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WARNING LETTER

WL 664804

Dear Mr. Jacquot:

The United States Food and Drug Administration (FDA) inspected your manufacturing and distributing facility, located at 5514 Langford Ct, Concord, CA 94521, on June 1 through 29, 2023. The inspection revealed significant violations of the FDA’s regulations for Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, Title 21, Code of Federal Regulations Part 111 (21 CFR Part 111).

In addition, FDA reviewed the labels for some of your products and the websites www.pacificbiologic.com and www.balanceandharmony.com in July 2023. The review of your labels and websites reveals that claims made for several of your products cause them to be drugs under sections 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. §§ 321(g)(1)(B)] because they are intended for use in the cure, mitigation, treatment, or prevention of disease. Furthermore, several of your products are misbranded drugs under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)] because they fail to bear adequate directions for their intended use(s).

At the close of the inspection, on June 29, 2023, our investigator provided you with a Form FDA 483, Inspectional Observations (FDA 483). We acknowledge receipt of your response received via email dated July 14, 2023, which included your intended corrections to the observations of concern noted on the form FDA-483. However, the response was not adequate as further described in this letter. Your response targets completion of procedures to establish specifications by (b)(4). Additionally, your response references forms or procedures that were not provided for review. We address your response more specifically below.

Unapproved New Drugs

We reviewed your websites www.pacificbiologic.com and www.balanceandharmony.com and we determined you take orders there for your products ArteClear Circulation 2, Headache Release, Natura-Mune – 2, Pain Release, and Attack 2. The claims on your website establish that these products are drugs under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. 321(g)(1)(B)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. As explained further below, introducing or delivering these products for introduction into interstate commerce for such uses violates the Act. You can find the Act and FDA regulations through links on FDA’s home page at www.fda.gov.

Examples of some of the website claims that provide evidence that your products are intended for use as drugs include:

ArteClear Circulation 2

On your webpage: https://pacificbiologic.com/shop/cardio-heart-health/circulation/

• “ArteClear: Circulation 2…cardio-protective ...formula, ischemic heart disease, post heart attack recovery…”

Headache Release

Your product name: “Headache Release”
Your Information Panel: “Suggested Dosage ... Reduce the dosage and frequency as the condition improves.”

On your webpage: https://pacificbiologic.com/shop/sleep-stress-anxiety-support/headache-release/
• “Non-aspirin”
• “If you suffer from frequent headaches or migraines, you know how debilitating they can be. Fortunately, Pacific BioLogic’s Headache Release formula offers natural relief for headaches and migraines.”
• “Dosage ... Best taken at the very onset. May be helpful to prevent onset of a migraine if taken at the onset of symptoms.”
• “Corydalis”, an ingredient in the product, is listed under “[R]elieve pain and spasms”

Natura-Mune – 2

On your webpage: https://pacificbiologic.com/shop/immune-support/natura-mune/
• “This formula is recommended to be included in a supplement support program when treating chronic deficiency-type diseases because of its superior balance and gentle strengthening qualities.”
• “Categories: Cold & Flu ... Oncology Support”
• “More recently there have been extensive clinical studies that have identified a number of compounds in them [fungi and mushrooms, ingredients in Natura-Mune 2] that ... inhibit bacterial, viral, and tumor growth.
• “Cat’s Claw and Pau d’Arcu[sic] [ingredients in Natura-Mune 2] are two well-known (and studied) South American herbs that have some similar properties. They have been used extensively to treat chronic illnesses and degenerative conditions.”
• “Suggested Dosage ... Use higher dosage for more severe-immune compromised conditions.

Pain Release

Your product name: “Pain Release”
Your Information Panel: “Suggested Dosage: 1 – 4 capsules ... adjusting dosage according to level of pain and trauma”

On your webpage: https://pacificbiologic.com/shop/bone-joint-health/pain-release/
• “Regulates body pain and spasms due to trauma, sprains, or fractures. Best if taken during the critical first 24-48 hours after injury.”
• “Pacific BioLogic’s Pain Release is a powerful supplement that provides natural support for those who suffer from chronic pain or inflammation. If you are looking for an effective solution to relieve pain and inflammation without resorting to over-the-counter painkillers or prescription medications, Pain Release may be just what you need.”

