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?
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
What are the pre-clinical authorisation requirements
Acute and chronic toxicity
Mutagenicity and carcinogenicity
What are the pharmaceutical data authorisation requirements
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
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)
Give the key details from the legal regulation from 2006 (EU)
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?
52 NCAs (33 human)
4500 scientific experts
Patients and consumers
EMA committees CHMP
Committee for human medicinal products
Prepares opinions on questions concerning medicines for human use
EMA committees PDCO
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:
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:
-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
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