Developing, optimising, and manufacturing Advanced Therapy Medicinal Products (ATMP's), such as Cell and Gene Therapy (CAGT) products is extremely complex. The choice of a reliable Contract Development Manufacturing Organisation (CDMO) is one of the most critical steps determining your product’s future. You need a competent, trustworthy and flexible partner who is ready for new challenges and is going to satisfy your product’s needs. A great CDMO should also be an advisor as the partnership is going to benefit you both.
During the selection process several aspects should be considered with the potential CDMO partner choice. This blog covers typical frequently asked questions (FAQ) and features related to the process of the CDMO selection in the context of the CAGT developing, the process optimisation and the manufacturing.
Based on our experience, ProPharma is sharing this knowledge with you to help you succeed in developing, optimising and manufacturing CAGT product for cancer treatment.
Definition (Collins dictionary):
Autologous - originating from the recipient rather than from a donor
Allogenic - being genetically different, while belonging to the same species
Key Factors for CDMO Selection for Cell and Gene Therapy Manufacturing
1. Technical Expertise
No two CDMOs are the same – they all have different strengths and specialities. Most of the differences are placed in technical expertise and practical experience to deliver on what you are looking to achieve. During selection of CDMO you need ask CDMO to answer for several questions like:
Does the CDMO have GxP experience?
GxP experience can be the key to ascertaining the correct manufacturing process and satisfying regulatory requirements. Today it exceeds traditional GMP, but should incorporate other aspects, such as laboratory, clinical, distribution, manufacturing, or governance. In the digital age it is important to look at the data and analytical standards to ensure proper validation of results. Failing to do so may be a costly mistake.
Does the CDMO have the experience with selected cells of your interest?
The number of CAGT cancer treatments increases exponentially for allogenic and autologous products. The most common cells used for production CAGT are: T-cells, NK cells and others. It is an important part of the CDMO selection as this speeds up production and increases the quantity of cells isolated from the starting material.
Does the CDMO have access to the cellular material?
Access to the appropriate cellular material is one of the most important aspects during production of allogenic CAGT. Support of both fresh and frozen types has a number of advantages and it could impact the final product. It is good to find out during the search for a CDMO, one that has the possibility to access to the hight quality and appropriate genotype of the cellular material.
Does the CDMO have experience with delivery system which you required?
Currently, there is only a few delivery technologies available for genome editing: viral (lentivirus, retrovirus, adenoviruses and adeno-associated viruses) and non-viral (electroporation, cell squeezing and nanoparticles). It is the most crucial step during production of CGT as it is projecting the efficiency of genetically transformed cells and has an impact on the product critical quality attributes (CQA). Having experience and supporting your product requirements should be discussed during technical meetings.
Does the CDMO have experience with gene editing technology?
There is several gene editing technology available that are commercially used for modification of the cell’s genome. The most common are Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9 (CRISPR-Cas9) system, designer nucleases (transcription activator-like effector nucleases (TALEN) and zinc-finger nucleases (ZFN)) and transposons. It is good to discover does the CDMO provide the service of gene editing technology which your product required.
Does the CDMO have the experience with an expansion system, which your process requires?
A further information which you need to consider it the availability of the expansion systems. All cells required to be feed for proliferation. They are several expansion/feeding systems available on the market and they differ: plates, flasks, bags and bioreactors (G-rex, wave and stirred tank etc.).
Does the CDMO have cell the banking capacity for producing allogenic CGT?
Another important factor is to discover if the candidate has capacity to perform GMP cell banking. This service is crucial for production allogenic GCT as you want the next batch to have this same count of cell interest and genetic properties. This is required to prepare Master Cell Bank (MCB) and Working Cell Bank (WBC). GMP MCB is a source of high quality material for product manufacturing over the lifecycle of a product. There is less standardisation in GMP cell banks development in the CAGT field as each company/university uses their own process.
Does the CDMO have experience required for analytical testing of the product characterisation?
