Document:

AlphaRx, Inc.: Exhibit 10.1 - Prepared by TNT Filings Inc.

 

Exhibit 10.1 

AlphaRx Retains Patheon to Manufacture Clinical Materials 

Thursday December 16, 9:27 am ET 

MARKHAM, ON, Dec. 16 /CNW/ - AlphaRx Inc. (OTC BB:ALRX.OB - News), an
emerging biopharmaceutical company utilizing proprietary drug delivery
technology to develop novel formulations of drugs, is pleased to announce that
Patheon Inc., a leading provider of drug development and manufacturing services
to the international pharmaceutical industry, has been retained to manufacture
clinical materials for Indaflex's clinical trials scheduled to begin early 2005.

Michael Lee, President and CEO of AlphaRx commented,
"Selecting Patheon for such a critical task was a relatively easy decision,
given Patheon's status as an industry leader. We have no doubt that Patheon will
handle all of AlphaRx's needs in a timely, professional and efficient manner."

About Indaflex 

Indaflex is AlphaRx's topical NSAID (Non-Steroidal Anti-inflammatory Drug)
formulation intended to start clinical development soon for use in the treatment
symptoms of arthritis. Arthritis is the most common chronic condition in North
America and afflicts an estimated 10% of the world's population. Indaflex's
active ingredient, Indomethacin, has a long-standing and proven clinical
treatment record. With AlphaRx's enhanced proprietary delivery system, the
company believes Indaflex's clinical effectiveness will be significantly
enhanced compared to other topical preparations. Topical Indaflex delivery, is
intended to circumvent the significant GI side-effects found with orally
ingested NSAID's. 

About AlphaRx Inc. 

AlphaRx is an emerging biopharmaceutical company utilizing proprietary drug
delivery technology to develop novel formulations of drugs that are insoluble or
poorly soluble in water or have yet to be administrable to the human body with
an acceptable delivery method. AlphaRx's broad product pipeline consists of
drugs with a strong commercial potential that can be dramatically improved
through the application of its proprietary BCD(TM) drug delivery technology. 

Forward Looking Statements: 

This release contains forward-looking statements within the meaning and
pursuant to the Safe Harbor provisions of the Securities Litigation Reform Act
of 1995 and involve risks and uncertainties that may individually or mutually
impact the matters herein described, including but not limited to product
development and acceptance, manufacturing, competition, regulatory and/or other
factors, which are outside the control of the Company.AlphaRx, Inc.: Exhibit 10.2 - Prepared by TNT Filings Inc.

 

PATHEON PROPOSAL # : ALP-FTR1-0400-0504-R4

	 	 	 	 
	1.	Parties:	Patheon lnc.("Patheon")	AlphaRx, Inc. ("Client")
	 	 	 	 
	 	 	2100 Syntex Court 	200-168 Konrad Crescent
	 	 	Mississauga, Ontario L5N 7K9 	Markham, ON L3R 9T9
	 	 	Canada	Canada
	 	 	 	 
	2.	Product:	Indaflex Cream (one strength)	 
	 	 	 	 
	3.	Indication:	Arthritis	 
	 	 	 	 
	4.	Contract:	This Proposal (including the
    Project Scope, Budget Summary, Standard Terms and Conditions for
    Pharmaceutical Development Services ("Terms and Conditions") when accepted
    by Client shall become a contract binding on the parties ("Contract").
	 	 	 	 
	5.	Description of Service:	See Project Scope (Part A).	 
	 	 	 	 
	6.	Payment and Currency:	See Budget Summary (Part B). See	 
	 	 	 	 
	7.	Legal Terms:	Terms and Conditions (Part C).	 
	 	 	 	 
	8.	Effective Date:	26-November-04	 
	 	 	 
	9.	Term:	From the Effective Date until
    completion by Patheon of the pharmaceutical development services
    ("Services").
	 	 	 	 
	10. 	Confidentiality: 
	The Confidentiality Agreement
    entered into between the parties shall apply to all confidential information
    about the parties and the Services to be conducted under this Contract and
    such Confidentiality Agreement is deemed to be incorporated herein by
    reference. If the Confidentiality Agreement expires or terminates prior to
    the expiration or termination of this Contract, then the terms of the
    Confidentiality Agreement shall nonetheless continue to govern the parties'
    obligations of confidentiality for the term of this Contract and for 5 years
    thereafter.

	 	 
	Patheon Inc.	AlphaRx, Inc.
	 	 
	By:	 	 	By:	 	 
	Name:	 	 	Name:	 	 
	Title:	 	 	Title:	 	 
	Date:	 	 	Date:	 	 
	 
	
    CONFIDENTIAL

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04

 

 

PART A: 

Indaflex Cream (one strength) 

Clinical Trial Material Manufacturing 

For 

AlphaRx, Inc. 

