FDA/ PQRI Conference Sept 16 and 17, 2014

Peter J. Kitz VP, Quality, Global Pharmaceutical

Bristol-Myers Squibb

2

Agenda Acknowledgements

PIC/S

Inspection Results (EFPIA survey)

Challenges

Consequences

Opportunities

Discussion

EFPIA

Stephan Roenninger

3

4

Observer:

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Training opportunities

International GMP harmonisation : By taking part in the meetings of the PIC/S Committee, PIC/S Participating Authorities are involved in the development and harmonisation of international GMP guides and guidelines. The PIC/S Committee also actively promotes the uniform interpretation of GMP and Quality Systems for GMP Inspectorates.

Networking

High standards

Sharing of information

Rapid Alert System

Facilitating the conclusion of other

Benefits (ref. PIC/S website)

There are also indirect benefits to industry when their relevant regulatory authority becomes a member of PIC/S. These benefits may include the following:

Cost savings

Export facilitation

Enhanced market access

Reduced duplication of inspections

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Foreign Inspections Reported 2003 - 2013

Number of companies 25 16 25 22 23 24 23 24 22 22 22

Numbers of foreign inspections have stabilised at a high level

Source: EFPIA Annual Inspection Survey, May 2014

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Average Duration of Foreign Inspections by Country (EU as 1) Country counted only if more than 4 inspections performed

Significant resources involved in foreign inspections +

11

d

-3

d

> 10 inspector days

10 - 5 inspector days

< 5 inspector days

D 2012

Insp

ecto

r days

= N

um

ber

of

insp

ecto

rs *

Insp

ecti

on d

ays

Without paper based inspections

+3

d

Training included?

Source: EFPIA Annual Inspection Survey, May 2014

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Number of Foreign Inspections in 2013 ordered by country (EU as one; >1 inspections)

≤ 10

>50

50-10

Group 1

Group 2

Group 3

& 6 countries with 1 foreign inspection

Source: EFPIA Annual Inspection Survey, May 2014

9

Statistics: Inspections per Site

41 % of the sites receiving multiple inspections

However the driver for multiple inspections can not be determined from the survey data

Number of Inspections per manufacturing site

Source: EFPIA Annual Inspection Survey, May 2014

10

Statistics: Inspections per Company

Medium size companies receive the most inspections

67 foreign inspections 24 inspectorates

distributed over 78/128 sites

5 foreign inspections by 4 inspectorates

distributed over 5/12 sites

40 foreign inspections by 17 inspectorates

distributed over 31/32 sites

Source: EFPIA Annual Inspection Survey, May 2014

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Number of Inspections by Countries Performing foreign inspections 2008 - 2013

Countries with increasing trends

*

*Only performs foreign inspections in LA countries and accepts GMP certificates from most PIC/s member inspectorates Source: EFPIA Annual Inspection Survey, May 2014

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Number of Inspections by Countries Performing foreign inspections 2008 - 2013

Source: EFPIA Annual Inspection Survey, May 2014

13

Number of Inspections by Countries Performing foreign inspections 2008 - 2013

Source: EFPIA Annual Inspection Survey, May 2014

14

Overview of Inspection Activities 2013

Conducting and receiving inspections involves considerable regulator and industry resources

Inspections Days

Different inspectorates performed foreign inspections in 2013 (EU inspectorates = 1)

31

Foreign Inspections 521

Domestic Inspections at research-based industry with major activities located in Europe and US

614

Foreign inspector days 4181

Domestic inspector days – spent by regulators only, industry resources not included

4555

Source: EFPIA Annual Inspection Survey, May 2014

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Summary of the 2013 Survey Data Numbers of foreign inspections stabilised at a high level

Data sound, consistent, and comparable with previous years No joint inspections were reported Still no impact observed in the data from the EU/US inspection program

1/3 of the sites still receive multiple inspections High level of domestic inspections coincide with a high level of foreign

inspections

Resource Inspections among PIC/S member and accession inspectorates: There is

no trend of decreased overlap of inspections by PIC/S inspectorates

Europe and US is the focus of foreign inspections In addition to US FDA and EU a big workload for foreign inspections is

coming from Japan and emerging markets (e.g. South Korea, Brazil, Turkey, Kenya, Mexico)

Inspectorates from emerging markets mainly focus on sites in EU & US Inspectorates from emerging markets are all non-PIC/S members (to

date)

Source: EFPIA Annual Inspection Survey, May 2014

Key Points

Inspected companies need 10 times more resources for inspection preparation and conduct than regulators

The preparation effort is driven by specific requirements from individual inspectorates

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Resources Inspector Industry

Preparation for specific requirements by individual inspectorates

4 man days (experience from industry audits)

90 man days

On site 8 man days (average from the survey)

55 man days

Post-inspection 4 man days (experience from industry audits)

15 man days

Sum 16 man days 160 man days

Fees/Travel - Approx. 30’000 EUR

Source: EFPIA Annual Inspection Survey, May 2014

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Countries Performing Foreign Inspections 61 countries have performed foreign inspections from 2003 to 2013;

31 countries performed foreign inspections in 2013 (35 in 2012; 35 countries in 2011)

• Algeria • Argentina • Australia • Belarus • Botswana • Brazil • Canada • Chile • China • Chinese Taipei • Columbia • Costa Rica • Croatia • Egypt • Ethiopia • EU-countries2

