prevention and m a n a g e m e n t o f a va ila b ilit y p ro b le m s: An in d u st ry p e rsp e c t ive 9 November 2018 Multi -stakeholder workshop HMA/EMA task force on availability of authorised medicines for human and veterinary use

1

Medicines shortages

Causes & main drivers of shortages

Scenarios leading to shortages

Communication of shortages

Availability of medicines

2

Causes and main drivers of shortages

Regulatory Manufacturing Quality Economic Supply chain

Products not authorized Regulatory time

lag NA NA NA NA

Products authorized but not

launched

National

requirements

Manufacturing

capacity

Natural disasters

NA

Market

attractiveness

Company size

NA

Products

authorized

and

marketed but

unavailable

due to

shortages

Temporary NA

Manufacturing lag

times

GMP issues

Surges in demand

API and excipient

supply

Pricing

mechanisms

Tender practices

Cost-containment

measures

Supply

quotas and

parallel

export

Logistical

Inefficiency

Permanent NA Manufacturing

capacity NA

Commercial

withdrawals NA

3

Scenarios leading to shortages: Pricing mechanisms • Low price policies • Inadequate volumes • Price regulation that do not allow for price

adjustments to reflect changes in costs of: • Goods (e.g. ingredients) • Manufacturing (e.g. FMD) • Regulatory procedures (e.g. Art 57) • Distribution (e.g. increased cost of ingredients)

4

Scenarios leading to shortages: Tender practices

Less suppliers

on the market

Price-only tender

Single supplier (single-winner tenders)

Short lead times

Severe penalties More frequent medicines shortages

5

Scenarios leading to shortages: Cost -containment measures

Suppliers retraction

s hortages

Underfunding

Payback mechanisms

Price cuts

Payment delays

Market unpredictability

6

Scenarios leading to shortages: Commercial withdrawals

Commercial withdrawals

Pricing mechanisms

Tender practices

Cost-containment

measures

Unpredictability

7

• Vaccine manufacturing is highly complex with long lead times and can be

unpredictable. • Short-term response to unexpected changes of demand is difficult. • Significant increase of capacity post-autorisation:

— takes time (5 to 10 years are needed to build and license a new facility) — results from decision based on assumptions and taken at risk.

Manufacturing of most vaccines shipped today began in 2016

2015 2016 2017 2018 2019 2020

Manufacturing operations starting today for most vaccines to be shipped in 2021

2021

Today: November 2018

Vaccine supply example

• What are manufacturers doing to improve vaccine supply? • continuously invest in more robust and efficient manufacturing and

control processes to increase production of high quality vaccines meeting European standards

• invest in additional capacity (expansion of existing facilities and establishment of new facilities ).

• Industry measures alone will not be sufficient as the root causes of vaccine shortages/unavailability are driven to a significant extent by external factors:

• changes of national immunisation programmes in the world • unpredictable changes of epidemiology • complexity of worldwide regulatory requirements.

Vaccine supply specificity

• Vaccines Europe recommendations* to establish sustainable vaccine supply:

• establish early and continuous dialogue between manufacturers and public health authorities to better anticipate the evolution of vaccine recommendations

• introduce procurement practices which would enable to better manage risk and optimise vaccine supply

• optimise existing capacity by streamlining regulatory requirements in Europe and across regions.

• Vaccines Europe stands ready to work: • with all relevant stakeholders on feasible solutions to improve vaccine

supply (eg. in Joint Action on Vaccination) • with HMA/EMA taskforce on implementation of the guidance on

notification of shortages for vaccines.

