Drug Development Process

Question 1

What are the phases of drug development ?

Answer 1

1. Discovery and Development
2. Preclinical Research
3. Clinical Development
4. FDA review
5. FDA Post-Market Safety Monitoring

Question 2

What is the Discovery in Discovery and Development?

Answer 2

This stage is generally the Target Discovery and Target validation stage.

Question 3

What is the Development in Discovery and Development?

Answer 3

Once researchers identify a promising compound for development, they conduct experiments to gather information.
- Assay Development and Screening
- High Throughput Screening
- Hit to Lead
- Lead Optimization
- Active Pharmaceutical Ingredients.

Question 4

What is Target Discovery and Target Validation

Answer 4

researchers discover new drugs through researching new insights of a disease that could stop or reverse the effect of a disease, this could also mean the testing of molecular compounds to see its benefits against a large number of disease. Discovery could also mean discovering ways of overcoming the existing treatments that have unanticipated effects and discovering new technologies that provide new ways to target or manipulate genetic material.
Validating the targets, researchers use modern tools and techniques such as diseases association or bioactive molecules or antibodies etc. Another way of validation is the Sanger Whole Genome CRISPER library.

Question 5

What is Pre-Clinical Research

Answer 5

Researchers must determine the efficacy and the safety of the drug through in vivo research. Pre-clinical trails test the new drug on non-human subjects for efficacy, toxicity, and pharmacokinetics (PK) information, these trials are conducted by scientists in vitro and in vivo with unrestricted dosages.

Question 6

What stages are included in Pre-clinical Research?

Answer 6

• Absorption, Distribution, Disposition, Metabolism and Secretion (ADDMS)
• Proof of Principle/ Proof of Concept
• In vivo, In vitro and Ex vivo Assays
• In Silico Assays
• Drug Delivery

Question 7

What is ADDMS?

Answer 7

Absorption, distribution, disposition, Metabolism and Secretion is a Pharmacokinetic (PK) process of measuring the ways the new drug affects the body. It involves mathematical description of each effect.

Question 8

What is Proof of Principle (PoP) or Proof of Concept (PoC)?

Answer 8

PoP are studies that are successful in preclinical trails and early safety testing. PoC is used almost interchangeably with PoP. Successful PoP/PoC studies lead to the programme advancement to the Phase II studies of dosage.

Question 9

What are In Vivo, In Vitro and Ex Vivo Assays?

Answer 9

In Vivo - are the development of new drugs using mice, rats and dog models.
In Vitro - is research conducted in a laboratory.
Ex Vivo - uses animal cells or tissue from a non-living animals, research examples like finding effective cancer treatment reagents. In ex vivo assays, a cell is always used as the basis for small explant cultures that improve a dynamic, controlled and sterile environment.

Question 10

What is In Silico Assay?

Answer 10

They are test systems or biological experiments performed on a computer or via computer simulation.

Question 11

What is Drug Delivery?

Answer 11

New drug delivery includes oral, topical, membrane, intravenous and inhalation. they are used for target delivery or controlled release of new drugs. The goal is to prevent the drug from interacting with healthy tissues while still being effective.

Question 12

What is Oral drug delivery?

Answer 12

They are reliable, cost-effective and convenient for patients. They may not deliver precise dosage to target area but is an ideal for prophylactic vaccinations and nutritional regimens. Delayed action, stomach enzyme destruction, absorption inconsistencies, or patients with gastrointestinal issues or upset can occur, and patients must be conscious during administration.

Question 13

What is Topical Drug Delivery?

Answer 13

This involves ointments, creams, lotion, or transdermal patches that deliver a drug by absorption into the body. Topical delivery is more useful for patients skin or muscular condition, it is preferred by patients due to non-invasive delivery and their ability to self-administer the medicine.

Question 14

What is Parenteral (IM, SC, or LP membrane) Drug Delivery?

Answer 14

Parenteral drug delivery utilizes bodily membranes, including intramuscular (IM), intraperitoneal (IP), or subcutaneous (SC). It is often used for unconscious patients and avoids epithelial barriers that are difficult for drugs to cross.

Question 15

What is Parenteral (Intravenous) Drug Delivery?

Answer 15

Intravenous injection is one of the fastest drug delivery absorption methods. IV injection ensures entire dosage of drugs enters the bloodstream, as it is more effective than IM, SC, or LP membrane methods.

Question 16

What is Parenteral (Inhalation) Drug Delivery?

Answer 16

Inhalation drug delivery gets the drug rapidly absorbed into the mucosal lings, nasal passage, throat, or mouth. Problems with inhalation delivery include difficulty delivering the optimum dosage due to small mucosal surface areas and patient discomfort. Pulmonary inhalation drug delivery uses fine drug powders or macromolecular drug solutions. Lung fluids resemble blood, so they can absorb small particles easily and deliver them into the bloodstream.

Question 17

What is the Formulation Optimization & Improving Bioavailability in Drug Delivery?

Answer 17

Formulation optimization is ongoing throughout the pre-clinical and clinical stages. It ensures drugs are delivered to the proper place at the right time and in the right concentration.

