Cell and Gene Manufacturing - Why Paper is the Enemy of Quality

Cell and Gene Manufacturing - Why Paper is the Enemy of Quality

Vivi Korba

Vivi Korba

Upstream Engineer

Cell and gene therapy companies are emerging from years of laboratory-scale development through preclinical tests and pivotal clinical trials, ultimately reaching FDA approval and product commercialization.

As a result, the Cell, and Gene Therapy (CGT) market is expanding rapidly, with a Compound Annual Growth Rate (CAGR) of over 30% expected for the period 2021−2025. This increase is attributed to the potential of CGT to treat and potentially cure debilitating diseases. These include relapsed or refractory B-cell acute lymphoblastic leukemia, spinal muscular atrophy, and Leber congenital amaurosis.

What is Cell and Gene Therapy?

CGT is a subfield of biomedical research and an emerging field of experimental medicine that plays a vital role in modern healthcare due to benefits such as cell-cell interaction, remodeling, regenerative capacity, and gene regulation.

CGT involves extracting cells, proteins, or genetic material (DNA) from the patient (or a donor) and altering these to provide a highly personalized therapy, which is injected into the patient. This technique can potentially address complex diseases, such as motor neuron disease, cancers, and many rare disorders for which there are currently no effective treatments. It seeks to prevent, treat and cure rare disorders and acquired infections, as well as to reduce the underlying causes of these diseases, and may offer longer-lasting effects than traditional medicines.

What is Cell and Gene Therapy?

Market Overview

Recent years have seen a steady acceleration in the number of CGT treatments on the market. More than 75 will be launched (including individual markets, such as Japan, Russia, and South Korea) by the end of 2022. Many more are in development, offering the hope of revolutionary healthcare.

The US dominates the global CGT market, with the highest absolute growth of more than 500% and a CAGR of around 36%.


An exponential rise in the clinical pipeline, coupled with a rising number of regulatory approvals for advanced therapies, has mainly driven the market.

Market participants are focusing efforts on boosting their market presence, considering promising growth opportunities in the contract development of cellular and gene-modified therapies. Also, biomanufacturers are signing strategic alliances with contract manufacturers to accelerate the R&D of their candidate programs.



  1. According to a report from the American Society of Cell & Gene Therapy, the industry will rise as more products are developed, used more frequently, and tested in clinical studies.
  2. According to the BioPharma Dive Report 2021, biotech firms actively involved in regenerative drugs and therapies reported funding of USD 14 billion in just the first half of 2021, with an estimated total of USD 19.9 billion for the entire year.
  3. There were 16 and 18 new products in development for cystic fibrosis and sickle cell anemia, respectively, in 2021. The burden of rare diseases is growing, and governmental support for the treatment of uncommon diseases is increasing, which is fueling the expansion of the global CGT market.

Traditional Pharma vs. Cell and Gene Therapy Manufacturing

While chemical medications can be generated in uniformly huge quantities since their production is comparatively well-defined, the CGT manufacturing process is intricate, time-consuming, and frequently results in tiny production volumes.

CGT treatments are often produced by growing cells in a bioreactor, a vat designed to maintain carefully calibrated conditions. They require complex biotech manufacturing processes. therefore, it is vital that these types of drugs are managed with care and monitored closely. Because the cells are alive, “every time you run a reactor, the result can be a bit different,” says Chris Love, a chemical engineer in MIT’s Biomanufacturing Research Program. This inherent variability makes the process both expensive and unpredictable.

Complex biologic compounds, such as cell and gene therapies, require care and attention throughout the biomedical manufacturing process to ensure that their structure maintains integrity, ensuring the product’s desired integrity and potency.

The manufacturing process to turn these cells into living medicine is extremely complex, requiring highly trained scientists to perform long and technical processes. This level of complexity adds a significant cost burden and has been a considerable barrier to realizing the potential of CGT in the clinic.

Manufacturing Challenges

Many of the challenges biologics manufacturing faces can be attributed to process issues, such as paper-based QA/QC and the slow establishment of the Chemistry, Manufacturing, and Control (CMC) process for CGT. The costs of manufacturing and quality control for those that have made it to market are so high that these potentially curative therapies are expensive and are sometimes only provided as a last resort to patients resistant to other therapies.