Proposal No.: ALP-FTR1-0400-0504-R4 

Dated: 26-November-04 

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 2 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04

	
    Table of Contents

	 	 	 
	1. 	PROJECT SCOPE	4
	 	 	 
	2. 	ENVIRONMENTAL, HEALTH AND SAFETY	4
	 	 	 
	3. 	ANALYTICAL DEVELOPMENT	5
	3.1.	Cleaning Residuals Assay (Evaluation and
    Validation)	6
	3.2.	Drug Product Potency and Related Substances
    Assay (Method Transfer)	6
	3.3. 	Drug Product Preservative Assay (Method
    Transfer)	6
	 	 	 
	4. 	MICROBIOLOGY	7
	 	 	 
	5.	CTM BATCH - PHASE I	7
	 	 	 
	6.	PLACEBO & VEHICLE CLINICAL TRIAL MATERIAL
    (CTM) MANUFACTURING	8
	 	 	 
	7.	ACTIVE CLINICAL TRIAL MATERIAL (CTM)
    MANUFACTURING - PHASE II	9
	 	 	 
	8.	STABILITY - ACTIVE CTM BATCH - PHASE I	9
	 	 	 
	9.	STABILITY - ACTIVE CTM BATCH - PHASE II	10
	 	 	 
	10.	PROJECT MANAGEMENT	12
	 	 	 
	HIGH LEVEL TIMELINE	13

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 3 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04

1. Project Scope 

Patheon will perform manufacturing and analytical services in
order to manufacture Indaflex Cream for Client. Analytical methods will be
assessed to support the Clinical Trial Material Manufacturing. 

It is assumed that the physical and chemical stability of the formulation has
been established by Client. 

Patheon will perform manufacturing and analytical services in
order to transfer Indaflex Cream from Client to Patheon. The Client acknowledges
that Patheon has explained to the Client and that the Client understands and
accepts any risk associated with manufacturing the CTM batch of Indaflex Cream
without first having completed feasibility batches. 

A discount will be applied to project at the CTM manufacturing
stage. 

The Budget Summary for this Project Scope is presented in Part
B. 

Patheon will commence the Services described in this Project Scope following
the execution of the Contract by both parties. 

2. Environmental, Health and Safety 

Prior to the commencement of analytical method development,
formulation development and manufacturing activities, a thorough review by
Patheon of the Environmental, Health and Safety (EH&S) requirements for
Indomethacin will be completed. The Budget Summary for this Project Scope
assumes that the EH&S review will determine that Indomethacin can be safely
handled at Patheon. A summary report of the evaluation will be provided to the
Client. 

If it is determined by Patheon's Environmental Health and
Safety personnel that any of the active ingredients are a Category III or
Category IV compound (an occupational exposure level) then an air sampling
method will be required at Client's expense prior to commercialization. Patheon
reserves the right, in its sole and absolute discretion, to conduct an air
sampling method on Category I and II compounds, at such price and upon such
terms as may be mutually agreed to between the parties prior to
commercialization. 

Prior to commercialization, Patheon will evaluate the Indaflex Cream and the
proposed launch volume and, at the Client's request, select the appropriate 

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 4 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04

Patheon facility for commercialization. The Patheon facility used for
performance of the Services will not necessarily be the facility available for
commercialization. 

Patheon will not receive any active pharmaceutical
ingredients (API) from the Client until a MSDS has been received, Patheon has
completed the categorization of the API and that the Client has completed and
returned the EH&S Survey to Patheon. 

3. Analytical Development 

Patheon will perform the required method transfer, method
development and method validation work required to support the manufacture of
the Indaflex Cream. Analytical protocols will be drafted by Patheon for
validation activities only and submitted to the Client for approval prior to
execution with the exception of the Cleaning Residuals Assay, which will be
approved internally by Patheon. Upon completion of the method transfer and
development activities, a summary of the data will be provided to the Client.
The analytical methods have been based upon HPLC unless otherwise stated 

An analytical report will be provided to the Client once the
method validation is complete. If method validation is not specified in the
title of an analytical method under this Project Scope, then the validation of
such analytical method is not included in this Project Scope and the additional
method validation costs will be quoted separately by Patheon. 

Patheon will receive and release the active pharmaceutical
ingredients (API) for Clinical Trial Material (CTM) manufacture based on the
following: (i) Identification testing; and (ii) the accompanying Certificate of
Analysis (COA) from the API Vendor (Client qualified) and COA from the Client.
For commercial manufacture, Patheon will complete full release testing of the
API 

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 5 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04

3.1. Cleaning Residuals Assay (Evaluation and Validation) 

Patheon will evaluate and validate the test method required
for testing cleaning residuals in order to support the manufacturing program.
The evaluation and validation will challenge the following parameters: 

	-	System Suitability	-	Range
	-	Linearity	-	Precision
	-	Quantitation Limit	-	Robustness
	-	Detection Limit	-	Specificity
	-	Accuracy	-	Solution Stability

3.2. Drug Product Potency and Related Substances Assay (Method Transfer)

Patheon Inc will be qualified to use drug product potency and
related substances assay to support Clinical Trial Material Manufacturing.  Inter-Laboratory Qualification involves the comparison of two different series
of laboratory analyses for the same lot of material/product. This verifies that
both laboratories (i.e., the originating and receiving laboratories) are
following the same procedure accurately and producing results that are precise
and equivalent. The following parameters will be performed at both Patheon Inc
and the originating laboratory:

	
    -
	System Suitability	-	
    Quantitation Limit
	-	Stability of Standard and
    Sample Solution	-	Detection Limit
	-	Repeatability	 	 

3.3. Drug Product Preservative Assay (Method Transfer)

Patheon Inc will be qualified to use drug product
preservative assay to support Clinical Trial Material Manufacturing.
Inter-Laboratory Qualification involves the comparison of two different series
of laboratory analyses for the same lot of material/product. This verifies that
both laboratories (i.e., the originating and receiving laboratories) are
following the same procedure accurately and producing results that are precise
and equivalent. The following parameters will be performed at both Patheon Inc
and the originating laboratory:

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 6 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04 

- System Suitability 

- Stability of Standard and Sample
Solution 

- Repeatability 

4. Microbiology 

Patheon will validate the test methods required for Microbial Limit Tests (MLT)
in order to support the manufacturing program. 

