NEW PRODUCT INTRODUCTION - Addressing the Pitfalls of Progressing From Pilot to Product Through Effective New Product Introduction

INTRODUCTION

Introducing a new pharmaceutical product – new production introduction (NPI) – involves transforming an approved product into a refined product ready for clinical trials or commercializa­tion. It is the cornerstone of successful product development and tech transfer of marketed products.

Whether introducing a completely new product, reformulat­ing an existing formulation, or changing the process or equip­ment of an existing product, having an effective NPI strategy is crucial to avoid challenges stemming from miscommunication, poor knowledge transfer, or elsewhere. Inadequate planning in­creases the risk of quality issues during the scale-up of new pro­duction processes. Addressing this issue can be costly and time-consuming, delaying project progress.

The following explores the risks and challenges pharmaceu­tical companies face when undertaking NPI to ensure new prod­ucts successfully reach the market and patients. It also examines the strategies contract development manufacturing organizations (CDMOs) are adopting to ensure the smooth delivery of these projects from discovery to commercialization.

AN INCREASING RELIANCE ON CDMOS WITH NPI EXPERTISE

Offering potential benefits, including capacity, cost efficiency, access to specialized expertise, and global reach, the pharma in­dustry continues to rely heavily on CDMOs to deliver critical med­icines to patients with certainty. This is reflected in the expanding global CDMO market, which was valued at around USD $155.7 billion in 2023 and is expected to grow to USD $291.1 billion by 2032, with a compound annual growth rate (CAGR) of roughly 7.20%.(1)

An integral part of the success of these partnerships is the CDMO’s NPI experience and expertise. Consisting of managing the design and manufacturing of new therapeutics, NPI forms the basis and foundation of success for any commercial or clinical supply project. It is the process of taking an idea for a novel phar­maceutical product from a working prototype to a refined product ready for clinical trial or commercialisation. As a comprehensive process, it involves a series of stages, including design, develop­ment, testing, production, and market launch, encompassing both product development and technology transfer.

UNDERSTANDING THE COMPLEXITIES OF NEW PRODUCTION INTRODUCTION

Due to the complexity of product de­velopment and technology transfer, deliv­ering innovations from pilot to product can come with several key considerations that must be navigated to ensure NPI success:

Communication is Important
As the project progresses from discov­ery to pilot to product, communication be­tween each team is critical. Without effective collaboration between teams, siloed working can result in misunder­standings, errors, and delays, potentially impacting product quality and project suc­cess. The teams must organize and attend regular meetings to ensure projects re­main on track and any risks are quickly identified and mitigated.

Comprehensive Knowledge Transfer is Vital
When a CDMO partner begins sup­porting a project, development is typically already underway, with customers having a prototype or pre-developed formulation. In the case of tech transfer, the product is often already established.

In these situations, the knowledge re­lated to the products needs to be trans­ferred efficiently and accurately. This could include sharing a detailed technology transfer plan, comprehensive manufactur­ing descriptions, and technical gap analy­sis documents. Without access to this information, the CDMO might risk form­ing the wrong conclusion or will need to spend time and resources repeating the research and development to attain this in­formation.

Preventing these risks relies on strong communication between all parties, ensur­ing a clear definition of the scope of work, and ensuring those involved are aware of the quality project plan (QPP) before proj­ect initiation.

Robust Regulatory Strategies are Necessary
A well-defined regulatory strategy is needed to ensure compliance with relevant regulations, guidelines, and standards. It also guides the compilation of necessary data, documentation, and validation infor­mation required for the submission of reg­ulatory documents, such as drug master files (DMFs) and marketing authorization applications (MAAs).

A clear understanding of the regula­tory strategy is required throughout prod­uct and process development and tech transfer to ensure compliance and miti­gate risk. This involves defining the activi­ties needed to demonstrate stability and validation, going hand in hand with defin­ing the QPP and scope of work.

Steps Must be Taken to Ensure Equipment is Like-to-Like
Another common challenge that can impact the success of tech transfer to a CDMO if not carefully navigated is the transfer of processes to equipment that is not like-to-like, for example, if a process is moved from one model of a granulator to another. As a result, process parameters may require adaptation. Process modeling is essential in these circumstances to make sure that even when changing equipment, the process will be run within a defined de­sign space, ensuring accurate and reliable manufacturing.

Inadequate planning increases the risk of quality issues. This is particularly true during the scale-up of new production processes, as pilot-stage equipment may not be compatible with clinical or commer­cial manufacturing capacity. Addressing this issue can be costly and time-consum­ing, delaying project progress.

Standard Processes Must be Maintained

Without a project management strat­egy that follows a standardized process, drug developers and manufacturers can­not expect to keep to timelines and secure success throughout product development and tech transfer.

A structured NPI process relies on having a project management workbook, risk assessments, transparent communica­tion, and collaboration between teams (particularly with governance teams), and stage gating. Having a stage gate process means drug developers and manufactur­ers can stop during certain tech transfer or development stages to ensure the neces­sary objectives, activities, and deliverables are met before moving forward. This helps to manage risk, ensure quality, and streamline the transition from one phase to the next.

With the assistance of CDMOs, pharma companies can prevent quality is­sues, eliminate risks, and have production processes that are scalable from the outset, enabling a seamless journey as the project moves from discovery to commercializa­tion. However, to achieve this, the CDMO needs to apply the right NPI strategy.

