Pharmaceutical Technology Editors

According to an FDA August 6, 2021 announcement, KVK Tech is voluntarily recalling two lots of Atovaquone Oral Suspension, USP 750 mg/5mL because of customer complaints of unusual grittiness in the product. The company has determined that the grittiness was most likely caused by extremely cold weather during shipment.

Because the product must be protected from freezing temperatures, exposure to extremely low temperatures during shipment may cause product changes, according to the company, which can make it less effective.

The recalled lots are labeled 16653A and 16654A and have expiration dates of December 2022. The company stated in a press announcement that it is unaware of any adverse events associated with the recall. Adverse events may be reported to FDA through the agency’s MedWatch program.

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KVK Tech is voluntarily recalling two lots of Atovaquone Oral Suspension, USP 750 mg/5mL because of customer complaints of unusual grittiness in the product.

Atovaquone Oral Suspension Recalled

On August 6th, 2021, FDA announced that they had approved Nexviazyme for intravenous infusion to treat patients one year or older with Pompe Disease. It has been granted Fast Track, Priority Review, and Breakthrough Therapy designations, in addition to an orphan drug designation.

Pompe Disease is a condition that causes excess build-up of glycogen (which is typically broken down into glucose and released into the bloodstream to provide energy to cells) in skeletal and heart muscles, according to the agency. This causes muscle weakness and can lead to premature death from respiratory or heart failure.

Nexviazyme is an intravenous drug designed to reduce glycogen levels. A study was done wherein 100 patients with Pompe’s Disease were randomly given either Nexviazyme or another FDA approved enzyme-replacement therapy. The results found similar levels of efficacy between Nexviazyme and the approved therapy.

“Today’s approval brings patients with Pompe disease another enzyme replacement therapy option for this rare disease,” said Janet Maynard, deputy director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, in a press release. “The FDA will continue to work with stakeholders to advance the development of additional new, effective, and safe therapies for rare diseases, including Pompe disease.”

FDA has approved the intravenous medication Nexviazyme for treatment of Pompe Disease.

FDA Approves New Treatment for Pompe Disease

AGC Biologics, a biopharmaceutical contract development and manufacturing organization (CDMO), announced on Aug. 5, 2021 that it has finalized the acquisition of a commercial manufacturing facility in Longmont, Colo., previously owned by Novartis Gene Therapies. The facility significantly expands AGC Biologics’ capacity for producing cell and gene therapies, with additional space to expand.

The 622,000-ft2 facility is located 16 miles away from AGC Biologics’ large-scale stainless-steel mammalian facility in Boulder, Colo., and is expected to begin full-scale operations by the fourth quarter of 2021. Not only does the acquisition allow AGC Biologics to expand its cell and gene therapy footprint to the United States, it also enables the CDMO to continue rapidly expanding its process development and good manufacturing practice capacity for both early and late clinical/commercial demand.

AGC Biologics also announced major cell and gene therapy facility expansion projects at its Heidelberg, Germany, and Milan, Italy facilities in 2020 and 2021, respectively.

“The Longmont facility is just one of the company-wide expansion initiatives that AGC Biologics has been working on,” said Patricio Massera, CEO, AGC Biologics, in a company press release. “With our ongoing global expansion, we look forward to continuing to help our partners bring life-saving treatments to the market.”

AGC Biologics has acquired Novartis’ Longmont, Colorado, manufacturing facility for the commercial production of cell and gene therapies.

AGC Biologics Acquires Cell and Gene Therapy Commercial Manufacturing Facility

regarding near-infrared (NIR) analytical procedures. The guidance applies to new drug applications (NDAs), abbreviated new drug applications (ANDAs), and supplemental NDAs and ANDAs for small-molecule drugs. FDA will address recommendations for NIR methods used in biologics under a future revision of the guidance.

The guidance provides the agency’s recommendations for the development, validation, and use of NIR-based analytical procedures in evaluating a drug product’s identity, strength, quality, purity, and potency. The recommendations address the application of concepts described in FDA and International Council for Harmonisation guidelines to NIR analytical procedures that use chemometric models. It also discusses submitting NIR documentation in applications.

The guidance does not discuss the development and validation of NIR analytical procedures or the setup, qualification, maintenance, or calibration of NIR instruments. The concepts of the guidance can be applied to other analytical technologies.

The guidance aids in the development, validation, and use of near infrared-based analytical procedures.

FDA Issues NIR Guidance

FDA issued a warning letter to Syntec Pharma Corp., located at 96 Gazza Boulevard, Farmingdale, New York 11735, dated July 6, 2021. The warning letter summarized deviations from current good manufacturing practice (CGMP) for APIs.

