NIMPs (v IMPs): Definitions and Practical Approaches

1 NIMPs (v imps ): Definitions and Practical Approaches Esther Sadler-Williams Global Director Strategic Development and Innovation 18th November 2015 2015 Catalent Pharma Solutions. All rights reserved Note: contributions are based on the individual s knowledge and expertise; this presentation should not be construed as a statement or opinion by Catalent Pharma Solutions. Disclaimer 2015 Catalent Pharma Solutions. All rights reserved 1 2 Agenda Current Status Definitions - Practical Approaches to Management Sourcing Labelling and Packaging Traceability, Complaints, Recalls, Adverse Events Impact of New CT regulations Summary 2015 Catalent Pharma Solutions. All rights reserved Current Status - Define a NIMP? Background Medication Concomitant meds Escape / Rescue meds Diagnostic / Endpoint Medications Preventive Medication Not being tested Challenge / Physiologic response meds Commercial products?

2 Standard of Care (SOC) 2015 Catalent Pharma Solutions. All rights reserved 3 4 Current Status Regulatory Environment Currently no regulations around NIMPs Guidance from the European Commission* Defines NIMPs , provides examples, and required filing documentation Non- investigational medicinal Product (NIMP)* A medical product not defined within the description of an IMP and maybe considered a background (SOC), challenge, concomitant, endpoint or rescue medication (escape) dosed for preventive, diagnosis or therapeutic reasons. It can be provided by sponsor or study site. investigational medicinal Product (IMP)** A pharmaceutical form of an active or placebo being tested or used as a reference in a clinical trials including products with a marketing authorization but used or assembled (formulated or packaged) in a way different to the authorised form, or when used in an unauthorised indication or when used to gain further information about the authorised form.

3 *Euradlex Volume 10 Chapter III March 2011 and **EU Directive 2001/20/EC; April 2001 2015 Catalent Pharma Solutions. All rights reserved Who and how to determine NIMP v IMP? 2015 Catalent Pharma Solutions. All rights reserved 5 Which functional area is responsible for classification of study medication as either a NIMP or IMP? (select only one choice) Quality may often determine Should have MA off label use more challenging Each case is different, depends on Category and how its used How drug regiment selected Source Presentation thus many just define as imps ! Has your organization been challenged by a country Health Authority when classifying a clinical trial material Summary of ISPE survey ISPE Survey of 57 companies on various experiences with imps Most companies (78%) managed more than 25 protocols per year 30% of companies don t distinguish between NIMPs an imps Sourcing 25% central; 58% local (22% sponsor controlled, 22% trial site order, 14% site inventory) 66% added some form of label to NIMP commercial packaging 6 2015 Catalent Pharma Solutions.

4 All rights reserved Practical Approaches - Sourcing of NIMPs Sourcing Strategy will impact Practical management of imps Central, Local or Blended Approach Conduct availability analysis Consider MA status, availability, cost, import duties Central Sourcing; bought in a single country to supply all Processes similar to imps Local Sourcing; purchased in country where it will be used Country affiliate, third party or clinical site Specific considerations for Clinical site sourcing If used as per MA no additional labelling unless competent authority specifies 2015 Catalent Pharma Solutions. All rights reserved 7 Summary of NIMP Sourcing Strategy 2015 Catalent Pharma Solutions. All rights reserved 8 Practical Approaches - Labelling of NIMPs IMP labelling requirements do not apply to NIMPs some EU competent authorities have stickering requirements Trial ID Sponsor For Clinical Trial Use only Labelling of Commercially available product Is it labelled according to MA?

5 Ensure protocol defines product as a NIMP 2015 Catalent Pharma Solutions. All rights reserved 9 How does your organization typically label commercially available NIMPs ? Practical Approaches - Packaging and Labelling of NIMPs Generally approach depends on sourcing strategy Central Sourcing Re-label if ocountry specific language not available oSeparating from commercial marketing presentation single blisters removed from carton oAltered commercial pack authorities may consider as IMP oIf labelled need retain sample and QP release Local sourcing Country requirements may apply May need to consider auxiliary label or sticker o For clinical trial use only , Kit ID # Supports traceability and any integration to IRT Generally no retains or QP release as above details not considered as GMP label 2015 Catalent Pharma Solutions.

6 All rights reserved 10 Practical Approaches for NIMPs - Other Traceability: Records should document chain of custody Should be able to reconstruct movements of NIMPs No regulatory requirements for returns and accountability for NIMPs But would be good practice To monitor safe handling and deviations from prescribed storage conditions that may impact the integrity of a NIMP To potentially support investigation of an adverse event for which the root cause may be a problem linked to drug To support a commercial recall If IRT used for traceability need to affix ID label Complaints and Recalls Should be part of Site Qualification process; Aligned to sourcing strategy but suggest manage as per imps Adverse Event Management As imps 2015 Catalent Pharma Solutions. All rights reserved 11 Impact of New CT regulations In Very Little!

7 NIMPs will become Auxiliary medicinal Products (AMPs) definition : medicinal product used for the needs of the clinical trial as described in the protocol but not as an investigational medicinal Product. Authorised in any member state (unauthorised) - can be used in justified cases (para 53) Be certain it s a AMP! If required for the Its an IMP Do not have to label AMP If commercial label provides all the information (para 57) Unauthorised AMP- labelling requirements same as IMP Specifics around radiopharmaceuticals Subjects should not have to pay for AMPs 2015 Catalent Pharma Solutions. All rights reserved 12 Summary NIMPs Be certain about your justification for categorisation Consider carefully sourcing strategy if appropriate to needs of protocol and clinical sites If sourcing locally often can minimise packaging and labelling needs May wish to consider identifier auxiliary label for traceability The future: New CT regs will provide more guidance than previously Other than a name management will be similar to today 2015 Catalent Pharma Solutions.

8 All rights reserved 13 NIMPs (and imps ) Thank you for your attention Esther Sadler-Williams Catalent Pharma Solutions +44-7711 853242 2015 Catalent Pharma Solutions. All rights reserved 14 discover more. CATALENT PHARMA SOLUTIONS 14 SCHOOLHOUSE ROAD SOMERSET, NJ 08873 + 1 866 720 3148 Summary of Approaches for NIMPs Sourcing Strategy for NIMP Sponsor label Overlay Funded or re-imbursed by Sponsor Return to sponsor for Destruction Return for local Destruction Return to Site Inventory CENTRAL Yes Yes Yes Yes* No No Yes Yes Yes* No Locally Sourced at Site Yes Yes Yes Yes* No No Yes Yes Yes* No No No No No* Yes * Local destruction may be permissible 2015 Catalent Pharma Solutions. All rights reserved 16