What it is and what it is used for

for

The full name of this medicine is BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension. It will be referred to as BCG-medac in the rest of this leaflet. BCG-medac contains weakened (attenuated) Mycobacterium bovis bacteria with low infectious potential. BCG-medac stimulates the immune system and is used to treat bladder cancer and to prevent bladder cancer from coming back after bladder surgery. BCG-medac is administered directly into the bladder through a tube.

What you need to know before you take it

e BCG-medac Do not use BCG-medac if • if you are allergic to viable BCG (Bacillus Calmette-Guérin) bacteria or any of the other ingredients of this medicine, especially polysorbate 80 and polygeline (listed in section 6.). • you are HIV-positive. You may need to have a blood test for HIV. • you have problems with your immune system caused by illness (e.g. leukaemia, lymphoma) or other medicines you are taking (e.g. immunosuppressive therapy, such as chemotherapy or corticosteroids). • you have or think you have TB (tuberculosis). • you have had radiotherapy to the bladder or adjacent regions. • you are breast-feeding or pregnant. • you have had surgery through the urethra (TUR; transurethral resection), a sample of your bladder tissue (bladder biopsy) was taken or you suffered injury by catheter (traumatic catheterisation) during the previous 2 – 3 weeks. • you have bladder perforation. • there is visible blood in your urine (macrohaematuria). • you have a urinary tract infection (UTI) or cystitis (inflammation of the bladder). This must be treated first. pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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BCG-medac must not be used for administration under or into the skin, into the muscle or vein or for vaccination. It must be administered directly into the bladder by instillation. Warnings and precautions Your doctor will give you a patient alert card, which you should always carry with you (see also section 4). Talk to your doctor or pharmacist before using BCG-medac • if you have a fever or presence of blood in the urine. Treatment with BCG-medac should be postponed. • if you have a low bladder capacity as it may decrease even more after the treatment. • if you are HLA-B27 (human leukocyte antigen B27) positive as the risk of inflammation of the joints could be increased (reactional arthritis). • if you have arthritis with inflammation of the skin, eyes, and the urinary tract (Reiter's syndrome). • if you have a localised dilatation of a blood vessel (aneurysm) or prosthesis. You may get an infection of implants or grafts. • if you have liver problems or take drugs which may affect the liver. This is particularly important if anti-tuberculosis drugs are considered. General hygiene After intravesical instillation sit down to urinate to prevent spray of urine to avoid contamination of surrounding area with BCG bacteria. It is recommended to wash your hands and genital area after urinating. This applies especially to the first urination following BCG treatment. If skin lesions are contaminated, an appropriate disinfectant should be used (ask your doctor or pharmacist). Detection of Bacillus Calmette-Guérin The detection of BCG bacteria is generally difficult. A negative test result does not rule out an infection with BCG outside the bladder. Patients with contact to immunosuppressed persons If you are treated with BCG-medac you must comply with general hygienic standards as stated above. This is of utmost importance if you are in contact with immunosuppressed persons, as BCG bacteria can be harmful to patients with a weak immune system. However, man-to-man transmission of the bacteria has not been reported yet. Sexual transmission Sexual intercourse should be avoided or a condom should be used for one week after BCG therapy to prevent sexual transmission of BCG bacteria. Other medicines and BCG-medac Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is especially important with the following medicines: • medicines for TB (e.g. ethambutol, streptomycin, p-aminosalicylic acid (PAS), isoniazid (INH) and rifampicin); • antibiotics (fluoroquinolones, doxycycline or gentamicin); • medicines which affect the immune system (immune-suppressants); • chemotherapy or radiotherapy.

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Pregnancy, breast-feeding and fertility Pregnancy You should not have BCG-medac if you are pregnant or you think you might be pregnant. Breast-feeding You should not have BCG-medac when you are breast-feeding. Fertility BCG may affect sperm production. Men should seek advice about the possibility of sperm preservation before starting BCG-medac. Driving and using machines This medicine could have an effect on your ability to drive or operate machines. Do not drive or operate machinery until you know what effect BCG-medac has on you. Talk to your doctor, nurse or pharmacist if you are unsure about anything.