The cost allocated to this Service in the Budget Summary of
Part B is the per sample price and will vary depending on the number of samples
required for method validation. If a worst case scenario approach were taken,
the cost would be based upon testing MLT at two dilutions and/or the usage of
the largest volume of diluent(s) based on specification. Testing will be done in
compliance with USP/NF. Client will be billed based on the actual number of
samples required in order to successfully validate Indaflex Cream.

It is assumed that the preservative effectiveness of the
formulation has been established. If this has not been done, a preservative
effectiveness test can be conducted at an additional cost.

5. CTM Batch - Phase I 

Patheon will manufacture batch
of Indaflex Cream under cGMP conditions. All excipients will undergo complete
analytical release testing in compliance with USP/NF requirements. Patheon will
prepare a master batch record, which will be provided to the Client for approval
prior to manufacturing, that specifies manufacturing procedures and acceptance
criteria. This batch will be packaged into laminated tubes (50g).

Clinical Manufacturing Process Train 

The following in-process and finished product testing is
based upon one set of analysis for each of the described tests. If additional
sample testing is required (e.g. more than one analysis) these will be
considered as additional activities for which a separate costing will be
provided to the Client. 

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 7 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04 

	Bulk Analysis:	Cream Analysis:

6.
Placebo & Vehicle Clinical Trial Material (CTM) Manufacturing 

Patheon will manufacture batch under cGMP
conditions. These batches will be manufactured back to back. All excipients will
undergo complete analytical release testing in compliance with USP/NF
requirements. Patheon will prepare a master batch record, which will be provided
to the Client for approval prior to manufacturing, that specifies manufacturing
procedures and acceptance criteria. This batch will be packaged into laminated
tubes (50g). 

Clinical Manufacturing Process Train:

The following in-process and finished product testing is
based upon one set of analysis for each of the described tests. If additional
sample testing is required (e.g. more than one analysis) these will be
considered as additional activities for which a separate costing will be
provided to the Client. 

	Bulk Analysis:	Cream Analysis:

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 8 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04 

7. Active
Clinical Trial Material (CTM) Manufacturing - Phase II

Patheon will manufacture batch of Indaflex Cream under cGMP conditions.
This batch will be manufacture back to back with the placebo CTM batch. All
excipients will undergo complete analytical release testing in compliance with
USP/NF requirements. Patheon will prepare a master batch record, which will be
provided to the Client for approval prior to manufacturing, that specifies
manufacturing procedures and acceptance criteria. This batch will be packaged
into laminated tubes (50g).

Clinical Manufacturing Process

The following in-process and finished product testing is
based upon one set of analysis for each of the described tests. If additional
sample testing is required (e.g. more than one analysis) these will be
considered as additional activities for which a separate costing will be
provided to the Client. 

	Bulk Analysis:	Cream Analysis:

Stability - Active CTM Batch - Phase I

Patheon shall design a stability program for phase I to monitor packaged
batch of Indaflex Cream under ICH conditions. Additional samples will be stored
as contingency samples if required to generate data for long-term stability of
the product. 

The following storage conditions and test-points are suggested for testing:

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 9 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04 

The analytical data used for the release of each lot manufactured at Patheon
will be considered as 

Cost efficiencies for analytical testing have been built into
the stability program based upon the in a given month.
The cost for this stability program assumes that all lots will be placed on
stability at the same time. If these lots are not placed on stability at the
same time, the cost will be adjusted accordingly through Change of Scope
Agreement. 

Therefore, the stability sample breakdown is:

The following standard tests are usually performed as part of the Stability
Program: 

- Potency & Related Substances

- Weight loss

- Preservative 

- Physical Testing (including viscosity)

- MLT 

9. Stability - Active CTM Batch - Phase II 

Patheon shall design a stability program to monitor

CTM packaged batch of Indaflex Cream under ICH conditions.  Additional
samples will be stored as contingency samples if required to generate data for
long-term stability of the product. 

The following storage conditions and test-points are suggested for testing:

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 10 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04 

The analytical data used for the release of each lot manufactured at Patheon
will be considered as 

Cost efficiencies for analytical testing have been built into
the stability program based upon the in a given
month. The cost for this stability program assumes that all lots will be placed
on stability at the same time. If these lots are not placed on stability at the
same time, the cost will be adjusted accordingly through Change of Scope
Agreement. 

Therefore, the stability sample breakdown is:

The following standard tests are usually performed as part of the Stability
Program: 

- Potency & Related Substances

- Weight loss

- Preservative

- Physical Testing (including viscosity) 

- MLT annually

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 11 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04 

10. Project Management

Patheon will provide project management support to monitor
the progress of the project against established timelines and will provide the
Client with frequent updates. The project manager will coordinate regular
biweekly teleconference meetings and quarterly face-to-face meetings. The fee
for project management is in the Budget Summary.

 

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 12 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04 

High Level Timeline

The attached High Level Timeline is presented at this stage
as a projected estimate of the duration and achievable milestones, based upon
Patheon's experience and history. The High Level Timeline should not be taken as
part of an agreed legal deliverable of this proposal.

