Zydus Lifesciences Limited

Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of prescription drug products. FDA has reviewed the records you submitted in response to our November 7, 2025 request 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, Zydus Lifesciences Limited, FEI 3005430968, at Village Swaraj Majra, P.O. Baddi, Tehsil-Nalagarh, Solan Himachal Pradesh.

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 of drugs as described in your response to our 704(a)(4) request 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 withhold from use each lot of components, drug product containers, and closures until the lot had been sampled, tested, or examined, as appropriate, and failed to test samples for conformity with all appropriate written specifications for purity, strength, and quality (21 CFR 211.84).

Your firm manufactures prescription (b)(4) drug products containing talc. (b)(4) USP is composed of more than (b)(4)% talc. Both talc and asbestos are naturally occurring minerals that may be found in close proximity in the earth. Asbestos is a potential contaminant in talc and is a known human carcinogen when inhaled.1,2 Additionally, published scientific literature dating back to the 1960s has suggested a possible association between the use of (b)(4) containing talc in the (b)(4) area and the incidence of (b)(4), potentially linked to asbestos contamination of the talc.3 The (b)(4) you produce can be used on areas of the body which may be an exposure risk (e.g., inhalation or (b)(4) area). Your product is also labeled for use in (b)(4). Your drug product, (b)(4) USP, is considered a higher-risk drug as it pertains to patient safety regarding asbestos contamination of talc due to the risk of inadvertent inhalation or potential use in the (b)(4) area.

You have not demonstrated that you have appropriately tested incoming talc, a drug component, used in the manufacture of your (b)(4) drug products. For example, your internal testing procedures and specifications are written in accordance with the current United States Pharmacopeia (USP) specification for absence of asbestos, however, your records do not demonstrate you are testing to current USP requirements. For asbestos testing your data refers to identification testing by Infrared (IR) Spectroscopy. Current USP absence of asbestos procedure (b)(4) by Infrared (IR) Spectroscopy includes the evaluation of the presence of tremolite chlorite and serpentines, through scale expansions of spectra at the required wavenumbers at (b)(4) cm-1, and in the range of (b)(4) cm-1 to (b)(4) cm-1. Your instrument reports for the identification spectroscopy was from (b)(4) cm-1 to (b)(4) cm-1 wavenumbers and did not include any scale expansions. Your identification spectra does not evaluate for the presence of serpentines in the range of (b)(4) cm-1 and (b)(4) cm-1. Furthermore, review of the available spectral data reveals absorption features in the (b)(4) cm⁻¹ and (b)(4) cm⁻¹ region across multiple lots, which encompasses the critical (b)(4) cm⁻¹ range specified for tremolite/chlorite detection, yet no scale expansion analysis was documented in any of the analytical records as per the current USP monograph.

As a manufacturer, you have a responsibility to sample, test, and examine, as appropriate, drug components before use in production to ensure acceptable specifications for identity, strength, quality, and purity are met. Because you have not performed appropriate testing that detects asbestos in your talc components, among other things, you failed to assure the acceptability of these drug components for use in manufacture of your drug products.

In response to this letter, provide:

Using an independent laboratory, appropriate asbestos testing results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of talc (drug component) used in the manufacture of your drug products within expiry. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for asbestos.

A comprehensive independent assessment of your laboratory practices, procedures, methods, and specifications. Based on this review, provide a detailed plan to remediate deficiencies and evaluate the effectiveness of corrections in your laboratory system.

A full risk assessment for drug products that are within expiry which contain any ingredient at risk for asbestos contamination. Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain asbestos. Appropriate actions could include customer notifications and drug product recalls for any contaminated lots.

2. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products are manufactured in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).

Your quality unit (QU) did not effectively exercise its authority to ensure appropriate testing is conducted. Your records submitted for talc identification testing by IR spectroscopy show that an out-of-specification (OOS) wavenumber result was removed from an infrared instrument report and multiple passing wavenumbers were added. These changes allowed a failing identification test to appear as if it met release specifications. Your QU failed in its responsibility to maintain data integrity and provide adequate oversight of testing procedures, demonstrating a lack of authority and control over critical quality decisions. Furthermore, a review of all submitted certificates of analysis for talc show a pattern of numerous wavenumbers that may be statistically unlikely and raises concerns regarding the authenticity of the reported results. Between 2022 and 2025, out of 29 approved analytical results, 21 reports have identical maxima at (b)(4), and (b)(4) cm⁻¹ across different lots and dates.

Your QU is responsible for fully exercising its authority and responsibilities, including responsibility for approving or rejecting all procedures or specifications impacting the identity, strength, quality, and purity of the drug product. Your firm’s quality systems are inadequate. See FDA’s guidance document ICH Q10 Pharmaceutical Quality System, as well as 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/71553/download and https://www.fda.gov/media/71023/download, respectively.

In response to this letter, provide:

Results from a comprehensive investigation into the extent of the data anomalies identified in this letter and a report including any corrective and preventative action for the investigation for drugs distributed to the United States. To aid in your investigation, you may refer to FDA’s guidance document Data Integrity and Compliance with Drug CGMP: Questions and Answers for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/media/119267/download.

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 representative batches within expiry and their related information before the QU disposition decision

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.

If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff may also allow you to meet obligations you may have to report permanent discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(a). This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.

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 refusing admission of articles manufactured at Zydus Lifesciences Limited, FEI 3005430968, at Village Swaraj Majra, P.O. Baddi, Tehsil-Nalagarh, Solan Himachal Pradesh 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.4 Specify what you have done to address any 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. If you have information that you believe demonstrates that your products are not in violation of the FD&C Act and FDA regulations, include that information for our consideration.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3005430968 and ATTN: Nancy Espinal.