How pharmaceutical drugs are developed

The development of pharmaceutical drugs is a long process that could take up to 12 years, and of course, can cost companies billions of rand. For every new drug that is approved for use, thousands of drugs that were in development are scrapped.

Why? There is a rigorous vetting process for the creation of medications, both chemical and herbal variety. This is for safety to regulate the legal amounts of each compound so that chemical medication ratios aren’t unbalanced or fatal. 

Certain medicines are not suitable for the elderly, much like how babies and young children are not allowed to take certain medications. It has to do with how the ageing process changes the way our body processes certain ingredients. 

The elderly usually have long-term health conditions and need treatment with multiple medications. This means that there is a greater chance of experiencing unwanted drug side effects, Affinity Health reported in 2018.

Medicines are made up of active ingredients and inactive ingredients.

Active drug ingredients in drugs

Active ingredients give the medicine we use its medicinal effect.

In pain medications, particularly over-the-counter variations, the active ingredient is paracetamol. The other ingredients will differ from brand to brand, but paracetamol is what relieves the pain. 

Atorvastatin is the active ingredient in cholesterol-lowering medicines, while ascorbic acid (vitamin C) is added to some multivitamins to assist with the absorption of the vitamin into the bloodstream.

Inactive ingredients in drugs

Inactive ingredients, or excipients, are all the other non-active ingredients used in medicine, explains Therapeutic Goods Administration. Some inactive ingredients are essential for the medicine to function as intended. These are the ingredients to look out for, and they may cause unfavourable reactions in the body. 

Some examples of types of inactive ingredients are preservatives, flavourings and colourants. Other non-active yet common ingredients are fillers that help a tablet stick together and certain manufacturing aids.

A manufacturing or processing aid is a substance that helps make the medicine but is not meant to stay in it. Sometimes medicines have trace amounts of these substances like soy oil as a lubricant, or eggs to culture the vaccines etc. But they are not considered medicinal drug ingredients.

The numbers

Globally, the projected growth estimate for drug discovery will be about $71 billion dollars by 2025, double what it was in 2016. For every 25 000 compounds that are discovered and developed in university laboratories, 25 get to be tested on humans in clinical trials, and only five make it to the market. Just in August 2018, globally, there were about 281 000 registered clinical drug trials on the go. 

Discovery and development

Drug discovery starts in university laboratories where researchers with funding from research bodies, government, grants or the pharmaceutical industry conduct scientific studies of diseases. The initial studies are conducted at a cellular or molecular level. 

The scientific study leads to the identification of a gene or protein that a new treatment could interfere with, thereby blocking off the disease. Researchers then search for compounds from plants, fungi or marine animals that become a key ingredient in drug development. Researchers usually consider around 10 000 compounds before settling on 10 to 20 compounds that could interfere with the disease process, The  Pharmaceutical Journal reports.

Preclinical Research

The drug is created from the study of compounds. At every step of the way, supporting reports are written for scrutiny later in the final review phase. First preclinical trials are done, and this involves testing on animals and safety and efficacy checks. These tests are done before any of the molecules are given to humans. Only about half the candidate compounds make it through the preclinical phase, and only five to 10 make it into clinical research. 

Clinical Research

Once a drug is cleared through preclinical research, it moves on to clinical research, which is a key step in drug development, as it involves testing on humans across the world at designated sites. 

Pharmaceutical companies and regulatory authorities have specific testing standards that include:

• The professionals involved in scientific testing.
• Selection criteria for the humans being tested.
• The setting where the tests are conducted.
• Clinical trial registration with close scrutiny by pharma professionals. 

In phase 1, small doses of the compound are given to 20 to 100 healthy volunteers who are closely monitored. About half the compounds will be deemed safe to move to phase 2, which examines the efficacy of the compound on volunteer patients who have the disease that the drug is meant to treat. To limit giving volunteers potentially harmful substances, only 100 to 500 patients take part, and they are stringently monitored and assessed. It is in phase 2 that the right dosage, oral or intravenous method of delivery and the dosing interval is worked out. Most products fail owing to safety issues, intolerable side effects and treatment ineffectiveness.

In phase 3, the drugs that make it through will be tested on 1 000 to 5 000 patients worldwide at designated sites. It is to reconfirm the efficacy in a large group of patients and to fine-tune the best dosage regimen. The pharmaceutical company has to supply safety and efficacy data that its drug is beneficial to the treatment of the disease before it can be submitted for a licensing application to a regulatory authority. At least 10% of drugs will still fail at this late stage. 

Drug Review

By the time a medicine gets to the review phase with a regulatory authority, the drug development testing could easily have been on the go for 10 to 15 years. In phase 4, pharmaceutical companies submit research and findings documents for a final review before approval. It usually takes 6 to 10 months after submission is accepted before the regulatory authority responds to the pharmaceutical company.

Still more tests

Once the licence is granted to market the medicine, it’s still not the end of the process. Health authorities look at the cost and efficacy of the treatment before they determine if the medicine is affordable enough to offer to health departments. 

It is always advisable to get your medication from a registered chemist, and all prescriptions and medicine recommendations need to come from a medical professional. This is general knowledge, but lesser known is that even the trusted medication from trusted dispensaries can contain undesirable ingredients, with even worse side effects.