BSMA 2018 Foster City, California Conference Proceedings

Eminent executives of Life Sciences addressed how new product introduction can be enhanced by optimizing the critical transition from clinical to commercial management in the supply chain at the 11^th Annual Conference of the Bio Supply Management Alliance (BSMA) held on the 11th of October in Foster City (CA).

Kevin Webb, a 25-year veteran of biopharma and aerospace, led the forum consisting of Bill Coakley, Sr. Director, Global Supply Chain Planning, BioMarin Pharmaceuticals; Dan O’Donnell, CEO, Aquilon Consulting; Jan Pieter Kappelle, Vice President, Strategy, 4G Clinical; Jason Dean, Director, Bracket; and Khalid Shah, Vice President & Head of Pharmaceutical Operations and Supply Chain, Exelixis.

(Photo:  names of persons left to right same as list above).

It was emphasized that close colaboration between Supply Chain, Commercial and Regulatory Affairs, with participation by Product/Program Management, is always important but critically so during launch planning and execution. The traditional autonomy of Clinical Trials, Manufacturing and Commercialization can be integrated to significantly improve cost, time, quality and success of drug development and delivery.

Several factors should be considered for a successful new product launch, namely:

1. Establishing the desired timing of first shipments following approval notification for the US, EU and RoW.
2. Process development following approval where the requirements for capacity scale-up, related validations & regulatory approvals are formulated along with cost reduction and dosing delivery methods.
3. Clinical and Market strategy for studies and/or study subjects in RoW countries to support local filings for approval
4. Product strategies for Label expansion and additional indications.

Within the context of these elements, the Supply Chain team must consider and manage demand, supply, master data and the supply chain business processes. 

Demand Management: As is standard practice in demand management, all sources of demand must be captured and integrated.

***Commercial forecast granularity across the launch window should provide enough detail to allow effective planning and contingency modeling

• Weekly or monthly vs. quarterly or end-of-year targets
• Naïve and transitioning clinical patients
• Timing of pricing and reimbursement agreements with payors and inclusion on formularies
• Timing of demand well-coordinated with the Regulatory Affairs tea

***Named Patient Sales (NPS), another source of commercial demand and often from second or third-tier markets, can occur at any time after the first primary markets receive approval.

• Treating physicians in those countries can request their local Ministry of Health to purchase product that has been approved in another market, typically US or UK and occasionally French or German label.
• NPS demand can continue indefinitely until local approval is received.

***Clinical forecast (plan) for patient transition to commercial therapy and study site closure

• Potential for relocated or traveling patients returning to home countries following approval
• Potential additional studies for label expansion or phase 4 requirements (Post Approval Measures/Post Marketing Requirements)
• Clinical patients may continue on clinical product in “extension studies” while awaiting local commercial regulatory approval.

***Manufacturing and Process Development

• Additional validations (e.g. new DP production), process changes (consuming capacity), stability lots or retains

Supply Management: Product supply and availability can be risky during launch, particularly for global launches.  Too little inventory of the correct label (country) can slow or stall an otherwise successful launch and too much inventory risks scrap costs from expired product or revenue impacts as payors lobby to discount short-dated product. 

***Certainty of dating at approval

• If stability data is strong and extends well beyond relevant manufacturing lead times (DS, DP), the Supply Chain and Operations team may be more aggressive in producing supply ready for launch. If not the case, agility may be the key to a successful launch. 

***Timing of final label text and scheduling launch pack/label lot(s)

• The highly structured approval process used by the EMA can simplify planning for initial pack jobs however, there are additional local requirements that vary in some European countries. So called “Blue Box requirements” include a PZN number in Germany to be printed on the carton and stickers placed on the carton for France and Italy.  Supply readiness commitments to the Commercial team will need to reflect these lead times. 
• In the US, initiation of label negotiations is usually an indicator that the FDA is nearing completion of their review. While the Sponsor and the FDA can exchange multiple mark-ups during these negotiations, the FDA can change the text with their final approval (the company Regulatory Labeling group and company Leadership usually review the final text for any changes before initiating the launch).   If the company desires a quicker launch and feels confident based on label negotiations with the FDA, labeling a small “launch lot” at risk may be an option.  Place your bets wisely.  

