Table 6A.

Overview of published stress studies related to polysorbate degradation using increased temperatures. Temperature, pH, buffer conditions, study duration, polysorbate concentration, and polysorbate quality are summarized. Abbreviations: His: histidine, d: day, m: month, MC: multicompendial, AO: all-oleate, AL: all-laurate, AcOH: acetate, HP: high-purity, SR: super-refined, AAPH: 2,2-azobis(2-amidinopropane) dihydrochloride, BHT: butylated hydroxytoluene, BHA: butylated hydroxyanisole.

Study	Temperature / °C	pH	Buffer	Study duration	Polysorbate / % (w/v)	Polysorbate
Kranz et al. (2019) (Kranz et al., 2019)	40	6.0	10 mM His, 8 % (w/v) sucrose	17 d	0.04	PS20 MC PS80 MC/AO
	40	6.0	10 mM His, 8 % (w/v) sucrose, 50 μM EDTA	7 d 17 d	0.04	PS20 MC/AL PS80 MC/AO
	40	5.5	10 mM AcOH, 8 % (w/v) sucrose	17 d	0.04	PS20 MC/AL PS80 MC/AO
Bensaid et al. (2022) (Bensaid et al., 2022)	25	6.0	20 mM His, 20 mg·mL-1 mAb1, 10 % (w/v) sucrose	3 m	0.02	PS80 MC/AO
	40			1 m
	40	5.0, 6.0	20 mM citrate, 20 mg·mL-1 mAb, 10 % (w/v) sucrose, 30 ppb Fe(lI)Cl2 x 4 H2O	1 m	0.05	PS80 MC
	40	7.0	20 mM His, 20 mg·mL-1 mAb, 10 % (w/v) sucrose, 30 ppb Fe(lI)Cl2 x 4 H2O	1 m	0.05	PS80 MC
	40	5.0, 6.0	20 mM AcOH, 20 mg·mL-1 mAb, 10 % (w/v) sucrose, 30 ppb Fe(lI)Cl2 x 4 H2O	1 m	0.05	PS80 MC
Dahotre et al. (2018) (Dahotre et al., 2018)	2-8	5.4	His-AcOH	0, 12, 18, 24 m	0.04	PS20 (quality not defined)
	2-8	5.5	His-AcOH	13, 32 m	0.02	PS20 (quality not defined)
Kishore et al. (2011) (Kishore et al., 2011a)	5	6.0	20 mM His, 10 mg·mL-1 mAb1, 240 mM trehalose	12 m	0.05	PS20 or PS80 (quality not defined)
	5	6.0	20 mM His, 10 mg·mL-1 mAb2, 240 mM trehalose	12 m	0.01-0.04	PS20 and PS80 (quality not defined)
	5	6.0	25 mM Na-AcOH, mAb3 10 mg·mL-1, 125 mM NaCl	12 m	0.025	PS20 (quality not defined)
	5	5.5	20 mM His/His-Cl, mAb4 25 mg·mL-1, 240 mM trehalose	24 m	0.02	PS80 (quality not defined)
Doshi et al. (2020) (Doshi et al., 2020a)	40	5.5	His-AcOH, 10 mg·mL-1 IgG1 mAb, sucrose	1 m	0.03	PS20 HP/SR
	25			3 m
	2-8			12 m
Gopalrathnam et al. (2018) (Gopalrathnam et al., 2018)	5, 25	5.5-6.0	10 mM His, 150 mM NaCl, 5, 40, 70, 100, 120 mg·mL-1 LY2951742 antibody	10 m	0.05-0.06	PS80 (quality not defined)
Borisov et al. (2015) (Borisov et al., 2015)	40	-	Water, 1.5-10 mM AAPH	19 h 40 h	0.004	PS20 (quality not defined)
	40	-	Water, 1.5-10 mM AAPH	12.5 h 40 h	0.004	PS80 (quality not defined)
Kranz et al. (2020) (Kranz et al., 2020)	40	6.0	His 10 mM, 8 % (w/v) sucrose, 10 ppb Fe(II)SO4	12 d	0.04	PS20 MC/AL PS80 MC/AO
Ha et al. (2002) (Ha et al., 2002)	40, 50, 60	-	Water	8 w	Neat and 20	PS80 NF grade Low peroxide PS80
Yao et al. (2009) (Yao et al., 2009)	40	7.0	100 mM Sodium phosphate, 0.1 mM EDTA	-	-	PS20 PS80 high grades
Kishore et al. (2010) (Kishore et al., 2011b)	5, 25, 40	5.5	20 mM His, 240 mM trehalose, 10 mg·mL-1 mAb1 or placebo	12 m	0.05 or 0.03	PS20 or PS80 (quality not defined)
Liu et al. (2021) (Liu et al., 2022a)	25	6.0	Water	11-20 m	0.05	PS80 MC/ChP
Donbrow et al. (1978) (Donbrow et al., 1978a)	25, 40, 60, 70	6.0	Buffer, potassium iodide	30 d	1	PS20 (quality not defined)
Doyle et al. (2019) (Doyle et al., 2019)	50	5.5	10 mM His, citrate, phosphate	30 d	0.02	PS80 MC
Schmidt et al. (2020) (Schmidt et al., 2020)	40	-	Water	7 w	10	PS20 and PS80 containing either no antioxidant or BHT or BHA at a concentration of 0.02 % (v/w)
Zhang et al. (2018) (Zhang et al., 2018)	40	5.5	20 mM Na-AcOH or 20 mM His, or His-AcOH	8 w	0.02	PS20 HP
Schröter et al. (2020) (Schröter et al., 2021)	RT	Acidic	Water + trifluoroacetic acid (0.5 mM), 10 mM H2O2, 0.1 mM Fe(II)SO4	5 w	10	PS80 (no BHT, 1 mM BHT, 0.3 mM BHT)
	40	Acidic	Water + trifluoroacetic acid (0.5 mM), 1.5 mM AAPH	5 w	10	PS80 (no BHT, 1 mM BHT, 0.3 mM BHT)
Zhang et al. (2017) (Zhang et al., 2017)	40	1 7 11	Water, 1.5 mM AAPH	12, 24, 36, 48 h	0.1	PS20 AL
Agarkhed et al. (2012) (Agarkhed et al., 2013)	25	6.0	10 mM His, NaCl, glycine, 5 mg·mL-1 mAb	6 d	0.01	PS80 (SR, NF, ultrapure)