Contract Manufacturing and Pandemic Resilience
By Angela Holley and Scott Cohon, WDPrx - Woodfield Pharmaceutical, LLC | 10.14.20
The Evolving Scope of Research, Product Development and Tech Transfer
The current business environment presents an opportunity to re-examine benefits to pharmaceutical manufacturers from outsourcing Research and Development and Technology Transfer projects to contract manufacturer partners.
Research and development
Selection of a contract manufacturing organization (CMO) with a proven track record for quality and value is a vital component contributing to profitability for manufacturers on the path to commercialization.
The current business environment is increasingly competitive especially for manufacturers of generic medications. Supply chain volatility affecting procurement and transportation of raw materials and demand projection of finished goods are acute challenges of the pandemic.
More entrenched business trends add further pressure on manufacturers. Continued consolidation among large wholesale organizations decreases sales outlets. Heightened government regulatory scrutiny requires substantial resources to oversee licensing and compliance. Aggressive procurement strategies by large buying groups require lower prices, reducing profitability.
Providing confidence amid uncertainty
Several benefits are accrued by manufacturers associated with CMO partners with the experience to achieve objectives despite difficult business conditions. Many of these advantages are related to the time value of money.
Small and virtual manufacturers are especially sensitive to maintaining tight budgets and staff levels. Difficult decisions are made regularly that compare head count and expertise required internally against outsourced capabilities provided by external partners.
For example, virtual manufacturers with scientists on staff may lack a compliant facility to conduct activities under regulatory GMP conditions. In addition to maximizing human resources, challenges also exist optimizing physical infrastructure, job descriptions and responsibilities, information technology assets, logistics and other requirements.
Outsourcing allows subject matter experts at the CMO to present a roadmap for successful R&D strategy. They may also make contributions to build client business beyond commercial manufacture including support for logistics services. The relationship between manufacturers and CMO partners allows each party to focus on their core capabilities to reach successful outcomes and achieve common goals.
By entrusting reputable CMO partners with the responsibility to create and implement a master plan for product development, manufacturers benefit from cost control oversight and other efficiencies that result in expedited submissions to regulatory agencies and faster commercialization.
Consolidation of services
Most procedures, whether in pharmaceutical development or in unrelated activities, increase in cost based on the transportation and labor involved in completing the process. For example, filling your car up with gas at one station and taking it to another for a wash increases overall cost and decreases efficiency. The same principle applies to pharmaceutical R&D and contract manufacturing. Selecting a CMO partner with comprehensive services and a wide range of expertise consolidates responsibility with a concentrated group as opposed to awarding separate contracts for related services along the roadmap to different companies.
Consolidation of effort
Duplication of effort is an additional expense often incurred by the piecemeal allocation of R&D and product development to multiple CMO firms. Rigorous Quality Assurance requirements are built into GMP guidelines to assure process integrity. A CMO with the ability to perform functions throughout the entire development roadmap reduces potential duplication of effort that is a byproduct when multiple CMO partners undertake separate QA procedures to verify work performed by other firms along the path to commercialization.
With multiple tasks consolidated under one roof, responsibilities are concentrated with fewer team members, providing manufacturers with a clear pathway for streamlined oversight of activities. With this structure, roles are clearly defined, decisions are more easily transmitted to all parties, communication is simplified and direct, minimizing misunderstanding and potential program delay.
Economies of scale
Volume discounts available to CMO partners for bulk purchases of API, excipients and componentry are passed on to manufacturers affording them savings difficult to achieve without outsourcing.
Manufacturers working with limited budgets often allocate sufficient funds to develop and submit a project. The decision to outsource research and development makes available to manufacturers the entire knowledge base of the CMO including the availability of all human resources required to bring the project to successful conclusion.
