Table 2.
Variability in product-related factors contributing to injection-site pain across available references for and biosimilar formulations of a) adalimumab and b) etanercept
| a) | |||||||
|---|---|---|---|---|---|---|---|
| Product-related factors contributing to SC ISP | Humira (concentrated) (adalimumab) [90] |
Humira (classic) (adalimumab) [90] |
Imraldi (SB5) [91] |
Amgevita (ABP 501) [92] | Idacio (MSB11022) [93] | Hulio (FKB327) [94] | Hyrimoz (GP2017) [95] |
| Citrate | No | Yes | Yes | No | Yes | No | Yes |
| Needle gauge |
AI: 29 PFS: 29 |
AI: 27 PFS: 27 |
AI: 29 PFS: 29 |
AI: 27 PFS: 29 |
PFS: 29 PFP: 29 |
PFS: 29 PFP: 29 |
PFS: 27 PFP: 27 |
| Latex | No | Yes | No | Yes | No | No | Yes |
| pH | 5.2a | 5.2 | 5.2 | 5.2 | 5.2 | 5.2 | 5.2 |
| Volume (mL) for 40 mg injection | 0.4 | 0.8 | 0.8 | 0.8 | 0.8 | 0.8 | 0.8 |
| Complete formulation |
• Mannitol • Polysorbate 80 • Water for injection |
• Mannitol • Polysorbate 80 • Citric acid monohydrate • Disodium phosphate dihydrate • Sodium chloride • Sodium citrate • Sodium dihydrogen phosphate dihydrate • Sodium hydroxide (for pH adjustment) • Water for injection |
• Sorbitol • Polysorbate 20 • Citric acid monohydrate • Histidine • Histidine hydrochloride monohydrate • Sodium citrate • Water for injection |
• Sucrose • Polysorbate 80 • Glacial acetic acid • Sodium hydroxide (for pH adjustment) • Water for injection |
• Mannitol • Polysorbate 80 • Citric acid monohydrate • Disodium phosphate dihydrate • Sodium chloride • Sodium citrate • Sodium dihydrogen phosphate dihydrate • Sodium hydroxide (for pH adjustment) • Water for injection |
• Sorbitol (E420) • Polysorbate 80 • Methionine • Monosodium glutamate • Hydrochloric acid (for pH adjustment) • Water for injection |
• Mannitol • Polysorbate 80 • Adipic acid • Citric acid monohydrate • Sodium chloride • Hydrochloric acid (for pH adjustment) • Sodium hydroxide (for pH adjustment) • Water for injection |
| b) | ||||||
|---|---|---|---|---|---|---|
| Product-related factors contributing to SC ISP | Enbrel (etanercept) [96] |
Benepali (SB4) [97] |
Erelzi (GP2015) [98] |
Nepexto (YLB113) [99] |
||
| Citrate | No | No | Yes | Yes | ||
| Needle gauge |
PFP: 27 PFS: 27 |
PFP: 27 PFS: 27 |
PFP: 27 PFS: 27 |
PFP: 27 PFS: 27 |
||
| Latex | Yes | No | No | No | ||
| pH | 6.3 | 6.2 | 6.3 | 6.3 | ||
| Volume (mL) for 50 mg injections | 1.0 | 0.98 | 1.0 | 1.0 | ||
| Complete formulation |
• Mannitol • Sucrose • Trometamol • Sodium phosphate monobasic dihydrate • Sodium phosphate dibasic dihydrate • Sodium chloride • L-arginine hydrochloride • Water for injection |
• Sucrose • Sodium dihydrogen phosphate monohydrate • Disodium hydrogen phosphate heptahydrate • Sodium chloride • Water for injection |
• Sucrose • Citric acid anhydrous • Sodium citrate dihydrate • Sodium chloride • L-lysine hydrochloride • Sodium hydroxide (for pH adjustment) • Hydrochloric acid (for pH adjustment) • Water for injection |
• Glycine • Sucrose • Sodium citrate • Sodium dihydrogen phosphate dihydrate • Sodium chloride • Water for injection |
||
AI autoinjector, ISP Injection-site pain, PFP prefilled pen, PFS prefilled syringe, SC subcutaneous, SPC Summary of Product Characteristics
aBased on US Food and Drug Administration (FDA) principal investigators’ data; the classic formulation is based on 2014 FDA Product Information