Attack 2
On your webpage: https://pacificbiologic.com/shop/immune-support/attack_2/
• [ingredients in the product Attack 2] “... Andrographis, Viola, Chrysanthemum Flower, Oregon Grape Root, and Licorice root. These herbs work well together to cover a very wide spectrum of bacterial and viral strains. Much research has been done on the benefits of Andrographis. Its properties include analgesic, anti-viral, anti-inflammatory, expectorant …”

Your products are not generally recognized as safe and effective for the above referenced uses and, therefore, the products are “new drugs” under section 201(p) of the Act [21 U.S.C. § 321(p)]. With certain exceptions not applicable here, new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d), 355(a)]. FDA approves a new drug on the basis of scientific data and information demonstrating that the drug is safe and effective.

This is a repeat observation from the Warning Letter issued to you on April 17, 2014, and the items discussed with you in the Regulatory Meeting held on May 19, 2015.

Misbranded Drugs

A drug is misbranded under section 502(f)(1) of the Act [21 U.S.C. 352(f)(1)] if the drug fails to bear adequate directions for its intended use(s). “Adequate directions for use” means directions under which a layperson can use a drug safely and for the purposes for which it is intended (21 CFR 201.5). Prescription drugs, as defined in section 503(b)(1)(A) of the Act [21 U.S.C. 353(b)(1)(A)]), can only be used safely at the direction, and under the supervision, of a licensed practitioner.

Your products ArteClear Circulation 2, Natura-Mune – 2, and Attack 2 are intended for prevention or treatment of one or more diseases that are not amenable to self-diagnosis, prevention, or treatment without the supervision of a licensed practitioner. Therefore, it is impossible to write adequate directions for a layperson to use these products safely for their intended purposes. Accordingly, your products listed above fail to bear adequate directions for their intended use and, therefore, the products are misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)]. The introduction or delivery for introduction into interstate commerce of these misbranded drugs violates section 301(a) of the Act [21 U.S.C. § 331(a)].

Adulterated Dietary Supplements

Your dietary supplement products are adulterated within the meaning of section 402(g)(1) of the Act [21 U.S.C. § 342(g)(1)] because the products have been prepared, packed, or held under conditions that do not meet the Current Good Manufacturing Practice (CGMP) regulation for dietary supplements (21 CFR Part 111).

The significant violations documented during the inspection include, but are not limited to, the following:

1. You failed to establish required specifications:

• for each component that you use in the manufacture of a dietary supplement, as required by 21 CFR 111.70(b). Specifically, you failed to establish identity specifications for all components used in the manufacture of your dietary supplements, including ArteClear, Cholesterol, ArteClear Circulation 2, Pain Release, Grounded, and Attack 2.
• for dietary supplement labels (label specifications) and for packaging that may come in contact with dietary supplements (packaging specifications), as required by 21 CFR 111.70(d). Specifically, when asked by the FDA investigator, you stated that you (b)(4) deliver the blended/milled ingredients to your contract manufacturer to encapsulate and bottle the capsules for you as per your verbal instructions.
• product specifications for the identity, purity, strength, and composition of the finished batch of the dietary supplement, and for 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(e) for each dietary supplement that you manufacture. Specifically, when asked by the FDA investigator, you stated you do not have finished product specifications for your finished dietary supplement products, including ArteClear Cholesterol, ArteClear, Circulation 2, Pain Release, Grounded, and Attack 2.