The relationship between manufacturers and their CMO partners highlights the difference between experience and expertise. Experience includes the skills and requirements needed to perform a task. Expertise involves the utilization of existing industry and government relationships that fortify experience to benefit the client. As specialists in R&D and formulation development, CMO firms interact on a regular basis with familiar contacts working within regulatory authorities. Smaller manufacturers with a limited product pipeline may not know the proper person to reach for specific questions or answers as the project moves from product formulation and process development, analytical method development and validation, through manufacturing, release, stability testing and the associated documentation needed for FDA submission, if required.
An example of CMO benefits
There are several real-world examples detailing how manufacturers, especially smaller and virtual companies, leverage the above advantages of CMO outsourcing to complete projects in less time and with improved cost efficiency compared with alternative methods.
A typical recent example involved a virtual manufacturer of generic products which entered into an agreement to outsource new product development of an oral suspension. The comprehensive program included product formulation and process development, R&D prototyping, registration batches and ANDA Submission. Each milestone and associated tasks were outlined and included in the project roadmap provided to the client.
Pre-formulation and process development
The selection of API and other specialty chemicals required for production of the suspension involved testing and research to confirm compatibility and legal authority, production of lab batches to finalize components and qualification of packaging components. This phase required approximately ninety (90) days from inception to milestone completion.
Research conducted in the formulation stage is converted into models suitable for full analytical procedures, testing, manufacture of R&D batches, stability testing and analytical method development with validation. This stage was conducted concurrently with the previous phase and was completed in approximately 180 days.
After accelerated stability studies were completed, the process for registration batches began. This stage involved manufacture of demonstration batches, additional studies performed on the product, registration batch production with testing of packaged finished product, production documents, long-term stability studies and reporting. Milestones set at this stage were completed within 10 months.
After additional work which was contracted outside the scope of this agreement, data was gathered and managed by the CMO to support ANDA submission with the FDA. The Chemistry, Manufacturing and Controls (CMC) documents were complete and available early within this stage as document coordination and preparation were integrated into previous stages as a work product confirmed with each milestone of progress measurement.
Engaging a CMO with the experience and expertise to present manufacturers with a complete and detailed roadmap for research, development, production and submission of a pharmaceutical medication for regulatory approval takes on added importance during a pandemic. Timelines and delivery dates that could be relied on in the past are no longer valid. Manufacturers must increasingly rely on the knowledge inherent in specialized CMO firms to navigate the uncertainty to bring projects to completion in a timely manner to support business goals.
Imagine the relationship between manufacturers and CMO partners as an NFL football game with both organizations playing on the same team. The process of R&D and formulation development represents the kick-off starting the game. The team has endured many practices to develop the tools and skills required to play. The FDA approval of the successful ANDA submission is similar to the team winning the football game at the end of regulation play.
Extending the football analogy, technology transfer by a manufacturer to a trusted CMO is represented in the NFL game by the successful completion of a ong forward pass down the field to a wide receiver. Multiple skills including clear communication, coordinated timing and the ability to avoid challenges along the route describe this difficult football maneuver and also the requirements for successful technology transfer.
Tech transfer fundamentals
Moving from the initial decision to engage in a technology transfer program until the manufacture of the product in the new location with reproducible quality is a complex endeavor.
Pharmaceutical manufacturers engage in technology transfer with trusted contract manufacturing partners to decrease expenses and increase efficiency. Successful technology transfer projects require detailed advance planning to assess and anticipate all potential issues and avoid unnecessary program costs.
The selection of a CMO for technology transfer offers the manufacturer an opportunity to increase value with improved process efficiencies and equipment design by building operational excellence principles into the work. When following pharmaceutical Quality by Design (QbD) procedures, the CMO documents a comprehensive plan evaluating original methodologies and implementing process improvements for more effective risk management.
Roadmap for success
The challenges to successful technology transfer when working with virtual manufacturers are often heightened because there may be a lack of complete historical data about the product involved with the transfer. Some virtual manufacturers may rely on expertise from the contract manufacturer about scale-up and other pharmaceutical development and manufacturing areas to enable a streamlined transition to the production site.
CMO as cost control monitor
Experienced CMO partners guide manufacturers to anticipate expenses for regulatory and legal fees, API, CAPEX (costs associated with specific equipment and machinery), labor, stability studies, packaging trials, exhibit batches and analytical method transfer charges.
