Drug Discovery and Drug Development: Process, Steps, and Penicillin Case Study

This report explores the process and steps involved in drug discovery and development, with a case study on the discovery of penicillin. It covers target identification, preclinical research, clinical development, FDA review, and post-market monitoring. The report also discusses the challenges and complexities of drug development, as well as the importance of ensuring safety and efficacy. The report is relevant to anyone interested in the pharmaceutical industry, healthcare, or medical research.

DRUG DISCOVERY AND DRUG
DEVELOPMENT

ABSTRACT
Drug discovery and development is the long process being adapted by the researcher to
find out particular medicine that could be used to treat the patient so that they could have better
health. Discovery & Development, Preclinical Research, clinical Development, FDA review and
post market monitoring are five steps that are mainly involved in drug discovery and
development process. Furthermore, it can be stated that the penicillin was major medical
breakthrough and was first effective antibiotic that could be used to kill the bacteria. Thus, this
contribute in curing the serious illnesses were possible even if the patient is being suffering from
any type of the diseases. The discovery of penicillin drug has been done by Alexander Fleming
in 1928 by accidently, so antibiotic is word that is being used to describe the penicillin.
The study has presented crucial information related to background of the diseases, target,
drug on the market and the manner in which it can be effectively treated. Furthermore, it has
analyses, evaluate and interlink each individual step in the process of discovery and development
of the penicillin drug. At last depicted the overall key finding related to the objective of the study
and future improvement that could helps in development of drug.

TABLE OF CONTENTS
ABSTRACT.....................................................................................................................................2
INTRODUCTION...........................................................................................................................4
MAIN BODY...................................................................................................................................6
Analysis, evaluating and interlink between individual step related to process of discovery and
development of relevant drug......................................................................................................6
CONCLUSION AND FUTURE DIRECTION.............................................................................12
REFERENCES..............................................................................................................................14

INTRODUCTION
Drug discovery is the process through which the new candidate medication are
discovered, it involve key steps such as discovery and development, preclinical research, clinical
development, FDA review and post market monitoring. In another words, it is process that
involves potential development of new medicines through wide range of disciplines, chemistry,
biology and pharmacology. This is process that aim at “identifying the compound therapeutically
useful in curing and treating diseases”. Several stages followed in development of drug
contributed in making the medicine more safe, effective for being used for treatment of people.
All regulatory requirement need to be followed by the researcher while developing the drug in
order to avoid any complication in future scenario. Since many years, people make use of
different plant and mineral to treat illnesses, therefore there are various ingredients that are being
utilised to make a specific medicine (Dugger, Platt and Goldstein, 2018). Medicine are chemical
or compound that are mainly used to prevent diseases, ease symptoms and helps in diagnosis of
illnesses. With changes in trends and development of technology, there has been advancement in
the method that are used to cure patient and save their life. there are varieties of sources through
which the medicine come, likewise, there are some that mix together number of chemicals, for
example penicillin. In addition to this, introducing a new drug with a market is too complex and
time-consuming process such as it is estimated that on an average $2.6 billion and 10 years needs
to be incurred by the organisation to introduce the drugs.
Such as, for the long time the remedies are being on trial-and-error method and are being
confused about the ideas that could be work effectively to treat the patient. Over 1500 and 1600,
people Europe started making use of Opium through milky sap from the poppy plant and treat
pain. So, Laudanum is mixture of opium, herb and alcohol that contribute people in saving from
pain, coughing, insomnia and diarrhoea. In Europe, there are many type of diseases but few
medicine that really did anything so Laudanum was used to treat all problem starting from cold
to Black Plague (Ghosh and et.al., 2020). But unfortunately, it lead in becoming more addictive,
as more and more people has started in taking medicine to get cured. Then, the scientist has get
knowledge related to chemistry and biology which lead in development of pharmaceutical
medicine by 1804 by Friedrich Serturner, a German scientist. But the serturner that has been
used as medicine across worldwide in hospital has become addiction to its own drug thus people
are being warned to make careful use of it.

