specifications, or any other requirements of this part, including those specifications and other requirements that, if not met, may result in a risk of illness or injury, as required by 21 CFR 111.560(a)(2). For example:
- AER #1009 – in October 2011, a consumer reported an allergic reaction to Super Cordyceps, Lot #090009. Your firm’s report indicated that Lot #090009 was not from any of your batches within the past month and no further investigation was documented. However, upon review of your firm’s released batches, Super Cordyceps, Lot #090009 was released on 10/25/2010 by your firm and has an expiration date of 09/2013.
- AER #1008- a customer reported on 06/01/2011 that her husband’s blood pressure increased when taking Amyloban 3399. Your firm did not document any further investigation or findings.
- AER #1005- a customer reported on 07/12/2010 that her tongue was burned when she took Super Lion’s Mane. Your firm did not document any further investigation or findings.
- Your firm did not make and keep written procedures for laboratory operations, including written procedures for the tests and examinations that you conduct to determine whether specifications are met, as required by 21 CFR 111.325(b)(1). Specifically, your firm performs in-process acceptance testing (for hardness and pH) but does not have established procedures or documentation for laboratory tests performed and the corresponding results obtained. The documentation for laboratory tests and examinations must include the results of the testing and examination [21 CFR 111.325(b)(2)(ii)].
- Your firm failed to make and keep any material review and disposition decision on a returned dietary supplement, as required by 21 CFR 111.535(b)(2). Specifically, three of your product return reports did not document the disposition of the returned products, as follows:
- RA #48039 dated 08/12/2010 for Super Tremella and Collagen/Pearl with SX was returned after the customer stated she was allergic to an ingredient.
- RA #829 dated 07/21/2010 for Super Lion’s Mane related to AER #1005, the customer complained her tongue was burned when she took Super Lion's Mane Lot #040040.
- RA #48035 dated 06/28/2010 for Amyloban 3399 related to AER #1003, the customer reported aches in her thighs when taking Amyloban 3399 Lot #059020.
Your firm did not identify each unique lot within each unique shipment of labels in a manner that allows you to trace the lot to the supplier, the date received, the name of the label, the status of the label (e.g., quarantined, approved, or rejected); and to the dietary supplement that you distributed, as required by 21 CFR 111.160(d)(1). Further, your firm’s quality personnel did not approve the packaging and labels for use in the manufacture of a dietary supplement and release them from quarantine, as required by 21 CFR 111.160(c)(3). For example, a new label was created in February 2011 for your Heart Mate product, which was initialed and dated by (b)(4). However, the proof does not include a date and approval signature by the individual who is responsible for approving labels nor does it include a unique identifier.
The above violations cited in this letter are not meant to be an all-inclusive list of violations in your products and their labeling. It is your responsibility to ensure that your products are in compliance with the Act and its implementing regulations. You should take prompt action to correct the violations cited in this letter and prevent their recurrence. Failure to do so may result in enforcement action by FDA without further notice, such as seizure and/or injunction.
We also have the following comments:
- You could not provide written records of calibrations, inspections, and checks of automated, mechanical, and/or electronic equipment in accordance with 21 CFR 111.35(b)(4).
- We suggest that you have data to support the "best used by date" established in your firm’s finished product specifications and applied to your firm’s finished dietary supplement products, including Breast Mate, Heart Mate, Prost Mate and Brain Mate (see 72 FR 34752 at 34856; June 25, 2007).
We received your written response related to the FDA Form 483, on July 25, 2012. We do not address that response because it arrived more than 15 working days after the close of the inspection. Consistent with FDA’s federal register notice of August 11, 2009 announcing its program to facilitate the timely issuance of warning letters (74 FR 40211-12), FDA will evaluate your December 2, 2012 response along with any response to this warning letter.
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 these violations. Your response should include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete the corrective actions within fifteen working days, you should state the reason for the delay and provide the date when you will correct any remaining violations.
Your response should be sent to the following address: U.S. Food and Drug Administration, 10 Waterview Blvd., Parsippany, New Jersey 07054. If you should have any questions regarding any issue in this letter, please contact Andrew Ciaccia, Compliance Officer.
New Jersey District Office