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Postapproval Pharmacovigilance Review Confirms Comparable Safety Between Sandoz Biosimilars, Originators


Authors of a review of available postapproval pharmacovigilance data assessing 8 Sandoz biosimilars concluded that these biosimilars “can be used as safely as their respective reference biologics.”

doctor filling syringe | Image credit: natali_mis - stock.adobe.com

Image credit: natali_mis - stock.adobe.com

Authors of a review of available postapproval pharmacovigilance data assessing 8 Sandoz biosimilars concluded that these biosimilars “can be used as safely as their respective reference biologics.”

Altogether, they reviewed pharmacovigilance data representing more than 1.3 billion patient days of post-approval exposure of the 8 approved Sandoz biosimilars worldwide, based on periodic safety update reports (PSURs). The authors reviewed pharmacovigilance data from PSURs (called periodic benefit-risk evaluation reports in some regions) and assessment reports authored by health authorities.

Despite published data demonstrating efficacy and safety, according to the reviewers, health care providers, patients, and policy experts still have “lingering concerns” about the long-term safety of biosimilars. Since pre-approval trials are limited to selective populations and may be underpowered to detect relatively rare safety concerns, post approval safety data are important to provide information on the safety of a biosimilar product in routine, real-world use.

Therefore, the authors aimed to summarize the real-world safety experience of multiple biosimilars from a single marketing authorization holder. To the reviewers’ knowledge, this was “one of the largest summaries of real-world post-approval biosimilar safety experience to date.”

Sandoz has biosimilar approvals in more than 90 countries. Their first biosimilar launch was over 18 years ago. Sandoz launched the first biosimilar in the European Union (EU), a somatropin product (Omnitrope, Nomazc, and Scitropin A), in 2006, and it has since received approval for 7 more biosimilars: adalimumab (Hyrimoz/Hefiya), epoetin alfa (Binocrit, Abseamed, Epoetin alpha Hexal, and Novicrit), etanercept (Erelzi), filgrastim (Zarzio, Zarxio, and Filgrastim Hexal), infliximab (Zessly, Ifixi, Ixifi, Ixifi2, and Xilfya), pegfilgrastim (Ziextenzo), rituximab (Rixathon, Riximyo, and Arasamila).

Based on the pharmacovigilance data from the most recent reporting intervals for each biologic, overall, the reviewers found there were no new or changed safety concerns, and no changes unique to the Sandoz biosimilars were made to the safety information. Overall, changes made to the labels, core data sheets, or risk management plans were those corresponding to changes made to the reference biologic.

For example, during the most recent reporting interval, “weight increased” was added to the adalimumab reference product’s label as an “undesirable effect”, resulting in a change to the Sandoz biosimilar core data sheet and labels as well. Similarly, changes to the definitions of safety concerns and the removal of some safety concerns from the risk management plan for the Sandoz epoetin alfa biosimilar were made to align with those made to that of the originator. For the etanercept reference product, headache was added as a new adverse event, and for the pediatric population inflammatory bowel disease and uveitis were removed as adverse drug reactions; the corresponding updates were made to the Sandoz biosimilar core data sheet and labels.

Sandoz’s filgrastim risk management plan was updated to include glomerulonephritis as an important potential risk, in alignment with all other filgrastim products. A new safety signal of Kaposi’s sarcoma was validated for infliximab by the Pharmacovigilance Risk Assessment Committee, and the labels of all infliximab products were updated. Safety information was updated for all pegfilgrastim biosimilars including Sandoz’s biosimilar to include Stevens-Johnson syndrome as an adverse drug reaction plus warnings on thrombocytopenia, myelodysplastic syndrome, and acute myeloid leukemia.

Potential risks on the Sandoz rituximab label were updated to match those of the reference product, and the summary of product characteristics was updated for all rituximab products to add the risk of serious viral infections. The Sandoz somatropin label, along with those of all other somatropin products were updated to add a warning for pancreatitis and to add multiple adverse reactions including face edema, headache, and hypothyroidism.

According to the reviewed pharmacovigilance data reflecting over 1.8 million doses of Sandoz’s rituximab biosimilar and 1.3 billion patient treatment days worldwide for their other 7 biosimilars, the authors said, “all Sandoz biosimilars demonstrate an overall favorable benefit-risk profile that is consistent with their respective reference biologics. As a result, patients and their caregivers can be confident in their safety.”

They added that given the high standards for biosimilars by major health authorities, “it is reasonable to believe that similar conclusions about safety may be reached for other biosimilars approved in those regions.” Indeed, they noted, 93 biosimilars had been approved in the EU and 42 in the US by September 2023, and at that time none had been withdrawn for safety reasons, and no adverse events specific to a biosimilar had been added to a product label.


Sagi S, Anjaneya P, Kalsekar S, Kottke A, Cohen HP. Long-Term real-world post-approval safety data of multiple biosimilars from one marketing-authorization holder after more than 18 years since their first biosimilar launch. Drug Saf. 2023;46(12):1391-1404. doi:10.1007/s40264-023-01371-8.

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