Speeding Up Drug Development/ Manufacturing with CDMO Partnerships
Demand is growing for more rapid drug development and commercialization timelines. Expediting development and manufacturing time frames allows drug makers to provide vital therapies quicker to the patients who need them.
The industry strives to standardize and simplify the long-haul processes from developing to manufacturing drugs. Comprehensive strategies, including deep knowledge of the regulatory requirements, enable specialized contract development and manufacturing organizations (CDMOs) to streamline workflows, reducing production costs and increasing efficiency. The benefits of biopharma-CDMO partnerships drive the growth of the CDMO outsourcing market. Between 2023 and 2030, CDMO outsourcing is predicted to grow at a compound annual growth rate of 9.2%, reaching a value of $287 billion.1
Growing numbers of biotechnology and pharmaceutical companies seek support from CDMOs, highlighting the importance of focusing on the technology transfer process to prevent delays in project execution. As it is integral to all stages of drug development, manufacturing, and commercialization, accelerating tech transfer is vital to speeding up end-to-end drug development and manufacturing.
Successful tech transfer relies on seamless communication to stay ahead of evolving global regulatory compliance, and a focused approach to process capabilities ensures quality through every stage of a drug manufacturing project. Understanding the consequences of any changes in manufacturing processes also means the process can be applied within the regulatory compliance guidelines.
Integrating Speed into Manufacturing Processes
Drug product (DP) manufacturing relies on the congruent operations of multiple units. By considering the time spent on process optimization before manufacturing begins, CDMOs can accelerate DP timelines to ensure clinical studies are supplied on time and commercial products can meet the drug supply forecast.
Manufacturing processes with speed integrated to accelerate timelines include:
Flexible Capacity
Performing a robust facility fit/gap assessment based on the capabilities of a drug maker and its CDMO partner is the first step to comparing processes and identifying any equipment, cleaning validation, or unique requirements, which prevent delays and provide a flexible approach to DP manufacturing. A CDMO should have the flexible capabilities to provide vials of various sizes, ranging from 2 mL to 100 mL, across drug delivery modalities to support successful and timely production.
Offering commercial labeling and serialization during the transition from clinical to commercial manufacturing also allows for continuous end-to-end manufacturing at the same facility, a distinct advantage in drug manufacturing. Speed to market increases through eliminating potential regulatory and logistical obstacles, the time required for bulk shipping validation, and profit-and-loss events at a different CDMO site.
Right-First-Time Manufacturing
The concerted teams of DP scientists in tech transfer and operations, as well as experts in quality assurance and regulatory compliance, must conduct rigorous risk assessments to determine critical quality attributes (CQA) and design the optimal critical process parameters to achieve the right first time manufacturing processes.
Engineering batches to assess any changes required based on the fit/gap assessment, such as product shear studies, the impact of temperature durations, light sensitivity, and product uniformity during the formulation, filtration, and filling are essential considerations.
Data generated from mixing studies, pump speeds, filtration schemes, subsequent filter flushing, cycle development studies, and product exposure to light and room temperature during the inspection and packaging provide the framework and guidelines to ensure the optimal process to achieve right-first-time manufacturing.
The knowledge management system built into the working fabric of the CDMO, in sync with the drug maker, plays a critical role in the lifecycle management of all DP tech-transfer projects. Transitioning from engineering runs to clinical batch, process validation batch and finally the commercial phase of production, the data generated and lessons learned are invaluable to the success of manufacturing, maintaining original regulatory submission dates, and building product launch inventory.
Media Fills
Media fill assessments to support aseptic process simulations ensure that routine and non-routine interventions are performed and that the type of intervention is acceptable to the drug makers' quality assurance and regulatory compliance teams. Media fill assessments will determine if three media fills are required or if a bracketing approach can be applied to reduce cost and expedite the overall project execution. Regulatory bodies require submissions to include one process-specific media fill data the CDMOs need to implement. If the manufacturing process is outside the bracketing approach, three media fills are performed to meet regulatory dossier acceptance as part of common technical documents, or CTD, the package provided to regulatory authorities.
Robust Supply Chains
Access to new equipment, such as an oxygen reduction system and headspace analysis unit, new technology, and understanding of the DP contact pathway materials such as single-use mixers and mixing bags, single-use filling assemblies, stainless steel, or hybrid filling assemblies including raw materials and primary packaging facilitate timelines to ensure robust supply chains. Constant communication with tech transfer and DP operations teams creates a proactive supply chain to withstand change and avoid prolonged lead times for materials to meet deadlines. Collaboration with multiple suppliers, called dual sourcing strategy, maintains a stable supply of raw materials needed for manufacturing and mitigates delays in the primary and secondary materials, resulting in on-time delivery of final drug products.
Tech Transfer Is the Basis of On-Time Delivery
Tech transfer impacts manufacturing processes, validation approaches, control strategies and continuous optimization. Efficient tech transfer is therefore essential for on-time delivery as product and process knowledge must be effectively transferred between the CDMOs and drug makers to prevent issues and ensure continuous success throughout manufacturing. On-time delivery should consider the following:
Critical Quality Attributes and Critical Process Parameters
A clear understanding of the product's critical quality attributes (CQAs) and the manufacturing process's critical process parameters (CPPs) defines the success of tech transfer and the overall manufacturing project. Early technical discussions outlining the management of the DP tech-transfer timelines are significant to guarantee that batches are manufactured to schedule, focusing on manufacturing readiness and training of the operations team that will execute the protocol and batch record processes.
Keys To Highest-Quality, On-Time Tech Transfer Of Drug Product, In Addition To the Items Discussed In Right-First-Time Manufacturing Section Above:
- Thorough and complete knowledge management transfer of an existing or new manufacturing process from the drug maker to the CDMO, and vice versa.
