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WARNING LETTER
CMS# 574921

June 28, 2019

VIA UPS OVERNIGHT

Mr. Adil Palwala
CEO and Owner
Scientific Solutions Global LLC
326 Westbury Avenue
Carle Place, NY 11514

FEI #3013847493

Dear Mr. Palwala:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Scientific Solutions Global LLC (FEI: 3013847493), located at 326 Westbury Avenue, Carle Place, New York, from December 11, 2018, to January 2, 2019.

This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 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 Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

In addition, the inspection revealed that your firm manufactures unapproved new drugs—BIOTEMPER COLD PAIN RELIEF THERAPY, UREA 20, bare20, UREA 40, UREA 40+, bare40, bare40+Salicylic Acid, and bare40+Hyaluronic Acid—in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a). Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d). These violations are described in more detail below.

We reviewed your January 21, 2019, response in detail. We acknowledge that you no longer distribute your BIOTEMPER over-the-counter (OTC) drug product. You indicated that you will seek other contract facilities to produce OTC drugs on your behalf. However, your response is inadequate because you did not provide sufficient details about the corrective actions you made to bring your operations into compliance with CGMP, nor how you would ensure drugs made on your behalf at contract manufacturers will be in compliance with CGMP.

During our inspection, our investigator observed specific violations including, but not limited to, the following.

1. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a))

During our inspection, your firm stated that it does not perform any finished drug product release testing on BIOTEMPER and UREA 40+Salicylic Acid. Additionally, your firm stated that there is no system in place for the testing and release of drug products from your facility.

In response to this letter, provide:

? A list of chemical and microbial test methods and specifications used to analyze each lot of your drug product before a lot disposition decision and associated written procedures.

? A summary of results obtained from testing retain samples of all drug products within expiry that have been distributed in the United States. Include results for identity and strength of active ingredients and all other appropriate chemical and microbial quality attributes.

2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and (2)).

During our inspection, your firm stated that it does not perform identification testing to confirm the identity of received raw materials or components.

Instead, your firm used results from your suppliers’ certificates of analysis (COA) without establishing the reliability of your suppliers’ analyses through appropriate validation and without conducting at least one specific identity test on each incoming lot of components. Under 21 CFR 211.84(d)(2), you may not rely on your suppliers’ COA to verify the identity of your components.

In response to this letter, provide:

? Your updated SOP describing in detail how you plan to test each component lot for conformity with all appropriate written specifications for identity, purity, strength, and quality.

? A commitment to test each lot of components received for identity, regardless of supplier COA verification programs.

? If you accept your suppliers’ COA in lieu of testing each component lot for purity, strength, and quality, describe how you plan to establish the reliability of your suppliers’ test results for these attributes at regular intervals. Provide your timeline for implementing these corrective actions.

? A complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed corrective actions and preventive actions (CAPA) plan that remedies documentation practices and ensures that you retain complete and accurate records.

3. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess, and your firm’s quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)).

During our inspection, your firm stated that it does not perform any process validation for any of the drug products you manufactured.

The purpose of process validation is to establish scientific evidence that a process is capable of consistently delivering quality product. Sampling and testing of in-process materials and drug products requires control procedures to monitor output and validate performance of manufacturing processes that may cause variability in drug product characteristics. Samples must be representative of the batch, provide appropriate statistical confidence, and meet predetermined specifications. See FDA 's guidance document Process Validation: General Principles and Practices for approaches that FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.

In response to this letter, provide:

? A comprehensive review of your manufacturing processes to determine your current state of control.

? A data-driven and scientifically sound validation program that identifies and controls all sources of variability such that your manufacturing processes will consistently meet appropriate manufacturing standards and parameters. This includes, but is not limited to, evaluating suitability of equipment for its intended use, ensuring quality of input materials, and determining the capability and reliability of each manufacturing process step and control.

? Include a timeline for performing process performance qualification for each of your drug products. Describe your program for monitoring batch-to-batch variation to ensure an ongoing state of control. Also, include your process performance protocol(s) and your written procedures to qualify equipment and facilities.

4. Your firm failed to establish a quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).

During our inspection, our investigator observed that your firm failed to establish an adequate quality unit (QU). Your QU failed to ensure that adequate specifications were established for the drug products you manufacture. Also, your QU failed to meet its responsibility to ensure each batch was tested for, and conformed to, all appropriate attributes before distribution. Additionally, your QU failed to establish a stability program to support the expiry of the drug products that are manufactured and distributed in the U.S. market.

An effective pharmaceutical quality system ensures that each drug product batch released for distribution meets all appropriate manufacturing standards and test specifications.

In response to this letter, provide:

? A comprehensive assessment with CAPA to ensure your QU is given the authority and resources to effectively function in accordance with 21 CFR 211.22(a). The assessment should also include, but not be limited to:

o A determination of whether procedures used by your firm are robust and appropriate
o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices
o A complete and final review of each batch and its related information before the QU disposition decision
o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products

Quality Systems

Your firm’s quality systems are inadequate. See 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 Consult Recommended

Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant, qualified as set forth in 21 CFR 211.34, to assist your firm in meeting CGMP requirements.

