life sciences & healthcare reviewing hot regulatory...

Life Sciences & Healthcare

Mike Meakin

Vice President – Global Quality, Regulatory & Compliance

Life Sciences & Healthcare Longboat Key - 11th October 2012

Reviewing Hot Regulatory Challenges, New EU GDP “Good Distribution Practices”

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Longboat Key 11th October 2012Compliance & Patient Safety First!

Introduction

Logistics Changes – global enlargement, manufacturing, patents, volumes, litigation

Regulatory Trends

� GDPs evolving into GMPs – Harmonisation ICH & PIC/s

� GCCMP - TTSPP Time Temperature-Sensitive Pharmaceutical Product (WHO TRS 961)

� QRM (ICH Q9 & ISO 14971) – Risk based Approach

� Supply Chain Integrity – SSFFC – Counterfeits, Theft, Diversion, Adulteration, Expiry

� Licensing, Contractors, Bona Fides

Challenges:

� Regulation – greater and greater regulation – increase costs

� Infrastructure – Pharma grade – Plants & Facilities HVAC

� Capacity – SISPQ cross contamination

� Validation

Growing Markets – BRIC-TM

� Importing countries

� Exporting countries

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DHL Life Sciences GxP Footprint

DHL has over150 Life Sciences &Healthcare facilities Globally

Over 100 warehouses operating to GxP requirements

GMP Facilities Pharma & ISO 13485

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Longboat Key 11th October 2012Compliance & Patient Safety First! 44

Life Science & Healthcare Quality Systems - Patient Safety!

Patient safety

• Protecting the patient – mistakes can harm even kill!

Product quality

• GMP compliant must have SISPQ characteristics

Compliance

• Customer quality assurance agreements

1898 – Heroin marketed for coughs! - Harrisons Tax Act 1914

1902 – Biologics Control Act – 22 children from contaminated vaccines

1906 – FDA formed

1937 – Elixir Sulfanilamide tragedy

1939 – Faddis MF. Eliminating errors in medications.

1940 – Winthrop Sulfathiazole – Phenobarbital contamination

1961 – Thalidomide withdrawn – Drug Amendment Act 1962

1972 – Fatalities Devonport Hospital Lot D1192/C Evans Medical

1982 – Tylenol laced with Cyanide in Chicago (tamper resistant)

2000 – To Err is Human – Bill Clinton

2008 – Melamine adulteration 6 babies die 860 hospitalized – 2 executions!

2009 – Heparin recall – 1800 adverse events 246 deaths - 86 fit profile*

2011 – Isotab (isosorbide mononitrate) c150 deaths 450 serious ARs

Quality objectives (DRA, GAMP, GDP)

History – result more legislation

* 12 Chinese companies supplied 11 countries

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GDP - Robust recall process – understanding PDA TR 55

*Epal – European Pallet Association **CHEP - Commonwealth Handling Equipment Pool

Heat Treated Mark Epal Pallet

NON HT Epal* Pallet

Heat Treated Mark CHEP** Pallet

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Understanding the need for GDP?

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LSPs also have commercial and legal challenges

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Contamination Issues What can Go Wrong

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Can we trust suppliers - Counterfeiters Paradise?

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With over 30 different GDP Worldwide and several recent updates,

the regulatory world is also changing

Regulatory Changes in many Countries including BRIC-TM

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China, India, Turkey,

South Korea

• USP <1079> Good Storage & Shipping Practices

• USP <1083> draft – GDP Supply Chain Integrity

• IATA PCR Ch 17 – T&TS Label 1 July 2012

• AFNOR NF S99-700, Oct 2009

• ASTM D3103 – Thermal Insulated Performance

• ISTA 7D & 7E – Thermal Transport Packaging

• No 39 Revised 2007 T-C Medicinal Prdoucts

• No 46 Issued 2009 – GDP last mile

• No 52 Issued 2011 – GDP Pharma Supply Chain

• No 53 Issued 2011 – Stability Testing

• No 55 Issued 2012 – Detect/Mitigate TBA/TCA

• No 58 Issued 2012 – Risk Management TCD New PDA Guidance coming out

STANDARDSPROCESS – PDA Technical Support

BRIC-TMl Changes

AS OF SEPT, 2012

Supply Chain Integrity/GCCMP

IATA Labeling Standard

Brazil, Mexico Argentina, Australia,

Canada, Czech, Egypt,

Ireland, Italy, Romania,

Malaysia, Saudi Arabia,

UAE, Singapore, South

Africa, Venezuela

DHL GxP Policy

New EU GDP Focus on EU GDP

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New EU GDP Guidelines: 30+ Worldwide GDPs –

