01
Tissue procurement
Cartilage biopsy or placental tissue collected under aseptic surgical conditions at licensed partner hospitals. Chain of custody documented from procurement to release.
Manufacturing at LUHS, Kaunas.
Manufacturing operations are based at the Lithuanian University of Health Sciences (LUHS), Kaunas.
KELI-operated facility at LUHS, Kaunas
Manufacturing takes place in a KELI-operated Grade A–D cleanroom at the Lithuanian University of Health Sciences (LUHS) campus in Kaunas.
Lithuanian University of Health Sciences
Kaunas, Lithuania — Host institution
Closed-system manufacturing
Cell expansion workflows use closed bioreactor and multilayer cell factory systems. Process controls are designed to align with EU GMP Annex 2 for ATMPs; authorisation is limited to the scope of each product and permit.
02
Cell isolation and primary culture
Enzymatic digestion and primary chondrocyte or MSC isolation in ISO-classified cleanrooms. Identity, viability, and sterility tested at each stage.
03
Expansion — multilayer cell factory
High-surface-area multilayer cell factory systems used for large-scale MSC and chondrocyte expansion, supporting both autologous and allogeneic workflows.
04
Expansion — closed bioreactors
MSCs and chondrocytes expanded in closed bioreactor systems (Eppendorf BioFlo 320), eliminating open-vessel handling and enabling precise environmental control.
05
Supernatant harvest and exosome concentration
Conditioned medium is harvested from expanded MSC cultures. Exosomes are isolated and concentrated by tangential flow filtration (TFF). Placenta-derived exosomes · preclinical.
06
Quality control and release
QC methods address sterility, mycoplasma, endotoxin, identity, potency, and stability. RECARTA release falls within its product-specific authorisation; other programs require their own regulatory pathways.
Equipment
Multilayer Cell Factory
Scalable surface-area expansion
Eppendorf BioFlo 320
Closed bioreactor expansion
Automated Cell Counting
Viability and count — Ph. Eur. 2.7.29
Tangential Flow Filtration
Concentration and buffer exchange
Quality Control — Drug Product
Quality-control methods are designed around Ph. Eur. monographs and EU GMP Annex 2 expectations for ATMPs. Release is subject to the relevant product authorisation.
Safety
- Bacterial and fungal sterility (Ph. Eur. 2.6.27)
- Absence of mycoplasma (Ph. Eur. 2.6.7)
- Endotoxin (Ph. Eur. 2.6.14)
- Air, personnel and surface environmental monitoring
Identity and Viability
- MSC identity by flow cytometry: CD90 ≥98%, CD73 ≥98%, CD105 ≥97%
- Exclusion markers: CD31, HLA-DR, CD45 ≤0.3%
- Viability and cell count (Ph. Eur. 2.7.29): ≥80% viability, 50–150 MM PL-MSC per dose
- Genome stability: ≥12 months in gaseous phase of liquid nitrogen
Potency
- T-cell proliferation inhibition assay
- Reduction of inflammation (TNF-α, IL-6 suppression)
- Kynurenine secretion assay (HPLC-MS and absorbance)
Three distinct regulatory credentials
RECARTA is approved under EU Hospital Exemption in Lithuania, with product-specific ATMP manufacturing permit No. 25. Full site GMP licence: application in progress. Grade A–D cleanroom at LUHS, Kaunas.
Tissue establishment licence No. 6005
Tissue establishment licence
State Accreditation Service for Health Care Activities (VASPVT)
- Issued
- 10 Jun 2024
- Valid until
- Indefinite
Authorises KELI (UAB Kelifarma) to operate as a tissue bank: procurement, processing, storage, and distribution of musculoskeletal/cartilage tissues and placental tissues. Address: Sukilėlių pr. 15, Kaunas.
EU TE Code LT017796
Tissue Establishment Authorisation
National Bureau on Transplantation (NTB), Lithuania — EU Competent Authority
- Issued
- Active (last updated July 2024)
- Valid until
- Active
EU-registered tissue establishment. Authorised activities: procurement, donation, testing, preservation, processing, storage, distribution, import and export of musculoskeletal/cartilage and placental tissues.
Manufacturing Permit No. 25
Permit to Manufacture ATMPs for Specific Patients
State Medicines Control Agency (VVKT), Lithuania
- Issued
- 26 Mar 2025
- Valid until
- 26 Mar 2027
Authorises manufacture of RECARTA — autologous chondrocyte ATMP (1.33–2.67 million cells/cm², implantable suspension, pre-filled syringe) from patient knee cartilage biopsies.
State Accreditation Service for Health Care Activities
State Medicines Control Agency (VVKT)
NVSC — National Public Health Centre
NTB — National Transplantation Bureau
Manufacturing at LUHS, Kaunas.
Discuss current manufacturing capabilities. KELI-101 is manufactured in-house at LUHS.