Pharmaceutical Development Services Agreement between Patheon, Inc. (formerly MOVA Pharmaceutical Corporation) and Cornerstone Biopharma, Inc. dated August 8, 2007
This agreement is between Patheon, Inc. (formerly MOVA Pharmaceutical Corporation) and Cornerstone Biopharma, Inc. Patheon will provide pharmaceutical development services for Spectracef Tablets, including analytical method development, formulation development, feasibility trials, and stability testing. The agreement outlines the project scope, payment terms, and legal conditions. Patheon is responsible for managing the project and providing regular updates. The contract remains in effect until the completion of the specified services.
1. Parties: | MOVA Pharmaceutical Corporation (MOVA) P.O. Box 8639 Caguas, Puerto Rico 00726 | Cornerstone Biopharma, Inc. (Client) 2000 Regency Parkway Suite 255 Cary, NC 27511 |
2. Product: | Spectracef Tablets ([***]mg Strength) (Product) | |
3. Indication: | Antibiotic | |
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 Services: | See Project Scope (Part A). | |
6. Payment and Currency: | See Budget Summary (Part B). | |
7. Legal Terms: | See Terms and Conditions (Part C). | |
8. Effective Date: | , 2000 | |
9. Term: | From the Effective Date until completion by MOVA of the pharmaceutical development services (Services). | |
10. Date of | ||
Confidentiality | ||
Agreement | December 4, 2006 | |
11. Date of PatheonPartner | ||
External User Account / | ||
Access Form | , 2000 [if applicable] | |
12. Date: | , 2000 |
MOVA Pharmaceutical Corporation | Cornerstone Biopharma, Inc. | |||||||||
By: Name: | /s/ Miguel Hernandez | By: Name: | /s/ Brian Dickson | |||||||
Title: | PDS Director | Title: | C.M.O. |
08-August-2007
1. | PROJECT SCOPE | 4 | ||||
2. | ENVIRONMENTAL, HEALTH AND SAFETY | 4 | ||||
3. | ANALYTICAL SERVICES | 4 | ||||
3.1. Cleaning Residuals Assay (Method Verification) | 4 | |||||
3.2. Product Potency and Related Substances Assay (Method Development) | 4 | |||||
3.3. Product Dissolution Assay Profile by HPLC (Method Development) | 4 | |||||
4. | FORMULATION DEVELOPMENT | 5 | ||||
4.1. Feasibility Trials I | 5 | |||||
4.2. Feasibility Trials II | 5 | |||||
5. | STABILITY FORMULATION DEVELOPMENT BATCH | 6 | ||||
6. | PROJECT SUPPORT | 6 | ||||
7. | HIGH LEVEL TIMELINE | 6 | ||||
8. | GENERAL INFORMATION | 6 | ||||
Standard Assumption: | 6 | |||||
PART B: BUDGET SUMMARY | ||||||
PART C: LEGAL TERMS AND CONDITIONS |
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Formulation Development
Cornerstone Biopharma, Inc
Spectracef Tablets ([***]mg Strength) Formulation Development
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| Environmental, Health and Safety |
| Analytical Development and Services |
| Formulation Development |
| Stability |
| Cefditoren pivoxil |
| MOVAs categorization = Category 3 |
| Protocols (except for development work) |
| Reports (data summary will be generated for development work) |
3.1. | Cleaning Residuals Assay (Method Verification) | |
3.2. | Product Potency and Related Substances Assay (Method Development) | |
3.3. | Product Dissolution Assay Profile by HPLC (Method Development) |
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| Spectracef Tablets, [***]mg Strength | |
| 5 Batches |
| Process evaluation up to granulation stage |
| Approximately 2-3 kilograms | |
| Bulk packaged | |
| Process i.e. Mixing and granulation | |
| cGMP | |
| No QA review |
| Potency and Related substances (final two batches only) | |
| Physical testing including appearance, particle size, bulk/tapped densities, flow properties etc. (all batches) |
| Spectracef Tablets, [***]mg Strength | |
| 4 Batches | |
| Approximately 6-9 kilograms | |
| One batch will packaged into HDPE bottles (i.e. 30s) for stability | |
| Process: |
| Batch 1: Mixing and granulation | ||
| Batch 2: Mixing, granulation and compression | ||
| Batch 3: Mixing, granulation, compression and coating | ||
| Batch 4 (packaged batch): Mixing, granulation, compression and coating |
| cGMP | |
| No QA review |
| Blend uniformity | |
| Physical testing including appearance, particle size, bulk/tapped densities, flow properties etc. |
| Blend uniformity | |
| Content uniformity | |
| Dissolution (profile by HPLC) | |
| Potency and Related substances | |
| Physical testing including appearance, hardness, thickness, friability and disintegration |
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| 1 batches for stability testing (Stability Batch) |
=> 1, 2, 3, and 6 months for 25°C ± 2°C / 60% ± 5% RH