Your response to the FDA-483, received on July 14, 2023, is not adequate because in your response you state that your procedures for establishing identity specifications would be completed by December 2023 but you did not provide any copies of the procedures you mention in your response (such as QA-402 Product Specifications for Identity, Purity, Strength, and Composition, QA-403 Establish Product Specifications for Limits, QA-404 Component Specifications for Purity, Strength, and Composition and QA-405 which you say you intend will establish limits for contamination) or provide any written specifications for your components, packaging, labeling, or finished dietary supplement products.

Once you have established these specifications, you must determine whether the specifications that you establish under 21 CFR 111.70 are met, as required by 21 CFR 111.73 and 21 CFR 111.75. Specifically, before using a component, you must conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient, as required by 21 CFR 111.75(a)(1)(i), unless you petition the agency under 21 CFR 111.75(a)(1)(ii) and the agency exempts you from such testing. You must also confirm the identity of other components and determine whether other applicable component specifications established in accordance with 21 CFR 111.70(b) are met, as required by 21 CFR 111.75(a)(2). Further, for a subset of finished dietary supplement batches that you identify through a sound statistical sampling plan (or for every finished batch), you must verify that your finished batch of the dietary supplement meets product specifications for the identity, purity, strength, composition, and for limits on those types of contamination that may adulterate or that may lead to adulteration of the finished batch of the dietary supplement, as required by 21 CFR 111.75(c). You must also make and keep certain records, including records of the specifications you establish, in accordance with 21 CFR 111.95. After establishing the above specifications, you must also collect representative samples of each unique lot of components, packaging and labels that you use to determine whether the components, packaging and labels meet established specifications, as required by 21 CFR 111.80(a).

This is a repeat observation from the Warning Letter issued to you on April 17, 2014, and the items discussed with you in the Regulatory Meeting held on May 19, 2015.

2. You failed to prepare and follow a written master manufacturing record (MMR) for each unique formulation of dietary supplement that you manufacture, and for each batch size, to ensure uniformity in the finished batch from batch to batch, as required by 21 CFR 111.205(a). Specifically, when asked by the FDA investigator to provide specific MMRs, you said you did not have written MMRs for your finished products Headache Release, ArteClear Blood Pressure, and Natura-Mune 2.

The written MMRs that you were able to provide failed to include all of the required information, in accordance with 21 CFR 111.210. Specifically, your MMRs for ArteClear Cholesterol ArteClear Circulation 2 and Grounded failed to include the following information:
• An accurate statement of the weight or measure of each component to be used [21 CFR 111.210(c)];
• The identity and weight or measure of each dietary ingredient that will be declared on the Supplement Facts label and the identity of each ingredient that will be declared on the ingredients list of the dietary supplement [21 CFR 111.210(d]); A statement of theoretical yield of a manufactured dietary supplement expected at each point, step, or stage of the manufacturing process where control is needed to ensure the quality of the dietary supplement, and the expected yield when you finish manufacturing the dietary supplement, including the maximum and minimum percentages of theoretical yield beyond which a deviation investigation of a batch is necessary and material review is conducted and disposition decision is made [21 CFR 111.210(f)];
• Written instructions, including the following [21 CFR 111.210(h)]:
o Specifications for each point, step, or stage in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record [21 CFR 111.210(h)(1)];
o Procedures for sampling and a cross-reference to procedures for tests or examinations [21 CFR 111.210(h)(2)];
o Specific actions necessary to perform and verify points, steps, or stages in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the MMR.
 Such specific actions must include verifying the weight or measure of any component and verifying the addition of any component [21 CFR 111.210(h)(3)(i)]; and
 For manual operations, such specific actions must include [21 CFR 111.210(h)(3)(ii)]:
 One person weighing or measuring a component and another person verifying the weight or measure [21 CFR 111.210(h)(3)(ii)(A)]; and
 One person adding the component and another person verifying the addition [21 CFR 111.210(h)(3)(ii)(B)].
• Corrective action plans for use when specifications are not met. [21 CFR 111.210(h)(5)]

Your response to the FDA-483, received on July 14, 2023, states that you did not fill out the document correctly and that the requirements for your MMRs can be found in document QA-500. We are unable to determine the adequacy of your corrective actions because you did not provide a copy of document QA-500. You also failed to provide MMRs for your finished products Headache Release, ArteClear Blood Pressure, and Natura-Mune 2 and you failed to provide updated MMRs for your finished products ArteClear Cholesterol, ArteClear Circulation 2, and Grounded.

