WARNING LETTER
Biomic Sciences, LLC dba ION Intelligence of Nature
MARCS-CMS 667601 —
May 09, 2024
Delivery Method:
VIA UPS
Product:
Food & Beverages
Recipient:
Recipient Name
Dr. Zachary Bush
Recipient Title
Owner
Biomic Sciences, LLC dba ION Intelligence of Nature
4351 Seminole Trail
Charlottesville
,
VA
22153-2823
United States
Issuing Office:
Division of Human and Animal Food Operations East II
United States
May 9, 2024
WARNING LETTER
CMS #667601
Dear Dr. Bush,
The U.S. Food and Drug Administration (FDA) conducted an inspection of your facility located at 4351 Seminole Trail, Charlottesville, Virginia from June 12 through August 31, 2023. Based on inspectional findings and review of the product labels collected during the inspection, as well as review of your website at www.Intelligenceofnature.com, we have identified significant violations of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations. You can find the Act and FDA regulations through links on FDA’s home page at www.fda.gov.
At the conclusion of the inspection on August 31, 2023, our investigator provided you with a Form FDA 483, Inspectional Observations (FDA 483). We acknowledge receipt of your responses dated September 22, October 31, and November 15, 2023; and April 24, 2024. We address your responses below, when relevant information from such response(s) pertained to a particular issue.
Adulterated Human Drugs
FDA Tested Samples
FDA conducted laboratory testing of a lot of ION Intelligence of Nature Sinus Support Nasal Spray drug product and results demonstrate that this drug product is adulterated within the meaning of section 501(a)(1) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 351(a)(1), in that it consists in whole or in part of any filthy, putrid, or decomposed substance.
FDA laboratory analysis determined that a sample of your ION Intelligence of Nature Sinus Support Nasal Spray drug product was grossly contaminated with microorganisms. This gross contamination is particularly concerning because your drug product is a nasal spray.
FDA laboratory testing of ION Intelligence of Nature Sinus Support Nasal Spray drug product lot 2302081HGA found gross microbial contamination. The individual sample results varied between 510,000 and up to 1,100,000 colony forming units (CFU)/mL for total aerobic microbial count and between 290 and up to 1,100 CFU/mL for total yeast and mold counts. Therefore, this drug product is adulterated under section 501(a)(1) of the Act.
Microorganisms identified included
Microbacterium sp., Fictibacillus sp., Bacillus sp. (primarily B. malikii)
, and
Paenibacillus sp.
The high bioburden in conjunction with the route of administration with this drug product poses a high risk of harm to vulnerable patients.
On September 22, 2023, the FDA held a teleconference with you. During the teleconference, you agreed to conduct a voluntary recall of all lots of ION Intelligence of Nature Sinus Support Nasal Spray.
On September 29, 2023, you voluntarily recalled all lots of ION Intelligence of Nature Sinus Support Nasal Spray, ION Sinus, and Restore Sinus Spray products to the consumer level due to microbial contamination identified as
Microbacterium sp., Fictibacillus sp., Bacillus sp.
(primarily
B. malikii
), and
Paenibacillus sp
., as noted on the following FDA website:
https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/biomic-sciences-issues-voluntary-nationwide-recall-ion-sinus-support-ion-sinus-and-restore-sinus
Drug CGMP Violations
The inspection of your facility from June 12 through August 31, 2023, identified significant violations of FDA’s regulations for Current Good Manufacturing Practice (CGMP) for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Act, 21 U.S.C. 351(a)(2)(B).
During our inspection, our investigators observed specific violations including, but not limited to, the following.
1. Your firm failed to conduct, for each batch of drug product, appropriate laboratory testing, as necessary, required to be free of objectionable microorganisms (21 CFR 211.165(b)).
Your firm released finished drug product without adequate testing for critical microbial attributes (i.e., testing to ensure absence of objectionable microorganisms). Without appropriate testing of each lot of drug product required to be free of objectionable microorganisms prior to release, you did not have scientific evidence that the lots were free of microbial contamination that is objectionable in view of its intended use. Particularly for a drug product that is intended for use as a nasal spray, it is essential that your drug products are tested for microbial contamination to minimize the risk of patient exposure to significant numbers or harmful species of microorganisms, harmful microbial metabolites and/or toxins, and drug spoilage or degradation.
