Biological medicines

What they are

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

Their use

Use of biological medicines, including biosimilars, is well established in clinical practice. Biologic medicines are increasingly used to treat a number 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.  

Natural variation

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

Biosimilar medicines

What they are

When an existing licensed biological medicine is approaching loss of exclusivity, biosimilar medicines may be developed to compete commercially. The existing biological medicine is known as the Reference Product (RP). A biosimilar medicine is a type of biological medicine that is highly similar in structure and function to the RP. The similarity is demonstrated by data confirming clinical efficacy, safety and immunogenicity equivalence. Biosimilar medicines cannot be launched on to the market until after the loss of exclusivity of the RP.

Further information can be found on our understanding biosimilar and generic market entry article. 

NHS England provides guidance on biosimilar medicines.

Differences between generic medicines and biosimilars

Biosimilar medicines have no clinically meaningful differences from their RP; 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 RP. 

Biosimilars

A biosimilar medicine is a highly similar copy of its RP. 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 RP.  

Use of biosimilar medicines in the NHS

Since approval of the first biosimilar (Omnitrope®) in 2006, many others have been approved in the UK for multiple clinical conditions.   

Regulation of biosimilar medicines

Regulatory principles

The safety and efficacy of the RP is already well known. Therefore, the focus of biosimilar development is to demonstrate a high degree of similarity to the RP rather than to re-establish patient benefit. 

Approval process

The MHRA outlines guidance on the licensing of biosimilar products in the UK.

For a biosimilar medicine to be approved: 

• a detailed clinical comparability exercise must be completed by the manufacturer, including physicochemical and biological characterisation 
• a confirmatory pharmacokinetic (PK) trial must demonstrate equivalence to the RP, with no clinically meaningful differences in safety and efficacy 
• 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 RP)
• product quality is assured by the regulatory process 

Extrapolation of approved indications

The approval process proves that biosimilars are highly similar to their RPs. Therefore, evidence of clinical efficacy is usually required for only one indication. This is extrapolated to other indications, to avoid unnecessary repetition of clinical trials.  

Biosimilars will generally receive a licence for all their RP’s indications, unless some indications are still covered by additional patent protection. This results in the award of a ‘skinny label’, with the protected indications omitted. 

Post-marketing pharmacovigilance

Adverse effects experienced during use of biosimilars must be reported via the Yellow Card scheme. Biosimilars are black triangle medicines when first licensed, and as such, they require additional monitoring. Reporting is essential to reassure clinicians and patients that, should any unforeseen safety issues become apparent, they are detected and acted upon. 

Interchangeability

The MHRA highlights that: 

• biosimilars are interchangeable with the RP 
• biosimilars of the same RP are also interchangeable  

NHS Experience

There is significant experience of intentional switching between products. Once the MHRA authorises a product as a biosimilar, the prescriber should consider it therapeutically equivalent to the RP in the authorised indications. This is supported by a systematic review of real-world data.  

Switching patients from the RP to a biosimilar, if this is the best value biologic, has become standard clinical practice. ‘Switching’ describes a collaborative managed process to change the patient’s prescribed treatment from their existing biologic medicine to a biosimilar.  

Guidance

Where NICE has recommended the RP, the same guidance applies to the biosimilar medicine.  

NHS England supports a ‘best value first’ approach for biological medicines. Further information about implementation of best value biologics through NHS commissioning and contracting systems can be found in the NHS commissioning framework for best value biological medicines. 

Substitution and consent

Biosimilars should be prescribed by brand name in line with MHRA guidance, to prevent inadvertent switching.

Switching should be a managed process involving both prescribers and patients. Decisions about initiating treatment with a biosimilar, or switching should be shared, and both parties aware of the brand name of the product received. This is important for traceability and reporting purposes if there are any suspected safety issues relating to the RP or biosimilar medicine. 

Different organisations may have different approaches to consenting patients for biosimilar switching. Examples of general patient information leaflets and switching approaches are available via the biosimilar best practice zone of the NHS Futures workspace, the NHS Biosimilar Hub. Register with your NHS email address to gain access.  

Using biosimilars

We’ve created resources, including molecule specific patient information leaflets and implementation checklists, to support the introduction of biosimilars identified by NHS England as priority molecules: 

Further resources for other medicines are added to align with NHS procurement and commissioning timetables. 

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