3. You failed to prepare a batch production record (BPR) every time you manufactured a batch of dietary supplements, as required by 21 CFR 111.255(a). Specifically, you did not prepare a BPR for any of your finished products, including but not limited to Grounded, (Lots 204049, 204023, 204024), Headache Release (Lot 204043), ArteClear Blood Pressure (Lot 204032), Natura-Mune 2 (Lot 204038), ArteClear Cholesterol (Lot 204041), and ArteClear Circulation 2 (Lot 203986), as well as for the products Pain Release, Grounded, and Attack 2.

4. You failed to review all product complaints to determine whether any product complaints involved a possible failure of a dietary supplement to meet any of its specifications, or any other requirements of part 111, including those specifications and other requirements that, if not met, may result in a risk of illness or injury, as required under 21 CFR 111.560(a)(1). You also failed to make and keep a written record of every product complaint related to good manufacturing practice, as required by 21 CFR 111.570(b)(2). Specifically, during the inspection you stated that you remembered you had your herbal and dietary supplement products returned but that you could not recall when or what herbal and dietary supplement products had been returned.

Your response to the FDA-483, received on July 14, 2023, states that you have located your file for the Complaint Report Log (QA-301 L), Return Authorization Form, Consumer Complaint Medical Question Form, and Consumer Complaint & Adverse Event Reporting (AER) form; however, we are unable to evaluate the adequacy of your corrective actions because you did not provide the referenced documents for review.

5. You failed to make and keep records of any material review and disposition decision on a returned dietary supplement, as required by 21 CFR 111.535(b)(2). Specifically, during the inspection you stated that you remembered you had your herbal and dietary supplement products returned but you could not recall when or what herbal and dietary supplements were returned.

In your response to the FDA-483, received on July 14, 2023, you referenced a procedure QA-301, “Returned Merchandise.” You did not provide a copy of this procedure. You did not provide evidence of any material review and deposition of returned dietary supplements.

6. You failed to collect and hold reserve samples of each lot of packaged and labeled dietary supplements that you distribute, as required by 21 CFR 111.83(a). Specifically, you told an FDA investigator that you do not currently collect and hold reserve samples of the products that you distribute. You stated that you have not collected reserve samples since 2018, and that you no longer collect reserve samples due to a lack of space within your (b)(4).

In your response to the FDA-483, received on July 14, 2023, you referenced a procedure QA-401, “Collecting and Reserve Samples.” You did not provide a copy of this procedure. You also stated that you will figure out a way to record and label the storage container used for this purpose, but you provided no evidence of your corrective action plan, such as a reserve sample log.

7. Your quality control personnel failed to ensure that your manufacturing, packaging, labeling, and holding operations ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record (MMR), as required by 21 CFR 111.105. Specifically, the components listed in your master manufacturing records do not match the components listed on the dietary supplement product label. For example:
• The MMR for your product Grounded lot #204023 and lot #204024 list the component Inositol NF/FCC; however, Inositol is not listed on the Grounded product label.

We note that the MMR for your product Attack 2 lot #204009 lists the component White Mulberry bark; however, White Mulberry bark is circled by hand, and Andrographis is handwritten beside it. Therefore, it is unclear whether the MMR lists the component White Mulberry bark and Andrographis as being added during manufacturing, or whether the MMR lists Andrographis as being added twice during manufacturing, once on its own, and once to replace the White Mulberry bark component. The product label lists both White Mulberry bark and Andrographis as dietary ingredients in the Attack 2 product.

