The InternationalPharmaceutical Regulatory and Compliance Congress

and Best Practices ForumBrussels, June 6-8, 2007

The pharmaceutical industryand the regulations

Girolamo Sirchia MD, FRCP Edin

former Minister of Health, Italy

Starting points

Innovative drugs are of paramount importance for human beings

Medicinal products are ethical goods Regulations

• Ref.: EFPIA (2006) The Pharmaceutical Industry in Figures

Ref.: EFPIA (2006) The Pharmaceutical Industry in Figures

Innovative drugs stem from research

Research and development

are mainly designed, managed and paid

by Big Pharma

1. Critical issues in pharmaceutical innovation

1.1. Research and development investments

1.2. Marketing pressure

1.3. Clinical trials

1.4. Priority medicines

1.5. Accessibility of medicines

1.6. Counterfeit medicines

1.1. Research and development

investments

Pharmaceutical R&D costs

are very high on account

of the high attrition rate

during the drug development process

Ref.: EFPIA (2006) The Pharmaceutical Industry in Figures

• Ref.: EFPIA (2006) The Pharmaceutical Industry in Figures

1.2. Marketing pressure

Big investments require big returns Marketing

Marketing is addressed to prescribing physicians but also the involvement of Patient Associations, journalists and the media, politicians and civil servants is not uncommon

The mainstayof the industry marketing action:

❶ Advertisements directed to physicians

❷ Visits to physicians by sales representatives

➌ Gifts to physicians and their Institutions

➍ Direct-to-consumer advertising (USA)

A number of cases have brought to

lights an unhealthy relationship

between manufacturers and the

medical profession which demonstrate

how Company practices frequently

cross the divide separating patient

welfare from profit-seeking behaviour

1.3. The ethical problem of research: Clinical Trials

design and management of trials

the choice of comparators and ATV

drafting of papers by ghost-writers

relations with investigators

The risks of influencing the results and

only publishing the results desired

1.4. The ethical problem of research: priority medicines

predominance of drugs

for the most common pathologies

of industrialised countries

Priority Medicines for Europe and the World (Kaplan and Laing, 2004)

1. Infections due to antibacterial resistance2. Pandemic influenza3. Cardiovascular disease (secondary prevention)4. Diabetes (Type 1 and Type 2)5. Cancer6. Acute stroke7. HIV/AIDS8. Tuberculosis9. Neglected diseases10. Malaria11. Alzheimer disease12. Osteoarthritis13. Chronic obstructive pulmonary disease14. Alcohol use disorders: liver diseases and dependency15. Depression in the elderly and adolescents16. Postpartum haemorrhage17. Smoking cessation

1.5. Accessibility of Medicines

Access to essential drugs by developing countries:

November 14th, 2000: 4th WTO Conference of

Ministers – Doha DeclarationAugust 30th, 2003: WTO General Council – Decision

December 18th, 2005: WTO Conference of Ministers –

Reconfirmation of the Decision

May 17th, 2006: the EU (Parliament and Commission)

– Regulations on the granting of mandatory licences

Briefly

The decisions enabled given countries

in a particular state of need

to produce pharmaceutical products

protected by patents

for their own internal needs,

and excluding export sales

1.6. Counterfeiting of drugs

7% of all drugs sold in the world

are fake

Serious consequences

for public health

and the industries (WHO)

Frequency of counterfeiting

Less than 1% in developed countries

10 to 30% in Africa, Asia, South America

20% in the States of the former URSS

50% of drugs bought on the web

Challenges

for pharmaceutical industries

Industry reputation

Operation difficulties

Industry reputation

• Transparency

• Access to medicines

• Pricing

• Safety

Operation difficulties

• Cost-containment policy• Bureaucracy• Harmonisation• Pricing and reimbursement criteria• Access to the market• Patent challenges• Parallel importation• Counterfeits• Generics

(Courtesy of Dr. Thomas Lönngren)

ChallengesChallenges

2. Recommendations. States should:

2.1. Support pharmaceutical industry to achieve specific targets

2.2. Assure fast pricing and reimbursement procedures

2.3. Control pharmaceutical expenditure

2.4. Develop phase IV studies and improve pharmacovigilance

2.5. Promote independent research

2.6. Promote solidarity

2.1. Sustain the pharmaceutical industry to increase the production of innovative drugs

Administrative simplification in testing, registering, pricing, reimbursement

Recognition and reward of innovation

Incentives for ATV (premium prices)

