Ebvallo is indicated as monotherapy for treatment of adult and paediatric patients 2 years of age and older with relapsed or refractory Epstein-Barr virus positive post- transplant lymphoproliferative disease (EBV+ PTLD) who have received at least one prior therapy. For solid organ transplant patients, prior therapy includes chemotherapy unless chemotherapy is inappropriate.

Ebvallo should be administered under the supervision of a physician experienced in the treatment of cancer in a controlled setting where adequate facilities for handling of adverse reactions, including those requiring urgent measures, are available. Posology Treatment consists of multiple doses for injection containing a dispersion of viable T cells in one or more vials. The recommended dose of Ebvallo contains 2 × 106 viable T cells per kg of the patient’s body weight. Dose calculations Patient weight (kg) × target dose (2 × 106 viable T cells/kg) = Viable T cells to be administered Viable T cells to be administered ÷ Actual concentration (viable T cells/mL)* = Volume of thawed cell dispersion required (mL)** *See the accompanying Lot Information Sheet (LIS) and carton for information pertaining to the actual concentration of cells per vial. **Volume of thawed cell dispersion requires dilution, see section 6.6. Note: The viable T-cell concentration on the LIS and carton is the actual concentration of each vial. This may be different than the nominal concentration listed on the vial label, which should not be used for dose preparation calculations. Each vial contains 1 mL deliverable volume. The medicinal product is administered over multiple 35-day cycles, during which patients receive Ebvallo on days 1, 8 and 15, followed by observation through day 35. A response is assessed at approximately day 28. The number of cycles of the medicinal product to be administered is determined by the response to treatment shown in Table 1. If a complete or partial response is not obtained, patients may be switched to an Ebvallo lot with a different HLA restriction (up to 4 different restrictions) selected from the existing product inventory. Table 1: Treatment algorithm Response observeda Action Complete response (CR) Administer another cycle of Ebvallo with the same HLA restriction. If the patient achieves 2 consecutive CRs (maximal response), no further treatment with Ebvallo is recommended. Partial response (PR) Administer another cycle of Ebvallo with the same HLA restriction. If the patient achieves 3 consecutive PRs (maximal response), no further treatment with Ebvallo is recommended. Stable disease (SD) Administer another cycle of Ebvallo with the same HLA restriction. If the subsequent cycle results in a second SD, administer Ebvallo with a different HLA restriction. Progressive disease (PD) Administer another cycle of Ebvallo with a different HLA restriction. Indeterminate response (IR) Administer another cycle of Ebvallo with the same HLA restriction. If the subsequent cycle results in a second IR, administer Ebvallo with a different HLA restriction. a Complete response at the end of a cycle followed by partial response or other response at any subsequent cycle is considered progressive disease. Monitoring It is recommended to monitor vital signs immediately prior to each Ebvallo injection, within 10 minutes following the conclusion of the injection and 1 hour after the initiation of the injection (see section 4.4). Missed dose If a patient misses a dose, the missed dose should be given as soon as reasonably possible. Special populations Elderly No dose adjustment is required in patients = 65 years of age (see section 5.1). Ebvallo should be used with caution in elderly (see section 4.4). Hepatic and renal impairment No dose adjustment is required for patients with hepatic or renal impairment (see section 5.2). Paediatric population Posology and administration in paediatric patients 2 years of age and older are the same as for adult patients. The safety and efficacy of Ebvallo in paediatric patients below 2 years of age have not yet been established. No data are available. Method of administration Ebvallo is for intravenous use only. Administration • Administer Ebvallo as a single dose intravenously after dilution. • It is recommended to flush the intravenous line prior to Ebvallo administration. • Connect the final medicinal product syringe to the patient’s intravenous catheter (24-gauge or larger catheter size) and inject over 5 to 10 minutes. • Once Ebvallo is fully dispensed from the syringe, flush the intravenous line with = 10 mL of sodium chloride 9 mg/mL (0.9%) solution for injection. For detailed instructions on preparation, accidental exposure and disposal of the medicinal product, see section 6.6.