Tips for setting up MPA approved GMP manufacture facilities within a small cell therapy company
Christmas presents arrived on time for Amniotics AB in 2020, with the approval of their manufacturing authorization approval and certificate of GMP compliance from the Swedish Medical Products Agency. Added to the tissue establishment approval they received in October 2020, Amniotics AB is currently, to our knowledge, the only Swedish company to hold all valid permits required to in-house manufacture their Advanced Therapy investigational Medicinal Product (ATiMP) for clinical trial. The first manufactured product is expected to be lung specific amniotic fluid derived MSC for treatment of COVID-19.
Jan Talts, Chief Operating Officer (COO) of Amniotics AB says, “We are very proud to have completed the building of a facility and setting up a pharmaceutical quality system to be able to produce our own ATiMP for the clinical trials we are planning. We can now take our research from bench to bedside in order to contribute towards life changing regenerative treatment of severe diseases with inflammatory and fibrotic origin.”
The following is a summary of info from Kåre and Jan for how and why they decided to take the path of setting up their own GMP facility.
For a small company to start up their own GMP manufacture facility and receive these MPA approvals is no small feat and many would have questioned if it were even possible. However, the strategic benefits of controlling the whole chain of production is extremely attractive from receiving clinical start materials to developing and manufacturing the clinical product eliminating issues including delays based on CMO activities as well as securing future IP potential. Further, for Amniotics AB, the potential to produce ATMPs from other tissue specific MSC populations will no doubt benefit from the tight links between collection, process development and production developed within the company.
Kåre Engskilde, Chief Executive Officer (CEO) of Amniotics AB says, “It is quite unique for a biotech to control the full value chain, and it enables us to produce our ATiMPs right in time for clinical trials, as well as for global expansions without having to rely on a CMO. Further, the facility is set up with expansion potential, so that we can even take in processes from other Biotechs, and use the team’s strong capabilities as a CMO.”
The secret it seems to Amniotics AB success is recruitment of the required competence and sustained support from an innovative management board. Jan Talts is the mastermind behind the cleanroom facility, who designed the strategy of the physical structures, the quality systems and personnel required to build a facility that would be MPA compliant. MPA advice meetings were held to verify plans for the clean rooms and GMP processes and mock inspections from QA services were employed to fine tune.
Was the ATMP regulatory guide produced by the SDP1 Swelife-ATMP project useful? Yes and no. The guide was produced around the same time as the facility was being designed so did not become available until the vast majority had been planned, however the guide acted as a great resource to check off that the plans ticked all of the right boxes.
Lessons learned that may be useful to others thinking to take this path;
For Amniotics AB the design of this facility was to address needs now and in the future. Future plans may include acting as a CMO for cell therapy products. The facility has 3 class B rooms operational with 2 class A biosafety cabinets but capacity to expand to 6 class B and 5 class A for potentially more than one product to be produced at one time.
How is it possible to run a GMP facility with small numbers of employees? Ironically, outsourcing! Cleaning, QP, QA support, IP and regulatory services were contracted to allow dynamic use of resources based on current needs. Amniotics staff fulfil the QA, QC and production roles. The aseptic processing industries provides a great source of personnel, though getting the right people and treating them well are critical to a well-functioning outfit.
The first product is intended to be a lung specific MSC population purified from term amniotic fluid, donated at Skåne University Hospital, and expanded to a batch size around 1 billion cells. The MSCs have angiogenic, anti-fibrotic and inflammation modulatory properties that have been shown preclinically to reduce fibrosis and modulate inflammatory responses, thus the product has the potential to treat patients suffering from respiratory diseases with a fibrotic component. A clinical trial for COVID-19 is expected to start in the first half of 2021.
Learn more about the Amniotics AB tissue specific MSC populations on their website. We look forward to seeing how the production and trials progress for this innovative Swedish ATMP startup.
Takara Bio Europe, currently holds a tissue establishment (2017), certificate of GMP compliance and manufacturing authorization approval from LV to manufacture GMP cell banks based on hESC (2018) and hiPSC (2020) at their facility in Gothenburg, Sweden.
ATiMP is distinct from ATMP in that it is produced for clinical trial purposes, not for commercialization.
Cell or gene based pharmaceuticals intended to treat or prevent an infection are regulated as vaccines. In this case of the Amniotics AB MSC product for COVID-19, ATMP sCTMP regulations apply due to the intention to treat pathologies caused by the infection.
Remember that it is LV/MPA approval that is required for ATMP manufacture and not IVO approval, which is relevant only for transplantation handling of tissues, not manufacture from those tissues.