FDA found that Syntec’s methods, facilities, or controls for manufacturing, processing, packing, or holding didn’t conform to CGMP, and their APIs were 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).

On October 7–28, 2020, FDA inspected the company’s drug manufacturing facility. The deviations observed by the investigators were as follows.

According to FDA’s warning letter, Syntec failed to have adequate controls to prevent cross-contamination between API, including receipt, storage, weighing, repackaging, and relabeling of API in the same room using non-dedicated equipment and without appropriate procedures.

During FDA’s inspection, the company stated they didn’t repackage any highly potent API. However, FDA found the company repacked a lot of lomustine. The company also acknowledged inappropriate storing of lomustine and human chorionic gonadotrophin, which were stored at room temperature instead of refrigeration as required by the manufacturers’ certificates of analysis to prevent degradation.

FDA found that Syntec kept weed killer, engine antifreeze coolant, and dry wall repair products in the same room where API and packaging components were stored. The inspectors also found comingled personal food items and unidentified products in unlabeled aluminum bags in the refrigerator where API and chemicals were stored.

Syntec’s response measures to these findings—to divide the pharmaceutical storage area into four sections by using a separate shelf for each of the following categories: cytotoxic compounds, beta-lactam, other potent compounds, and other API—were determined inadequate by FDA.

In addition,FDA stated Syntec failed to establish adequate written procedures for cleaning non-dedicated production equipment used for the API. The company also didn’t document the usage and cleaning of repackaging equipment. For example, Syntec didn’t document equipment used or whether cleaning was performed after repackaging lomustine (lot (b)(4)) on/around April 9, 2020.

According to FDA’s investigation, the company also lacked adequate quality unit (QU) oversight for the manufacture of their APIs. For example, the QU failed to:

Perform adequate testing and approve the results for the API prior to release and distribution,

Have stability data to support retest or expiration dates, as well as storage conditions, of API when repackaging them into different container-closure systems from their original ones,

Establish specifications for the API received, and more.

FDA also reviewed the company’s list of suppliers, and the drug products from three of their API suppliers were subject to an import alert at the time they imported drugs from these firms. Two of these suppliers had been issued warning letters by FDA, explaining issues related to CGMP compliance that caused the drugs to be adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

FDA instructed Syntec to correct any deviations 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 deviations may also prevent other Federal agencies from awarding contracts,” FDA stated in the letter.

Syntec receives warning letter where FDA finds deviations from CGMP for APIs.

FDA Issues Warning Letter to Syntec Pharma Corp

On Aug 03, 2021, BeiGene, a global biotechnology company specializing in cancer therapeutics, announced plans to build a new campus for R&D and manufacturing in Hopewell, NJ. The company plans to acquire approximately 42 acres of land for the site, where it will build a facility for commercial-stage biopharmaceutical manufacturing and clinical R&D and where it will house the BeiGene Center for Pharmacovigilance Innovation. The acquisition of the property is expected to close in the third quarter of 2021, and construction of the campus is expected to be completed in mid-2023.

BeiGene said in a company press release that it chose Hopewell for its central location and proximity to deep and rich pharmaceutical research, development, and manufacturing talent. The site will also complement the company’s plans to expand its footprint in the region. BeiGene plans to recruit hundreds of new hires to support continued growth.

“We are proud to be building our campus in New Jersey, and we’re grateful for the warm welcome BeiGene has received across the state,” said John V. Oyler, co-founder, chairman, and CEO of BeiGene, in the press release. "With a global team of over 6900 and growing, including our existing presence in Ridgefield Park, NJ, BeiGene’s expansion into the Princeton area furthers our commitment of translating groundbreaking science into quality, innovative cancer therapies. We are excited to connect more with the deep talent pool in the region as we plan to diversify and further expand.”

“BeiGene continues to grow, and, as a key part of that growth, we are making a significant investment in the United States that will expand our current capabilities. This endeavor, once complete, will further expand and diversify our global supply chain and build new manufacturing capabilities for our world-class pipeline,” said Michael Garvey, global head of Technical Operations at BeiGene, in the press release. “We are excited to begin the planned construction of our buildings to house colleagues in a variety of disciplines as well as the manufacturing portion of the campus, which is expected to initially produce biologics and potentially small-molecule cancer treatments.”

BeiGene plans to build a new campus for R&D and commercial-scale biopharmaceutical manufacturing in Hopewell, NJ.