Qkine have recently released a range of growth factors and cytokines specifically designed to be suitable for cell and gene therapy manufacturing. Most recombinant protein manufacturers would describe these as 'GMP grade' but we haven't, so why are the products labelled cell therapy grade and not GMP grade?Â
What is GMP?
Good manufacturing practices (GMP)Â is a set of practices and quality controls, record-keeping and adherence to precise manufacturing protocols for the production of medicines, food and cosmetics under strict regulatory standards. It ensures that medicinal, cosmetic and food products are produced consistently according to quality standards and are safe for humans to consume and use.Â
Although GMP-grade is a recognized term within the growth factor space, it is not an accreditation that can be strictly applied to products outside of the pharmaceutical, cosmetic or food industries.Â
From its conception Qkine decided to do things differently and has never subscribed to producing low quality proteins.  More comparable to other suppliers’ premium grade proteins, our research use products already undergo extensive testing for identity, purity and sterility.  Taking the next step to manufacture in accordance with GMP principles has meant surprisingly few changes to our manufacturing and QC processes. However, due to the inaccuracy of the term ‘GMP grade’ we have decided to use the less ambiguous term ‘cell therapy grade’ and be completely transparent on our manufacturing quality controls, data and documentation.Â
Other practices and controls
ISO standards are internationally agreed-upon documents that provide specifications, guidelines, or characteristics for a variety of activities or their results, aiming to ensure products, services, and systems are safe, reliable, efficient, and of good quality.  Â
ISO 9001 sets the criteria for a robust quality management system and focuses on customer satisfaction and continuous improvement of processes to meet customer needs. It requires documentation of a quality management system (QMS) to ensure a customer focus, good leadership, engagement of people, a process approach, risk management and continual improvement. Â
Qkine has been ISO 9001:2015 certified since September 2021, was recertified in August 2024 and has recently transitioned to a new QMS system and undertaken an audit to ensure continued compliance. Read more.
ISO 20399:2022
Materials that come into contact with but are not intended to be present in the final cellular therapeutic product are referred to as ancillary materials. This includes all components that make up culture media and variation in their lot-to-lot composition can reduce the ability to produce consistent cell and gene therapy products.Â
ISO 20399 is the first ISO standard to specifically address the issues concerning ancillary materials and clearly lays out the expectations of both suppliers and users. This document is separate from the standards governing cell processing requirements and lays a framework for developing a risk-based approach to ensure consistent manufacture and performance of ancillary materials.Â
As the responsibilities of the standard are shared between users and suppliers to qualify the ancillary materials for the user’s processes, it is not a standard that can be audited for the certification of a single company.  However, the principles of ISO 20399 can be adopted to ensure the highest quality ancillary materials, and this is what Qkine has elected to do.Â
GMP vs ISO 20399
Qkine cell therapy grade proteins align with both GMP standards and ISO 20399, read on for more on what the requirements of these standards are, and how Qkine has aligned its manufacturing processes with them.Â
GMP standards
ISO 20399
Qkine Cell Therapy Grade
Establish and implement an effective quality assurance systemÂ
Manufacturers of AM shall implement a QMS
ISO 9001 sets the criteria for a robust quality management system and focuses on customer satisfaction and continuous improvement of processes to meet customer needs.
The Qkine quality management system has been implemented to comply with the requirements of ISO 9001: 2015 and is applicable to the development, manufacture and supply of proteins and related products.
Qkine has been ISO 9001:2015 certified since September 2021, was recertified in August 2024 and has recently transitioned to a new QMS system and undertaken an audit to ensure continued compliance.
Employ competent and appropriately qualified personnel who receive initial and ongoing verified training
We are a company founded and run by scientists to provide a service and support innovation in stem cell biology and regenerative medicine. Â
Records of onboarding, ongoing role-specific training and external training are stored in our centralized eQMS system. Mentoring and cross-role training schemes allow our staff to learn new skills and develop their careers. Â
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Locate and maintain premises and manufacturing equipment to suit the intended operations and to permit effective cleaning and maintenanceÂ
Control contamination through the manufacturing process, environmental controls, segregation, engineering controls, use of dedicated equipment and cleaning process
Qkine opened its state-of-the-art biomanufacturing and R&D facility in Cambridge in 2023. Â
CTG products are manufactured in ISO 14644-compliant cleanroom environments. The main Purification Laboratory meets ISO Class 7 standards, while the Media Laboratory and Gowning Area meet ISO Class 8 standards.
