1. ExLPharma’s4th Clinical Supply Forecasting Summit Highlights April 13-14, 2010 Philadelphia, PA

2. Drug Supply and Use Optimal Techniques for Clinical Supply Forecasting and Making Better Use of Drug Supplies 2

4. Drug Properties (e.g., shelf life, dosage form)

5. Supply Chain

6. Supplies Forecast

7. Packaging

8. Labeling

9. DistributionShould be comprehensive so that the clinical supply team has one place to access information 3

11. Lengthy Plans; years out (typically 3-4)

12. Studies will only have the most basic of details

13. Flexible – program will change over time

14. Due to the vagueness, may not be a good candidate for forecasting tools4

16. Usually packing against a planned manufacture

17. Future oriented; but not quite as far into the future as a program

18. Still a need to be flexible; study events will change the course of supplies over time

19. Usually good candidates for forecasting tools5

22. Patient Compliance

23. Recruitment

24. Drop out rateNumber of Visits Another obvious core of demand; visit windows can impact the packaging amounts needed in a study Number of Centers Each center that needs an initial shipment adds to the forecasted demand Number of Countries Every country with a local distribution depot adds to the demand due to loss in flexibility in supplies 7

25. Drug / Packaging Properties Component Restrictions Humidity conditions Availability / Limited Distributors of components (e.g., foil envelopes, blister pack plastic) Cold Chain Out of temperature shipments; need to pack more Dosing Restrictions Limits in available strengths to make up the dose can also add to the forecast – use of multple unit kits 8

26. Efficient and Fit for Purpose To lessen the amount forecasted, when possible Simple packaging Multi-protocol packaging Multi-language booklet labels Avoid expiration dates on the labels Ease ‘switch-out’ when replacing expiring stocks Bar-coding Ease fulfilment (pick and pack) of orders The more flexible supplies are, the less overage is needed in the forecast 9

30. Components used to handle a drug’s stability conditions (e.g., humidity) may not be capable of supporting the legal requirements (foil envelopes)12

32. Screen failues, drop-outs and lengthy study times all affect the amount of drug needed

33. Country recruitment levels need to be accurate to support the forecast

34. Competitive recruitment impacts need as demand will fluctuate among participating markets

35. Faster enrolling countries lessen the demand need for those that are slower in recruiting

36. Late starts impact supply needs/plans13

38. Adaptive Randomizations

39. Center vs. Centralized Balancing14

40. Have you used Pooled Supplies?

41. What Does Pooling of Clinical Supplies Mean? Supplies that are primary packaged so that they can be used across multiple protocols Supplies that are primary packaged and labeled for multiple protocols and distributed for predetermined study Supplies that are primary packaged and labeled and distributed to allow for use across multiple protocols All of the Above

42. Pooling Definition All of the above – Pooling Definition- use of an allocated pool of supplies that are uniquely labeled such that they can be used across sites within a protocol and across protocols within a program.

43. Agenda What is Program Pooling Key Considerations in Executing an Effective Pooling Plan Uncovering what the Potential Cost Savings are to Clinical Supplies Working with Regulators to Ensure Complaint Pooling Activities Key Take Home Messages

44. All pools are not created equal…

45. What Does Pooling of Clinical Supplies Mean? Supplies that are primary packaged so that they can be used across multiple protocols Supplies that are primary packaged and labeled for multiple protocols and distributed for predetermined study Supplies that are primary packaged and labeled and distributed to allow for use across multiple protocols

46. Pooling until Shipment Subject 1001 Protocol A, Site 1 Shipment Dispensing Protocol 1252 Protocol 1253 Protocol 1254 Container is commutable until shipment Labeling Options Protocol ID added to label when shipping (via ancillary label) All Protocol IDs associated with the pool on label, specify protocol when shipping (via circle or highlight) Container is “married” to the protocol and site at Shipment, System must be designed to capture protocol specificity for container at shipping Re-supply algorithm is protocol-specific IVRS system is not needed Protocol: 1253

48. Labeling Options:

49. Umbrella Pool ID on Label

50. If needed, Protocol ID added when Dispensing

51. All Protocol IDs on Label, specify protocol when dispensing (via circle or highlight)

52. Container is “married” to the site at shipment

53. container is “married” to the protocol at dispensing

54. Re-supply algorithm considers needs of all protocols running at site in poolAdvantageous when same sites are running multiple protocols in the pool

55. Overview of Program Level Supplies A500 Pooled Supply A500_____________ (Program # on Label) Upon protocol approval IVR adds it to its list of “approved protocols for shipping studies” Study 1 Study n Study 2 Study 4 Study 5 Study 3 Site 1 Upon site approval IVR adds site to its list of “approved sites for dispensing” to the POOLED supplies Site 2 Site 3 Protocol number added manually to label at study sites AFTER IVR links container # and protocol # at the time of drug assignment Bottle Labels Labeled supplies ready to use in study

56. Theory to Practice

58. Investigator specifies Protocol, Subject and Visit and system selects suitable container (i.e., container ID is “married” to Protocol ID at dispensing)

59. Label can provide space to record or apply ancillary label with specific protocol ID upon dispensing, if deemed important

61. Key Considerations Distribution / Labeling From which depot will the supplies for each country originate? What are the label requirements for each country? Are there additional unique labeling requirements?

62. Common Logistical Concerns Alignment of invoices with shipping documents and import license. Multiple investigators at a single site without central pharmacy Proper interpretation of shipping documentation Clinical supply reconciliation Contractors seeking verification of any dossier updates prior to shipment.

63. Other Pooling Challenges Regulatory Acceptability (pooling not well understood) Annex 13 (section 26) Local Laws Labeling options must be agreed to by each country in advance. May need to have separate pools due to differences in expiry dating or other labeling variations. IVR/IWR must be designed to support pooling approach

64. Potential Savings

65. Pooling Benefits Supply commutability translates to flexibility and responsiveness. Protocols can be ramp up rapidly using a pre-exiting pool New Protocols can be added to pool downstream (dependent on labeling approach) Fewer packaging & labeling campaigns to prepare and release. Generally will achieve some supply savings (reduction of waste)

66. Where will you see a reduction in cost API Directly correlated with overall drug product savings Drug Product Demand quantities Packaging/labeling Campaigns Container types Containers Label Prints

67. Where will you see a reduction in cost QA Decrease number of releases Distribution Number of shipments if multiple protocols at same site Value Added Tax (VAT) Time = money Takes Supply Chain off of critical path when clinical plan changes

68. 4 protocols in pool, 2 dosage forms,35 countries, over 350 sites

69. Partnering with Regulators

70. Partnering with Regulators Know your facts Regulation or interpretation Many countries look to Europe What have other companies done Ensure regulators understand and are comfortable with IVR technology Provide information on concept and controls associated with system High light benefits not in terms of cost but in terms of patient safety Present solutions to challenges Small steps can bring you to your goal Pilot one program Company specific waiver Resources ISPE

71. Key Take Home Messages Pooling can be done many different ways There can be logistical and Importation Challenges but they can be overcome Pooling adds greater flexibility in your program Many benefits NOT just cost

72. Still have any questions? For additional information on ExLPharma’s Clinical Supply Forecasting Summits, please visit www.exlpharma.com