APPROVALS.
BMS WILL COMPLY WITH ALL APPLICABLE LAWS IN
CONNECTION WITH THE DEVELOPMENT AND COMMERCIALIZATION OF COMPOUNDS AND
PRODUCTS.
BMS (BY ITSELF OR THROUGH ITS AFFILIATES, LICENSEES, (SUB)CONTRACTORS
OR AGENTS, AS APPLICABLE) SHALL USE COMMERCIALLY REASONABLE EFFORTS TO DEVELOP
AND COMMERCIALIZE AT LEAST ONE COMPOUND OR PRODUCT.
FOR CLARITY, IT IS
UNDERSTOOD AND ACKNOWLEDGED THAT COMMERCIALLY REASONABLE EFFORTS IN THE
DEVELOPMENT OF A PRODUCT IN A PARTICULAR COUNTRY MAY INCLUDE SEQUENTIAL
IMPLEMENTATION OF CLINICAL TRIALS AND/OR INTERVALS BETWEEN CLINICAL TRIALS FOR
DATA INTERPRETATION AND CLINICAL PROGRAM PLANNING AND APPROVAL, TO THE EXTENT
SUCH IMPLEMENTATION IS CONSISTENT WITH THE SCIENTIFIC, TECHNICAL AND COMMERCIAL
FACTORS RELEVANT TO DEVELOPMENT OF SUCH PRODUCT IN SUCH COUNTRY.
ALL INDS,
NDAS, MAAS AND OTHER REGULATORY FILINGS AND APPROVALS FOR PRODUCTS SHALL BE
OWNED BY BMS.
IN ADDITION TO ISIS' RESPONSIBILITIES WITH RESPECT TO THE CMC
SECTION OF THE IND IN ACCORDANCE WITH THE RESEARCH PLAN,
9
UPON REQUEST BY BMS, ISIS SHALL PROVIDE BMS WITH A REASONABLE LEVEL OF
ASSISTANCE IN THE PREPARATION OF REGULATORY FILINGS FOR PRODUCTS AND IN
INTERACTIONS WITH ANY REGULATORY AUTHORITY IN CONNECTION WITH THE DEVELOPMENT OF
PRODUCTS; PROVIDED THAT IF BMS REQUESTS SUCH ASSISTANCE IN EXCESS OF [***]
AGGREGATE HOURS OF ASSISTANCE, BMS SHALL REIMBURSE ISIS FOR ITS TIME INCURRED IN
PROVIDING SUCH ASSISTANCE IN EXCESS OF SUCH [***] HOUR LIMIT AT THE AT THE
THEN-APPLICABLE ISIS FTE RATE PER HOUR, PLUS ANY REASONABLE OUT-OF-POCKET
EXPENSES INCURRED BY ISIS IN PROVIDING SUCH ASSISTANCE.
SUCH REIMBURSEMENT
SHALL BE MADE TO ISIS WITHIN 30 DAYS AFTER SUBMISSION OF AN INVOICE BY ISIS
REASONABLY DETAILING ISIS' TIME EXPENDED, TOGETHER WITH REASONABLE
SUBSTANTIATION OF ANY OUT-OF-POCKET EXPENSES INCURRED.
SECTION 4.2
IND-ENABLING AND INITIAL PHASE I SUPPLY OF API.
ISIS
WILL BE RESPONSIBLE FOR THE MANUFACTURE AND SUPPLY OF AN APPROXIMATELY [***]
BATCH OF API FOR THE LEAD COMPOUNDS IDENTIFIED UNDER THE RESEARCH PLAN AND
DESIGNATED BY THE JRC TO ENTER IND-ENABLING STUDIES AS SPECIFIED IN THE RESEARCH
PLAN.
SUCH API SHALL BE MANUFACTURED WITH SYSTEMS, PROCESSES AND PROCEDURES
CONSISTENT WITH CGMP PRACTICES.
SUCH API SHALL BE DELIVERED AND PROVIDED AS A
SERVICE FOR BMS WITH A SUPPLY SERVICES FEE BEING $[***] PER GRAM OF API (WHICH
IS ISIS' GOOD FAITH ESTIMATE OF ITS FULLY BURDENED COST OF MANUFACTURE OF SUCH
API).
BMS SHALL BE ENTITLED TO CONDUCT QUALITY INSPECTIONS OF MANUFACTURING
AREAS, WAREHOUSES, LABORATORIES AND ANY RELATED FACILITIES UPON REASONABLE
NOTICE TO ISIS AND AT MUTUALLY CONVENIENT TIMES IN CONNECTION WITH THE
MANUFACTURE OF API BY ISIS UNDER THIS AGREEMENT.
BMS SHALL BE PERMITTED TO
OBSERVE OPERATIONS RELATED TO API MANUFACTURING AND TESTING.
BMS SHALL BE
ENTITLED TO REVIEW ISIS PROCEDURAL DOCUMENTS AND ANY RELATED SUPPORTING
DOCUMENTATION FOR COMPLIANCE WITH CGMP REGULATIONS.
BMS SHALL BE ENTITLED TO
CONDUCT BATCH RECORD AUDITS ON SITE AT THE MANUFACTURING FACILITY, OR ANY OTHER
SITE WHERE THE BATCH RECORDS ARE STORED, OF EACH BATCH OF API MANUFACTURED BY
ISIS UNDER THIS AGREEMENT.
IF, FOLLOWING A GMP AUDIT OF A FACILITY BY BMS, BMS
REASONABLY BELIEVES THAT A DEFAULT