Eur Ing Charles A.

Smith CEng MIET MInstMC

A Smart Approach to the Introduction of

Serialisation in Pharmaceutical Corporations

Horizon 2014

Who are Horizon?

Horizon are an Engineering & Consultancy Company
Key areas of activity:
SMART Serialisation : from audit to validation, customised
or turn key projects
SMART Manufacturing
Provide a range of other Engineering solutions
Ireland - Benelux - France
Horizon 2014

Agenda

International Regulatory Drivers for Serialisation

Business Drivers for Serialisation
Serialisation Terms
Global Differences in Requirements
Key Influencing Factors
Process Mapping
Risk Assessment
Best Practices for International Serialisation Projects
Horizon 2014

International Regulatory Drivers for

Serialisation
Counterfeit Drugs
Dangers
No actual active ingredient
Wrong strength (too high/low) of active ingredient
Drugs contaminated with dangerous materials
Expired Drugs can be toxic

Horizon 2014

International Regulatory Drivers for

Serialisation
Counterfeit Drugs
Increasing level of counterfeit drugs in the supply chain
World Health Organisation report of counterfeit levels:
1% in developed world
10% global
Higher in regions - Asia, Africa and Latin America
Estimate that up 50% of drugs purchased on the internet are
counterfeit

Horizon 2014

International Regulatory Drivers for

Serialisation
Counterfeit Drugs
Last 4 years Interpol Police
action on counterfeit websites
2009 153 sites shutdown
2010 297 sites shutdown
2011 13500 sites shutdown
2012 18000 sites shutdown

Horizon 2014

Shut Down Web Sites

20000
15000
10000
5000
0
2009

2010

2011

2012

International Regulatory Drivers for

Serialisation
Drug Reimbursement Fraud
Many countries have seen multiple claims for the same
issued drug
No unique numbering on the issued drugs - difficult to
check multiple claims
Significant cost of fraudulent claims - impacts on care that
can be given to other patients

Horizon 2014

Business Drivers for Serialisation

Counterfeits from an Industry Perspective
Corporations seeing more counterfeits returned as
Customer Complaints and via notifications from Ministries
of Health.
Overall appearance of counterfeits improving
Potential for counterfeits to both damage the Corporations
reputation and cause product recalls
Transfer of products to other markets
Relabeling of expired product
Horizon 2014

Business Drivers for Serialisation

Recent Counterfeit Examples
July 2013 FDA Roche Avastin Cancer Drug
identified via wholesalers in Egypt, Switzerland,
Denmark, UK
Counterfeit BDMI company also handled Amgens
Neupogen (white blood cell stimulator) and
Genentechs Rituxan
Aug 2013 Kiev, Ukraine Cascade Medical Products
$37m counterfeit products seized no batch
numbers, expiry dates or instruction leaflets
Nov 2013 FDA identify counterfeit herbal and
nutritional product contained prescription active
ingredient

Horizon 2014

Business Drivers for Serialisation

Other business drivers
Recall management easier to identify product distributed
International Supply Chain Management
Reduce the chance of counterfeit product entering the normal
complex supply chain
Improved control of product stock control of expiry status and
inventory at different locations

Horizon 2014

Some Serialisation Terms

Serialisation - include a known unique serial number on products
Track (forward) - Determining the downstream locations of products in the supply
chain (Where now? Where going?)
Trace (backward) - Identifying the upstream history of where a product has been at
what times (Where has it been?)
Aggregation data structure of distributed product (in identified shipping Case/Pallet)

Horizon 2014

Serialisation Terms
EPCIS Electronic Product Code
Information Services
GS1 International Standards body coding
GTIN Global Trade Identification Numbers
Subset NTIN National Trade Item Numbers

AI Application Identifiers 01 GTIN, 10 Batch,

17 Expiry Date, 21 Serial Number
GLN Global Location Numbers
GS1 DataMatrix ECC200
GS1 128 Linear

RFID Examples
SSCC Mixed Pallets

Horizon 2014

Global Serialisation Activity

Aggregation
Serialisation
Serialisation under discussion

13

Horizon 2014

Key Recent Regulation Developments

US HR 3204 Drug Quality & Security Act - Nov 2013
2017 - Manufacturers to include SNI (US product code),
Lot, Expiry Date to Cartons and Shipping Cases.
Manufacturers must provide in electronic format a
Transaction History at Lot Level (not sGTIN or serialised
SNI). Moving to verification at point of dispense.
2023 - Full aggregation in place throughout all distribution
phases
Likely to pre-empt Californias Electronic Pedigree Rules
Horizon 2014

Key Recent Regulation Developments

Brazil Anvisa Serialisation / Track & Trace Dec 2013
3 Years - Manufacturers to include Unique Medicines Identifier
(UMI) which includes Serial Number, Lot, Expiry Date and
Anvisa Registration Number (Brazils product code) as 2D data
matrix and human readable form to hospital packs.
Deadline of 2 years for Pharmaceutical Companies to submit a
comprehensive report on the traceability of at least 3 batches
which will be submitted to the Anvisa technical committee