3.How to use BCG-medac Dosage You will be given BCG-medac by experienced healthcare professionals only. Administration Before BCG-medac is given Do not drink any liquid for 4 hours before the treatment You will be asked to urinate immediately before BCG-medac is given to you. Being given your medicine A small flexible tube (catheter) will be passed into your bladder. This will remove any urine that is still in your bladder. BCG-medac is then run into your bladder through this tube. The tube will then be removed. After it has been given BCG-medac will be left in your bladder for 2 hours. During this time you should move around a little. This makes sure that treatment is spread around your entire bladder wall. Do not drink any liquid for 2 hours after you have been given BCG-medac. After 2 hours you should empty your bladder in a sitting position to avoid splashing your urine around the toilet. During the next 6 – 48 hours If you need to urinate again, also do this while sitting down. Every time you urinate, add two cups of household bleach to the toilet. Leave the bleach and urine to stand in the toilet for 15 minutes before flushing pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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Drink plenty of fluid for 48 hours after each BCG-medac treatment.

How to take it

BCG-medac is given once a week for 6 weeks (induction therapy). After this some people have 'maintenance therapy', where you may be given more doses. Your doctor will talk to you about this. If you use more BCG-medac than you should Overdose is unlikely to occur as one vial of BCG-medac corresponds to one dose instilled into the bladder. There are no data indicating that an overdose may lead to any other symptoms than the described side effects (see section 4).

4.

Possible side effects

Like all medicines, this medicine can have side effects, although not everybody gets them. The side effects of BCG treatment are frequent but generally mild and temporary. Adverse reactions usually increase with the number of BCG treatments. Show your patient alert card to your treating physicians. The most serious side effect is a severe systemic BCG infection. Tell your doctor immediately if you experience the following symptoms which can occur at any time and are sometimes delayed, and may develop weeks, months or even years after your last dose: • • • •

•

Fever above 39.5 °C during at least 12 hours or fever above 38 °C lasting for weeks; night sweats Weight loss of unknown origin Feeling increasingly unwell (e.g. tired, weak or exhausted) Signs of inflammation that may present as o breathing difficulties, chest pain or a cough, o liver problems: a feeling of pressure in right upper abdomen or, liver function test abnormalities (especially an enzyme called alkaline phosphatase), or o pain and redness of the eye, vision problems or blurry vision swelling of your lymph glands

Systemic BCG infection/reaction If the bladder is accidently injured during treatment with BCG or BCG is administered into a muscle or vein this can result in a severe general infection with BCG. Severe systemic BCG infection can lead to BCG sepsis. BCG sepsis is a life-threatening situation. Talk immediately to your physician if you experience a symptom or sign that worries you. It is importance to carry the alert card with you and show it to the doctors and nurses treating you to ensure appropriate treatment should a delayed BCG infection occur. Below is a complete list of side effects of BCG-medac: Very common: may affect more than 1 in 10 people • Feeling sick (nausea) • Bladder inflammation (cystitis), inflammatory reactions (granulomata) of the bladder. These