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Traceability The traceability requirements of cellbased advanced therapy medicinal products must apply. To ensure traceability the name of the product, the batch number and the name of the treated patient should be kept for a period of 30 years after expiry date of the product. Tumour flare reaction (TFR) TFR has occurred with Ebvallo use, generally within the first few days after receiving treatment. TFR presents as an acute inflammatory reaction involving tumour sites which may include a sudden and painful increase in the tumour size or enlargement of disease-involved lymph nodes. TFR may mimic progression of disease. Patients with high tumour burden prior to treatment are at risk of severe TFR. Depending on the location of the tumour or lymphadenopathy, complications (e.g. respiratory distress and cognitive disorders) may arise from mass effect, including compression/obstruction of adjacent anatomic structures. Analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) or localised radiotherapy could be considered prior to Ebvallo administration for those patients in whom the location of the tumour could potentially lead to complications. Patients should be closely monitored for signs and symptoms of TFR, especially during the first cycle. Graft-versus-host disease (GvHD) GvHD has been reported after treatment with Ebvallo. This could be related to the decrease or discontinuation of immunosuppressive therapies for the treatment of PTLD rather than to a direct action of Ebvallo. The benefit of treatment with Ebvallo versus the risk of possible GvHD should be considered. Patients should be monitored for signs and symptoms of GvHD, such as skin rash, abnormal liver enzymes in the blood, jaundice, nausea, vomiting, diarrhoea and bloody stools. Solid organ transplant rejection Solid organ transplant rejection has been reported after treatment with Ebvallo. Treatment with Ebvallo may increase the risk of rejection in solid organ transplant recipients. This could be related to the decrease or discontinuation of immunosuppressive therapies for the treatment of PTLD rather than to a direct action of Ebvallo. The benefit of treatment with Ebvallo versus the risk of possible solid organ transplant rejection should be considered prior to the start of treatment. Patients should be monitored for signs and symptoms of solid organ transplant rejection. Bone marrow transplant rejection There is a potential risk of bone marrow transplant rejection based on humoral or cell- mediated immune reactions. No event of bone marrow transplant rejection has been reported in clinical studies. Patients should be monitored for signs and symptoms of bone marrow transplant rejection. Cytokine release syndrome (CRS) CRS has been reported after treatment with Ebvallo. Patients should be monitored for signs and symptoms of CRS, such as pyrexia, chills, hypotension and hypoxia. Diagnosis of CRS requires excluding alternate causes of systemic inflammatory response, including infection. CRS should be managed at the physician’s discretion, based on the patient’s clinical presentation. Immune effector cell-associated neurotoxicity syndrome (ICANS) ICANS has been reported after treatment with Ebvallo. Patients should be monitored for signs and symptoms of ICANS, such as depressed level of consciousness, confusion, seizures and cerebral oedema. Diagnosis of ICANS requires excluding alternate causes. Infusion-related reactions After injection of Ebvallo, infusion-related reactions such as pyrexia and non-cardiac chest pain have been reported. Patients should be monitored for at least 1 hour after treatment for signs and symptoms of infusion-related reactions. Hypersensitivity reactions Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) in Ebvallo. Transmission of infectious agents Ebvallo is obtained from human donor blood cells. Donors are screened and have tested negative for relevant communicable disease agents and diseases, including HBV, HCV and HIV. Although tabelecleucel lots are tested for sterility, mycoplasma and adventitious agents, a risk of transmission of infectious agents exists. Some tabelecleucel lots are manufactured from donors who are cytomegalovirus (CMV) positive. All lots are tested to ensure no detection of adventitious agents, including CMV. During clinical development, tabelecleucel lots derived from CMV- positive donors were administered to CMV-negative patients when an appropriate lot derived from a CMV-seronegative donor was unavailable; in this subpopulation no seroconversions were observed. Healthcare professionals administering Ebvallo must, therefore, monitor patients for signs and symptoms of infections after treatment and treat appropriately, if needed. Blood, organ, tissue and cell donation Patients treated with Ebvallo must not donate blood, organs, tissues and cells for transplantation. Sodium content This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ‘sodium-free’. Elderly population There are only limited data available for the elderly population. Based on available data, the elderly population (= 65 years of age) may be at increased risk of serious adverse events leading to hospitalisation/prolonged hospitalisation, psychiatric disorders, vascular disorders, and infections and infestations. Ebvallo should be used with caution in elderly patients.

