Chapter 8 - Liscensing Drugs And Post-Licensing Surveillance Flashcards Preview

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Flashcards in Chapter 8 - Liscensing Drugs And Post-Licensing Surveillance Deck (56):

What does "high-quality" medicine mean?

The medicine contains the active ingredient in the states dose
It doesn't contain anything but the stated excipients
The stability, dissolution; bioavailability will be within acceptable limits


What does drug "efficacy" mean?

The medicine has been shown to have a positive effect in patients with the target disease
There is a reasonable expectation that it will provide some benefit to this patient


What does medicine "safety" mean?

Relative absence of harm


What are the phases of product development?


Phase I - human volunteers
Phase II - small clinical trials
Phase III - large scale clinical trials
Phase IV - post-marketing


What is the point of pre-clinical in terms of product development?

Animal toxicology tests


What is the point of phase I in terms of product development?

Human pharmacology


What is the point of phase II in terms of product development?

Effects in patients


What is the point of phase III in terms of product development?



What is the point of phase IV in terms of product development?

Safety in normal use
Further development


What are the pre-clinical authorisation requirements

Acute and chronic toxicity
Mutagenicity and carcinogenicity
Reproductive toxicology


What are the pharmaceutical data authorisation requirements

Manufacturing process
Pharmaceutical form


What are the human pharmacology authorisation requirements

Healthy volunteer studies
Pharmacokinetics and dynamics


What are the clinical authorisation requirements

Demonstrating efficacy in the proposed indications and population
Controlled studies comparing drug against placebo and/or active treatments
Where appropriate, long-term and special groups e.g. Children, elderly
Safety analysis of adverse events in all patients using the drug against comparators


What are the "proposals for" authorisation requirements

Summary of product characteristics
Patient information leaflet


List the 5 steps in the application process

1. Application from pharmaceutical company
2. Details supporting dossier
3. Assessment by toxicologist, pharmacist and physician
4. Assessment report reviewed by expert advisory committee
5. Decision to grant or refuse by 'competent authority'


What are the three criteria for which authorities base their decisions for product application on


Cost not taken into account, risk-benefit evaluation is the key issue


Why do we need an authorisation process

Ensure quality, safety, efficacy and the benefits of a medicine outweigh the risks
Promote public health in relation to medicines
Protect the public


What is the basic legal framework from which authorisation works

A medicine may not be marketed without a licence
Attached to the licence is the summary of product characteristics (SPC)
A medicine may only be advertised in accordance with the SPC
Individuals and companies who offend may be prosecuted


What is the benefit-risk balance

The process of weighing u and balancing all the available evidence on risks and benefits on the same scale. It varies depending on the indication and population


What is pharmacovigilance?

The promotion of public health in relation to medicines while ensuring the patients protection towards potential adverse drug reactions


Who is the uk regulator?

Medicines and healthcare products regulatory authority - MHRA


Who is the EU regulator?

European Medicines Agency (EMA) and European Commission (EC)


Who is the international regulator

World health organisation (WHO)... Not really a regulator but supports member states with standards, information, guidelines


What is the role of EMA

Oversight of:
Development of medicines, authorisation of new innovative medicines, EU level pharmacovigilance and 'decisions' on major benefit risk questions, coordination of EU activities, EU data sources


What is the role of national agencies?

Oversight of national manufacturing, national pharmacovigilance, authorisation of national generics, clinical trials approval, inspection and enforcement


Describe what is meant by a centralised procedure

Authorisation across Europe by EC

Scientific and procedural work done by the EMA and its committees


Explain what is meant by a mutual recognition or decentralised procedure

Multiple identical national authorisations
Nation competent authorities eg Agence Nationale de Sécurité des Medicaments et des produits de Santé


Describe what is meant by a national procedure

Authorisation in 1 member state only given by a national competent authority


Give the key details from the legal directive from 2001 (EU)

Basic legislation laying down the rules on authorisation, pharmacovigilance, manufacturing, inspection, advertising, and marketing


Give the key details from the legal regulation from 2004 (EU)

Established the EMA and the centralised procedure


Give the key details from the legal directive from 2001 (EU)

Clinical trials directive


Give the key details from the legal regulation from 2000 (EU)

Orphan medicines


Give the key details from the legal regulation from 2006 (EU)

Paediatric regulation


Give the key details from the legal regulation from 2007 (EU)