Once the project has been awarded to Patheon and the relevant
legal documentation is in place, a revised Timeline detailing set milestones and
duration of deliverables will be agreed upon between Patheon and the Client. The
revised Timeline would likely have a similar duration and would be based upon
resources and the availability of manufacturing time at the initiation of the
project. 

AlphaRx, Inc. 

Indaflex Cream (one strength) - Clinical Trial Material Manufacturing 

Page 13 of 18 

CONFIDENTIAL 

Patheon Proposal # ALP-FTR1-0400-0504-R4

26-November-04 

Part B: Budget Summary

THE FOLLOWING COSTS ARE ALL QUOTED IN:           
CAD

All amounts quoted are valid for sixty (60) days from the date of this
Proposal

	
      2.0   ENVIRONMENTAL HEALTH AND SAFETY	 	 	
    CAD   
	          
    ACTIVITY	PRICE
	 	 	 	 	 	 	 
	          
    EH&S Assessment	 
	 	 	 	 	 	 	 
	
      3.0   ANALYTICAL DEVELOPMENT	 	 	
    CAD   
	          
    ACTIVITY	 	 	HOURS	PRICE	HOURS	PRICE
	 	 	 	 	 	 	 
	       
    3.1 Cleaning Residuals Assay (Method Evaluation and Validation)	 	 	 	 	 	 
	                      
    Protocol/benchwork	 	 	 	 	 	 
	                      
    Final Report	 	 	 	 	 	 
	 	 	 	 	 	 	 
	       
    3.2 Drug Product Potency and Related Substances Assay (Inter Lab
    Qualification)	 	 	 	 	 	 
	                      
    Protocol/benchwork	 	 	 	 	 	 
	                      
    Final Report	 	 	 	 	 	 
	 	 	 	 	 	 	 
	       
    3.3 Drug Product Preservative Assay - Per Preservative (Inter Lab
    Qualification)	 	 	 	 	 	 
	                      
    Protocol/benchwork	 	 	 	 	 	 
	                      
    Final Report	 	 	 	 	 	 
	 	 	 	 	 	 	 
	                     
    TOTAL (Analytical Development)	 	 	 	 	 	 
	 	 	 	 	 	 	 
	
      4.0   MICROBIOLOGY DEVELOPMENT AND
    VALIDATION	 	 	
    CAD   
	          
    ACTIVITY	 	 	HOURS	PRICE	HOURS	PRICE
	 	 	 	 	 	 	 
	Preparation	 	 	 	 	 	 
	 	 	 	 	 	 	 
	No. of Trials	No. of Materials	No. of Pharmacopia	 	 	 	 	 	 
	One	1	1	 	 	 	 	 	 
	Two	1	1	 	 	 	 	 	 
	Three	1	1	 	 	 	 	 	 
	Four	1	1	 	 	 	 	 	 
	 	 	 	 	 	 	 
	TOTAL (Micro Development and
    Validation) - Number of Trials Assumed =	 	 	 	 	 	 
	 	 	 	 	 	 	 
	pH check	 	 	 	 	 	 
	Bioburden	 	 	 	 	 	 
	PET - USP	 	 	 	 	 	 
	PET - EP/BP	 	 	 	 	 	 
	Additional Organism	 	 	 	 	 	 
	 	 	 	 	 	 	 
	
      5.0   CTM MANUFACTURING - Phase I	 	 	
    CAD   
	          
    ACTIVITY	SHIFTS	HOURS	PRICE	SHIFTS	HOURS	PRICE
	 	 	 	 	 	 	 
	Per Batch:  
    Manufacturing	 	 	 	 	 	 
	                    
    Packaging	 	 	 	 	 	 
	                    
    Analytical Support	 	 	 	 	 	 
	                    
    Project Support	 	 	 	 	 	 
	 	 	 	 	 	 	 
	
    First Batch
	 	 	 	 	 	 
	 	 	 	 	 	 	 
	            
    TOTAL (CTM Manufacturing)	 	 	 	 	 	 
	 	 	 	 	 	 	 
	
      6.0   PLACEBO CTM MANUFACTURING	 	 	
    CAD   
	          
    ACTIVITY	SHIFTS	HOURS	PRICE	SHIFTS	HOURS	PRICE
	 	 	 	 	 	 	 
	Per Batch:  
    Manufacturing	 	 	 	 	 	 
	                    
    Packaging	 	 	 	 	 	 
	                    
    Analytical Support	 	 	 	 	 	 
	                    
    Project Support	 	 	 	 	 	 
	 	 	 	 	 	 	 
	    
    First Batch	 	 	 	 	 	 
	    
    1  Vehicle Batch Manufactured Back-to-Back from Placebo Batch	 	 	 	 	 	 
	        
    Cost Savings Per Additional Batch:	 	 	 	 	 	 
	        
    Cost Per Additional Batch:	 	 	 	 	 	 
	 	 	 	 	 	 	 
	     
    Additional Batches	 	 	 	 	 	 
	 	 	 	 	 	 	 
	     
    TOTAL (CTM Placebo Manufacturing)	 	 	 	 	 	 

Page 14 of 18 

CONFIDENTIAL 

    	
      7.0   ACTIVE CTM MANUFACTURING - Phase II	 	 	
    CAD   

    	          
    ACTIVITY	SHIFTS	HOURS	PRICE	SHIFTS	HOURS	PRICE

    	 	 	 	 	 	 	 

