Week 2:
Regulation of Medicines:
Background:
- Developing new medicines = timely and costly
o On average 10-12 years to develop a new medicine
o Many compounds that are synthesized and tested never reach the market lots of money invested in these
failures. So, charge a lot to compensate for this loss to recoup on this investment
- As a result drug patented for 20 years
o After this expires, other companies can make cheaper versions of the same drug
An Example: Lipitor:
- After patent expired, super cheap options came out. No longer profitable. Made drugs more accessible.
Evergreening:
- Making minor modifications to a patented drug in order to extend its patent protection.
- A balance needs to be struck
o Without high profit margins, too risky to invest in medicine creation stifling innovation
Balancing Competing Interests:
Improving the health outcomes of the population Keeping the pharmaceutical industry in the UK [profitable
and major employer- a lot of tax revenue for the govt]
1. Making drugs as widely available as possible 1. Good intellectual property protections
2. Making drugs as cheap as possible for 2. Licensing processes not too cumbersome
NHS/consumers 3. Product liability scheme not too harsh [as to not stifle
3. Making licensing process very stringent innovation]
4. Strict liability for drug related injuries
What is a medicine?
- ‘Medicinal products’ are defined in the Human Medicines Regulations 2012, regulation 2(1)
- Needs to be marketed as a medicine, and function as a medicine
- A product is a medicinal product, and needs a marketing authorisation if either:
o It is marketed for the treatment or prevention of disease, or
o It is used for diagnostic purposes, or to alter physiological function
- Decided by the Medicines and Healthcare Products Regulatory Agency (MHRA)
Lifestyle drugs and enhancements:
- Some drugs being used for reasons that they aren’t prescribed
o Cognitive enhancement drugs for study or gaming
Increased medicalisation:
- Common experiences reframed as illnesses [as to sell the drugs]
- ‘A pill for every ill’.
- E.g.
o Ageing
o Heartburn
o Social phobia
Selling diseases:
- Normalising depression as to sell more drugs telling people to go to the doctors
- Viagra
- Female impotence campaign creating an issue for women to tackle and marketing new drugs e.g. ADDYI [libido for
women]
Marketing Authorisation: How to regulate the medicine:
- S 58(4): Marketing authorisation only if…
o (a) the applicant has established the therapeutic efficacy of the product to which the application relates;
o (b) the positive therapeutic effects of the product outweigh the risks to the health of patients or of the public
associated with the product…
Information about the tests they’ve done, how they’re going to market it etc
But if it’s a similar drug to one that already exists [a me-too drug], can make the process faster
Medicine authorised for 5 years and then have to recheck
Complementary and alternative medicines:
- Herbal Remedies Traditional Herbal Medicines Registration Scheme
o The normal requirement for medicines to be proven to be efficacious …is replaced by a requirement to
demonstrate 30 years traditional use…
As it can be hard to have tests
If you’ve created it yourself,
Don’t have to show that it works, but have to show that it is safe
30 years probably does work/has some benefit [assumption]
o Demonstration of an adequate period of traditional use contributes to assurance as regards safety.
o Evidence of sustained traditional use may also help to indicate that efficacy is at least plausible.
- Homeopathic medicines
, o Simplified registration scheme data must demonstrate quality of the product and show it is dilute enough to
guarantee safety.
Product should not make claims to therapeutic efficacy.
o National rules scheme must establish quality, safety and efficacy
Product can claim to relieve or treat minor symptoms or conditions.
But evidence only such that homeopathic practitioners in UK would accept it
Much lower demands, don’t need to convince a ‘reasonable person’ or a ‘doctor’
- Should complementary and alternative medicines be held to less rigorous standards than conventional medicines?
Classification of medicines:
- The MRA classifies medicines into one of three categories:
o prescription-only medicines (POM);
o suppliable by a pharmacist without prescription (P);
o general sale list medicines, which can be sold over the counter and do not need to be dispensed by a
pharmacist (GSL).
Human medicines regulations:
- Regulation 62(3)
o When deciding whether a medicine ought to be prescription only, the MHRA must consider whether it:
(a) is likely to present a direct or indirect danger to human health, even when used correctly, if used
without the supervision of a doctor or dentist; or
(b) is frequently and to a very wide extent used incorrectly, and as a result is likely to present a direct
or indirect danger to human health; or
(c) contains substances or preparations of substances of which the activity requires, or the side effects
require, further investigation;
(d) is normally prescribed by a doctor or dentist for parenteral administration [ie intravenously or by
injection].