The target discovery of drug or the first phase is related to identification of target of specific
diseases. In another words, the target is intracellular signalling or molecular integral to gene
regulation, for example Nucleic acid sequence or may be protein. In order to decided that target
of focus research efforts, individual need to ensure molecule is druggable or activity that can
modulated by exogenous compound. Moreover, another key steps that is involved in discovery
of drug is target validation in which after the target has been selected, researcher take steps to
demonstrate about involved progress in given diseases and the activities that need to be regulated
(Hansen and et.al., 2017). It is most important and precise steps involved in success of drug
development process. Lead compound identification is process that focus on creating a
compound that could interact with selected target. So, researcher make use of screening
experiment in order to identify the possible naturally occurring compound that can be repurposed
as drug. The fourth step associated with the process is lead optimisation in which the one
compound has been identified that need to be optimised for safety and efficacy. Preclinical drug
development is also included in process of drug development in which extensive testing has been
done on animal model with an motivate to extract whether they are being safe for human trails.
Finally, clinical trial are being done to understand the positive and negative outcome of the drug
on individual (Mohs and Greig, 2017).
The main aim of the report is to understanding the
“ discovery and development of drug” and the manner in which it is being used by the people
living in the society to ensure their health and well-being. So, in short the scientific aim to have
more information related to penicillin drug discovery and development from the moment of its
discovery until released on the market stating the preclinical trials clinical trials on humans.
Along with that, what all side effects of the medicine and other improvement that could be done
related to the drug for fruitful results (Cochran, Conery and Sims, 2019). Thereby, this report
depicts significant information related to the process of discovery and development of relevant
drug in well-structured and organised manner. At last covered conclusion and future direction on
the basis of finding and evaluation that need to be adapted by the organisation and people living
within the society.

MAIN BODY
Analysis, evaluating and interlink between individual step related to process of discovery and
development of relevant drug
The secondary research has helped in knowing that there is an interlink between the
individual steps that are being taken in context of process of discovery and development of
relevant drug that could be used in medicine. Target is produced within the pharmaceutical
industry, so in general terms it is naturally existing cellular involve in pathology of interest
related to drug in development. In 2011, for the therapeutic drug target of FDA approved drugs,
435 human genome products have been identified. There are many drugs on the market that are
used for development of new medicine for health and safety of people. The four main process
that actually lead in development and process of drug overtime over time frame in the market
from initial research to be approved by FDA. The discovery of penicillin drug has been made by
the scientist named as Alexander Fleming that has saved million of lives (Steinberg and Carling,
2019). In 1922, Fleming discovered lysozyme that is an enzyme which weak antibacterial
properties that are being inhibited because of bacteria growth. Hair, tears, skin and fingernails
and other are various areas in which the Lysozyme has been found out by the scientist. So,
nearly after ten years of research in 1937, while investigation the substance and microorganism
by both Ernst Chain and Howard Florey work solely on the “Pencilling project”. In 1941, the
Albert Alexander has develop life threatening infection from cut. Initially show sign of recovery,
supply of penicillin quickly ran out thus the Albert infection returned. Initially US
pharmaceutical companies is reluctant to commitment to large scale penicillin production. But
eventually the demand of the penicillin has increased that contribute in more development.
After trial and error of three years they have developed the pure penicillin and started
trialling on animal to find out the outcome and make necessary changes. Likewise, in 1940 there
are only four that have given pencilling survived out of eight mice that has been infected with
deadly streptococci bacteria. With the first human trial of penicillin the consequence of team
production problem and shortage of penicillin has become apparent (Steinberg and Carling,
2019). Over past 40 years, the complexity in drug development has increased in manifold as it
require preclinical testing, investigation of new drug application, clinical test before marketing

