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PACKAGE LEAFLET

CélulaVET™ MSC

SUMMARY OF PRODUCT CHARACTERISTICS

 

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

CélulaVET™  MSC suspension for injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 1 ml dose contains:

Active substance:

4.5-6×10Equine allogeneic adipose-derived mesenchymal stromal cells

Excipients (1ml):

HypoThermosol® FRS preservation medium

3. PHARMACEUTICAL FORM

Suspension for injection.

Equine allogeneic adipose-derived mesenchymal stromal cell suspension: Slightly opaque suspension.

4. CLINICAL PARTICULARS

4.1 Target species

Horses and dogs

4.2 Indications for use, specifying the target species

Reduction of mild to moderate recurrent lameness associated with non-septic joint inflammation/degeneration in horses.

Treatment of soft tissue injuries in horses.

Reduction of mild to moderate recurrent lameness associated with non-septic joint inflammation/degeneration in dogs.

Treatment of soft tissue injuries in horses.

4.3 Contraindications

Do not use in cases of hypersensitivity to the active substance or to any of the excipients.

4.4 Special warnings for each target species

The product has been demonstrated to be efficacious in horses showing mild to moderate lameness as a result of joint, tendon, ligament or musculoskeletal injuries/disease. The efficacy of the product was demonstrated in a pivotal field trial after single administration of the product.

4.5 Special precautions for use

Special precautions for use in target animals

In order to avoid thrombosis in small vessels when administering intraarticular injections, the correct placement of the needle is critical.

Special precautions to be taken by the person administering the veterinary medicinal product to animals.

It is essential that the person administering the product adheres to aseptic techniques and maintain a sterile environment during administration.

4.6 Adverse reactions (frequency and seriousness)

Mild increases in lameness and injection site reactions, such as mild to moderate increases in joint swelling and mild increases in temperature at the injection sites, were common and limited to the  first week after use of the product. The use of NSAID should be avoided during these mild reactions as symptoms should subside spontaneously, within 3-4 days, in the absence of secondary complications, such as infections introduced at the time of administration. Maintaining an aseptic field of work is paramount.

The frequency of adverse reactions is defined using the following convention:

  • very common (more than 1 in 10 animals treated displaying adverse reaction(s))

  • common (more than 1 but less than 10 animals in 100 animals treated)

  • uncommon (more than 1 but less than 10 animals in 1,000 animals treated)

  • rare (more than 1 but less than 10 animals in 10,000 animals treated)

  • very rare (less than 1 animal in 10,000 animals treated, including isolated reports).

4.7 Use during pregnancy, lactation

The safety of the veterinary medicinal product has not been established during pregnancy and lactation. Use only accordingly to the benefit-risk assessment by the responsible veterinarian.

4.8 Interaction with other medicinal products and other forms of interaction

Do not administer simultaneously with systemic or intra-articular corticosteroids and antibiotics as these products have been shown to elicit an adverse effect, resulting in cell death. Product safe to be used in conjunction with HA, PRP and A2M, as prescribed by registered veterinary practitioners.

4.9 Amounts to be administered and administration route

Route of administration:  Intraarticular use, intra-lesional injection, intra-venous injection

Dosage: 

Horses: 4,5 – 6x106 million cells per vial

Intra-articular: 2-6x106 million cells per joint, depending on site/size.

Intralesional: 2-6x106 million cells per site depending on size of lesion

The contents of the product vial can be diluted with sterile saline for ease of administration.

Preparation of the suspension for injection:  The product is shipped, and should be maintained after receipt, at 2-8oC (degrees Celsius). The veterinary product must be administered by a veterinary surgeon taking special precautions to ensure sterility of the injection process. The product must be manipulated and injected using sterile techniques and in a clean environment. The product needs to be administered within 72 hours of the date of preparation provided by the manufacturer.

Remove the vial from the shipping container and ensure the contents of the vial are homogenised by gently inverting/stirring the vial contents in a circular motion. Remove the cap of the vial. To maintain sterility the vial can be cleaned with an alcohol swab if necessary. Using a needle with a diameter greater than or equal to 22G, aspirate the cell suspension into a syringe. The entire dose can be injected into one large joint, or the contents can be diluted by adding 1ml sterile saline to the vile and aspirating 1ml of the suspension into two separate syringes to treat two smaller joints. The product needs to be administered immediately after preparation.

Dogs: 4,5 – 6x10 6  million cells per vial

Intra-articular: 1-3x10 6  million cells per joint, depending on site/size.

Intralesional: 1-3x10 6 million cells per site depending on size of lesion

Preparation of the suspension for injection:  The product is shipped, and should be maintained after receipt, at 2-8 C. The veterinary product must be administered by a veterinary surgeon taking special precautions to ensure sterility of the injection process. The product must be manipulated and injected using sterile techniques and in a clean environment. The product needs to be administered within 72 hours of the date/time of preparation provided by the manufacturer.

Remove the vial from the shipping container and ensure the contents of the vial are homogenised by gently inverting/stirring the vial contents in a circular motion. Remove the cap of the vial, to maintain sterility the vial can be cleaned with an alcohol swab if necessary. Using a needle with a diameter greater than or equal to 22G, aspirate the cell suspension into a syringe. The entire dose can be injected into one large joint, or the contents can be diluted by adding 1ml sterile saline to the vile and aspirating 1ml of the suspension into two separate syringes to treat two smaller joints. The product needs to be administered immediately after preparation.

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

No documented cases.