The most crucial aspect to ascertain during meeting with CDMO is analytical capabilities of the potential partner. These analytical tests, such as safety, purity, identity, quantity, potency, or stability, are important as they are mandatory to obtain the Certificate of Analysis (CoA) for the final product and be able to release it to the market. Product or process specific analytical tests could be performed as well, for instance checking for the presence of the residual imputes or phenotyping of the finished product. Test plan depends on your product requirements and needs to be discussed with the CDMO before signing contract.
Does the CDMO have technology transfer experience?
Technology transfers are yet another important step in the product development process. Excellence in pharmaceutical technical transfers is a must for organizations calling themselves market leaders. It is highly advised that the selected CDMO has the experience in tech transfer, not limited to the origin laboratory but also between their own manufacturing facilities or contractors. Expertise in handling separate regulatory requirements is helpful in transnational deployments.
Does the CDMO have possibility of stability study and storage of allogenic final drug product?
Next point, which need to be established during the selection process is to find out if a potential partner has the capacity for performing stability study following governance guidelines as they usually take 18 months.
Does the CDMO have GMP availability to run your project?
When you are launching a new drug product with the goal of speed-to-market or being first-to-market, you need to find out your future partner has GMP production availability as it is can be the difference between making it to market on time.
2. Regulatory and Compliance History
The next important element during the evaluation is to note whether your prospective partner has a proven track of record in the regulatory and compliance history. This information will allow you to go smoothly from the discovery phase into the human clinical trials. Global regulators require companies developing new drugs to complete a Clinical Trial Application (CTA). In the US the appropriate regulatory body is the Federal Drug Agency (FDA), which issues an Investigational New Drug (IND) application. It is important for your future manufacturing partner to have experience with preparing IND dossiers or have a legal partner to help.
3. Size of CDMO
Currently, there are around 100 CDMOs around the world capable of CAGT manufacturing. The size of CDMOs range from university-based, -affiliated, or -spun out up to big, established and recognised. The choice of the size will have significant impact on almost all aspect of the manufacturing and registration process. During choosing manufacturing partners you have to define what kind of constrains are non-negotiable, for instance does this CDMO will have enough skilled workers and capacity for all production steps.
4. Location
Another parameter which you need to consider is the physical location of the CDMO. At first, you need to find out where you want to perform your clinical trials as there are different regulations applying to different markets, as well as there is also the associated shipping cost and time. The majority of CDMOs (around 50) are in the United States and Canada, followed by the EU (around 40), and the UK (around 10). In Asia and Australia there is also around 10 CAGT CDMOs.
5. Cost
Subsequent part relates to the total cost of development, optimisation, and costs of production per GMP batch. The prices between CDMO is vary significantly as each CDMO has different costs. To gain understanding of the cost types, cost structure and cost scaling one should interview a number of potential CDMO partners and ask them to prepare comprehensive answers. In this way you should receive streamlined results that will allow you to make correct business decision.
6. Communication
Effective communication with CDMO is another key element in building the success. Having good and open communication with the CDMO will allow you to make ad-hoc changes and adaptations during the development, optimisation, and manufacturing of CAGT product. Answering emails and phones in reasonable time is expected from both parties. It is also advised to have your own project manger/product owner who will keep the record of agreed decisions.
7. Miscellaneous
Generally, it is advised to have a person with the production process knowledge to be present in the CDMO site during development, optimisation and manufacturing to troubleshoot any issue arising during the process. This approach will speed up the production, ensure quality, and minimise problems during production of CAGT. It is quite common approach for big commercial producers of CGT, which are in need of use the CDMO partner.
Are you in the process of developing a cell and gene therapy product?
Regardless of where you are in the development lifecycle or what your current needs are, we have the skills, capabilities, and expertise you need on your side. Interested in learning more about how we can help you identify and select the best contract manufacturing organization/contract development manufacturing organization for your needs? Do you need help with technology transfer?
Contact us today to learn more.