- Empowerment of team subject matter experts to discuss technical questions and solutions directly with their peers. Then, ensure solutions or possible issues are shared with the larger project team well in advance so quality and regulatory teams can assess any impact on a current or pending submission.
- Planning for potential roadblocks: A review of the lessons learned from previous manufacturing processes, deviation events, new regulatory guidelines, and expectations adds to the overall knowledge of the joint team members and creates an environment of continuous learning and improvement. The free exchange of information among scientists and experts in tech transfer, DP operations, quality assurance, supply chain management, regulatory compliance, and project management is critical in identifying obstacles downstream in the process well in advance.
- Meeting with the production operators early in the tech-transfer process to review new procedures and include their insights leads to a better understanding of possible manufacturing challenges. In addition, any processing steps should be specified using batch record language and terms commonly applied at the CDMO, which reduce deviations and result in clean, efficient drug product processing.
- Integrating batch record and tech-transfer protocol terms that meet regulatory compliance and dossier package requirements leads to golden batches, a right-first-time mindset, and faster batch release timing.
Comprehensive Protocols and Structured Framework
Standard operating procedures (SOPs) provide a structured framework with detailed guidelines, processes, and protocols. Implementing comprehensive SOPs ensures consistency, smooth knowledge transfer, regulatory compliance through quality control, and, ultimately, the efficiency of CDMO tech transfer.
Quality Systems Ensure Timely Batch Release
Commercial batches should be released within a defined period of 30 days after the production date. Having all the required elements in place upon final DP completion enables CDMOs to release batches immediately.
Quality systems can ensure timely batch release. These include:
Quality Testing
Quality control (QC) testing demonstrates that the product meets GMP guidelines and is safe for patients. Analytical testing methods have long lead times, making analytical method transfer a crucial step that QC and project management should track. Transferring analytical expertise to QC personnel requires high attention to detail, a thorough understanding of the product and solid internal communication with the drug maker when challenges arise. Determining SISPQ (safety, integrity, strength, purity and quality) is a key aspect of QC testing that ensures the final product meets the drug maker's and patient's needs.
Review and Monitoring by MSAT
Commercial batches are reviewed by the Manufacturing, Science & Technology (MSAT) team. Careful monitoring of CQAs ensures that the commercial production process remains in a validated state of control. Process and product monitoring reports present data quarterly or semi-annually across the industry. The schedule for MSAT reviews is defined in the quality agreement, and out-of-tolerance or out-of-specification data is evaluated as part of the continued process verification program and communicated transparently with the drug maker. Changes in the manufacturing process are evaluated for the impact on the established process performance qualification and regulatory filings and reviewed cross-functionally with the drug maker.
Executed Batch Record Release Review
Executed batch records include CPPs from all manufacturing processes and real-time documentation from each step, including equipment, drug formulations, and software systems. Manufacturing and quality teams collaborate for any batch-related deviations. A comprehensive root cause analysis and solid corrective and preventative action (CAPA) plan support on-time batch release and provide improvements/mitigation actions to the manufacturing process.
Integrated Capabilities Shorten Timelines
The ability to manufacture the drug substance (DS) and DP at a single site means that CDMOs can further accelerate end-to-end project timelines. Conditionally releasing the DS facilitates the subsequent DP manufacturing steps, reducing the overall batch release timelines. Retaining a small amount of DS for QC testing also allows the remainder of the product to progress to aseptic and sterile fill/finish. The conditional release creates flexible drug production, which enables parallel DS batch release and DP manufacture, and accelerates batch release and project timelines while ensuring a safe and high-quality product.
A Strong Regulatory Understanding Ensures Compliance
Compliance with regulatory requirements for all procedures in drug development/manufacturing ensures the quality and safety of the product administered to patients. Within tech transfer, a quality-driven infrastructure enables the on-time release of batches; ensures deviations from critical quality parameters, CQAs, and SOPs are resolved; and helps DP operators and quality experts collaborate to take proper actions.
A strict quality management system (QMS) provides a quality, safety, and efficacy framework. With a strict QMS, every raw material and component of the drug manufacturing process is well characterized and defined to meet all GMP regulations. By building quality into the manufacturing process, a robust QMS eases the process of regulatory compliance, streamlining regulatory approval and reducing commercialization timelines.
Meeting the Demand for Quicker Timelines in the Future
The growing reliance on CDMOs highlights the importance of a drug development/manufacturing partner that can meet the drug maker's needs while accelerating timelines. Tech transfer processes built with regulatory compliance in mind are a solution CDMOs can use to meet the demand for quicker development/commercialization timelines. Teamwork and cross-functional collaboration with all stakeholders are the most important factors in achieving the highest-quality, on-time tech transfer of drug products.
Choosing a CDMO partner with best-in-class tech transfer capabilities, integrated quality systems and the most up-to-date regulatory compliance processes ensures that drugmakers can bring products to the patients who need them safely and efficiently.
Reference
- Global Contract Development And Manufacturing Organization (CDMO) Outsourcing Market (skyquestt.com) https://www.skyquestt.com/report/contract-development-and manufacturing-organization-outsourcing-market.
Author Details
Jinhyeok Jeong - Senior Director, Drug Product Inspection and Packaging, Samsung Biologics.
Jinhyeok Jeong has over 19 years of experience in drug product operation. Before joining Samsung Biologics in 2012, he worked at Dongwha pharmaceutical company, focusing on drug products and ointments
Publication Detail
This article appeared in Pharmaceutical Outsourcing:Vol. 25, No. 1Jan/Feb/Mar 2024Pages: 16-19
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special
offers from Pharmaceutical Outsourcing – all delivered right to your inbox! Sign up now!