- Regulation 62(4)(c)
o The Secretary of State should also take into account whether a medicine is likely, if incorrectly used, to present
a substantial risk of medicinal abuse, lead to addiction, or be used for illegal purposes.
Medicines can be reclassified e.g. prescription only down to suppliable by a pharmacist.
More convenient for patients and cheaper for the NHS
BUT lose the ‘learned intermediary’ so leaflets become much more important.
Online pharmacies:
- Range of legitimacy
- You order drugs online and don’t know what you’re receiving whether its safe, etc.
o If something goes wrong, difficult to find them and try to gain compensation, especially as they are offshore
jurisdictions
- It’s an offence to sell drugs without the right to do so, but not illegal to buy prescription drugs
Pharmacovigilance:
- Important to continue to monitor drugs when they reach the market:
o More people and wider demographics
o Trialled over a longer period of time
- Manufacturers are under a duty to record any adverse drug reactions reported to them and to report them to the European
Medicines Agency’s Eudravigilance web-system.
Yellow card scheme:
- Enables people to report any adverse reactions to drugs [either patients, or doctors or nurses]
Pharmacovigilance failures: Seroxat:
- Evidence showed that this antidepressant wasn’t safe for under 18s it increases the risk of suicidal behaviour
o But they didn’t report this
- Studies 329 and 277:
o Clinical trials of Paroxetine (Seroxat/Paxil)
in children and adolescents suffering from Major Depressive Disorder
o Trials involved 545 children and adolescents in 11 countries
o Completed by May 1998.
o Data submitted to MHRA in May 2003
Committee for the safety of medicines June 2003:
- Overall the data raise serious concerns about hostility, emotional liability and suicidal behaviour in children using
paroxetine, and particularly adolescents.
- There is no good evidence of efficacy in major depressive disorder in the population studied.
- Therefore, the balance of risks and benefits in this population is clearly negative.
Intentional non-disclosure?
- They weren’t found liable for not telling doctors about Seroxat
o Because apparently the law wasn’t sufficiently clear
- As a result of this shocking case, new legislation created a duty of candour.
- Regulation 75(1): ‘the holder of a UK marketing authorisation must provide the licensing authority with any new
information that might entail the variation of the authorisation.’
Regulation of Medicines:
Background:
- Developing new medicines = timely and costly
o On average 10-12 years to develop a new medicine
o Many compounds that are synthesized and tested never reach the market lots of money invested in these
failures. So, charge a lot to compensate for this loss to recoup on this investment
- As a result drug patented for 20 years
o After this expires, other companies can make cheaper versions of the same drug
An Example: Lipitor:
- After patent expired, super cheap options came out. No longer profitable. Made drugs more accessible.
Evergreening:
- Making minor modifications to a patented drug in order to extend its patent protection.
- A balance needs to be struck
o Without high profit margins, too risky to invest in medicine creation stifling innovation
Balancing Competing Interests:
Improving the health outcomes of the population Keeping the pharmaceutical industry in the UK [profitable
and major employer- a lot of tax revenue for the govt]
1. Making drugs as widely available as possible 1. Good intellectual property protections
2. Making drugs as cheap as possible for 2. Licensing processes not too cumbersome
NHS/consumers 3. Product liability scheme not too harsh [as to not stifle
3. Making licensing process very stringent innovation]
4. Strict liability for drug related injuries
What is a medicine?
- ‘Medicinal products’ are defined in the Human Medicines Regulations 2012, regulation 2(1)
- Needs to be marketed as a medicine, and function as a medicine
- A product is a medicinal product, and needs a marketing authorisation if either:
o It is marketed for the treatment or prevention of disease, or
o It is used for diagnostic purposes, or to alter physiological function
- Decided by the Medicines and Healthcare Products Regulatory Agency (MHRA)
Lifestyle drugs and enhancements:
- Some drugs being used for reasons that they aren’t prescribed
o Cognitive enhancement drugs for study or gaming
Increased medicalisation:
- Common experiences reframed as illnesses [as to sell the drugs]
- ‘A pill for every ill’.