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.

Use of Contract Manufacturers

Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.

You are responsible for the quality of your drugs regardless of agreements in place with your contract facility. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act to ensure safety, identity, strength, quality, and purity. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/media/86193/download.

Unapproved New Drug Charges

BIOTEMPER COLD PAIN RELIEF THERAPY

BIOTEMPER COLD PAIN RELIEF THERAPY is a “drug” as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because it is intended for the diagnosis, cure, mitigation, treatment, or prevention of disease and/or under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because it is intended to affect the structure or any function of the body. Specifically, this product is intended for use as an external analgesic.

Examples of claims observed on the product label and labeling, which includes the product website www.biotemper.com, that establish the intended uses, as defined in 21 CFR 201.128, of the product include, but may not be limited to, the following:

Statements that appear on the product label:

“FOR ARTHRITIS, SPRAINS, SORE MUSCLES, BRUISES, & BACK PAIN Active Ingredient . . . Menthol 10%”

Statements that appear on the website, www.biotemper.com (i.e., URL imprinted on the product label):

“Many have already experienced the herbal pain relief of Menthol and Arnica, BioTemper combines them to achieve an effective level of pain relief . . . BIOTEMPER is a PAIN RELIEVER that is a fast acting pain relief. It is effective and long lasting for people with Arthritis, Back Pain, Bursitis, Carpal Tunnel, Chronic Pain, Fibromyalgia, Golfer’s Elbow, Heel Pain, Hip Pain, Joint Pain, Muscle Pain, Neck Pain, Nerve Pain, Neuropathy, Plantar Fasciitis, Repetitive Strain Injuries, Sciatica, Severe Migraine and Headache, Shin Splints, Shoulder Pain, Sports Injuries, Tendinitis, Tennis Elbow, and All Other Aches and Pains and General Muscle Pain.”

OTC drug products such as BIOTEMPER COLD PAIN RELIEF THERAPY that are intended for external analgesic indications such as the temporary relief of minor aches and pains of muscles and joints are being evaluated as part of the OTC Drug Review. They have been proposed to be classified as generally recognized as safe and effective and not misbranded under the Tentative Final Monograph (TFM) for External Analgesic Drug Products for Over-the-Counter (OTC) Human Use (48 Federal Register (FR) 5852, February 8, 1983) if they meet each condition in the TFM and each general condition in 21 CFR 330.1.

Pending the promulgation of a final rule, FDA generally does not intend to pursue regulatory action against products marketed in accordance with the conditions proposed in the TFM and each general condition in 21 CFR 330.1. Such marketing, however, is subject to the risk that a final rule may require reformulation and/or relabeling or FDA approval through the “new drug” procedures of the FD&C Act (section 505). However, BIOTEMPER COLD PAIN RELIEF THERAPY does not meet these conditions for the reasons explained below.

The labeling for and formulation of BIOTEMPER COLD PAIN RELIEF THERAPY are not consistent with the condition proposed for external analgesic drug products, see TFM for External Analgesic Drug Products for OTC Human Use (48 FR 5852 at 5868, February 8, 1983). Specifically, the product website identifies arnica as an active ingredient in the product with the following claim, “Many have already experienced the herbal pain relief of Menthol and Arnica, BioTemper combines them to achieve an effective level of pain relief.”

According to 21 CFR 201.66(b)(2), an “active ingredient” means any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of humans. The website claims for this specific ingredient demonstrates that arnica is an “active ingredient” as defined in 21 CFR 201.66(b)(2) because the ingredient is intended to furnish pharmacological activity.

Arnica, as an active ingredient, is not included in the OTC Drug Review for external analgesic or any other uses. Further, the external analgesics TFM does not include any claims related to bursitis, carpal tunnel, fibromyalgia, nerve pain, neuropathy, plantar fasciitis, sciatica, severe migraine and headache, and tendonitis; however, all of these indications for use are included in the labeling for BIOTEMPER COLD PAIN RELIEF THERAPY.

Furthermore, we are not aware of any adequate and well controlled clinical trials in the published literature that support a determination that BIOTEMPER COLD PAIN RELIEF THERAPY is generally recognized as safe and effective for its labeled indications. Additionally, we are not aware of a similar OTC drug product that, as formulated and labeled, was available in the United States market on or before the inception of the OTC Drug Review.

Therefore, BIOTEMPER COLD PAIN RELIEF THERAPY is a new drug within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p) because it is not generally recognized among scientific experts as safe and effective for the drug uses described in its labeling.

“New drugs” may not be introduced or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FD&C Act is in effect for the drug. BIOTEMPER COLD PAIN RELIEF THERAPY is not the subject of an FDA-approved new drug application. Therefore, marketing this product in the United States is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d), and violates section 505 of the FD&C Act.

