Unassociated Document


     

     

     

    Technical
Agreement for Distribution Services

     

    1.       Contracting
Parties

     

    
      
        
          	
                  Contract
      Giver:

                	 	
                  Gentium
      S.p.A

                
	
                  Name
      and Address:

                	 	
                  Piazza
      XX Settembre, 2

                
	 
      	 	
                  22079
      Villa Guardia, Como

                
	 
      	 	
                  Italy

                


        

      

    

     

     

    (Hereafter
referred to as "Gentium")

     

    
      
        
          	
                  Contract
      Acceptor:

                	 	
                  IDIS
      Limited

                
	
                  Name
      and Address:

                	 	
                  IDIS
      House

                
	 
      	 	
                  Churchfield
      Road

                
	 
      	 	
                  Weybridge

                
	 
      	 	
                  Surrey

                
	 
      	 	
                  KT13
      8DB

                
	 
      	 	
                  United
      Kingdom

                


        

      

    

     

    (Hereafter
referred to as "IDIS")

     

    Terms
used but not defined herein shall have the meanings given to them in the Supply
and Distribution Agreement.

     

    2.       Changes
to this Agreement

    
      
        	
                2.1.  

              	All changes to this agreement must be agreed by both
      parties following written submission by the requesting
  party.


      

       

    

    
      
        
          
            
              
                
                  
                    
                      	
                              No

                            	
                              Details
      of changes / Reason

                            	
                              Date

                            
	
                              1.

                            	 
      	 
      
	
                              2.

                            	 
      	 
      
	
                              3.

                            	 
      	 
      


                    

                  

                

              

            

          

        

      

    

     

    3.       Purpose
of the Agreement

    
      	
              3.1.  

            	
              The
      purpose of this agreement is to describe the technical aspects of the
      storage and the distribution of certain finished products of Gentium
      carried out by IDIS.

            


    

    
      	
              3.2.  

            	
              The
      regulations of this agreement apply to all orders referring to the product
      list (see Schedule 1), which have been agreed upon signing the Technical
      Agreement and before the notice has taken effect. They also apply to
      orders, which have already been given to IDIS on behalf of Gentium, as
      long as they have not yet been carried
out.

            


    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      	
              3.3.  

            	
              Gentium
      is responsible for marketing the
product.

            


    

     

    
      	
              4.  

            	
              Basis

            


    

    
      	
              4.1.  

            	
              IDIS
      shall comply with the legal regulations that apply to its area of
      responsibility.

            


    

    
      	
              4.2.  

            	
              IDIS
      is in the possession of a valid wholesale dealer’s license issued by the
      UK Medicines and Healthcare Products Regulatory Agency. IDIS shall
      maintain its systems to support its license. In the event that IDIS loses,
      or is at risk of losing its wholesaler dealer’s license IDIS shall
      immediately notify Gentium.

            


    

    
      	
              4.3.  

            	
              Gentium
      and IDIS appoint responsible contact persons (refer to
      Schedule 2).

            
	 	

              Both
      must inform each other of every amendment to the agreement in writing.
      Amendments are also part of this
agreement.

            


    

    
      	
              4.4.  

            	
              IDIS
      shall implement and update an effective quality management system (QMS),
      including the performance of internal audits and the implementation of the
      resulting corrective actions.

            


    

    
      	
              4.5.  

            	
              IDIS
      shall ensure that all staff affected by this agreement shall be
      appropriately trained with the valid standard operating procedures (SOP)
      and further regulations of Gentium and incorporating any necessary
      amendments into IDIS SOPs which are validated by
  Gentium.

            


    

    
      	
              4.6.  

            	
              IDIS
      shall allow the responsible persons of Gentium to carry out quality
      assurance audits providing reasonable notice has been
    given.

            


    

    
      	
              4.6.1.  

            	
              These
      audits shall be limited in scope to the area’s and systems directly
      related to Gentium’s product.

            


    

     

    
      	
              5.  

            	
              Responsibilities

            


    

    
      	
              5.1.  

            	
              Gentium
      is responsible for:

            


    

    
      	
              5.1.1.  

            	
              Ensuring
      product and packaging elements meet Italian regulatory
      requirements.