| Potency and Related substances | |
| Dissolution (profile by HPLC) | |
| Physical testing including appearance and moisture |
1. | The approach used would be outlined in a more detailed protocol prepared by MOVA and on request approved by the Client. Further studies may be required in the later development stages of the project. Where required these would be discussed and agreed separately with the Client. | ||
2. | It is assumed that the API and/or formulation do not absorb/adsorb to any metal, glass or other components used during the processing and analytical testing of the batch. The fees for any investigational work associated with the API and/or formulation interacting with components are not included within this proposal. | ||
3. | The identification of unknown impurities detected during the study is not included as part of this proposal. |
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| Sink condition | | Specificity | |||
| Selection of medium, apparatus speed | | Accuracy | |||
| Optimization of medium cone. & pH | | Repeatability | |||
| System suitability |
| System Suitability | | Quantitation Limit (if applicable) | |||
| Stability of Standard and Sample Solution | | Detection Limit (if applicable) | |||
| Repeatability |
| System Suitability | | Repeatability | |||
| Linearity | | Quantitation Limit (if applicable) | |||
| Stability of Standard and Sample Solutions | | Detection Limit (if applicable) |
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| System Suitability | | Repeatability | |||
| Linearity | | Solution Stability | |||
| Specificity | | Quantitation Limit (if applicable) | |||
| Range | | Detection Limit (if applicable) | |||
| Accuracy |
| System Suitability | | Intermediate Precision | |||
| Linearity | | Repeatability | |||
| Specificity | | Solution Stability | |||
| Range | | Quantitation Limit (if applicable) | |||
| Accuracy | | Detection Limit (if applicable) |
| System Suitability | | Repeatability | |||
| Linearity | | Solution Stability | |||
| Specificity | | Robustness | |||
| Range | | Quantitation Limit (if applicable) | |||
| Accuracy | | Detection Limit (if applicable) | |||
| Intermediate Precision |
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Once a project has been awarded to MOVA, a similar budget will be presented to the Client that will
include Unique Identity Numbers for invoicing purposes only.
2.0 ENVIRONMENTAL HEALTH AND SAFETY | USD | |||||||
ACTIVITY | PRICE | |||||||
EH&S Assessment | [***] | |||||||
3.0 ANALYTICAL DEVELOPMENT | USD | |||||||
ACTIVITY | PRICE | PRICE | ||||||
3.1 Cleaning Resicuals Assay (method Verification) | ||||||||
Protocol | $[***] | |||||||
Benchwork | [***] | |||||||
Report | [***] | [***] | ||||||
3.2 Product Potency and Related Substances Assay (Method Development) | ||||||||
Benchwork | [***] | |||||||
Data Summary | [***] | [***] | ||||||
3.3 IR Product Dissolution Assay by HPLC (Method Development) | ||||||||
Benchwork | [***] | |||||||
Data Summary | [***] | [***] | ||||||
TOTAL (Analytical Development) | [***] | |||||||
4.0 FORMULATION DEVELOPMENT | USD | |||||||
ACTIVITY | PRICE | PRICE | ||||||
Protocol Preparation | [***] | |||||||
Report Writing and Data | [***] | |||||||
4.1 Feasibility Trials I | ||||||||
Manufacturing | [***] | |||||||
Analytical Support | [***] | |||||||
Project Support | [***] | [***] | ||||||
4.2 Feasibility Trials II | ||||||||
Manufacturing | [***] | |||||||
Analytical Support | [***] | |||||||
Project Support | [***] | [***] | ||||||
TOTAL (Formulation Development) | [***] |
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5.0 STABILITY FORMULATION DEVELOPMENT BATCH | USD | |||||||
ACTIVITY | PRICE | |||||||
Number of Lots 1 | ||||||||
Total Samples 8 | ||||||||
Protocol Generation | Subtotal | |||||||
[***] |
Pullpoint Month | T = 1 | T = 2 | T = 3 | T = 6 | T = 9 | T = 12 | T = 18 | T = 24 | T = 36 | |||||||||||||||||
40°C /76% RH | x | x | x | x | ||||||||||||||||||||||
25°C/60% RH | x | x | x | x | ||||||||||||||||||||||
Samples per pullpoint | 2 | 2 | 2 | 2 | ||||||||||||||||||||||
Cost per pullpoint | [***] | [***] | [***] | [***] | [***] | [***] | [***] | [***] | [***] |
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 Formulation Development Batch) | [***] |
BUDGET TOTAL* (High Potency, Cat. 3) | USD | [***] | ||
Estimated Total (Low Potency, Cat. 1 & 2) | USD | [***] | ||
Deposit** | USD | [***] |
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STANDARD TERMS AND CONDITIONS
FOR PHARMACEUTICAL DEVELOPMENT SERVICES
