Transcript Pedigree and Serialization

Drug Pedigree and Serialization
December 5, 2008
Robert Yocher, M.H.Sc., RAC, FRAPS, CQE
Vice President, Regulatory Affairs and
Corporate Quality Compliance
Genzyme Corp.
Why Pedigree?
Challenges Presented by Globalization
• Increasing volume of imported products
• Imports coming from countries with less
well developed regulatory systems
• More outsourcing of manufacturing
• Greater complexity in supply chains
• Greater opportunities for economic fraud
Challenges*
• Number of Foreign Sites Making FDA Regulated
Drug Products More Than Doubled Since 2001 from
1,200 to 2,800
• Number of Drug Products Manufactured at Foreign
Sites More Than Doubled Since 2001 (by Registered
Sites from 18,000 to 43,000)
• Many Possible “Points of Entry”
– International Mail Branches (14 total)
– Express Consignment Facilities (29 total)
– Number of Ports
– in State (312 total)
The existing U.S. supply chain safety system for FDAregulated products, including drugs, is not adequate to
meet the growing challenges presented by globalization
•
*from “Supply Chain Safety: Pharmaceutical Electronic Track- and-Trace” by Jeffrey Shuren, M.D., J.D.
Associate Commissioner, U.S. Food and Drug Administration presented Nov.17, 2008
Counterfeiting
• FDA warns of two dozen websites selling counterfeit
drugs in 2007
• Thai national extradited for Cialis counterfeits and
sentenced with two others Feb 2008
• (July 2008) – Defendant arrested sold counterfeit
Zyprexa, Casodex, Tamiflu, Aricept & Plavix to
undercover agents July 2007
• Guilty Pleas in Counterfeit Toothpaste Investigation:
(August 2008) – Imported tubes of counterfeit Colgate
toothpaste from China lacked fluoride and some
contained microorganisms, such as bacillus spores, and
diethylene glycol (DEG)
Legislation
• 1988 Federal Prescription Drug Marketing Act
(PDMA)
• As modified by the Prescription Drug
Amendments of 1992, Pub. L. No. 102-353, the
PDMA is intended to provide legitimate
participants in the drug distribution system with a
history of the drug’s source—a “pedigree” of the
drug to prevent counterfeit, diverted, or
adulterated products from reaching consumers.
PDMA
• Implementing regs-final rule in 1999, stayed as
the result of a pending lawsuit by secondary
prescription drug distributors
• The FDA appealed in April 2007, claiming that
congressional intent requiring pedigree be
traced back to the original manufacturer is clear
in the PDMA.
• Pending a final decision in the court case, FDA
has indicated that it will not initiate enforcement
actions against any wholesaler for failing to
provide a pedigree that goes back to the
manufacturer.
FDAAA Section 913
• 505D(a) – In general,
– The Secretary shall develop standards and identify
and validate effective technologies for the purpose of
securing the drug supply chain against counterfeit,
diverted, sub-potent, substandard, adulterated,
misbranded, and expired drugs.
• 505D(b)(1) - General
• Secretary shall prioritize and develop standards
for– Identification
• – Tracking and Tracing
• – Authentication
• – Validation
FDAAA
• 505D(b)(2) – Standard numerical identifier
• The Secretary shall develop a standardized
numerical identifier
• Harmonize with international consensus
standards, to the extent practical
• To be applied to Rx drug at point of
manufacturing and repackaging
• Pallet or package level
• No later than 30 months after enactment (March
2010)
FDAAA
• Federal register notice standards
• Comments included
– uniform, national standards
– Step-wise approach preferred for developing
standards---identification number first
– Risk-based implementation
Proposed Legislation
– FDA Globalization Act– Under development but
pedigree requirement may include drug ingredients
– May include Buyer-Matheson
– Drug and Device Accountability Act– Cannot distribute
unless provide an electronic statement of each prior
sale, purchase, or trade, including transaction date
and the names and addresses of all parties to the
transaction. Includes drug ingredients.
State Laws to Fill Fed Void
• At least 29 states, including California and
Florida, have adopted their own pedigree
laws. (4 more states pending and 1
withdrawn)
• State laws with diverse, potentially
conflicting pedigree requirements makes it
increasingly difficult for prescription drug
manufacturers and distributors to comply
the law.
Source: http://www.healthcaredistribution.org/gov_affairs/.state/state_legis-static.asp
Individual companies are strongly encouraged to consult with their company's legal counsel to determine their specific
compliance requirements for PDMA and all federal and state regulations. HDMA disclaims any or all liability arising from
reliance on any statements or materials.