No

Pregnancy There are no available data with tabelecleucel use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with tabelecleucel. It is not known if tabelecleucel has the potential to be transferred to the foetus or can cause foetal harm when administered to a pregnant woman. Ebvallo is not recommended during pregnancy and in women of childbearing potential not using contraception. Pregnant women should be advised on potential risks for the foetus. There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with Ebvallo. Breast-feeding It is unknown whether tabelecleucel is excreted in human milk. A risk to the newborns/infants cannot be excluded. Breast-feeding women should be advised of potential risks to the breast-fed child. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from tabelecleucel therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no data on the effect of tabelecleucel on fertility.

Ebvallo has minor influence on the ability to drive and use machines, e.g. dizziness, fatigue (see section 4.8).

Summary of the safety profile The most common adverse reactions were pyrexia (31.1%), diarrhoea (26.2%), fatigue (23.3%), nausea (18.4%), anaemia (16.5%), decreased appetite (15.5%), hyponatraemia (15.5%), abdominal pain (14.6%), neutrophil count decreased (14.6%), white blood cell count decreased (14.6%), aspartate aminotransferase increased (13.6%), constipation (12.6%), alanine aminotransferase increased (11.7%), blood alkaline phosphatase increased (11.7%), hypoxia (11.7%), dehydration (10.7%), hypotension (10.7%), nasal congestion (10.7%) and rash (10.7%). The most serious adverse reactions were tumour flare reaction (1%) and graft-versus-host disease (4.9%). Tabulated list of adverse reactions The safety database is comprised of data from 340 patients (EBV+ PTLD and other EBV-associated diseases) from clinical studies, an expanded access protocol, and compassionate use requests. Frequencies of adverse reactions were calculated in 103 patients from the ALLELE study and Study EBV-CTL-201 for which all events (serious and non-serious) were collected. In the rest of the clinical development program, only serious events were collected. Adverse reactions reported from clinical trials are presented below in Table 2. These reactions are presented by system organ class and by frequency. Frequencies are defined as: very common (= 1/10); common (= 1/100 to < 1/10); uncommon (= 1/1,000 to < 1/100); rare (= 1/10,000 to < 1/1,000); very rare (< 1/10,000). Table 2: Adverse reactions identified with Ebvallo System organ class (SOC) Adverse reaction Frequency Infections and infestations Upper respiratory tract infection Skin infection Common Common Neoplasms benign, malignant and unspecified (including cysts and polyps) Tumour pain Tumour flare reaction Common Common Blood and lymphatic system disorders Anaemia Febrile neutropenia Very common Common Immune system disorders Graft-versus-host diseasea Common Metabolism and nutrition disorders Decreased appetite Hyponatraemia Dehydration Hypomagnesaemia Hypokalaemia Very common Very common Very common Common Common System organ class (SOC) Adverse reaction Frequency Hypocalcaemia Common Psychiatric disorders Confusional state Delirium Disorientation Common Common Common Nervous system disorders Dizziness Headache Depressed level of consciousness Somnolence Peripheral sensory neuropathy Common Common Common Common Common Cardiac disorders Tachycardia Common Vascular disorders Hypotension Hot flush Cyanosis Very common Common Common Respiratory, thoracic and mediastinal disorders Hypoxia Nasal congestion Wheezing Pneumonitis Upper-airway cough syndrome Pulmonary haemorrhage Very common Very common Common Common Common Common Gastrointestinal disorders Diarrhoea Nausea Abdominal painb Constipation Colitis Abdominal distension Flatulence Dyschezia Very common Very common Very common Very common Common Common Common Common Skin and subcutaneous tissue disorders Rashc Pruritus Skin ulcer Skin hypopigmentation Very common Common Common Common Musculoskeletal and connective tissue disorders Muscular weakness Arthralgia Back pain Myalgia Arthritis Common Common Common Common Common System organ class (SOC) Adverse reaction Frequency Joint Stiffness Soft tissue necrosis Common Common General disorders and administration site conditions Pyrexia Fatigue Chills Chest paind Pain Localised oedema General physical health deterioration Very common Very common Common Common Common Common Common Investigations Neutrophil count decreased White blood cell count decreased Aspartate aminotransferase increased Alanine aminotransferase increased Blood alkaline phosphatase increased Lymphocyte count decreased Blood creatinine increased Blood lactate dehydrogenase increased Platelet count decreased Blood fibrinogen decreased Very common Very common Very common Very common Very common Common Common Common Common Common Injury, poisoning and procedural complications Post procedural oedema Common a Graft-versus-host disease (GvHD) includes GvHD in gastrointestinal tract, GvHD in liver, rash maculo-papular (skin GvHD) b Abdominal pain includes abdominal pain, abdominal discomfort, abdominal pain lower c Rash includes rash, rash erythematous, rash maculo-papular, rash pustular d Chest pain includes musculoskeletal chest pain, non-cardiac chest pain Description of selected adverse reactions Tumour flare reaction (TFR) TFR was reported in 1 patient (1%). The event was Grade 3 and the patient recovered. The onset was on the day of dosing and the duration was 60 days. Graft-versus-host disease (GvHD) GvHD was reported in 5 (4.9%) patients. Two (40%) patients had Grade 1, 1 patient (20%) had Grade 2, 1 patient (20%) had Grade 3, and 1 (20%) patient had Grade 4 events. No fatal events were reported. Four (80%) patients recovered from GvHD. The median time to onset was 42 days (range: 8 to 44 days). The median duration was 35 days (range: 7 to 133 days). Immunogenicity There is potential for immunogenicity with Ebvallo. There is currently no information indicating that potential immunogenicity to Ebvallo impacts safety or efficacy. Paediatric population There are limited data in paediatric patients (see section 5.1). Eight patients were = 2 to < 6 years of age, 16 patients were = 6 to < 12 years of age, 17 patients were = 12 to < 18 years of age. Frequency, type and severity of adverse reactions in children were similar to adults. The adverse reactions of alanine aminotransferase increased, aspartate aminotransferase increased and osteomyelitis were reported as serious only in paediatric patients. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store.

