Medicinal Products

Biological and Biosimilar Medicinal Products

What is a biological medicinal product?

A biological medicinal product is a medicinal product that contains an active substance produced or excreted from biological sources (human, animal, or microbiological).

Due to manufacturing procedures and their origin, active substances of biological medicine shave significantly complex structure as compared to chemical active substances.

Some of the active substances of biological medicines may be found in human body, like insulin, growth hormone, or erythropoietin.

Biological medicines are:

  • immunological medicinal products (vaccines, toxins, sera and allergen products),
  • medicinal products from human blood or plasma (i.e. albumin or immunoglobulin),
  • medicinal products produced by biotechnology (procedures involving live systems or organisms),
  • advanced therapy medicinal products (medicnal products based on gene therapy, somatic cell therapy or tissue engineering)
  • other medicinal products produced from biological sources (i.e. heparin or pancreatin).

What is a biosimilar medicinal product?

A biosimilar medicinal product is a medicinal product with a proven similarity in terms of quality, biological activity, safety and efficacy as the approved original biological medicinal product.

Due to complex active substance structure and manufacturing procedure of biological medicinal products it is unlikely to produce a biological medicine with a completely identical active substance structure as the original biological medicine. Therefore, the standard approach in development and approval of generic chemical medicines, based on bioequivalence with original medicine, may not be applied to biosimilar medicinal products, but rather their similarity with original medicines should be proved through further studies during the product development and marketing authorisation procedure.

How are biosimilar medicinal products approved?

All biosimilar medicinal products currently approved in the Republic of Croatia have been authorised via centralised procedure for granting marketing authorisation, which means that the European Medicines Agency (EMA) scientifically reviewed the products and the European Commission has granted marketing authorisations. The quality, efficacy and safety assessment at the EMA is carried out at the highest scientific and technical level involving experts from all the EU Member States. The scientific opinion is adopted at the Committee for Medicinal Products for Human Use (CHMP) and the Pharmacovigilance and Risk Assessment Committee (PRAC). Within the scope of its work, the CHMP is additionally advised from working groups of experts with narrow specialisation in biological medicinal products (Biologics Working Party, BWP) and biosimilar medicinal products (Biosimilar Medicines Working Party, BMWP).

In order to obtain marketing authorisation, the manufacturer is required to perform comprehensive testing as evidence that the biosimilar medicinal product is very similar to the original biological medicinal product in terms of quality, safety and efficacy.

The biosimilar medicinal product development begins with a comprehensive physico-chemical and biological characterisation of active substance as well as non-clinical in vitro studies and these data determine the scope and type of non-clinical in vivo studies and clinical studies in human that must be carried out to prove the similarity. Taking account that the original biological medicine has been approved in the European Union for years and its clinical benefits have been proved, certain studies carried out on the original medicines do not need to be repeated to approve the biosimilar medicinal product. Due to this reason, the development, scope of studies and data based on which the biosimilar medicine is approved, must be studied on a case-by-case basis.

The European Medicines Agency has published many scientific guidelines ensuring qulity, safety and efficacy standards of biosimilar medicines that are accessible under the link European Medicines Agency's scientific guidelines on biosimilar medicines.

Biosimilar medicinal product are manufactured according to the equally rigorous standards as all other medicines, which is confirmed by competent authorities' inspections of manufacturers.

The scientific reliability of the biosimilar approval approach is substantiated by the rich European experience ensuring a number of quality safe and efficient biosimilar medicinal products to patients.

The information on all centrally approved biosimilar medicines, including the summary of product characteristics, may be found under the link Human Medicines - Biosimilars.

Do biosimilar medicinal products differ from originator biological medicinal products with regards to their quality, efficacy and safety?

Given a high degree of similarity of a biosimilar medicinal product with the originator biological medicinal product and a same benefit-risk ratio, as demonstrated during the process of grating marketing authorisation, there are no obstacles of using either of the two approved medicinal products.

Is there a greater risk of forming antibodies against a biosimilar medicinal product compared to the originator biological medicinal product?

Antibodies can be formed following the use of any biological medicinal product, and biosimilar medicinal products are not linked to a greater risk of antibody formation.

Are a biosimilar medicinal product and the originator biological medicinal product mutually interchangeable in the treatment of patients?

Scientific research conducted so far has not reported risks related to biosimilar interchangeability.

The direct interchangeability (known also as direct, automatic or generic substitution) is a notion that includes a substitution of the prescribed medicinal product with its parallel at the level of pharmacy, which does not require advising and special surveillance of the prescribing doctor. The direct interchangeability is only possible for generic medicinal products, whereas for biological medicinal products, direct interchangeability is not applicable.

A biosimilar medicinal product and originator biological medicinal product can be used interchangeably in the treatment of patients, under medical surveillance and monitoring of the patient's health condition. The prescribing doctor should decide on the appropriateness of the substitution for the individual patient, accordingly inform the patient about the substitution, and monitor the patient's health condition and treatment outcomes.

However, it is not recommended to frequently substitute medicinal products with the same biological active component during the treatment of a single patient, as no sufficient data exists regarding the efficacy and/or safety of such practices. Furthermore, the substitution of medicinal products with the same biological active component can make it more difficult to associate delayed adverse reactions to medicinal products that have provoked them.

An active post-authorisation safety monitoring is mandatory for all medicinal products and in the case of biological medicinal products, due to their specific characteristics, adverse reactions should be further monitored, reported and analysed at the level of product brand and batch number in order to ensure a precise traceability.

In summary, each biological medicinal product can be used for treatment of diseases and conditions within its authorised indication, regardless whether the medicinal product is biological or biosimilar, whereas the appropriateness of substitution for the individual patient should be decided by the prescribing doctor after having taken in consideration all the relevant above-mentioned facts.

A publication of the European Commission entitled What you need to know about biosimilar medicinal products is available here.

A publication co-edited by the European Commission and the European Medicines Agency entitled Biosimilars in the EU Information guide for healthcare profesionals is available here.

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