Possible side effects

may be an essential part of the anti-tumour activity. • Frequent urination with discomfort and pain. This may affect up to 90% of the patients. • Inflammatory reactions of the prostate gland (asymptomatic granulomatous prostatitis) • Temporary systemic BCG reactions such as fever below 38.5 °C, flu-like symptoms (malaise, fever, chills) and general discomfort • Fatigue pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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Common: may affect up to 1 in 10 people • Fever higher than 38.5 °C • Muscle pain (myalgia) • Diarrhoea • Abdominal pain • Incontinence Uncommon: may affect up to 1 in 100 people • Severe systemic BCG reaction/infection, BCG sepsis (see below for more detailed information) • Deficiency of cells in the blood (cytopenia) • Anaemia (decrease in haemoglobin in the blood) • Reiter's syndrome (arthritis with inflammation of the skin, eyes, and the urinary tract) • Inflammation of the lungs (miliary pneumonitis) • Inflammatory reactions of the lung (pulmonary granuloma) • Inflammation of the liver (hepatitis) • Skin abscess • Skin rash, joint inflammation (arthritis), joint pain (arthralgia). In most cases, these side effects are signs of an allergic (hypersensitivity) reaction to BCG. In some cases it may be necessary to discontinue treatment. • Urinary tract infection, presence of blood in the urine (macroscopic haematuria) • Abnormally small bladder (bladder retraction), abnormally low urine flow (urinary obstruction), bladder contracture • Inflammation of the testes (orchitis) • Inflammation of the epididymis (epididymitis) • Inflammatory reaction of the prostate gland (symptomatic granulomatous prostatitis) • Low blood pressure (hypotension) • Abnormal liver function test Rare: may affect up to 1 in 1,000 people • Vascular infection (e.g. infected localised dilatation of a blood vessel) • Kidney abscess Very rare: may affect up to 1 in 10,000 people • BCG infection of implants and surrounding tissue (e.g. aortic graft infection, cardiac defibrillator, hip or knee arthroplasty) • Inflammation of the lymph nodes of the neck (cervical lymphadenitis), regional lymph node infection • Allergic (hypersensitivity) reaction (e.g. oedema of eyelids, cough) • Inner eye inflammation (chorioretinitis) • Conjunctivitis ("pinkeye"), uveitis (inflammation of the uvea of the eye) • Vascular fistula • Vomiting, intestinal fistula, inflammation of the peritoneum (peritonitis) • Infection of bone and bone marrow by bacteria (osteomyelitis) • Bone marrow infection • Psoas abscess (abscess of the muscle of the loin) • Inflammation of the testes (orchitis) or epididymis (epididymitis) resistant to antituberculous therapy • Infection of the glans penis • Swelling in your arms or legs Not known: frequency cannot be estimated from the available data • Inflammation of the blood vessels (possibly in the brain) • Genital disorders (e.g. vaginal pain) • Painful sexual intercourse (dyspareunia) • Severe immunologic reaction with fever, enlarged liver, spleen and lymph nodes, jaundice and rash (haemophagocytic syndrome) pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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• • •

Renal failure, inflammation of the kidney tissue, chambers, pelvis (pyelonephritis, nephritis [including tubulointerstitial nephritis, interstitial nephritis and glomerulonephritis]) Absence or low level of sperm in semen (azoospermia, oligospermia) Elevation of Prostatic specific antigen (PSA, a prostate laboratory test)

Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme (Website: www.mhra.gov.uk/yellowcard) or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

5.

How to store it

BCG-medac

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the label and carton after EXP. Store in a refrigerator (2 °C – 8 °C). Do not freeze. Store in the original package in order to protect from light. After reconstitution the product should be used immediately.

6.

Contents of the pack and other information

What BCG-medac contains The active ingredient is viable BCG (Bacillus Calmette-Guérin) bacteria (seed RIVM derived from seed 1173-P2). After reconstitution one vial contains: BCG seed RIVM derived from seed 1173-P2, viable units 2 x 108 to 1.5 x 109 The other ingredients of the powder are: polygeline, glucose anhydrous and polysorbate 80. The other ingredients of the solvent are: sodium chloride and water for injections. What BCG-medac looks like and contents of the pack BCG-medac consists of a white or almost white powder or porous cake with shades of yellow and grey and a colourless, clear solution used as solvent. There are packages of 1 or 3 or 5 or 6 vials with or without catheter(s) and Luer-Lock to conical connector(s). Not all pack sizes may be marketed. Marketing Authorisation Holder and Manufacturer medac Gesellschaft für klinische Spezialpräparate mbH Theaterstr. 6 22880 Wedel Germany Local representative: medac Pharma Scion House pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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Stirling University Innovation Park Stirling, FK9 4NF

This leaflet was last revised in 11/2024. ————————————————————————————————————————–The following information is intended for healthcare professionals only:

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Treatment of symptoms, signs and syndrome Symptoms, signs or syndrome 1. Symptoms of vesical irritation lasting less than 48 hours 2. Symptom of vesical irritation lasting more or equal to 48 hours

3. Concomitant bacterial infection of urinary tract 4. Other genitourinary undesirable effects: symptomatic granulomatous prostatitis, epididymitis and orchitis, urethral obstruction and renal abscess

