Upcoming RAPS Programs:

1
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview 26 September 2006
Stephen Goldner, JD, RAC, Principal Officer,
Regulatory Affairs Associates LLC Karl Nobert,
JD, Kirkpatrick Lockhart LLP Norman Howe, PhD,
Senior Partner, Validation Compliance Institute
LLC

• Upcoming RAPS Programs
• RAPS 2006 Annual Conference Exhibition 15
  18 October 2006, Baltimore
• Regulatory Strategy Forum Tools for Designing a
  Global Regulatory Strategy
• 4 6 December, Charlotte
• Risk Management Webcast 13 December 2006
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  the RAPS website at http//www.raps.org
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  p

2
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Stephen Goldner, JD, RAC
• Principal Officer
• Regulatory Affairs Associates LLC

3
Rx PedigreeFDA Regulation History

• 1999
• Final Regulations Published
• 21 CFR 203 to take effect Dec. 2000
• 2000
• 203.3(u) 203.50 delayed

• June 2006
• FDA announces effective date for 203.3(u)
  203.50 no delays beyond December 1, 2006

4
Draft Compliance Policy Guide160.900

• CPG Goal
• Clarify FDA intent on prioritizing
  pedigree-related enforcement
• Four determining factors

5
Draft Compliance Policy Guide160.900

• Factor 1 High Value in U.S. Market
• Is the drug a high priced/specialty product for
  a serious or life-threatening disease?
• Is the drug in high demand?
• Is there a shortage of the drug?

6
Draft Compliance Policy Guide160.900

• Factor 2 Prior Indications of Counterfeit Drug
  Activity
• Are there prior cases of the drugs being
  counterfeited or diverted in the U.S.?
• Is there a history of false pedigrees associated
  with the product?

7
Draft Compliance Policy Guide160.900

• Factor 3 Reasonable Probability (for
  newly-approved drugs)
• Foreseeable that the drug may be counterfeited
  or diverted based upon Factors 1 or 2
• Does the drug have priority review status?
• Is the drug expected to have a large market value
  based on similar drug classifications?

8
Draft Compliance Policy Guide160.900

• Factor 4 Other Violations of Law
• Enforcement of 21 USC 353(e)(1)(A)
• 21 CFR Part 203

9
Draft Compliance Policy Guide160.900

• Based on the 4 Factors FDA has already identified
  20 drugs requiring a high priority for pedigree
  enforcement

10
Important DefinitionsSection 203.3

• Authorized Distributor of Record
• A distributor with an established ongoing
  relationship with a manufacturer to distribute
  such manufacturers products
• Ongoing Relationship
• An association through a written agreement
  authorizing distribution of the manufacturers
  product for a period of time or number of
  shipments or identifying the specific drug
  products

11
Important RequirementSection 203.50

• Identifying statement for sales by unauthorized
  distributors
• Seller shall provide to purchaser a statement
  identifying each prior sale, purchase, or trade
  of such drug BEFORE completion of ANY wholesale
  distribution to another wholesale distributor or
  retail pharmacy

12
Rx Pedigree Statement
13
Record Retention by All Distributors

• Required by section 203.60
• Must be retained by all wholesale distributors of
  drug product
• Required of authorized and unauthorized
  distributors
• Retention for 3 years

14
Section 203.60 Request and ReceiptForms, Reports
and Records

• Electronic and handwritten signatures to
  electronic records are permitted
• Combinations of paper and electronic records may
  be used.

15
State of Florida Regulations

• Effective July 1, 2006
• Applies to all prescription drugs labeled for
  human use including brand-named and generic
  prescription drugs, and some medical devices
  containing a prescription drug
• No exceptions for authorized distributor of
  record

16
Florida Rx Pedigree Regulations

• Both wholesale distributors and repackagers must
  provide a pedigree when distributing an API
• A wholesale distributor or repackager must
  authenticate information on the pedigree a
  pharmacy, practitioner or hospital is not subject
  to this requirement
• Except for drop shipment transactions, a pedigree
  must be received prior to or contemporaneously
  with receipt of prescription drugs

17
Florida Rx Pedigree Regulations

• Who must provide a pedigree?
• Anyone, including a repackager, who is engaged in
  the wholesale distribution of a prescription drug
  from, within, or into the state of Florida
• 2 exceptions

18
Florida Rx Pedigree Regulations

• Who must provide a pedigree?
• 2 exceptions
• Manufacturer of a prescription drug
• A member of an affiliated group that distributes
  a prescription drug to a member warehouse or
  retail pharmacy. The affiliated group must be
  composed of at least 50 retail pharmacies,
  warehouses, or repackagers.

19
Florida Rx Pedigree Regulations

• To whom must the pedigree be provided?
• Every person who receives a prescription drug
  from a wholesale distributor or repackager,
  including
• a manufacturer
• a repackager
• a pharmacy
• a medical practitioner

20
Authenticating a pedigree and how to do it

• Authenticate
• To affirmatively verify, before the distribution
  of a legend drug, that each transaction listed on
  the pedigree has occurred.
• Upon receipt, a wholesaler must review records
  required under this section for
• Accuracy and completeness, considering the total
  facts and circumstances surrounding the
  transactions and the wholesale distributors
  involved, and
• Authenticates each transaction listed on a
  pedigree

21
Who must authenticate a pedigree?

• A wholesale distributor or repackager must
  authenticate the information on the pedigree
• A pharmacy, practitioner, or hospital is not
  subject to this requirement.

