SUMMARY OF PRODUCT CHARACTERISTICS. Generic Name: Influenza vaccine (human, live attenuated) Pandemic, Freeze dried

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1 SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT Generic Name: Influenza vaccine (human, live attenuated) Pandemic, Freeze dried Brand Name: NASOVAC 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 1 dose: Each vial of Influenza vaccine (human, live attenuated) Pandemic, Freeze dried after reconstitution with 0.5 ml of sterile water for inhalation contains 1 dose of 0.5 ml, containing not less than EID 50 of the live attenuated influenza virus reassortant of the pandemic (H1N1) 2009 virus: A/California/7/2009 (H1N1) like strain. 5 dose: Each vial of Influenza vaccine (human, live attenuated) Pandemic, Freeze dried after reconstitution with 2.5 ml of sterile water for inhalation contains 5 doses, each of 0.5 ml, containing not less than EID 50 of the live attenuated influenza virus reassortant of the pandemic (H1N1) 2009 virus: A/California/7/2009 (H1N1) like strain. This vaccine complies with the WHO recommendation and EU decision for the pandemic. This is available as both a monodose and multi-dose container. See section 6.5 for the number of doses per vial. For excipients, see section PHARMACEUTICAL FORM SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 is supplied as a vial containing lyophilized cake in USP type 1 glass vials. An ampoule containing 0.5 ml (1 dose) or a vial containing 2.5 ml (5 dose) sterile water for inhalation as diluent is also supplied along with the vaccine. 4. CLINICAL PARTICULARS 4.1. Therapeutic indications Prophylaxis of influenza in an officially declared pandemic situation (see sections 4.2 and 5.1). Pandemic influenza vaccine should be used in accordance with official guidance. Page 1 of 8

2 4.2. Posology and method of administration Each lyophilized vaccine vial is reconstituted using 0.5ml (Single dose) or 2.5 ml (five dose) of sterile water for inhalation that is supplied along with the vaccine, using the supplied syringe and vial adapter. Each reconstituted vial contains 1 or 5 doses of 0.5 ml each of vaccine. A dose of 0.5 ml is administered as 0.25 ml per nostril using a 0.5/1.0 ml syringe and a spray device. The sprayer device creates a fine spray that primarily deposits the vaccine in the nose and nasopharynx. A single intranasal dose is recommended for people above 3 years of age. Adults (18-49 years), elderly ( 50 years) and children and adolescents (3-17 years) of age: A single dose of 0. 5 ml by intranasal route. A second dose of vaccine could be given after an interval of at least 21 days. There is no clinical experience in children below 3 years of age. For further information, see section Contraindications Hypersensitivity SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 is contraindicated in individuals with a history of hypersensitivity, especially anaphylactic reactions, to eggs, egg proteins, gentamicin, gelatin, or arginine or with life-threatening reactions to previous influenza vaccinations Concomitant Pediatric and Adolescent Aspirin Therapy and Reye s syndrome SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 is contraindicated in children and adolescents (3-17 years of age) receiving aspirin therapy or aspirin-containing therapy, because of the association of Reye s syndrome with aspirin and wild-type influenza infection Special warnings and special precautions for use Caution is needed when administrating this vaccine to persons with a known hypersensitivity (other than anaphylactic reaction) to the active substance(s), to any of the excipients, and to residues e.g. eggs, chicken proteins, etc. As with all vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine. Page 2 of 8

3 Do not administer SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 to children <36 months of age since there is no clinical data available. SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 should not be administered to any individuals with asthma or children < 5 years of age with recurrent wheezing because of the potential for increased risk of wheezing post vaccination unless the potential benefit outweighs the potential risk. Do not administer SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 to individuals with severe asthma or active wheezing because these individuals have not been studied in clinical trials. If Guillain-Barré syndrome has occurred within 6 weeks of any prior influenza vaccination, the decision to give SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 should be based on careful consideration of the potential benefits and potential risks. If the pandemic situation allows, immunisation shall be postponed in patients with severe febrile illness or acute infection. The vaccine can be given to people with minor illnesses (e.g., diarrhea or mild upper respiratory tract infection with or without fever). However, if nasal congestion is present that might limit delivery of the vaccine to the nasal lining, then delaying of vaccination until the nasal congestion is reduced should be considered. People who are in contact with others with severely compromised immune systems, should not get SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 should under no circumstances be injected. Administration of SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009, to immunocompromised persons should be based on careful consideration of potential benefits and risks. There is no clinical data available on the use of this vaccine in immunocompromised persons. Antibody response in such patients may be insufficient. The safety of SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 in individuals with underlying medical conditions that may predispose them to complications following wild-type influenza infection has not been established. SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 should not be administered unless the potential benefit outweighs the potential risk. SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 may not protect all individuals receiving the vaccine. Page 3 of 8

4 4.5. Interactions with other medicinal products and other forms of interaction Do not administer SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 to children or adolescents who are receiving aspirin therapy or aspirin - containing therapy [see Contraindications (4.3.2)]. The concurrent use of SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 with antiviral agents that are active against influenza A and/or B viruses has not been evaluated. However, based upon the potential for antiviral agents to reduce the effectiveness of SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009, do not administer this vaccine until 48 hours after the cessation of antiviral therapy and antiviral agents should not be administered until two weeks after administration of this vaccine unless medically indicated. If antiviral agents and SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 are administered concomitantly, revaccination should be considered when appropriate. There are no data on co-administration of SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 with other vaccines. However, if co-administration with another vaccine is indicated, immunisation may be carried. It should be noted that the adverse reactions may be intensified. There are no data regarding co-administration of SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 with other intranasal preparations. The immunological response may be diminished if the patient is undergoing immunosuppressant treatment. Following influenza vaccination, false positive results in serology tests using the ELISA method to detect antibodies against HIV1, Hepatitis C and especially HTLV1 have been observed. The Western Blot technique may disprove the false positive results and confirm the true results. The transient false positive reactions could be due to the IgM response by the vaccine Pregnancy and lactation Data from vaccinations with unadjuvanted interpandemic trivalent vaccines in pregnant women do not indicate that adverse foetal and maternal outcomes were attributable to the vaccine. Animal teratogenicity studies are ongoing with SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) It is not known whether SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Healthcare providers need to assess the benefit and potential risks of administering the vaccine to pregnant women. It is not known whether SII Pandemic influenza vaccine (human, live attenuated) A Page 4 of 8

