FDA Knowledge Base For Topical Pain Products

FDA KNOWLEDGE BASE FOR TOPICAL PAIN PRODUCTS

PRICE OR BUY

NOVEMBER 1, 2011

 

The labeled active ingredients in ArNeu are camphor 3.1% and menthol 3.0%. Both ingredients at the labeled concentration are included in the tentative final monograph (TFM) for OTC external analgesic drug products (48 FR 5852, February 8, 1983), and the TFM proposes to include this combination of active ingredients for use in counterirritant drug product that is labeled for use for the temporary relief of minor aches and pains associated

**(reduce inflammatory pain is not a definitive claim and is not a new finding in its relations to pain but does relate from recognized literature that formed 21 CFR 348.0, would contribute to the relief of pain.)

  1. Abstract: Implantable medical devices are finding increasing use in the treatment of diseases traditionally targeted with drugs. It is well established that the cholinergic anti-inflammatory pathway serves as a physiological regulator of inflammatory responses, but stimulation of this pathway therapeutically by electrical stimulation of the vagus nerve can also diminish excessive or dysregulated states of inflammation. Recent data from a wide variety of animal models, as well as evidence of reduced vagal tone in rheumatoid arthritis and other inflammatory diseases, support the rationale for, and feasibility of, developing implantable vagal nerve stimulation devices to treat chronic inflammation in humans. Ann Rheum Dis 2011;70:i67-i70 doi:10.1136/ard.2010.138677 **(Further expand on the references and comments within Federal Registers that pertain to in 21 CFR 348.0 speaking about chemical reactions developing an electrical charge in order to disrupt inflammatory processes. The original panel and their referenced materials provided such information back in the 70’s if one understood physiology, there fore it is felt in order to provide a quality product a non destructive / non human approach is needed to measure a products ability, not effectiveness or claim a new concept.  The patent is directed towards quality of the active ingredients after production and before making available for human use as per 21 CFR 348.0, power source (as development is under prototype), or any other needs of the future.
  2. A topically (externally) applied drug that causes irritation or mild inflammation of the skin for the purpose of relieving pain in muscle, joint, or viscera distal to the site of application by stimulating cutaneous sensory receptors. Ref.: Register/Vol. 48, No. 27/Tuesday, February 8, 1983/Proposed Rules, page 5867 **(Describes relieving pain, knowing that pain is the result of inflammation and identified such in recording in the Federal Register, concerning 21 CFR 348.0).  This results by effecting the immediate area, while also addressing distal in reducing pain ,aka inflammation, relief is acknowledged in distal muscle, joints and viscera (vascular or soft tissue organs))
  3. A topically (externally) applied drug that causes irritation or mild inflammation of the skin for the purpose of relieving pain in muscle, joint, or viscera distal to the site of application by stimulating cutaneous sensory receptors. Ref.: Register/Vol. 48, No. 27/Tuesday, February 8, 1983/Proposed Rules, page 5867 **(Knowing that cutaneous receptoris any or a combination of the various types of sense organs found in the dermis or epidermis, usually a mechanoreceptor, thermo receptor, or nociceptor, addressed as c fibers or a delta fibers)
  4. Such ingredients penetrate the nerve endings and cause a temporary reversible charge  in the nerve membrane, preventing the development of the electrical current at a given point in a nerve fiber that transmits the impulses along a nerve Ref.: Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979 **(It was realized that counterirritants physiological activity was being created by the chemical reaction electrical charge, but studies show that chemical themselves do not penetrate the nerve endings but the nerve ending do respond to the chemical response in the area of contact)
  5. Evaluation of the effects on pain. Certain musculoskeletal disorders a accompanied by inflammation that causes swelling, tenderness, and redness as well as pain: Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979, page 69862
  6. Inflammation is characterized by heat, redness, swelling and tenderness of the affected tissues Ref.: Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979 **(Defines that swelling, tenderness, redness & pain is caused by inflammation that accompanies musculoskeletal disorders, where musculoskeletal disorders are referenced in; “International Statistical Classification of Diseases and Related Health Problems 10th Revision Version for 2007”. World Health Organization. 2007.{See List Attached Within This Booklet, aka ”icd codes”, M00-M99})

with simple backache, arthritis, strains, bruises, and sprains.

  1. “For the temporary relief of minor aches and pains of muscles and joints” (which may be followed by: “associated with “(select one or more of the following: “simple backache,” arthritis,” “strains,” “bruises,” and “sprains.”)

**(These are the claims but a definition of the words should be allowed in order to provide better understand and safety to consumers as not to misdiagnose on their own what a pain is physiologically as long as it does not lead to a diagnosis and I haven’t found any rules that says definitions are not allowed?)