5. Fever less than 38.5 °C lasting less than 48 hours 6. Cutaneous eruption, arthralgias or arthritis or Reiter`s syndrome

Treatment Symptomatic treatment Discontinue therapy with BCG-medac and start treatment with quinolones. If after 10 days no complete resolution is observed, administer isoniazid (INH)* for 3 months. In case of antituberculous treatment, therapy with BCG-medac should definitively be discontinued. Postpone BCG-medac therapy until the urinalysis is normalised and treatment with antibiotics is completed Discontinue therapy with BCG-medac. Consider a consultation with a specialist for infectious diseases. Administer isoniazid (INH)* and rifampicin*, for 3 to 6 months according to severity. In case of antituberculous treatment, therapy with BCG-medac should definitively be discontinued. Symptomatic treatment with paracetamol.

Discontinue therapy with BCG-medac. Consider a consultation with a specialist for infectious diseases. Administer antihistaminic or non-steroidal anti-inflammatory drugs. Cortisone therapy should be considered in case of an immune-mediated reaction. If no response, administer isoniazid* for 3 months. In case of antituberculous treatment, therapy with BCG-medac should definitively be discontinued. 7. Systemic BCG reaction/infection** Definitely discontinue treatment with BCG-medac. Consider a without septic shock signs consultation with a specialist for infectious diseases. Administer a triple drug antituberculous therapy* for 6 months **see definition systemic BCG reaction and low dose corticosteroid therapy. 8. Systemic BCG reaction/infection Definitely discontinue treatment with BCG-medac. with septic shock signs Administer immediately a triple antituberculous therapy* combined with high-dose, quick-acting corticosteroids. Seek the opinion of a specialist for infectious diseases. *Caution: BCG bacteria are sensitive to all antituberculous medicinal products currently used, except for pyrazinamide. If a triple antituberculous therapy is necessary, the combination usually recommended is isoniazid (INH), rifampicin and ethambutol. Important information on the use of BCG-medac BCG-medac may only be used by experienced healthcare professionals. Ensure suitable storage (see section 5) and the integrity of the packaging. BCG-medac should be administered in the conditions required for intravesical endoscopy. BCG-medac must not be administered subcutaneously, intradermally, intramuscularly, intravenously or for vaccination against tuberculosis. The Luer-Lock catheter connector of the solvent bag may only be used for intravesical instillation! Basic principles and protective measures for the use of BCG-medac In general, direct contact with BCG-medac should be avoided. BCG-medac is a medicinal product that can cause infection in humans and pose a risk to healthcare professionals. A hazard may occur if the medicinal product is able to enter the body via injured skin, if aerosols are inhaled, droplets get into the eyes or come into contact with mucous membranes, or if ingested. Do not eat, drink or smoke in pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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the work areas and do not store any food, drinks or tobacco products here. BCG-medac must not be handled in a room in which cytotoxic medicinal products are being prepared for intravenous use, nor handled by personnel who are preparing cytotoxic medicinal products for intravenous use. The medicinal product must not be handled by persons with a known immunodeficiency. It is recommended that closed, splashproof protective gown, disposable gloves, an FFP2 respirator mask and safety goggles with side shields are worn as personal protective equipment during handling. BCG-medac may only be transported in closed containers (for storage conditions after reconstitution, see section 5). After finishing work, wipe down the work surfaces with suitable disinfectant solution. After working and in the case of contact with skin, disinfect your hands using hand disinfectant, allow them to dry, wash them and use skin care products. Tuberculin cutaneous tests The intravesical treatment with BCG-medac could induce sensitivity to tuberculin and complicate subsequent interpretation of tuberculin cutaneous tests for mycobacterial infection diagnosis. Therefore, reactivity to tuberculin should be measured before administration of BCG-medac. Preparation of the reconstituted intravesical suspension Before use, the medicinal product must be resuspended under aseptic conditions using sterile 0.9% (9 mg/ml) sodium chloride solution (see instructions for use, step 7). The catheter should be placed with special care to avoid injuries to the urethral and urinary bladder epithelium, which can lead to systemic BCG infection. Use of a lubricant is recommended to minimise the risk of traumatic catheterisation and to make the procedure more comfortable. Women might need less lubricant than men. It has not been observed that a possible antiseptic effect of the lubricant may influence the efficacy of the product. Drain the bladder after catheterisation to reduce the amount of lubricant potentially introduced before you administer BCG-medac. The suspension is mixed by gently swirling before use. Macroscopically visible particles have no influence on the efficacy and safety of the medicinal product. The contents of the vial are intended for single use/single dose only. Any remaining suspension must be disposed of. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Behaviour in the event of emergencies and spillage of BCG-medac Wear protective clothing and avoid stirring up dust. Cover the spilled BCG-medac suspension with cellulose and moisten it with a disinfectant that is proven to be effective against mycobacteria. After wiping up the spilled BCG-medac suspension, clean the surface again with disinfectant solution and allow it to dry. Spillage on the skin should be treated using a suitable disinfectant. First aid Always consult a doctor in case of contamination. In case of contact with the skin: remove contaminated clothing. Disinfect and clean the skin and check for contamination of wounds. In case of contact with the eyes: rinse the affected eye with sufficient eyewash solution or, alternatively, with water. Remove contact lenses if applicable. In case of ingestion: rinse mouth with plenty of water. In case of inhalation: ensure a sufficient supply of fresh air. For further information regarding the catheter please see the corresponding instructions for use.