approval from FDA. There are five key steps that are involved in development and process of
drug and each of them are interlinked with another. Likewise,
Step 1: Discovery and Development
Step 2: Preclinical Research
Step 3: Clinical Development
Step 4: FDA Review
Step 5: FDA Post-market Safety Monitoring.
Are the five stages that has been followed by the researcher to develop new drug that could be
supply to the people for their cure and treatment.
Discovery and development is the first steps that analysis the new insight and
technologies that are present in external environment and the manner in which they could be
possible used to find alternative method to make treatment of diseases. In another words, the
discovery of the drug helps in understanding the way new medicine has been discovered.
Historically, the drug has been found by identifying the active ingredient that are made from
traditional medicine, then classical pharmacology is being utilised to investigate chemical
libraries. Furthermore, the Human DNA was sequenced, reverse pharmacology has been used to
found remedies for existing diseases by doing testing. There are various factors that has
contributed in spur drug discovery such as diseases processes, existing treatment, molecular
compounds test and new technologies (Ileana Dumbrava, Meric-Bernstam and Yap, 2018).
Likewise, in start with thousand of different compounds that are being narrow down with time
frame, so after the promising compound are been identified and determined, the development
phase of drug started. Many detailed things needed to be considered while development of drug
to avoid its negative impact to maximum extend. So, efforts need to be learned more about the
dosage amount drug should be, the way it is effective and what are its potential side effects.
While, in current scenario, the development of drug involves screening hits, optimisation of hit
in order to reduce the potential side effect of drug and medicinal chemistry. All these has
contributed in improving the oral bioavailability, metabolic stability and efficacy through
effectively following the drug development process.

Target identification and validation helps in identification of specific gene or protein
that plays significant role in diseases in context of making record of therapeutic characteristic.
Target are unusable as drug, efficacious and safe and capable of meeting commercial and clinical
requirement. In order to validate the target, researcher make use of different method such as cell-
based molecules, signalling pathway analysis, functional analysis and diseases association. The
excellent source of drug discovery target are Duolink PLA and Sanger Whole
Genome CRISPER library. Hit discovery process is step that is being followed after target
validation to compound screening assay are developed (Devine and et.al., 2018). Assay
Development & Screening are test system evaluate effect of new drugs candidate at molecular,
cellular and biochemical levels. High throughput screening make use of robotics, data
processing and control software, sensitive detectors and liquid handling devices to rapidly
conduct millions of pharmacological, genetic test and eliminating the hours of painstaking
testing by scientist. It helps in identification of antibodies, active compounds and genes that
adversely affect the human molecules. Hit to lead process is also involved in discovery and
development of drug, in which small molecule hit from HTS are being evaluated and optimised
in limited way to lead compound. Lead optimisation is process that is used to synthesized and
modified in order to improve the potency and reduce the side effect of the drug that are being
manufactured. In this experimental testing is being done through making use of ADMET tool
and animal efficacy model in order to design the drug candidate (Torshizi and Wang, 2018).
Active pharmaceutical ingredients can be said as biologically active ingredients in drug
candidate that product effects, maximum number of drug are being developed through making
use of API. While the HP API i.,e High Potency Active Pharmaceutical Ingredients are molecule
that are much more effective at smaller dosage level in comparison with the standard of API.
Pharmacological potency, occupational exposure limits and toxicity are the basis on which the
drug are being classified and used in complex drug development having more than 10 steps.
The second steps related to discovery and development of drug is preclinical
research so that they can be easily provided to the people for their respective treatment. Once
the lead compound is being completed then the drug development process start with preclinical
research in order to determine the efficacy and safety of drugs. As provide the drug before
testing may results in potential serious health problem on the individual (Jackson, Czaplewski
and Piddock, 2018). In it the scientist makes test of new ideas for biomedical prevention

