EX-10.8



 Exhibit 10.8 

TECHNICAL AGREEMENT ON THE 

MANUFACTURE OF CAPSULES 

VB-201 
 for 

VASCULAR BIOGENICS 
 Prepared by: J
McLachlan 
 ENCAP DRUG DELIVERY 
 Encap Ref:
EN1378;Vascular Biogenics Technical Agreement 
 Revision : 03 

Print date: 03 Aug 2012 
  
 



 

  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  

 CONTENTS 
  

									
	1.	  	Scope of agreement	  	 	3	  
	2.	  	Parties to agreement	  	 	3	  
	3.	  	Products	  	 	3	  
	4.	  	Quality standards	  	 	4	  
		  	4.1	  	Manufacturer’s Licence	  	 	4	  
		  	4.2	  	Compliance with GMP	  	 	4	  
		  	4.3	  	Product specifications	  	 	4	  
		  	4.5	  	Starting materials	  	 	4	  
		  	4.6	  	Batch Manufacture	  	 	4	  
		  	4.7	  	Storage and shipping	  	 	4	  
		  	4.8	  	Third party laboratory	  	 	4	  
			
	5.    	  	Responsibilities	  	 	4	  
		  	5.1	  	General and regulatory responsibilities	  	 	5	  
		  	5.2	  	Product-related responsibilities	  	 	6	  
		  	5.3	  	Validation, deviations, changes, complaints and recalls	  	 	8	  
		  	5.4    	  	Audit	  	 	9	  
			
	6.	  	Signatories	  	 	10	  

 Attachments: 

Attachment 1: Product manufacturing and technical release specifications 

Attachment 2: Starting materials provided by Encap 

Attachment 3: Manufacturing document references 

Attachment 4: Contact Personnel 

  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  


	1.	SCOPE OF AGREEMENT 

 This Technical Agreement is made in support of Capsules VB-201 (also
known as CI-201) between Encap Drug Delivery and Vascular Biogenics Ltd (VBL) and is subject to the Proposals and Standard Terms and Conditions executed between the parties in advance of each project related manufacture. 

Vascular Biogenics is investigating formulations of VB-201 for use in humans and requires manufacture of bulk capsules for use in clinical
trials. The new formulations for these products have been identified from project work at Encap on behalf of VBL. 
 This agreement details
the technical terms under which the contract will operate. It defines the products, quality standards, identifies the responsibilities of each party and defines supporting documentation. It identifies contacts for quality issues The document is
drawn up in accordance with Encap’s Standard Operating Procedure 0063 on generating a technical agreement for standard manufacture of licensed products (SOP 0063). 

Encap and VBL may, from time to time, agree Addenda to this agreement in writing. The Addenda will apply for particular supplies (strengths and
numbers) and will apply the Quality Standards and responsibilities described in this Technical Agreement. Such Addenda may also provide for related new strengths, as may be agreed from time to time. 

 

	2.	PARTIES TO AGREEMENT 

  

			
	 Contract Giver:
	  	Vascular Biogenics Ltd.,6 Jonathan Nethanyahu St. Or Yehuda, 60376 (Israel)
		
	 Contract receiver
	  	Encap Drug Delivery, Oakbank Park, Livingston, UK EH53 0TH

  

	3.	PRODUCT REGULATORY REFERENCES 

  

					
	 Product
	  	 Investigative

Medicinal Product

Authorisations held

byVascular Biogenics
	  	 Country

	Capsules VB-201	  	Individual references client responsibility.	  	Europe and/or USA


  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  


	4.	QUALITY STANDARDS 

  

	4.1	Manufacturer’s Licence 

 MW Encap Ltd, trading as Encap Drug Delivery, holds a
Manufacturer’s Licence from the MHRA (UK) for the manufacture of Investigative Medicinal Products (IMP’s ) (reference MAIMP/13485). 
  