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Instructions for users of BCG-medac Constituents and application of the instillation set <with catheter, without Luer-Lock to conical connector> Main constituents of the instillation set

Main constituent A B C C1 C2 C3 C4 D D1 E

Description Vial with powder Protective cover Solvent bag with 0.9% (9 mg/ml) sodium chloride solution Vial connector with protective cap and break-open seal Luer-Lock catheter connector with protective cap and break-open seal Pressure clamp Filling port without application function Luer-Lock catheter Lubricant Disposal bag

Connecting the vial to the solvent bag 1.

Lay out the disposal bag (E) ready for direct disposal of the set after instillation to prevent contamination.

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2.

Remove the flip-off cap from the vial (A) and disinfect the stopper according to local regulations.

3.

Tear open the protective cover (B) of the solvent bag (C) and remove the protective cover completely.

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4.

Remove the protective cap from the vial connector (C1).

5.

Push the connector onto the vial up to the stop.

Mixing the powder with the solvent 6.

Bend the break-open seal inside the tube of the vial connector (C1) up and down multiple times to break the seal.

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7.

Hold the solvent bag so that the vial is below it. Squeeze the solvent bag multiple times to transfer enough solvent into the vial. Make sure that the vial is not filled completely to allow for the subsequent transfer of the suspension into the solvent bag. Some solvent may remain inside the bag. Swirl the vial slowly to minimise heavy foaming while mixing the medicinal product with the solvent. If there is a lot of foam, leave the vial to rest briefly (a few minutes). The contents of the vial have to form a homogeneous suspension. This may take a few minutes.

8.

Turn the solvent bag upside down and hold it so that the vial is above it.

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Hold the vial. Squeeze the solvent bag multiple times until the vial is completely empty. If any powder remains inside the vial, repeat steps 7 and 8. From a microbiological point of view the medicinal product should be used immediately. If the medicinal product is not used immediately, please see section 5 "How to store BCG-medac". The suspension should not be instilled at refrigerator temperature in order to prevent the patient from feeling the need to urinate resulting in a shortened exposure time.

Catheterisation 9.

Catheterise the patient according to local regulations and the instructions for use using the enclosed Luer-Lock catheter (D) and lubricant (D1) or another suitable catheter and/or lubricant. Empty the urinary bladder using the catheter.

Connecting the catheter to the solvent bag 10.

To mix any sediments, rotate and swirl the bag before connecting it. Do not administer the suspension at refrigerator temperature. Remove the protective cap from the catheter connector (C2). Connect the patient's Luer-Lock catheter (D) with the catheter connector (C2) of the solvent bag.

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Instillation 11.

Bend the break-open seal inside the tube of the catheter connector (C2) up and down multiple times to break the seal. Hold the patient's catheter steady while doing so.

12.