There are no data regarding with Ebvallo.

Pharmacotherapeutic group: not yet assigned, ATC code: not yet assigned Mechanism of action Ebvallo is an allogeneic, EBV-specific T-cell immunotherapy which targets and eliminates EBV-infected cells in an HLA-restricted manner. Ebvallo has an equivalent mechanism of action to that demonstrated by endogenous circulating T cells in the donors from which the medicinal product is derived. The T-cell receptor of each clonal population within Ebvallo recognises an EBV peptide in complex with a specific HLA molecule on the surface of target cells (the restricting HLA allele) and allows the medicinal product to exert cytotoxic activity against the EBV-infected cells. Pharmacodynamic effects Across multiple clinical studies, systemic cytokine levels of IL-1ß, IL-2, IL-6 and TNFa did not meaningfully change from baseline after administration of Ebvallo. Clinical efficacy and safety ALLELE is an ongoing, multicentre, open-label, single-arm, Phase 3 study in 43 adult and paediatric patients with EBV+ PTLD following solid organ transplant (SOT) or haematopoietic cell transplant (HCT) after failure of previous therapy. Patients were assigned to prespecified cohorts based on transplant type and treatment failure of prior therapy for EBV+ PTLD. The SOT cohort (29 patients) consisted of SOT patients who had failed rituximab monotherapy (13 patients) and SOT patients who had failed rituximab plus chemotherapy (SOT-R+C, 16 patients). The HCT cohort (14 patients) consisted of HCT patients who had failed rituximab. Eligible patients had a prior HCT or SOT (kidney, liver, heart, lung, pancreas, small bowel or any combination), a diagnosis of biopsy-proven EBV+ PTLD with radiographic measurable disease, and failure of rituximab monotherapy or rituximab plus any concurrent or sequentially administered chemotherapy regimen for treatment of EBV+ PTLD. The most commonly administered chemotherapy combination was cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone. Patients with Grade = 2 graft-versus-host disease (GvHD), active central nervous system (CNS) PTLD, Burkitt lymphoma, classical Hodgkin lymphoma, or any T-cell lymphoma were excluded. Patients received standard prophylactic anti-viral therapy until 30 days after the last dose of Ebvallo. Table 3 summarises the demographics and baseline characteristics from the SOT-R+C and HCT indicated cohorts. Table 3: Summary of demographics and baseline characteristics in ALLELE from cohorts SOT-R+C and HCT Ebvallo SOT EBV+ PTLDa,b Ebvallo HCT EBV+ PTLDa After rituximab and chemotherapy (N = 16) After rituximab (N = 14) Age Median years (min, max) 39.2 (16.7, 81.5) 51.9 (3.2, 73.2) Male, n (%) 7 (43.8) 8 (57.1) ECOG score (age = 16)c patients in the age group 16 13 ECOG < 2 9 (56.3) 10 (76.9) ECOG = 2 6 (37.5) 3 (23.1) Missing 1 (6.3) 0 Lansky score (age < 16)c patients in the age group 0 1 Lansky < 60 0 0 Lansky = 60 0 1 (100) Elevated LDH (age = 16), n 12 (75.0) 11 (84.6) Ebvallo SOT EBV+ PTLDa,b Ebvallo HCT EBV+ PTLDa After rituximab and chemotherapy (N = 16) After rituximab (N = 14) (%) PTLD-adapted prognostic indexd (age = 16), n (%) Low risk 1 (6.3) 1 (7.7) Intermediate risk 6 (37.5) 6 (46.2) High risk 8 (50.0) 6 (46.2) Unknown 1 (6.3) 0 PTLD morphology/histology, n (%) DLBCL 10 (62.5) 10 (71.4) Othere 4 (25.0) 3 (21.4) Plasmablastic lymphoma 2 (12.5) 1 (7.1) Extranodal disease 13 (81.3) 9 (64.3) Prior therapies Median number of prior systemic therapies (min, max) 2.0 (1, 5) 1.0 (1, 4) Rituximab monotherapy, n (%) 10 (62.2) 14 (100) Rituximab monotherapy as first line, n (%) 9 (56.3) 14 (100) Chemotherapy-containing regimenf, n (%) 16 (100) 3 (21.4) DLBCL = diffuse large B-cell lymphoma; EBV+ PTLD = Epstein-Barr virus positive post-transplant lymphoproliferative disease; ECOG = Eastern Cooperative Oncology Group; HCT = haematopoietic cell transplant; LDH = lactate dehydrogenase; max = maximum; min = minimum; SOT = solid organ transplant; SOT-R+C = SOT patients who had failed rituximab plus chemotherapy a Patients received at least one dose of Ebvallo. b SOT types included kidney, heart, liver, lung, pancreas, bowel and multiviscera. c Percentages for ECOG and Lansky scores were based on the number of patients in the corresponding age group. d Disease risk for PTLD patients was assessed