Misbranded Dietary Supplements

In addition, we reviewed product labels collected during the inspection and have determined the Pain Release, Headache Release, ArteClear Circulation 2, and Grounded dietary supplements you manufacture and distribute are misbranded under section 403 of the Act [21 U.S.C. § 343] because they do not comply with the labeling requirements for dietary supplements. Specifically, we identified the following:

1. Your products Pain Release, and Headache Release, ArteClear Circulation 2, and Grounded are misbranded within the meaning of section 403(i)(2) of the Act 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(h)(2). For example,

Pain Release
• The product label declares “Boswellia resin”, but this is not the common or usual name of the dietary ingredient. The label must list the standardized common name given in the reference Herbs of Commerce, “Frankincense.”
• The product label declares “Notoginseng”, but this is not the common or usual name of the dietary ingredient. The label must list the standardized common name given in the reference Herbs of Commerce, “Tienchi Ginseng.”
• The standardized common name for Drynaria fortune given in the reference Herbs of Commerce is “drynaria.”
• The product label declares “Corydalis”, but this is not the common or usual name of the dietary ingredient. The label must list the standardized common name given in the reference Herbs of Commerce, “Corydalis yanhusuo.”
• Your product labels declare “capsules of plant origin”, but this is not a common or usual name for an ingredient.

Headache Release
• The product label declares “Citrus viride”, but this is not the common of usual name of the dietary ingredient. The label must list the standardized common name given in the reference Herbs of Commerce, “Tangerine.”
• Although the Latin binomial name is declared, it must be placed in parentheses following the standardized common name “Wood Betony.”
• The standardized common name for Chrysanthemum x morifolium given in the reference Herbs of Commerce, is “chrysanthemum.”
• The product label declares “Pueraria spp.”, but this is not the common of usual name of a dietary ingredient. The label must list the standardized common name given in the reference Herbs of Commerce for the specific species, and in the absence of a standardized common name, the Latin binomial name.
• The standardized common name for Gastrodia elata given in the reference Herbs of Commerce, is “Gastrodia.”

ArteClear Circulation 2
• The product declares “BioPerine ® (Trademark of Sabinsa Corp.)”, which is a trademarked term and not the common or usual name for the ingredient.

Grounded
• “MSM” is not the common or usual name for the ingredient Methylsulfonylmethane.

2. Your products Pain Release, Headache Release, and ArteClear Circulation 2 are misbranded within the meaning of section 403(s)(2)(C) of the Act [21 U.S.C. § 343(s)(2)(C)], in that the labels fail to identity the part of the plant or fail to express the name in English, as required by 21 CFR 101.4(h)(1). For example,

Pain Release:
• The dietary ingredient “Notoginseng Radix” uses the Latin term “radix” for the plant part. The name must be expressed in English.
• The label does not list the plant part for myrrh, sappan wood, and Schefflera arboricola. If the whole or entire plant is used, that information must be listed.

Headache Release:
• The label does not list the plant part for Stachys officinalis, Chrysanthemum morifolium, and Uncaria rhynchopylfa. If the entire or whole plant is used, that information must be declared.

ArteClear Circulation 2
• The label does not list the plant part for Cayenne pepper.

3. Your products “Pain Release”, “Headache Release”, “ArteClear Circulation 2”, “Natura-Mune 2”, “Attack 2”, “ArteClear Cholesterol”, “ArteClear Blood Pressure” and “Grounded” are misbranded within the meaning of section 403(q)(5)(F) of the Act [21 U.S.C. § 343 (q)(5)(F)] in that the presentation of the nutrition information on the labeling of your products is not in accordance with 21 CFR 101.36 and 101.9. For example:

