Ensuring Quality and Availability of ARV Drugs

1
Ensuring Quality and Availability of ARV Drugs

• Tom Layloff
• Quality Assurance Manager
• Supply Chain Management System

2
Process for Quality Assurance of ARVs

• All FDA approved products must be produced in
  compliance with current Good Manufacturing
  Practices which includes
• Using APIs which meet the guidelines of the
  International Conference on HarmonizationAdopted
  World-wide
• Having on file with the FDA an approved Drug
  Master File which describes the synthetic path
  and purification processes
• Using excipient materials which meet their
  required standards
• Manufacturing with a validated process
• Using equipment cleaned with a validated procedure

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What makes a Quality ARV?

• A Quality ARV Product Must Be
• Produced in Accordance with their approved
  application materials. Which requires
• Dosage form uniformity
• Bioavailability
• Tentatively approved products have been shown to
  be bioequivalent to US innovator products
• Produced in Accordance with Good Manufacturing
  Practices
• Stored in accordance with conditions shown to be
  appropriate through stability studies.

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What can Suppliers do to Ensure ARV Drug Quality?

• Purchase from FDA approved manufacturers
• Purchase products with sufficient remaining
  expiry period to allow distribution to and
  consumption by the patient within the remaining
  period.
• Maintain supply chain conditions to assure
  product quality.
• SCMS will share with FDA product labeling and
  analytical testing results

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Assuring Product Availability

• For Industry to respond to the anticipated
  scale-up in production it is important to have
  market
• Predictability
• For efficient manufacturing it is critical to be
  able to program production to ensure that
  equipment and materials are optimally used.
• Predictability Threats
• Poor forecast data
• Changes in treatment regimens
• Viral mutations
• Product cost changesnew API synthesis routes
• Sustainability to amortize investments
• Sustainability threats
• Shift in US Government Priorities
• An effective vaccine

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Standard Production Process
From G.K.
Raju, MIT
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Manufacturing Optimization
From G.K.
Raju, MIT
8
Production Cycle TimesHow Long Does It Take to
Produce a Batch of Product?Average 171 Days
Data from G.K. Raju, MIT
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Production Challenge

• Maintaining the availability of a product with an
  expiry period of two years and a cycle time of
  171 days. Inventory nightmare when countries
  require the import of products with 80 of expiry
  remaining.

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ARV Availability Issues

• Active Pharmaceutical Ingredients
• Manufacturers have been alerted to expected
  demand increases and scale-up likely is underway
• However the level of scale-up and sustainability
  remain unknown so it is likely shortages will
  occur.
• Formulation capacity may not an issue if the
  profit margins are sufficient. Producer of food
  supplements may convert to fill demand but that
  capacity is not available now.
• Manufacturers need accurate and timely
  information for projecting production
• SCMS will work with ALL stakeholders in country
  to develop accurate national forecasts and demand
  estimates
• The demand estimates will be shared among
  stakeholders to assist in planning to avoid
  duplications of efforts.

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Availability Issues

• Procedures and partners need to exist to
  transport products from manufacturers and
  suppliers to countries
• Challenges include unpredictable customs
  clearance and weak infrastructure
• Central warehouses should have sufficient storage
  capacity and conditions to maintain product
  quality
• SCMS will be implementing Regional and Local
  Distribution Centers to buffer stock movements to
  minimize overloads and improve delivery response
• Compliance with WHO for Good Storage and
  Distribution Standards
• Temperature controls, stock management, orderly
  storage, equipment maintained, security, incoming
  goods quarantine

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Significant Challenges

• ICH Market products generally stability tested to
  Climatic Zone I/II 25/60 RH to set expiry
  dates.
• The most HIV/AIDS affected world markets are
  located in Climatic Zone III/IV 30/65RH
• Monitoring supply chain thermal challenges
• Supply Chain Security
• SCMS will institute Point-of-Use product quality
  monitoring to assure suitability for intended
  use.

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Significant Challenges

• Providing TA to build in country appropriate
  sustainable infrastructure to assure product
  quality and minimize the distribution of
  counterfeit and sub-standard products.
• Import monitoring
• Supply chain monitoring-warehouses and
  distribution system
• Point-of-Use product surveillance