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Students Activity Sheet #1

Name: _________________________________________________________________ Class number: _______

Section: ____________ Schedule: ________________________________________ Date: ________________

Lesson title: Overview of Drug Discovery and Development & Materials:

Understanding the Biology of the Disease {Pen, highlighters, & students
Lesson Objectives: activity sheet}

At the end of the lesson, you should be able to: References:

1. Discuss important terms related to drug discovery and 1. Mahan, Vicki. (2014). Clinical
development, appropriate terms associated with health and Trial Phases. International Journal
disease. of Clinical Medicine. 05.
2. Discuss the classification, basic characteristic features of 1374-1383.
diseases. 10.4236/ijcm.2014.521175
3. Identify the drug discovery processes. 2. Ahmed, N. (2007). Biology of
4. Describe different stages of drug development processes. disease. New York: Taylor &
Francis. Retrieved July 22, 2020,
3. Zhong W.Z., Zhou S.F. Molecular
science for drug development and
biomedicine. Int. J. Mol.
Sci. 2014;15:20072–20078.
doi: 10.3390/ijms151120072
[email protected]

Productivity Tip: Start training yourself to take this as a challenge. Do not take this as a burden. What you
input in your heart and brain will reflect in your performance. Use your talents to your advantage. Sing out
some terms, Make stories, or draw the concept. Try to collaborate your hobbies with your studies to make
things fun.

A. LESSON PREVIEW/REVIEW
Introduction ( 3 mins)
Drug discovery is the process through which potential new therapeutic entities are identified, using a
combination of computational, experimental, translational, and clinical models (see, e.g., Despite advances in
biotechnology and understanding of biological systems, drug discovery is still a lengthy, costly, difficult, and
inefficient process with a high attrition rate of new therapeutic discovery. Drug design is the inventive process
of finding new medications based on the knowledge of a biological target. In the most basic sense, drug design
involves the design of molecules that are complementary in shape and charge to the molecular target with
which they interact and bind.

Biology of Disease is concerned with the scientific study of disease, and is one of the foundations of
medical science and practice. It encompasses all aspects of disease, including knowledge of the causes and
effects of disease, and the organism's response to disease. Proper knowledge of the causes and effects of
disease allow researchers to design a product to stop or reverse the effects of the disease. Drug discovery is
important because it aims to recognize new molecular entities that may be of importance in the treatment of
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diseases.

Activity 1: What I Know Chart, part 1 (5 mins) Answer only the first column, “What I know”. Leave the third
column “What I Learned” blank at this time.
What I Know Questions: What I Learned (Activity 4)
1. What is an Active
pharmaceutical ingredient?
2. Why do drugs have to undergo
keen observation before
introduced to the market?
3. Does every disease have a
pathogenesis? (Yes, they have,
No, they don`t.)

B.MAIN LESSON
Activity 2: Content Notes (66 mins)

DRUG DEVELOPMENT
The entire process of taking a newly discovered compound or drug through regulatory approval to the
point of marketing. During the development, the new drug or the compound should adhere to high standards in
the conduct, analysis and interpretation of preclinical and clinical studies for its smooth passage through the
regulatory approval phase and eventually to marketing. Pathways of drug development are discovery,
pre-clinical development and clinical development. It is the mission of pharmaceutical research companies to
take the path from understanding a disease to bringing a safe and effective new treatment to patients.
Scientists work to piece together the basic causes of disease at the level of genes, proteins and cells. Out of
this understanding emerge “targets,” which potential new drugs might be able to affect. This whole process
takes an average of 10-15 years.

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1. Discovery & Development

1.1 Target Identification & Validation

Target identification finds a gene or protein (therapeutic agent) that plays a significant role in disease.
When identified, therapeutic characteristics are recorded. Targets are efficacious, safe, usable as drugs, and
capable of meeting clinical and commercial requirements. Researchers use disease association, bioactive
molecules, cell-based models, protein interactions, signaling pathways analysis, and functional analysis of
genes to validate targets, or in vitro genetic manipulation, antibodies, and chemical genomics.

1.2 Hit Discovery Process

Following target validation, compound screening assays are developed.

1.3 Assay Development & Screening

Assays are test systems that evaluate the effects of the new drug candidate at the cellular, molecular, and
biochemical levels.

1.4 High Throughput Screening

High Throughput Screening (HTS) uses robotics, data processing/control software, liquid handling devices,
and sensitive detectors to rapidly conduct millions of pharmacological, chemical, and genetic tests, eliminating
hours of painstaking testing by scientists. HTS identifies active compounds, genes, or antibodies that affect
human molecules.

1.5 Hit to Lead

In the Hit to Lead (H2L) process, small molecule hits from an HTS are evaluated and optimized in a limited
way into lead compounds. These compounds then move on to the lead optimization process.

1.6 Lead Optimization

In the lead optimization (LO) process, the lead compounds discovered in the H2L process are
synthesized and modified to improve potency and reduce side effects. Lead optimization conducts
experimental testing using animal efficacy models and ADMET tools, designing the drug candidate.

1.7 Active Pharmaceutical Ingredients

Active pharmaceutical ingredients (APIs) are biologically active ingredients in a drug candidate that
produce effects. All drugs are made up of the API or APIs and excipients. (Excipients are inactive substances
that deliver the drug into the human system.). High Potency Active Pharmaceutical Ingredients (HP APIs) are
molecules that are effective at much smaller dosage levels than standard APIs. They are classified based on
toxicity, pharmacological potency, and occupational exposure limits (OELs), and used in complex drug
development involving more than ten steps.

The drug discovery process ends when one lead compound is found for a drug candidate, and the process of
drug development starts.

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2. Preclinical Research
Once a lead compound is found, drug development begins with preclinical research to determine the efficacy
and safety of the drug. Researchers determine the following about the drug:

• Absorption, distribution, metabolization, and excretion information

• Potential benefits and mechanisms of action
• Best dosage, and administration route
• Side effects/adverse events
• Effects on gender, race, or ethnicity groups
• Interaction with other treatments
• Effectiveness compared to similar drugs

3. Clinical Development
Once preclinical research is complete, researchers move on to clinical drug development, including clinical
trials and volunteer studies to fine-tune the drug for human use.

3.1 Phase I – Healthy Volunteer Study

3.2 Phase II and Phase III – Studies in Patient Population

3.3 Pharmacodynamics (PD) Biomarkers

PD biomarkers are molecular indicators of the drug’s effects on the target human area, and link
drug regimen and biological responses. This data can help select rational combinations of
targeted agents and optimize drug regimens and schedules. Rationality and hypothesis-testing
power are increased through the use of PD endpoints in human trials.

3.4 Pharmacokinetic Analysis

Pharmacokinetic analysis is an experimental trial that determines the theory of how a new drug
behaves in the human body. The volume of distribution, clearance, and terminal half-life are
defined through compartmental modeling.

3.5 Bio analytical Method Development and Validation

Bio analytical methods detect analytes and metabolites such as drug or biomarkers in biological
or human samples to determine drug efficacy and safety. The complete bio analytical assay
consists of sample collection, clean-up, analysis, and detection.

3.6 Patient Protection – GCP, HIPAA, & Adverse Event Reporting

Human patients must always be protected during clinical trials, and Good Clinical Practices (GCP), the
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Health Insurance Portability and Accountability Act (HIPAA), and adverse event reporting to IEC/IRB regulates
and ensures their safety.

4. FDA Review

Once the new drug has been formulated for its best efficacy and safety, and the results from clinical trials are
available, it’s advanced forward for holistic FDA review. At this time, the FDA reviews and approves, or does
not approve, the drug application submitted by the drug development company.

5. Reasons for Drug Failure

New drug applications may fail for a variety of reasons, including toxicity, efficacy, PH properties, bioavailability,
or inadequate drug performance.

Toxicity: If the toxicity of a new drug is too high in human or animal patients, the drug may be rejected
due to safety concerns about its use following manufacture.

Efficacy: If a new drug’s efficacy is not high enough or evidence is inconclusive, the FDA may reject it.

PK Properties or Bioavailability: PK properties or poor bioavailability due to low aqueous solubility, or

high first-pass metabolism, may also cause a drug to fail FDA review. PK causes of drug failure include
inadequate action duration and unanticipated human drug interactions.

Inadequate Drug Performance: If the new drug performs the desired function, but only at a shallow
level, the FDA may reject the application in favor of a formulation that performs better.