at baseline using the PTLD-adapted prognostic index (based on age, ECOG score and serum LDH level). e Morphologies not clearly DLBCL or plasmablastic lymphoma were categorized as Other and were consistent with PTLD. f Chemotherapy regimens could have also been combined with rituximab or other immunotherapy agents. The primary efficacy endpoint was objective response rate (ORR) per evaluation by independent oncologic response adjudication (IORA), using Lugano classification criteria with lymphoma response to immunomodulatory therapy criteria (LYRIC) modification. ORR was obtained following administration of Ebvallo with up to 2 different HLA restrictions (one restriction switch). Ebvallo was selected for each patient from an existing product inventory based on an appropriate HLA restriction. The treatment plan consisted of administration of Ebvallo by intravenous injection at 2 × 106 viable T cells/kg on days 1, 8 and 15 followed by observation through day 35, during which a response was assessed at approximately day 28. The number of cycles of Ebvallo administered to patients was determined by the response to treatment as shown in Table 1 (see section 4.2). Seventeen (39.5%) patients required treatment with an Ebvallo lot that had a different HLA restriction (restriction switch). Of these 17 patients, 15 received one restriction switch, 2 received 2 restriction switches and 5 (29.4%) patients achieved a first response following the first restriction switch. Table 4 summarises efficacy results from the SOT-R+C and HCT indicated cohorts. Table 4: Summary of efficacy results in ALLELE from cohorts SOT-R+C and HCT Ebvallo SOT EBV+ PTLDa Ebvallo HCT EBV+ PTLDa After rituximab and chemotherapy (N = 16) After rituximab (N = 14) Objective response rateb, c, n (%) 95% CI 9 (56.3) 29.9, 80.2 7 (50.0) 23.0, 77.0 Best overall responsec, n (%) Complete response 5 (31.3) 6 (42.9) Partial response 4 (25.0) 1 (7.1) Stable disease 0 3 (21.4) Progressive disease 4 (25.0) 2 (14.3) Not evaluable 3 (18.8) 2 (14.3) Time to responsec (first complete response or partial response) Median (min, max) time to response, months 1.1 (0.7, 4.1) 1.0 (1.0, 4.7) Duration of responsec Median (min, max) follow-up in response, months 2.3 (0.8, 15.2) 15.9 (1.3, 23.3) Median DOR, months (95% CI) 15.2 (0.8, 15.2) 23.0 (15.9, NE) Patients with durable response (DOR > 6 months), n 4 6 Median duration of complete response, months (95% CI) 14.1 (6.8, NE) 23.0 (15.9, NE) CI = confidence interval; DOR = duration of response; EBV+ PTLD = Epstein-Barr virus positive post-transplant lymphoproliferative disease; HCT = haematopoietic cell transplant; KM = Kaplan-Meier; max = maximum; min = minimum; NE = not estimable; SOT = solid organ transplant; SOT-R+C = SOT patients who had failed rituximab plus chemotherapy a Patients received at least one dose of Ebvallo. b Objective response rate was the proportion of patients who achieved a response (complete response or partial response). c Independent oncologic response adjudication (IORA)-assessed response. Special populations Elderly Based on limited data, no overall differences in efficacy were observed between patients = 65 years of age and younger. Seventeen patients were = 65 to < 75 years of age, 3 patients were = 75 to < 85 years of age, no patients were = 85 years of age. Paediatric population Paediatric patients with EBV+ PTLD 2 years of age and older were treated with Ebvallo. Eight patients were = 2 to < 6 years of age, 16 patients were = 6 to < 12 years of age, 17 patients were = 12 to < 18 years of age. Based on limited data, the efficacy and safety results in paediatric patients were consistent with those in adults. The Medicines and Healthcare products Regulatory Agency has deferred the obligation to submit the results of studies with Ebvallo in one or more subsets of the paediatric population in the treatment of Epstein-Barr virus associated post-transplant lymphoproliferative disorder (see section 4.2 for information on paediatric use). This medicinal product has been authorised under 'exceptional circumstances'. This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product. The Medicines and Healthcare products Regulatory Agency will review any new information which may become available every year and this SmPC will be updated as necessary.

