Indian firm warned for litany of violations related to API manufacturing

Regulatory NewsRegulatory News
| 16 February 2022 | By Joanne S. Eglovitch 

The US Food and Drug Administration (FDA) targeted Indian drug maker Indiana Chem-Port in a warning letter for multiple violations related to its manufacturing of active pharmaceutical ingredients (APIs), including numerous data integrity failings, such as missing batch records and destroyed retain samples. The letter also cited the presence “rust-like” residues on the surfaces of some equipment at the facility.
The warning letter was issued on 2 February and posted to FDA’s website on 15 February. It follows a five-day inspection of the company’s site in Gujarat, India that was conducted in August 2021.
The firm was criticized for failing to ensure that equipment surfaces in contact with APIs were clean. Inspectors found “rust-like residues” on equipment product contact surfaces. In addition, the firm affixed tape on paddles to prevent “black material” from screws from contaminating its API.
The company also lacked written procedures for cleaning non-dedicated equipment. Operators attested they cleaned equipment without following written procedures. The agency wrote “you lack assurance that your equipment is adequately cleaned to prevent cross-contamination from other products.”
The firm was cited for failing to evaluate the effect of changes in the API manufacturing process. For example, the company changed the amount of water added to the active substance, yet the change was not validated.
FDA reminded the firm that “failing to implement adequate process validation practices can result in insufficient understanding of process variables or failure to detect a drift in capability, which increases the risk of drug quality defects.”
The company also lacked an adequate API stability testing program. Instead, reserve samples that were manufactured in 2016 were stored in a reserve sample room that was not controlled for humidity. FDA said that “despite basing your retest dating on this batch, you destroyed batch records associated” with these retain samples. These records were destroyed while the product was in US distribution.
FDA said “you lacked adequate scientific data to assure that your [redacted] API will maintain its quality attributes throughout its purported shelf-life and storage conditions. This could adversely affect the quality of the drugs that your customers manufacture from your API.”
Additionally, the letter cited the firm for having a weak quality unit (QU) which was unable to “assure reliable operations.” For instance, the QU failed to ensure “good documentation practices” as investigators noted a batch manufacturing production logbook with “torn out” pages and “numerous signed and partially completed batch records” which lacked a “controlled copy” stamp. FDA noted that the firm destroyed batch retain samples while the product was still being distributed in the US.
FDA told the company to consult several guidances, including its 2018 guidance on data integrity, and the International Council for Harmonisation’s Q7 guidance on GMPs for APIs. The firm was also advised to hire a GMP consultant.
FDA placed the company on an import alert on 13 December 2021 and warned it may “withhold approval of new applications listing your firm as a drug manufacturer until any deviations are completely addressed and we confirm your compliance with CGMP.”
FDA’s action follows on the heels of another warning letter sent to Indian manufacturer Aurobindo in Telanga, Hyderabad, for similar violations related to the manufacturing of its APIs. (RELATED: Aurobindo warned for lax investigations, repeat GMP violations, Regulatory Focus 26 January 2022)
Warning Letter


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