266 although care would have to be taken to avoid microbial contamination or other manufacturing process irregularities in multiple cell lines growing in parallel under GMP con- ditions. Manufacturing scenarios using this approach are described in WO 2009/129814. We have earlier reported the use of Flp-In site-speciﬁc integration for the generation of stable polyclonal producer cell banks exhibiting sufﬁciently similar growth and pro- ductivity properties to allow consistent single-batch man- ufacturing of rpAb [13]. Sym001 (Rozrolimupab), which comprises 25 anti-Rhesus D speciﬁc antibodies, is pro- duced using this technology. At the time it was envisaged that the background for this consistency was the use of site- speciﬁc integration, which would serve to avoid genomic position effects with respect to growth properties of the cells, and at least to some extent result in equal expression levels. This technology where only one copy of the anti- body gene is stably integrated into the expressing clone does however limit the production level of the stable pro- ducer cell lines. This makes the SympressTM I technology best suited to support niche indications. The modiﬁcations implemented in SympressTM II employing random inte- gration in an improved cell line, a much higher copy number, use of a stringent DHFR selection system and implementation of FACS based sorting for high producers have led to a signiﬁcant improvement in overall produc- tivity (approximately 10-fold) while conserving the high batch-to-batch consistency observed with SympressTM I. This makes the SympressTM II platform suitable for manufacturing of drug substance for major indications. Acknowledgments We thank NIH Grant# U01 AI 70378-03 for supporting the anti-Vaccinia antibody work. 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