            


    

    
      	
              5.1.2.  

            	
              Providing
      IDIS with information relevant for the correct product
      handling

            


    

    5.1.2.1.  All
packaging shall reflect Gentium livery.

    
      	
              5.1.3.  

            	
              Making
      sure that the manufacturer is appropriately
  licensed.

            


    

    
      	
              5.2.  

            	
              IDIS
      is responsible for:

            


    

    
      	
              5.2.1.  

            	
              Complying
      with the cGDP (current Good Distribution Practices) guidelines and
      ensuring that the correct products are delivered to the consignee at the
      right time

            


    

    
      	
              5.2.2.  

            	
              A
      GDP compliant handling of the returned
products

            


    

    
      	
              5.2.3.  

            	
              Implementing
      an effective system for Recall

            


    

    
      	
              5.2.4.  

            	
              Performing
      visual inspection on received goods (e.g. integrity of shipment
      containers, completeness of shipment against shipment documents
      etc.)

            


    

    
      	
              5.2.5.  

            	
              IDIS
      shall inform Gentium of any negative quality or safety issues regarding
      Gentium products should they become aware of
  any.

            


    

    
      	
              5.2.6.  

            	
              Additional
      activities/requirements as defined in the ‘Supply and Distribution
      Agreement’: maintenance of the named patient program database, processes
      of a controlled distribution, and aspects with regard to drug
      safety

            


    

    
      	
              5.2.7.  

            	
              Managing
      drug in line with the process flow in schedule
4

            


    

    
      	
              5.2.8.  

            	
              Reporting
      any received adverse events notifications to Gentium in accordance with
      the process detailed in schedule 5

            


    

     

    
      	
              6.  

            	
              Facilities
      

            


    

    
      	
              6.1.  

            	
              IDIS
      shall manage the warehouse in accordance with GDP as well as storing
      the      Gentium products delivered on
      behalf of Gentium duly.

            


    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      	
              6.2.  

            	
              IDIS
      shall protect the Gentium products from damaging impacts and from access
      by unauthorized persons.

            
	 	

              Damaging
      impacts include but are not limited to:

            
	 	

              -
      damaging variations in temperature and humidity

            
	 	

              -
      dust and smell

            
	 	

              -
      animals, insects

            


    

    
      	
              6.3.  

            	
              IDIS
      shall inform Gentium immediately if Gentium products become visibly
      damaged or risk getting visibly
damaged.

            


    

    
      	
              6.4.  

            	
              IDIS
      shall maintain the storage rooms and facilities in accordance with GDP and
      to calibrating measuring instruments (e.g. temperature/humidity loggers)
      on a regular basis in accordance with
GDP.

            


    

    
      	
              6.5.  

            	
              IDIS
      shall keep the storage rooms in an orderly and tidy condition. Cleaning is
      done following a written cleaning
program.

            


    

    
      	
              6.6.  

            	
              IDIS
      shall appoint reliable personnel for the distribution orders, having the
      required theoretical and technical
  qualifications.

            


    

    
      	
              6.7.  

            	
              IDIS
      shall obtain written approval from Gentium if the stored goods are
      transferred into another warehouse other than the one in Unit 3,Canada
      Road, Byfleet, Surrey, United Kingdom. The same applies to changes of
      locations or any change within the warehouse, which may affect the
      storage, and handling of the
products.

            


    

     

    
      	
              7.  

            	
              Product
      Data

            


    

    
      	
              7.1.  

            	
              Gentium
      shall forward IDIS the relevant product data necessary for carrying out
      the tasks well in advance and for keeping IDIS updated with current
      product information should there be any changes or
    amendments

            


    

    
      	
              7.2.  

            	
              IDIS
      shall maintain product related data in line with regulatory
      requirements.

            


    

     

    
      	
              8.  

            	
              Storage,
      Delivery and Transportation

            


    

    
      	
              8.1.  

            	
              The
      handling of processes is defined in the existing QMS of IDIS based on
      SOPs. These are:

            


    

    
      	
              8.1.1.  

            	
              Incoming
      goods: Quarantine, release,
documentation

            


    

    
      	
              8.1.2.  