2. See: Terminology, Definitions, Intent…(aka tdi pages 1- 26)

However, your labeling promotes the use of the product to reduce inflammatory pain and suggest a novel dosage form/route of administration with the following statement:

  1. Inflammation is characterized by heat, redness, swelling and tenderness Ref.: Federal Register, Vol. 44, No. 234, Tuesday, December 4, 1979
  2. Inflammation is a pathological process that occurs in the blood vessels and adjacent tissues Ref.: Federal Register, Vol. 44, No. 234, Tuesday, December 4, 1979

**(Inflammation and pain are not the same but the allowed identifiers are caused by inflammation as cited within the Federal Registry)

  1. See: Terminology, Definitions, Intent…(aka tdi pages 1- 26)

 “Electrical: a PATENTED PROCESS found ONLY in ArNeu, combines the metabolic waste that occurs due to stress with ArNeu to develop electricity that may reduce inflammatory pain”.

**(Research is showing that we are the only product who is measuring electrical output of the chemical reaction where it is hoped that more companies will become more aware that their products may be evaluated in other forms other than individual uncontrolled responses that may be selected due to ease.) (Without a component of electrical occurrence there cannot be a chemical reaction as described by drugs so this isn’t nothing new or inventive it is only a tool to measure activity using the approved active ingredient percentages for the problems described a concept of peruse quality assurance approach but makes no claims as to the effectiveness, but should evolve into a testing device to determine the possibility in measuring how long a product is effective providing a measurement for terms as “long lasting” within  the near future.  Which I believe is something that NIH has processed study grants in hopes of discovering.)

  1. Derivative Action. The application of irritants often subdues inflammation in deep-seated organs.  This counterirritation was formerly supposed to act simply by mechanical withdrawl of the blood from the inflamed area to the area of “counterirritation.”  This explanation is certainly incorrect.  It is now believed that the circulation is the distant organs is modified by reflexes along homologous nerve paths in a sense a reversal of the “referred pain” which occur in definite skin area when the corresponding viscera are irritated. Referenced in Federal Register, Vol. 44, No. 234, Tuesday, December 4, 1979 as Ref. 21 “A manual of Pharmacology and Its Applications to Therapeutics and Toxicology” **(Understanding, nerves don’t uptake chemicals but do transmit electrical impulses they are referring to the reflexes due to electrical signals traveling through nerve paths to reduce pain a component of inflammation.)

 

Claims associated with inflammation are not included in the TFM for use in a counterirritant product with these active ingredients at their labeled concentrations.  Furthermore the patented process described may rise newness issues as described in Title 21 Code of Federal Regulations Part 310.3(h)(5) (21 CFR 310.3(h)(5)).

**(There were not claims designating inflammation as a new drug in any way in by formulation, dosage or application, but rather provides a definition as not to confuse consumers as to what the interpretation and supplied definition of the Panel’s finding as described by the Panel and recorded in the  Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules, that lead to the specific identifiable characteristic, but does list as a component of conditions that are allowable claims in regards to “pains of muscles and joints” as allowed Part 348.50(b)(1), as referenced in the following statements as the intent of the “Panel’s findings on external analgesic drug products are set out….” (Page 69769 Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules), “Category 1, Conditions under which OTC external analgesic recognized as safe and effective and are not misbranded” (Page 69769 Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules).  In specific the mentioning of inflammation is not a claim but a reference as described and used in the context seen below)

