Table 7.

Additives to mitigate oxidative polysorbate degradation. The different antioxidants/chelators, polysorbate qualities/concentrations, buffer conditions, excipients, protein, and stressors that have been tested are summarized.

Antioxidant/ chelators	PS quality	[PS] / % (v/w)	Buffer	pH	Excipient	Protein / mg·mL-1	Stress	Study
1.5/15 mM Met/Cys	PS80	∼0.24	TRIS	7.6	NaCl, EDTA	rhCNTF & rhNGF	H2O2/alkyl hydroperoxide	Knepp et al. (1996) (Knepp et al., 1996)
Meta	PS20d	0.04	AcOH	5.5	NaCl, mannitol	<50 mAb	25/40 °C	Kranz et al. (2020) (Kranz et al., 2020)
10 mM Met	PS20 HP / PS20 HP RO	0.2	<15 mM His-AcOH	5.5	Sucrose	-	40 °C	Doshi et al. (2021)b (Doshi et al., 2021b)
1 mM Met	PS80d	0.05-0.06	10 mM His		Water	-	5 ppm Fe2+	Gopalrathnam et al. (2018) (Gopalrathnam et al., 2018)
Ca. 1.3 mM Met	PS80d	0.02	20 mM His	5.5	8.5 % (w/v) sucrose	25 mAb	5/25/40 °C	Yarbrough et al. (2019) (Yarbrough et al., 2019)
10, 35 mM Met	PS80 AO	0.15	His-AcOH	5.5	Water	-	40 °C + light + stainless steel	Doshi et al. (2021)c (Doshi et al., 2021a)
10 mM Met	PS20 HP & SR	0.03	His-AcOH	5.5	Sucrose	10 mAb	40 °C	Doshi et al. (2020) (Doshi et al., 2020a)
1 mM BHT	PS20d & PS80d	10	-		Water	-	40 °C	Schmidt et al. (2020) (Schmidt et al., 2020)
0.3, 1 mM BHT	PS80d	10	-		Water	-	10 mM H2O2 + 0.1 mM Fe2+ + 25°C	Schröter et al. (2021) (Schröter et al., 2021)
0.3, 1 mM BHT	PS80d	10	-		Water	-	1.5 mM AAPH + 40 °C	Schröter et al. (2021) (Schröter et al., 2021)
0.3, 1 mM BHT	PS80d	10	-		Water	-	air + 40 °C	Schröter et al. (2021) (Schröter et al., 2021)
50 μM EDTA	PS80 AO	0.04	10 mM His	6.0	8 % (w/v) sucrose	-	10 ppb Fe2+	Kranz et al. (2019) (Kranz et al., 2019)
EDTAa	PS20d	0.04	AcOH pH	5.5	NaCl, mannitol	<50 mAb	25/40 °C	Kranz et al. (2020) (Kranz et al., 2020)
1, 10, 20 μM EDTA	PS80 MC/AO	0.02	20 mM His	6.0	10 % (w/v) sucrose	20 mAb	5/50 ppb Fe2+ + 25/40 °C	Bensaid et al. (2022) (Bensaid et al., 2022)
0.17 mM EDTA	PS80d	0.02	20 mM His	5.5	8.5 % (w/v) sucrose	25 mAb	5/25/40 °C	Yarbrough et al. (2019) (Yarbrough et al., 2019)
1, 10, 100, 1000 μM EDTA	PS80 MC	0.02	10 mM His	5.5	Water	-	Stainless steel + 50 °C	Doyle et al. (2019) (Doyle et al., 2019)
342 μM EDTA	PS80d	0.06	10 mM His	5.5-6.0	150 mM NaCl	-	5 ppm Fe2+ + 25 °C	Gopalrathnam et al. (2018) (Gopalrathnam et al., 2018)
0.5 mM DTPA	PS80 AO	0.15	His-AcOH	5.5	Water	-	40 °C + light + stainless steel	Doshi et al. (2021)c (Doshi et al., 2021a)

^aconcentration of methionine and EDTA not given.

^bDoshi et al. (2021), Evaluating a modified high purity polysorbate 20 designed to reduce the risk of free fatty acid particle formation.

^cDoshi et al. (2021), A comprehensive assessment of all-oleate polysorbate 80: free fatty acid particle formation, interfacial protection, and oxidative degradation.

^dquality not specifically given.