PIC/s looking at new EU GDP as a Global standard

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Updated and Newly Issued Regulations and Guidelines

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DHL Yellow Book – Annex K results on GDP issues

Annex K: D

HL Life

Sciences & Health

care GxP Audit T

ool

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Challenges meeting GSP & GDP

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New EU GDP Guidelines – GMP ≠ GDP

GMPs Continue to Evolve into GDP & GWP

GDP + QMS = SCI

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Other Implications Directive 2011/62 amending 2001/83

�Falsified Medicines Directive and

unique identifiers having a impact

on Good Traceability Practice

�USP 1083 – GDP – Supply Chain

Integrity is doing something similar

in the USA linking USP 1079

�PDA TR 52 – is showing how to

assess logistics providers

�PIC/s – have GDP on their 2015

Road map may also adopt EU GDP

�Impact pedigree and serialisation

finish with a few pictures and a

short video

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DHL responded to the EU GDP in Dec 11

- Over 20 specific comments in 25 pages

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Proposed new EU GDP Chapters 1-3

Chapter 1:Quality Management:

• A QMS has to be in place Deviation Reporting, CAPA, Change Control

• QRM intorduced based on ICH Q9

Chapter 2 Personnel:

• Responsible Person in each distribution point (permanence)

• Delegation possible ? Documented deputyships for other personnel

• Hygiene & Training

Chapter 3: Premises and Equipment:

• Temperature & environment control – Temp Mapping

• Qualification & validation

• CSV – Computer Systems Validation

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Anja Verstegen+7

Peter Klaessens WSC

Jay Rijnen QP Manufacturing

Cees Schaap QP- Distribution

NETHERLANDS

Chloe ShihAileen Zhu

CHINA

Mike Meakin

VP - Global Quality Regulatory & Compliance


Evgenia Egorova

RUSSIA

Melissa MalesicKonni SynderAmy NicholsMonica Hinderer Licenses

USA

Maria Assunta Sgro

Erika Garganese

Margherita Bubbico

Roberto Bigagli

Alberto Ugazio +3

ITALYBerna Tuncel

TURKEY

Roberto Azcuaga + 15

Carol Candlish QP

David Burnett QP

David Stevens QP

Paul Sellwood

Andrew Watkins

Pete Rhodes

Niall Spare

Patrick Train

Claire Macintosh

UNITED KINGDOM

Sally Verdurmen

Dirk Ledegen

Francoise Rogister

Gaellle Blondeau

Alain Warnier

Martina Immel

Kristin Vandenbussche

BELGIUM

Estelle Harris

Reshma Chunder

Yolanda van Vuuren

Malani Moodley

Verna Crouse (Cons)

SOUTH AFRICA

Elodie Hantz

Vincent Boudy

Sylvain Moraud (V)