            	
              Handling
      of quality deficiencies

            


    

    
      	
              8.1.3.  

            	
              Incoming
      and outgoing of goods: According to the FEFO principle (first expiry -
      first out), or the FIFO principle (first in - first out),
      respectively

            


    

    
      	
              8.1.4.  

            	
              Commissioning
      and distribution of products

            


    

    
      	
              8.1.5.  

            	
              Recall
      procedures

            


    

    
      	
              8.1.6.  

            	
              Destruction
      of damaged or expired goods

            


    

    
      	
              8.1.7.  

            	
              Drug
      safety procedures

            


    

    
      	
              8.1.8.  

            	
              Complaint
      handling

            


    

     

    
      	
              9.  

            	
              Duty
      of Information

            


    

    
      	
              9.1.  

            	
              IDIS
      must immediately inform Gentium if:

            


    

    
      	
              9.1.1.  

            	
              An
      inspection by an authority regarding the contracting products is
      announced

            


    

    
      	
              9.1.2.  

            	
              Measures
      are taken by competent authorities regarding Gentium
    products.

            


    

    
      	
              9.1.3.  

            	
              IDIS
      learns about a serious product safety, quality of efficacy
      problem/issue

            


    

    
      
        	
                9.2.  

              	
                Gentium
      must inform IDIS of the supply chain details e.g. site of manufacturer,
      packaging/assembly, storage prior to product arriving at IDIS. This shall
      be listed in Schedule 3

              


      

      
        
          	
                  9.3.  

                	
                  Gentium
      shall provide IDIS with copies of licenses held by Gentium nominated
      manufacturer, packaging/assembly site or storage
  site.

                


        

         

        
          
            
            

          

          
            
            

            
              

            

          

          
            
            

          

        

         

      

    

    
      	
              10.  

            	
              Confidentiality

            


    

    
      
        	
                10.1
        

              	
                Information
      shared by either party concerning the Products will remain confidential in
      accordance with the Confidentiality Agreement and Supply and Distribution
      Agreement, which shall survive termination of this
    Agreement.

              


      

       

    

    
      
        	
                11.  

              	
                

                  Quality
      Control

                

              


      

      
        
          
            	
                    11.1.
        

                  	
                    

                      Gentium
      shall be responsible for full product testing in accordance with
      their    internal procedures, specifications, methods
      of analysis and any relevant Marketing Authorisation of the Products
      detailed in Schedule 1.

                    

                  


          

          
            
              
                	
                        11.2.   

                      	
                        Gentium
      shall be responsible for forwarding a Certificate of Analysis for each
      batch to IDIS.

                      


              

              
                
                  
                    	
                            11.3.   

                          	
                            Gentium shall be responsible for forwarding a
      Certificate of Compliance for each
      batch to IDIS.

                          


                  

                   

                

              

            

          

        

      

    

    
      	
              12.  

            	
              Sub
      Contracting

            


    

    
       

      
        
          	
                  12.1.
        

                	
                  With
      the exception of courier services, IDIS shall not subcontract any
      activities  of the product without prior consent of
      Gentium.

                


        

         

      

    

    
      	
              13.  

            	
              Table
      of Responsibilities

            


    

     

    
      
        
          
            
              
                
                  	
                          13.1.

                        	
                          Responsibilities

                        	
                          GENTIUM

                        	
                          IDIS

                        
	
                          1

                        	
                          Adverse
      event notification

                        	 
      	
                          X

                        


                

              

            

          

        

      

    

     

    
      
        
          
            
              
                
                  
                    	
                            13.2.

                          	
                            Product
      Data & Quality Control

                          	
                            GENTIUM

                          	
                            IDIS

                          
	
                            1

                          	
                            Transmission
      of product-related logistic

                          	
                            X

                          	 
      
	
                            2

                          	
                            Correct
      handover and maintenance of product data

                          	
                            X

                          	
                            X

                          
	
                            3

                          	
                            Provide
      TSE Certification regarding product status to IDIS

                          	
                            X

                          	 
      
	
                            4

                          	
                            Provide
      Certificate of Analysis for each product batch

                          	
                            X

                          	 
      
	
                            5

                          	
                            Provide
      Certificate of Compliance for each product batch

                          	
                            X

                          	 
      


                  

                

              

            

          

        

      

    

     

    
      
        
          
            
              
                
                  	
                          13.3.