Hold the solvent bag with the vial upside down above the bag. Squeeze the solvent bag gently with the other hand so that the medicinal product is slowly instilled into the patient's urinary bladder. Continue to squeeze until the solvent bag and the vial are empty.

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13.

Squeeze the remaining air out of the solvent bag to empty the catheter as much as possible.

After instillation 14.

Closing the pressure clamp (C3) prevents a reflux of fluid into the catheter and minimises the risk of contamination. Alternatively, you can keep the solvent bag compressed while performing steps 15 and 16.

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15.

Remove the catheter carefully from the bladder without disconnecting the solvent bag from the catheter. Avoid contamination from splashing droplets.

16.

Dispose of the product according to national regulations using the disposal bag. The contents of the vial are intended for single use/single dose only. Any remaining suspension must be disposed of.

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Instructions for users of BCG-medac Constituents and application of the instillation set <with catheter and Luer-Lock to conical connector> Main constituents of the instillation set

Main constituent A B C C1 C2 C3 C4 D D1 E F

Description Vial with powder Protective cover Solvent bag with 0.9% (9 mg/ml) sodium chloride solution Vial connector with protective cap and break-open seal Luer-Lock catheter connector with protective cap and break-open seal Pressure clamp Filling port without application function Luer-Lock catheter Lubricant Disposal bag Luer-Lock to conical connector

Connecting the vial to the solvent bag 1.

Lay out the disposal bag (E) ready for direct disposal of the set after instillation to prevent contamination.

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2.

Remove the flip-off cap from the vial (A) and disinfect the stopper according to local regulations.

3.

Tear open the protective cover (B) of the solvent bag (C) and remove the protective cover completely.

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4.

Remove the protective cap from the vial connector (C1).

5.

Push the connector onto the vial up to the stop.

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Mixing the powder with the solvent 6.

Bend the break-open seal inside the tube of the vial connector (C1) up and down multiple times to break the seal.

7.

Hold the solvent bag so that the vial is below it.

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Squeeze the solvent bag multiple times to transfer enough solvent into the vial. Make sure that the vial is not filled completely to allow for the subsequent transfer of the suspension into the solvent bag. Some solvent may remain inside the bag. Swirl the vial slowly to minimise heavy foaming while mixing the medicinal product with the solvent. If there is a lot of foam, leave the vial to rest briefly (a few minutes). The contents of the vial have to form a homogeneous suspension. This may take a few minutes.

8.

Turn the solvent bag upside down and hold it so that the vial is above it. Hold the vial. Squeeze the solvent bag multiple times until the vial is completely empty. If any powder remains inside the vial, repeat steps 7 and 8. From a microbiological point of view the medicinal product should be used immediately. If the medicinal product is not used immediately, please see section 5 "How to store BCG-medac". The suspension should not be instilled at refrigerator temperature in order to prevent the patient from feeling the need to urinate resulting in a shortened exposure time.

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Catheterisation 9.

Catheterise the patient according to local regulations and the instructions for use using the enclosed Luer-Lock catheter (D) and lubricant (D1) or another suitable catheter and/or lubricant. Empty the urinary bladder using the catheter. Note for use with self-selected catheter with conical connector: The enclosed Luer-Lock to conical connector (F) must be used to connect the bag to the selfselected catheter (not shown). To do this, the following additional steps must be carried out:

• Remove the protective cap from the catheter connector (C2, see step 10).
• Rotate and swirl the bag before connecting to remix any sediments.
• Connect the Luer-Lock to conical connector (F) to the catheter connector (C2) of the bag.
• Carefully connect the bag with the connector (F) to the patient's catheter.
• Then proceed with step 11.

Connecting the catheter to the solvent bag 10.

To mix any sediments, rotate and swirl the bag before connecting it. Do not administer the suspension at refrigerator temperature. Remove the protective cap from the catheter connector (C2). Connect the patient's Luer-Lock catheter (D) with the catheter connector (C2) of the solvent bag.

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Instillation 11.

Bend the break-open seal inside the tube of the catheter connector (C2) up and down multiple times to break the seal. Hold the patient's catheter steady while doing so.

12.