4.11 Withdrawal period(s)

Zero days.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

This product contains equine mesenchymal stromal cells (eMSCs) derived from adipose tissue. The eMSCs counteract catalytic inflammatory processes through modulating the immune response and promotes chondroprotective and anti-inflammatory mechanisms, which promote the production of extracellular matrix components that promote joint health.

5.2 Pharmacokinetic particulars

After injection of the product the stem cells do not migrate or distribute from the treated joint and synovia to tissues surrounding the synovial space.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

HypoThermosol® FRS preservation medium

6.2 Major incompatibilities

In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.

6.3 Shelf life

Shelf life after reconstitution according to directions: Use immediately, alternatively use within 72hours date/time of preparation provided by the manufacturer if stored and transported chilled (2-8 °C).

6.4 Special precautions for storage

Store and transport chilled (2-8 °C). Use within 72hours date/time of preparation provided by the manufacturer

6.5 Nature and composition of immediate packaging

Equine mesenchymal stromal cell suspension:

Glass vial with rubber stopper and plastic cap

6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements.

 

7. MARKETING AUTHORISATION HOLDER

Cellula Staminale (PTY) LTD (2022/775438/07)

SOUTH AFRICA

8. REFERENCES

Barrachina, L., Remacha, A.R., Romero, A., Vitoria, A., Albareda,, J., Prades, M., et al. 2018. Assessment of effectiveness and safety of repeat administration of proinflammatory primed allogeneic mesenchymal stem cells in an equine model of chemically induced osteoarthritis. BMC Vet Res. 14(241):doi.org/10.1186/s12917-018-1556-3.

Broeckx, S.Y., Suls, M., Beerts, C., Vandenberghe, A., Seys, B., Wuertz-Kozak, K., et al. 2014a. Allogenic mesenchymal stem cells as a treatment for equine degenerative joint disease: a pilot study. Curr Stem Cell Res Ther. 9(6):497-503

Broeckx, S., Zimmerman, M., Crocetti, S., Suls, M., Mariën, T., Ferguson, S.J., et al. 2014b. Regenerative Therapies for Equine Degenerative Joint Disease: A Preliminary Study. PLOS ONE 9(1): e85917. https://doi.org/10.1371/journal.pone.0085917

Broeckx, S.Y., Seys, B., Suls, M., Vandenberghe, A., Mariën, T., Adriaensen, E., et al. 2019a. Equine Allogeneic Chondrogenic Induced Mesenchymal Stem Cells Are an Effective Treatment for Degenerative Joint Disease in Horses. Stem Cells Dev. 28(6):410-422

Broeckx, S.Y., Martens, A.M., Bertone, A.L., Van Brantegem, L., Duchateau, L., Van Hecke, L., et al. 2019b. The use of equine chondrogenic-induced mesenchymal stem cells as a treatment for osteoarthritis: A randomised, double-blinded, placebo-controlled proof-of-concept study. Equine Vet J. 51(6):787–794

Chen, X., Gan, Y., Li, W., Su, J., Zhang, Y., Huang, Y. et al. 2014. The interaction between mesenchymal stem cells and steroids during inflammation.: Cell Death Dis. (2014)5:e1009; doi:10.1038/cddis.2013.537

Da Silva Meirelles, L., Chagastelles, P.C., Nardi, N.B. 2006. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J. Cell Sci. 119(11):2204–2213.

Edmonds, R. E., Garvican, E. R., Smith, R. K. W., Dudhia J. 2017. Influence of commonly used pharmaceutical agents on equine bone marrow-derived mesenchymal stem cell viability Equine Vet J. 49(3):352-357.

Freitag, J., Bates, D., Boyd, R., Shah, K., Barnard, A., Huguenin, L., et al. 2016. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy - a review. BMC Musculoskel Dis.17:230.

Fu, Y., Karbaat, L., Wu, L., Leijten, J., Both, S.K., Karperien, M. 2017. Trophic effects of mesenchymal stem cells in tissue regeneration. Tissue Eng Part B Rev. Dec;23(6):515-528. doi: 10.1089/ten.TEB.2016.0365.

Kong, L., Zheng, L.Z., Qin, L., Ho, K.K.W. 2017. Role of mesenchymal stem cells in osteoarthritis treatment. J Orthop Trans. 9:89–103.

Leibacher, J. & Henschler, R. 2016. Biodistribution, migration and homing of systemically applied mesenchymal stem/stromal cells. Stem Cell Res. Ther. 7(7):doi 10.1186/s13287-015-0271-2

Mao, A.S. & Mooney, D.J. 2015. Regenerative medicine: Current therapies and future directions. Proceedings of the National Academy of Sciences 112(47):14452-14459, https://doi.org/10.1073/pnas.1508520112

Otto, W.R. & N.A. Wright. 2011. Mesenchymal stem cells: from experiment to clinic. Fibrogenesis Tissue Repair. 4:20.

Patel, D.M., Shah, J., Srivastava, AS. 2013. Therapeutic potential of mesenchymal stem cells in regenerative medicine.  Stem cells international 2013 (2013).

Pezzanite, L., Chow, L., Soontararak, S., Phillips, J.,  Goodrich, L., Dow, S. 2020. Equine Amikacin induces rapid dose-dependent apoptotic cell death in equine chondrocytes and synovial cells in vitro. Vet J. 2020;52:715–724.

Punzón, E., Salgüero, R., Totusaus, X., Mesa-Sánchez, C., Badiella, L., García-Castillo, M. 2022. Equine umbilical cord mesenchymal stem cells demonstrate safety and efficacy in the treatment of canine osteoarthritis: a randomized placebo-controlled trial. J. Am. Vet. Med. Assoc. 260(15):1947-1955.

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