  1. “which are applied to the skin to relieve the symptoms of pain, itching, or irritation and which as a group are designated “external analgesic.” The Panel identified symptoms in and under the skin, due to trauma, irritating chemicals, allergic reactions, toxins, physical agents such as infrared or ultraviolet radiation, or systemic disease.  External analgesics, like all other OTC medications, are intended to provide relief for symptoms that are self-limiting.” : Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules, page 69772 **(This acknowledges the complexity of events that may result in pain, itching or irritation, while addressing that external analgesics is only to be used for the relief of symptoms of the before mentioned events, limiting later to “muscle and joint pains”.)
  2. “4. Bioavailability. The rate and extent to which the active drug ingredient or therapeutic moiety is absorbed from a drug product and becomes available at the site of drug action.: Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules, page 69772 **(Rate of bioavailability in Patent 7,704,522 does not reference any changes in ingredient active ingredients nor demonstrates a change in therapeutic moiety absorption but does provide a way to measure the bioavailability. Furthermore it should be noted that a process of measuring a products activity as show was developed to demonstrate that products are being made and supplied to the public substandard in order to decrease manufacturing cost and increase profits.)
  3. “The Panel stresses that in most cases continued contact of a film of the active ingredient is essential for efficacy. The medium in which an active ingredient is incorporated must provide not only the necessary solubility and stability, but must also maintain contact of the active ingredient with the lesion of the skin.”: Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules, page 69774 **(Don’t know where the CDER has referenced a novel dosage form/route of administration, unless it is somewhere we state to leave a film on top of the skin when applying.  This provides evidence that any type of external analgesic counterirritant that directs a user to rub a product completely in had developed a “novel dosage form/route of administration” which should be addressed in order to detour from lessening efficiency.)
  4. Topical counterirritants are included among the external analgesics because they are applied to the intact skin for the relief of pain. They differ from the anesthetics, analgesics, and antipruritic agents, however, in that the pain relief they produce results from stimulation….occurs in structures of the body other than the skin areas to which they are applied as, for example in joints, muscles, tendons, and certain viscera (Ref. 21).: Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules, page 69779 **(They have just described the biomechanical/ physiological responses that occur distal to the area of application in order to relieve pain, that results from inflammation.)
  5. Certain musculoskeletal disorders are accompanied by inflammation that causes swelling, tenderness, and redness, as pain.: Federal Register Vol. 44, No.234, Tuesday December 4, 1979, page 69862: Headings 6. Evaluation of counterirritants and claims for deep-seated pain/(1)Evaluation of the effects of pain **(Here is was known that in order to have pain there was the presence of either swelling, redness or tenderness due to inflammation, so inflammation was recognized as the precursor to pain)
  6. Derivative Action. The application of irritants often subdues inflammation in deep-seated organs.  This counterirritation was formerly suppose to act simply by mechanical withdrawl of the blood from the inflamed area to the area of “counterirritation.”  This explanation is certainly incorrect.  It is now believed that the circulation is the distant organs is modified by reflexes along homologous nerve paths in a sense a reversal of the “referred pain” which occur in definite skin area when the corresponding viscera are irritated. Referenced in Federal Register, Vol. 44, No. 234, Tuesday, December 4, 1979 as Ref. 21 “A manual of Pharmacology and Its Applications to Therapeutics and Toxicology” **(Understanding, nerves don’t uptake chemicals but do transmit electrical impulses they are referring to the reflexes due to electrical signals traveling through nerve paths to reduce pain a component of inflammation.)
  7. Counterirritation is, as a rule, useful only in chronic inflammation. Referenced in Federal Register, Vol. 44, No. 234, Tuesday, December 4, 1979 as Ref. 21 “A manual of Pharmacology and Its Applications to Therapeutics and Toxicology **(Again referencing that inflammation is address to reduce the pain)
  8. The Panel used the terms in the above list of indications because it believes these terms would be understood by the general population. These are not necessarily terms which physicians would use in specific diagnosis.: Federal Register, Vol. 44, No. 234, Tuesday, December 4, 1979 **(Here it addresses that although indications are listed it is acknowledged that profession would need to be more specific in understanding and identifying a diagnosis)

 

In addition the label includes a patent number, 7,704,522.  As the patent number is included in the product labeling, all information in the patent is considered labeling.  Claims found in this patent include: treatment of diabetic neuropathy, post hepatic neuralgia, scleroderma, sinusitis, and edema.  We are not aware of a product with this formulation, for topical application, to treat pain associated with the above stated conditions having been available in the U.S. market as an OTC drug at the inception of the OTC Drug Review.

  1. The Panel used the terms in the above list of indications because it believes these terms would be understood by the general population. These are not necessarily terms which physicians would use in specific diagnosis. : Federal Register, Vol. 44, No. 234, Tuesday, December 4, 1979 **(Here it addresses by the panel and they acknowledged, that professionals would need to be more specific in understanding and identifying, recognizing that although the public may accept pain, swelling, bruising, strain and sprain, they are not specific enough to not to rule out items that could provide more harm, although this seem to be a little out of date due to the availability of information today compared to the 70s, but we will work within the guidelines.)