You also stated during the inspection that you add
(b)(4)
to numerous drug product formulations to control microbial growth. Preservatives are not a substitute for a comprehensive approach to preventing objectionable microorganisms from contaminating your drug product and cannot be relied on to reduce in-process bioburden during manufacturing. Additionally, long term use of medicinal compounds containing
(b)(4)
may
(b)(4)
. Levels of
(b)(4)
exposure that have led to
(b)(4)
documented and therefore, it is not possible to establish minimum levels that are safe.
In your September 22, 2023, response, you state that you stopped producing and discontinued sales of the current formulation of ION Intelligence of Nature Sinus Support but plan to market a nasal product in the future. You state that you are revising your written procedures for quality unit (QU) responsibilities, including to specifically establish adequate testing of your finished product and water used in production of your products. You also state that you are revising procedures to ensure all applicable tests impacting the identity, strength, quality, and purity of your products are established and performed.
In response to this letter, clarify whether you plan to resume manufacturing drug products at this facility in the future for marketing in the United States. We request that you notify this office before you market such drug products.
2. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).
Your firm failed to establish an adequate QU with responsibilities to ensure adequate oversight for the manufacture of your drug products. For example, your QU failed to ensure:
Adequate procedures that are designed to prevent objectionable microbiological contamination of drug products (21 CFR 211.113(a)).
Adequate testing of components with potential for microbiological contamination that is objectionable in view of its intended use (21 CFR 211.84(d)(6)).
Procedures are followed to adequately establish, review, and approve master manufacturing records prior to use (21 CFR 211.100(a)).
Adequate batch records to document the mixing and packaging of your drug product (21 CFR 211.188).
Establishment of an adequate stability program to support expiration dating of your drug products (including microbiological attributes) (21 CFR 211.166(a)).
Adequate documentation for QU review and release of drug product. (21 CFR 211.22(a)).
Additionally, your QU was unaware of the identity of numerous proprietary components used to manufacture many of your drug products, and therefore could not have fulfilled their QU responsibilities to ensure all components meet established specifications for identity, strength, quality, and purity.
Your firm’s quality systems are inadequate. You may refer to FDA’s guidance document
Quality Systems Approach to Pharmaceutical CGMP Regulations
for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.
CGMP Consultant Recommended
Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements if your firm intends to resume manufacturing drugs for the U.S. market. The qualified consultant should also perform a comprehensive six-system
1
audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.
Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.
Adulterated & Misbranded Dietary Supplements
Adulterated Low Acid Canned Food Dietary Supplements
The inspection of your facility on June 12 through August 31, 2023, identified serious violations of the Emergency Permit Control regulation Title 21, Code of Federal Regulations (CFR), Part 108 (21 CFR Part 108) and the Thermally Processed Low-Acid Foods Packaged in Hermetically Sealed Containers regulation (21 CFR Part 113). These violations cause your products to be adulterated within the meaning of section 402(a)(4) of the Act, 21 U.S.C. 342(a)(4), in that they were prepared, packed, or held under insanitary conditions whereby they may have become contaminated with filth or rendered injurious to health.
As a manufacturer of low acid canned food products, you are required to comply with the Act and the Federal regulations relating to the processing of low-acid foods packaged in hermetically sealed containers. The Emergency Permit Control regulations were issued, in part, pursuant to section 404 of the Act, Emergency Permit Control, 21 U.S.C. 344. A temporary emergency permit may be required for thermally processed low-acid foods packaged in hermetically sealed containers whenever a processor has failed to fulfill the requirements of 21 CFR 108.35, including registration and filing of process information, and the mandatory requirements in 21 CFR Parts 113. Regulations specific to the processing of LACF products are described in 21 CFR 108 and 21 CFR 113.
1. You did not register with the FDA as a commercial processor of low-acid foods. A commercial processor of low-acid foods is required, not later than 10 days after first engaging in the manufacture, processing, and packaging of thermally processed low-acid foods in hermetically sealed containers in any state, as defined in section 201(a)(1) of the Act, to register and file a Form FDA 2541 (food canning establishment registration) with the FDA, as required by 21 CFR 108.35(c)(1). However, your firm processes Ion Gut Support, a low-acid food, without registering with the FDA.