The expenses listed above are able to be estimated in advance with reasonable certainty. Costs, on the other hand, are unanticipated charges that affect successful results. Failure to take these potential problems into account early in the planning stage may spell disaster for the entire transfer. Costs include incorrect analytical methods, outdated documentation, poorly defined procedures and ambiguous understanding of process parameters.
Well-defined expenses clearly conveyed to all parties create efficiencies and support successful technology transfer. However, unanticipated costs generate inefficient use of time and labor delaying development, manufacturing, regulatory submissions and approval.
Insights for smooth workflow
Although each transfer involves a unique set of circumstances, three general guidelines help assure a successful tech transfer relationship.
A proven project management plan is the first step to successful technology transfer projects. Assembling the project management team requires participation of stakeholders from the manufacturer and CMO with the skills, tools and expertise required to achieve objectives.
Good project management begins by establishing a mutual definition of a successful project outcome. Define the elements of a successful project at the start and work backwards to set realistic expectations. Based on project deliverables, the team creates a Technology Transfer Documentation Package that identifies tasks, assigns resources, sets due dates and agrees on tech transfer milestones. The manufacturer and CMO analyze the existing process including original formulations, analytical methods and production methods. A review of original equipment determines whether modification in the new facility is required. Training procedures are examined to assure clear understanding of individual and team responsibilities and to confirm GMP compliance.
If any questions arise from the Technology Transfer Documentation Package, it may be necessary to seek input from the previous manufacturer if available to reduce cost and gain information helpful during the production process. A Quality Assurance and Regulatory Compliance review increases manufacturer confidence in the CMO by analyzing documentation for completeness and up-to-date production records. This examination extends to SOP protocols concerning processing, packaging and cleaning; confirming that analytical testing methods meet SUPAC guidelines; conducting packaging line trials and completing a comprehensive health and safety review.
Complete the task
Throughout the process, the CMO monitors the original success parameters to remain focused on the roadmap. In constant communication with the manufacturer, the CMO project manager relies on transparent and honest dialog for effective problem resolution.
Glue holds it together
Technology transfer projects are sometimes fraught with well documented challenges due to miscommunication, lack of knowledge or experience. These problems are compounded due to the involvement of multiple parties with vested interest in the manufacture, regulatory approval and commercial sale of the original product. An experienced CMO partner possesses the resources to manage the scientific, manufacturing, compliance and communications priorities for successful technology transfer. Small and large manufacturers rely on their CMO to overcome obstacles and realize their vision within set budgets and timelines. By selecting a reputable CMO for technology transfer, manufacturers gain cost control, proven expertise and equally as important, peace of mind.
The manufacturer and CMO collaboration with research and development, product formulation and technology transfer, when properly conceived and implemented, optimizes the probability of commercial success.
As disruptive technologies change the financial model of the conventional pharmaceutical industry, it is incumbent on manufacturers together with CMO partners to increase the breadth and scope of their traditional alliance. Manufacturers seeking greater productivity must deepen associations with CMO firms expanding their value proposition by offering more services along the entire supply chain.
Additional opportunities for value creation exist downstream in the supply chain. For example, a progressive CMO partner may also contribute with solutions including serialization, licensing, logistics, distribution, packaging, labeling and financial services through relationships with Third Party Logistics providers.
Coupled with upheaval from technological innovation is the unprecedented business uncertainty caused by the coronavirus pandemic. Manufacturers and CMO firms must together develop supply chain resilience with innovative strategies to preserve and enhance productivity and patient satisfaction.
Angela Holley is Director of Business Development at WDPrx – Woodfield Pharmaceutical, LLC, a contract development and manufacturing organization (CDMO) specializing in non-sterile liquids including gels and suspensions.
Scott Cohon is the Director of Sales and Trade Relations at Woodfield Pharmaceutical, LLC., responsible for identifying evolving requirements of manufacturers and implementing services that support commercialization strategies.