1. | Services: |
(a) | MOVA agrees to perform the pharmaceutical development services described in the Project Scope (Services). | ||
(b) | Parties must agree on changes, deletions or additions to the Services (Changes). | ||
(c) | Minor Changes shall be confirmed by electronic mail, facsimile or other written document Significant Changes (such as a request by the Client to change the Project Scope) shall be confirmed by a Change of Scope Agreement. |
2. | Payment and Deposit: |
A. | Payment |
(a) | Client shall pay MOVA for the Services as outlined in this Contract and for any Changes which shall be invoiced separately at MOVAs then prevailing hourly rates. | ||
(b) | If Client causes any delay to MOVAs provision of Services for reason within its control (such as a delay in responding to a MOVA inquiry or a delay in the delivery of the active pharmaceutical ingredient (API)), then MOVA shall be entitled to charge the Client for any additional costs incurred in the provision of the Services as a result of the delay. | ||
(c) | MOVA invoices may be issued upon completion of each milestone set out in the Budget Summary and shall be due and payable within 30 days of the date of such invoice. If Client anticipates not being able to meet the net 30 day terms, then Client may request that MOVA forward each invoice to the facsimile number and/or email address stipulated by the Client from time to time to ensure that it has the full 30 days to process payment. Interest on past due accounts will accrue at a rate of [1.5%] per month. |
B. | Deposit (if Applicable as per the Budget Summary) |
(a) | Prior to the commencement of the Services, Client shall deliver to MOVA the deposit (Deposit) set out in the Budget Summary. | ||
(b) | Deposit shall be held by MOVA until the Services are fully completed or until this Contract expires or is terminated in accordance with Section 4. | ||
(c) | Deposit shall be credited towards the final invoice for the Services and any remaining balance shall be returned to the Client. | ||
(d) | MOVA may apply all or a portion of the Deposit against any accounts overdue in excess of 60 days from the date of the invoice. | ||
(e) | MOVA may, at its option, suspend all Services until such time as any outstanding invoices have been paid in full and the original amount of the Deposit has been replenished. |
3. | Supply of API and Materials: |
(a) | Client shall, at its expense, supply MOVA with sufficient quantities of the API for MOVAs use in performing the Services. | ||
(b) | The costs of all third party suppliers fees and the purchase of project specific items (such as raw materials, excipients, packaging, special equipment, tooling, change parts, laboratory columns and reagents, reference standards including those under the applicable United States Pharmacopoeia, the National Formulary, the British Pharmacopoeia, the European Pharmacopoeia or the Japanese Pharmacopoeia) necessary for MOVA to perform the Services shall be purchased by MOVA and charged to Client at MOVAs cost plus an additional 15% as a handling charge. | ||
(c) | If applicable, MOVA and the Client will cooperate and provide such |
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assistance to each other as may be reasonably necessary to permit the import of the API and other materials into the country where the Services will be performed. |
4. | Termination: |
(a) | Either party may terminate this Contract if the other party is in material breach of any provisions of this Contract and the other party fails to remedy such breach within 30 days of the 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 days requested by Client shall, at MOVAs option, be deemed to be a termination of the Contract. | ||
(d) | Upon completion or expiry of the Contract or if the Client terminates the Contract for any business reason or if MOVA terminates the Contract because of: (i) Clients failure to cure any default within the 30 day notice period; or (ii) Client rescheduling any part of the Services beyond the 120 days, then Client shall pay to MOVA: |
| any fees and expenses due to MOVA for the Services rendered up to the date of completion, expiry or termination; | ||
| all actual costs incurred by MOVA to complete activities associated with the completion, expiry or termination and close of the Services rendered up to the date of completion, expiry or termination including, without limitation disposal fees that may be payable in respect of any materials and supplies owned by the Client to be disposed of by MOVA; and | ||