Reward of Companies that invest in research and manufacture in the country

2.2. Pricing and reimbursement

Pricing, reimbursement

and reimbursement access time

within the EU is the prerogative

of single States. This leads to

differences between States

(Courtesy of Dr. Thomas Lönngren)

In line with EU Directive

in number of days

Average time delay between registration and effective market access

p7-8 – Situation

521

357317

240

220

000

529092

105124

175

227

249315

380478

488495

PolandGreeceSlovakiaBelgiumFranceCzech Rep.ItalyPortugalNorwaySpainHungaryNetherlandsFinlandSwitzerlandIrelandCyprusSwedenEstoniaAustriaGermanyUKUSA

Note In Poland no new innovative products have been reported as reimbursed for the past six yearsSource: IMS, 2004

The capacity of the national authorities

to recognise an innovative drug

and make it reimbursable with a price

that recognises the level of therapeutic

efficacy is one of the objectives of

the European Pharmaceutical Forum

The Paediatric Exclusivity Provision (Section 505A of the US FDA Modernization Act, 1997)

Additional 6 months of patent protection in return for performing studies in children

as specified by FDA

A very similar program has been developed and adopted in EU

Has been a success from the perspective of conducting trials for labelling in children

Overcompensates blockbuster products

It is believed by many that it would be

appropriate for EMEA to propose

a “Geriatric Exclusivity Provision”

to the European Parliament similar to

the Paediatric Exclusivity Provision

and with similar advantages

In Italy a network of long-term care and

geriatric hospitals is being organized.

More than 5000 beds are available

for clinical trials on acute and chronic

fragile old people

2.3. Controlling pharmaceutical spending

Natural increase

Appropriate drug use

Drugs for prevention

Aggressive marketing

The use of drugs for prevention

(statins, smoking dissuaders, etc.)

2.4. Aggressive marketing

Relations between industry and investigators – Register of Trials

Relations between industry and prescribing physicians

(Should we eliminate the sponsorship of congresses,CME, etc.?)

① Brennan et al, 2006 ③ Am. Med. Ass. J. of Ethics, 2006② The Prescription Project, 2007 R. Smith, ④ 2005

2.5. Pharmacovigilance (1)

The European Commission believes that the pharmacovigilance system must be

improved

Cooperation between the States is indispensable in order to evaluate in an independent manner relative efficacy and safety in the clinical practice of innovative drugs

2.5. Pharmacovigilance (2)

The identification, design and prioritization of large phase 4 drug trials of public health importance represent a major medical, social and scientific effort that currently lacks a champion in the USA (Psay and Weiss, 2007)

The Institute of Medicine’s Committee on Drug Safety has proposed a public-private partnership to help define key public health questions that merit investment in large, long-term phase 4 trials (2007)

2.6. Indipendent research

Given that: ⒜ the research and development of drugs are important

for humankind

⒝ industry is the largest investor in pharmaceutical

research but manages the trials

⒞ high costs require industries to maximise revenues

and thus invest in drugs with the largest market

it is necessary that developed States invest

in independent research

2.7. Access to essential drugs by developing countries:

The initiatives hitherto implemented

are insufficient

Forms of health aid have

a considerable diplomatic value

If we continue to believe that the bonds between persons and peoples

can only be entrusted to contractual

market relations without friendship

and without respect for the rights of all

to human values and essential goods

(such as food, water, housing and health),

our fate will be sealed

(His Holiness Benedictus XVI, Message for the World Peace Day, 2007)

A good start could be

to study arrangements

for making investments

by States and Companies

in favour of countries

with poor economies remunerative

Conclusion: some political agreements are needed for an international roadmap

1. State investments

Attention to the pharmaceutical industry Independent research Independent pharmacovigilance Supervision on the system’s ethical

compliance Support to developing countries

ctd.

2. Harmonisation between States (simpler and more harmonised regulations)

3. Independent information for physicians and the public

on the correct use of drugs

The USA and the EU

should work together

to lead the improvement

In the EU Vice President Günter

Verheugen has recently proposed

a Commission Communication

pointing to an EU single market

for pharmaceuticals.

A first step in the right direction

(Courtesy of Dr. Thomas Lönngren)

EMEA roadmap 2010EMEA roadmap 2010

– Safety of medicinal products

– Earlier availability of new medicinal products

– Support to innovation

– Transparency, communication and provision of information

– Reinforcing the EU medicines network