wvc 2013 merck millipore frank appel ensuring critical vaccine supply

Ensuring Critical Vaccine Supply: Raw Materials Perspective

Frank Appel, Senior Manager

Europe Vaccines Segments I Process Solutions I Merck Millipore

World Vaccine Congress – Lille, Oct. 2013

At a Glance

“... Manufacturing vaccine is a complex,

time-consuming, capital intensive, and

highly regulated process requiring an

efficient supply chain and supportingefficient supply chain and supporting

infrastructure of highly qualified staff, and

reliable and continuous supplies of utilities..”“The Vaccine Industry: Does it Need a Shot in the Arm?” National Health Policy Forum

Background Paper. 25 January 2006. A publication of GlaxoSmithKline Government

Affairs, Public Policy and Patient Advocacy

2

"Got a few problems going from lab scale to full-scale manufacturing!"

World Vaccine Congress 2013 , 16-17 April

Facility

Equipment

Process Each source is a potential

Ensuring Safety: A real challenge & business risk

Case Studies of Microbial Contamination in Biologic Product Manufacturing Suvarna, K., Lolas, A., Hughes, P., Friedman, R. Biotechnology Manufacturing Team, Division of Manufacturing and Product Quality, Office of Compliance, Center for Drug Evaluation and Research, Food and Drug Administration

Process

Materials

Utilities

Personnel

Each source is a potential

entry point for adventitious agents

and poses varying levels of risk

3 World Vaccine Congress 2013 , 16-17 April

The Reality of Upstream Contamination*

Contamination events in Upstream Processing have broadly affected the plasma, vaccine and recombinant protein industry.

2012: Leptospiralicerasiae

1980s:HIV 1994:

2009:Vesivirus 2117

2011:Mycobacteriacontaminated

bioreactor

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1950s-60s: Simian 40

in Polio Vaccine

licerasiaecontaminated seed

train bioreactor

HIVcontaminated

Factor VIII

1994:Hepatitis C

contaminated IgG

1996: Minute Virus of Mice

contaminated bioreactors

Vesivirus 2117contaminated bioreactors

2010: Porcine

Circovirusin Rotavirus

Vaccine

2012: Bacillus

thuringiensiscontaminated

bioreactor

*This timeline highlights only major contamination eventsWorld Vaccine Congress 2013 , 16-17 April

BioSafety Strategy / The Pathogen Safety Tripod

Sourcing Testing Clearance

Selection of Screening of raw Removal or

ContaminationRisk Mitigation

Main differences:

The inclusion of an upstream sterility process step provides a high level of

sterility assurance. The inclusion of an upstream virus clearance process

step provides a high level of risk reduction.

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Selection of

low-risk raw

materials

Screening of raw

materials and drug

process samples

for microbial

contamination

Removal or

inactivation of

microbial

contamination


Secure the Entire Supply Chain

DIN ISO 13485 and DIN ISO 14971 Medical Devices Act

66

SOP describes the Merck process for supplier qualification

according to valid international guidelines

US GMP Guidelines /

Code of Federal Regulation

ICH Q7

EU GMP Guidelines / Pharmaceutical Inspection Convention


Supplier Identification ProcessQualification Process for Raw Materials

Batch CoA, Multi

Merck MilliporeQualifier and Manufacturer

Dedicated to GMP requirementsPurchasing, Quality Control & Assurance

Production & Warehousing, Reg. Affairs & Marketing

ChemicalRaw MaterialManufacturer

Supplier

PharmaceuticalsManufacturer

Final dosage formsStrongly regulated

Authority&

Patients

Process change

control for GMP

Batch CoA, Multi pharmacopoeial

decl., EMPROVE,

Regulatory support

Competence in chemicals and pharma-

ceuticals productions

Qualifier competence:Safe and reliable pharma supply

chain, products, and services

Competence in chemicals production

Reproducible and safe production process

ApprovalProof safe processes and drugs

Production of safe drugs for consumers and authorities

Supplier Qualification

Supplier Qualification

Authorization


EMPROVE®

A new safety thinking for raw materials

Industry challenges are increasing:

� Regulatory scrutinity

EMPROVE®

� High quality chemicals� Comprehensive testings ( i.emicrobiology, endotoxins) � Regulatory scrutinity

� Standardization need� Quality ensurance

microbiology, endotoxins) � Lot to lot consistency� Max product safety� Dossier is in line with the Common Technical Document part 3 "Quality" (CTD format), ideal for worldwide product approval


Minimize regulatory risk and exposure

Approaches to Ensuring Critical Supply

Inventory Management� Forecast visibility for bill of materials (BOM)� Vaccine manufacturer managed inventory� Vendor managed inventory� Vendor technical support − e. g. Commissioning a new manufacturing line

Risk Assessment � Each unit operation and supplier should be

included in the risk assessment.

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Equipment service schedules� May need acceleration due to increased

production

Secondary Sourcing� Forecast visibility

Human Resource Management� Hiring/sourcing/re-assignment of operators− New operators will need to be sourced from other areas− New operators will need to be trained to handle increased demand− Training of operators on specific unit operations


Inventory Management Options

Option 1: Full Risk Mitigation Inventory based on Return To Back Orders (RTO)

� Purchased inventory held at vaccine manufacturing site

� Provides total risk protection

� Significant investment

Option 2: Safety Stock Program (Vendor Managed Inventory)Option 2: Safety Stock Program (Vendor Managed Inventory)

� Vendor to hold specified quantity of product reserved (BOM)� Rotation of Safety Stock (to prevent aging)

Option 3: Vaccine Manufacturer places 12 month Standing Order

� PO placed for anticipated 12 month requirement broken down by estimated dates for product delivery and quantity

− Raw material inventory is reserved 30 days in advance of standing order ship date.o Mitigates the risk of raw material supply disruption due to back orders.

o Requires active vaccine manufacturer / vendor monitoring of consumption & demand


Summary� How to ensure the supply chain?

− Efficient Supply Chain

− Qualification process

− Inventory Management

− Risk Assessment

− Secondary Sourcing− Secondary Sourcing

� How can you prevent unnecessary process changes ?

− Use the right, regulatory-compliant raw materials already during the first R&D

and process design steps

� How to reduce supplier qualification effort & incoming goods testing?

− Emprove® suppliers are approved and audited by an comprehensive Inquiry

Check-list ( + sample testing) / Validation Report Emprove® Dossier

World Vaccine Congress 2013 , 16-17 April11

We are Engaged in the Vaccine Market

Greater customer insights

Enhanced R&D

Increased innovation

Mobius® single-usemanufacturing

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Global manufacturing & distribution capabilities

Broader salescoverage

R&D capabilities

Comprehensiveproduct

offering

innovation

Viresolve®

Purification withion exchangers

Emprove®


wvc 2013 merck millipore frank appel ensuring critical vaccine supply

Documents

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