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Biomedical technology > Drug discovery & development > Flashcards

Drug discovery & development Flashcards

1
Q

what is the average cost of new drug developmnent 2022/23

A

$2.5 billion

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2
Q

how much did is cost to develop a new drug in the late 20th centrury?

A

between 100 (1970s) to 600 (1990-2000) $million

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3
Q

why do pharma companys charge so much formedication

A

the drugs costs alot to develop, and the trials in particular are very prensive

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4
Q

Breifly describe the porcess of drug discovery and development

A
  1. Identify protein target
  2. do assays to understand interactions - things that target?
  3. narrow down to a smaller number of compounds
  4. do more specific assays
  5. file for an IND (investigational new drug)
  6. pre clinical trials
  7. clinical trials: phase 1 - understand dose and safety, phase 2 - optimise parameters, does it actual work, phase 3 - perform multinational study on thousands of patients to see statistical significance
  8. go to drug regulatory authories and ask for compound approval
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5
Q

how long can the drug discovery and preclincal stages take?

A

6.5 years

start with 10000 compounds down to 250

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6
Q

how long can stage 3 (clinical trials) take?

A

7 years

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7
Q

how long can stage 4 FDa review take

A

1.5 years

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8
Q

name the main stages of therapeutic drug development

A

 Discovery & Development
Research for a new drug begins in the laboratory.
 Pre-clinical Research
Drugs undergo laboratory and animal testing to answer basic questions about safety.
 Clinical Research
Drugs are tested on people to make sure they are safe and effective.
 Clinical Authority Review
Review teams thoroughly examine all of the submitted data related to the drug or device and make a decision to approve or not to approve it.
 Clinical Authority Post-Market Safety Monitoring
FDA monitors all drug and device safety once products are available for use by the public.

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9
Q

how do researchers discover new drugs?

4

A
  1. New insights into a disease process that allow researchers to design a product to stop or reverse the effects of the disease.
  2. Many tests of molecular compounds to find possible beneficial effects against any of a large number of diseases. (assays that tell if where the drug binds etc what are the effecrs of this)
  3. Existing treatments that have unanticipated effects. (drugs wit other indications are repurposed for other disease, eg rituximab initially for cancer but onw used in Multiple sclerosis and other autoimmune conditions)(cuts down the time and cost of the drug development)
  4. New technologies, such as those that provide new ways to target medical products to specific sites within the body or to manipulate genetic material.
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10
Q

how long does drug discovery take (min)?

A

5-6 years

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11
Q

Once researchers identify a promising compound for development, they conduct experiments to gather information on what things?

8

A
  1. How it is absorbed, distributed, metabolised, and excreted.
  2. Its potential benefits and mechanisms of action.
  3. The best dosage.
  4. The best way to give the drug (such as orally or injection).
  5. Side effects or adverse events that can often be referred to as toxicity.
  6. How it affects different groups of people (such as by gender, race, or ethnicity) differently.
  7. How it interacts with other drugs and treatments.
  8. Its effectiveness as compared with similar drugs.
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12
Q

what are pharmacokinetics

A

Pharmacokinetics is the study of what the body does to a drug. Understanding this is key in drug discovery and development.

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13
Q

what pharmacokinetic properties are investigated in drug discovery and development?

LADMET acronym

A
  • Liberation: release of a drug from its administered form
  • Absorption: movement of a drug from where it is liberated into the bloodstream
  • Distribution: process by which a drug passes from the bloodstream to body tissues and organs
  • Metabolism: chemical reactions that change drugs into compounds which are easier to eliminate
  • Excretion: elimination of unchanged drug or metabolite from the body
  • Toxicity: harmful side-effects a drug may have
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14
Q

what is the medical defininition of preclinical study

A

A study to test a drug, a procedure, or another medical treatment in animals. The aim of a pre-clinical study is to collect data in support of the safety of the new treatment.

Required before clinical trials in humans can be started

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15
Q

what preclinical tests are required prior to clinical trials?

A

Mechanism of action (MOA),
efficacy in relevant models,
pharmacodynamics,
pharmacokinetics,
toxicity analysis
(monitoring, examine tissues at the end, control group)

must provide detailed information on dosing and toxicity levels. After preclinical testing, researchers review their findings and decide whether the drug should be tested in people.

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16
Q

what are the two types of preclinical research

A

The two types of pre-clinical research are:
* in vitro and in vivo

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17
Q

Researchers are required to use good laboratory practices (GLP), defined in medical product development regulations, for preclinical laboratory studies. These regulations set the minimum basic requirements for what things?

A
  1. study conduct
  2. personnel
  3. facilities
  4. equipment
  5. written protocols
  6. operating procedures
  7. study reports
  8. and a system of quality assurance oversight for each study to help assure the safety of the regulated product
18
Q

when was the first publication of a mouse used as an animal model?

A

1902

19
Q

who regulates animal experimentation in the UK?