    	Per Batch:   Manufacturing	 	 	 	 	 	 

    	                    
    Packaging	 	 	 	 	 	 

    	                    
    Analytical Support	 	 	 	 	 	 

    	                    
    Project Support	 	 	 	 	 	 

    	 	 	 	 	 	 	 

    	     First
    Batch	 	 	 	 	 	 

    	     1 
    Additional Batches Manufactured Back-to-Back from the Placebo	 	 	 	 	 	 

    	        
    Cost Savings Per Additional Batch:	 	 	 	 	 	 

    	        
    Cost Per Additional Batch:	 	 	 	 	 	 

    	 	 	 	 	 	 	 

    	      Additional
    Batches	 	 	 	 	 	 

    	 	 	 	 	 	 	 
	      DISCOUNT (10%)	 	 	 	 	 	 
	 	 	 	 	 	 	 

    	       TOTAL
    (CTM Manufacturing)	 	 	 	 	 	 
	 	 	 	 	 	 	 

    	
      8.0   STABILITY - CTM Phase I	 	 	
    CAD   

    	          
    ACTIVITY	 	HOURS	PRICE	 	HOURS	PRICE

    	 	 	 	 	 	 	 

    	         
    Number of Lots	 	 	 	 	 	 

    	         
    Total Samples	 	Hours	Subtotal	 	 	 

    	                     
    	 	 	 	 	 	 

    	         
    Protocol Generation	 	 	 	 	 	 

    	 	Cost per Sample	# of Samples	Subtotal	 	 	 

    	         
    Microbiology	 	 	 	 	 	 

    	         
    Analytical Support (1 sample per pullpoint)	 	 	 	 	 	 

    	         
    Analytical Support (2 samples per pullpoint)	 	 	 	 	 	 

    	         
    Analytical Support (3 - 4 samples per pullpoint)	 	 	 	 	 	 

    	         
    Analytical Support (5+ samples per pullpoint)	 	 	 	 	 	 
	 	 	 	 	 	 	 

    	       TOTAL
    (Stability - Validation)	 	 	 	 	 	 
	 	 	 	 	 	 	 

	
      9.0   STABILITY - ACTIVE CTM BATCH	 	 	
    CAD   

	          
    ACTIVITY	 	 	 	 	HOURS	PRICE
	 	 	 	 	 	 	 
	         
    Number of Lots	 	 	 	 	 	 
	         
    Total Samples	 	Hours	Subtotal	 	 	 
	                     
    	 	 	 	 	 	 
	         
    Protocol Generation	 	 	 	 	 	 
	 	Cost per Sample	# of Samples	Subtotal	 	 	 
	         
    Microbiology	 	 	 	 	 	 
	         
    Analytical Support (1 sample per pullpoint)	 	 	 	 	 	 
	         
    Analytical Support (2 samples per pullpoint)	 	 	 	 	 	 
	         
    Analytical Support (3 - 4 samples per pullpoint)	 	 	 	 	 	 
	         
    Analytical Support (5+ samples per pullpoint)	 	 	 	 	 	 
	 	 	 	 	 	 	 
	       TOTAL
    (Stability - CTM)	 	 	 	 	 	 
	 	 	 	 	 	 	 
	
    BUDGET TOTAL (Low Potency. Cat. 1 & 2)	 	 	 	 	
    CAD	 
	 	 	 	 	 	 	 
	
    Deposit	 	 	 	 	 	 
	
    * The manufacturing cost given in this proposal is based upon
    the assumption that the drug substance is classified as a Category 3
    material in accordance with Patheon's Categorization System.  If it is
    determined through Patheon's Environmental Health and Safety Review that the
    drug substence is not categorized as a Category 3, the manufacturing cost
    will be revised through a Change of Scope to reflect handling charges for a
    Category 1, 2 or 4 product.**Client will pre-pay
    for all Services provided under the Contract.

Page 15 of 18 

CONFIDENTIAL 

PART C:

