Siddha Flower Essences, LLC., dba Siddha Remedies

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Siddha Flower Essences, LLC., dba Siddha Remedies, FEI 3014145088, at 2350 Eastman Ave., Suite 107, Oxnard, from April 22 to 29, 2025.

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations 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 human and animal 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, we reviewed your firm’s drug listing submissions in FDA’s electronic Drug Registration and Listing System (eDRLS) and found that you failed to update your human over-the-counter (OTC) homeopathic drug listings as required under section 510(j) of the FD&C Act, 21 U.S.C. 360(j), and 21 CFR Part 207.

Thus, your drugs are not properly listed, and your firm has not fulfilled its listing obligations under 510(j) of the FD&C Act, U.S.C. 360(j), and 21 CFR 207, which is prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p), and will render a drug misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o). The introduction or delivery for introduction of a misbranded drug into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). These violations are described in more detail below.

We reviewed your May 20, 2025 response to our Form FDA 483 in detail.

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

1. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals. Your firm also failed to conduct microbiological testing before use of each lot of a component with potential for objectionable microbiological contamination in light of its intended use (21 CFR 211.84(d)(1) and 211.84(d)(2)) and (21 CFR 211.84(d)(6)).

You manufacture aqueous oral homeopathic drug products intended for children as young as 2 years old.

Purified Water

You failed to test your purchased bulk water to assure it was of acceptable quality for use in drug production. You also failed to establish the reliability of your component supplier at appropriate intervals. Your firm has not demonstrated that the water was suitable for its intended use and minimally met the USP purified water monograph.

Pharmaceutical-grade water must be suitable for its intended use. Each lot must be tested to ensure conformance with appropriate chemical and microbiological attributes. Routine monitoring of microbial counts as well as characterization and identification of contamination is integral to ensuring water is of acceptable quality for use in manufacturing operations.

Of particular note, you stopped testing the water after 2022, but you continued to use it as a component of your pediatric drug products. Prior to stopping, you did not test the water for Burkholderia cepacia complex (BCC), a contamination risk in non-sterile water-based drug products, which has been linked to multiple instances of opportunistic infections. For further information regarding the significance of BCC and other objectionable contamination of non-sterile, water-based drug products, see FDA’s advisory notice, at https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-drug-manufacturers-burkholderia-cepacia-complex-poses-contamination-risk-non-sterile.

Botanical

You also failed to perform adequate testing of botanical components that may pose potentially toxic effects. Without adequate component controls, you lack scientific evidence to assure component identity, safety, quality, and conformance to appropriate specifications.

In your response, you acknowledge insufficient expertise, quality unit (QU) oversight, and resources. You also commit to improving component controls (e.g., specifications, procedures, testing) and propose various timelines for completion. However, you did not provide clear interim plans for drug production until corrections are completed. Also, you have not confirmed the reliability of your contract testing laboratories, nor have you evaluated the impact of using inadequately controlled components on the quality and safety of drug products distributed within the United States.

In response to this letter, provide:

A comprehensive, independent review of your material system including, but not limited to:o evaluating all suppliers of materials (components, containers, and closures) to determine if they are reliable and appropriately qualifiedo an assessment of all materials to determine whether they are consistently of acceptable qualityo adequacy of the supplier qualification program, and its selection, qualification, and disqualification provisionso a summary of your systemic corrective action and preventive action (CAPA) to remediate the vendor qualification program and prevent use of unsuitable components, containers, and closures.

The chemical and microbiological quality control specifications you use to test and release each incoming lot of the components you use in manufacturing and corresponding test results (e.g., total counts, identification to detect objectionable microbes, such as BCC).

A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s certificates of analysis (COA) instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.

A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer.

A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.

2. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

You failed to adequately investigate finished drug product sample results that were out of limit (OOL) for microbiological contamination. For example, you failed to identify a root cause and implement adequate CAPA. You state that you have rejected and destroyed the contaminated batch, however, you could not provide supporting documentation.

You also failed to characterize and identify gram-negative growth recovered in finished drug product samples to evaluate whether it is objectionable based on intended use. Microbiological contamination of aqueous drug products poses an unacceptable risk to children as gram-negative bacteria have been linked to opportunistic infections.

In your response, you state your firm lacks qualified personnel and has insufficient QU oversight and resources. You also commit to performing CAPA including a retrospective review of discrepancies for potential product impact. However, your response in inadequate. You did not provide a clear timeline for CAPA completion (e.g., BCC testing) or clear interim plans for drug production until you determine the full scope of impact to drug quality and safety.

Well-documented, thorough, and scientifically sound investigations are necessary to identify the root cause and implement appropriate and effective CAPA.

In response to this letter, provide:

A comprehensive, independent assessment of the design and control of your firm’s manufacturing operations, with a detailed and thorough review of all microbiological hazards.

A detailed risk assessment addressing the hazards posed by distributing drug products with potentially objectionable contamination. Specify actions you will take in response to the risk assessment, such as customer notifications and product recalls.

Complete investigations of all batches with potential objectionable microbial contamination or an out-of-limit (OOL) microbiological result (whether or not later invalidated). The investigations should detail your findings regarding the root causes of the contamination.

Appropriate microbiological batch release specifications (e.g., total counts, identification of bioburden to detect objectionable microbes, such as BCC) for each of your drug products including the specific date test results indicated drug products met all specifications.

All chemical and microbial test methods used to analyze each of your drug products.

A summary of results from testing retain samples of all drug product batches within expiry. You should test all appropriate quality attributes including, but not limited to, microbiological quality (total counts and identification of bioburden to detect any objectionable microbes) of each batch. If testing yields an OOS result, indicate the corrective action you will take, including notifying customers and initiating recalls.