Vaccine supply specificity

* http://www.vaccineseurope.eu/wp-content/uploads/2017/06/VE-paper_priorities_vaccination_policy-22-05-2017.pdf

Good practices in communication o f sh o rt a g e s

Concerning Art.23 of Directive 2001/83/EC, Member states (EC) consider: • Communication between MAHs

and NCAs is generally functioning • MS communicate with industry to

monitor shortage situations

Ad-hoc technical meeting under the Pharmaceutical Committee on shortages of medicines, 25 May 2018

11

Current co m m u n ica t io n p ra c t ice s • Significant differences and variations across Member States – Need for

increased convergence and harmonisation • A need for simplification of the notification process (at the national and

central level) – Development of an unique portal

12

Risk assessment

Communication to Supply chain

Public domain

Good practices in communication o f sh o rt a g e s Hypothetical system of detection and assessment of a medicine shortage

Communication must be well planned to avoid worsening shortages

Supply Chain Stakeholders . J oint Supply Chain Actors Statement on Information and Medicinal Products Shortages . (2016).

MAHs

Patients

NCAs

Level of neces sary

information

Supply chain actors

13

Good practices in communication o f sh o rt a g e s

Define risk to patient

Access to Therapies

No alternatives

Alternative products available

Similar therapy

Exact products available but in

other presentations

Pro

duct

indi

catio

ns Life supporting

or life sustaining

Fatal or severe irreversible harm if the patient is not

treated Risk level A Risk level A Risk level B

Acute short term or chronic long

term

Severe harm but reversible if patient is not treated with

the product Risk level A Risk level B Risk level C

Other Indications Inconvenience if patient is not treated with the product Risk level B Risk level C Risk level C

14

Conclusions • Medicine shortages are a multi -factorial issue that must be tackled in

strict collaboration with all stakeholders (regulators, industry, supply -chain, payers).

• Efficient communication is essential: • Simplification and harmonisation are needed; • Ensure all supply chain actors receive sufficient information.

• Product specificities should be considered when it comes to shortages • Single-source vs multi -source products; • Vaccines, sterile products, etc.

• Medicine shortages and availability are different issues that should not be confused.

• Industry and supply chain will continue working together to find solutions.

15

16 www.efpia.eu

Availability of medicinal products

• A product is available in a country if it is developed, obtains market authorization and is placed on the market in the given country.

• As an ambition companies want to launch in as many countries as possible and as fast as possible.

• However a number of factors can impact companies’ ability to launch their products on all markets:

• Availability of a functioning healthcare system with adequate expertise and infrastructure (as reflected by the level of health expenditures)

• Pricing & reimbursement processes (including potential spill-overs through External Price Referencing – will impact on the launch sequence)

• Level of regulatory requirements • Size of the population • Availability of IP rights • Cost to bring the product to the market (including whether local revenue

will sustain local infrastructure) • Availability vs delays

17 www.efpia.eu

The Patients W.A.I.T. Indicator gives a snapshot of the 2 parameters at a cut-off date (December 2017)– data from medicines cohorts dropping out of the reference period are not updated in subsequent surveys. Waiting times reflected in the Patients W.A.I.T. Indicator include any delay, whether attributable to companies or to competent authorities. The Patients W.A.I.T. Indicator is not a measurement of the delays as defined in the “Transparency” Directive. Delays under the “Transparency” Directive reflect the number of days that national competent authorities need to make their decisions regarding price and inclusion of medicines in the positive list, where applicable. These delays do not include the time needed to prepare submissions under relevant national regulations, which may also include clock-stops for supply of additional information during the process; neither do “Transparency” Directive delays include time required to complete other formalities before a new medicine can be made available in a given country.

EFPIA Market Access Delays analysis

18 www.efpia.eu

The rate of availability, measured by the number of medicines available to patients in European countries as of 2017: for most countries this is the point at which the product gains access to the reimbursement list.

Rate of Availability (%)

Chart1

SerbiaSerbiaSerbia

LatviaLatviaLatvia

LithuaniaLithuaniaLithuania

EstoniaEstoniaEstonia

BulgariaBulgariaBulgaria

CroatiaCroatiaCroatia

PolandPolandPoland

HungaryHungaryHungary

IrelandIrelandIreland

PortugalPortugalPortugal

SlovakiaSlovakiaSlovakia

BelgiumBelgiumBelgium

SloveniaSloveniaSlovenia

FranceFranceFrance

Czech Rep.Czech Rep.Czech Rep.