US State Regulatory Requirements
• The California Pedigree Law effective date has been
delayed until 1/1/11
– “…based on the effort exhibited thus far by industry, the expectations
of the Board that this effort will continue unabated in the intervening
period, the express assurances by industry of full implementation by
January 1, 2011,…
– There is the potential for additional modifications to
the law in the current or future legislative sessions
• SB 1270 (Cedillo) Allows Board to extend to unspecified date
• SB 1307 (Ridley-Thomas) Clarifies unique Identification
number is to be included in the pedigree
• TBD (“PHRMA” bill) Allows grandfathering and inference
US State Regulatory Requirements
• There is the potential for other states to
implement regulatory requirements prior to
1/1/11
– The majority of states are defining regulations
based upon the “Normal Distribution” concept
with pedigree starting at the wholesaler
– Oregon and New York are two states where
legislation similar to California has been
proposed
US Federal Regulatory Requirements
• FDA
– Requirements similar to California are expected as a
result of the FDAAA 2007
• [By March 2010] the Secretary shall develop a standardized numerical
identifier (which, to the extent practicable, shall be harmonized with
international consensus standards for such an identifier) to be applied to a
prescription drug at the point of manufacturing and repackaging (in which
case the numerical identifier shall be linked to the numerical identifier
applied at the point of manufacturing) at the package or pallet level,
sufficient to facilitate the identification, validation, authentication, and
tracking and tracing of the prescription drug.
• “… [CABOP] to continue its partnership work with the FDA on the
development of federal unique identifier standards, to ensure that California
and federal standards remain consistent.”
• The FDA has requested comments and information by May 19, 2008
regarding technologies used for the identification, validation, tracking and
tracing, and authentication of prescription drugs.
US Federal Regulatory Requirements
–Requirements are expected if reimportation is allowed
• The President -elect has indicated his support for
re-importation with product tracking requirements
–Visible issues with sourcing raw
materials (i.e., Heparin) and product
from outside the US may result in
upstream tracking requirements
CA delay until 1/1/2011
• Remaining Drivers:
• Turkey has just announced a pedigree law to be
implemented 1/1/2009,
• the Florida pedigree law is still in effect and our trading
partners have expressed a strong desire to eliminate
paper pedigrees,
• France has a mandate for the vignette to be a 2D
barcode which includes lot number and expiration date
for 12/31/2010,
• the US FDA has a mandate to implement a national
program no later than 4/1/2010,
• the serialization of product at the unit level is a keystone
of business process changes to eliminate costly shipping
errors
Proposed Legislation
EC Proposed Legislative Changes
• Traceability– Unique and centrally accessible record of
all past transactions, accessible by all parties
• Mass serialization*
• Transparency of Wholesalers– Routine GDP certificates
issued after each inspection
• Database of wholesaler compliance with GDPs*
• APIs– Mandatory notification of importation*
• Mandatory audits by manufacturers and importers*
* public comments generally expressed support
Other Country Regulatory
Requirements
• European Requirements
– Turkish Ministry of Health
• Item level 2D Datamatrix containing SGTIN, Expiry Date, Batch
Number
• Data submitted to TMOH DB
• All manufacturers have system integrated 1/01/09
• 12 more months for consumption of existing drugs in the market
by 1/1/10
– Italy
• Today: Bollini label with National ID number and data submission
of daily shipment quantities
• Future: Timing TBD for transition to GS1 number and item level
serialization data submission
– France
• Transition from 7 digit 1D to 14 digit Datamatrix Vignette label
• Transition between 1/1/09 and 12/31/2010
• No data exchange requirements
Identification across Europe : Overview of National
Codification Systems
GS1 EAN Code Structure (13 digits)
Nordisk Varenummer (13 digits)
Spanish Codigo National (13 digits)
PZN (Germany/Austria)
Belgium ABP code (16 digits)
France CIP code 13 (13 digits)
Italian Bollino (AIC code – 9 digits)
Greek EOF sticker
Portuguese code
KNMP Code (Netherlands)
Source: EFPIA
Identification across Europe:
Perspective 2011+
EFPIA’s visions is to have a
unique harmonised coding
solution throughout European
based on the 2D Data matrix
bar code.
2D Data Matrix
Source: EFPIA
International Medical Products AntiCounterfeiting Task (IMPACT)
• World Health Organization’s International
Medical Products Anti-Counterfeiting Task
Force (IMPACT)
• Developing a Toolkit with:– Experience from different
countries
– Model legislation & regulations
– Training materials and methodologies
– Tools and manuals to assist national authorities in
implementing activities
– Tools and methodologies for the assessment of
national/regional situations
Largest and most coordinated international
public/private public health effort for counterfeit
medical products
Summary
• Challenges brought on by globalization
have resulted in increased opportunity for
economic fraud
• State, Federal and International efforts are
underway to slow counterfeiters.
• Pedigrees and serialization are two tools
for tracking and tracing drug shipments
• Harmonization and standardization is
crucial to success
Summary
• A global problem requires a global solution
• Greater supply chain accountability
• Increased supply chain transparency
• Know and audit your business partners,
particularly suppliers/distributors
• Safety is everybody’s responsibility!