Hold the solvent bag with the vial upside down above the bag. Squeeze the solvent bag gently with the other hand so that the medicinal product is slowly instilled into the patient's urinary bladder. Continue to squeeze until the solvent bag and the vial are empty.

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13.

Squeeze the remaining air out of the solvent bag to empty the catheter as much as possible.

After instillation 14.

Closing the pressure clamp (C3) prevents a reflux of fluid into the catheter and minimises the risk of contamination. Alternatively, you can keep the solvent bag compressed while performing steps 15 and 16.

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15.

Remove the catheter carefully from the bladder without disconnecting the solvent bag from the catheter. Avoid contamination from splashing droplets.

16.

Dispose of the product according to national regulations using the disposal bag. The contents of the vial are intended for single use/single dose only. Any remaining suspension must be disposed of.

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Instructions for users of BCG-medac Constituents and application of the instillation set <without catheter, without Luer-Lock to conical connector> Main constituents of the instillation set

Main constituent A B C C1 C2 C3 C4 E

Description Vial with powder Protective cover Solvent bag with 0.9% (9 mg/ml) sodium chloride solution Vial connector with protective cap and break-open seal Luer-Lock catheter connector with protective cap and break-open seal Pressure clamp Filling port without application function Disposal bag

Connecting the vial to the solvent bag 1.

Lay out the disposal bag (E) ready for direct disposal of the set after instillation to prevent contamination.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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2.

Remove the flip-off cap from the vial (A) and disinfect the stopper according to local regulations.

3.

Tear open the protective cover (B) of the solvent bag (C) and remove the protective cover completely.

4.

Remove the protective cap from the vial connector (C1).

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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5.

Push the connector onto the vial up to the stop.

Mixing the powder with the solvent 6.

Bend the break-open seal inside the tube of the vial connector (C1) up and down multiple times to break the seal.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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7.

Hold the solvent bag so that the vial is below it. Squeeze the solvent bag multiple times to transfer enough solvent into the vial. Make sure that the vial is not filled completely to allow for the subsequent transfer of the suspension into the solvent bag. Some solvent may remain inside the bag. Swirl the vial slowly to minimise heavy foaming while mixing the medicinal product with the solvent. If there is a lot of foam, leave the vial to rest briefly (a few minutes). The contents of the vial have to form a homogeneous suspension. This may take a few minutes.

8.

Turn the solvent bag upside down and hold it so that the vial is above it.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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Hold the vial. Squeeze the solvent bag multiple times until the vial is completely empty. If any powder remains inside the vial, repeat steps 7 and 8. From a microbiological point of view the medicinal product should be used immediately. If the medicinal product is not used immediately, please see section 5 "How to store BCG-medac". The suspension should not be instilled at refrigerator temperature in order to prevent the patient from feeling the need to urinate resulting in a shortened exposure time.

Catheterisation 9.

Catheterise the patient according to local regulations and the instructions for use using a suitable catheter and lubricant. Empty the urinary bladder using the catheter.

Connecting the catheter to the solvent bag 10.

To mix any sediments, rotate and swirl the bag before connecting it. Do not administer the suspension at refrigerator temperature. Remove the protective cap from the catheter connector (C2). Connect the patient's catheter with the catheter connector (C2) of the solvent bag.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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Instillation 11.

Bend the break-open seal inside the tube of the catheter connector (C2) up and down multiple times to break the seal. Hold the patient's catheter steady while doing so.

12.

Hold the solvent bag with the vial upside down above the bag. Squeeze the solvent bag gently with the other hand so that the medicinal product is slowly instilled into the patient's urinary bladder.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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Continue to squeeze until the solvent bag and the vial are empty.

13.

Squeeze the remaining air out of the solvent bag to empty the catheter as much as possible.

After instillation 14.

Closing the pressure clamp (C3) prevents a reflux of fluid into the catheter and minimises the risk of contamination. Alternatively, you can keep the solvent bag compressed while performing steps 15 and 16.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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15.

Remove the catheter carefully from the bladder without disconnecting the solvent bag from the catheter. Avoid contamination from splashing droplets.

16.

