Technical Agreement for Distribution Services

1. Contracting Parties

Contract Giver:		Gentium S.p.A
Name and Address:		Xxxxxx XX Xxxxxxxxx, 0
		00000 Xxxxx Xxxxxxx, Xxxx
		Xxxxx

(Hereafter referred to as "Gentium")

Contract Acceptor:		IDIS Limited
Name and Address:		XXXX Xxxxx
		Xxxxxxxxxxx Xxxx
		Xxxxxxxxx
		Xxxxxx
		XX00 0XX
		Xxxxxx Xxxxxxx

(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.

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 Xxxx 0,Xxxxxx Xxxx, Xxxxxxx, Xxxxxx, Xxxxxx Xxxxxxx. 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/ Xxxx Xxxxxxxxx

Name: Xxxx Xxxxxxxxx

Title: Executive Vice President and Chief Financial Officer

Date: February 26, 2009

SIGNED for and on behalf of

IDIS (TRADING AS IDIS LIMITED)

/s/ Xxxxx Xxxxxxxxx

Name: Xxxxx Xxxxxxxxx

Title: Responsible Person

Date: November 3, 2008

/s/ Xxxx Xxxxx

Name: Xxxx Xxxxx

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 XXXX Xxxxx Xxxxxxxxxxx Xxxx Xxxxxxxxx Xxxxxx XX00 0XX Xxxxxx Xxxxxxx Telephone No: 00000 000000 Fax No: 00000 000000		Xxx Xxxxxxx 00 Xxxxxxxxxxx Xxxxx Xxxxx 0000 Xxx Xxxx, XX 00000 Telephone No: 000-000-0000 E-mail Address: xxxxxxxx@xxxxxxx.xxx

Xxxxx Xxxxxxxxx Responsible Person At above address Direct Telephone No: 00000 000000 Email address : xxxxxxxxxx@xxxxxxxxxx.xxx		Xxxx Xxxxxxxxx At above address Direct Telephone No: 000-000-0000 Email address: xxxxxxxxxx@xxxxxxx.xxx

Xxxxx Xxxxxx Supply Chain Manager At above address Direct Telephone No: 00000 000000 Email address: xxxxxxx@xxxxxxxxxx.xxx		Xxxxxxx Xxxxxxxxx Xxxxxx XX Xxxxxxxxx 0, 00000 Xxxxx Xxxxxxx (Xxxx) Xxxxx Direct Telephone No: x00 000 000 000 Email address: xxxxxxxxxx@xxxxxxx.xx

		Xxxxxxxxx Xxxxxxxxx At above address Direct Telephone No: x00 000 000 000 Email address: xxxxxxxxxx@xxxxxxx.xx

		Xxxxxxxx Xxxxx At above address Direct Telephone No: x00 000 000 000 Email address: xxxxxx@xxxxxxx.xx

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:

Xxxxxx Xxxxxxx (xxxxxxx@xxxxxxx.xx) x00 000 000 000

Xxxxxxxxx Xxxxxxxxx (xxxxxxxxxx@xxxxxxx.xx) x00 000 000 000

Xxxxxxx Xxxxxxxx (xxxxxxxxx@xxxxxxx.xx) x00 000 000 000

Xxxxxxx Xxxxxxxxx (xxxxxxxxxx@xxxxxxx.xx) x00 000 000 000

Xxxxxxxx Xxxxx (xxxxxx@xxxxxxx.xx) x00 000 000 000

Xxx Xxxxxxx (xxxxxxxx@xxxxxxx.xxx) 212-332-1664

Xxxxxxx Xxxxx (xxxxxx@xxxxxxx.xx) x00 000 000 000

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

Contact for Invoicing:

Xxx Xxxxxxx (xxxxxxxx@xxxxxxx.xxx) 212-332-1664

XXXXXXXXXXXXXXX@xxxxxxx.xx x00 000 000 000

Contact for provision of monthly sales report:

Xxxxxxx Xxxxxxxx (xxxxxxxxx@xxxxxxx.xx) x00 000 000 000

Xxxxxxx Xxxxxxxxx (xxxxxxxxxx@xxxxxxx.xx) x00 000 000 000

Xxx Xxxxxxx (xxxxxxxx@xxxxxxx.xxx) 212-332-1664

Xxxx Xxxxxxxxx (xxxxxxxxxx@xxxxxxx.xxx) 000-000-0000

Xxxxxxxxx Xxxxxxxx (xxxxxxxxx@xxxxxxx.xx) x00 000 000 000

Xxxxxxxx Xxxxx (xxxxxx@xxxxxxx.xx) x00 000 000 000

Schedule 4 – Process Flow

Schedule 5 – Pharmacovigilance

Gentium Pharmacovigilance Representatives

Xxxxxxxxx Xxxxxxxx, Ph.D.

Drug Safety Manager,

Medical Department

TEL: x00.000.000.000

FAX: x00.000.000.000

xxxxxxxxx@xxxxxxx.xx

Xxxxxxx Xxxxxxxxx

Senior Vice-President, Scientific Director

Tele: x00-000-000-000

Mobile: x00-000-000-0000

xxxxxxxxxx@xxxxxxx.xx

IDIS Pharmacovigilance Representatives

Telephone : x00 (0) 0000 000 000

Fax : x00 (0) 0000 000 000 - FAO Technical Enquiries

Email : xx@xxxxxxxxxx.xxx

Schedule 6 – Access Form

Schedule 7 – Free of Charge Form

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Technical Agreement for Distribution Services

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