• The title, “Supplement Facts”, should be set to full width of the nutrition label, in accordance with 21 CFR 101.36(e)(1).
• The nutrition information, i.e., the Supplement Facts label, must include the required title, subheadings, usage of heavy and light bars, and hairlines within the box [21 CFR 101.36(e)].
• The dietary ingredients comprising the “Proprietary Blend” fail to have hairline rules centered between the lines of text such that the hairline rules separate the dietary ingredients above from the dietary ingredients below, in accordance with 21 CFR 101.36(c)(2) and (e)(5).
• Your product labels which do not declare a proprietary blend must bear the quantitative amounts by weight of each other dietary ingredient under the heading “Amount Per Serving”, in accordance with 21 CFR 101.36(b)(3).
• Your product labels present the nutrition information as per capsule and not on a per serving basis, which is not in accordance with 21 CFR 101.9(b).
• Your product “Headache Release” incorrectly declares the servings per container [21 CFR 101.9(b)(8)].
• Your product labels “Pain Release” and “ArteClear Cholesterol” do not declare the components of the “Proprietary Blend” in descending order of predominance by weight, as indicated by the Master Manufacturing Record (MMR) [21 CFR 101.36(c)(2)].

Grounded

• The source of the dietary ingredients, niacin, vitamin B6, magnesium, and zinc must be declared in accordance with 21 CFR 101.36(d).
• The quantitative amount by weight per serving of the proprietary blend does not use metric measures in appropriate units (i.e., 3000 units must be declared in the next higher set of units, e.g., 6000 mg must be expressed as 6 g), in accordance with 21 CFR 101.36(b)(3)(ii)(A). Furthermore, the dietary ingredients comprising the proprietary blend are not indented under the title “Proprietary Blend”, in accordance with 21 CFR 101.36(c)(2).
• Potassium must not be listed within the Supplement Facts label because the serving contains less than 2% of the Recommended Daily Intake (RDI), which is considered zero. Any (b)(2)-dietary ingredient not present, or in amounts that can be declared as zero in section 101.9(c), shall not be declared (e.g., amounts corresponding to less than 2 percent of the RDI for vitamins and minerals) in accordance with 21 CFR 101.36(b)(2)(i).

4. Your product “Circulation 2” is misbranded within the meaning of section 403(r)(6) in that the product makes structure/function claims but fails to bear the required dietary supplement disclaimer, in accordance with 21 CFR 101.93(b)-(e).

This letter is not intended to be an all-inclusive statement of violations that may exist at your facility or in connection with your products. 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 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.

We also offer the following comments:

Regarding your labels
• For the product “Grounded” Lithium orotate is misspelled.
• For the product “Pain Release”, the dietary ingredient sappanwood should be one word.
• For the product “ArteClear Circulation 2”, the standardized common name for Panax ginseng given in the reference Herbs of Commerce is “Oriental ginseng.” However, we would not object to use of “Asian ginseng” as given in the 2nd edition (2000) of Herbs of Commerce.

Regarding your response

In your response to the FDA-483, received on July 14, 2023, you outline your plan to provide all new and updated SOPs by (b)(4). We note that this does not constitute a reasonable timeframe given many of these citations are repeat citations from past inspections, and given you received a Warning letter in 2014 and participated in a Regulatory Meeting in 2015 about many of these citations. Please provide an updated timeline for the completion of your new and updated SOPs.

Please notify FDA in writing, within fifteen working days of receipt of this letter, of the specific steps you have taken to correct these violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction.

Your written response should be sent to:

Sergio Chavez, Director, Compliance Branch
Food and Drug Administration
Office of Human and Animal Foods Division West 5
1201 Harbor Bay Pkwy
Alameda, CA 94502

Refer to Unique Identification Number 664804 when replying.

If you would prefer to send your response electronically, please email it to ORAHAFWEST5FirmResponses@fda.hhs.gov. Please include the name of your firm and the Unique Identification Number in the title of the e-mail message.

If you have any questions regarding this letter, please contact Elodie X. Tong-Lin, Compliance Officer, at Elodie.Tong-Lin@fda.hhs.gov.

Sincerely,
/S/

Darla R. Bracy
District Director | FDA San Francisco District
Program Division Director
Office of Human and Animal Food Operations – West Division 5