 

**(The interpretation and understanding of Claims within allowed patented processes is incorrect, disregarding the guidelines and procedures set forth by the U.S. Patent and Trademark Office.  No where within the allowable claims did the U.S. Patent Office allow the incorporation of the above descriptions of diabetic neuropathy, post hepatic neuralgia, scleroderma, sinusitis, and edema as stated, but rather provides some meaning from pain to inflammation to musculoskeletal.  It is also noted under inflammation and musculoskeletal conditions ref:

 

  1. Evaluation of the effects on pain. Certain musculoskeletal disorders a accompanied by inflammation that causes swelling, tenderness, and redness as well as pain: Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979, page 69862 & Inflammation is characterized by heat, redness, swelling and tenderness of the affected tissues Ref.: Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979 **(Defines that swelling, tenderness, redness & pain is caused by inflammation that accompanies musculoskeletal disorders, where musculoskeletal disorders are referenced in; “International Statistical Classification of Diseases and Related Health Problems 10th Revision Version for 2007”. World Health Organization. 2007.{See List Attached Within This Booklet, aka ”icd codes”, M00-M99})

Although the original application did address and make claims to provide evidence in reducing symptoms of inflammation that have been proven to reduce the resulting pain it had to be removed because of complexity.  The Claims do address the composition of Camphor and Menthol and a process on how to measure the resulting activity, but makes not claims on superior effectiveness or change of the physiological results as describe with 21 CFR 348.0 and its supporting Federal Register of supporting statements, comments, references and definitions (see in part and not exclusively;  21 CFR 348.0, Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules, Federal Register/Vol. 48, No. 27/Tuesday, February 8, 1983/Proposed Rules)  The items addressed, diabetic neuropathy, post hepatic neuralgia, scleroderma, sinusitis, and edema, were used to provide a distinctive description to the patent reviewer, knowing that the reviewer may not be widely medically versed in the understanding of the physiological components of minor aches and pains of muscle and joints as inflammation being addressed by an external analgesic counterirritant but is recognized within the teachings of and noted in 21 CFR 348.0, Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules, Federal Register/Vol. 48, No. 27/Tuesday, February 8, 1983/Proposed Rules) as noted below:) (Also when evaluating topical analgesic there has definitely been a significant level of potency that has followed faster / quick manufacturing processes, there by lessening the efficiency of topical analgesic through the industry but is not address within the scope of the FDA as providing Safe and Effective OTC products to the consumer, although assays are showing consistent levels, which I plan to prove as more funds are available so more noninvasive measuring techniques may be observed through normal use and observation within a clinic, may you understand I suffered for decades due to substandard care and products and now I am watching very closely for an opportunity to correct the situation, how ever small a contribution it may be.

  1. Inflammation is characterized by heat, redness, swelling and tenderness of the affected tissues : Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979 (No explanation required)

 

**(I have identified several aspect of violations within informational sites both public and private specifically NIH and MedPlus where counterirritants studies make claims that an ingredient not listed under § 348.12 is useful as a counterirritant through University and / Private company avenues should these individuals allowed to comment and they sure don’t apply a FDA considered not as not being reviewed?  This correlates as counterirritant with a specific trauma and or disease, being used to widen the definition so that a mis understanding may not occur.)

Therefore, ArNeu, as currently formulated and labeled, does not appear to be eligible for the OTC Drug Review.  As a result, Arneu would likely be a “new drug,” as defined by Section 201(p) (21 U.S.C. § 321(p)) of the Federal Food, Drug, and Cosmetic Act (the Act) in that it is not generally recognized as safe and effective for the conditions for which it is promoted.  New drugs may not be legally marked in the United States without prior approval from FDA as described in Section 505(a) [21 U.S.C. § 355(a)] of the Act.

Referenced Citation: Section 201(p) (21 U.S.C. § 321 (p) of the Federal Food, Drug and Cosmetic Act

(21 U.S.C. § 321 (p)  3 The term “new drug” means—

(1) Any drug (except a new animal drug or an animal feed bearing or containing a new animal drug) the composition of which is such that such drug is not generally recognized  among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, as safe and effective for use under the condition prescribed, recommended, or suggested in the labeling thereof, except that such a drug not so recognized shall not be deemed to be a “new drug” if at any time prior to the enactment of this Act [enacted June 25, 1938] it was subject to the Food and Drugs Act of June 30, 1906, as amended, and if at such time its labeling contained the same representations concerning the conditions of its use; or

(2) Any drug (except a new animal drug or an animal feed bearing or containing a new animal drug) the composition of which is such that such drug, as a result of investigations to determine its safety and effectiveness for use under such conditions, has become so recognized, but which has not, otherwise than in such investigations, been used to a material extent or for a material time under such conditions.

http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/FDCAct ChaptersIandIIShortTitleandDefinitions/ucm086297.htm#ftn3

 

 

 