| any additional costs incurred by MOVA in connection with the Services that are required to fulfill applicable regulatory and contractual requirements. |
(e) | Client shall arrange for the pickup from the MOVA site of all materials and supplies owned by Client within 5 days after the earlier of the completion, termination or expiration of this Contract. MOVA shall charge a $30.00 per square foot per month storage fee for all materials and supplies stored at the MOVA site after the fifth day following the completion, termination or expiration to the Contract. |
5. | Intellectual Property: |
(a) | The term Intellectual Property includes, without limitation, rights in patents, patent applications, formulae, trade-marks, trade-mark applications, trade-names, trade secrets, inventions, copyright, industrial designs and know-how. | ||
(b) | For the term of this Contract, Client hereby grants to MOVA, a non-exclusive, paid-up, royalty-free, non-transferable license of Clients Intellectual Property which MOVA must use in order to perform the Services. | ||
(c) | All Intellectual Property generated or derived by MOVA in the course of performing the Services, to the extent it is specific to the development, manufacture, use and sale of the Clients Product that is the subject of the Services, shall be the exclusive property of Client. | ||
(d) | All Intellectual Property generated or derived by MOVA in the course of performing the Services which are not specific to, or dependent upon, Clients Product and which have application to manufacturing processes or formulation development of drug products or drug delivery systems shall be the exclusive property of MOVA. MOVA hereby grants to Client, a non-exclusive, paid-up, royalty-free, transferable license of such Intellectual Property which Client may use for the manufacture of Clients Product. |
6. | Indemnity: |
A. | Indemnification by Client |
Subject to Sections 6B and 6C(c), Client shall defend, indemnify and hold MOVA, its affiliates and their respective directors, officers, employees and agents (collectively, MOVA Indemnitees) harmless from and against any and all third-party actions, causes of action, costs (including reasonable legal fees), claims, damages, liabilities and expenses (collectively. Losses) relating to or arising from: |
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| the manufacture (except as may be contemplated by the Services) or distribution of the Clients Product or the use of the Clients Product by patients either as part of or outside of the scope of any clinical trials; | ||
| the performance of the Services in accordance with the terms of this Contract; | ||
| any misrepresentation, negligence or willful misconduct by Client or any of its affiliates and their respective directors, officers, employees and agents (collectively, Client Indemnitees); | ||
| any breach by the Client of the Clients obligations or warranties under this Contract; or | ||
| any claim of infringement or alleged infringement of any third partys intellectual property rights in respect of the Clients Product. |
This indemnity shall not apply to the extent that such Losses are: |
| determined to have resulted from the negligence or willful misconduct of MOVA; or | ||
| for which MOVA is obligated to indemnify the Client Indemnitees pursuant to Section 6B. |
B. | Indemnification by MOVA |
Subject to Sections 6A and 6C(c), MOVA shall defend, indemnify and hold the Client Indemnitees harmless from and against any and all Losses resulting from, relating to or arising from the breach by MOVA of any of its obligations or warranties under this Contract except to the extent that such Losses are: |
| determined to have resulted from the negligence or willful misconduct of Client; or | ||
| for which Client is obligated to indemnify the MOVA Indemnitees pursuant to Section 6A. |
C. | Limitation of Liability | ||
(a) | If MOVA fails to materially perform any part of the Services in accordance with the terms of this Contract, then Clients sole remedy, subject to subparagraph (b), shall be to request MOVA to: |
| repeat that part of the Service at MOVAs costs provided that Client provides the API; or | ||
| reimburse Client for the price for that part of the Service, excluding the cost of the API. |
(b) | Under no circumstances whatsoever shall MOVA reimburse Client for the cost of the API. | ||
