1. Dean R Hatt

2. Opening Thought  In a regulated GLP environment, we are sometimes reluctant to change, believing what we have always done, and what we have previously been inspected for, is the safest option  This may not, however, be the most efficient or flexible use of resource, so should be look outside the box ?>

4. Agenda  Introduction to Dispense  (inside the box)  Why look outside the box ?  Unlocking the Box  Summary

5. Introduction to Dispense  Dispense is a single, integrated product designed for the management of test materials, from receipt through the various formulations that take place in the course of a typical study.  Batches of test materials and vehicles are logged into the system, with expiry dates, and used in the definition of individual formulations for a study.

6. Introduction to Dispense  System prompts for weights and volumes, and records weights and data in a fully GLP compliant fashion  Accountability of test materials is achieved by periodically checking the theoretical amounts used against the actual amounts.  All test materials, vehicles, formulation and sample containers, and balances are barcoded  To ensure correct containers are used  To ensure balances are calibrated prior to use

8. Introduction to Dispense  System can be used to prepare liquids, fill capsules and make diets and blends  Test materials can be solid, liquids or units  It allows direct formulations (weigh test material + add vehicle), but also serial dilutions and premixes  It uses displacements to calculate amount/weight of vehicle to add (weigh vehicle) or to record weight of vehicle added (QS to volume)

9. Introduction to Dispense  It has standard (system steps) that are hard coded and require the system to read/check barcodes, request (volumes/weights) and record (weights)  It allows user defined steps that provide textual instructions for the user

10. Dispense Development Milestones  Booking in as a vehicle  F5 Key to force a weighing / use a different ‘similar’ batch of test material  F6 Key to record comments against any step  Addition of dates for aliquots  Link with In life ‘Provantis’ system  Link with Quantos automated weighing system  Link to stored C of A’s

11. Why Look outside the Box ?  When you first demo Dispense, you want it to replicate what you do in your manual preparation  When you use Dispense routinely, and suddenly you have to record manually, you want your manual proformae to replicate Dispense  Dispense calculations + step-wise process makes sense

12. Why Look outside the Box ?  Dispense data is easily viewable and provides, through a fully GLP compliant audit trail, an accurate record of the formulation process  Looking outside the box and recording everything on Dispense, provides a one-shop place to record all formulation data

13. Unlocking the Box  Booking in as a Test Material  Restriction: A prepared solution/suspension can only be used on the same ‘formulation set up’ and if prepared by serial dilution, can only be used once.  Booking any formulation in as a Test Material can allow it to be used on multiple formulation set ups and studies.

14. Unlocking the Box  Formulation in capsules  The system allows a test material to be weighed into a capsule or a liquid formulation to be used, but not to add a formulation to a capsule  Simply, a formulation is made on Dispense, booked in as a Test Material, and then used to fill a capsule

15. Unlocking the Box  Customised Labels / Reports  As Dispense uses crystal reports, user defined labels and reports can be produced and standard labels and reports, can be modified to suit the individual client.  A micro label has been created without barcodes and Dispense-specific information and approx 50% of size, to allow labelling of samples sent to third parties.

16. Unlocking the Box  Packing for Inhalation studies  Dispense is designed to prepare a formulation, however, it can be used to record steps of any process  Here, the formulation definition is built up around a weigh test material step using user defined steps with the operator recording data using the F6 key

17. Unlocking the Box

18.  Intra-nasal Device Testing  This takes things one step further with no weighings in the definition  Here, the formulation definition is built up using just user defined steps with the operator recording data using the F6 key

19. Unlocking the Box

20.  Excipient as Test Material  There are times when an excipient needs to be a test material e.g Methylcellulose, when making 1% (w/v) Methylcellulose, with the water as the vehicle  However, it is sometimes easier to add an excipient e.g Tween 80, to a final formulation, as a test material

21. Unlocking the Box  Addition of Vehicle to Pre-weighed Drug  Here, the exact quantity of test material has been provided in a container and to weigh it out would cause loss  A calculation is made manually as to how much vehicle needs to be added, and this is recorded on Dispense  This formulation can then be booked in as a Test Material if subsequent serial dilution is needed.

22. Unlocking the Box

23.  Addition of Analytical Diluent  Dispense allows for preparation of a formulation and subsequent sampling,but does not have ability to dilute a sample  Here, you can see how we utilise Dispense to record the weight/volume of diluent added to a sample

24. Unlocking the Box

25.  Addition of Analytical Diluent  This can be taken further by having multiple dilution steps all the way down to the analytical range

27. Unlocking the Box  Addition of Analytical Diluent  This can be taken further by having multiple dilution steps all the way down to the analytical range  You can also prepare standards and QC’s using the system

29. Unlocking the Box- Summary  Allows easy access to all formulation & analysis data  Fully GLP compliant  Can use the system for items it was not designed for  Booking in as test material  Liquids in capsules  Customised labels  Inhalation packing / device testing  Excipients as test materials or vehicles  Use of pre-weighed test material  Sample dilution and analytical standards/QC’s  Anything else !

30. Unlocking the Box- Summary  We would however like Dispense to be able to do some of these things from within the box ! Ability to Book in as a Test Material with a simple key stroke. Ability to dilute a sample with a simple key stroke

31. Unlocking the Box – Final Thought