Generics and Biosimilars
What is a generic drug?
The Austrian Medicinal Products Act defines what a generic drug is:
- §1 (19) "Generic medicinal product" means a medicinal product which must contain the same active substance in the same quantity and must also have the same pharmaceutical form (e.g. tablets, solution, suppositories) as the already authorised medicinal product from which it is derived (reference medicinal product, see below). It must also demonstrate the so-called bioequivalence (i.e. the substitutability of two medicinal products with the same active substance) with the reference medicinal product through appropriate studies.
- §1 (20) "Reference medicinal product" (the originator) means a medicinal product authorised in Austria or in the European Economic Area.
When and how is a generic drug approved?
This is also precisely regulated in the Austrian Medicinal Products Act. This so-called "generic authorisation" defines what pharmaceutical companies have to demonstrate:
- § 10 Generic marketing authorisation: The applicant must be able to prove that the medicinal product is a generic of a reference medicinal product:
- This must be demonstrated by a bioequivalence study and normally the generic medicinal product cannot be placed on the market in the EU until ten years have elapsed since the first authorisation of the reference medicinal product.
What is a bioequivalence study?
This is laid down in a guideline issued by the European Medicines Agency (EMA): a bioequivalence study is a study that compares whether the blood of the test subjects contains exactly the same amount of active substance from the generic (test product) at the same time and in the same amount as from the reference product (originator).
This study is a clinical trial within the meaning of the Medicinal Products Act (Arzneimittelgesetz). The basic assumption here is: essentially similar blood levels of the active substance and thus concentrations at the site of action guarantee essentially the same effect of efficacy and safety of the drug. The results of this study must be within certain limits. These limits are accepted throughout the EU and laid down in a guideline issued by the EMA.
Where are differences between the originator and the generic drug possible?
- In the case of excipients, if they have no influence on the action of the medicinal product.
- The manufacturing process may be different.
- For example, it is allowed that the generic drug is a tablet and the originator is a capsule.
- However, for each generic drug, as for the originator, the complete pharmaceutical quality documentation must be submitted. In this respect, there is no difference between originator and generic product.
A generic drug only receives approval,
- if the results of the bioequivalence study are within the specified limits,
- if the safety profile of the generic corresponds to that of the reference product,
- if it has been proven that the excipients used and the manufacturing process have no influence on the availability of the generic drug in the body,
- if the internationally established quality standards for the performance of a bioequivalence study are met,
- if all regulatory criteria are met (Summary of Products Characteristics, Package Leaflet, Labelling,...).
It is only when all these criteria are met that a generic drug is marketed and therefore there is no cause for concern for prescribers or patients as regards the approval of generic drugs.
Biosimilars are the successor to complex biological drugs and are used to treat severe chronic diseases. They are equivalent to their reference products in terms of efficacy, safety and quality.
A 'biosimilar' medicine is a biological medicinal product that is similar to an already authorised original biological medicinal product (reference medicinal product) in the European Economic Area (EEA). Biological medicines are made by a biological source, such as a bacterium or yeast, or isolated from a biological organism, e.g. the human body or an animal.
Comparability between the reference and the biosimilar medicinal product is the core principle of a biosimilar development. Similarity to the reference medicinal product in terms of quality characteristics, biological activity, safety and efficacy based on a comprehensive comparability exercise needs to be established in a stepwise approach.
- First step - quality comparability (comparability of the physicochemical characteristics and biological activity)
- Second step - non-clinical comparability (comparative non-clinical studies)
- Third step - clinical comparability (comparative clinical studies)
A biosimilar medicinal product and its reference medicinal product are expected to have highly comparable safety and efficacy profiles and are generally used to treat the same conditions. As information on the safety and efficacy of the reference medicine is already available, the amount of information needed for authorisation of a biosimilar is usually less than the amount needed for approval of an original biological medicine.
Biosimilars can only be authorised for use once the period of data exclusivity on the original 'reference' biological medicine has expired.
Further information on biosimilars can be found on the European Medicines Agency (EMA) website.
The Consensus Information Document “What I Need to Know about Biosimilar Medicinal Products” published on the European Commission website addresses frequently asked questions (including Q&A for patients and physicians):
For scientific guidelines on biosimilar medicines follow the link:
For a list of biosimilar medicines approved by the EMA and further information on these products: