Questions on drug discovery and development

1. How are drugs discovered and developed.

 Chosen a disease
 Identification of drug target
 Identify a bioassay
 Identification of a lead compound
 Structural activity relationship
 Lead optimization
 Preclinical trial
 Investigational new drug application ( patent the drug)
 Clinical trail
 Regulatory approval
 Post approval monistoring
2. What are orphan drugs
 Orphan drugs are medications that are developed to treat rare
diseases or conditions that affect fewer than 200,000 people
in the United States
i. Give three reasons for the successful implementation of
the orphan drug act by pharmaceutical industries.
Three reasons for the successful implementation of the Orphan
Drug Act by pharmaceutical industries are:
 Tax incentives for research and development of orphan
drugs.
 Waiver of FDA fees for orphan drug applications.
 Seven-year market exclusivity for approved orphan drugs
3. What do you understand by the following terms as used in drug
discovery and development.
i. Bioassay;
A test that measures the biological activity of a substance
by its effect on living cells or tissues ¹.
 ii. Lead compound;
A chemical compound that shows promising activity
against a biological target and is used as a starting point for
drug development.
iii. Pharmacophore;
The part of a molecule that is responsible for its
biological activity and binds to a specific receptor.
iv. Drug patent’
Drug patent: A legal protection granted to the inventor of
a new drug that prevents others from making, using, or
selling the drug for a certain period of time.

4. What do you understand by structural activity relationship of a

drug;
is the relationship between the chemical structure of a drug
and its biological activity

i. Give three importance of SAR in drug discovery and

development:
 To optimize the potency of a drug by modifying its chemical
structure.
 To improve the selectivity of a drug by modifying its
chemical structure.
 To reduce the toxicity of a drug by modifying its chemical
structure.

5. List and explain 5 possible reasons for poor efficacy of drug

candidate in in vivo model:
 Poor pharmacokinetics (absorption, distribution, metabolism,
and excretion).
 Inadequate dosing.
 Lack of target engagement.
  Inappropriate animal model.
 Poor translation from in vitro to in vivo
6. Give two limitation of computer aided drug design:
 They do not allow conformational movement in the target.
 Inaccurate representation of the reality since the lack of
consideration of the dynamic nature of biological systems
7. Thalidomide is actually a mixture of two compound, draw their
structures and list the physiological effect of each:
Thalidomide is a mixture of two compounds, (R)-thalidomide and (S)-
thalidomide. The physiological effects of each compound are:
 (R)-thalidomide: Sedative and antiemetic effects.
 (S)-thalidomide: Teratogenic effects
8. Explain how structural based design was used to developed an
inhibitor with improved selectivity for TACE over MMP – 1
and MMP – 9:
 By identifying the structural differences between the active
sites of the enzymes and designing a molecule that
selectively binds to the active site of TACE
9. How can the pharmaceutical industry increase the probability
if technical success (p(TS)). By:
 Focusing on drug targets with a high probability of success.
 Using predictive models to identify potential safety and
efficacy issues early in the development process.
 Using biomarkers to monitor the safety and efficacy of
drugs in clinical trials
i. What are the major causes of phase ii and phase iii
attrition:
 Lack of efficacy.
 Safety issues.
 Poor pharmacokinetics.
 Inadequate dosing
 10. What is investigational new drug application:
is a request for authorization from the FDA to
administer an investigational drug or biological product to human after
a successful preclinical trial.
i. Give the three main types of IND and explain:
 Investigator IND: Filed by a physician who both initiates and
conducts an investigation, and under whose immediate
direction the investigational drug is administered or
dispensed.
 Emergency Use IND: Allows the FDA to authorize use of an
experimental drug in an emergency situation that does not
allow time for submission of an IND.
 Treatment IND: Allows patients with serious or life-
threatening conditions to gain access to experimental drugs
prior to final FDA approval
ii. What is IND
11. What is new drug application and what is it goal:
is a request for FDA approval to market a new drug in the United
States, it involve all detail information such as what was doing during
clinical test, the component of the drug, the behavior of the drug in the
body, preclinical result and how the drug is been manufactured,
processes and package. The goal of an NDA is to demonstrate that the
drug is safe and effective for its intended use.
- The FDA reviewer approves a new drug application after
reviewing the data from preclinical studies and clinical trials and
determining that the benefits of the drug outweigh its risks
i. What are the decision which allow FDA reviewer to approve a
new after reviewing the new drug application:
The goals of the NDA are to provide enough information to permit
FDA reviewers to reach the following key decisions:
 Whether the drug is safe and effective in its proposed use(s),
and whether the benefits of the drug outweigh the risks.
  Whether the drug's proposed labeling (package insert) is
appropriate, and what it should contain.
 Whether the methods used in manufacturing the drug and the
controls used to maintain the drug's quality are adequate to
preserve the drug's identity, strength, quality, and purity.

12. What do you understand by abbreviation of new drug

application and give it significance in drug discovery and
development:
This are which is submitted to FDA for the review and
potential approval of generic drug product.
i. What is a generic drug product:
 A generic drug product is a medication that contains the
same active pharmaceutical ingredient (API) and
bioavailability as the original brand-name formulation.
13. What do you understand by the following
i. Supplemental new drug application:
 Compilation of information on the safety and efficacy of a
marketed drug that is submitted to the FDA to request
approval for changes to an already approved drug product,
such as a new indication, dosage form, strength, or route of
administration or Compilation of information on the
safety and efficacy of a marketed drug that is submitted to
the FDA in order to quest approval to market the drug for
another indication.
ii. Scale up post approval changes:
 refer to changes made to the manufacturing process of a
drug after it has been approved by the FDA. These changes
may include modifications to the equipment, site of
manufacture, batch size, or manufacturing process
iii. Scale up:
  Involve an increase in the batch size from small scale to a
larger scale
14. Give the different level of changes proposed by SUPAC
guideline:
 Proposed chemistry
 Manufacture and controls test for each level change
 In vitro dissolution testing and / or in vivo bioequivalence
test for each level change
 Required documents to support filling.
i. Give the importance of SUPAC guideline
 The SUPAC guideline is important because it provides
recommendations to pharmaceutical companies on how to
make necessary changes to their products while
maintaining product quality, safety, and efficacy,
ultimately benefiting both the company and the patients
they serve
ii. Give 4 proposed changes in drug product manufactured.
 Changing the manufacturing process to improve efficiency
or reduce costs.
 Changing the formulation to improve stability or
bioavailability.
 Changing the packaging to improve shelf life or ease of
use.
 Changing the manufacturing site to improve quality or
reduce costs