SkinFactory 2.0: GMP-in-a-box

Worldwide, more than 50 million people suffer from large skin defects requiring surgical interventions to restore skin function. Today, the standard of care is harvesting a thin layer of healthy patient’s own skin (autograft) and transplanting this onto the wounds. These skin grafts contain the outer layer of skin (epidermis), but only remnants of the underlying layer of connective tissue (dermis). The latter is a disadvantage as the dermis is essential to control and regulate scarring. Most of the time, autografting induces the development of scars with disfiguring, painful and discomforting outcome. Scars can impair mobility, growth and may require intense homecare and psychosocial rehabilitation as well as a high number of follow-up corrective surgeries. This leads to significant high costs for medical procedures and long hospitalization periods. In addition, patients may experience psychologic challenges that prevent them from partaking in social activities and employment, which leads to indirect costs of lost labor potential.

To solve this problem, CUTISS aims at bio-engineering customized, human skin autografts (denovoSkin™) starting off from very small biopsies of healthy patient’s own skin. DenovoSkin™ possesses the right features to minimize scarring after transplantation. It is composed of both dermal and epidermal layers, and includes a collagen type I hydrogel, which makes it possible to generate highly remodellable and expandable grafts. DenovoSkin™ received a Swissmedic, EMA and FDA Orphan Drug Designation (ODD) for the treatment of burns and is currently in clinical phase II in Europe.

It is CUTISS’ vision to allow access to its proprietary technology worldwide to all those patients in need. Our envisaged innovation with this project is to create a standardized and automated GMP-in-a-box (Good Manufacturing Practice) production process (SkinFactory 2.0) that can replicate the production process anywhere, facilitating a global reach while ensuring denovoSkin™´s quality and efficacy. This aims at replacing the manual GMP production of skin grafts ì, which is not cost-effective and not scalable.

For the automated GMP-in-a-box factory, it was essential to have a multi-disciplinary specialist in house, with expertise in cell biology, product development and quality assurance. This specialist - the Innovation Associate (IA) – was hired thanks to the contribution of current SkinFactory 2.0 INNOSUP project. The grant allowed CUTISS to overcome the recruitment barriers of being a relatively unknown, small start-up enterprise that could not compete with larger companies due to limited visibility, brand awareness, (perceived) career opportunities, salary and recruitment budget. The INNOSUP grant allowed CUTISS to offer a competitive package to attract candidates with the specialist knowhow and experience. The ability to support the relocation efforts of the candidate and the training program offered through the grant where key factors for CUTISS to stand out as an employer.

SkinFactory 2.0 project specific objectives to be achieved with the contribution of the IA, were:

1. Formulating functional requirements for the automation companies (in charge to develop automation of the manufacturing process of denovoSkin™)
2. Ensuring that the design of the production modules complies with these requirements
3. Providing hands-on feedback from on-site testing of the production modules
4. Setting up the first benchtop MVP

MAIN RESULTS DELIVERED BY THE IA
- Translated user needs and requirements of the manual production process of denovoSkin™ into design input requirements for the automated manufacturing devices (Biopsy Kit, Cell Isolation Device and Tissue Formation Device). Ensured application of design and process risk assessments.
- Evaluated design architectures and feedback on usability and technical issues.
- Planned and executed R&D studies for the evaluation of devices and for device design relevant questions
- In collaboration with the engineering service provider, tested the first biopsy kit and cell isolation prototype, as well as developed and evaluated the second improved prototypes.
- [In collaboration with the research and technology provider] translated the manual process for the assembly of cells into a 3D construct and growth into a skin graft ready for transplantation to the patient into a first semi-automated concept.
- Evaluated commercially available cell wash systems. The Sepax C-Pro (Cytiva Lifesciences) was identified as a suitable instrument and a process was defined for its use.
- All modules of the automated production MVP have been tested in isolation or combination with one other module.
- The basics of Medical Device/Engineering quality management system have been established.

The development of a successful prototype will allow for further adaptation and validation into a market ready prototype, and subsequent market introduction of SkinFactory 2.0 a standardised and automated GMPin-a-box for the production of denovoSkin™. This innovation will increase the cost-effectiveness of denovoSkin™ and thereby increase the eligibility for reimbursement by health care insurance, which will offer CUTISS the horizon to access a much wider market (i.e. public hospitals in addition to private hospitals). In particular, CUTISS will be able to save up to 65% of the cost of production of denovoSkin™.

Subsequently, the automated production process can be used as a technology platform for the development of additional tissue-based products. This will open up new horizons for CUTISS such as the automated production of next generation pigmented skin grafts (MelSkin™), a new bio-engineered tissue product that CUTISS is currently developing. In a greater vision, the automation platform could also be developed for the production of other bio-engineered tissues, e.g. cornea, bladder or urethra

Periodic Reporting for period 1 - SkinFactory 2.0 (SkinFactory 2.0: GMP-in-a-box)

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