- E.g.
o Ageing
o Heartburn
o Social phobia
Selling diseases:
- Normalising depression as to sell more drugs telling people to go to the doctors
- Viagra
- Female impotence campaign creating an issue for women to tackle and marketing new drugs e.g. ADDYI [libido for
women]
Marketing Authorisation: How to regulate the medicine:
- S 58(4): Marketing authorisation only if…
o (a) the applicant has established the therapeutic efficacy of the product to which the application relates;
o (b) the positive therapeutic effects of the product outweigh the risks to the health of patients or of the public
associated with the product…
Information about the tests they’ve done, how they’re going to market it etc
But if it’s a similar drug to one that already exists [a me-too drug], can make the process faster
Medicine authorised for 5 years and then have to recheck
Complementary and alternative medicines:
- Herbal Remedies Traditional Herbal Medicines Registration Scheme
o The normal requirement for medicines to be proven to be efficacious …is replaced by a requirement to
demonstrate 30 years traditional use…
As it can be hard to have tests
If you’ve created it yourself,
Don’t have to show that it works, but have to show that it is safe
30 years probably does work/has some benefit [assumption]
o Demonstration of an adequate period of traditional use contributes to assurance as regards safety.
o Evidence of sustained traditional use may also help to indicate that efficacy is at least plausible.
- Homeopathic medicines
, o Simplified registration scheme data must demonstrate quality of the product and show it is dilute enough to
guarantee safety.
Product should not make claims to therapeutic efficacy.
o National rules scheme must establish quality, safety and efficacy
Product can claim to relieve or treat minor symptoms or conditions.
But evidence only such that homeopathic practitioners in UK would accept it
Much lower demands, don’t need to convince a ‘reasonable person’ or a ‘doctor’
- Should complementary and alternative medicines be held to less rigorous standards than conventional medicines?
Classification of medicines:
- The MRA classifies medicines into one of three categories:
o prescription-only medicines (POM);
o suppliable by a pharmacist without prescription (P);
o general sale list medicines, which can be sold over the counter and do not need to be dispensed by a
pharmacist (GSL).
Human medicines regulations:
- Regulation 62(3)
o When deciding whether a medicine ought to be prescription only, the MHRA must consider whether it:
(a) is likely to present a direct or indirect danger to human health, even when used correctly, if used
without the supervision of a doctor or dentist; or
(b) is frequently and to a very wide extent used incorrectly, and as a result is likely to present a direct
or indirect danger to human health; or
(c) contains substances or preparations of substances of which the activity requires, or the side effects
require, further investigation;
(d) is normally prescribed by a doctor or dentist for parenteral administration [ie intravenously or by
injection].
- Regulation 62(4)(c)
o The Secretary of State should also take into account whether a medicine is likely, if incorrectly used, to present
a substantial risk of medicinal abuse, lead to addiction, or be used for illegal purposes.
Medicines can be reclassified e.g. prescription only down to suppliable by a pharmacist.
More convenient for patients and cheaper for the NHS
BUT lose the ‘learned intermediary’ so leaflets become much more important.
Online pharmacies:
- Range of legitimacy
- You order drugs online and don’t know what you’re receiving whether its safe, etc.
o If something goes wrong, difficult to find them and try to gain compensation, especially as they are offshore
jurisdictions
- It’s an offence to sell drugs without the right to do so, but not illegal to buy prescription drugs
Pharmacovigilance:
- Important to continue to monitor drugs when they reach the market:
o More people and wider demographics
o Trialled over a longer period of time
- Manufacturers are under a duty to record any adverse drug reactions reported to them and to report them to the European
Medicines Agency’s Eudravigilance web-system.
Yellow card scheme:
- Enables people to report any adverse reactions to drugs [either patients, or doctors or nurses]
Pharmacovigilance failures: Seroxat:
- Evidence showed that this antidepressant wasn’t safe for under 18s it increases the risk of suicidal behaviour
o But they didn’t report this
- Studies 329 and 277:
o Clinical trials of Paroxetine (Seroxat/Paxil)
in children and adolescents suffering from Major Depressive Disorder
o Trials involved 545 children and adolescents in 11 countries
o Completed by May 1998.
o Data submitted to MHRA in May 2003
Committee for the safety of medicines June 2003:
- Overall the data raise serious concerns about hostility, emotional liability and suicidal behaviour in children using
paroxetine, and particularly adolescents.
- There is no good evidence of efficacy in major depressive disorder in the population studied.
- Therefore, the balance of risks and benefits in this population is clearly negative.
Intentional non-disclosure?
- They weren’t found liable for not telling doctors about Seroxat
o Because apparently the law wasn’t sufficiently clear
- As a result of this shocking case, new legislation created a duty of candour.
- Regulation 75(1): ‘the holder of a UK marketing authorisation must provide the licensing authority with any new
information that might entail the variation of the authorisation.’