Horizon 2014

Key Regulation Developments

European Union Falsified Medicines Directive 2011/62/EU
Prescription medicines to include safety features
Unique serial number on each carton allowing verification at point of dispense
Tamper Evident Packaging

To be implemented as delegated act for EU Countries (expected

2014) with date of application 3 years after publication
Two European wide traceability repositories for drug data under
development to allow connection to national databases
European Directive for the Quality of Medicines & Health Care (EDQM) - eTACT
system trial
European Federation of Pharmaceutical Industries and Associations (EFPIA)
European Stakeholder Model (ESM)

Horizon 2014

Key Influencing Factors

SKU Stock Keeping Unit

Which countries?
On which packaging lines?
Manufacturing in which countries?
Cold Chain or other Features?

New Product Introductions

Build in serialisation to design

Packaging / Labelling Design

Larger area needed for printing
Must be visible for scanning

Horizon 2014

Equipment Aspects
Age of actual packaging lines
Upgrade or replace?
Physical layout/space for new
equipment
Equipment Capability printers
larger higher resolution Images
Reject Mechanisms
Equipment must be flexible and
configurable dependant on SKU /
country of export

Key Influencing Factors

Production Schedule
Spare capacity on lines
Production to stock for customer
supply forecasts
Plan for equipment modification
Allow for lower operational
efficiency during starting phases
Highest speed lines in continuous
use so difficult to schedule

Horizon 2014

Resources
Corporation resources
Equipment Supplier Capacity
External Systems Specialists

Infrastructure
EPCIS
Serial number provisioning
Solutions across manufacturing
and warehousing
Existing ERP / Warehouse
Systems and Master Data

Key Influencing Factors

Validation
Full development lifecycle driven by
risk assessment to show the systems
reliably meet their intended design
Standardisation where possible to
allow common unit testing
Configurable design with associated
testing to show functions for different
SKUs / countries
Change control to track different
Ministry of Health requirements

Horizon 2014

Process Mapping

Process Mapping allows better

understanding of existing process
(current state) and how it can be modified
(future state)
Multidiscipline team equipment /
automation / computer specialists,
operations safety needed to reflect:

Physical actions (SOP), equipment steps,

communications, and master data
Process phases Batch Setup, Normal batch
operation (rejects, sampling) and end of
Batch Processing
Even manual processes can be quite
complex

Horizon 2014

Process Mapping
Process Mapping needs to consider different levels and may need a different
expertise as part of project team:
Machinery level automation and integration with printing / vision systems
Plant Level systems how serial numbers are locally provisioned, and posting
of serialisation code activation, commissioning and destruction to EPCIS
servers
Warehouse systems to support the distribution process after product leaves
the manufacturing areas covering pallet and shipping case handling with
exceptions like product returns or physical damage
Corporate level interfaces from EPCIS servers through to the required
Ministry of Health Repositories.

Horizon 2014

Risk Management

A formal technique of risk analysis like

FMEA (Failure Mode and Effect
Analysis) provides a suitable method
of methodically reviewing the potential
risks associated with system
modifications for serialisation.
A multidiscipline team reviews the
process maps step by step through
stages of the process
For general guidance risk analysis see
ISPE GAMP 5 Section 5 and
Appendix M3 or ASTM E2500
Horizon 2014

Risk Management

For FMEA, the review looks at the stages in the process, the equipment / process
involved, the effects, ranking of severity, causes and probability of occurrence,
and the probability of detection to give a Risk Priority Number
At a higher project level, other risks also needs to be considered
Effective management project sponsorship
Project team members with insufficient experience / technical knowledge
Lack of user input from project stakeholders 3rd Party Service Providers (for
example distribution), Corporation Staff in other countries, outsourced
manufacturing companies, computer support groups and service levels
Learn the lessons from the Corporations Phase 1 Projects (Turkey / China)
Suppliers failing to deliver on time (supplier audit)

Horizon 2014

Risk Management
Specific Risks for serialisation include:
Operation of Packaging lines become dependant on the reliable operation of
computer servers and infrastructure.
Data loss associated with serialisation may require the potential reworking of
product
There is a potential for scope changes due to the evolving requirements
from National Ministries of Health

Horizon 2014

Some Best Practices for International

Serialisation Projects
Some specific best practices are suggested for Multinational Projects:
Note the cultural and operational differences faced by projects spanning
multiple countries. The ISPE Good Practice Guide - Global Information
Systems Control and Compliance provides some practical guidance
Put in place a strong project management team capable of handling the
range of technologies from Enterprise Level critical data management and
infrastructure, to equipment level packaging equipment.
Consider an early supplier assessment/audit of key system suppliers to
confirm that they have the capability to support, not only your corporations
requirements, but also their existing commitments to other customers.
Also at an early stage, develop a realistic project plan to execute such a
complex project within the production constraints of market supply.
Horizon 2014

Any Questions?
We can answer your specific
Questions or Needs
At PharmaPack booth 735

26

Horizon 2013