STANDARD TERMS AND CONDITIONS
FOR 

PHARMACEUTICAL DEVELOPMENT SERVICES

	1.	Services:	(c)	If applicable, Patheon and the Client will
    cooperate and
	 	(a)	Patheon agrees to perform the pharmaceutical
    development	 	provide such assistance to each other as may
    be reasonably
	 	 	services described in the Project Scope
    ("Services").	 	necessary to permit the import of the API and
    other materials
	 	(b)	Parties must agree on changes, deletions or
    additions to the	 	into the country where the Services will be
    performed.
	 	 	Services ("Changes").	 	 
	 	(c)	Minor Changes shall be confirmed by
    electronic mail,	4. 	Termination:
	 	 	facsimile or other written document.
    Significant	(a)	Either party may terminate this Contract if
    the other party is
	 	 	Changes (such as a request by the Client to
    change the	 	in material breach of any provisions of this
    Contract and the
	 	 	Project Scope) shall be confirmed by a Change
    of Scope	 	other party fails to remedy such breach
    within 30 days of the
	 	 	Agreement.	 	date of notice of such breach by the
    non-breaching party.
	 	 	 	(b)	Client may terminate this Contract
    immediately for any
	 	 	 	 	business reason.
	 	 	 	(c)	Any re-scheduling of any part of the Services
    beyond 120
	2.	Payment:	 	days requested by Client shall, at Patheon's
    option, be
	 	(a)	Client shall pay Patheon for the Services as
    outlined in this	 	deemed to be a termination of the Contract.
	 	 	Contract and for any Changes which shall be
    invoiced	(d)	Upon completion or expiry of the Contract or
    if the Client
	 	 	separately at Patheon's then prevailing
    hourly rates.	 	terminates the Contract for any business
    reason or if
	 	(b)	The costs of all third party suppliers' fees
    and the purchase of	 	Patheon terminates the Contract because of:
    (I) Client's
	 	 	project specific items (such as special
    equipment, change	 	failure to cure any default within the 30 day
    notice period; or
	 	 	parts, laboratory columns and reagents,
    reference	 	(ii) Client rescheduling any part of the
    Services beyond the
	 	 	standards under the applicable United States	 	120 days, then Client shall pay to Patheon: 
	 	 	Pharmacopoeia, the National Formulary, the
    British	 	- any fees and expenses due to Patheon for
    the Services 
	 	 	Pharmacopoeia, the European Pharmacopoeia or
    the	 	   rendered up to the date of completion, expiry or termination;
	 	 	Japanese Pharmacopoeia, and tooling)
    ("Project Specific	 	-  all actual costs incurred by Patheon to
    complete
	 	 	Items") necessary for Patheon to perform the
    Services shall	 	   activities associated with the completion,
    expiry or
	 	 	be charged to Client.	 	   termination and close of the Services
    rendered up to
	 	(c)	If Client causes any delay to Patheon's
    provision of Services	 	   the date of completion, expiry or termination
    including,
	 	 	for reason within its control (such as a
    delay in responding to	 	   without limitation disposal fees that may be
    payable in
	 	 	a Patheon inquiry or a delay in the delivery
    of the active	 	   respect of any materials and supplies owned
    by the
	 	 	pharmaceutical ingredient ("API")), then
    Patheon shall be	 	   Client to be disposed of by Patheon; and
	 	 	entitled to charge the Client for any
    additional costs incurred	 	- any additional costs incurred by Patheon in
    connection
	 	 	in the provision of the Services as a result
    of the delay.	 	   with the Services that are required to
    fulfill applicable
	 	(d)	Each Patheon invoice may be issued upon
    completion of each	 	   regulatory and contractual requirements.
	 	 	milestone set out in the Budget Summary and
    shall be due	(e)	Client shall arrange for the pickup from the
    Patheon site of all
	 	 	and payable within 30 days of the date of
    such invoice.	 	materials and supplies owned by Client

    days after the
	 	(e)	Prior to the commencement of any Services by
    Patheon	 	earlier of the completion, termination or
    expiration of this
	 	 	pursuant to this Contract, Client shall
    pre-pay to Patheon	 	Contract. Patheon shall charge a
	 	 	the amount of the estimated billings related
    to such	 	storage fee for all materials and supplies
    stored at the Patheon
	 	 	Services. Patheon will provide estimates of
    the monthly	 	site after the fifth day following the
    completion, termination or
	 	 	billings to the Client and update such
    estimates as	 	expiration of the Contract.
	 	 	required. On or before the first day of each
    month during	 	 
	 	 	the term of this Contract, Client shall
    forward to Patheon	5. 	Intellectual Property:
	 	 	payment for the estimated monthly billings
    for that	(a)	The term "Intellectual Property" includes,
    without limitation,
	 	 	particular month. To the extent that such
    estimated	 	rights in patents, patent applications,
    formulae, trade-
	 	 	monthly billings are increased by Patheon
    following	 	marks, trade-mark applications, trade-names,
    trade
	 	 	payment thereof, Client shall promptly
    forward to	 	secrets, inventions, copyright, industrial
    designs and 
	 	 	Patheon payment for the amount of such
    increase	 	know-how.
	 	 	These pre-payment amounts will be credited
    toward	(b)	For the term of this Contract, Client hereby
    grants to
	 	 	monthly invoices until the Services, as
    modified from	 	Patheon, a non-exclusive, paid-up,
    royalty-free, non-
	 	 	time to time, are fully completed or until
    this Contract	 	transferable license of Client's Intellectual
    Property which
	 	 	expires or is terminated for whatever reason.
    All pre	 	Patheon must use in order to perform the
    Services.
	 	 	payments shall be adjusted in the final
    invoice under this	(c)	All Intellectual Property generated or
    derived by Patheon in
	 	 	Contract. Patheon may, at its option,
    suspend, from time	 	the course of performing the Services, to the
    extent it is
	 	 	to time, all Services until such time as the
    pre-payment	 	specific to the development, manufacture, use
    and sale of
	 	 	amounts due have been received in full by
    Patheon.	 	the Client's Product that is the subject of
    the Services, shall
	 	 	 	 	be the exclusive property of Client.
	3.	Supply of API and
    Materials:	(d)	All Intellectual Property generated or
    derived by Patheon in
	 	(a)	Client shall, at its expense, supply Patheon
    with sufficient	 	the course of performing the Services which
    are not specific
	 	 	quantities of the API for Patheon's use in
    performing the	 	to, or dependent upon, Client's Product and
    which have
	 	 	Services.	 	application to manufacturing processes or
    formulation
	 	(b)	Other than Project Specific Items, all other
    materials (such as	 	development of drug products or drug delivery
    systems shall
	 	 	excipients, packaging, reference standards
    other than those	 	be the exclusive property of Patheon. Patheon
    hereby
	 	 	under the United States Pharmacopoeia, the
    National	 	grants to Client, a nonexclusive, paid-up,
    royalty-free,
	 	 	Formulary, the British Pharmacopoeia, the
    European	 	transferable license of
	 	 	Pharmacopoeia or the Japanese Pharmacopoeia,
    and raw	 	 
	 	 	materials) required to perform the Services
    shall be purchased	 	 
	 	 	by Patheon and charged to Client at 	 	 