Upon administration of Ebvallo, circulating EBV-targeting cytotoxic T lymphocytes show a 1.33-median fold increase from baseline to peak expansion. Responders demonstrate a 1.74-median fold increase whereas non-responders show a 0.67-median fold decrease. The specific timing of this expansion varies widely among patients; however, peak expansion has been shown to correlate with response to Ebvallo. Ebvallo is an ex vivo expanded T-cell product that is not genetically modified. Hence, the nature and the intended use of the product are such that conventional studies including absorption, distribution, metabolism and excretion are not applicable. Special populations Renal and hepatic impairment The safety and efficacy of tabelecleucel have not been studied in patients with severe renal or hepatic impairment. However, the influence of renal or hepatic impairment on the pharmacokinetics of tabelecleucel is considered to be very unlikely.

Ebvallo is comprised of human T cells that are not genetically modified; therefore, in vitro assays and studies in ex vivo models or in vivo models cannot accurately assess and predict the toxicological characteristics of this product in humans. Hence, conventional toxicology, carcinogenicity, genotoxicity, mutagenicity and reproductive toxicology studies have not been performed with Ebvallo. Studies conducted in immunodeficient animal models for EBV+ PTLD revealed no overt signs of toxicity (e.g. loss of activity or weight loss) associated with a single dose of Ebvallo.

Dimethyl sulfoxide Human serum albumin Phosphate buffered saline

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

4 years when stored in the vapour phase of liquid nitrogen at = -150 °C. The drug product lot manufacturing date (MFD) is provided on the vial. The expiry date is provided on the Lot Information Sheet (LIS) and carton. The medicinal product should be thawed and diluted within 1 hour from the start of thaw. Administration must be completed within 3 hours from the start of thaw (see section 6.6). Store between 15 °C to 25 °C after thawing and dilution are complete. Protect product from light. Do not refreeze. Do not irradiate.