It is necessary to keep thorough records of the chemical and biological procedures utilized to create each therapy. This record-keeping must be scalable as the medication progresses through the development, clinical trial, and manufacturing phases. However, with CGT, this is typically a manual procedure, resulting in the creation and storage of paper-based records. This approach has several rippling consequences. The subsequent QA and QC processes can only be provided by specialists with access to the physical records, functioning as a bottleneck to scaling. Manual record-keeping is time-consuming and prone to error.

Manufacturing requirements are also difficult to scale from the lab. The specificity of these treatments means that cross-contamination can have very serious consequences for patient health, creating a zero-defect requirement in its manufacturing. It is challenging to scale up biologics while maintaining product purity and batch-to-batch consistency from the laboratory levels needed for early analysis and preclinical testing to the larger-scale batches. Despite the encouraging industry initiatives underway, the industry has yet to realize the full potential of digital technologies to bring transformative change to its operational approach.

Why Do Cell Therapy Sponsors Select CDMOs?

Sponsors of cell therapies have two possibilities for production. Either develop internal manufacturing capabilities or hire a CDMO or CMO. Owning a production site would allow them to acquire internal knowledge, improve procedures, manage manufacturing capacity, and perhaps even save money in the long term if the drug is successful in finding a market. However, using CDMOs/CMOs can help increase capacity planning flexibility, lessen commitments to changing technology platforms, and need less upfront expenditure. Furthermore, CDMOs/CMOs already have cGMP facilities that were created to abide by regulatory authorities. They also have qualified personnel that can carry out the process, produce the product, and deliversdelivers it to hospitals and clinics, which is more significant. Some sponsors of cell therapy use a regional manufacturing strategy and CDMOs/CMOS to produce their products across different geographies.

The Importance of Digitalization

“Bringing the lessons of Industry 4.0 to CGT operations is critical to the continued growth of the CGT industry, not only in revolutionizing our approach to treat and cure diseases but in improving the health outcomes of people everywhere,” said Jeff Smith, McKinsey partner and a global leader of the firm’s CGT work. Digitalization promises to improve manufacturing performance and quality—from advanced analytics for higher bioprocessing productivity to AI in deviation reduction and digital-twin-based plant scheduling—and allow the mindsets and capabilities needed to enable, scale, and sustain CGT.

Throughput and the possibilities for fast and cost-efficient manufacturing would be significantly increased by establishing an entirely connected digital vein throughout the manufacturing process and supply chain. As a result, processes would be carried out more quickly and accurately, the risk of errors would be lower, and the door would be open for dispersed manufacturing.

Vimachem Pharma 4.0 Platform for Cell and Gene Therapies

Vimachem’s Pharma 4.0 Platform focuses on digital enablement and operational excellence in CGT manufacturing, accelerating digital transformation in biopharmaceutical manufacturing. It is vitally important to avoid mistakes and reduce the time and costs of filling in and handling paper records by making it easy for everyone to access and read electronic batch records.

The Vimachem Pharma 4.0 Platform enables CGT manufacturers to reduce deviations and more quickly release manufacturing batches based on review by exception, which aligns with right-first-time initiatives.

Frequently Asked Questions:

Q: What is Cell and Gene Therapy (CGT)?

A: Cell and gene therapy is a rapidly developing field.
Cell therapy tries to treat diseases by repairing or changing specific cell types, or by employing cells to transport a medication across the body. Cell therapy involves growing or modifying cells outside of the body before injecting them into the patient. The cells may come from a donor (allogeneic cells) or the patient (autologous cells).
Gene therapy seeks to treat diseases by adding, deleting, or altering genetic information to change how a protein or collection of proteins is generated in a cell.
CGT is the term for combined cell and gene therapies, and they function by changing genes in particular cell types and introducing them into the body.

Q: What are the main challenges CGT manufacturing is currently facing?

A: Paper-based QA/QC procedures are time-consuming and prone to error. Manually processed, old-fashioned paper-based records, scaling, and regulatory compliance have risen to the top of the conversation as new therapies progress through the trial pipeline. They lack the ease for tracking data and continuous improvement.
Q: How can digitalization help face CGT manufacturing challenges?

A: Digital transformation creates opportunities to link manufacturing systems in a way that has not previously been possible. Digitalization enables CGT manufacturers to reduce deviations and more quickly release manufacturing batches based on review by exception, which aligns with right-first-time initiatives. Companies that have embraced digitalization have reported a decrease in data input errors and a decrease in review time after production completes.



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