Generics and Biosimilars

Site: EUPATI Open Classroom
Course: Types of Medicines and Their Mode of Action and Use
Book: Generics and Biosimilars
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Date: Sunday, 23 June 2024, 11:55 PM

1. Generic medicines

(This section is organised in the form of a book, please follow the blue arrows to navigate through the book or by following the navigation panel on the right side of the page.)

When chemical medicines are first developed and approved, they are sold by a pharmaceutical company under a brand name. Once the protection for a product expires, e.g. patent or regulatory protection, the company no longer has exclusive rights to sell the medicine, and other companies can then manufacture and sell a comparable medicine with the same active ingredient; this new version is often referred to as a ‘generic’.

While two medicines, the original and the generic, will have different brand names and packaging, they will have the same active ingredients and, effectively, can be considered to be the same medicine. This could cause some confusion if it were not for the generic name of the active ingredient, which is shared by all brands of the medicine. This is common for pain medications, for which active ingredients, such as paracetamol, acetylsalicylic acid and ibuprofen, are used as the basis for many of the painkillers that can be bought in pharmacies.

Notably, approved generic medicines are regulated in the same way as the original medicines, and manufacturing facilities and conditions must equally be of a very high standard. The generic medicine is tested to ensure that it has the same properties as the original, bioequivalence has to be shown. This means that the generic medicine is absorbed in the body to the same extent and at the same speed as the original. However, the sometimes lengthy and costly steps of clinical trials to show efficacy and safety do not have to be repeated. Following the approval of a generic medicine, the company producing it must commit to collecting and reporting additional safety data.

Chemical medicines are less complex than biologic medicines and are therefore relatively inexpensive to manufacture. The key advantage for a generic medicine over the original is cost, with generics generally being cheaper than originals, and they are therefore preferred by many doctors and hospitals.

2. Biosimilars

The European legislation defines a biosimilar as ‘a biological medicine that has been developed to be similar to an existing biological medicine’. A biosimilar mimics the effects of a previously approved biologic medicine and is intended to treat the same disease or diseases.

Once the protection for a product expires, e.g. patent or regulatory protection, the company no longer has exclusive rights to sell the medicine, and other companies can then manufacture and sell a copy of the medicine with the same active ingredient. These copies have been given the name ‘similar biological medicinal products’ or ‘biosimilars’. Biosimilars and original biologic medicines will differ in appearance, brand name and packaging, although the dose and how the medicines are given (by injection under the skin, into a muscle or directly into a vein) remain the same.

2.1. General features

Biosimilars should not be confused with traditional generic medicines (the follow-on versions or copies of chemical medicines), which are considered to be identical to the original medicine (see the generics section for more details). Although the active substance is essentially the same, biosimilars may differ slightly from the original biologic medicine because they are often derived from a different biological (i.e. natural) source and produced using slightly different manufacturing processes. Importantly, before biosimilars are approved for use, it is necessary for manufacturers to show by way of clinical trials that, despite any minor differences that may exist, they are as effective at treating the target disease as the original biologic medicine, and do not cause any additional unwanted side effects.

Although biosimilars are similar to existing approved biologic medicines, they cannot necessarily be used interchangeably, as is the case with traditional generic medicines. In many countries, automatic generic substitution by the pharmacist (i.e., selecting a generic medicine in place of the original medicine) is often mandatory because it leads to substantial cost savings. Automatic substitution is not recommended for biosimilars because they are not identical to the original biologic medicine. In fact, several European countries, including the UK, Spain, France, Germany, the Netherlands, Italy and Sweden, do not allow biosimilars to be substituted automatically for the original biologic medicine. The decision whether to treat a patient with a biosimilar or the original biologic medicine must be made by a qualified doctor based on the available scientific evidence and the patient’s medical circumstances.

2.2. Use of biosimilars

Biosimilars are used to treat the same diseases as the original biologic medicine (see Biologics section for more details). A list of currently available biosimilars agents in Europe can be found on the EMA website.

2.3. Production process

Biosimilars are developed in the same way as the original biologic medicine they copy. They are manufactured using living cells that have had a vector carrying genetic information (deoxyribonucleic acid; DNA) inserted into them. This vector contains specific information that allows cells to produce the proteins that form the active components of biosimilars (see the Biologics section for more details). The exact source of the living cells (i.e. microorganism, animal or human) and the specific production techniques used to manufacture biosimilars may, however, vary from those used to manufacture the original biologic medicine. Nevertheless, biosimilars are produced to the same high standards required of the original biologic medicines.

2.4. Approval process

Biosimilars are regulated in the European legislation since 2003. Importantly, the regulatory approval requirements and post-marketing surveillance for biosimilars are much more rigorous than for traditional generic chemical medicines.

Unlike for generic chemical medicines, manufacturers are required to conduct clinical studies to demonstrate that the benefits (i.e. ability to treat a disease) and any potential risks (for example, the tendency to cause an immune response – an important consideration for biologic medicines) are comparable between the two medicines. Although the exact information required for approval is decided on a case-by-case basis, the amount of clinical data needed for a biosimilar is generally less than for the original biologic medicine. This is because the safety and effectiveness of the original medicine will have been well established over several years.

Consequently, some clinical studies will not need to be repeated for the biosimilar. The main aim of the evaluation is to establish that there are no major differences between the biosimilar and the original biologic medicine.

3. References