Advanced therapy medicinal products


What were the details of the 2010 EU pharmacovigilance legislation

1. Better collection of key information on medicines, improvement of analysis and understanding of data and information
2. Strengthening of the EU network (integrate benefit and risk, increased pro activity/planning, ensure robust and rapid EU decision-making)
3. Reduction in duplication/ redundancy (clear roles and responsibilities)
4. Increase in transparency and accountability (engage patients & healthcare professionals, provide better information on medicines)


Give 6 roles of the EMA

1. Evaluation of marketing authorisation applications
2. Coordination of pharmacovigilance at EU level
3. Provision of scientific advice on the development of medicines
4. Evaluation of applications for orphan designation in EU
5. Evaluation of paediatric investigation plans
6. Provision of good quality and independent information on medicines it evaluates to patients and health professionals


Who are the key stakeholders in the EU network?

European Parliament
52 NCAs (33 human)
4500 scientific experts
Patients and consumers
Healthcare professionals
Pharmaceutical industry


EMA committees CHMP

Committee for human medicinal products

Prepares opinions on questions concerning medicines for human use


EMA committees PDCO

Paediatric committee

Assess the content of paediatric investigation plan and adopting opinions on them


EMA committees PRAC

Pharmacovigilance risk assessment committee

Assesses and monitors safety issues for human medicines


EMA committees COMP

Committee for orphan medicinal products

Reviews application seeking 'orphan-medicinal-product designation'


EMA committees CAT

Advanced therapies committee
Assesses the quality, safety and efficacy of ATMP and following scientific developments in the field


EMA committees CVMP

Committee for veterinary Medicinal Products

Prepares opinions on questions concerning medicines for veterinary use


EMA committees HMPC

Committee for herbal medicinal products

Prepares opinions on herbal medicines


Definition of pharmacovigilance

The science and activity relation to the detection, assessment, understanding and prevention of adverse drug effects or any other drug related problem


What do we know about a medicine at the time of authorisation?

Dossier of evidence submitted by the companies on safety, quality, and efficacy


What do we NOT know about a medicine at the time of authorisation?

Full safety profile in normal clinical practice:
Rare ADRs
Delayed ADRs
ADRs from chronic exposure
ADRs in special populations
ADRs from off-label use


What limitations are there of pre-marketing data

Pre-clinical data has a Lowe predictive value

Clinical trial data provide provision evidence of safety but:
-too small
-limited duration
-do not represent the real world


What are the 5 burdens of ADRs

1. 5% hospital admissions due to them
2. 5% hospital patients suffer from them
3. 5th most common cause of hospital death
4. 197,000 deaths per year from ADRs in the EU
5. EU societal cost of ADRs = €79bn/yr


What are the four objectives of pharmacovigilance

1. Identify previously unrecognised hazards
2. Evaluate changes in risks and benefits and improve the safety of marketed medicines
3. Take action to promote safer use to optimise the safe and effective use of medicines
4. Provide optimal information to users


What do you assume if you are about to prescribe/use a medicine?

1. The medicine has been extensively tested by the company
2. The tests performed were reviewed in detail by the regulators
3. The medicine will be high-quality, effective and safe


Give the 7 steps undertaken in pharmacovigilance

1. Collect data on the safety of medicines
2. Manage and maintain those data
3. Signal detection - scrutinise the data to identify new or changing safety issues or the effectiveness of measures put in place to reduce risk
4. Evaluate safety issues and make recommendation to reduce risk
5. Take action to reduce risk
6. Communicate actions
7. Audit


Give 6 actions in pharmacovigilance that can reduce risks

1. Inform patients via warning in product information
2. Stop use in at-risk patients
3. Withdraw the product
4. Reduce the top dose (if dose dependent risk)
5. Introduce monitoring for early warning signs
6. Restrict the use to only the most severe patients


What is a yellow card?

Reports of suspected adverse reactions from patients and professionals


Why are reports of suspected ADRs so important?

1. Main source of safety issue / evidence of harm leading to action to protect public health
2. National data sets too small to detect safety issues well - research shows eudravigilance detects issues years earlier
3. Clear evidence of issues detected many decades after produce enters market


What is eudravigilance

Data processing network and management system for reporting and evaluating suspected ADRs during the development and following the market authorisation of medicinal products in the European economic area