	4.2	Compliance with GMP 

 Batches will be manufactured and assembled to comply with all
current European rules regarding Good Manufacturing Practices (EudraLex, Volume 4, 1997 and 21CFR parts 210 and 211). 
  

	4.3	Product specifications 

 Specifications for finished products are listed in (Attachment
1). Responsibilities for testing and release are defined in Table 5.2 
  

	4.4	Starting materials and packaging components 

 Specifications for starting materials are
listed in (Attachment 2). Responsibilities for sourcing and approval are defined in Table 5.2 
  

	4.5	Batch Manufacture 

 Batch manufacturing documents are defined in Attachment 3 

 

	4.6	Storage and shipping 

  

					
	4.6.1	  	API Storage:	  	[***]
			
	4.6.2	  	Product Storage:	  	[***]
			
	4.6.3	  	Product Shipping:	  	[***]

  

	4.7	Sampling and sample retention 

 Sampling and sample retention of starting materials and
product will be done according to standard Encap procedures 
  

	4.8	Third party laboratory 

 (not applicable). 

 

	5.	RESPONSIBILITIES 

  

					
	5.1	  	General and regulatory responsibilities	  	see Table 5.1
			
	5.2	  	Product-related responsibilities	  	see Table 5.2
			
	5.3	  	Validation, deviations, changes, complaints and recalls	  	see Table 5.3
			
	5.4	  	Audit	  	see Table 5.4


  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  

 Table 5.1: General and regulatory responsibilities 

 

					
	 ITEM
	  	 Responsibilities

	  	 Encap
	  	 Vascular Biogenics

	Organisation & Personnel	  	 •   Ensure personnel have appropriate training, skills, knowledge & experience to manufacture and test
Product
	  	 •   Confirm by audit

			
	Premises & equipment	  	 •   Provide properly designed, qualified & maintained premises, utilities & equipment
	  	 •   Confirm by audit

			
	Regulatory notifications	  	 •   Provide technical recommendations and information in support of Vascular Biogenics’s regulatory Variation
(s) (eg, formulation, process outline, test methods, specification limits)
	  	 •   Prepare and submit all product-specific documentation to regulatory
authorities
  
 •   Notify
Encap of intended country (ies) of use (Europe or USA)
  

•   Provide copy of regulatory approval documents to Encap to support product release

 
 •   Provide Encap with
updated IMPD submissions and approvals, according to ongoing project progress

			
	Marketing Authorisations (MA)	  	n/a	  	 •   Notify Encap of IMPD references and requirements arising from Variations

			
	Regulatory controls	  	 •   Meet Vascular Biogenics’s requirements on product regulatory controls
	  	 •   Notify Encap on regulatory controls in the specific market

			
	Use of Contract Analytical Laboratories (CAL)	  	 •   Approve Contract Analytical Laboratories (CAL)

 
 •   Notify Vascular Biogenics
of CALs prior to their use
	  	 •   Consent to the proposed use of CAL’s



  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  

 Table 5.2: Product-related responsibilities 

 

					
	 ITEM
	  	 Responsibilities

	  	 Encap
	  	 Vascular Biogenics

	Raw materials for process & packaging of Product	  	 •   Generate and approve internal specifications, according to initial advice
from Vascular Biogenics
  

•   Source, test & release starting materials of appropriate quality for processing of
Product, primary and second packaging components
  

•   Qualification of vendors

 
 •   Retain representative
samples
	  	 •   Notify Encap of the properties (chemistry, clinical, safety and handling) of
the active material
  

•   Provide initial specifications for Starting materials, packaging components & Product

 
 •   Confirmation of
compliance of materials supplied by Vascular Biogenics with TSE requirements. Approve the API supplier and notify Encap of the approval

			
	Product specification	  	 •   Generate specifications for bulk products (includes test methods) according to Vascular Biogenics
requirements
	  	 •   Define Vascular Biogenics requirements on initial specification