22
State of California regulations

• Effective January 1, 2007, but may be postponed
  until January 1, 2008
• All human prescription drugs i.e. dangerous
  drug

23
California Rx Pedigree Regulations

• A wholesaler or pharmacy may not sell, trade, or
  transfer a dangerous drug at wholesale without
  providing a pedigree
• A wholesaler or pharmacy may not acquire a
  dangerous drug without receiving a pedigree

24
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview
Karl M. Nobert, JD Associate Kirkpatrick
Lockhart Nicholson Graham LLP
25
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• The Act
• Prescription Drug Marketing Act (1987)
• Purpose
• Ensure that Rx drugs sold in the U.S. are safe
  and
• effective
• Increase safeguards to prevent introduction and
  retail
• sale of substandard, ineffective or counterfeit
  drugs

26
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Statutory Provisions
• Statement of Origin / Pedigree Requirements
• 21 U.S.C. 353(e)(1)(A)
• Drug Pedigree A statement of origin that
  identifies each prior sale, purchase or trade of
  a drug, including the dates of those transactions
  and the names and addresses of all parties to
  them.

27
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Pedigree Requirements
• Each person who is engaged in the wholesale
  distribution of Rx drugs and who is not the
  manufacturer or authorized distributor of record,
  shall, prior to each wholesale distribution of
  such drug, provide a statement to the person who
  receives the drug identifying each prior sale,
  purchase or trade of such drug
• 21 U.S.C. 353(e)(2)(A)

28
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Inspections
• Availability of request and receipt forms,
  reports, lists and records. 21 C.F.R.
  203.60(e)
• Any party required to create and maintain these
  records, shall make them available, upon
  request, to FDA or other Federal, State, or
  local regulatory and law enforcement officials
  for review and reproduction.

29
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Enforcement
• Phase-In Enforcement
• 4 Factors FDA will consider in its early
  enforcement efforts (Draft FDA Compliance Policy
  Guide 160.900)
• High Sales Value / Volume in U.S. Market
• Drug products with high market value or sales
  volume
• Targets of Counterfeiting and Diversion in the
  Past
• Reasonable Probability (applicable to newly
  approved drugs)
• Emphasis on New Drugs Factors 1 2
• Other Violations of the Law
• Enforcement in conjunction with other violations
  of the Act or other laws

30
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Application
• Two areas where FDA will likely apply the
  pedigree rules
• Counterfeit Drugs (Imitations meant to be
  fraudulently or deceptively passed off as
  genuine)
• Counterfeit Task Force
• Examples
• Diversion (An unauthorized rerouting or
  appropriation)
• Examples
• Penalties

31
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview
Norman Howe, PhD Senior Partner Validation
Compliance Institute LLC
32
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Youve seen the current regulatory situation.

Now Im guessing that youre asking yourself,
What am I going to do about it?
33
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview
The pharmaceutical logistics chain is far from
simple.

• What are the options available to meet the Drug
  Pedigree challenge?

34
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• The good news is that there are three contenders
  currently available
• Paper
• Bar codes
• Radio Frequency IDentification (RFID)
• The bad news is that there is no single solution
  to the problem.

35
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Paper is clearly not the silver bullet solution,
  so we wont spend any more time on it.

36
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Barcode Advantages
• We use them already.
• The costs have already been absorbed.
• The technology is well understood.

37
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Barcode Disadvantages
• Two dimensional bar codes cannot carry the
  information needed to identify drugs down to the
  individual package level.
• Three dimensional bar codes can, but they can be
  counterfeited even more easily than the
  drug/package itself.
• Line of sight access is required.
• Time consuming.

38
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Radio Frequency IDentification (RFID) wireless
  data collection technology that uses electronic
  tags for storing data.

39
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• RFID two categories, active and passive.
• Active RFID chips are powered by a battery and
  are able to transmit up to 1500 feet. Very
  expensive.
• Used for tracking trailers in yards and
  containers on the loading dock.

40
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Passive RFID three types, each of which has
  pros and cons.
• High Frequency (HF)
• Ultra High Frequency (UHF)
• Near Field UHF (NF)

41
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Conclusion unfortunately there is no single
  solution to the Drug Pedigree problem.
• For the next five years a composite of all three
  technologies will be needed.

42
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• How will FDA regulate electronic Drug Pedigree
  solutions with regard to validation and Part 11
  compliance?

43
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• FDA will phase in its enforcement activities
  following a risk based approach driven by four
  factors
• Factor 1, High Value in the US Market
• Factor 2, Prior Indicators
• Factor 3, Reasonable Probability
• Factor 4, Other Violations of Law.
• FDA Draft Compliance Policy Guide 160.900
  Prescription Drug Marketing Act Pedigree
  Requirements under 21 CFR Part 203 June 2006

44
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• PART 11--ELECTRONIC RECORDS ELECTRONIC
  SIGNATURES
• Subpart A--General Provisions
• Sec. 11.1 Scope.
• (b) This part applies to records in electronic
  form that are created, modified, maintained,
  archived, retrieved, or transmitted, under any
  records requirements set forth in agency
  regulations.

45
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Validation
• Any electronic solution to Drug Pedigree will
  likely be considered part of the finished drug
  package and therefore FDA will in all likelihood
  expect that system to be validated.

46
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Validation
• Your Drug Pedigree solution will be considered a
  continuation of the manufacturing process all the
  way to the consumer.

47
Prescription Drug Pedigree Webcast Legal and
Regulatory Overview

• Thank you!
• Stephen Goldner
• 248.855.5595 email SGoldner_at_RegAffairs.net
• Karl Nobert
• 202.778.9460 email KNobert_at_klng.com
• Norm Howe
• 734.740.9924 email HoweN_at_vcillc.com