UREA 20, UREA 40, UREA 40+, bare20, bare40, bare40+Salicylic Acid, and bare40+Hyaluronic Acid

UREA 20, bare20, UREA 40, UREA 40+, bare40, bare40+Salicylic Acid, and bare40+Hyaluronic Acid are “drugs” as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because they are intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because they are intended to affect the structure or any function of the body.

Specifically, UREA 20, UREA 40, and UREA 40+ are intended as corn and callus remover products, and bare20, bare40, bare40+Salicylic Acid, and bare40+Hyaluronic Acid are intended as combination antifungal/corn and callus remover products.

Examples of claims observed on the product label that establish the intended uses, as defined in 21 CFR 201.128, of the products include, but may not be limited to, the following:

UREA 20, UREA 40, UREA 40+

Statements that appear on the products’ labels:

“HEALS CORNS & CALLOUSES”

bare20, bare40, bare40+Salicylic Acid and bare40+Hyaluronic Acid

Statements that appear on the products’ labels:

“HEALS CORNS & CALLOUSES”

There are additional claims found on the product websites www.scisoglobal.com (which redirects to www.ureaeverything.com), that are imprinted on the labels for bare20, bare40+Salicylic Acid and bare40+Hyaluronic Acid and www.ureaeverything.com, that are imprinted on the labels for bare40 and bare40+Hyaluronic Acid. These additional claims establish their intended uses, as defined in 21 CFR 201.128, and include, but may not be limited to, the following:

“It is a concentrated and highly effective anti-fungal foot gel . . . is specially formulated to remove thick calluses and helps repair cracked heels with the most potent therapeutic ingredients including Tea Tree Oil and Aloe Vera extracts”

OTC drug products such as UREA 20, bare20, UREA 40, UREA 40+, bare40, bare40+Salicylic Acid, and bare40+Hyaluronic Acid intended as corn and/or callus removers are subject to the Final Rule for Corn and Callus Remover Drug Products, 21 CFR 358, Subpart F. The products bare20, bare40, bare40+Salicylic Acid, and bare40+Hyaluronic Acid are also subject to the Final Monograph for Topical Antifungal OTC Drug Products, 21 CFR Part 333, Subpart C because they are also intended for use as antifungals.

However, these products do not meet the Final Rule for Corn and Callus Remover Drug Products because salicylic acid is the only allowed active ingredient for use as a corn or callous remover; none of the aforementioned products include salicylic acid as the sole active ingredient. While the product bare40+Hyaluronic Acid includes salicylic acid as an active ingredient, it is not the sole active ingredient. Rather, bare40+Hyaluronic Acid also includes urea, tea tree oil, aloe vera and green tea as labeled active ingredients. Additionally, bare20, bare40, bare40+Salicylic Acid, and bare40+Hyaluronic Acid do not meet the conditions set forth in 21 CFR 358, Subpart F and 21 CFR Part 333, Subpart C because a combination antifungal/corn and callus remover product is not permitted under these final rules for corn and callus remover drug products or antifungal drug products.

Thus, as formulated and labeled, UREA 20, bare20, UREA 40, UREA 40+, bare40, bare40+Salicylic Acid, and bare40+Hyaluronic Acid do not comply with the rulemakings described above. Furthermore, we are not aware of sufficient evidence to show UREA 20, bare20, UREA 40, UREA 40+, bare40, bare40+Salicylic Acid, and bare40+Hyaluronic Acid, as formulated and labeled, are generally recognized as safe and effective. Therefore, these products are new drugs within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p).

As new drugs, UREA 20, bare20, UREA 40, UREA 40+, bare40, bare40+Salicylic Acid, and bare40+Hyaluronic Acid may not be legally marketed in the United States absent approval of an application filed in accordance with section 505(a) of the FD&C Act of the FD&C Act, 21 U.S.C. 355(a). UREA 20, bare20, UREA 40, UREA 40+, bare40, bare40+Salicylic Acid, and bare40+Hyaluronic Acid are not the subjects of FDA-approved applications, and therefore, the current marketing of these products violates section 505(a) of the FD&C Act, 21 U.S.C. 355(a). Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d).

Conclusion

Violations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing other violations.

Correct the violations cited in this letter promptly. Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction. Unresolved violations in this warning letter may also prevent other Federal agencies from awarding contracts.

Until these violations are corrected, we may withhold approval of pending drug applications listing your facility. We may re-inspect to verify that you have completed your corrective actions. We may also refuse your requests for export certificates.

After you receive this letter, respond to this office in writing within 15 working days. Specify what youhave done since our inspection to correct your violations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Please send your electronic response to orapharm1_responses@fda.hhs.gov. Please identify your response with FEI #3013847493 and refer to Warning Letter CMS# 574921.

If you have any questions, please contact Compliance Officer Juan Jimenez at juan.jimenez@fda.hhs.gov or 518-453-2314 X-1014.

 

/S/
Diana Amador-Toro
Program Division Director/District Director
U.S. Food and Drug Administration
OPQO Division I / New Jersey District