                        	
                          Storage,
      Delivery and Transportation

                        	
                          GENTIUM

                        	
                          IDIS

                        
	
                          1

                        	
                          Delivery
      of products in conformity with the local market as nominated by
      Gentium

                        	 
      	
                          X

                        
	
                          2

                        	
                          Determination
      of the storage conditions and way of shipment

                        	
                          X

                        	 
      
	
                          3

                        	
                          Adherence
      to storage conditions and way of shipment to user

                        	 
      	
                          X

                        
	
                          4

                        	
                          Compliance
      with GDP guidelines

                        	 
      	
                          X

                        
	
                          5

                        	
                          Handling
      of returned goods

                        	 
      	
                          X

                        
	
                          6

                        	
                          Handling
      of technical product complaints

                        	
                          X

                        	
                          X

                        
	
                          7

                        	
                          Recall
      procedures

                        	
                          X

                        	
                          X

                        
	
                          8

                        	
                          Incoming
      goods, control, inventory update

                        	
                          X

                        	
                          X

                        
	
                          9

                        	
                          Adherence
      to FEFO principle

                        	 
      	
                          X

                        
	
                          10

                        	
                          Shipments
      of products

                        	 
      	
                          X

                        
	
                          11

                        	
                          Destruction
      of damaged, returned and expired goods

                        	 
      	
                          X

                        


                

              

            

          

        

      

    

     

    
      
        
          
            
              
                
                  	
                          13.4.

                        	
                          Documentation

                        	
                          GENTIUM

                        	
                          IDIS

                        
	 
      	 
      	
                          X

                        	
                          X

                        


                

              

            

          

        

      

    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    IN
WITNESS whereof this Agreement has been entered into the day and year
written.

    
SIGNED
for and on behalf of

    Gentium
S.p.A.

    


    /s/ Gary
Gemignani                                             


    Name:
Gary Gemignani

    Title:  Executive
Vice President and Chief Financial Officer

    Date:
February 26, 2009

    


    


    SIGNED
for and on behalf of

    IDIS
(TRADING AS IDIS LIMITED)

    


    /s/ Maria
Kempshall                                           

    Name:
Maria Kempshall

    Title:    Responsible
Person

    Date:
November 3, 2008

    


    /s/ Tony
Dutta                                                    

    Name:  Tony
Dutta

    Title:     Operations
Director

    Date:
November 6, 2008

     

     

    Schedule
1 – Product List

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    Brand
Name:

    


    Generic
Name: Defibrotide

    


    Strength:
200mg

    


    Presentation:
2.5ml ampoule

    


    Form:
Solution                                           

     

    Storage:
Ambient

    


    Pack
size: 10 x 2.5ml ampoules

    


    Therapeutic
Area: Hematology-Oncology

                                                                            

    
      
        

        

      

      Brand
Name: Prociclide

    

    


    Generic
Name: Defibrotide

    


    Strength:
400mg

    


    Presentation: Blister
pack

    


    Form: Capsule                                                      

     

    Storage:
Ambient

    


    Pack
size: 1 x 21

    


    Therapeutic
Area:
Hematology-Oncology                                                                                     

    


    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    Schedule
2 – Contact Persons

     

    
      
        
          
            
              
                
                  	
                          Contract
      Acceptor

                        	 	
                          Contract
      Giver

                        
	 	 	 
	
                          Simon
      Estcourt

                          Director
      – Global Market Access

                           

                          IDIS
      House

                          Churchfield
      Road

                          Weybridge

                          Surrey

                          KT13
      8DB

                          United
      Kingdom

                           

                          Telephone
      No: 01932 824000

                          Fax
      No: 01932 824200

                        	 	
                          Tim
      Hillman

                           

                           

                          45
      Rockefeller Plaza

                          Suite
      2000

                          New
      York, NY 10111

                           

                           

                           

                          Telephone
      No: 212-332-1664

                          E-mail
      Address: thillman@gentium.com

                        
	 	 	 
	
                          Maria
      Kempshall

                          Responsible
      Person

                           

