Laboratory analysis of rifampin/rifapentine products

FDA continues to investigate the presence of 1-methyl-4-nitrosopiperazine (MNP) in rifampin or 1-cyclopentyl-4-nitrosopiperazine (CPNP) in rifapentine approved for sale in the U.S. These antibacterial drugs are used to treat tuberculosis; rifampin is also used to treat or prevent other serious infections.

The acceptable intake limits are 0.16 parts per million (ppm) for MNP in rifampin and 0.1 ppm for CPNP in rifapentine. These acceptable intake limits were calculated based on methods described in the 2018 ICH Guidance M7(R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk. To maintain the supply of these lifesaving medicines to patients, as a temporary measure the agency will not object to manufacturers distributing rifampin containing MNP below 5 parts per million (ppm). The agency also will not object to manufacturers temporarily distributing rifapentine containing CPNP below 20 ppm.

FDA is posting its laboratory results in the table below showing MNP in rifampin or CPNP in rifapentine products it tested. FDA is also collaborating with international regulators to share testing results for these products.

Company (Manufacturer)	Product	Lots Tested	MNP* level (micrograms-mcg/tablet or injection)	MNP* level (ppm)
Akorn	Rx Rifampin 300 mg	3185938, 3185931, 3184496, 3174136, 3191250	0.45-0.96	1.49-3.20
Akorn	Rx Rifampin 150 mg	3178340, 3174138, 3186047	0.44-0.52	2.95-3.47
Fresenius Kabi	Rx Rifampin Injection 600 mg	6123714	0.56	0.94
Lannett	Rx Rifampin 300 mg	26702.011A, 26702.001E, 18233439C	0.56-0.76	1.88-2.52
Lannett	Rx Rifampin 150 mg	26701.001D, 26701.002B	0.33-0.36	2.22-2.43
Lupin Pharmaceuticals Inc.	Rx Rifampin 300mg	A904639, A906770, A002982, A002983, A904704, A808691	0.39-0.63	1.31-2.08
Lupin Pharmaceuticals Inc.	Rx Rifampin 150mg	A000882, A808686, A904725, A002791	0.23-0.34	1.52-2.26
Mylan	Rx Rifampin Injection 600 mg	7008768, 7008694, 7008769	0.60-1.51	0.99-2.51
Sandoz/Epic	Rx Rifampin 300 mg	ME171080, ME190353, ME200197	0.56-0.80	1.86-2.66
Sandoz/Epic	Rx Rifampin 150 mg	ME190788, ME180471, ME190156, ME190470, ME190660	0.36-0.41	2.39-2.76
Sanofi Pharmaceuticals	Rx Rifampin Injection 600 mg	9J126, A9042, A8039, 9J1261	0.48-0.67	0.80-1.11

*1-Methyl-4-Nitrosopiperazine (MNP)

Company (Manufacturer)	Product/API	Lots Tested	CPNP level (microgram-mcg/tablet)	CPNP** level (ppm)
Sanofi	Rx Rifapentine 150 mg	9J2361, 0J0191, 0J1981	1.22-2.13	8.10-14.18

** 1-Cyclopentyl-4-Nitrosopiperazine