strategies in laboratory experiment or in animal. In 1928, it was fond that penicillin, in the form
of broth extracted from the mould when given to rabbits was fond to be non- toxic. In the 1940s,
pre- clinical trial of penicillin was performed on mice. This experiment was performed by
Heatley and his colleagues which played a key role in providing information about effect of
penicillin in vivo. A fatal dose of group A streptococcus was injected into eight mice. After a
duration of 1 hour, a single dose of 10 mg penicillin was injected in 2 mice while 5 mg was
given to another set of 2 mice. Following it, the mice were administered with three additional
doses of 5 mg penicillin at duration of 3, 5, 7 and 11 hours post infection ( Lobanovska and Pilla,
2017). In this experiment, four mice were not given penicillin and these served as controls. After
seventeen hours of initial infection, the mice in the control group died while those who received
a penicillin dose, survived. Through this observation, it was evident that penicillin is a potential
life- saving drug. This proof that penicillin contained antibiotic properties against bacterial
infections became the basis for its purification and mass production.
After completion of the preclinical research, the researcher have move to clinical drug
development by including volunteer studies, clinical trials to finetune the drug that could be used
for human. Clinical research is drug that is ready to be tested on the human being, so it is only
the method or way of knowing manner in which the person body will react to the drug. Lot of
work, planning and effort need to be made for planning clinical research such as number of
people that have participated, type of assessment and how long testing would be last.
Furthermore, it can be stated that the anything done while clinical research must meet with FDA
standards (Vamathevan and et.al., 2019). This complexity of clinical trial design, implementation
issue and associated cost are some of the reasons that could affect on trial carried during the
phase. So, necessary step has been taken to ensure that the clinical trial must be efficacious, safe,
and completed in accordance with the drug development budget by making use of effectively
methodology to ensure drug work the manner in which it has been intended (Tyers and Wright,
2019). At the same time the clinical research contributes in understanding or determining the
medication effectiveness through clinical examine the single ascending, multiple dose studies
and dose escalation in order to determined the best patient dosage.
Furthermore, this step has involved three phases for drug development such as Healthy
Volunteer Study and Studies in Patient Population. Such as it is the first phase of Healthy

Volunteer in which the drugs are being tested on human being that has involved less than 100
volunteers to effectively assess the safety, absorption, elimination effect on the body, along with
it the side effect for safe dosage range. While the phase 2 involves assessment of drug safety and
efficiency in respect to 100-500 patient that are receiving the standard drug previously used in
the treatment. So, this has helped in optimal dose strength through creating schedules, making
record of adverse events and risk associated with the drug for suggesting the best to the patient
or individual (Chopra and Sahu, 2019). In addition to this, third phase has enrol around 1000-
5000 patient that enable the medication labelling and proper instruction for effective use of
drug. The trial in the Phase 3 has required extensive collaboration with organisation such as
Institutional Review Board (IRB) and Institutional Review Board (IRB). Along with it, all the
rule and regulation need to be anticipated in full production of drug. Moreover, Biological
Samples Collection, Storage & Shipment, the clinical trial process involves collection, store and
shipping of biological samples from testing sites according to global standard and regulation.
Other temperature stabilising method and dry ice packs may be required for transport containers
that are having biological sample. Hence, there is different requirement apply to different types
of biological aspects. Pharmacodynamic (PD) Biomarkers are molecular that indicate about the
effect of drug on target human area, also link between the biological responses and drug
regimen. Thus, it contributed in effectively selecting the rationale combination of targeted
agents, optimisation of drug regimens and schedule (Berdigaliyev and Aljofan, 2020).
Pharmacokinetic Analysis is experimental trial that helps in determining the way new
drug behave in human body. Such as compartmental modelling helps in identification of volume
of distribution, terminal half-life and clearance. Bioanalytical Method Development and
Validation helps in detecting the metabolites and analytes with a motive to determine the
efficacy and safety of the drug. Sample collection, analysis, detection and clean up are consist in
bioanalytical assay. Human drug efficacy, biological sample are determined through stability,
while drug and drug metabolites are susceptible to degradation that lead in lowering the
concentration of drug over life of the drug (Abraham and Myers, 2021). Plasma, feces, urines
are some of the biological samples that are used to determine and analysis the properties and
effect of drug and its metabolites on human being. At the same time, necessary steps has been
taken to ensure that human are being protected while clinical trails, adverse event must be
reported to IEC/IRB regulates and ensure their safety.

