Anthony DeStefano presented on technological strategies for combating counterfeit medicines. He argued that standardized identification tools and spectral libraries are needed as most APIs and drug products are made outside the US. Industry requires sophisticated tools while governments can help drive standardization and broad detection. The USP could help provide standardized reference materials and spectral libraries to facilitate global identification efforts against counterfeits. Coordination between industry, governments, and organizations like USP is essential to addressing this global problem.

1. P R E S E N TAT I O N S
T E C H N O L O G I C A L S T R AT E G I E S :
THE LAST LINE OF DEFENSE
A N T H O N Y J . D E S T E FA N O , P H . D .
S R . V I C E P R E S I D E N T,
COMPENDIAL SCIENCE
U N I T E D S TAT E S P H A R M AC O P E I A
SEPTEMBER 28, 2012
N AT I O N A L P R E S S C L U B
WWW.SAFEMEDICINES.ORG

2. Technological Strategies: The Last
Line of Defense
Anthony J. DeStefano, Ph.D.
Sr. Vice President, Compendial Science
United States Pharmacopeia

3. A Global Problem Requiring Global Solutions
 About 80% of all API made outside the US
 Similar trends in Drug Product manufacturing
 Detection of counterfeit or substandard products
often impossible to detect visually – need a
technical solution
 Solutions need to be standardized to facilitate rapid
global transfer and adoption
 What are the roles of industry, government and the
pharmacopeia?
– How can we work synergistically and avoid duplication of
effort?
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4. Industry – Counterfeit vs. Substandard
 Industry needs the most sophisticated and specialized
technology
 Manufacturers must deal with
– Sub-standard materials
– Reverse-engineered nearly identical copies
 The latter require specialized tools
– Specialized microscopy to assess if the die used in the tablet
manufacture was one used by the company
– Examination of impurity profiles of API and excipients to correlate with
known sources of materials
 The former are also difficult – can’t be everywhere – how
do you find the material and stop its manufacture?
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5. Governments - Standardization
 Can help drive standardization
– Unified track and trace in the US
– Reach out globally to standardize
 Need to target a solution that really addresses the
issue
– Is tracking at the lot level sufficient or a burden that still leaves a
gap?
– Is tracking at the unit level feasible in a short time frame?
 Need to develop a compelling global case that the
gain is worth the pain
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6. Governments – Broad Reach
 How does one find counterfeits?
 Tools good enough to rapidly say “hold to assess
authenticity”
 Sufficient people/equipment to check materials
entering the country
– Very small percentage checked now
– Can’t stop the problem if we can’t detect it
 Technology needs to be standardized, portable,
inexpensive and readily available
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7. Examples of Tools Available
 Track and trace technology (e.g., bar code readers)
 Infrared spectroscopy (mid and near IR)
 Portable NMR
 Portable GC-MS
 Portable x-ray diffraction
 Microscopes
 HPLC and other traditional testing equipment
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8. The Need for Standardization
 Identification/verification tools are critical
 Only as good as the standards against which the
material is tested
 What does good look like, and how do you know?
 What is a “close enough” match with the database?
 How do you minimize false positives (manufacturer
risks) and false negatives (consumer risks)?
 Answers require standardization and industry,
governments and perhaps standard-setting bodies
working together
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9. Spectral Libraries – The Need for Standardization
 Spectral libraries (fingerprints against which the
material in question is matched) are no better than
the materials and methodology with which they are
constructed
 Materials and products vary
– Lot-to-lot differences (impurities, variations in formulation,
uniformity of manufacture)
– Regional differences (formulations for US, Africa,…)
– Changes during the shelf life of a product
 Methodology varies
– Sampling strategies
– Protocols for obtaining spectra
– Different manufacturers of the same technology – platform and
data analysis differences 9

10. A Role for the Pharmacopeia?
 USP currently has access to nearly 3000 drug
substance and drug product reference materials
 USP has a global presence, is used in over 140
countries and has worked with many government
across the globe
 As an independent third party, USP can provide
confidentiality and global reach
 Combined with industry and government efforts, may
be able to increase the “sets of eyes” out looking for
counterfeits
 May be able to provide some of the standardization
needed to make the current tools more effective
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11. USING ADVANCED TECHNOLOGIES TO STOP COUNTERFEITERS
Handheld Raman
Portable GC-MS
Portable NMR
Handheld XRF
GS1 Handheld
Barcode Scanner
Portable NIR-MSP Handheld NIR

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13. USP Spectral Library Development Process
Materials Method Data
Instrument Data
Acquisition, Development
Acquisition & (Attributes,
Acquisition & Analysis &
Storage &
Validation Retention DoE, Analyzer) Validation Validation
USP Quality Assurance SEAL (CoA & SOP)
Global Public
Education Technical
Awareness
Training Services
& Promotion

14. NASA USING SPECTRAL LIBRARY TO DETECT MINERAL
COMPOSITION ON MARS
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15. Summary
 Counterfeiters are many and sophisticated so the people
and equipment trying to stop them need to be as well
 Standardization is critical to speed and accuracy
– Minimize false positives or false negatives
 Coordination of efforts is critical
– Avoid duplication of effort
– Avoid missed opportunities to apply technology
– Avoid gaps in technology and optimize coverage
 Technological strategies, in all their manifestations, are
critical to success
 The public expects us to succeed - we need to provide
them with the protection they expect and deserve
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