(c) | Under no circumstances whatsoever shall either party be liable to the other in contract, tort, negligence, breach of statutory duty or otherwise for (i) any (direct or indirect) loss of profits, of production, of anticipated savings, of business or goodwill or (ii) any other liability, damage, cost or expense of any kind incurred by the other party of an indirect or consequential nature, regardless of any notice of the possibility of such damages. |
D. | No Warranty |
MOVA MAKES NO WARRANTY OF ANY KIND, EITHER EXPRESSED OR IMPLIED, BY FACT OR LAW, OTHER THAN THOSE EXPRESSLY SET FORTH IN THIS CONTRACT. MOVA MAKES NO WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE OR WARRANTY OF MERCHANTABILITY IN RESPECT OF THE CLIENTS PRODUCT. |
7. | Regulatory Filings: |
(a) | Client shall have the sole responsibility for filing of all documents with the applicable regulatory authority (such as the United States Food and Drug Administration (FDA), the Health Products and Food Branch of Health Canada or the European Medicine Evaluation Agency) (the Regulatory Authority) and to take any other actions that may be required for the receipt of approval from the Regulatory Authority for the commercial manufacture of the Clients Product. | ||
(b) | At least 21 days prior to filing any documents with the Regulatory Authority that incorporate data generated by MOVA, Client shall provide MOVA with a copy of the documents incorporating such data so as to give MOVA the opportunity to verify the accuracy and regulatory validity of such documents as it relates to the MOVA-generated data. | ||
(c) | If MOVA is selected as the commercial site of manufacture of the Product which is the subject of the Services under this Contract, then at least 21 days prior to filing with the Regulatory Authority any documentation which is or is equivalent to the FDAs Chemistry and Manufacturing Controls |
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(CMC) portion of the New Drug Application or of the Abbreviated New Drug Application, as the case may be, Client shall provide MOVA with a copy of the CMC portion as well as all supporting documents which have been relied upon to prepare the CMC portion. Such disclosure shall permit MOVA to verify that the CMC portion accurately describes the Services that MOVA has performed and the manufacturing processes that MOVA will perform pursuant to this Contract. |
8. | Shipping (if applicable): | |
Shipments (if applicable) of Clients Product shall be made EXW (as defined in INCOTERMS 2000) MOVAs shipping point unless otherwise mutually agreed. Risk of toss or of damage to such Product shall transfer to the Client when the Product is loaded onto the carriers vehicle by MOVA for shipment at the EXW point. The Product shall be transported in accordance with the Clients instructions. |
9. | Miscellaneous: |
A. | Assignment | ||
Neither this Contract, nor any of either partys rights hereunder, may be assigned or otherwise transferred by either party without the prior written consent of the other party, which consent shall not be unreasonably withheld. | |||
B. | Force Majeure | ||
Except for payment obligations, neither party will be responsible for delay or failure in performance resulting 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 MOVA 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. | 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. | |||
F. | Patheon Partner | ||
In order to participate in the PatheonPartner program, Client must submit a completed PatheonPartner External User Account/Access Form to its Patheon project manager. If applicable, the PatheonPartner External User Account/Access Form signed by the Client shall apply to the Clients use of the PatheonPartner website in respect of the Services. | |||
G. | Other Terms | ||
No terms, provisions or conditions of any purchase order or other business form or written authorization used by Client or MOVA 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 MOVA to object to such terms, provisions, or conditions unless such document specifically |
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refers to this Contract and is signed by both parties. | |||
H. | 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. | |||
I. | 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. | |||
J. | Facsimile | ||
This Contract may be signed in counterparts and by facsimile. | |||
K. | Choice of Law | ||
This Contract is governed by the laws of the Commonwealth of Puerto Rico, without regard to any conflicts-of-law principle that directs the application to another jurisdictions law. |
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