FDA warns Lupin subsidiary, aesthetics firm

Regulatory NewsRegulatory News | 29 June 2021 |  By 

The US Food and Drug Administration (FDA) sent warning letters to generic drugmaker Lupin, Inc. over good manufacturing practice (GMP) issues at one of its US-based subsidiaries’ facilities and medical aesthetics firm Aquavit Pharmaceuticals for marketing two devices without approved applications.
Novel Laboratories, Inc.
In its 11 June warning letter to Lupin subsidiary Novel Laboratories, Inc., FDA cites the firm for three GMP violations at its Somerset, New Jersey, facility.
FDA notes that the issues cited in the warning letter include repeat violations cited in recent warning letters concerning three Lupin facilities in India. (RELATED: Lupin warned by FDA for deficiencies at two facilities, Regulatory Focus 15 November 2017; FDA warns Chinese drug testing facility for refusing inspection, Regulatory Focus 1 October 2019)
“Repeated violations at multiple sites demonstrate that your company’s corporate oversight and control over the manufacture of drugs is inadequate. You should further comprehensively assess your company’s global manufacturing operations to ensure that systems and processes, and ultimately, the drug products manufactured, conform to FDA requirements at all your sites,” FDA wrote.
The warning letter follows a nearly two-months-long inspection that occurred from 10 September to 5 November 2020.
The first violation cite in the warning letter concerns the company’s establishment and adherence to equipment cleaning and maintenance procedures.
“Your cleaning procedures for non-dedicated equipment, including your tablet presses and [redacted], are inadequate. Our investigators observed drug reside from previously manufactured drug product inside the [redacted] on one of your tablet presses documented and released as clean by your quality unit,” FDA wrote, adding that the tablet press was used to manufacture several potent and non-potent drugs.
The investigator also observed residue in other areas and the warning letter notes that “cleaning and preventative procedures … did not include cleaning instructions for these areas or a regular inspection of the air ducts.”
While the firm performed analytical testing of the residue from the tablet press and duct, which confirmed the presence of active drug ingredients, FDA said the response was inadequate because the company “did not test reserve samples of drug products released to the US market and within expiry, that were manufactured on these pieces of non-dedicated equipment, for cross-contamination.”
Further, FDA wrote that another surface “was observed covered with residue, which provides no assurance of its integrity to prevent cross-contamination” and that “there is no assurance that you can prevent cross-contamination because your corrective action and preventative action (CAPA) plan fails to include cleaning the [redacted] duct at drug product changeover.” The warning letter calls on the company to test all reserve samples of drug product within expiry and released to the US market manufactured on the equipment and to conduct a “comprehensive, independent retrospective assessment of [its] cleaning effectiveness.”
The next violation cited in the warning letter concerns Novel Laboratories’ written procedures for production and process change control.
“You failed to adequately validate the manufacturing processes for temazepam 15mg and 30mg capsules before the transfer of product manufacturing to a new building. You did not adequately assess the process and equipment changes (e.g., charging order of the active pharmaceutical ingredient, different model [redacted] you made to your manufacturing operations, and failed to identify their impact to product quality,” FDA wrote. The agency notes that several batches manufactured with these changes had out-of-specification (OOS) test results.
Lastly, FDA admonished the firm for failing to establish and follow adequate written responsibilities and procedures for its quality control unit.
“Your cleaning validation protocol procedure for the review and approval to change the MACO limits did not require adequate QU oversight. Specifically, this procedure did not require QU review of the test methods and the approved cleaning [maximum allowable carryover] MACO limits, for potent and non-potent drug products manufactured on non-dedicated equipment. You did not ensure that each of these test methods had the capability to quantitate the newly established limits,” FDA wrote.
Additionally, FDA says the company failed to adequately complete annual product reviews (APR) as required under 21 CFR 211.180(e) and its own procedures, noting that several products had APRs due in 2019 that were still pending at the time of the inspection.
FDA also points out that the company had previously made “corporate-wide commitments to strengthen analytical method equivalency, cleaning validation procedures, and APR procedures across all sites and to have corporate quality assurance oversight of these areas.”
Aquavit Pharmaceuticals, Inc
FDA sent a warning letter to medical aesthetics firm to New York-based Aquavit Pharmaceuticals dated 17 June 2021 over the company’s promotion of two dermatological devices without obtaining premarket approval (PMA) or an investigational device exemption (IDE) for the products.
The two products are marketed as the Aquagold Fine Touch microchannel microinjector and the Advanced Skin Application Platform (A.S.A.P!) Micro Infusion System.
FDA said the two products are both adulterated, due to the lack of approved applications, and misbranded, as the company did not notify the agency of its intent to introduce the devices into commercial distribution.
According to FDA, statements on the company’s websites included claims that indicate the products are medical devices as they are intended to deliver “microdoses and microinjections of products [or] micro-droplets of serums into the skin for various medical purposes.” FDA also explains that both products are considered medical devices because they are intended to affect the structure or any function of the body as they include microneedles that penetrate beyond the stratum corneum into living layers of skin.
Novel Laboratories
Aquavit Pharmaceuticals


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