Simpler tests could slash biosimilar costs, widen patient access

Most of the drugs that we consume are called ‘small molecule drugs’. Their chemical structure is reasonably simple. Disprin, for instance, has a molecular weight of around 180 daltons. There is another breed of drugs that are very large, complex molecules. For instance, the molecular weight of insulin is around 5,800 daltons and that of the monoclonal antibody remicade, about 150,000 daltons. (One dalton is equal to one-12th the mass of a carbon-12 atom.)

Small molecule drugs also tend to have fixed structures that do not change for the duration of their use. In contrast, the complex molecules, which we call biologics, are produced in biological systems and therefore during their production slight variations in the structure may arise. However, these variations may have no impact on the stability of the molecule, its efficacy or its side effects.

When a company produces a small molecule drug for the first time, it seeks patent protection for that drug. That is, no competitor may make that drug for several years. It is only when the drug goes ‘off patent’ that competitors may make it.

In the absence of competition, the originator company can price the drug very high. Once there is competition, the competitor companies produce generics, which are copies of the original drug. They don’t undertake the research and development to make the drug and they may not spend as much on marketing and sales, so the costs of generics are also much lower. Most of the drugs that you and I take are generics and are priced very cheaply compared to the originator drug. A good example is Sovaldi, a drug used to treat hepatitis C: it originally cost $84,000 for a 12-week course in the US but that dropped to $1,000 once Indian generic firms started making it. Largely it is generic drugs that keep us in India alive and well.

Since biologics made by a generic firm will be produced by different biological systems, they may not be identical to those made by the originator company. Thus they are called biosimilars, not generics.

For many years, a debate has raged over how much proof is required for a manufacturer to prove that a given biosimilar will work as well as the original biologic drug. Therefore, whereas much simpler testing was required to show that a generic small molecule was working like the originator molecule, there are more elaborate and expensive tests for biosimilars.

Major drug regulators such as those of the US, the UK, and in Europe have been working to determine how they can simplify the requirements for approving a biosimilar, in view of the availability of modern analytical techniques. For example, the UK has removed animal trials and the US has planned to replace them with more human-relevant methods (like using organoids). In India, this requirement has not yet been updated although there is a proposal to waive animal studies on a case-by-case basis. Some have also argued that India should follow the practices of the UK and the US. The same holds for the more expensive clinical trials, which in the UK are currently required only in certain cases.

Biosimilars need to be made less expensively while ensuring efficacy and minimal adverse effects. The larger the number of affordable biosimilars, the more options we will have for our patients.

Gayatri Saberwal is a consultant at the Tata Institute for Genetics and Society.