CDMO Considerations for CGT/ATMP Companies

Converging naturally are the worlds of Cell & Gene Therapies and the CDMO. This convergence is necessary and timely. Given the exciting times of the growing biotechnology there are fewer and fewer options to make these products at scale to meet clinical needs much less commercial. This article takes the reader through the product lifecycle and helps the CGT companies make good decisions around their regulatory strategy, decision to build or buy, and then ultimately to whom and why.

- Christine Feaster, SVP, Strategic Operations

We are in an exciting time where biotechnology products are growing at such a rapid pace. Cell & gene therapies (CGT), Tissue engineered products and Advanced Therapy Medicinal Products (ATMPs) offer several new benefits. These benefits range from potential cures for genetic disorders, better more effective treatment options for what was once deemed incurable diseases, personalised medicines tailored to individual patients, and the possibility of long-lasting or even permanent treatment effects. These therapies represent a significant advancement in the field of medicine with the potential to revolutionise the treatment of various diseases.

In addition, the global cell and gene therapy market is expected to grow from US$6.58 billion in 2021 to US$8.57 billion in 2022 at a compound annual growth rate (CAGR) of 30.2 per cent. The cell and gene therapy market is expected to reach US$21.33 billion in 2026 at a CAGR of 25.6 per cent. 1 The outsourcing market is the largest, according to the report, remains North America. Despite current geopolitical ‘frictions,’ reshoring and the like, Asia is still estimated to have the highest growth during the next five years. This will be something to consider in your selection of CDMOs in the future.

From true end-to-end development through scale up and commercialisation, there are many unique considerations when starting out on this journey that can have a major impact on a make-or-break approval pathway of your advanced therapy. This includes deep technical and regulatory know-how, but also how to generate buy-in from investors and the board members. This becomes paramount as you have received or are looking to receive new funding for future growth of your company. In the very early stages of discovery and development for a new CGT/ATMP therapy and/or its delivery, it is typical for small quantities of investigational drug substance to be produced in a development lab within your company or even through an academic collaboration within a university lab setting.

This early material serves various purposes, including characterisation, small-scale animal studies for proof of concept and safety, analytical method development, and excipient uses for ideal stability. Data from this initial work may be used to demonstrate the potential of the technology or substance being developed, with the intention of attracting investment funds or collaborating partners to invest in the future commercial product.

After proof of concept (PoC) and funding, scaling up becomes necessary. This requires generating more material to demonstrate process and analytical controls, including the following:

• Adequate suitability of analytical methods
• Robust manufacturing processes
• Next stage stability studies and stability
• indicating methods
• Safety and efficacy in the clinical trial stages
• Proof of phase appropriate GMP controls where you are looking to prove consistency

Effectively managing the decision-making process involves balancing risk and speed to market, especially as you prepare for pre-clinical stages and thoroughly vet potential partners. Here’s how you can navigate the decisions about whether to outsource and the next steps once you've made that decision.

Smaller companies with a new product’s promise of a cure, may need to hire a Contract Development and Manufacturing Organization (CDMO) to start the journey. To make a build or buy decision, the following questions needs to be asked:

• Do you, as the CGT/ATMP company, have a facility already, or a plan to build a facility and have the time necessary (2-3 years) before you start?
• Do you have the financial support (stakeholders, VCs, etc.) to engage a CDMO?

In the broadest sense, the MarketsAndMarkets report estimates that the global pharmaceutical contract manufacturing market was worth $176.5 billion in 2023 and is projected to reach $258.3 billion by 2028, growing at a CAGR of 7.9 per cent.2 CDMOs provide an excellent match with the projected growth trajectory of CGT/ATMP companies.

There are specific reasons for this outlook, including the fact that CDMOs continue to grow at a record pace every day. Essentially, with new CGT/ATMP therapies you are looking at speed to market balanced with risk, technical

experience, and regulatory know-how. In many cases, the CDMO choice becomes an easy one to make for new companies who have never commercialised a product in the past. First, you need to find a CDMO that will focus development on iterative changes and focus manufacturing on process control and consistency. Next, you must choose the one that will balance speed to market and risk properly and have the technical and regulatory experience to take your product through the right stages. Below are some tips across the product lifecycle to consider.

1. The answers to these questions will help you and your company make the right choice for the five basic stages of lifecycle support population, geographic targets, potency of product, and the number of doses needed for launch and thereafter. Additionally, consider the growth trajectory in this area for future production.

2. You are the product expert. Your experience is necessary for the CDMO to be successful. Be available and provide product guidance throughout all stages.

3. You should have a Quality Agreement specifically outlining the requirements and expectations to help the 2 sides maintain clarity and trust.

Most sponsor companies will utilise the services of a CDMO at some point in the timeline of product development through commercialization and launch, as the CDMO plays a vital role in the cell therapy industry. Developing a successful CDMO relationship involves navigating a complex road forward, building a robust contract, and adopting a collaborative approach based on shared goals, open communication, and unwavering commitment to product quality and patient health.

The success of the Sponsor/CDMO relationship heavily depends on selecting the right partner initially (using some of the guidelines above) and on a clear understanding of what both companies need and bring to the table. Asking the right questions and providing truthful, transparent answers will result in choosing the right partners. Your CDMO will be an extension of your company. Remember that you are both on the same side and that open and timely communication throughout the journey will build trust and most likely lead to success in the relationship and increase the odds for commercialization success.

References are available at
www.pharmafocusasia.com

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About The Author:

Christine Feaster has been a pharmaceutical executive focused on quality manufacturing and new manufacturing modalities to ensure access and affordability of life saving medicine and treatments around the world. With 30 years’ experience in leadership roles in Quality, Quality Control and Analytical Methods development, Christine has worked for top 50 pharmaceutical companies and start-ups in creating robust quality systems that have withstood international inspections successfully. Working for USP for 11 years, Christine has had executive roles of increasing responsibility starting in Quality, Global Public Health and then transitioning her career into the Commercial side of the business.

Click here to read the article in Issue 56 of Pharma Focus Asia Magazine.