Biological medicines

What they are

Biological medicines are made or derived from a biological source. They are large, complex molecules, with examples including hormone therapies, insulin, vaccines, monoclonal antibodies and gene therapies.

Their use

Use of biological medicines, including biosimilars, in clinical practice is well established and rapidly increasing for a broad range of acute and chronic conditions such as cancer, rheumatoid arthritis and ulcerative colitis. Many biological medicines are high-cost therapies that add value for patients and the NHS when used appropriately.

Their manufacture

The manufacture of biological medicines is more complex than for chemically-derived molecules and may involve use of biotechnology (such as recombinant DNA).

Natural variation

Biological medicines will show a small degree of expected variation within their molecular structures. This occurs even between batches of the same product and is due to the variability of biological systems and manufacturing processes.

Biosimilar medicines

What they are

A biosimilar medicine is a type of biological medicine that is highly similar in structure and function to an existing biological medicine already approved for use. The similarity includes clinical equivalence and immunogenicity. Biosimilar medicines have proven clinical equivalence to the ‘reference’ medicine, i.e. the original product.

NHS England provides guidance on biosimilar medicines.

Differences between generic medicines and biosimilars

Biosimilar medicines have no clinically meaningful differences from their reference medicine; however, they are not quite the same as generic medicines.

Generic medicines

A generic medicine is an exact copy of a chemically synthesised licensed medicine and as such, generic medicines are directly interchangeable with their reference medicine.

Biosimilars

A biosimilar medicine is a highly similar copy of its reference medicine. Since it is not possible to replicate biological medicines exactly, a small degree of variation is expected and accepted so long as the biosimilar has no clinically meaningful differences from its reference medicine.

Use of biosimilar medicines in the NHS

Since the approval of the first biosimilar (Omnitrope®) many others have subsequently been approved. By 2006, at least 60 biosimilar medicines had been approved for use in different therapeutic areas in Europe.

Regulation of biosimilar medicines

Regulatory principles

The focus of biosimilar development is not to re-establish patient benefit but to demonstrate a high degree of similarity with the reference medicine.

Approval process

The MHRA outlines guidance on the licensing of biosimilar products in the UK. For a biosimilar medicine to be approved:

• The manufacturer must demonstrate through a clinical trial that the biosimilar has no clinically meaningful differences in safety and efficacy from the reference medicine.
• The range of variability allowed for a biosimilar is within defined and controlled limits (a degree of variability is also allowed between batches of the reference medicine).
• Product quality is assured by the regulatory process.

Extrapolation of approved indications

Since a biosimilar is highly similar to its reference product and this has been proved in one indication, its approval may be extrapolated to additional indications that are already approved for the reference medicine. This avoids the unnecessary repetition of clinical trials.

Post-marketing pharmacovigilance

Adverse effects experienced from the use of biosimilars must be reported via the yellow card scheme in the same way as they are for the reference product.

Reporting is essential to reassure clinicians and patients that, should any unforeseen safety issues become apparent, they are detected and acted upon in a timely manner.

Interchangeability

There is now significant experience of switching from reference medicines to their biosimilar versions, as well as switching from one biosimilar to another biosimilar.

National guidance and experience

MHRA Advice

Advice from the MHRA on interchangeability considers licensed biosimilar products to be interchangeable with reference medicines. They advise that:

• A prescriber can choose the biosimilar medicine over the reference medicine and expect to achieve the same therapeutic effect.
• All biological medicines, including biosimilars, should be prescribed by brand name.
• Both the patient and prescriber should be aware of the brand name of the product received.

NICE Guidance

NICE guidance on biosimilars advises that:

• If NICE guidance exists for a biological medicine, the same guidance applies to the biosimilar.
• NICE technology appraisal guidance often recommends treatment with the least expensive option, taking into account administration costs, dosages, mode of administration and treatment schedules. Biosimilars will often be the least expensive option when compared to their reference medicines.

NHS Experience

Experience with use of biosimilars in the NHS has shown that switching between a biosimilar and its reference medicine does not appear to impact efficacy, safety or immunogenicity.

Sharing decisions about treatment

Substitution of a biosimilar in place of the reference medicine without the knowledge of the patient or prescriber is not supported by the MHRA guidance.

Prescribers and patients should share decisions about initiating treatment with a biosimilar, or switching from treatment with the reference product to a biosimilar where appropriate.

Using biosimilars

We’ve created a number of specific resources to support the introduction of biosimilars:

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