CDMO CASE STUDY - AJILITY: Streamlining Drug Product Manufacturing

INTRODUCTION

In the current pandemic landscape, there is an increased focus on faster turnaround times. As drug developers race to get these critical therapies into the clinic and subsequently into commercial production, they are expediting the CDMO selection process along with tightening timelines for tech transfer, and the preparation and release process for fills.

Clinical timelines in general are usually very fast; and now, there is a stronger expectation that the CDMO can adjust quickly to meet the changing demands of the customers’ programs.

There is also a large influx of government-sponsored and funded programs that are increasing the overall demand for capacity and intensifying the pressure on CDMOs to provide flexible, high-quality service that can meet the expectations of customers and the public. Demand for capacity is at an all-time high as clients look for fill and finish services for COVID-19 and Emergency Use Authorization (EUA) therapeutics, and CDMOs struggle alongside other industries to manage the changing landscape of doing business during the pandemic.

In response to this ever-evolving environment, it is more important than ever for CDMOs to ensure they are proactive with how they plan, resource, and execute programs with their customers; rather than reacting to the larger challenges they are facing with supply chain and general product development.

While there has always a constant influx of drug products to the market, since the start of the pandemic, the speed and the number of vaccines, therapeutics, and candidates that have entered in clinical development has been extraordinary, making CDMOs and their capacity for manufacturing these products in high demand.

This past May, Ajinomoto Bio-Pharma Services announced two separate supply agreements with CytoDyn and with Humanigen to provide fill and finish manufacturing for their respective drug products, currently in clinical trials for COVID-19 patients.^1,2

PROACTIVE PLANNING

The CDMO industry prides itself on its flexibility, adaptability, and responsiveness to changing customer needs. Helping drug developers address the challenges their programs may encounter, and adapting to their needs, is at the core of a successful CDMO business model.

 Can CDMOs be more flexible? Offer more adaptive solutions? Provide more responsive services? How can customers get their life-saving treatments to the clinic faster? Those were the questions that Ajinomoto Bio-Pharma Services asked itself as the pandemic continued to spread.

In response to those questions and the changing landscape, the AJILITY^TM platform was established.³ The notable advantage of the AJILITY platform is the ability for clients to leverage Ajinomoto Bio-Pharma Services’ extensive experience in drug product manufacturing, technical knowledge, and regulatory support expertise to expedite therapeutics to the clinic, while maintaining the highest of quality standards. Fundamentally, the AJILITY Platform takes the burden off the client and allows Ajinomoto Bio-Pharma Services to drive, manage, and support clients’ drug product manufacturing, maximizing speed and success, and gives our clients peace of mind to partner with a CDMO that will prioritize these programs and drive them to completion.

AJILITY PLATFORM

In considering and developing the AJILITY platform, the Ajinomoto Bio-Pharma Services team worked through every step and aspect of the manufacturing process to define this service offering in order to provide a high level of support, ensuring a successful tech transfer or design of the clinical program from start to finish.⁴

There are some program details that tend to have a bigger impact on the timeline for tech transfer to a CDMO than others. Often, clients rely on input from consultants or historical precedent to dictate program decisions on things from components and method qualification to excipients and more.⁴

With AJILITY, the Ajinomoto Bio-Pharma Services team provides their experience to select and recommend a fast-tracking program that introduces fewer variables, speeding up the program timeline and minimizing the need for third-party support. Clients are able to select from in stock, preferred components and excipients from a long list of Ajinomoto Bio-Pharma Services GMP qualified vendors, rely on Ajinomoto Bio-Pharma Services personnel to set formulation details, fill tolerances and inspection-ready criteria based on expertise, and participate in an expedited review of methods and discussion/consultations as part of the proposal generation process.