 
 •   Definition of product
expiry date
  
 •   Agree
& sign final specifications

			
	Production & process control	  	 •   Manufacture of Product to cGMP standards

 
 •   Designate lot numbers for
raw materials and Product
  

•   Establish in-process controls

 
 •   Generate and approve
Master Batch Instructions and Records for manufacture
	  	 •   Confirm by audit

 
 •   Agree in-process control
testing strategy
  

•   Regulatory pharmaceutics sections to be made available to Encap

 
 •   Approve manufacturing
documentation

			
	Laboratory controls	  	 •   Starting materials and bulk product release testing against
specification
  
 •   Operate
to cGMP standards
  

•   Retain representative samples of starting materials, packaging components and products,
according to the relevant specification
	  	 •   Confirm by audit

 
 •   Agree retention time of
samples

			
	Product storage, labelling and packaging prior to shipment	  	 •   Store, label and pack the bulk Product as defined in the Product Specification, for full testing and assembly
by third party nominated by the client
	  	 •   Confirm by audit

 
 •   Assembly of IMP by
Vascular Biogenics or third-party nominated by Vascular Biogenics



  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  

 Table 2 (ctd) 
  

					
	 ITEM
	  	 Responsibilities

	  	 Encap
	  	 Vascular Biogenics

	Bulk Product Release (Investigative Medicinal product, IMP)	  	 •   Bulk product, for release to Vascular Biogenics, according to agreed specifications
	  	 •   Forward required batch-related documentation to VBL’s third-party
packaging contractor
  

•   Final technical release of bulk and assembled product, in compliance with the relevant
regulatory trial authorisation
  

•   Final release for use in clinic

			
	Shipment	  	 •   Notify Vascular Biogenics of proposed shipment date

 
 •   Ship Product to locations
designated by Vascular Biogenics under specified conditions
	  	 •   Acknowledge receipt

 
 •   Confirm by
audit

			
	Retention of records	  	 •   Retain all manufacturing and testing records including records associated
with the inspection and release of raw materials / starting materials and packaging components of the Product for (15) years
  

•   Notify Vascular Biogenics of intent to destroy records with option to return records to
Vascular Biogenics
	  	 •   Confirm by audit

 
 •   Vascular Biogenics to
approve destruction or return of records

			
	Stability testing	  	 •   (under separate agreement)
	  	 •   n/a

			
	Product Specification File (IMP)	  	 •   Generate and maintain internal file for product for trial in Europe
	  	 •   VBL to maintain main file



  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  

 Table 5.3 : Validation, deviations, changes, complaints and recalls responsibilities 

 

					
	 ITEM
	  	 Responsibilities

	  	 Encap
	  	 Vascular Biogenics

	Validation	  	 •   Premises, utilities and equipment; cleaning procedures

 
 •   Process validation

 
 •   Analytical method
validation
	  	 •   Confirm by audit

			
	Significant deviations, out of specification reports	  	 •   Evaluate & define follow up actions & final approval of deviations,
non conforming material reports (NMCR’s) & failed manufacture reports
  

•   Notify Vascular Biogenics of all significant deviations and out of specification
reports
	  	 •   Confirm by audit

			
	Change control procedures	  	 •   Proposed changes to be accompanied with rationale for change to Product
specific Process parameters, test methods, sampling plans, critical raw material specifications, process control Specifications, Product specifications, validation protocols, reports and key personnel

 
 •   Notify Vascular Biogenics
of significant changes to premises, equipment, utilities and senior technical staff
	  	 •   Confirm by audit

 
 •   Should Vascular Biogenics
propose changes, these will be subject discussion and agreement with Encap
  

•   Notify in writing if audit is required prior to start of next manufacturing run

			
	Complaints	  	 •   Provide support and responses to Vascular Biogenics
	  	 •   Receive complaint and co-ordinate relevant investigation and responses

 
 •   Notify Encap of
complaint

			
	Product recall	  	 •   Notify Vascular Biogenics of quality issues considered likely to require
recall
  
