wvc 2013 merck millipore frank appel ensuring critical vaccine supply
TRANSCRIPT
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
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"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
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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
World Vaccine Congress 2013 , 16-17 April
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
World Vaccine Congress 2013 , 16-17 April
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
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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
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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
World Vaccine Congress 2013 , 16-17 April
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
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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®
World Vaccine Congress 2013 , 16-17 April
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