FRANCE

Joana Ribeiro

PORTUGAL

Amelia Quijano

Juan Cejudo

SPAIN

Valerie Byrne

IRELAND

Farakh Rashid –

Validation Manager

Global Healthcare

Tom Young –

QA/RA Manager

Healthcare EMEA

Binu Panicker

Indrajit Sarkar

UAE

Ashraf Luca

Sarah Mansour

Marie Naim Morcos

EGYPT

Choi Wei Chai

Yun Ng

Fermin Joel Bagadiong

SINGAPORE

Kati Lottonen

SWEDEN

Katarzyna Gapska

Artur Spicak

POLAND

Wilfried Höra

Torsten Baeumer

GERMANY

Fernanda Teles

Rodrigo Bianconi RA

Fernanda Lago QA

Lucimeire Sola CSV

Juliana S. Filizzola+ 15 Pharmacists

BRAZIL

Kylie Coulson

Bronagh McVeigh 9+14

AUSTRALIA

Hikaru Shiba

Mizoumi Onuki

Naoshi Konogaya

Tatsuhito Hishida

Sayaka Mochizuki

JAPAN

Bernd Thomas

SWITZERLAND

Alfonso Roa

Leticia Pena

4 Responsible Persons

MEXICO

Miguel Sanshez

Luis Nunez - CainCo

PANAMA

Suyog Kudtarkar

INDIA

Katja Nolvi

FinlandMark Benzahia

Salem Al Suhaimy

Nasser Al Shammry

Mohammed Al Ghamdi

SAUDI ARABIA

Alexandra Karacs

HUNGARY

DHL employs over 60 dedicated full-time Pharmacists globally

Workforce 5% dedicated QA

Ratios 1:50 GDP 1:30 GMP

LSPs - Qualified People - Chapter 2 GDP & GMP

JT Kim

YJ Hur

Ephrem Song

SOUTH Korea

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Chapter 4: Documentation:

• Focus on record keeping and traceability of all transactions “batch numbers ->

safety features ?”

• Take the advantage of the electronic means

Chapter 5: Operations:

• Qualification of Suppliers

• Qualification of Customers – Bona fides – deliver to licensed premises

• Good Storage Practice (reception, delivery, packing, destruction, export etc )

Chapter 6: Complaints, Returns, Recalls, suspected Falsified Medicinal Products

• Complaints, Returns & Recalls

Chapter 7: Contract operations:

• QTAs Quality Technical Agreements between Sub contractors & Suppliers

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Chapter 8: Self-inspections:

• Independence – auditing

• Subcontractors in accordnace with GDP

Chapter 9: Transportation: (most contentious being modified?)

• Tranportation (24 hours)

• Containers packaging and labelling

• Special condition – controoled substances and radio active medicines

• Temperature Control during transport

Chapter 10: Specific provisions for Brokers:

• Regulating the middlemen “They gain, they have to share the pain!”

• Brokers need authorisation – Quality Systems etc too

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Validated temperature-control systems –

Refrigerated vehicles OQ & PQ undertaken in Climate Chambers?

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9.1 The required storage conditions

for medicinal products should be

maintained during transportation

within the defined limits as described on the packaging

information

9.19 Validated temperature-control systems (e.g.

thermal packaging, temperature-controlled

containers, and refrigerated vehicles) should be

used to ensure correct transport conditions are maintained between the distributor and customer.

Customers should be provided with a temperature

data to demonstrate that products remained within

the required temperature storage conditions during transit, if requested.

New EU GDP Guidelines:

DHL Yellow Book – 4 AreasActioned in Version 6.1

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Regulations, Guidelines & Customer Standards Develop

Into a LSP PQS Guidelines Includes cGMP

Customer requirements + QAA

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It is going to cost more?

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Compromised Integrity – Supply Chain Threats

The Falsified Medicines Directive has further requirements

The US FDA refers to 5 areas of threat to SCI:

� Counterfeit drugs

� Cargo Theft/Stolen drugs

� Diverted drugs

� Internationally adulterated drugs (EMA)

� Expired drugs

All the above feed into the need for Pedigree or Serialisation and

are linked with Supply Chain Integrity and new standards e.g. USP

1083

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Labeling - Challenging Regulatory Environment Traceability

Key:

Machine-readable law in place

Serialisation law discussed

Serialisation law in place

Track & Trace Law in Place

Track & Trace Law discussed

Swedish Trial 2009

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Thank You - Contact Details

Mike Meakin

Vice President

Global Quality & Regulatory Compliance

DHL Supply Chain

Newnham Drive

Heartlands Business ParkDaventry

NN11 8YG

United Kingdom

Phone +44 (0) 1327 308 400

Mobile +44 (0) 7774 299 402

[email protected]

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