**(ArNeu active ingredients and therapeutic uses are recognized, (Federal Register, Vol. 48, No. 27, Tuesday, February 8, 1983 and Federal Register, Vol. 44, No. 234, Tuesday, December 4, 1979) and recognized in several OTC Analgesic and Counterirritant product, definitions and standards  in the industry under TFM guidelines as being safely used as a Topical Analgesic or Counterirritant), The patent claims do not make any claims of making an effect on the skin or any claim as to the penetration of the counterirritant but does identify know measurable components of energy put off when the metabolic waste is present,  due to exertion by the body comes in contact with a counterirritant.  Again no recorded changes of the effectiveness or therapeutic advantages were described.  We do state that we are measuring the electrical energy produced by the chemical reaction)

 

  1. Certain musculoskeletal disorders are accompanied by inflammation that causes swelling, tenderness, and redness, as pain.: Federal Register Vol. 44, No.234, Tuesday December 4, 1979, page 69862: Headings 6. Evaluation of counterirritants and claims for deep-seated pain/(1)Evaluation of the effects of pain **(Here is was known that in order to have pain there was the presence of either swelling, redness or tenderness due to inflammation, so inflammation was recognized as the precursor to pain)
  2. An increase in blood flow results over the area of application of the medicament and in the vessels in the skin area subserved by the spinal segment receiving these cutaneous impluses.: Federal Register Vol. 44, No.234, Tuesday December 4, 1979, page 69862: Headings 6. Evaluation of counterirritants and claims for deep-seated pain/(5)Measurements of the skin(No further explanation is required)
  3. The Panel used the terms in the above list of indications because it believes these terms would be understood by the general population. These are not necessarily terms which physicians would use in specific diagnosis.: Federal Register, Vol. 44, No. 234, Tuesday, December 4, 1979 **(Here it addresses that although indications are listed it is acknowledged that profession would need to be more specific in understanding and identifying a diagnosis)

 

As stated, § 330.10 (a)(4)(iii) requires the benefit to risk ratio of a drug to be considered in determining its safety and effectiveness. **(Since the formulation makes no claim of effectiveness that differs in its use and concentration from the present TFM / OTC standards and the formulation does not differ in the active ingredient percentages as determined in 21 U.S.C. §348 I don’t see how this would be considered a new drug or new approach, when the item that was claimed as a patent is the manufacturing process and measuring of activity.)

 

  1. 348.12 The active ingredients of the product consists of any of the following within the established concentration for each ingredient: (b) Irritants that produce sensation.—(1) Camphor exceeding 3 percent to 11 percent. (2)Menthol 1.25 percent to 16 percent.” Ref.: Ref.: Federal Register/Vol. 48, No. 27/Tuesday, February 8, 1983/Proposed Rules, page 5868

&

  1. “That the conditions included in the monograph, under which the drug products would be generally recognized are safe and effective and not misbranded (Category I),” : Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules, page 69768 **(Since the concentration of camphor is 3.1% of the 11% allowed 72% below the maximum as described as being safe and menthol is 3.0% of the 16 % allowed, 81% below the maximum as described as being safe, I cannot understand how this concentration as allowed under § 348.12 could not be considered safe.  If not a safe concentration then please state how it has been determined not to be safe) & (Following the guidelines as outlined in TFM / OTC 21 CFR Part 348 and accompanying reference, descriptions, definitions of intent relating to both Ref.: Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules & Ref.: Federal Register/Vol. 48, No. 27/Tuesday, Tuesday, February 8, 1983/Proposed Rules it has significantly provided evidence that allowing individual interpretation and definition without regards to supporting documents to provide confusion.
  2. “Safety. Clinical use as confirmed that camphor is safe in the dosage range used as an OTC external analgesic” : Federal Register/Vol. 44, No. 234/Tuesday, December 4, 1979/Proposed Rules, page 69802
  3. Conditions that would cause the drug to be NOT generally recognized as safe and effective or to be misbranded, may be initially introduced or initially delivered for introduction into interstate commerce Ref.: Federal Register/Vol. 48, No. 27/Tuesday, Tuesday, February 8, 1983, page 5853 **(The formulation that is used in ArNeu is not new with several named products formulated in the same manner with near concentration of active ingredients and does meet the criteria of active ingredients as required by 21 CFR 348.0)

 

You should take prompt action to correct these violations.  Corrective actions will be assessed during future inspections of your firm.  If you have any questions or concerns regarding this matter please contact me at the above stated address or phone number.  Thank you for your attention in this matter.

 

**I left a message for you to call me on October 28, 2011 to discuss before putting this together and also sent a few faxes to be addressed that I haven’t received an answer that may provide me more insight into this matter.

 

To complete this process and determination correctly please review “Phrases and Claims” I have left a simple check off for someone to either “Allow” or “Disallow” following each statement, in order to speed the process up.