Activities to Be Conducted Before A Drug Is Sold in The EU Market.
Any business that is not operating in the European Union market is losing out on a huge chance to grow its revenue. The European Union currently comprises of 27 member countries. These countries make up the largest economies in the world thereby making the European Union market one of the most lucrative markets for any business. The EU is the largest market if one was to use Gross Domestic Product as the yardstick while it also comprises the third-largest population. It is these parameters that make the European Union market attractive to businesses across the globe. The member states have some sovereignty however some laws are made by the European Commission (EC) that are implemented across all states. The harmonization of laws is aimed at easing the flow of goods and services across the region. The harmonization also acts as a barrier for selling into the EU market for various companies as they are unable to meet some of the set regulations. For pharmaceutical companies, they have to meet set criteria before they can sell new drugs into this market.
Establishment
One of the first activities that a pharmaceutical company needs to do is to have an establishment in the EU region. As per the EU regulations, any entity that sells drugs in the EU market must either be established in the EU or have a representative with the authority to represent the institution in any matter. The business has three options for meeting this requirement. The business could opt to register a company in the EU, open a branch of an existing company or have a place of business within one of the EU countries ( Lewis, 2010) . The company should also consider the tax implications on each of the methods.
Delegate your assignment to our experts and they will do the rest.
Apart from having a representative or an establishment, EU regulations require that all pharmaceutical companies need to have a “qualified” person for each of the activities that they are going to perform. The individual needs to be readily available for any activity that they may be called upon to perform. The qualified person needs to meet a certain set of criteria to be classified as a qualified person.
Clinical Trials
For any drug to be sold in any market and not just the EU it has to undergo several clinical trials. It is however more complex passing the clinical trials set by the EU than in any other market. The strict rules and regulations make it hard for pharmaceutical companies to perform and pass clinical trials. These rules apply to all EU countries due to the harmonization of rules and regulations. The harmonization of clinical trials is a benefit to the companies as they do not have to meet new standards in different countries ( Lewis, 2010) . It also offers them an opportunity to access a wide range of patients in terms of race, ethnicity and lifestyle which is important for clinical trials.
Marketing Authorization
Before a drug is marketed in the EU market, the company needs to apply for a marketing authorization license which is valid for five years. While applying for this license the company is expected to submit certain details about the drug that it wants to market to the EU market ( Lewis, 2010) . Some of the details that the company will be expected to submit include:
The product’s common or scientific name
The invented name
Qualitative and quantitative particulars
Proposed therapeutic indications
Contraindications and adverse reactions
The results of pharmaceutical and preclinical tests and clinical trials ( Lewis, 2010) .
The pharmaceutical company needs to also decide on which marketing authorization to apply for. As per the changes made in the year 2005 in terms of legislation, companies now have three ways in which they can acquire the marketing authorization license. One of the ways is through the centralized procedure which is needed for drugs treating certain illnesses such as HIV/AIDS and Cancer ( Dennis, 2019) . Drugs that contain new medicinal substances that have not been approved in the region before also have to use this procedure. The second method is through national marketing authorization ( Dennis, 2019) . Drugs that do not fall in the category of having to go through the centralized procedure can be authorized on a country-to-country basis. The authorization is done through competent bodies in those countries ( Lewis, 2010) . Finally, a pharmaceuticals company could choose to use the mutual recognition procedure or decentralized procedure. In this process, the company wants to be able to sell its products in more than one country without necessarily having to apply in each of these countries ( Dennis, 2019) . In the mutual recognition procedure, the company needs to have an authorization from one of the member states. The company will then apply to have its drug recognized in the other member states. In the decentralized procedure, the company applies in a one-member state who then becomes its reference. This member state then prepares an assessment that is then presented to other member states for approval as well.
Describe the specific objectives of in-vitro studies.
Research studies and trials can be conducted in various environments depending on the subject being researched on. In-vitro is a Latin term that means “within the glass”. Research studies that are conducted outside a living organism and in most cases in test tubes are referred to as in-vitro. In-vitro studies could include looking into an animal, human cells and bacteria in culture. Conducting an in-vitro study creates a controlled environment, however, since the study occurs outside a living organism the results need to be considered with caution.
In-Vitro studies are conducted to achieve the following objectives:
Predicting effect on animals or humans – Some of the in vitro assays are conducted to prove the effects that a certain component will have on a human if ingested. The proofing needs to be done within a reasonable certainty ( Schneeman et.al, 2005) . The seriousness of the predicted harm needs to also be found as this can be used to come up with defence mechanisms.
Examine safety endpoints – In vitro studies are used to determine outcome measures due to the occurrence of a symptom, disease or even a laboratory abnormality ( Schneeman et.al, 2005) . The study will have a targeted outcome in terms of clinical research trials. In vitro studies help in determining primary, secondary and surrogate endpoints ( Schneeman et.al, 2005) . Primary endpoints are where the subjects are randomized and the trial powered. The secondary endpoint is an endpoint that is analysed post hoc and the trial is not randomized nor powered. On the other hand, surrogate endpoints are those endpoints that substitute clinical endpoints simply because it becomes a difficult task to study the clinical endpoint.
