The pharmaceutical industry 

Medicines have had an outstanding impact on humanity. Clear evidence of this is found in human life expectancy. Throughout the 20th and 21st centuries, improvements to the quality and accessibility of healthcare, coupled with a general increase in development and living standards, has led to a considerable increase in life expectancy. Major advances leading to longer and healthier lives include the discovery of the antibiotic penicillin, chemicals for chemotherapy, and a wide assortment of pain treatments, vaccines, and other medicines.

We must find a balance between meeting societal needs and preserving the natural environment with a more environmentally sustainable pharmaceutical industry. This section describes the basic processes in the development of medicines and recent Green Chemistry activities.

Types of drug molecule

The pathway to putting a medicine on the market begins by targeting an illness. The biological mechanisms that inhibit symptoms or treat the underlying cause of the disease are identified, and then chemicals are designed to have the desired biological activity. There are two generally types of active pharmaceutical ingredient (API), aptly called small molecules and big molecules. The small molecules are indeed small, chemical entities that are designed to be agonists or antagonists. The former bind to a receptor in the body and cause a response that is desirable as a medical treatment; the latter also bind to receptors in the body but do not cause a response, instead the antagonist regulates/prevents the action of agonists that are responsible for the illness. Small molecule pharmaceuticals are a triumph of 20th century science, including penicillin and ibuprofen. The 21st century has seen advances in large molecule APIs. These large molecules are peptides, chemically related to enzymes and muscle tissue. As with small molecule APIs, these can be naturally occurring and extracted or cultivated from organisms, or artificially synthesised by scientists. The most well known peptide medicine is insulin.

Vaccines work differently to medicines by mimicking a microorganism responsible for a specific disease, and prompting the immune system of the patient to develop a resistance. Vaccines are not included in this learning resource. For information on vaccines, please refer to the European Vaccination Information Portal or the British Society for Immunology.

Research and development

The creation of a new medicine will often involve making and testing thousands of chemicals. There is usually a 'lead compound' identified, a molecule that exhibits some biological activity but is far from optimum. This may be because of low efficacy (performance), or other properties that make it ineffective in the body (for example it may be unstable or rapidly excreted). Research and Development (R&D) medicinal chemists focus on the laboratory (gram scale) synthesis of a variety of analogues of the lead compound(s) for preliminary testing in cellular assays, aiming to prove or improve efficacy and safety while ensuring the drug's suitability for patient administration. Additionally, the chemist examines pharmacodynamics, the study of how drugs bind to their target sites and produce pharmacological effects, and pharmacokinetics, which involves the absorption, distribution, metabolism, and excretion (ADME) of drugs. 

Process chemists are concerned with designing practical, safe, and cost-effective methods for synthesising compounds on a larger scale, typically working on a single target molecule identified by the medicinal chemists and determining the most efficient route to that specific target. Process chemistry has traditionally stronger links to Green Chemistry because of the increased risk from working with larger quantities of chemicals, and the more severe consequences of any leaks or emissions. That said, the principles of Green Chemistry are more embedded in smaller scale operations now. The use of solvent selection guides is one example.

The road to large scale manufacturing

In 2019, the global pharmaceutical sector was confronted with significant obstacles as it strived to address the challenges posed by the SARS-CoV-2 pandemic. Over this crisis, a breakthrough was reported by researchers from Pfizer. They announced the identification of nirmatrelvir, a highly effective compound that inhibits the SARS-CoV-2 virus. The urgent need to assess the safety and efficacy of nirmatrelvir prompted swift movement through toxicological evaluations and clinical trials. This necessitated the rapid production of nirmatrelvir in large quantities, unprecedented in the industry’s history. 

A landmark achievement was reached with the development of a cost-effective production method for nirmatrelvir in just 13 weeks. This scaling-up process usually takes between 2 to 4 years. This pivotal advancement facilitated the expedited progress of nirmatrelvir from its initial synthesis in July 2020 to market in December 2021, within a mere 17-month span (compared to the typical 10 year period).

Regarding Green Chemistry, chemists were able to decrease the number of reactions in the synthesis of nirmatrelvir from 7 to 5. Further optimisation doubled the amount of product and halved the waste.