6. Post-market Monitoring
Following drug approval and manufacturing, the FDA requires drug companies to monitor the safety of its drug
using the FDA Adverse Event Reporting System (FAERS) database. FAERS helps FDA implement its
post-marketing safety surveillance program. Through this program, manufacturers, health professionals, and
consumers report problems with approved drugs.

UNDERSTANDING OF THE BIOLOGY OF THE DISEASE

TERMS:
● DISEASE
- Can be defined as any abnormality or failure of the body to function properly and this may require
medical treatment. The scientific study of diseases is called pathology.

● HEALTH
o Can be defined as an absence of signs and symptoms associated with any disease. This
definition has limitations in that there are circumstances where individuals believe they are ill
even though detectable indications of disease are not present.
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o Conversely, there are individuals who believe they are healthy but on detailed examination are
found to suffer from a serious disease.
For this reason, the World Health Organization (WHO) devised the more appropriate definition of health as a
state of physical, mental and social well-being and not merely the absence of disease

CHARACTERISTIC FEATURES OF DISEASES

● Etiology
o Refers to the cause of a disease.
o Etiological agents can be endogenous, in other words originating from within the body, or
exogenous, coming from outside the body.
o Endogenous agents include genetic defects and endocrine disorders, while exogenous agents
include microorganisms such as viruses, bacteria and fungi that cause infections, chemicals,
physical trauma and radiation.
o Many diseases are of unknown cause and are said to be idiopathic. An example of this is
hypertension, where more than 90% of cases are of unknown cause. The treatment of
idiopathic diseases is restricted to alleviating the symptoms.
o Some conditions are caused by the effects of treatment and are called iatrogenic diseases
(from the Greek word iatros, doctor).
o Occasionally a disease of unknown etiology is more commonly found in populations with
certain dietary, occupational or lifestyle conditions called risk factors.
▪ Smoking is a significant risk factor in the development of heart disease and lung
cancer. Some risk factors may be important in the development of the disease whereas
others may make the individual more susceptible to disease.

o Predisposing factors are conditions or situations that make an individual more susceptible to
disease. They include age, sex, heredity and environmental factors.
▪ Some diseases increase the risk of developing others. Thus some conditions increase
the risk of someone developing cancer and are said to be premalignant.
▪ This is seen in ulcerative colitis, an inflammatory condition affecting the large intestine
that increases the probability of developing bowel cancer in sufferers
▪ Some diseases predispose the patient to other conditions by allowing infectious agents,
not normally pathogenic, to cause disease.
▪ This is seen in opportunistic infections where a decline in the immunological functions
of an individual makes them susceptible to infections by microorganisms that are
normally nonpathogenic.

● Diseases are often described as being primary or secondary.

o Primary may refer to a disease of unknown cause or idiopathic, whereas secondary is used
to refer to a condition that arises from an existing disease. However, these terms are also often
used to describe the stages of a disease.

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● Every disease has a pathogenesis that describes the development of the disease or, more
specifically, how the etiological agent(s) acts to produce the clinical and pathological changes
characteristic of that disease.

Diseases have ‘natural histories’ that describe the typical patterns of how each disease usually progresses, its
effects and its duration. The effects of the disease on the patient are referred to as morbidity. The mortality of a
disease describes its possibility of causing death. This is usually expressed as a percentage. Some diseases
have a rapid, often severe onset that is described as acute. However, other diseases have a chronic onset and
develop gradually over a relatively longer time.

MANIFESTATIONS OF DISEASES

● The etiology of a disease and its pathogenesis produce clinical manifestations that include signs and
symptoms of the disease. A symptom is an indication that a disease is present and something of which
the patient complain.
● A sign is something that the clinician specifically looks or feels for. The term syndrome is often
applied to describe certain diseases that are characterized by multiple abnormalities that form a distinct
clinical picture

OUTCOME OF A DISEASE
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● The prognosis of a disease is its likely outcome. Prognoses can vary considerably between different
diseases and, of course, can be influenced by treatment. Hence when giving a prognosis, it is
necessary to clarify if the disease is following its natural course or whether there is, or needs to be,
medical or surgical intervention.
● A viral disease such as German measles (rubella) will normally resolve of its own accord, whereas a
broken leg or a heart attack needs treatment. With some diseases, especially some cancers, patients
may go through a period of good health with a reduction or disappearance of the symptoms and the
disease is said to be in remission. However, a relapse may occur with a return of the disease symptoms
following this period of apparent recovery. Diseases with a tendency towards remission and relapse
include acute lymphoblastic leukemia and ulcerative colitis.