 •   Provide
support , implement relevant investigations and provide responses to Vascular Biogenics
	  	 •   Assess need for recall

 
 •   Co-ordinate recall

 
 •   Notification to Encap

 
 •   Notification to
regulatory authority



  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  

 Table 5.4: Audit responsibilities 

 

					
	 ITEM
	  	 Responsibilities

	  	 Encap
	  	 Vascular Biogenics

	Audit	  	 •   Accommodate up to one day annual audits and ‘for cause’ (to
address significant Product quality issues) audits by Vascular Biogenics at mutually agreed dates
  

•   Provide a timely response to observations reported by Vascular Biogenics

 
 •   Allow access to areas of
the manufacturing facility where the Product related activities are being performed
  

•   Allow Vascular Biogenics to observe operations related to Product manufacture and testing
provided other Vascular Biogenics confidentiality is respected
  

•   Allow Vascular Biogenics to review all documentation associated with manufacturing and testing
of Product
  
 •   Issue
corrective action follow-up report
  

•   Allow Vascular Biogenics to review all documentation associated with Process and analytical
validation
	  	 •   Provide reasonable notice of intention to audit

 
 •   Hold an exit meeting to
discuss observations
  

•   Provide an audit report

 

			
	Regulatory inspection	  	 •   Notify Vascular Biogenics of pending regulatory agency inspections affecting manufacture or testing of
Product
	  	 •   Comment on proposed regulatory responses to observations relevant to
Product
  
 •   Provide, on
Encap request, on-site representative and involvement in technical discussions



  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  


	6.	SIGNATURES 

  

					
	Vascular Biogenics	  		  	Encap Drug Delivery
			
	 /s/ [Illegible]
	  		  	 /s/ J. Darling

	Name:	  		  	Name: J Darling
	Title (Quality)	  		  	Title: QA Manager / QP
			
	  
	  		  	 August 6, 2012

	Date:	  		  	Date:


  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  

 ATTACHMENT 1 

Listing of agreed capsule specifications 
  

					
	 PRODUCT
	  	 STRENGTH (mg)
	  	 REFERENCE

	[***]	  	[***]	  	[***]


  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  

 ATTACHMENT 2 

STARTING MATERIALS 
  

	1.	STARTING MATERIALS PROVIDED BY CLIENT* 

  

							
	 Encap raw
 material

reference
	  	Raw material title	  	Function	  	Compliance
	[***]	  	[***]	  	[***]	  	[***]

 [***] 
  

	2.	STARTING MATERIALS PROVIDED BY ENCAP* 

  

									
	 Product reference
	  	Raw material
reference	  	Raw material title	  	Function	  	Compliance
	[***]	  	[***]	  	[***]	  	[***]	  	[***]

 [***] 

  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  

 ATTACHMENT 3 

MANUFACTURING PARAMETERS 

Manufacturing Process 
 The
process is defined in specific batch processing instructions 
 Processing controls 

Process controls are defined in specific batch processing instructions 

(Fill weight) 
 Processing Instructions and
Records 
  

					
	 Product

Reference
	  	 Document
	  	 Preparation and filling

	[***]	  	[***]	  	[***]


  
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Technical Agreement between Encap Drug Delivery and Vascular Biogenics

 


  

 ATTACHMENT 4 

Contact Personnel 
  

					
	Vascular Biogenics	  		  	Encap Drug Delivery
			
	Quality	  		  	
			
	 /s/ Genya Mor
	  		  	 /s/ J. Darling

	Name: Genya Mor	  		  	Name: J Darling
	Title: Head of QA	  		  	Title: QA Manager
			
	Production	  		  	
			
	 /s/ Naamit Sher
	  		  	 /s/ J Savage

	Name: Dr. Naamit Sher	  		  	Name: J Savage
	Title: VP RA & Drug Development	  		  	Title: Production Director


  
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