Cell therapies are an integral part of the promising, fast-paced landscape of innovative therapies revolutionizing global health. In the race to develop the next best cell therapy product, manufacturers need to be acutely aware of the heavily regulated and stringent requirements for quality control in the manufacturing of these advanced therapy medical products. What does GMP-grade mean, and how are high-quality raw materials impacting the final product in this field?
Translation of any new discovery to a therapeutic application is an arduous and lengthy journey for all the stakeholders involved, be it researchers, patients, caregivers, biotech firms or regulators.
Not adhering to required standards – especially around quality and safety – in this translation process can be costly. It can lead to terminations of therapeutic development projects or shutdowns in production, with potentially high financial losses.
“When a product is used to directly treat humans, minor omissions could have grave consequences, such as failure to provide timely medical care to patients in need, or even cause patient harm,” highlighted Sheng Lu, Senior Director of Quality at ACROBiosystems, a biotechnology company that specializes in providing recombinant proteins, kits, antibodies, and other biopharmaceutical supporting services.
“Products for human use warrant more stringent quality and safety criteria, unlike for example, research-use-only products, which are used only in early stages of drug discovery and safety research.”
A case study of quality control gone wrong: Thalidomide
Dubbed as “the biggest man-made medical disaster ever,” there is perhaps no other lesson on the importance of quality control in therapeutic development that is more terrifying, or cautionary, than the Thalidomide crisis.
Thalidomide, a drug used to relieve discomfort in pregnant women, resulted instead in severe birth defects in thousands of children in the late 1950s to early 1960s. Following the tragedy, there was a rush to restrict access to Thalidomide and set more stringent drug safety and quality control measures.
Public backlash and legislative action led to the inclusion of good manufacturing practices (GMP) – a set of safety and quality control guidelines – into the US Food, Drugs and Cosmetic Act in 1962 as a required practice for pharmaceutical companies. The same year, the US FDA also published its first regulation on GMP.
By 1969, the WHO released a universal quality assurance guideline, recommending that all member countries adopt GMP systems for drug production as well as drug exports.
Today, GMP – adopted in more than 100 countries worldwide – has evolved to become a core part of quality assurance and risk mitigation. It ensures that products are consistent, safe and are controlled by appropriate quality standards for their intended use, as mandated by relevant regulatory bodies.
‘GMP-grade’: adapting requirements with advancements in science
“Today, manufacturing of GMP-grade products is not limited to upgrading the quality of the product to ensure high efficacy and safety alone,” said Lu. “It requires an elaborate and consistent upgrade of the quality management system overseeing the product’s entire manufacturing process.”
Such an upgrade does not only involve implementing manufacturing procedures and clean working environments that are GMP-validated alone. It also includes employing qualified and well-trained personnel, using instruments that are well-maintained and calibrated, and utilizing animal origin free raw materials purchased from approved suppliers.
For novel and innovative treatments like cell therapies that have a more complex preparation process, GMP standards remain equally critical, if not more so. Recognizing this, regulators from major global markets including the US, EU and China have issued guidelines on cell therapy products in recent years.
“Cell therapy regulations from different markets may have local specifications on GMP evidence compliance that consider contextual issues within these markets. However, they all emphasize a common theme – the use of quality management systems similar to any other therapy intended for human use,” explained Lu.
Essentially, raw materials, personnel, facilities, equipment, manufacturing processes, packaging, transportation, or any other factors that can affect a cell therapy’s quality, need to be monitored closely. They all need to meet stipulated standards to ensure that the resulting cell therapy is of consistently high quality.
The gap today: lack of GMP guidance on raw materials
Unlike the stringent GMP-grade regulations for cell therapy end-products, Lu pointed to a vulnerability in current requirements: “There is no specific GMP guidance regulating manufacturing of raw materials for cell therapies.
“Global guidelines – including ones from the FDA – advise priority should be given to the use of clinical-grade, low-risk materials, that have been manufactured under an ‘appropriate’ quality management system.”
Unfortunately, such a guideline is open to interpretation. In the absence of regulatory oversight, this often results in GMP being self-declared for raw materials without the documentation to back it up, lamented Lu.
This also has the potential unforeseen consequence of making it confusing for cell therapy manufacturers, and consequently prescribers, to discern whether the raw materials are – or need to be – of GMP quality.
Raising the bar: providing high-quality, safe and consistent raw materials
This is where more conscientious players like ACROBiosystems seek to advocate for upholding higher quality standards.
“When we refer to our raw materials as GMP-grade, here at ACROBiosystems, we control the quality in our raw material manufacturing process using the same exacting standards as the production of sterile medicine,” elaborated Lu.
ACROBiosystems’ portfolio consists of two product categories. The first comprises cell therapy-related raw materials including cytokines, nucleases and activation magnetic beads. The second category includes cell therapy quality testing products such as labeled recombinant proteins, cytokine assay kits, and neutralizing antibodies.
By virtue of conforming to standards set for sterile medicine, ACROBiosystems’ raw material products are of high quality and stability, providing good batch-to-batch consistency, with lot production and control records. Additionally, comprehensive safety studies conducted by the team and external auditors, such as impurities testing, virus clearance and inactivation, combined with the use of animal-free materials and processes, result in optimal safety profiles for the raw material products.
Working within the rapidly-evolving cell therapy landscape is challenging, acknowledged Lu. “Our team pays close attention to new regulations and trends in cell therapy, to ensure we stay up-to-date and adopt necessary requirements in our products while providing the necessary documentation.
“We are proud to offer comprehensive customer support such as regulatory advice upon request, with facilities available for both online and on-site audits. We can also design and develop customized products to support the rapid translation from research and development to clinical production.”
Future perspectives: continued focus on quality
Ultimately, all stakeholders involved have a common goal: meeting the high unmet clinical need that cell therapies target.
When asked for his thoughts on the key factors that enable successful and safe translation of cell therapy products from bench to bedside, Lu noted, “A reliable and robust manufacturing process of raw materials will continue to be the most crucial enabler.”
“Along with this, the use of high-quality, safe raw materials needed for manufacturing, and comprehensive regulatory support in this fast-paced landscape will also be important.”
Looking to the future, Lu remarked that regulators worldwide have increasingly tended to regulate cell therapy products in recent years like they would medicines. Thus, the quality strategy for cell therapy products across markets can be expected to have a continued focus on safety, purity, and consistency.
As a specialist provider of raw materials for these cell therapy products, this is the very quality strategy that will be mirrored in ACROBiosystems’ future approach as well, concluded Lu.
To partner with ACROBiosystems and use their GMP-grade raw materials to help successfully launch your cell therapy products, visit the company’s website.
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Images courtesy of ACROBiosystems.