CLASSIFICATION OF DISEASES

● Infectious-are caused when microorganisms such as viruses, bacteria, fungi, protozoa and helminths
enter and spread within the body.
● Immunological- occur in circumstances in which the immune system can cause damage to the body’s
own tissues
● Endocrine- arise from the over- or underproduction of hormones or from resistance to a particular
hormone perhaps because the cellular receptor is absent as the result of a mutation.
● Homeostatic- arise when mechanisms for controlling homeostasis are disrupted Nutritional- result from
an inadequate intake of nutrients.
● Toxic- are caused by the ingestion of a variety of poisons that may be encountered in the environment
Genetic- arise due to defects in the genes or chromosomes of individuals.
● Congenital- present at birth and may or may not have been inherited. They may arise due to a
developmental defect of known or unknown cause.
● Neoplastic- are characterized by the uncontrolled and abnormal growth of cells.
● Traumatic- are caused by physical injury and include mechanical trauma, extremes of heat or cold,
electrical shock and radiation.
● Degenerative- involve the progressive loss of body tissues and impairment of their functions usually
associated with aging.
● Psychogenic-originate in the mind. They may have a significant psychological or emotional
component.
● Iatrogenic- arise as a consequence of treatment. Idiopathic- are those of unknown cause.

INVESTIGATING DISEASES

● Proper investigation of disease is necessary to ensure a rapid and accurate diagnosis and to allow
appropriate treatment to be initiated as soon as possible.
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● The examination usually begins with the clinician asking the patient about his or her current and past
medical histories, current and previous medications, use of alcohol and tobacco, any family history of
disease and possibly occupational history. This is usually followed by a clinical examination to look for
signs of any abnormality.

● Since diseases typically present with recognizable signs and symptoms, the clinician may make a
diagnosis of the disease based on the clinical history and the examination and then initiate treatment. A
range of diagnostic services is also available to the clinician in modern health care systems.

Activity 3: Skill-building Activities (with answer key) ( 18mins + 2mins checking)

A. Analyse the definition for each terms. check the “T” box if it`s true and if it`s false Check the “F” Box and
write the correct definition of the term in the space beside the “T and “F” Boxes. Check your answers against
the Key to Corrections found at the end of this SAS. Write your score on your paper

Example.

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Palliative care To tell the family that there is a drug for cancer that can cure.
T ✔ F Palliative care is an approach that improves the quality of life of patients and their
families facing the problem associated with life-threatening illness

1. Active Pharmaceutical are biologically active ingredients in a drug candidate that produce effects.
Ingredients

T F

2. Pharmacokinetic are molecular indicators of the drug’s effects on the target human area, and link
drug regimen and biological responses.
T F

Occasionally a disease of unknown etiology is more commonly found in

3. Predisposing factors populations with certain dietary, occupational or lifestyle conditions called
predisposing factors
T F

4. Iatrogenic arise as a consequence of treatment. Idiopathic- are those of unknown cause.

T F

B. Differentiate the terms.

Ex. (Good & Bad – A pleasing action is called good. An inappropriate action is called bad.)

Disease & Health

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Active
pharmaceutical
ingredients &
Excipients

Exogenous agents &

Endogenous agents

Activity 4: What I Know Chart, Part 2 (4 mins) Instruction: To review what was learned from this session,
please go back to Activity 1 and answer the “What I Learned” column. Notice and reflect on any changes in
your answers.

Activity 5: CHECK FOR UNDERSTANDING (15 mins)

Instruction: Now it’s time for you to figure this one out on your own! Take time to read, analyse, and
understand the following scenarios. Choose your answer & write the letter beside the number.