                          At
      above address

                           

                          Direct
      Telephone No: 01932 824031

                          Email
      address : mkempshall@idispharma.com

                        	 	
                          Gary
      Gemignani

                           

                          At
      above address

                           

                          Direct
      Telephone No: 212-332-1666

                          Email
      address: ggemignani@gentium.com

                        
	 	 	 
	
                          Karen
      Jessep

                          Supply
      Chain Manager

                           

                          At
      above address

                           

                          Direct
      Telephone No: 01932 824143

                          Email
      address: kjessep@idispharma.com

                           

                        	 	
                          Massimo
      Iacobelli

                           

                           

                          Piazza
      XX Settenbre

                          2,
      22079 Villa Guardia (Como)

                          Italy

                           

                          Direct
      Telephone No: +39 031 385 217

                          Email
      address: miacobelli@gentium.it

                        
	 	 	 
	 
      	 	
                          Salvatore
      Calabrese

                           

                          At
      above address

                           

                          Direct
      Telephone No: +39 031 385 287

                          Email
      address: scalabrese@gentium.it

                        
	 	 	 
	 
      	 	
                          Margaret
      Hoyle

                           

                          At
      above address

                           

                          Direct
      Telephone No: +39 031 385 224

                          Email
      address:
mhoyle@gentium.it

                        


                

              

            

          

        

      

    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    Schedule
3 – Supply Chain Details

     

    Site of
manufacturer:  Villa Guardia (Co) Italy

     

    Site of
packaging/assembly:  Villa Guardia (Co) Italy

     

    Site of
storage prior to product arriving at IDIS:  Villa Guardia (Co)
Italy

     

    Pack
dimensions:

     

    Contact
for placement of purchase orders:

     

    Bianca
Colombo (bclombo@gentium.it)
+39 031 385 247

    Salvatore
Calabrese (scalabrese@gentium.it)
+39 031 385 287

    Roberta
Grandini (rgrandini@gentium.it)
+39 031 385 421

    Massimo
Iacobelli (miacobelli@gentium.it)  +39
031 385 217

    Margaret
Hoyle (mhoyle@gentium.it)  +39
031 385 224

    Tim
Hillman (thillman@gentium.com)  212-332-1664

    Armando
Cedro (acedro@gentium.it)
+39 031 385 254

     

    Product
lead-time from placement of purchase order:  90 days

     

    Contact
for Invoicing:

     

    Tim
Hillman (thillman@gentium.com)  212-332-1664

    AMMINISTRAZIONE@gentium.it
+39 031 385 417

     

    Contact
for provision of monthly sales report:

     

    Roberta
Grandini (rgrandini@gentium.it)
+39 031 385 421

    Massimo
Iacobelli (miacobelli@gentium.it)  +39
031 385 217

    Tim
Hillman (thillman@gentium.com)  212-332-1664

    Gary
Gemignani (ggemignani@gentium.com)  212-332-1666

    Francesco
Tescione (ftescione@gentium.it)
+39 031 385 222

    Margaret
Hoyle (mhoyle@gentium.it)  +39
031 385 224

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    Schedule
4 – Process Flow

     

      

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

      

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    Schedule
5 – Pharmacovigilance

     

      

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      
        
          
            	

                    Gentium
      Pharmacovigilance Representatives

                     

                    Francesco
      Tescione, Ph.D.

                    Drug
      Safety Manager,

                    Medical
      Department

                    TEL:
      +39.031.385.222

                    FAX:
      +39.031.385.241

                    ftescione@gentium.it

                    


                    Massimo
      Iacobelli

                    Senior
      Vice-President, Scientific Director

                    Tele:  +39-031-385-217

                    Mobile:  +39-348-711-2239

                    miacobelli@gentium.it

                     

                     

                     

                  
	

                    IDIS
      Pharmacovigilance Representatives

                    


                    


                    Telephone
      : +44 (0) 1932 824 026

                    


                    Fax
      : +44 (0) 1932 824 226 - FAO Technical Enquiries

                    


                    Email
      :
ps@idispharma.com

                  


          

        

      

    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    Schedule
6 – Access Form

     

      

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    Schedule
7 – Free of Charge Form