2. You must file the scheduled processes with the FDA for each low-acid food in each container size as required by 21 CFR 108.35(c)(2). This filing must occur not later than 60 days after registration and prior to the packing of a new product and include the processing method, type of retort or other thermal processing equipment employed, minimum initial temperatures, times and temperatures of processing, sterilizing value, or other equivalent scientific evidence of process adequacy, critical control factors affecting heat penetration, and source and date of the establishment of the process, for each product in each container size. Specifically, as noted during the inspection, your firm did not file a scheduled process with FDA for your Ion Gut Support product. Further, a scheduled process shall be established by a qualified person who has expert knowledge acquired through appropriate training and experience in the acidification and processing of, as required by 21 CFR 113.83
Your response indicates that you have initiated contact with a process authority,
(b)(4)
. We acknowledge that you have initiated actions. However, this violation remains uncorrected.
Scheduled process information for low-acid foods processed by retort must be submitted on Form FDA 2541d (Food Process Filing for Low-Acid Retorted Method) and low-acid foods controlled by water activity must be submitted on Form FDA 2541f (Food Process Filing for Water Activity/Formulation Control Method). More information on registration and filing can be found in the publication “Guidance for Industry: Submitting Form FDA 2541 (Food Canning Establishment Registration) and Forms FDA 2541d, FDA 2541e, FDA 2541f, and FDA 2541g (Food Process Filing Forms) to FDA in Electronic or Paper Format” available at http://www.fda.gov/food/guidanceregulation/guidancedocumentsregulatoryinformation/ucm309376.htm.
Violations of Dietary Supplement CGMPs
The inspection of your facility from June 12 through August 31, 2023, identified serious violations of the FDA’s regulations for Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, under Title 21, Code of Federal Regulations (CFR), Part 111 (21 CFR Part 111). These violations cause your Ion Gut Support dietary supplement to be adulterated within the meaning of section 402(g)(1) of the Act, 21 U.S.C. 342(g)(1), because it has been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements.
Your significant violations of dietary supplement CGMP requirements are as follows:
1. You failed to establish identity specifications for each component you use in the manufacture of a dietary supplement, as required by 21 CFR 111.70(b)(1); component specifications that are necessary to ensure that specifications for the purity, strength, and composition of dietary supplements manufactured using the components are met, as required by 21 CFR 111.70(b)(2); and limits on those types of contamination that may adulterate, or that may lead to adulteration, of the finished batch of the dietary supplement to ensure the quality of the dietary supplement, as required by 21 CFR 111.70(b)(3).
For your components, you purport to use your Biomic Sciences Component Specification sheets as your specifications for raw components
(b)(4)
, used in the manufacture of your Ion Gut Support. However, these specification sheets do not include identity specifications for any of these components, as required by 21 CFR 111.70(b)(1); do not establish component specifications for
(b)(4)
or components
(b)(4)
that will ensure the purity of your Ion Gut Support, as required by 21 CFR 111.70(b)(2); and do not establish contamination specifications for
(b)(4)
, as required by 21 CFR 111.70(b)(3).
(b)(4)
is susceptible to having contaminants not limited to microorganisms and heavy metals.
We have received your responses dated September 22, October 31, and November 15, 2023; and April 24, 2024. In your response dated September 22, you state that you are establishing identity component specifications and acceptance criteria using appropriate scientifically valid methods. However, you do not present any supporting evidence for us to evaluate your correction. Your response dated October 31 provides specifications that are for microbial contamination only and does not demonstrate that the requirements of 21 CFR 111.70(b) are met. Your November 15, 2023, and April 24, 2024, responses do not address this citation.
2. You failed to establish product specifications for the identity, strength, and composition of the finished batch of the dietary supplement, as required by 21 CFR 111.70(e). For example, your product label for ION Gut Support lists the content of Humic Extract (from Ancient Soil) in the product as 5 mg; however, you have not established a strength specification for a finished batch of product to ensure that the label claim is met. For each specification you are required to establish and must take specific actions, after they are established, to verify that the specifications are met, as required by 21 CFR 111.73 and 21 CFR 111.75. You must also ensure any tests and examinations you use to determine whether the specifications are met are appropriate, scientifically valid methods, as required by 21 CFR 111.75(h)(1), and you must make and keep records, in accordance with 21 CFR 111.95.
