The Pathway of Drug Development 



From my research across the industry and looking at the news regarding new products hitting the market, I kept seeing terminology such as ‘approved’ and seeing involvement from authorisations such as the EMA or the US FDA. It had me wondering what is the formal approach that pharmaceutical companies had to undergo for their products to reach the market.

Drugs have to be  subjected to rigorous testing and cost effective analysis. Every year we see groups of new drugs licensed but what we never see are the thousands of drugs that never make it through the whole process. The research and development journey of those new drugs that make it to the market will have taken around 12 years and cost around £1.15bn (pharmaceutical-journal.com 2018)

Drug creation: Research and Development


The journey first begins in university laboratory’s where researchers try to understand the process behind a disease on a cellular and molecular level. Through the understanding of the mechanism of the disease, potential treatments can be developed. Typically researchers discover new drugs through: new insight into the disease mechanism that allows researchers to design a product to stop or reverse this mechanism, many tests of molecular compounds to find possible beneficial effects and through new technologies such as those that can manipulate genetic material or target specific sites within the body. ( FDA.gov 2018) .Scientists after they have discovered the target in the disease mechanism will  look to natural compounds from plants and fungi and now more than ever using knowledge gained from the study of genetics and proteins to create new molecules using computers.

Thousands of compounds may be potential treatments at the earlier stages, but these numbers are whittled down to a smaller number through  rigorous testing. Compounds that show promise have further experiments conducted on them to see: how the drug is absorbed, metabolized and excreted, optimum dosage, best way to administer the drug, adverse side effects, how it acts on groups of people (gender, age, ethnicity) as well as how it compares with similar drugs out there. (FDA.gov)

The second stage undertook is pre-clinical research. Before testing the drugs on humans, researchers need to test the toxicity of the drug. These safety tests are conducted on computerized models, cells and animals.  Around half of candidates make it through this stage and these remaining compounds are ready to be tested in humans. In the UK, approval by the Medicines and Healthcare products Regulatory Agency (MHRA) is required before any testing in humans can occur. The company will put in a clinical trial application (CTA) which will be reviewed by scientific experts who will decide whether or not sufficient preliminary research has been conducted to allow testing in humans to go ahead.

The third stage is the clinical research stage.  This stage studies the way the drug will interact with the human body. The clinical trials will be split into three phases. The phase 1 trail tests the drug on a small group of healthy volunteers. Small doses of the drug will be administered to the group of 20-100 healthy volunteers who are closely supervised. The length of the study ranges to several months and the purpose is to investigate safety and dosage. From this stage approximately 70% of the drugs move forward. (fda.gov)

Phase 2 tests 100-500 patients with the disease and lasts from several months to two years. Purposefully a small amount of volunteers are chosen to avoid exposing a volunteer to a potentially harmful substance. The purpose of stage 2 is to investigate the efficacy of the drug and potential side effects.Most drugs that fail the clinical testing fail at the phase 2 trail, often because it’s found to be ineffective or have detrimental side effects. As a result approximately 33% of drugs move to phase 3 (fda.gov)

The final phase trial tests a much larger population of patients, often 1000 to 5000 across international sites. (Pharmaceutical journal.com 2018 ).The purpose of the phase 3 trials is to confirm the phase 2 findings on a much larger population and to identify the best dosage option. After all three phase trials have been completed, the clinical testing should provide data on safety and efficacy to demonstrate an overall benefit for the medicine to be able to be submitted for a licensing application.

After the drug has passed the clinical trials, the company has to submit it for marketing authorisation to the national regulatory authority. Within the UK, submissions are sent to the MHRA and USA to the Food and Drug Administration (FDA). However in Europe, submissions are often made to the EMA (European Medicines Agency), to obtain marketing authorisation for the whole of Europe rather than having to make individual applications to each country. The submissions to the marketing authority are a summary of the pre clinical trials and the clinical trials that were operated. With the summary detailing chemical makeup, results from the pre clinical and clinical, toxicity, manufacturing process and proposed labeling. (Pharmaceutical journal.com 2018)

In England and Wales even if approved, the process does not halt there. In order for the drug to be able to be distributed through the NHS, companies have to submit the drug to the National Institute of Health and Care Excellence (NICE). NICE assesses it’s cost  and efficacy to decide whether it is affordable  to be distributed through the NHS. Marketing authorisations can insist on further clinical trials to take place for pharmacovigilance  (post marketing safety surveillance). Or to be tested on specific targets like patients with complex medical problems that would have been tested on in the earlier clinical trials. This is very important as the clinical trials although extremely useful in providing the information cannot assess everything. The true state of a products safety evolves over the years that make a products lifetime in the workplace.  In the USA programmes are available that allow manufacturers, health professionals and consumers to report problems associated with approved drugs. The FDA also has the power to conduct either announced or unannounced routine inspections of its drug manufacturing facilities and has the power to shut them down.

A drug that shows promise for the foreseeable future will be patented by the company, so it means this company only had the right to market the drug exclusively. This is in order for the company to be able to recoup there development costs and to make a profit to cover the costs of drugs that failed during the testing process and to be able to continue innovation of new products. Due to the extensive testing and licensing period, half the patent period will usually have expired. Once the patent has expired, other companies have free reign to develop the drug. These companies must make sure that their drugs have the same dosage form, strength, safety, quality and intended use. (FDA. Gov)  because these drugs are comparable they don’t have to undergo clinical trials instead bio equivalence
studies are applied.

The relationship between drug manufacturers and regulatory agencies is becoming increasing open due to developments of drugs becoming more complex and expensive. As a result, regulatory authorities are demanding more information and agencies like MHRA and NICE have set up offices to provide advice and consultancy to these drug manufacturers to help ensure they generate the evidence they will need to have approval from these companies.

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