The Ebvallo carton must be stored in the vapour phase of liquid nitrogen at = -150 °C until immediately prior to preparation for administration. The liquid nitrogen vapour shipper provided can maintain the appropriate temperature from the sealing of the shipper until the scheduled dose. The temperature should be monitored regularly. Three temperature excursions up to -80 °C are permittable. For storage conditions after thawing and dilution of the medicinal product, see section 6.3.

Ebvallo is supplied in a cyclo-olefin copolymer 2 mL stoppered vials with a thermoplastic elastomer closure containing 1 mL deliverable volume of cell dispersion. The carton contains a variable number of vials (between 1 vial and 6 vials) according to the patient-specific dose required.

Precautions to be taken before handling or administering the medicinal product This medicinal product contains human blood cells. Healthcare professionals handling Ebvallo must take appropriate precautions (wearing gloves and glasses) to avoid potential transmission of infectious diseases. Preparation prior to administration The patient’s identity must match the patient identifiers (APIN and Institution Patient ID) on the accompanying Ebvallo Lot Information Sheet (LIS) and carton. Product- patient reconciliation must be performed by matching information on the LIS against 1) the carton (matching APIN and FDP Number) and against 2) the vial label (matching Lot Number and Donor ID). Do not prepare or administer Ebvallo if the patient’s identity or the product-patient reconciliation cannot be confirmed. Prior to thawing, ensure that the required dose calculations are completed (see section 4.2), all materials needed to prepare the dose are available, and the patient is onsite and has been clinically evaluated. Materials required for dose preparation • Sterile syringes: o Dosing syringe (select a syringe size that can accommodate required diluent [see Prepare the diluent] and cell dispersion volume) o Product draw syringe [select a syringe size that can appropriately measure and will accommodate the calculated volume of cell dispersion needed (see section 4.2)] • Diluent (sterile, non-pyrogenic multiple electrolytes solution for injection Type 1 pH 7.4) • Aseptic devices for transferring product (18-gauge unfiltered syringe needles, Luer Lock adapter, Luer Lock cap) Prepare the diluent • Select the appropriate diluent volume (30 mL for patient weight = 40 kg; 50 mL for patient weight > 40 kg). • Aseptically draw the selected volume of diluent into the dosing syringe. Thawing • The thawing process of Ebvallo can begin after the patient is onsite and has been clinically evaluated. • Remove the carton from the vapour phase of liquid nitrogen at = -150 °C. • Frozen vial(s) of Ebvallo should be placed inside a sterile bag during thawing to protect from contamination and thawed upright in a 37 °C water bath or dry thawing chamber. • Record the start of thaw time. While the medicinal product thaws, swirl the product vial(s) gently until fully thawed by inspection (approximately 2.5 to 15 minutes). Product should be removed from the thawing device immediately upon completion of thaw. • Dose preparation must be completed within 1 hour from the start of thaw. • Thawed or prepared product must not be refrozen. Do not irradiate. Dilution and dose preparation • Gently invert the vial(s) until the cell dispersion is mixed. • Aseptically withdraw the required cell dispersion volume from the provided product vial(s) into the product draw syringe using an 18-gauge unfiltered needle (see section 4.2). • Aseptically transfer the cell dispersion from the product draw syringe to the dosing syringe (previously filled with diluent). Ensure entire content is transferred from the product draw syringe. • Inspect the diluted Ebvallo in the dosing syringe: cell dispersion should appear as a translucent, hazy solution. If visible clumps appear, continue to gently mix the solution. Small clumps of cellular material should disperse with gentle manual mixing. • Maintain Ebvallo between 15 °C to 25 °C during dose preparation and administration. Dose preparation must be completed within 1 hour from the start of thaw. Administration must be completed within 3 hours from the start of thaw. Measures to take in case of accidental exposure In case of accidental exposure, local guidelines on handling of human-derived material should be followed, which may include washing of the contaminated skin and removal of contaminated clothes. Work surfaces and materials which have potentially been in contact with Ebvallo must be decontaminated with appropriate disinfectant. Precautions to be taken for the disposal of the medicinal product Unused medicinal product and all material that has been in contact with Ebvallo (solid and liquid waste) must be handled and disposed of as potentially infectious waste in accordance with local guidelines on handling of human-derived material.

Feb. 16, 2026

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