We have received your responses dated September 22, October 31, and November 15, 2023; and April 24, 2024. Your October 31, 2023, response provided finished product specifications for ION Gut Support (SPC-01). However, the documents you provided do not demonstrate that you have corrected the above-mentioned deficiencies. Your remaining responses did not address this issue.
3. You failed to quarantine components before you used them in the manufacture of a dietary supplement until quality control could conduct the required review and approval of such components, as required per 21 CFR 111.155(c). Specifically, during the inspection, our investigator observed that you did not place
(b)(4)
or
(b)(4)
, used in the manufacture of your Ion Gut Support, into quarantine for evaluation and release by Quality Control prior to use. Additionally, you have no records that document you quarantined, sampled, and analyzed select components prior to their use. As an example, you received
(b)(4)
from your supplier on January 17, 2022. You did not document the quarantine, sampling, or analysis of this component. You used this component on
(b)(4)
, to manufacture
(b)(4)
. You then used this
(b)(4)
in the manufacturing of Ion Gut Support, 8-oz., Lot 2303301HBA, which was released into commerce.
We received your responses dated September 22, October 31, and November 15, 2023; and April 24, 2024. In your October 31, 2023, response, you state you have established a quarantine area in “
(b)(4)
” and provided a photograph. However, you did not present any records or evidence that components are being quarantined, sampled, and analyzed in accordance with your written procedure. Your remaining responses did not address this issue. Therefore, your responses fail to demonstrate the sufficiency of your corrective actions.
4. Your batch production record failed to include all the information required under 21 CFR 111.260. Specifically, we reviewed your batch production record for Ion Gut Support and found it failed to contain the following required information:
The date and time of the maintenance, cleaning, and sanitizing of the equipment and processing lines used in producing the batch, or a cross-reference to records, such as individual equipment logs, where this information is retained (21 CFR 111.260(c)).
The identity and weight or measurement of water and
(b)(4)
components in the
(b)(4)
and
(b)(4)
respectively (21 CFR 111.260(e)).
Documentation, at the time of performance, of the manufacture of the batch, including the initials of the person responsible for weighing or measuring each component used in the batch, the initials of the person responsible for verifying the weight or measure of each component used in the batch, the initials of the person responsible for adding the component to the batch, and the initials of the person responsible for verifying the addition of components to the batch (21 CFR 111.260(j)(2)).
We have received your responses dated September 22, October 31, and November 15, 2023; and April 24, 2024. In your response dated October 31, 2023, you provided the MPR template for
(b)(4)
. However, it does not include all elements as required in 21 CFR 111.260. Your remaining responses did not address this issue.
5. You failed to establish and follow written procedures for calibrating instruments and controls you use in manufacturing or testing a component or dietary supplement, as required by 21 CFR 111.25(a). Specifically, you have not established written procedures for calibrating your
(b)(4)
, which you use in the manufacturing or testing of your Ion Gut Support.
We have received your responses dated September 22, October 31, and November 15, 2023; and April 24, 2024. However, none of your responses provided documentation to demonstrate that you have established and followed written procedures for calibrating your
(b)(4)
. Therefore, we cannot evaluate the sufficiency of your corrective actions.
Misbranding of Dietary Supplement Products
In addition, we reviewed your product labels collected during the inspection and have determined the Ion Gut Support dietary supplement product you manufacture and distribute is misbranded under section 403 of the Act, 21 U.S.C. 343, because it does not comply with the labeling requirements for dietary supplements. Specifically, we identified the following:
1. Your Ion Gut Support dietary supplement products are misbranded within the meaning of Section 403(i)(2) of the Act, 21 U.S.C. 343(i)(2), in that the product labels fail to declare all the common or usual names of each ingredient used, as required by 21 CFR 101.36 and 21 CFR 101.4.
The Supplement Facts panel of your product identifies “Humic Extract” as the active ingredient with only “Purified water” as the other ingredient. We reviewed and collected your batch production records, which document formulation, of all sizes of your Ion Gut Support product. According to your batch production records, your Ion Gut Support includes the following ingredients:
(b)(4)
purified water,
(b)(4)
.
Each ingredient must be declared by the common or usual name in descending order of predominance within the ingredient list unless an exemption is provided in 21 CFR 101.100, or a collective (generic) name is provided in 21 CFR 101.4.