____1. What is the purpose of pre-clinical testing?

a. To verify that a drug is sufficiently safe and effective to be tested in humans.
b. To undergo preliminary testing in healthy humans to monitor the effects of the drug.
c. Obtain FDA approval to test the drug in humans.
d. B and C

____2. Compounds “drop out” of the process because:

a. It took 25 years
b. Too expensive
c. Lack of efficacy
d. B and C

____3. Obtain FDA approval to test the drug in human

a. Pre-clinical testing
b. IND
c. Clinical trials
d. ANDA

____4. Which of the following is/are part of development process?

a. Pre-clinical
b. Clinical trials
c. IND
d. A and B
e. B and C

____5. In this stage, it is important to understand the disease.

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a. Pre-discovery
b. Discovery
c. Pre-clinical
d. Clinical

____6. FDA reviews all pre-clinical testing and plans for clinical testing to determine if the drug is safe enough
to move to human trials.
a. Clinical trials
b. Ongoing studies
c. IND
d. Pre-clinical

____7. Monitor the drug as it is used in the larger population to catch any unexpected serious side effects.
a. Clinical trials
b. Ongoing studies
c. IND
d. Pre-clinical

____8. The goal is formulation, scale up and production of the new medicine.
a. Clinical trials
b. Ongoing studies
c. IND
d. Manufacturing

____9. A drug is any substance that alters normal bodily function. A chemical substance of unknown structure
a. 1st statement is correct, 2nd statement is wrong
b. 1st statement is wrong, 2nd statement is correct
c. Both statements are correct
d. Both statements are wrong

____10. The entire process of taking a newly discovered compound or drug through regulatory approval to the
point of
marketing.
a. Drug discovery
b. Drug development
c. Drug marketing
d. AOTA

____11. The following are examples of symptom except:

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I. Nausea
II. Pain
III. Cough
IV. Fever
a. I,II,III
b. II,IV
c. AOTA
d. NOTA

____12. Characterized by the uncontrolled and abnormal growth of cells. These cells form benign or malignant
tumors Diagnostic test;
a. Degenerative
b. Neoplastic
c. Toxic
d. Homeostatic
e. A and B
____13. The term used to describe the cause of a disease is:
a. Manifestation
b. Etiology
c. Pathogenesis
d. Mortality
e. Epidemiology

____14. The following are predisposing factors except:

a. Age
b. Sex
c. Heredity
d. Lifestyle conditions

15- 20: What are the classification of disease?

ANSWER::_______________________________________________________________________________
________________________________________________________________________________________
________________________________________________________________________________________
___________________________

C. LESSON WRAP-UP

Activity 6: Thinking about Learning (5 mins)

A. Work Tracker You are done with this session! Let’s track your progress. Shade the session
number you just completed.
P1 P2
1 2 3 4 5 6 7 8 9 10
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B. Think about your Learning. Tell me about your thoughts! Today we talked about Drug Discovery and
Development & Understanding the Biology of the Disease. What surprised you about the lesson today? How
can you apply it to your profession?

_____________________________________________________________
_____________________________________________________________
_____________________________________________________________
_____________________________________________________________
_____________________________________________________________
________________________________________________________.

FAQs

1.) What was the first modern pharmaceutical medicine & what was it used for? The first modern,
pharmaceutical medicine was invented in 1804 by Friedrich Sertürner, a German scientist. He extracted the
main active chemical from opium in his laboratory and named it morphine, after the Greek god of sleep.
Doctors used morphine to treat severe pain, and we still use it for that purpose in hospitals today.
©Health technology, Science

2.) How do you study diseases? There is a lot of answer to it but one of the things scientists use is research
organism A research organism is any creature that scientists use to study life. Examples range from those with
just one cell, such as bacteria, to more complex ones, such as mice. Research organisms have many of the
same genes as human beings. When scientists discover a link between a particular gene and a human
disease, they typically find out what that gene does in a research organism. These findings can provide
important clues about what causes a disease and help to develop potential diagnostic tools and treatments that
are later tested in clinical trials.
©National Institute of General Medical Sciences

KEY TO CORRECTIONS
Activity #3

A. answer key NOTE: Answers may vary.

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B. NOTE: Answers may vary.

1,Disease & Health
-Disease - Can be defined as any abnormality or failure of the body to function properly and this may require
medical treatment
-health- Can be defined as an absence of signs and symptoms associated with any disease.
2. Active pharmaceutical ingredients & Excipients
-Active pharmaceutical ingredients (APIs) are biologically active ingredients in a drug candidate that produce
effects. excipients. (Excipients are inactive substances that deliver the drug into the human system.).
3. Exogenous & Endogenous agents
Endogenous agents in other words originating from within the body, exogenous, coming from outside the body.

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