A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, OOS results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality unit oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.

Your firm released finished drug product Temper Tamer lot# S22-26424D without testing for critical microbial attributes (e.g., total count, absence of objectionable microorganisms). Without testing each batch prior to release, you did not have scientific evidence that all oral drug product batches were free of objectionable microbial contamination.

In particular, your firm failed to conduct testing for BCC for non-sterile aqueous-based drug products at release and on stability. See FDA’s advisory notice mentioned above. In addition, see FDA’s guidance document, Microbiological Quality Considerations in Non-sterile Drug Manufacturing, for help minimizing the risks of harmful microbiological contamination of aqueous drugs at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/microbiological-quality-considerations-non-sterile-drug-manufacturing.

We acknowledge that you voluntarily initiated a recall of pediatric drug product Temper Tamer lot# S22-26424D on April 28, 2025. However, it is important to note that this CGMP violation was identified by your firm as a result of an FDA inspection conducted from April 25 to 29, 2025.

In your response, you acknowledge insufficient QU oversight, lack of qualified personnel, and lack of adherence to procedures. You also commit to improving finished product controls (e.g., specifications, procedures, testing), conducting a retrospective review, and proposing various completion dates. However, several details remain unclear. This includes, but is not limited to, a clear timeline for CAPA completion (e.g., BCC testing) and interim plans for your operations while you determine the full scope of the impact of your violations on the quality and safety of the drugs you produce.

In response to this letter, provide:

A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective action, such as notifying customers and product recalls.

4. 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 QU did not adequately oversee your drug manufacturing operations. For example, your QU failed to ensure:

Established procedures were followed (21 CFR 211.22(d))

Batch records were reviewed before drug product release (21 CFR 211.22(a))

Use of qualified contract testing laboratories (21 CFR 211.22(a))

Adequate effectiveness testing of the preservative system (21 CFR 211.160(b))

Adequate production and process controls were established (21 CFR 211.100(a))

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/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations.

In response to this letter, provide:

A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:o A determination of whether procedures used by your firm are robust and appropriateo Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practiceso A complete and final review of each batch and its related information before the QU disposition decision

Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products

A description of how top management supports quality assurance and reliable operations including, but not limited to, timely provision of resources to proactively address emerging manufacturing/quality issues and to assure a continuing state of control.

A comprehensive, independent assessment of your change management system. This assessment should include, but not be limited to, your procedure(s) to ensure changes are justified, reviewed, and approved by your quality unit. Your change management program should also include provisions for determining change effectiveness.

Section 510 of the FD&C Act, 21 U.S.C. 360, and 21 CFR Part 207 set forth the requirements for the registration of establishments and listing of drugs. Under 510(j) of the FD&C Act, 21 U.S.C. 360(j), and 21 CFR 207.57(b), registrants are required to update drug listing information twice each year, in June and December. Under 21 CFR 207.57(b)(2) registrants may satisfy the listing update requirement with respect to unchanged listing information by making a single “no changes” certification during the October 1st through December 31st annual registration period. If the drug listing data is not updated or certified, the outdated listing data will be inactivated at the next scheduled FDA inactivation period.1 You failed to update or certify your human OTC homeopathic drug listings as required.

Therefore, your human OTC homeopathic drugs are not properly listed under section 510(j) of the FD&C Act, rendering these drugs misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o). The introduction or delivery for introduction of a misbranded drug into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). In addition, failure to properly list a drug in accordance with 510(j) of the FD&C Act is prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p).

Complete, accurate, and up-to-date establishment registration and drug listing information is essential to promote and protect patient safety. FDA relies on establishment registration and drug listing information for several key programs, including drug establishment inspections, supply chain security, and post-market surveillance. Establishment registration and drug listing information is also widely used outside FDA for purposes such as electronic prescribing and electronic health records, insurance reimbursement, and patient education.

We note that during the inspection, your firm was notified that your human OTC homeopathic drugs were listed as “Inactivated-Uncertified” in eDRLS, and you have failed to update these drug listings. If you cease manufacturing and distributing any drug, then you must discontinue that listed drug in eDRLS by adding an end marketing date which corresponds to the expiration date of the last lot in commercial distribution. It is your responsibility to ensure that all drugs manufactured at your establishment comply with all establishment registration and drug listing requirements under section 510 of the FD&C Act, 21 U.S.C. 360, 21 CFR Part 207, and all other applicable FDA regulations. Registration and listing information and instructions on how to properly register an establishment or submit drug listings can be found at Electronic Drug Registration and Listing Instructions.

Sections 510(b)(1) and (j)(1) of the FD&C Act [21 U.S.C. 360(b)(1), (j)(1)] require that manufacturers of drugs, including animal drugs, register their manufacturing establishments with FDA and provide the agency with a list of all the drugs they manufacture. Drugs that are manufactured in an establishment that is not duly registered or that have not been listed with FDA are misbranded under section 502(o) of the FD&C Act.

You have been manufacturing animal drugs in a facility that is not registered with FDA as an animal drug manufacturer. Further, you have incorrectly listed your animal drug products under the human drug establishment registration. Accordingly, these animal drugs are misbranded. Introduction or delivery for introduction of a misbranded animal drug into interstate commerce is prohibited under section 301(a) of the FD&C Act.

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. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective action and preventive action 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.

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 facilities. 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/regulatory-information/search-fda-guidance-documents/contract-manufacturing-arrangements-drugs-quality-agreements-guidance-industry.

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.

Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.

Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3014145088 and ATTN: CDR Matthew Schnupp, PharmD, BCSCP.