The United States Pharmacopeia has recently published chapter <63>
Mycoplasma Tests. Biopharmaceutical companies conducting mycoplasma testing as a lot release assay for unprocessed bulk material will need to comply with this new regulation once it becomes effective later this year. In this article, we compare the language of USP <63> to that of the existing regulation (European Pharmacopoeia chapter 2.6.7 Mycoplasmas) and guidance (1993 Points to Consider in the Characterization of Cell Lines used to Produce Biologics).
The United States Pharmacopeia's (USP) new chapter <63> Mycoplasma Tests
was intended to fill a void in the USP for mycoplasma testing, which had been addressed previously within the FDA's 1993 Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals (PTC) and the European Pharmacopoeia (EP) chapter 2.6.7 Mycoplasmas.2–3 A separate regulatory document (21 CFR 610.30)4 will not be considered here because the language contained therein is specific to mycoplasma testing of live and inactivated viral vaccines. Because there had been some methodological differences between the FDA guidance and EP 2.6.7, the industry was hoping that the new USP chapter would serve to harmonize mycoplasma testing as much as practically possible, and would not lead to additional points of discrepancy.
Chapter <63> was published in the USP 33/NF 28 issuance that became available on November 1, 2009. USP 33/NF 28 was originally scheduled to become effective on May 1, 2010, but was retracted because of monograph errors that were introduced during conversion to a new format. The announcement to that effect was posted on the USP website on January 12, 2010.5
USP 33/NF 28 was re-issued in March 2010 with an official date of October 1, 2010.
MILLENNIUM: THE TAKEDA ONCOLOGY COMPANY
COMPARISON OF USP <63>, 1993 PTC, AND EP 2.6.7
A quick look at the new USP chapter <63> indicates that the text and tables comprising that chapter were based in large part on EP 2.6.7, with only certain aspects being derived from the 1993 PTC. A comparison of the three documents (USP <63>, 1993 PTC, and EP 2.6.7) reveals methodological differences in only a few areas. These include the assessment of nutritive properties of the solid growth media (agar) used for mycoplasma testing, the assessment of inhibitory substances in the test material, the incubation temperature ranges to be used, and the number and types of positive controls to be used. The substantive methodological differences between the new USP chapter <63>, EP 2.6.7, and the 1993 PTC are outlined in Table 1.
Table 1. Methodological differences between the new USP chapter <63>, EP 2.6.7, and the 1993 PTC