Published: 3 December 2020


The Medsafe Files – Episode 14: Biosimilar medicines

Published: 3 December 2020
Prescriber Update 41(4): 71

December 2020

Key Messages

  • A biosimilar is a biological medicine that is highly similar to another biological medicine that has already been approved in New Zealand.
  • Medsafe applies the European Medicine Agency requirements when approving biosimilars for the New Zealand market.
  • Biosimilars must meet international standards for quality, safety, and efficacy, as are used for all biological medicines.
  • Biosimilars undergo extensive studies to demonstrate comparable pharmaceutical quality, safety, efficacy, and immunogenicity to their biological reference medicine.

Biosimilars are biological medicines that are highly similar to already approved biological medicines (the reference or innovator medicines). They are becoming increasingly common in clinical practice as more innovator biological medicines come off patent.

Characteristics of biological and biosimilar medicines

Biological medicines contain active ingredients that have been derived from a biological source, such as living cells and organisms. They are used for the treatment of a wide range of conditions such as diabetes, autoimmune diseases and cancers.1

Typically, biological medicines contain a protein as the active ingredient, and the size and complexity of these proteins can vary greatly. The manufacturing process for biological medicines is usually more complex than that used for chemically-derived medicines and will often involve living cell systems and recombinant DNA technology.

Biological medicines are inherently variable

Biological sources demonstrate inherent variability when producing proteins. Not only do they produce the protein of interest, but they will produce it with minor variations, for example, small amounts of shortened proteins or proteins with different sugar molecules attached (glycosylation). When manufacturing biological medicines, this inherent variability is controlled within defined limits to ensure consistent safety and efficacy of the medicine. Therefore, batches of the same biological medicine can have minor differences even though they are manufactured using the same manufacturing process.

Biosimilars are highly similar but not identical to the reference medicine

Due to the inherent variability associated with biological medicines, along with the impact of using manufacturing processes that are specific to each manufacturer, minor differences can occur between the biosimilar and reference medicine. Consequently, a biosimilar medicine differs from a generic medicine in that the active ingredient is defined as being ‘highly similar’ rather than ‘identical’ to a reference medicine.

During the regulatory approval process, the biosimilar medicine must demonstrate that any minor differences to the reference medicine do not have any clinically meaningful impact on safety and efficacy. This is demonstrated in a clinical trial involving patients.

Approval of biosimilars in New Zealand

Medsafe uses the European Medicine Agency (EMA) regulatory requirements for approving biosimilar medicines because they have the most developed regulatory guidelines for biosimilars.1

Biosimilars must meet international standards for quality, safety, and efficacy as are used for all biological medicines, although data requirements may vary. Equivalent pharmaceutical quality data requirements are applied to both the reference and biosimilar medicines, but the clinical data requirements for these medicines differ (see Table 1).

Table 1: Comparison of clinical data requirements for biological reference medicines and biosimilars

Biological reference medicine Biosimilar medicine
  • Clinical trials demonstrate safety and efficacy in all claimed therapeutic indications.
  • Trials compare the reference medicine with a placebo or the current standard of therapy using defined endpoints
  • Trials performed in the intended patient population.
  • Clinical trials show clinical equivalence with the reference medicine.
  • Trial population may be healthy volunteers or patients, depending upon the toxicity of the medicine.
  • By demonstrating high similarity to the reference medicine, the biosimilar can mostly rely on the efficacy and safety information obtained for the reference medicine.

The data requirements for a biosimilar medicine rely on comparability studies with the reference medicine, including both quality and clinical comparability. The aim of the clinical comparability studies is to confirm that there are no differences between the two products that could affect efficacy and safety, including immunogenicity. If a biosimilar is shown to have comparable safety and efficacy to the reference medicine for one indication, the safety and efficacy data may be extrapolated to other indications. While this is the usual approach, extrapolation requires consideration of a number of factors including the mode of action of the biological medicine and its use across different clinical settings. Biological medicines are usually complex substances and their mode of action may involve multiple receptors or binding sites that may contribute differently to each indication. Also, in different clinical settings, safety and efficacy data for one indication (eg, rheumatoid arthritis) may not be directly applicable to an indication in another therapeutic area (eg, oncology) where the mode of action, dosage or pharmacokinetics may differ. In these situations, additional non-clinical or clinical studies may be required to prove the biosimilar is comparable to the reference medicine for the extrapolated indication.

Potential immunogenicity

Immunogenicity is the ability of proteins and other biological medicines to cause unwanted immune responses. Serious adverse reactions (eg, anaphylaxis) are considered rare. The more common immunogenicity response is the development of anti-drug antibodies (ADAs).1 Many biological medicines are intended for long-term treatment of chronic conditions and the development of ADAs can negate the therapeutic effect of the biological medicine or reduce its efficacy.2

Clinical immunogenicity studies in patients are generally required for all biological medicines, including biosimilars. The immunogenicity studies provide data on the incidence, titre, and persistence of ADAs, assess the clinical impact and describe measures to manage the potential risk of immunogenicity (eg, special monitoring or use of concomitant medication to reduce infusion reactions).1

Monitoring safety of biosimilars

Biosimilar medicines are monitored in New Zealand in the same way as other biological medicines, including the requirement for sponsors to submit periodic benefit risk evaluation reports (PBRERs) to Medsafe.3,4

Please report suspected adverse reactions to a biosimilar medicine to the Centre for Adverse Reactions Monitoring (CARM). The brand and batch number should be included in this report.

More information


  1. European Medicines Agency. 2019. Biosimilars in the EU: Information Guide for Healthcare Professionals. URL: (accessed 27 July 2020).
  2. Pratt, KP. 2018. Anti-drug antibodies: emerging approaches to predict,reduce or reverse biotherapeutic immunogenicity. Antibodies 7(2):19. DOI: 10.3390/antib7020019 (accessed 27 July 2020).
  3. Medsafe. 2018. The Medsafe Files – Episode Five: Pharmacovigilance. Prescriber Update 39(1): 6–7. URL: (accessed 24 September 2020).
  4. Medsafe. 2020. Guideline on the Regulation of Therapeutic Products in New Zealand: Part 8: Pharmacovigilance (Edition 2.2). URL: (accessed 24 September 2020).
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