NorwayNorwayNorway

SwedenSwedenSweden

SpainSpainSpain

FinlandFinlandFinland

SwitzerlandSwitzerlandSwitzerland

NetherlandsNetherlandsNetherlands

ItalyItalyItaly

AustriaAustriaAustria

DenmarkDenmarkDenmark

UKUKUK

GermanyGermanyGermany

Available

Not Available

Data N/A

Rate of Availability

0.0547945205

0.3287671233

0.6164383562

0.1438356164

0.8561643836

0

0.198630137

0.801369863

0

0.2123287671

0.7876712329

0

0.2328767123

0.7671232877

0

0.2808219178

0.7191780822

0

0.3082191781

0.0342465753

0.6575342466

0.3698630137

0.595890411

0.0342465753

0.3904109589

0.6095890411

0

0.397260274

0.3356164384

0.2671232877

0.4109589041

0.5890410959

0

0.4657534247

0.5342465753

0

0.4931506849

0.5068493151

0

0.5068493151

0.4931506849

0

0.5273972603

0.4657534247

0.0068493151

0.5342465753

0.2808219178

0.1849315068

0.5547945205

0.3424657534

0.102739726

0.59

0.38

0.03

0.6849315068

0.3150684932

0

0.6917808219

0.3082191781

0

0.7054794521

0.2945205479

0

0.7260273973

0.2739726027

0

0.7739726027

0.2260273973

0

0.7876712329

0.2054794521

0.0068493151

0.8219178082

0.1780821918

0

0.8493150685

0.1506849315

0

Sheet1

CountryAvailableNot AvailableData N/A

Serbia5%33%62%

Latvia14%86%0%

Lithuania20%80%0%

Estonia21%79%0%

Bulgaria23%77%0%

Croatia28%72%0%

Poland31%3%66%

Hungary37%60%3%

Ireland39%61%0%

Portugal40%34%27%

Slovakia41%59%0%

Belgium47%53%0%

Slovenia49%51%0%

France51%49%0%

Czech Rep.53%47%1%

Norway53%28%18%

Sweden55%34%10%

Spain59%38%3%

Finland68%32%0%

Switzerland69%31%0%

Netherlands71%29%0%

Italy73%27%0%

Austria77%23%0%

Denmark79%21%1%

UK82%18%0%

Germany85%15%0%

EMA approved100%0%0%

19 www.efpia.eu

The average time between marketing authorisation and patient access - the number of days elapsing from the date of EU marketing authorisation (or effective marketing authorisation in non-EEA countries) to the day of completion of post-marketing authorisation administrative processes

Length of market access delays (average)

For most countries patient access equates to granting of access to the reimbursement list, except for hospital products in FI, NO, SE where some products are not covered by the general reimbursement scheme and so the zero-delay is artificially declining the median and average. In France, some innovative products without competitors can be made available prior to market authorisation under the system of Temporary Authorisations. As these are not taken into account in the analysis, the average for France is higher than in reality.

Chart1

Serbia

Portugal

Poland

Lithuania

Bulgaria

France

Slovenia

Croatia

Latvia

Estonia

Slovakia

Belgium

Ireland

Hungary

Italy

Spain

Czech

Austria

Norway

Sweden

Finland

Netherlands

Denmark

Switzerland

UK

Germany

Average

Average delay (days)