During the tech transfer and manufacturing process, Ajinomoto Bio-Pharma Services works with quality in mind, incorporating additional flexibility into the process by performing compendial methods verifications in parallel with manufacturing activities, and working concurrently on batch documentation reviewing to support a quick release. Performing risk assessments early in clinical development is another tactic customers use to fast track the clinical process and expedite the path to filing. Release timelines are often subject to great variability based on issues that arise during the manufacturing process. Deviations result in investigations that can significantly impact the timeline for release. Working with an experienced CDMO can leverage know-how on the front end to save headaches on the back end.

Clients also benefit from remote site auditing. Current travel restrictions and concerns are making the standard in-person audit difficult, and the compliance team at Ajinomoto Bio-Pharma Services has developed a virtual and online site visit and audit experience to ensure customers are meeting their quality obligations for selecting or maintaining a qualified vendor. Through the use of the portal systems and virtual site tours, clients can be assured they will be able to perform a thorough review of the facilities and quality systems and have connections with the subject matter experts to meet their program requirements and quality standards. Other efficient tools for speeding up time to release include working from templated batch documentation to quickly generate a Master Batch Record (MBR), utilizing an existing library of packaging and labeling components, and employing existing validated shipping configurations and preferred couriers.

The Ajinomoto Bio-Pharma Services regulatory team provides guidance with e-submissions and EUAs, discussing your program needs and working with regulatory agencies to tailor procedures to your program. Ajinomoto Bio-Pharma Services has a long history of working with the FDA on these types of submissions and is uniquely qualified to support these types of programs be it for COVID or other indications.

FOCUSED TECH TRANSFER

Tech transfer activities for bringing a new product or process into the facility are usually rate-limited by analytical method transfers, availability of components, and formulation specifics. Especially in early stage novel therapeutics, there are often gaps between the state of the methods for in-process control and product analysis and what is suitable for cGMP operations.

Likewise, with the formulation process, these early stage programs have been performed on a bench top with inadequate attention having been paid to the scale and process characterization needed to ensure a successful cGMP operation. Many times this is an education process between both the customer and the CDMO, with the rate-limiting terms needing clarification to be in place prior to a run. A clinical-to-commercial program typically involves fewer unknowns, but includes long lead time activities that may or may not propose a risk to a customer’s timeline depending on the quality of the process characterization activities that the customer and CDMO focused on during clinical development.

With the AJILITY platform, leveraging Ajinomoto Bio-Pharma Services’ experience to ensure the best fit for the product and the facilities, the time to manufacturing is greatly reduced, and many of the challenges that typically occur can be planned for or altogether avoided. Qualifying and transferring a product to a new CDMO can be a stressful and difficult ordeal for clients, and the AJILITY platform is a key resource for getting patients the therapeutics they need. Late-stage development also has time and cost hurdles that can be circumvented by designing these early stage programs in such a way as to leverage as much information as possible in late-stage and decrease the scope of work needed to get from clinical to commercial scale.

TAILORED DRUG PRODUCT MANUFACTURING

Once tech transfer activities are finalized, drug product manufacturing can bring its own challenges to work through, from batch record completion and engineering studies to fill line availability, which individually and together can traditionally slow programs down.

To overcome these hurdles and reduce variables, the AJILITY platform offers several areas to gain time-savings. For example, there is the potential to skip engineering studies prior to cGMP operations (dependent on the product), using the existing library of mixing and product contact parts to minimize compatibility studies, and fill line flexibility allows clients to benefit from capacity availability. Ajinomoto Bio-Pharma Services has multiple filling lines for all standard formats, including vials, syringes, and cartridges. Taking advantage of Ajinomoto Bio-Pharma Services’ extensive experience in manufacturing a wide variety of drug products and working together on these program considerations can significantly cut down the manufacturing timeline.

ENSURED PRODUCT QUALITY

Well-designed product quality and analytical programs are critical to ensure a successful final product. Ajinomoto Bio-Pharma Services’ on-site laboratories are equipped with sophisticated equipment, enabling our scientists to employ a full range of methodologies and techniques to characterize clients’ products and develop test methods to validate a product’s quality through its life cycle.

