Dive Brief:
- After a November 2014 warning letter following an inspection of Biotest Pharmaceuticals' Boca Raton facility (now owned by ADMA Biologics), the Food and Drug Administration has announced a successful close-out for the April 2018 follow-up compliance inspection.
- The original warning letter noted quality control deviations from current good manufacturing practice requirements in the manufacture of the plasma product Bivigam.
- ADMA has optimized the production process and submitted a prior approval supplement to amend the Biologics License Application for Bivigam, and has a user fee action date of Oct. 25, 2018. Relaunch is expected by the end of the first quarter of 2019.
Dive Insight:
The close-out draws a line under four years of discussion over the manufacturing of Bivigam (intravenous human immune globulin), used for the treatment of primary humoral immunodeficiencies, which potentially affect up to 250,000 people in the U.S. Bivigam was first approved in December 2012.
The story began when the FDA issued a warning letter to Biotest Pharmaceuticals in 2014 following an inspection of the Boca Raton facility where Bivigam was manufactured.
The problems cited in the original letter included a failure to validate the minimum and maximum process and mixing times, and failure to update the FDA about all changes to the product, production process, quality controls, equipment, facilities, responsible personnel or labeling. Regulators described these as "an indication of your quality control unit not fulfilling its responsibility to assure the identity, strength, quality, and purity of your biological drug intermediates."
The FDA carried out another cGMP inspection in 2016, and production was halted by Biotest at the end of the same year. ADMA acquired Biotest Pharmaceuticals' Therapy Business Unit (BTBU) in June 2017, including the target's Boca Raton facility. At the time, Adam Grossman, president and CEO of ADMA Biologics, said "We now have the authority to be in direct communication with the FDA in order to further support our efforts to remediate the outstanding BTBU warning letter."
In a more recent statement, Grossman said his company is "pleased that the FDA has determined our responses to be satisfactory for the April 2018 FDA compliance inspection and … closed this inspection."
"We believe that we have successfully remediated the production and significant compliance issues… as evidenced by the successful production of three conformance batches for Bivigam, which were the basis for our June 2018 PAS submission," he added.