STRATEGIES TO DELIVER WITH CERTAINTY THROUGHOUT NPI

To minimize these risks and overcome the challenges of NPI, drug developers must ensure their chosen CDMO partner has a comprehensive and effective plan in place. Effective communication between teams throughout the project’s journey is vital, as is comprehensive technology transfer support to share knowledge and expertise at each stage.

When selecting a CDMO to support NPI, drug developers should carefully con­sider if their potential partner can offer the following factors needed to secure success:

Applying a Science-led Approach to Ensure Effective NPI
A science-led approach to decision-making is integral to the success of tech transfer and product development, relying on the design of experiments (DoE) and quality by design (QbD) (based on risk as­sessment and available data) while lever­aging statistical tools and modeling. DoE is a powerful tool to optimize formulations and processes, minimizing drug develop­ment risks at the earliest stage of the NPI process and enhancing efficiency during scale-up from bench to clinic to commer­cial. As a result, quality is built in from the beginning and helps to ensure that prod­ucts meet their quality target product pro­file (QTPP). A CDMO backed by a dedicated network of scientists can provide vital support in delivering in this area.

When applying a fact-based ap­proach from the start of the product devel­opment or tech transfer project, the CDMO must evaluate all the processes and materials. This includes examining the critical process parameters (CPPs) and ma­terial attributes to gain a greater under­standing of how they are related to the quality attributes. A supporting risk assess­ment can further help developers and manufacturers identify the critical param­eters of the process and quality attributes.

The CDMO can leverage a statisti­cally supported trial design to confirm the critical parameters and attributes identi­fied. Consequently, those then will be used to define the design space. The knowledge obtained from the trials can be used when upscaling to determine the best process for commercial production independent of the used equipment size or type.

A structured project management process and a scientific approach based on DoE principles, help assess and ad­dress risks and identify and quantify the in­fluence of critical parameters. With this approach, the CDMO can have a proto­type formula suitable for the desired man­ufacturing process after 1-2 days, consuming only a small amount of API.

An Example: A Science-led Approach to OSD Manufacturing: In oral solid dose (OSD) manufacturing, tablet, capsule, and granular formats require powder with suit­able flowability. A powder’s flowability will consist of a two-digit number of different impact parameters, including particle size, particle shape, loss on drying, porosity, and density. It is critical to investigate the quantitative impact of these parameters flowability of the powder.

Within a powder characterization lab, CDMOs can measure the different param­eters in a scientific-approach trial design using a few grams of active pharmaceuti­cal ingredient (API) to identify the critical components impacting flowability. From an excipient database, the CDMO can then select suitable excipients to enhance flowability and use this to design the for­mulation in silico. The formulation can then be blended for prognosis to verify the improvement in flowability, with the CDMO iteratively changing the formula based on the measurements to maximize the success rate.

Global Project Management
To standardize tech transfer processes and increase efficiency, global CDMOs with multiple locations to support cus­tomers must consider implementing a project management organization with harmonized rules and structure. Working with the local teams, the global project management organization can provide state-of-the-art tech transfer processes ap­plied with rigor and discipline. The project should follow a structured yet malleable development process of continuous moni­toring and rigorous controls to deliver ef­ficacious and safe therapeutics at speed.

Efficiency & Resource Leverage
By leveraging resources across the or­ganization, CDMOs can minimize hands-on time and ensure projects can be completed more quickly and effectively. With a scientific network that is efficient and adept at transitioning between facili­ties with a clearly defined handover, the right CDMO partner can minimize delays by guaranteeing the prompt communica­tion of knowledge to the right expert at the right time. This can drive time and cost savings for drug developers, helping to deliver critical therapies to patients sooner.

Experience
CDMOs with a long history of per­forming tech-transfer between their sites as well as to and from third parties will un­derstand how to scale up, tech-transfer, and validate processes rapidly with a focus on product quality. A strong track record of smooth tech transfers can provide drug developers with the confidence that their CDMO partner will onboard their small and large molecule projects seamlessly.

Comprehensive Support
By supporting all aspects of the tech-transfer process, from consideration of the equipment available at the new site and understanding critical process parameters, to handover of manufacturing and quality control methods, CDMOs can en­sure the transfer process is as smooth and seamless as possible.

Forming the foundation for the success of any product de­velopment or tech transfer, CDMOs must also be able to sup­port technology and scale, offering all the technologies in small, pilot, and full scale.

Transparency
Complete transparency is critical during the tech transfer process. All process documentation, including successful runs and any failures or issues, must be made fully transparent be­tween parties to ensure complete information transfer. This re­lies on clear and frequent communication between parties and teams.

Harnessing effective communication, collaboration, and process management, the right CDMO can scale, transfer, and validate processes rapidly while mitigating risks and complying with stringent regulations.

UNLOCKING THE SECRETS TO EFFECTIVE NPI IN THE FUTURE

As increasing numbers of pharma companies seek part­nerships with CDMOs in the future to alleviate needs for ca­pacity, expertise, and global access, drug developers must carefully consider whether their prospective partners can deliver NPI success. Effectively navigating the complexities of NPI re­quires careful planning, open communication, and robust proj­ect management. By partnering with a CDMO that applies a fact-based approach, has a global project management or­ganization, and offers comprehensive support, pharmaceutical companies can overcome the challenges of NPI and bring their products to the market with certainty.

REFERENCE

1. https://www.zionmarketresearch.com/report/pharmaceutical-cdmo-market