Table III: Viral clearance on POROS HQ (1000 cm/hr, 5-cm bed height).
The DNA and BSA binding capacity data of five anion exchangers is summarized in Table II. POROS HQ 50 demonstrated the highest
DNA binding capacity of the five AEX products assessed. The C5/C50 ratio is a measure of the mass transfer capability of the
resin/membrane and a way to characterize the efficiency of binding. The more efficient the mass transfer capability of a product,
the less effect flow rate has on capacity. As the C5/C50 ratio approaches 1.0 the resin/membrane becomes more efficient. The
POROS HQ C5/C50 ratio is as efficient as the membranes and significantly more efficient than Fractogel TMAE and Q Sepharose
FF for DNA binding. The capacity at 5% breakthrough on the 5 cmL column at 1000 cm/hr was compared to the capacity on a 20
cmL column run at 300 cm/hr. POROS HQ had minimal change in performance in the two formats as compared to the other two resins.
In addition, with POROS HQ, the DNA capacity is high under a wide range of operating conditions (30-35 mg/mL at pH 6.0–9.5
with 150 mM NaCl and >20 mg/mL at pH 7.0 with up to 400 mM NaCl, data not shown). POROS HQ ranked second highest for BSA C5
dynamic binding capacity and shows similar capacity and mass transfer efficiency similar to the membrane products.
Figure 2: Effect of load conductivity on viral clearance capability of POROS HQ.
POROS HQ in FT mode demonstrated good viral clearance capability for XMuLV up to 150 mM NaCl (18 mS/cm) at pH 7.0, as summarized
in Table III and Figure 2. The MVM model virus showed good clearance up to 50 mM NaCl (8 mS/cm) in this new AEX FT format
suggesting that a shorter column run at a faster operational flow rate can achieve good viral and impurity clearance. The
conductivity of the load appears to have an effect on both viruses. MVM is a poorly charged virus so minimal salt is needed
to neutralize the charge and decrease the binding. However, it is a small virus and can easily access the pores, so binding
performance is flow rate independent. XMuLV, on the other hand, is significantly larger and highly charged. With the higher
salt (18 mS/cm), the hydrodynamic radius of the virus is most likely changing, allowing for more optimal perfusion into the
Table IV: Large scale operating cost model for POROS HQ versus conventional AEX resin (2700 L at 5 mg/mL, 13.5 kg monoclonal
Table IV presents a cost model comparing POROS HQ 50 in this short-bed format to a traditional resin and membrane process.
The POROS HQ product load time in the new format is seven times faster than the traditional resin step and three times faster
than the membrane. The total process time is six times faster than the traditional resin process and almost two times faster
than the membrane. In addition, the optimized HQ format uses four times less buffer than the traditional resin step. One of
the benefits of using a resin is the reusability at commerical scale, and POROS HQ allows for aggressive cleaning and sanitization,
yielding excellent cycling and reuse performance. This study shows the cost difference for one cycle compared to 50 cycles
and the cost benefit of reuse compared to a single-use membrane.