• Ghana • Guatemala • Gulf States (GCC) • Honduras

• India • Indonesia • Iran • Iraq • Ivory Coast • Japan • Jordan • Kazakhstan • Kenya • Lebanon • Libya • Malaysia • Mexico • Morocco • New Zealand • Nigeria • Oman • Papua New Guinea • Pakistan • Peru

• Russia • Saudi Arabia • Sierra Leone1

• Serbia • Singapore • South Africa • South Korea • Sudan • Syria • Switzerland • Tanzania1 • Thailand • Tunisia • Turkey • Uganda • Ukraine • USA • Venezuela • WHO • Yemen • Zimbabwe

1 new in 2013 2 EU countries as one inspectorate only active in previous years; no reports in 2013

17 Source: EFPIA Annual Inspection Survey, May 2014

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Joint / Concurrent Inspections Reported

Fact: Zero joint inspections reported in 2013

Possible influences, industry view: Positive and negative experience in the past Linked often with a parallel assessment pilot Programs started before US-FDA joined PIC/S Very few Industry volunteers and little participation Benefits of a joint inspections is not clear Arguments: Results of the joint inspections are unpredictable

Regulators experience? Is there an assessment of the outcome of the pilots? Will regulators continue organising joint inspections?

Source: EFPIA Annual Inspection Survey, May 2014

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Mutual Recognition and/or Mutual Reliance

Resources could be better leveraged by mutual recognition or reliance on inspection outcomes from trusted inspectorates

Exchange of inspection reports and companies responses Seems not to reduce the number of inspections

Seems to be used as preparation resources

Basis for reliance in a trusted inspectorate What qualifies a trusted inspectorate?

(e.g. MRA/MOU, Confidentiality agreements)

PIC/S membership only?

Are there legal boundaries to allow better use of synergies?

Why do I need to see it myself?

Cultural issues?

How can we respect the reasonable needs of individual countries for a win-win situation (e.g. PIC/S, TTIP)?

How can industry facilitate this process?

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Challenges

Intellectual Property

Confidentiality

Trust

Regulatory Diversity

Serialization

Cross Contamination

Stability/ Degradation

Validation

Example: South Africa

Multiple Pharmacopeias

Consistent application ICH Q8-11 during inspections

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Consequences

Resources

Cost

Patient Access

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EFPIA and PhRMA propose that consistent, effective and balanced risk based regulatory

oversight, allowing for improved resource utilisation, can be further enhanced by:

Continued regulatory agency collaboration

To drive harmonisation and optimise use of global inspections resources:

For domestic inspectorates to act as primary overseeing body, and by mutual

recognition of each other’s systems or reliance of inspection outcome.

Harmonized GMP and GDP standards

To support consistent interpretation of regulatory requirements.

Harmonized regulatory inspection processes including

Inspectorates certification process,

Inspection planning and documentation: standard data packs for on-site and paper

based inspections for faster provision of information, and better use of resources,

Risk based approach to inspection

Inspection findings and reports: standard terminology for the categorisation of

observations and standard reporting template,

Sharing of inspection results in database,

Globally accepted GMP/GDP certificate format to document compliance of an

inspected site.

Enhanced Good Manufacturing and Good Distribution Practices (GMP/ GDP) Inspection Efficiency

Source: EFPIA Annual Inspection Survey, May 2014

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Opportunities Trust

Collaboration

Efficiencies/ Coordination

Expand MRAs

Colombia Model

Rx-360 Example

Science/ Risk Based Methodology

Cost savings/ Product Cost/ Access

Harmonization between ICH and PIC/s

Advocacy – Broad Industry Involvement

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Thank You

Questions?

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Back Up Slides

MRA partners status of European Union

• Australia: Fully operational

• Canada: In operation, except for preapproval inspections and medicinal products derived from blood or blood plasma

• Israel: Operational with some exclusions

• Japan: Operational on 29 May 2004 - with limited scope

• New Zealand: Fully operational

• Switzerland: Fully operational

• USA: Not in operation

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America

• Canada • Argentina

• USA

• Brazil • Mexico *

Africa

• South Africa - Chair

• Uganda • (Zambia) • (Zimbabwe)

Australia

• Australia

• New Zealand

Asia

• Chinese Taipei

• Indonesia

• Japan

• Malaysia

• Singapore

• South Korea

• Hong Kong, China • Iran • Philippines • Thailand • Kazakhstan*

(Bhutan) • (China) • (Oman) • (Saudi Arabia)

Europe

• Austria

• Belgium

• Cyprus

• Czech Republic (H/V)

• Denmark

• Estonia

• Finland

• France (H/V)

• Germany

• Greece

• Hungary (H) • Iceland

• Ireland

• Israel

• Italy

• Latvia

• Liechtenstein

• Lithuania

• Malta

• Netherlands

• Norway

• Poland

• Portugal

• Romania

• Slovak Republic

• Slovenia

• Spain

• Sweden

• Switzerland

• United Kingdom (H/V)

• Ukraine

• Turkey • Armenia* • Belarus* • (Bulgaria) • (Croatia) • (Georgia) • (Hungary (V)) • (Russia) • (Serbia)

Accession Country: membership evaluated *Pre-accession country: in preparation for accession (Country): interested countries/parties

Partner

• EDQM

• EMA

• UNICEF

• WHO • (ASEAN)

Status 01.07.14