Page 16 of 18 

CONFIDENTIAL 

	 	 	such Intellectual Property which Client may
    use for the	 	OF MERCHANTABILITY IN RESPECT OF
    THE CLIENT'S
	 	 	manufacture of Client's Product.	 	PRODUCT.
	 	 	 	7.	Regulatory Filings:
	6,	Indemnity:	 	(a)	Client shall have the sole responsibility for
    filing of all
	 	A.	Indemnification by Client	 	 	documents with the applicable regulatory
    authority (such as
	 	 	Subject to Sections 6B and 6C(c), Client
    shall defend,	 	 	the United States Food and Drug
    Administration ("PDA"), the
	 	 	indemnify and hold Patheon, its affiliates
    and their respective	 	 	Health Products and Food Branch of Health
    Canada or the
	 	 	directors, officers, employees and agents
    (collectively,	 	 	European Medicine Evaluation Agency) (the
    "Regulatory
	 	 	"Patheon Indemnitees") harmless from and
    against any and	 	 	Authority") and to take any other actions
    that may be
	 	 	all third-party actions, causes of action,
    costs (including	 	 	required for the receipt of approval from the
    Regulatory
	 	 	reasonable legal fees), claims, damages,
    liabilities and	 	 	Authority for the commercial manufacture of
    the Client's
	 	 	expenses (collectively, "Losses") relating to
    or arising from:	 	 	Product.
	 	-	the manufacture (except as may be
    contemplated by the	 	(b)	At least days prior to filing any
    documents with the
	 	 	Services) or distribution of the Client's
    Product or the use	 	 	Regulatory Authority that incorporate data
    generated by
	 	 	of the Client's Product by patients either as
    part of or	 	 	Patheon, Client shall provide Patheon with a
    copy of the
	 	 	outside of the scope of any clinical trials;	 	 	documents incorporating such data so as to
    give Patheon
	 	-	the performance of the Services in accordance
    with the	 	 	the opportunity to verify the accuracy and
    regulatory validity
	 	 	terms of this Contract;  	 	 	of such documents as it relates to the
    Patheon-generated
	 	-	any
    misrepresentation, negligence or willful misconduct	 	 	data.
	 	 	by Client or any of its affiliates and their
    respective	 	(c)	At least  days prior to filing with the
    Regulatory Authority
	 	 	directors, officers, employees and agents
    (collectively,	 	 	any documentation which is or is equivalent
    to the PDA's
	 	 	"Client Indemnitees"); « any breach by the
    Client of the	 	 	Chemistry and Manufacturing Controls ("CMC")
    portion of
	 	-	any breach by the Client of the
    Client's obligations or	 	 	the New Drug Application or of the
    Abbreviated New Drug
	 	 	warranties under this Contract;
    or	 	 	Application, as the case may be, Client shall
    provide
	 	-	any claim of infringement or alleged
    infringement of any third	 	 	Patheon with a copy of the CMC portion as
    well as all
	 	 	party's intellectual property rights in
    respect of the Client's	 	 	supporting documents which have been relied
    upon to
	 	 	Product.	 	 	prepare the CMC portion so as to permit
    Patheon to verify
	 	 	 	 	 	that the CMC portion accurately describes the
    work that
	 	This indemnity shall not apply to
    the extent that such Losses are:	 	 	Patheon has performed and the manufacturing
    processes
	 	-	determined to have resulted from the
    negligence or willful	 	 	that Patheon will perform pursuant to this
    Contract.
	 	 	misconduct of Patheon; or	 	(d)	If Client does not provide Patheon with the
    documentation
	 	-	for which Patheon is obligated to indemnify
    the Client	 	 	requested above within the time stipulated
    and if Patheon
	 	 	Indemnitees pursuant to Section 6B. B.	 	 	reasonably believes that Patheon's
    relationship with the
	 	 	 	 	Regulatory Authority may be jeopardized,
    Patheon may, in
	 	B. Indemnification by Patheon	 	 	its sole discretion, delay or postpone the
    Regulatory
	 	Subject to Sections 6A and 6C(c),
    Patheon shall defend,	 	 	Authority inspection which is or is
    equivalent to the FDA's
	 	indemnify and hold the Client
    Indemnitees harmless from and	 	 	pre-approval inspection ("PAI") until such
    time as Patheon
	 	against any and all Losses
    resulting from, relating to or arising	 	 	has reviewed the requested documentation and
    is satisfied
	 	from the breach by Patheon of any
    of its obligations or warranties	 	 	with its contents.
	 	under this Contract
    except to the extent that such Losses are:	 	(e)	If in Patheon's sole discretion, acting
    reasonably, Patheon
	 	-	determined to have resulted from
    the negligence or	 	 	determines that any of the information
    provided by the Client
	 	 	willful misconduct of Client; or	 	 	is inaccurate or deficient in any manner
    whatsoever (the
	 	-	for which Client is obligated to indemnify
    the Patheon	 	 	"Deficiencies"), Patheon shall notify the
    Client in writing of
	 	 	Indemnitees pursuant to Section 6A. C.	 	 	such Deficiencies. Until such Deficiencies
    have been
	 	 	 	 	 	resolved or agreement has been reached with
    the Client for
	 	 	 	 	 	such resolution, Patheon reserves the right
    not to participate
	 	C. Limitation of Liability	 	 	in the PAI. In such event, Patheon's
    non-participation in the
	 	(a)	If Patheon fails to materially perform any
    part of the Services	 	 	PAI shall not be construed as a breach of any
    of its
	 	 	in accordance with the terms of this
    Contract, then Client's	 	 	obligations under this Contract.
	 	 	sole remedy shall be to request Patheon to:	 	 	 
	 	-	repeat that part of the Service at Patheon's costs	 	 	 
	 	 	provided that Client provides the API; or	 	 	 
	 	-	reimburse Client for the price
    for that part of the	8.	Shipping (if applicable):
	 	 	Service, excluding the cost of the API.	Shipments (if
    applicable) of Client's Product shall be made (as
	 	(b)	Under no circumstances whatsoever shall
    Patheon reimburse	defined in INCOTERMS 2000)
    Patheon's shipping point unless
	 	 	Client for the cost of the API.	otherwise mutually agreed. Risk
    of loss or of damage to such Product
	 	(c)	Under no circumstances whatsoever shall
    either party be	shall transfer to the Client when
    the Product is loaded onto the carrier's
	 	 	liable to the other in contract,
    tort, negligence, breach of statutory	vehicle by Patheon
    for shipment.  The Product shall be
	 	 	duty or otherwise for (i) any
    (direct or indirect) loss of profits, of	transported in accordance with
    the Client's instructions.
	 	 	production, of anticipated
    savings, of business or goodwill or (ii)	 	 	 
	 	 	any other liability, damage, cost
    or expense of any kind incurred	9.	Miscellaneous: 
    
