India’s Sun Pharmaceutical, which has had a host of problems at some of its manufacturing facilities in India, narrowly escaped another warning letter for one of its U.S. facilities. Instead, the citation has been hung around the neck of Frontida BioPharm, which bought the Philadelphia plant in June with big plans to expand the operation.
The letter is tied to a month-long inspection made of the facility from mid-June to mid-July of 2015 when Sun still owned the the former Mutual Pharmaceuticals plant. According to the warning letter, the FDA reviewed the responses Frontida made since buying the facility for an undisclosed sum and taking on its 250-person workforce but decided to issue the warning anyway.
Frontida is a newly formed CDMO that is an affiliate company of Frontage Laboratories. Frontage is a long-standing CRO in Pennsylvania, New Jersey and China that is controlled by Chinese CRO Hangzhou Tigermed.
"Since we have newly acquired the facilities, Frontida is working diligently, with Sun's support, to promptly respond to the matters raised by the FDA," Frontida BioPharm Chief Operating Officer Ron Connolly said in an emailed statement.
The warning letter outlines some serious issues at the facility. According to inspectors, the plant’s quality unit “knowingly released 27 lots of various strengths of clonidine HCl tablets in March 2015, despite evidence that the active pharmaceutical ingredient (API) to make them “was potentially contaminated.” Mutual had hired a testing lab to check the API after being notified by the API supplier of possible cross-contamination issues, but the lab made it clear its test could not detect low-level contamination and said the results shouldn’t be used for batch release, the FDA said.
In another situation, Sun’s operation knew in April 2015 that benzophenone had leached into felodipine tablets from the ink and varnish on the primary container label and might have been the source of stability test failure for impurities. But the FDA says the plant’s managers didn’t recall the lot until the inspectors raised questions when they showed up two months later.
On top of that, the FDA cited the facility for poor record keeping, like reports signed with only one name or missing dates.
The FDA laid out a 5-part action plan it wants Frontida to take, including explaining how it will ensure that its ‘quality unit will adequately exercise its authority.”
The Philly plant is one of two former Mutual Pharmaceutical facilities that Frontida in June agreed to buy from Sun. The other is in Aurora, IL. Sun had bought the facilities from Japan’s Takeda in 2012 but was on the cusp of closing the plants when Frontida bought them, The Philadelphia Inquirer has reported.
Sun is well versed in the impact of FDA plant actions. The agency late last year issued a warning letter to Sun Pharmaceutical for its plant in Halol, India, a facility that accounts for about 15% of its U.S. sales. The remediation work Sun has been doing since the FDA issued a Form 483 at the facility has disrupted its U.S. supplies and hampered its sales. The Indian drugmaker also is upgrading four plants it got from its buyout last year of competitor Ranbaxy Laboratories that have been banned for some years from shipping to the U.S. because of problems the FDA uncovered there.
- here’s the warning letter