Principles of Discovery of Medicines & Development Planning Report

This report provides a comprehensive analysis of the principles of medicine discovery and development planning, focusing on the interconnectedness of pharmacovigilance, clinical safety, and regulatory affairs. It delves into the roles and responsibilities of each, highlighting their significance in ensuring drug safety and efficacy. The report uses the case of Zydelig (idelalisib) to illustrate how the current EU legislative framework protects and enhances public health during the post-authorization phase of a medicine's lifecycle. It examines the EU Pharmacovigilance system, including the roles of the National Competent Authorities, the European Medicines Agency (EMA), and the European Commission. The report also discusses the recommendations and precautions associated with Zydelig, showcasing the EU's commitment to patient safety through continuous monitoring and risk management. It emphasizes the importance of regulatory affairs in drug development, from conception to marketing, and the critical role of clinical trials in generating evidence for market access. The report concludes by underscoring the EU's proactive, patient-centered approach to promoting public health by ensuring the availability and safe use of medicines.

Running head: PRINCIPLES OF DISCOVERY OF MEDICINES & DEVELOPMENT
PLANNING
Principles of Discovery of Medicines & Development Planning
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1PRINCIPLES OF DISCOVERY OF MEDICINES & DEVELOPMENT PLANNING
1. Relationship between pharmacovigilance, clinical safety and regulatory affairs
Pharmacovigilance and its relation with clinical safety
Pharmacovigilance (PV) can be referred to as the activities and science related to the
assessment, understanding, detection and prevention of the critical impacts or other medicine-
related issues (Maigetter et al. 2015). It plays a significant role in healthcare system by means
of discovery, assessment and monitoring of the interactions among the drugs and their impacts
among the human beings. WHO has defined the term as “the science and activities relating to
the detection, assessment, understanding and prevention of adverse effects or any other drug-
related problem” (Raza and Jamal 2015) Its aim is to bolster the safety of patient in terms of
medicine usage by means of providing a system for collecting, distributing and assessing the
drug safety.
Clinical safety on the other hand is a pharmacological science that is related to the
collection, detection, assessment, monitoring and prevention of the adverse reactions of drugs.
It is to mention that both Pharmacovigilance and clinical safety refer to the same function of
gathering and reporting the reactions of drugs in human beings. However, the main difference
lies among them is in terms of the values of the data that are generated. It is to mention that in
the Pharmacovigilance model, more complicated and larger datasets are analysed. This further
generates significant insight into the way drugs perform in the real world. Valuable data are
generated on the basis of how the medicines are performing in the patient sub-populations and
across the states of the diseases (Zhang and Meltzer 2016). On the other hand, in the clinical
safety, the data are collected during the clinical trials and they are reported on in the post
marketing environment. The information is then used by the regulatory agencies for making
decisions regarding which drug to be registered. With the same, it is also to note that like the

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clinical safety, Pharmacovigilance was comprises of the safety operations, agreements on
exchange of safety data, risk management etc.
Ways in which Pharmacovigilance, clinical safety and regulatory affairs are linked
Furthermore, it is to mention that like Pharmacovigilance and clinical safety, regulatory
affairs too is an essential part of the healthcare industry. According to Hernandez et al. (2017),
regulatory affairs are focused on the development of the global regulatory strategies for the
new and the novel products, collaboration with the other regulatory bodies all around the world
for setting different standards for the new technologies, support the activities on clinical
development, filling-up of the regulatory related submissions and ensure the regulatory
compliance all through the product life cycle. According to Walker et al. (2016), the regulatory
specialists are expected for being highly passionate about the efficiency and safety of the
medical and drug devices. They play a very important part in the process of communication
between their company and the different regulatory bodies like the FDA, EMA etc. It is to
mention that regulatory affairs are also known as government issues. There is an intersection in
between Pharmacovigilance and regulatory affairs and it can be seen in a growing need for the
exchange of information, that is, for the “Risk Management Plan (RMP), Pharmacovigilance
System Master File (PSMF) and the Summary of Product Characteristics (SmPC)” etc.
The regulatory affairs are involved with about each and every aspect of development of
drugs and medicines by means of commercialisation. They are also involved in the activities of
post-commercialisation. For instance, the activities that comprise of the expansion of the data
and information for modifying the present label on the marketed product or the submissions for
the new indicators or the Pharmacovigilance are part of the regulatory affairs. It is also related
to the clinical safety. Krageloh et al. (2018) in this context have claimed that the regulatory
affairs prevail for the methods of updating the information of the product and the

3PRINCIPLES OF DISCOVERY OF MEDICINES & DEVELOPMENT PLANNING
implementation of the other safety measures. There is a great impact of the regulatory affairs
on the clinical trials as majority of the clinical operations goes hand in hand with the regulatory
associates. Each of the drugs and medicines go through some strict regulations prior to hitting
the market and consumption of the human beings and even afterward (Jacques et al. 2016). The
trained and skilled staffs of regulatory affairs are involved in all the different stages of the
development of drugs and medicines, right from the conception to the clinical trial to the
marketing and the approval. It is to note that the clinical trials are very important for the
development of the new therapeutic products and the generation of the efficacy and safety that
are required for the attaining the regulatory approval. With the same, they also effectively
generate the evidence that are needed for gaining the market access and the reimbursement.
Although the clinical safety and trials are important, but at the same time, they are also very
risky. It is very important to make sure the safety of the patients come first and therefore, the
clinical safety and trails must comply with all the necessary regulations and the processes of
approval. In this way, pharmacovigilance, clinical safety and regulatory affairs are related to
each other.
2. How the current EU legislative framework aims to protect and enhance public health
in the post authorisation phase of the lifecycle of a medicine.
The EU Pharmacovigilance system
The current EU Pharmacovigilance system is supported by regulatory framework that is
comprised of the NCAs (National Competent Authorities), the EMA (European Medicines
Agency), the EC (European Commission) and a legal framework that is aimed at establishing
the responsibilities and roles along with the procedures and principles (Santoro et al. 2017). It
is to mention that EU has a very vital role to play in the field of enhancing the public health,
while stopping and managing the diseases, reducing the different sources of danger towards the