The fill-finish process is conducted within an enclosed, automated system located in the Purification Laboratory. This system is equipped with an ISO 14644-1 Class 5 HEPA filter. Both particulate and microbial levels are regularly monitored in the Purification and Fill-Finish areas. Prior to each production run, a UV sterilization cycle is performed within the fill-finish machine, including sterilization of the dispensing tips. To ensure the integrity of aseptic filling operations, media fill validation - also known as aseptic process simulation (APS) - is performed annually. This validation uses Vegetable Peptone Broth (VPB), a vegetable-based, animal-free medium specifically formulated for media fill testing.
Access to manufacturing areas is restricted to authorized personnel. Entry is controlled through a dedicated gowning area, and personnel are required to wear ISO Class 7-compliant cleanroom lab coats. External footwear is strictly prohibited. Cleaning is carried out by trained staff using specialized lint-free materials, with all procedures documented in the company’s Electronic Lab Notebook (ELN). The use of cardboard, notepads, or printed documents such as SOPs is prohibited in all cleanroom areas.
Any failure to meet particulate or microbial level requirements - before, during, or immediately after the manufacture of a Cell Therapy Grade product - will result in the batch being deemed unsuitable for this grade.
Carry out Manufacture operations in accordance with good manufacturing practice and with pre-established instructions and proceduresÂ
Known aspects of the manufacturing process that impact the quality and consistency of AM products shall be controlled, documented and communicated
Every stage of the Qkine animal-free protein manufacturing employs Standard Operating Procedures (SOPs). SOPs are fundamental to assure consistency from lot to lot and guarantee the highest quality of products.Â
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All documents within the QMS are stored in a 21 CFR Part 11 compliant eQMS system so that they are available for use when needed, changes are controlled with an audit trail, and documents are on an automatic review cycle.
Appropriately staff and equip quality control laboratories to carry out the necessary testing of finished productsÂ
Design and validate performance assays to demonstrate the effect of the ancillary material on cells, perform suitably specific identity tests, measure the purity of the product, conduct tests for safety such as sterility, endotoxin, mycoplasma, and identify all components with their relative concentrations
Qkine cell therapy grade products are subject to extensive quality controls to ensure their safety, purity and identity.Â
Read more about cell therapy grade manufacturing.
Ensure consistency between batchesÂ
The AM supplier should demonstrate the lot-to-lot consistency
Qkine tests the bioactivity of each new lot produced vs previous lots for consistency in bioactivity in supplied proteins. Lots which are significantly different from previous lots are disposed of and not moved into the supply chain. Read more.
Retain batch documentation for at least one year after the expiry date
All batch documentation is retained for a minimum of 3 years beyond the expiry date.
Retain samples of each batch of finished product for at least one year after the expiry date
Samples from all lots are retained for a minimum of 3 years beyond the expiry date.
Document and thoroughly investigate all process deviations, product defects and any complaint concerning a defect.
Implement a nonconformity process to include plans for implementing effective corrective actions
Any report of a deviation from specifications, whether from an internal or external source, is documented and fully investigated using an 8D problem solving process. The root cause is defined and verified and corrective and preventative actions implemented to address the immediate concerns and prevent recurrence. The entire process is documented within our eQMS system and available to all members of Qkine for reference.
Conduct repeated self-inspections as part of the quality assurance system and to propose any necessary corrective measures.
Manufacturers of AM shall undergo regular audits
A schedule of the audit dates and areas of the QMS to be audited over the year is agreed at the first QMS Management Review meeting of each Financial Year.  Â
The areas to be audited are determined based upon date since last audit, frequency and severity of nonconformities, company strategy, Board risk assessment. The schedule may be amended to reflect changes in the business processes, strategy or operations.
An external audit of the ISO 9001 QMS is carried out annually by BSI and customer or third-party audits may be conducted by arrangement.
GMP-aligned products are animal origin-free in line with regulatory recommendations.
Conduct a risk assessment for animal-derived components based on the risk for the intended use
As part of our ongoing commitment to quality in every aspect of the company, animal origin-free production is taken into consideration from the very earliest planning stages of design and development. Before being incorporated into a procedure, newly sourced materials must be reviewed and approved by our Quality team.
We continuously work with our suppliers to confirm and certify that the chemical components used within the manufacture of Qkine products are derived from non-animal and non-human sources and that the processes and components used in their own manufacture are animal-free.
Read more on why animal-free products are important for cell therapy manufacturing.