FDA Review is done after the preclinical and clinical research has represented that the
drug are both safe and effective to be used by the researcher. The developer of the drug can
submit the research to FDA, In another words, approval from FDA of new drug will helps in
effectively market the same. For medication review, a new drug application should be submitted
with complete detailed information about the type of medicine. Moreover, the application have
all key information or finding starting from prior stage, at the same time before approval of new
drug the FDA require more study or may ask additional questions. 6-10 months are required to
complete the review so it is integral part of developing a drug. But even after the approval of
drug by the FDA there may be chances of continuous monitoring of its safety (Li and et.al.,
2018). The FDA performed all crucial activities in order to ensure that the drug are being reach
safe on market by watching the manner in which they have been advertised and if any issue is
associated with it. So in case any of the problem occur with the drug FDA take necessary steps to
overcome the same and delivered maximum benefits to the people. Likewise, the application and
necessity of drug for the patient are two factor on which the new drug regulatory approval
timeline is done such as fast track, standard and accelerated approval. The approval time can be
upto one year if the standard or priority review is being required as compared accelerated
approvals, fast track and many more. BLA application must be submitted to the FDA after the
clinical trial has demonstrated the drug efficacy and safety. So, it studies data, take decision
related to whether the specific grant need to be approved or not. Furthermore, the orphan drug
are being intended to treat the diseases in effective manner but these drug may not get quick
approval.
Reliable Pharmaceutical development is the last stage of drug development that explained
that it is easy to see the number of efforts and work that has been implemented in order to
developed new drugs. Development of pharmaceutical is complex process that involves why a
particular thing is being offered, approve of multiple drugs, analysis of their outcome or effect on
health and well-being of individual living in the society. Post market monitoring is stage that is
accomplished or start when the drug approval and manufacturing has been done as per
requirement of FDA. This organisation needs to monitor the safety of its drug through making
use of FDA Adverse event reporting system database, this helps in effective implementation of
post marketing safety surveillance program (Li and Lou, 2018). Therefore, it can be stated that

this process helps in effectively reporting the associated problem with approved drugs by the
health professionals, consumers and manufacturers.
In 1946 the penicillin drug has become available in United Kingdom to people use for the
first time that has led in making transformation in medicine across worldwide. At the same time
the bacteria have also evolved to become resistant to penicillin and other antibiotics. Therefore,
currently the scientist are facing issue related to development of new antibiotics (Muttenthaler,
and et.al., 2021).
CONCLUSION AND FUTURE DIRECTION
From the above report it can be concluded that development of the drug by researcher is
through getting new insight about the diseases process to find out alternative method that could
be used to overcome the diseases. Penicillin heralded has dawn of antibiotic age, as before its
introduction of there has been no effective treatment for infection likewise, the rheumatic fever,
gonorrhoea and pneumonia. At the same time, many test of molecular compound are being done
to extract possible beneficial effects against large number of diseases. The drug development
process involves five stages such as Discovery & Development, preclinical research, clinical
development, FDA review and post market monitoring. Discovery of the drug has also helped in
changing the course of modern medicine significantly as before there has been limited treatment
to cure patient. At the same time the antibiotic resistance crises has also helped in understanding
that the how dangerous could a world without antibiotics. So, it encouraged further discovery of
the drug for people. The study has also helped in learning that lot of time, efforts need to be
invested to develop and bring drug in the market. Therefore, the main motivate behind the
development of penicillin drug is to bring more efficient and safer treatment for the patient as
quickly as possible by making use of medical evaluation.
Future direction for improving the process of discovery and development of the drug is
that chemical entities that have potential to become therapeutic agents. Discovery of drug is also
being done through analysing the existing treatment available that have unanticipated effects on
human being. New technology and method also contribute in providing new ways of targeting
medical products to specific sites within the body. While, it can be stated that the penicillin drug
are being developed by identifying the potential benefits, mechanism of action and the way it is
absorbed, metabolised and excreted. Development also take place to understand what are the best

method that could be used to provide drug to the patient for its better outcome. Moreover, with
increase in number of diseases, the scientist are involved in race of find and developing new
antibiotics that can be used to treat patient. At last, it can be concluded that cooperative efforts
made by all such as healthcare professional, government and other individual can easily
contribute in encouraging the development of penicillium drug to cure and treat people living in
the society.

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