Dispose of the product according to national regulations using the disposal bag. The contents of the vial are intended for single use/single dose only. Any remaining suspension must be disposed of.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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Instructions for users of BCG-medac Constituents and application of the instillation set <without catheter, with Luer-Lock to conical connector> Main constituents of the instillation set

Main constituent A B C C1 C2 C3 C4 E F

Description Vial with powder Protective cover Solvent bag with 0.9% (9 mg/ml) sodium chloride solution Vial connector with protective cap and break-open seal Luer-Lock catheter connector with protective cap and break-open seal Pressure clamp Filling port without application function Disposal bag Luer-Lock to conical connector

Connecting the vial to the solvent bag 1.

Lay out the disposal bag (E) ready for direct disposal of the set after instillation to prevent contamination.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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2.

Remove the flip-off cap from the vial (A) and disinfect the stopper according to local regulations.

3.

Tear open the protective cover (B) of the solvent bag (C) and remove the protective cover completely.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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4.

Remove the protective cap from the vial connector (C1).

5.

Push the connector onto the vial up to the stop.

Mixing the powder with the solvent 6.

Bend the break-open seal inside the tube of the vial connector (C1) up and down multiple times to break the seal.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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7.

Hold the solvent bag so that the vial is below it. Squeeze the solvent bag multiple times to transfer enough solvent into the vial. Make sure that the vial is not filled completely to allow for the subsequent transfer of the suspension into the solvent bag. Some solvent may remain inside the bag. Swirl the vial slowly to minimise heavy foaming while mixing the medicinal product with the solvent. If there is a lot of foam, leave the vial to rest briefly (a few minutes). The contents of the vial have to form a homogeneous suspension. This may take a few minutes.

8.

Turn the solvent bag upside down and hold it so that the vial is above it.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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Hold the vial. Squeeze the solvent bag multiple times until the vial is completely empty. If any powder remains inside the vial, repeat steps 7 and 8. From a microbiological point of view the medicinal product should be used immediately. If the medicinal product is not used immediately, please see section 5 "How to store BCG-medac". The suspension should not be instilled at refrigerator temperature in order to prevent the patient from feeling the need to urinate resulting in a shortened exposure time.

Catheterisation 9.

Catheterise the patient according to local regulations and the instructions for use using a suitable catheter and lubricant. Empty the urinary bladder using the catheter. This pack does not contain a catheter. Use the enclosed connector (F) to connect the bag to the patient's catheter with a conical connector (not shown). To do this, the following additional steps must be carried out:

• Remove the protective cap from the catheter connector (C2, see step 10).
• Connect the connector (F) to the catheter connector (C2) of the bag.
• Carefully connect the bag with the connector (F) to the patient's catheter.
• Then proceed with step 11.

Connecting the catheter to the solvent bag pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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10.

To mix any sediments, rotate and swirl the bag before connecting it. Do not administer the suspension at refrigerator temperature. Remove the protective cap from the catheter connector (C2). Connect the patient's catheter with the catheter connector (C2) of the solvent bag.

Instillation 11.

Bend the break-open seal inside the tube of the catheter connector (C2) up and down multiple times to break the seal. Hold the patient's catheter steady while doing so.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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12.

Hold the solvent bag with the vial upside down above the bag. Squeeze the solvent bag gently with the other hand so that the medicinal product is slowly instilled into the patient's urinary bladder. Continue to squeeze until the solvent bag and the vial are empty.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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13.

Squeeze the remaining air out of the solvent bag to empty the catheter as much as possible.

After instillation 14.

Closing the pressure clamp (C3) prevents a reflux of fluid into the catheter and minimises the risk of contamination. Alternatively, you can keep the solvent bag compressed while performing steps 15 and 16.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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15.

Remove the catheter carefully from the bladder without disconnecting the solvent bag from the catheter. Avoid contamination from splashing droplets.

16.

Dispose of the product according to national regulations using the disposal bag. The contents of the vial are intended for single use/single dose only. Any remaining suspension must be disposed of.

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

46

pal (UK) BCG-medac 2 x 108 – 1.5 x 109 cfu Powder and solvent for intravesical suspension UK National version: 11/2024 <not-for-print>

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