	 	 	by the other party of an indirect
    or consequential nature,	
    A.   
	Assignment
	 	 	regardless of any notice of the
    possibility of such damages.  	 	Neither this Contract, nor any of
    either party's rights hereunder,
	D.	 No Warranty	 	may be assigned or otherwise
    transferred by either party without
	 	PATHEON MAKES NO WARRANTY OF ANY
    KIND, EITHER	 	the prior written consent of the
    other party, which consent shall not
	 	EXPRESSED OR IMPLIED, BY FACT OR
    LAW, OTHER THAN	 	be unreasonably
    withheld.  
	 	THOSE EXPRESSLY SET FORTH IN THIS
    CONTRACT.	
    B.
	 
    Force Majeure
	 	PATHEON MAKES NO WARRANTY OF
    FITNESS FOR A	 	Except for payment obligations, neither party
    will be
	 	PARTICULAR PURPOSE OR WARRANTY	 	responsible for delay or failure in
    performance resulting

Page 17 of 18 

CONFIDENTIAL 

	 	from acts beyond the reasonable control and
    without the
	 	fault or negligence of such party, including,
    but not limited to,
	 	strikes or other labour disturbances,
    lockouts, quarantines,
	 	communicable disease outbreaks, riots, wars,
    acts of
	 	terrorism, fires, floods, storms,
    interruption of or delay in
	 	transportation, defective equipment, lack of
    or inability to
	 	obtain fuel, power or components or
    compliance with any
	 	order or regulation of any government entity.
	C.	Survival
	 	Any termination or expiration of this
    Contract shall not affect
	 	any outstanding obligations or payments due
    hereunder
	 	prior to such termination or expiration, nor
    shall it prejudice
	 	any other remedies that the parties may have
    under this
	 	Contract, The Confidentiality Agreement and
    sections 4, 5,
	 	6 and 7 of the Contract shall survive the
    expiration or
	 	termination of this Contract.
	D.	Independent Contractors
	 	The parties are independent contractors and
    this Contract
	 	shall not be construed to create between
    Patheon and the
	 	Client any other relationship such as, by way
    of example
	 	only, that of employer-employee, principal,
    agent, joint-
	 	venturer, co-partners or any similar
    relationship.
	E.	Other Terms
	 	No terms, provisions or conditions of any
    purchase order or
	 	other business form or written authorization
    used by Client
	 	or Patheon will have any effect on the
    rights, duties or
	 	obligations of the parties, or otherwise
    modify, this Contract,
	 	regardless of any failure of Client or
    Patheon to object to
	 	such terms, provisions, or conditions unless
    such document
	 	specifically refers to this Contract and is
    signed by both
	 	parties.
	F.	Insurance
	 	Each party shall maintain during the term of
    this Contract
	 	general liability and product liability
    insurance. Either party
	 	may request evidence of such insurance.
	G.	Entire Agreement
	 	This Contract constitutes the complete
    agreement
	 	between the parties with respect to this
    subject matter
	 	and supersedes all other prior agreements and
	 	understandings, whether written or oral. Any
	 	modifications, amendment or supplement to
    this Contract
	 	must be in writing and signed by authorized
	 	representatives of both parties.
	H.	Facsimile
	 	This Contract may be signed in counterparts
    and by facsimile.
	I.	Choice of Law
	 	This Contract is governed by the laws of the
    Province of
	 	Ontario and the laws of Canada applicable
    therein, without
	 	regard to any conflicts-of-law principle that
    directs the
	 	application to another jurisdiction's law.

Page 18 of 18 

CONFIDENTIAL

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00086-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00086-of-00352.parquet"}]]