979

637

632

563

535

500

494

479

467

436

419

411

408

391

383

374

356.3823529412

329

291

281

250

228

155

123

111

106

Sheet1

Average

Serbia979

Portugal637

Poland632

Lithuania563

Bulgaria535

France500

Slovenia494

Croatia479

Latvia467

Estonia436

Slovakia419

Belgium411

Ireland408

Hungary391

Italy383

Spain374

Czech356

Austria329

Norway291

Sweden281

Finland250

Netherlands228

Denmark155

Switzerland123

UK111

Germany106

20 www.efpia.eu

The average time between marketing authorisation and patient access - the number of days elapsing from the date of EU marketing authorisation (or effective marketing authorisation in non-EEA countries) to the day of completion of post-marketing authorisation administrative processes

Length of market access delays (average)

In most countries patient access equates to granting of access to the reimbursement list, except for hospital products in DK, FI, NO, SE where some products are not covered by the general reimbursement scheme and so the zero-delay is artificially declining the median and average. In France, some innovative products without competitors can be made available prior to market authorisation under the system of Temporary Authorisations. As these are not taken into account in the analysis, the average for France is higher than in reality.

Chart1

SerbiaSerbiaSerbiaSerbia

PortugalPortugalPortugalPortugal

PolandPolandPolandPoland

LithuaniaLithuaniaLithuaniaLithuania

BulgariaBulgariaBulgariaBulgaria

FranceFranceFranceFrance

SloveniaSloveniaSloveniaSlovenia

CroatiaCroatiaCroatiaCroatia

LatviaLatviaLatviaLatvia

EstoniaEstoniaEstoniaEstonia

SlovakiaSlovakiaSlovakiaSlovakia

BelgiumBelgiumBelgiumBelgium

IrelandIrelandIrelandIreland

HungaryHungaryHungaryHungary

ItalyItalyItalyItaly

SpainSpainSpainSpain

CzechCzechCzechCzech

AustriaAustriaAustriaAustria

NorwayNorwayNorwayNorway

SwedenSwedenSwedenSweden

FinlandFinlandFinlandFinland

NetherlandsNetherlandsNetherlandsNetherlands

DenmarkDenmarkDenmarkDenmark

SwitzerlandSwitzerlandSwitzerlandSwitzerland

UKUKUKUK

GermanyGermanyGermanyGermany

# of Products

Maximum delay

Minimum delay

Average

No. of products in sample

Delay (days)

8

1254

519

979

45

1259

39

637

25

1081

169

632

11

1237

256

563

25

1081

43

535

56

1042

168

500

72

1099

84

494

40

969

180

479

21

1017

60

467

30

979

74

436

54

1017

134

419

68

1050

163

411

51

1259

71

408

44

862

72

391

138

1349

77

383

83

1490

41

374

68

1289

45

356.3823529412

49

702

194

329

77

1185

0

291

79

1156

46

281

75

1081

0

250

99

1028

37

228

115

942

21

155

73

738

18

123

117

798

0

111

123

644

6

106

Sheet1

# of ProductsMaximum delayMinimum delayAverage

Serbia81254519979

Portugal45125939637

Poland251081169632

Lithuania111237256563

Bulgaria25108143535

France561042168500

Slovenia72109984494

Croatia40969180479

Latvia21101760467

Estonia3097974436

Slovakia541017134419

Belgium681050163411

Ireland51125971408

Hungary4486272391

Italy138134977383

Spain83149041374

Czech68128945356

Austria49702194329

Norway7711850291

Sweden79115646281

Finland7510810250

Netherlands99102837228

Denmark11594221155

Switzerland7373818123

UK1177980111

Germany1236446106

prevention and management of availability problems: An industry perspectiveMedicines shortagesCauses and main drivers of shortagesScenarios leading to shortages:�Pricing mechanismsScenarios leading to shortages:�Tender practicesScenarios leading to shortages:�Cost-containment measuresScenarios leading to shortages:�Commercial withdrawalsSlide Number 8Slide Number 9Slide Number 10Good practices in �communication of shortagesCurrent communication practicesGood practices in �communication of shortagesGood practices in �communication of shortagesConclusionsSlide Number 16Slide Number 17Slide Number 18Slide Number 19Slide Number 20