4PRINCIPLES OF DISCOVERY OF MEDICINES & DEVELOPMENT PLANNING
public health while coordinating the different health related strategies among the Member
States.
Case of Zydelig
Zydelig is a well-known cancer medicine and is typically used for treating the CLL
(Chronic Lymphocytic Leukaemia) or follicular lymphoma. CLL is an A type cancer of WBC
(white blood cells) known as B lymphocytes (Ghamlouch, Nguyen-Khac and Bernard 2017).
Although the medicine is very effective for treating the two cancer types, there are also other
risks that are associated with it. One of the most common side effects associated with the
medicine is infections like that of lung infection and cytomegalovirus infection, lymphocytosis,
diarrhoea, fever, rise in blood fat level and neutropenia. Also there are studies that evaluated
the usage of the medicine in the patients with the different lymphoma have failed two
treatments. It is effective for only 54% of the patients with the chronic Lymphocytic
Leukaemia or follicular lymphoma having either a partial or a complete response towards the
treatment (Keating 2015).
The EMA (European Medicines Agency) has noted that the data and information from
the main studies demonstrate that there is a high rates of responses with the Zydelig among the
patients suffering from the same. The medicine was also very effective in the treatment of the
patients suffering from the chronic lymphocytic leukaemia whose cancer cells have about 17p
of deletion that result in very poor outcome. With the same, it is also to mention that the safety
of the Zydelig was regarded as acceptable. The EMA agency therefore founded that the
benefits of Zydelig are way better and greater compared to the risks that are associated with it
and therefore, the agency recommended that it can be approved for the usage for the treatment
of the chronic lymphocytic leukaemia and follicular lymphoma in Europe (Yang et al. 2015).

5PRINCIPLES OF DISCOVERY OF MEDICINES & DEVELOPMENT PLANNING
However, it is to mention that the EU government and the agency also has provided a
set of recommendations and precautions that are to be followed while the use of the medicine
for the parts of both the doctors and the patients. It has been made compulsory for them to
follow the same and in this way the EU government has taken a step to ensure safe and
effective usage of Zydelig. The recommendations and precautions are given under the product
characteristics and the leaflet of the package too. With the same, like it is for all the other
medicines, the data on the usage of the medicine are monitored on a continuous basis. With the
same, the government has also taken actions to evaluate any type of side effects that are
reported with the usage of the medicine and it is also taking action to protect the patients.
Role played by the EU legislative framework in improving public health in the post
authorisation phase of the lifecycle of a medicine
While medicines bring high number of benefits to the society by means of saving
human lives and decrease their suffering, there are certain chronic drug reactions that
demonstrate a key cause of human illness and death. The case of drug zydelig demonstrates a
clear understanding about the EU legislative framework and its concern in terms of public
health in Europe (Santoro et al. 2017). It is clear that the framework is aimed at protecting and
enhancing the public health in the phase of post-authorisation of the lifecycle of a medicine. In
this way, it is continuously working towards promoting and protecting the public health in
Europe by means of a risk proportionate, proactive, patient-centred and transparent approach.
With the same, an objective behind doing this is promoting and protecting the health of public
by means of supporting the accessibility and availability of the medicines along with the ones
that fulfil the earlier unmet needs of medicines and decreasing the load of the chronic drug
reactions. This further helps in minimising the risks that are linked with the phase of post-
authorisation.

6PRINCIPLES OF DISCOVERY OF MEDICINES & DEVELOPMENT PLANNING
The legislation in this way further optimises the rational and safe usage of medicines by
means of pursuing different objectives. The very first objective is to strength the evidence base
in the phase of post-authorisation for enabling better process of regulatory decision making and
then it is to improve the patient safety by means of avoiding the unwanted risks to the patients
as an outcome of the medicines usage. According to Onken et al. (2014), the mission of EMA
is to boost the scientific excellence in the process of evaluating and supervising the medicines,
for the advantage of the public health. This is in line with the legal responsibilities and roles of
the agency in order to give the best scientific advice on questions related to the quality
evaluation, efficacy and safety of the medicinal products that are referred to it as per the EU
legal provisions. The legislation in this way further optimises the rational and safe usage of
medicines by means of pursuing different objectives. It ensures improved risk-minimisation
tools, effective post-authorisation follow-up and this further helps in completing the initiatives
of the agency in this area. In this way, it is continuously working towards promotion and
protection of the public health in Europe by means of a risk proportionate, proactive, patient-
centred and transparent approach.

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Hernandez, J.J., Pryszlak, M., Smith, L., Yanchus, C., Kurji, N., Shahani, V.M. and Molinski,
S.V., 2017. Giving drugs a second chance: overcoming regulatory and financial hurdles in
repurposing approved drugs as cancer therapeutics. Frontiers in oncology, 7, p.273.
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Keating, G.M., 2015. Idelalisib: a review of its use in chronic lymphocytic leukaemia and
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