Effect of compounds on specific organs – Several in vitro experiments are conducted to gain information on the risks possessed by certain compounds on specific body organs and cells. Some of the experiments include using isolated cells, isolated organs, microorganism and subcellular organelles ( Schneeman et.al, 2005) . Tests could also use molecular entities which include receptors, enzymes, transport proteins, gene fragments and isolated membranes ( Schneeman et.al, 2005) . One of the advantages of conducting in vitro studies to test these risks is based on their application of a reductionist approach which gives further information on the mechanisms of action for the compound which is difficult to achieve through a whole animal study.
What practices and regulations are in place to ensure scientific data from Clinical Trials is reliable?
Clinical trials are an important aspect of the medical field. Clinical trials are whereby a researcher tries to find out the viability of a drug including the relevant dosage for that drug. Due to greed and failure to follow the set code of ethics thee has been numerous cases where researchers have falsified clinical trials data ( Gardner, Lidz & Hartwig, 2005) . It is on this background that certain rules and regulations have been set up to ensure that clinical trials data is not falsified. Below are some of the expected practices and regulations:
Safety Pharmacology – One of the safety measures when carrying out pharmacology studies is to ensure that an assessment is carried out on how the drug affects the respiratory, cardiovascular and the central nervous system ( ICH M3, 2010) . The assessment on these systems needs to be carried out before the drug is exposed to humans and per the ICH guidelines.
Toxicokinetic and pharmacokinetic studies – For safety measures on humans when conducting an in-vitro study, the metabolic data on animals and the exposure data needs to be collected first before subjecting the drug to humans for clinical trials ( ICH M3, 2010) . It is also expected that before the trials are conducted on a large portion of humans data on absorption, metabolism, distribution and excretion needs to be collected from humans.
Repeated dose toxicity studies – When conducting a clinical trial you must conduct a repeated dose toxicity study. To perform this study, the researcher needs to consider certain factors such as duration, scope and therapeutic indications of the clinical trial ( ICH M3, 2010) . As a principle, the period of the toxicity study conducted on two mammalian species where one needs to be a non-rodent needs to be the same or exceed when being conducted on humans.
Clinical Development Trials – A researcher is expected to conduct a clinical trial on a minimum of two mammals where one needs to be a non-rodent for not less than two weeks ( Krishnankutty, Bellary, Kumar & Moodahadu, 2012) . The results from this trial can, therefore, be deemed as valid since ample time was taken to study the reactions since some of the side effects could prop up after a while. Where a researcher decides to conduct longer clinical trials they are required to perform repeated-dose toxicology studies.
Marketing Authorization – Marketing carries the risk of exposing a drug to a large population of people depending on the reachability of the means of advertising used. Due to this risk and the unpredictability of clinical trials researchers are expected to perform longer nonclinical tests ( ICH M3, 2010) . This helps reduce the risk tremendously as all variables will have been tested before the drug or the clinical trial results are marketed to the target population.
Estimation of the first dosage in humans’ trial - one of the major risks that the subjects who act as the first human subjects face are the initial dosage. To come up with this dosage various profiles need to be considered by the researcher. These profiles include toxicological profile, pharmacological dose-response and pharmacokinetics ( ICH M3, 2010) . When conducting the nonclinical safety studies the data collected from the most relevant and sensitive animal should be given more credit than that of the other animals. The dosage will then be determined by comparing various factors by finding a weighted average of the pharmacodynamics, molecule details and the design of the clinical trial.
Exploratory clinical studies – In some cases, more knowledge on the mechanics of the human body are needed rather than testing the new drug with other mammals. This is achieved by conducting a streamlined exploratory clinical study. Exploratory clinical studies are used to find certain parameters relating to the human body which include pharmacodynamics, pharmacokinetics among other biomarkers. In conducting exploratory studies the certain level of supporting data is needed since humans will be exposed to a substantial amount of risk ( ICH M3, 2010) . The data to be collected varies depending on the extent that the human will be exposed in terms of the dosage and the duration.
Multiple Dosage Studies – A researcher is expected to carry out a research that will determine the pharmacodynamics and pharmacokinetics of the human body which does not necessarily support the maximum dosage that can be tolerated ( ICH M3, 2010) . Here the maximum clinical dosage is exposed to multiple subjects and the toxicity of the molecule observed. It is from this data that a figure is arrived at on the best dosage for the drug.
Bibliography
Dennis, A., 2019. Distribution and marketing of drugs in the EU. Practical Law UK Signon . Available at: https://uk.practicallaw.thomsonreuters.com/0-618-7218?transitionType=Default&contextData=(sc.Default)&firstPage=true&bhcp=1 [Accessed December 6, 2019].
Gardner, W., Lidz, C.W. and Hartwig, K.C., 2005. Authors' reports about research integrity problems in clinical trials. Contemporary clinical trials , 26 (2), pp.244-251.
ICH M3 (R2), 2010. Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.
Krishnankutty, B., Bellary, S., Kumar, N.B. and Moodahadu, L.S., 2012. Data management in clinical research: an overview. Indian journal of pharmacology , 44 (2), p.168.
Lewis, M., 2010. Bringing a Drug to Market in the European Union: Regulatory, Corporate, and Taxation Issues. In Emerging Life Sciences - Companies (pp. 245–261).
Schneeman, B.U.C., Azarnoff, D., Christiansen, C., Clark, A., Farnsworth, N., Fugh-Berman, A., Gansler, T., Gibson, J., Gillis, C., Goldman, S. and Guzelian, P., 2005. Dietary supplements: a framework for evaluating safety. Review of Liver-Related Risks for Chaparral .
