From the spark of the therapeutic idea until the placement of a drug on a pharmacy shelf, any novel treatment has a long way ahead. Most of them take decades to be available for patients, and the average cost of developing a new therapy rises to up to millions of euros. This drain of time and money is due to the many steps in between: choosing a candidate therapeutic molecule, testing its efficiency, developing a strategy to deliver it… And yet, this hard work would become useless if, once it is designed, the therapy shows severe side effects that harm patients. Thus, a great part of the efforts that go into the development of a therapeutic product is invested in ensuring that the drug is completely safe for humans.
In this path, a main milestone is evaluating its biosafety, meaning whether the product is toxic for humans. ”The basic principle is that every substance has a certain degree of toxicity. But, as the ancient physician Paracelsus said: ’the dose makes the poison‘”, says Dr Daniel Pérez, Chief Innovation Officer at Nanoimmunotech and partner of the New Deal project.
One of Nanoimmunotech’s goals is to determine the dose range of the New Deal’s therapeutic product that shows no severe side effects. This is called therapeutic window and it will ultimately determine if the treatment is feasible. If the side effects appear in a dose higher than the therapeutic one, these effects won’t show up in a normal use. On the other hand, if in order to be effective the drug needs a dose that produces side effects worse than the disease itself, it would be useless. ”The best example is ibuprofen. This molecule is toxic for the kidney, but the drug dose needed to be effective is less than the one that can trigger this side effect.”, explains Dr Pérez. Another important test is biocompatibility: checking how the product will behave once it enters the body. This is particularly important to decide how the drug should be administered. ”For instance, a biocompatibility analysis could check if any substance derived from the product can reach out the blood torrent and, if so, what effects it could trigger”, explains Dr Pérez.
And there are further considerations. Any product that is used in humans must be tested for the presence of microorganisms in order to avoid infections. This is relevant not only for the final product but also for its production processes. “A drug must be sterile; therefore, we need to check if it suffers contamination during the manufacture and also during the storage of the product.”, says Dr Pérez. The evaluation process also tests how stable the product is by ascertaining how long its properties stay the same.
There are some safety tests that are crucial because they check for features that may interfere with the therapeutic principle of the candidate treatment. In the case of the New Deal project, it is important to perform tests to detect endotoxins, substances that can trigger immune responses on humans. “The drug that the new Deal project is developing has a very clear motivation: to inhibit inflammation in IBD. Thus, the immune aspect is vital and any artefact that affects it must be reduced”, states Dr Pérez.
Testing all these parameters leads to a better understanding of the product properties. ”Our role in the New Deal project is to characterize the resulting therapeutic product “, summarises Dr Pérez. Knowing the composition of the therapeutic product, how it will behave in the body and its therapeutic window allows not only to minimise side effects on patients, but also to optimize the design process, as Dr Pérez explains, “All the safety parameters must be clear as soon as possible, because if you keep moving forward on the product development, you can’t change what you have already set.”