***Requirement for commercial scale-up of manufacturing capacity or other process changes after market approval

• Timing of supply availability from prior approval type changes (Prior Approval Submission, Type II) can be difficult to predict. Close coordination with Regulatory Affairs and Commercial is critical to ensure smooth supply to new patients. 
• Consideration should be given to changes that will be included in Rest-of-World countries: only after US and/or EU approval or incorporated in the original filing. Coordinating lots to countries that have approved changes is critical, and often difficult, to prevent shipping unapproved product.

***Reallocating product

• Reallocating product can be a way to optimize supply, adjust to problematic launch forecasts, and add a nice profitability boost from product originally written-off by accounting when it was allocated (labeled) for clinical use. To properly reallocate labeled product, a delabel-relabel protocol must be written and validated and ideally done before a high-stress situation necessitates an expedited event. 

***Don’t forget your Logistics group! After all other activities are in place, they must deliver a viable product to a happy customer. 

• Shipping qualification methods and data are a component of the regulatory filing and questions about shipping methods to support clinical studies are possible during pre-approval inspections. However, care needs to be taken that shipping methods consider commercial volumes and locations (i.e. routes from northern to southern hemisphere), customs brokerage requirements and timing, and local country of origin requirements (definitions vary by country).
• If active shipping containers will be used, lead times to position these containers at the distribution center can be quite long, up to several weeks.

Master Data & Process Management: Systems tools and organizational structure play a big role in successfully transitioning a product from clinical management to commercial management with minimal drama.  Data integrity and visibility to the organization are critical to analysis and well-informed decision making and effective execution.   Having these structures and processes in place during the late-stages of the clinical program will minimize problems during commercial launch.

***Data Management Systems and Tools

• The location of product data (i.e. demand, supply, inventory, configuration) during the clinical phases may be different than where this data will be located to support the commercial supply chain. If separate systems are used (clinical specific software, spreadsheets), data mapping will be required and careful planning will be required to ensure data accuracy and currency (refreshes) during the transition.
• Consideration should be given to differences in the planning parameters between clinical and commercial. Lot sizes, lead times, yields, routings and recipe definitions, cost data, potentially expiry data, buyer/planner assignments are just a few examples of data that will need to be reviewed for potential changes.  If processes don’t already incorporate it, consider that recipe (BOM & routings) changes may require Quality Specification (“QA Spec”) changes as well.
• Supply chain definitions used by the Operations group, e.g. the approved product‑critical components of the supply chain such as manufacturers of drug product, drug substance and final packaging may need to be updated. These definitions often guide the Operations teams on which contract manufacturers have been approved, and can be used, for each commercial market.  If commercial scale-up is anticipated as a global launch progresses, or if redundant manufacturers will be implemented, updates to the “approved supply chain” documentation must be made, coordinating with the Regulatory Affairs group on approval dates.  

***Organization & Process

• If the Planning team utilizes dedicated clinical and commercial planners, the responsibilities must be transitioned while recognizing the priorities of each environment. If the clinical supply chain is managed outside of the Operations group, such as within Clinical Operations, differences in policies and processes may need to be integrated for purposes of the launch (e.g. S&OP).
• Sales & Operations Planning (S&OP) may need to be updated to include the new product. A decision must be made regarding inclusion of the new product launch activities within the current S&OP constructs or use of a separate launch process.  If separate, linkages must be made into the S&OP process.  Shared resources and inventory for clinical and commercial supply (e.g. drug substance) should be managed mutually within the S&OP process to maintain aligned business priorities.
• Regulatory approval timing will affect the demand and supply of both clinical and commercial product, of course. Consequently, Regulatory Affairs may be required to participate more closely in the S&OP process than would routinely be the case outside of product launch windows.   Tracking of planned and actual approvals dates, and refresh frequency of this information, must be incorporated into the inventory planning process.

Summary

Regulatory approval and launch of a new product is an exciting time for a company. In addition to their routine activities, the Supply Chain team must be hyper-vigilant about many other activities beyond balancing supply and demand.  Very often managing uncertainly, the “stock in trade” for the Supply Chain team, is put to its highest test.  This is particularly true of smaller and less mature companies that may have limited resources, processes and technology.  However, it can be equally true for larger companies that may be organizationally and geographically dispersed.  Early initiation of planning, close collaboration, and providing clear information to company Leadership regarding capabilities is critical to ensure a successful, if not accelerated, product launch.