In your response, you state your components, other than humic extract, are processing aids to create the extraction. However, you provide no evidence these components are not present in the finished product. Further, the
(b)(4)
product (which is a product that consists of:
(b)(4)
are added after the extraction process. Thus, they are not processing aids as defined under 21 CFR 101.100(a)(3)(ii). Therefore, your response is inadequate.
2. Your Ion Gut Support products are misbranded under 403(q)(5)(F) of the Act, 21 U.S.C. 343(q)(5)(F), because the presentation of the nutrition information on the labeling of each product label does not comply with 21 CFR 101.36. For example:
The Supplement Facts label is not enclosed in a box by using hairlines (21 CFR 101.36(e)(2)).
A heavy bar is not placed under the “Serving Per Container” heading (21 CFR 101.36(e)(6)(i)).
A light bar is not placed under the heading “Amount Per Serving” (21 CFR 101.36(e)(7)).
A heavy bar is not placed under the final other ingredient (21 CFR 101.36(e)(6)(iii)).
The title, “Supplement Facts”, and headings are not bolded (21 CFR 101.36(e)(1)).
There is no provision in the regulation for an Other Ingredients list to appear within the Supplement Facts label.
In your response, you state you will address items within the Supplement Facts label. However, you do not present sufficient evidence to demonstrate corrections. Therefore, your response is insufficient for us to evaluate corrections.
3. Your Ion Gut Support product is misbranded within the meaning of Section 403(q)(1)(A) of the Act, 21 U.S.C. 343(q)(1)(A), because the Supplement Facts label does not include all intended groups as noted in the label directions. If a product is for persons within more than one group, the percent of Daily Value for each group shall be presented in separate columns. Your product’s Supplement Facts labels do not clearly include all the intended groups with the serving size and nutrition information in separate columns in the Supplement Facts label, as required by 21 CFR 101.36. For example, your Frequently Asked Questions found on your website, https://intelligenceofnature.com/pages/frequently-asked-questions#skin, and the product’s bottle labeling provide directions for use for adults and children under 3; however, both those intended groups are not declared on your product’s Supplement Facts labels.
In your response, you state you will change the directions of use to indicate oral use only and specify the use is for children four years and older. You do not present sufficient evidence to demonstrate corrections. Therefore, your response is inadequate.
4. Your Ion Gut Support product appears to be misbranded within the meaning of Section 403(s)(2)(B) of the Act, 21 U.S.C 343(s)(2)(B), in that the statement of identity provided on the principal display panel is “mineral supplement”, but there is no mineral declared as a dietary ingredient, in accordance with 21 CFR 101.3(g).
In your response dated September 22, 2023, you state you will update your labeling by March 31, 2024. However, you did not present sufficient evidence to demonstrate corrections. Therefore, we cannot evaluate the sufficiency of your corrective actions.
Conclusion
This letter is not intended to be an all-inclusive statement of violations that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.
This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may result in legal action including, without limitation, seizure and injunction.
Please notify FDA in writing, within 15 working days of the receipt of this letter, of the specific steps you have taken to correct any violations. 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 corrective actions within 15 working days, state the reason for the delay and time within which you will do so. If you believe that your products are not in violation of the Act, include reasoning and any supportive information for our consideration.
Your written reply should be directed to Compliance Officer Andrew J. Howard at U.S. Food and Drug Administration, 11155 Dolfield Boulevard, Suite 117, Owings Mills, MD 21117. An emailed response is also acceptable. Files greater than 100 megabytes may be submitted as smaller files in separate emails. If you have any questions regarding this letter, please contact Andrew J. Howard by telephone, at (410) 779-5125, or by email, at Andrew.Howard@fda.hhs.gov.
Sincerely,
/S/
Robin M. Rivers
Acting Program Division Director
Philadephia District Office
Human & Animal Food East, Division 2
Office of Regulatory Affairs
U.S. Food and Drug Administration
Robin.Rivers@fda.hhs.gov
___________________
1
i.e., Quality System, Facilities & Equipment System, Materials System, Production System, Packaging & Labeling System, and Laboratory Control System per FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations.
Content current as of:
05/28/2024
Regulated Product(s)
Food & Beverages