A

the Home Office

Every person who wants to work with animals has to take the test (the establishment also has a license)

20
Q

in order to minimise the use of animals whta can be an okay replacement

A

organoids

21
Q

how have we begun to reduce the turnover of animal models

A

add a dye to tumour and image it instead of killing and taking

22
Q

what is clinical research?

A

to studies, or trials, that are done in people

23
Q

before clinical research can begin what needs to be considered?

A

what they what to accomplsih according to each of the different Clinical Research Phases and begin the Investigational New Drug Process (IND),

24
Q

what are the main phases of clinical research period?

A
  1. Designing clinical trials
  2. Clinical research phase studies
  3. The Investigational New Drug (IND) process
  4. Asking for assistance from the regulatory agencies
  5. IND Review Team
  6. Approval

after which clinicians will usually take over

25
Q

Before a clinical trial begins, researchers review prior information about the drug to develop research questions and objectives such as?

A
  • Who qualifies to participate (selection criteria)
  • How many people will be part of the study
  • How long the study will last
  • Whether there will be a control group and other ways to limit research bias
  • How the drug will be given to patients and at what dosage
  • What assessments will be conducted, when, and what data will be collected
  • How the data will be reviewed and analysed
26
Q

what is the typical series of clincial trials

A

early, small-scale, Phase 1 studies to late-stage, large scale, Phase 3 studies

27
Q

what is needed for a company to file an application to market the drug?
what follows this?

A

If a drug developer has evidence from its early tests and preclinical and clinical research that a drug is safe and effective for its intended use

The medicinal drug regulatory review team thoroughly examines all submitted data on the drug and makes a decision to approve or not to approve it.

28
Q

what is an NDA?

A

A New Drug Application (NDA) tells the full story of a drug. Its purpose is to demonstrate that a drug is safe and effective for its intended use in the population studied.

29
Q

what must developers inclde in an NDA ?

A

A drug developer must include everything about a drug—from preclinical data to Phase 3 trial data—in an NDA. Developers must include reports on all studies, data, and analyses. Along with clinical results, developers must include:
* Proposed labelling
* Safety updates
* Drug abuse information
* Patent information
* Institutional review board compliance information
* Directions for use

30
Q

what is ‘labelling’?

A

In cases where FDA determines that a drug has been shown to be safe and effective for its intended use, it is then necessary to work with the applicant to develop and refine prescribing information. Labelling accurately and objectively describes the basis for approval and how best to use the drug.

31
Q

what happens when there are remaining issues after submitting NDA

A

. Sometimes FDA requires the developer to address questions based on existing data. In other cases, FDA requires additional studies. At this point, the developer can decide whether or not to continue further development. If a developer disagrees with an FDA decision, there are mechanisms for formal appeal.

32
Q

what is the FDA advisory committee?

A

Often, the NDA contains sufficient data for FDA to determine the safety and effectiveness of a drug. Sometimes, though, questions arise that require additional consideration. In these cases, FDA may organise a meeting of one of its Advisory Committees to get independent, expert advice and to permit the public to make comments. These Advisory Committees include a Patient Representative that provides input from the patient perspective

33
Q

what are the main reasons compouds faild (durg attrition)?

A

Poor Pk profile (41%)
Lack of efficacy (31%)
Toxicity (22%)
market reasons (6%)

Market reasons – another company created a better drugs while you were working on it, or demand drops

34
Q

what reasons are there than a drug may have slowed development?

A
  • Synthetic complexity
  • Low potency
  • Ambiguous toxicity finding
  • Inherently time-intensive target indication
  • Poor biopharm properties
35
Q

what drug is a good exmple of translational failure?

A

TGN1412

36
Q

what is CD28?

A

CD28 is a co-stimulator on T cells

37
Q

what was the outcome of the TGN1412 clinical trial?

what are the details?

A

6 healthy men tested in London in 2006, developed multiple system failure. They got sick within 90 minutes because all of their T cells got activated.
Cytokine storm

38
Q

compare what happened in the TGN1412 animal trials to what probably happened in the london trial

A
  • In monkeys, TGN1412 activated only the regulatory t cells which damp other elements of the immune response. so the researchers hoped that the durg would help treat autoimmun diseases by suppressor inflammatory immune cells that attach the patients own tissue
  • In london, as well as actvating regulatory T cells, TGN1412 swithced on helper T cells which produce chemical messengers, cytokines to koost other elements of the immune repsonse, this mass activation of T cells caused a devastating cytokine storm - a flood of inflammatory molecules that swept through the patients body
39
Q

what is required to switch on a T cell?

A

two signals: a general activtaion trigger (costimulation by CD28 or Cd80)
and a specific antigen bound to MHC

40
Q

what is super-antibody T cell activation and how did TGN1412 cause it?

A

when an antibody overrides both signalls needed for normal T cell activation to acitvate all T cells with a CD28 receptor, not just those specific for a particular antigen

41
Q

Followup studies showed what techniques could have predicted this outcome?

A
  • different methods of introducing the antibody
  • humanised mice
  • just the FAB

Biomedical technology (9 decks)

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