The AJILITY platform offers time-savings for analytical services while sustaining product quality with concurrent and in parallel reviews and method verifications, minimized analytical transfer scope, and satellite ID samples for bulk drug substance lots sent back to the drug substance manufacturer to decrease the cost and time associated with method transfer.

EFFICIENT PACKAGING &SHIPPING

In order to support a product’s clinical performance and market success, Ajinomoto Bio-Pharma Services offers in-house labeling and packaging solutions that provide greater safety and efficiency for your supply chain with our Drug Supply Chain Security Act compliant track and trace service. On-site storage and distribution services minimize supply chain risk inherent to third party sites and makes the supplier management process simpler for our clients

Customers using the AJILITY platform are able to choose from an existing library of packaging and labeling components, use validated shipping configurations and preferred couriers and allow Ajinomoto Bio-Pharma Services personnel to schedule the shipments, and have drug product lots shipped, often under quarantine if the situation permits. Shipping is one less thing clients need to worry about with the AJILITY platform.

AGILE REGULATORY SERVICES

Ajinomoto Bio-Pharma Services has a long history of partnering with our clients on unique programs that require prompt attention and a strong regulatory strategy. Our agile regulatory team works to expedite processes allowing us to manufacture your product faster with process performance qualification and commercial manufacturing in mind.

Collaborating with a regulatory service group that has expertise in EUA product requirements, has an established e-submission policy with the FDA, a CMC section authoring program, concurrent batch documentation review, and can advocate for your program with regulatory agencies and provide the guidance and support to get your therapeutic reviewed and approved quickly and efficiently.

Using the AJILITY platform, Ajinomoto Bio-Pharma Services’ regulatory team is available to assist with and has contributed to numerous clinical and marketing application submissions, and is ready to help with your regulatory submissions, clinical filings, and commercial launches. Clients need a team that has the experience and insight to help navigate any obstacles and progress these critical vaccines and therapies to clinics.

REMOTE ACCESS MONITORING

The ability to observe the manufacturing process is something that varies among CDMOs. Ajinomoto Bio-Pharma Services offers a personalized, secure, and remote viewing platform for clients to monitor their filling process through our ClientConnect^TM portal. This provides the clients with the ability to monitor the operations in real time and to stay connected to their product even when they cannot be physically present.

Ajinomoto Bio-Pharma Services remote auditing procedures additionally provide clients with technology platforms to support live, interactive conversation/interviews, guided walk-through of operational areas, and the ability to review documents and data.

DESIGNED FOR SPEED

While the pandemic has presented a unique opportunity for our customers to capitalize on Ajinomoto Bio-Pharma Services’ regulatory and manufacturing expertise through our AJILITY integrated drug product manufacturing platform, the AJILITY program will be available beyond the pandemic for any therapeutic program that needs flexible and responsive support for expediting your life-saving therapeutic to the clinic. With AJILITY, clients can move from signature to filling in as little as 6 weeks. For more information about the AJILITY platform, visit AjiBio-Pharma.com/AJILITY.

REFERENCES

1. Ajinomoto Bio-Pharma Services Press Release 5 May 2020.
2. Ajinomoto Bio-Pharma Services Press Release 27 May 2020.
3. Ajinomoto Bio-Pharma Services Press Release 30 June 2020.
4. AJILITY Platform Brochure. Available: https://ajibio-pharma.com/wp-content/ uploads/2020/08/AJILITY-Brochure.pdf

 To view this issue and all back issues online, please visit www.drug-dev.com. 

Dustin Campbell is the Associate Director of Commercial Operations at Ajinomoto Bio-Pharma Services, a global CDMO that specializes in a wide variety of manufacturing services supporting the Bio-Pharmaceutical and Small Molecule manufacturing industry. Mr. Campbell has a degree in Molecular Biology from the University of California San Diego and 15 years of industry experience working in Drug Substance and Drug Product manufacturing, Technology Transfer and Project Management.