Akron Formulations India Private Limited

Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our March 25, 2024 request, and subsequent correspondence, for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Akron Formulations India Private Limited, FEI 3017000602, at 134 - B, IDA - Bolaram, Hyderabad, Telangana 502325.

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations, parts 210 and 211 (21 CFR, parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 351(a)(2)(B)).

Following review of records and other information provided pursuant to section 704(a)(4) of the FD&C Act, significant violations were observed including, but not limited to, the following:

1. Your firm failed to establish an adequate 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)).

The records and information you provided did not demonstrate that you have adequately qualified your active pharmaceutical ingredient (API) suppliers. For example, you used API from the following three suppliers that were subject to an import alert (IA) at the time your drug products were manufactured and shipped to the United States:

• (b)(4) (FEI (b)(4)), which has been on Import Alert 66-40 ("Detention Without Physical Examination of Drugs From Firms Which Have Not Met Drug GMPs") since (b)(4). The CGMP deviations included failure to validate and monitor the water (b)(4) system to ensure that water is of appropriate quality and suitable for its intended use; for example, the firm failed to test its source water, which emanated from a nearby river and passed through farmland, where it was subject to agricultural runoff and animal waste, and was stored in an (b)(4) tank (b)(4) that was open to the environment. You used Docusate Sodium from (b)(4) as the API in OneLAX Docusate Sodium Liquid Stool Softener Laxative.

• (b)(4) (FEI (b)(4)), which was placed on Import Alert 99-32 (“Detention Without Physical Examination of Products from Firms Refusing FDA Foreign Establishment Inspection”) on (b)(4), and then on Import Alert 66-79 ("Detention Without Physical Examination of Drugs From Foreign Establishments Refusing FDA Inspection") on (b)(4). You used (b)(4) from this firm as an API in multiple products, including (b)(4).

• (b)(4) (FEI (b)(4)), which was placed on Import Alert 99-32 (“Detention Without Physical Examination of Products from Firms Refusing FDA Foreign Establishment Inspection”) on (b)(4), and then on Import Alert 66-79 ("Detention Without Physical Examination of Drugs From Foreign Establishments Refusing FDA Inspection") since (b)(4). You used (b)(4) from this firm as the API in (b)(4).

You are responsible for ensuring that the drugs you distribute are manufactured in compliance with all relevant CGMP requirements for drugs. Up-to-date information regarding IAs can be found at the following FDA website: https://www.accessdata.fda.gov/cms_ia/ialist.html.

In your 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 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.

• A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.

2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).

You did not adequately establish laboratory controls to ensure all drug products you manufactured possessed appropriate quality attributes, (b)(4), or (b)(4) systems to ensure their microbiological quality and safety.

Inadequate Drug Product Testing

The records and information you provided indicate that you did not test numerous drug product batches for Burkholderia cepacia complex (BCC) organisms. In some cases, such as OneLAX Docusate Sodium Liquid Stool Softener Laxative, no batches were tested for BCC organisms prior to release because the product specifications in effect at the time did not include it as a specification. In other cases, such as (b)(4), some batches were not tested for BCC organisms prior to release despite the product specifications in effect at the time including it as a specification. Of note, BCC is a known organism of concern in drugs containing docusate sodium, and has been associated with historical outbreaks, see the following website for further information:https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-2017-burkholderia-cepacia-contamination

Inadequate (b)(4) Testing

You lacked appropriate specifications to ensure the (b)(4) used as a component in your drug products was suitable for the intended use of your drug products. Specifically, the records and information you provided state that you do not test (b)(4), which is produced and stored at ambient temperatures, for BCC organisms.

Failure to Conduct (b)(4) Testing ((b)(4))

Before beginning distribution, you did not adequately study (b)(4) in your finished drugs products to evaluate the ability of the (b)(4) system to inhibit the growth of certain objectionable organisms. Your firm manufactured (b)(4) drug products with (b)(4) expiry periods, including ones labeled for use in infants and children. The records and information you provided state that you have not conducted AET on your drug products.

In your response to this letter, provide:

• A comprehensive assessment of your laboratory practices. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.

• A comprehensive 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 into all batches with potential objectionable microbial contamination or an OOS 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 (i.e., total counts, identification of bioburden to detect objectionable microbes) for each of your drug products.

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

• A summary of results from testing reserve samples of all drug product batches within expiry. You should test 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 actions you will take, including notifying customers and initiating recalls.

• A procedure for your (b)(4) system monitoring that specifies routine microbial testing of (b)(4) to ensure its acceptability for use in each batch of drug products produced by your firm.

• The revised action/alert limits for total counts and objectionable organisms used for your (b)(4) system. Ensure that the total count limits for your (b)(4) are appropriately stringent in view of the intended use of each of the products produced by your firm.

• A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the system consistently produces (b)(4) that meets (b)(4), USP monograph specifications and appropriate microbial limits.

• Appropriate scientific studies to evaluate AET for your (b)(4) multi-dose drug products. AET by USP <51> testing should be performed at a range of (b)(4) concentrations and should be inclusive of concentrations at or below that listed in the formulation for each drug product. In addition to initial USP <51> studies on your formulations, one of the primary batches of the drug product should be tested for (b)(4) effectiveness (in addition to (b)(4) content) at the end of the proposed shelf life. The drug product specification should include a test for (b)(4) content, and this attribute should be tested in all stability studies.

On October 15, 2024, you issued a voluntary recall of OneLAX Docusate Sodium Liquid Stool Softener Laxative due to CGMP violations. The company announcement was posted to the FDA website: https://www.accessdata.fda.gov/scripts/ires/?Event=95511.

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 actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

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.

FDA placed products offered for import into the United States from your firm on Import Alert 66-40 on November 26, 2024.

Correct any violations promptly. 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 inspect to verify that you have completed corrective actions to any violations.

Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Akron Formulations India Private Limited, at 134 - B, IDA - Bolaram, Hyderabad, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

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 3017000602 and ATTN: Russell Riley.