Question 18

What is Clinical Drug Development Process?

Answer 18

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

Question 19

What stages/ phases are involved in the Clinical Process?

Answer 19

• Complexity of Study Design, Associated Cost & Implementation Issues.
• Clinical Trails - Dosage Escalation, Single Ascending & Multiple Dose Studies.
• Phase I - Healthy Volunteer Study,
• Phase II and III - Studies in Patient Population.
• Biological Samples collection, storage and shipment.
• Pharmacodynamic (PD) Biomarkers
• Pharmacokinetic Analysis
• Bioanalytical Method Development and Validation.
• Drug (analyte) & Metabolite Stability in Biological Samples
• Blood, Plasma, Urine & Feces Sample Analysis For Drug and Metabolites
• Patient Protection.

Question 20

What is the Complexity of Study Design, Associated Cost & Implementation Issues?

Answer 20

This may affect the trails carried out in this phase. The trails must be safe and efficacious and be completed under the drug development budget, using a methodology to ensure the drug works as well as possible for its intended purpose.

Question 21

What are the clinical trials?

Answer 21

This determines the proper dosing effectiveness and clinical trial examine dose escalation, single ascending and multiple-dose studies to determine the best patient dosage.

Question 22

What is Phase I?

Answer 22

Phase I - the purpose of this phase is to test the safety and dosage. This phase is the first time the drug is tested on humans, less than 100 volunteers will help researchers assess the safety and pharmacokinetics, absorption, metabolic, and elimination effects on the body, as well as any side effects for safe dosage ranges.

Question 22

What is Phase II?

Answer 22

Phase II - assesses the drug safety and efficacy in an additional 100-500 patients, who may receive a placebo or standard drug previously used as treatment. Analysis of optimal dosage strength helps create schedules while adverse events and risks are recorded. The purpose of this phase the Efficacy and side effects of the drug

Question 23

What is Phase III?

Answer 23

Phase III - enrols 1000-1500 patients, enabling medication labelling and instruction for proper drug use. This phase requires extensive collaboration, organization and Independent Ethics Committee (IEC) or Institutional Review Board (IRB) coordination and regulation in anticipation of full-scale production following drug approval. The purpose of Phase III for efficacy and monitoring of adverse reactions.

Question 24

Biological Samples Collection, Storage and Shipment

Answer 24

During clinical trials, biological samples are collected, stored and shipped from testing sites according to global standards and regulations. Transport containers of biological samples may include dry ice packs or other temperature-stabilizing methods.

Question 25

Pharmacodynamic (PD) Biomarkers

Answer 25

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.

Question 26

Pharmacokinetic Analysis

Answer 26

This 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 modelling.

Question 27

Bioanalytical Method Development and Validation

Answer 27

Bioanalytical methods detect analytes and metabolites such as drug or biomarkers in biological or human samples to determine drug efficacy and safety. Complete assay includes sample collection, clean-up, analysis and detection.

Question 28

Drug (analyte) & Metabolite Stability in Biological Samples

Answer 28

Drugs and drug metabolites are susceptible to degradation, which can lower drug concentration over the life of the drug, so stability is important in determining human drug efficacy

Question 29

Blood, Plasma, Urine & Feces Sample Analysis for Drug and Metabolites

Answer 29

Biological samples used in clinical trials include blood, plasma, urine, and feces to determine and analyse various properties and effects of the drug and its metabolites on humans.

Question 30

Patient Protection- GCP, HIPAA, & Adverse Event Reporting

Answer 30

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

Question 31

What happens to FDA Review?

Answer 31

FDA review is for new drugs which have been formulated for their best efficacy and safety, with the results available to be reviewed and approved or not approved by the FDA

Question 32

Regulatory Approval Timeline

Answer 32

Timeline may be standard, fast track, breakthrough, accelerated approval, or priority review depending on its application and necessity for patients. Standard or priority review may have an approval timeline may be up to a year. Fast track, breakthrough or accelerated approvals may be sooner.

Question 33

Reasons for Drug Failure

Answer 33

• Toxicity - if the toxicity of the new drug is too high in human or animal patients, it may be rejected due to safety concerns.
• Efficacy - if a new drugs efficacy (effectiveness) is not high enough or evidence is inconclusive, the FDA may reject it
• PK Properties or Bioavailability: PK (what the body does to the drug) 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 favour of a formulation that performs better.

Question 34

What is Post-Market Monitoring?

Answer 34

Following 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-market safety surveillance program. Through this program, manufacturers, health professionals and consumers report problems with approved drugs.

Question 35

Process Scale-Up Differences and Difficulties

Answer 35

Drug development involves generating progressively larger medicine batch sizes, and changes in processes for different-sized batches may cause unexpected difficulties, Use of the right pharmaceutical equipment can be helpful, as well as the discovery of parameters that affect critical process parameters (CPPs).
All regulations and safety indications must be observed carefully, and human and animal clinical trial subjects treated professionally and with the utmost care.