5 (H1N1) 2009 is excreted in human milk. Therefore, as some viruses are excreted in human milk and additionally, because of the possibility of shedding of vaccine virus and the close proximity of a nursing infant and mother, caution should be exercised if SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 is administered to nursing mothers Effects on ability to drive and use machines The vaccine is unlikely to produce an effect on the ability to drive and use machines Undesirable effects In a Phase I study in 50 healthy adults, the vaccine was found safe. There was no serious adverse event nor any unsolicited event reported. The incidence of solicited local reactions was as follows: 8 % and 8% (nasal discomfort), 8% and 4% (stuffy nose), 28 % and 4% (sneezing), 8 % and 4% (runny nose), 20 % and 8% (headache), 8 % and 0% (chills), 12 % and 4% (fatigue), 16 % and 4% (sore throat), 12 % and 0 % (cough), 8 % and 0% (myalgia), 8 % and 0% (arthralgia), 8 % and 0% (irritability), 0 % and 4 % (loss of appetite), 8 % and 0% (nausea) and 0 % and 8 % (diarrhoea) in vaccine and placebo groups, respectively. The incidence was similar in both the study groups. Almost all the reactions were mild in intensity. All of them resolved without any sequelae within 2-3 days and did not require any treatment. No hematological, biochemical and urine parameter was affected. There was no effect on vital functions. The study showed that the vaccine was very safe. In large Phase II/III study, the vaccine was again found safe. There was no serious adverse event. The incidence of solicited local reactions was as follows: 8.1% and 1.9 % (runny nose), 5.6 % and 4.4 % (stuffy nose), 3.1 % & 1.9 % (nasal discomfort), 6.2 % and 8.9 % (sneezing), 0.6 % and 0.0 % (loss of smell), 0.0 % and 0.6 % (red eyes), 0.6 % and 1.9 % (lacrimation) and 0.6 % and 0.0 % (facial swelling) in vaccine and placebo groups, respectively. The incidence of solicited systemic reactions was as follows: 0.0 % and 0.6 % (fever), 7.5 % and 3.2 % (headache), 3.7 % and 2.5% (fatigue), 1.2 % and 0.0 % (sore throat), 5.0 % and 5.7 % (cough), 2.5 % and 1.9 % (myalgia), 1.9 % and 3.2 % (arthralgia), 0.6 % and 1.3 % (irritability), 1.9 % and 0.6 % (loss of appetite), 0.6 % and 0.0 % (nausea) in vaccine and placebo groups, respectively. The incidence was similar in both the study groups. Almost all the reactions were mild in intensity. There were a few unsolicited event reported in both the groups. These were chicken pox, coryza, cough, fever, pain in abdomen, running nose, swelling of right foot, stye, coryza, cough, diarrhoea, fever, and pyoderma of face with incidence ranging from 0.6 to 2.5 % in both the groups. The incidence was similar in both the groups. All of them resolved without any sequelae. Moreover, none of them were causally related to study vaccines. There was no effect on vital functions. Page 5 of 8

6 4.9. Overdose No case of overdose has been reported. 5. PHARMACOLOGICAL PROPERTIES 5.1. Pharmacodynamic properties SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 is a live monovalent vaccine for administration by intranasal spray. The influenza virus strain in SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 is (a) coldadapted (ca) (i.e., it replicates efficiently at 25 o C, a temperature that is restrictive for replication of many wild-type influenza viruses); (b) temperature-sensitive (ts) (i.e., it is restricted in replication at 39 o C, a temperature at which many wild-type influenza viruses grow efficiently); and (c) attenuated (att) (it does not produce classic influenza-like illness in the ferret model of human influenza infection). The cumulative effect of the antigenic properties and the ca, ts, and att phenotypes is that the attenuated vaccine virus replicates in the nasopharynx to induce protective immunity. Immune mechanisms conferring protection against influenza following receipt of Intranasal Live attenuated influenza vaccines are not fully understood, though it is wellestablished that these vaccines provide clinical protection to the majority of the vaccinees. Likewise, naturally acquired immunity to wild-type influenza has not been completely elucidated. Serum antibodies and mucosal antibodies may play a role in prevention and recovery from infection. However, it is well known that there are no correlates of protection for live attenuated influenza vaccines. In a Phase I study in 50 healthy adults aged years, virus replication was found in 16 % of vaccine recipients by RT-PCR. Seroconversion for mucosal IgA was seen in 24 % of vaccinees. In the Phase II/III study in 330 healthy subjects of different age group, the seroconversion rates with HAI were 10.6 %, with MN were 12.4 %, with IgA, were 23.4 % and with IgG, this was seen in 29.8 % of vaccinees. As is the practice for live attenuated influenza vaccines, a cumulative seroconversion was calculated by totaling the number of individuals who seroconverted with at least one of the four assays. This was estimated at 53.4 % seroconversion with SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) These results are in line with those reported with other live attenuated influenza vaccines Pharmacokinetic properties Not applicable. Page 6 of 8

7 5.3. Preclinical safety data SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 has undergone Single-dose and Repeated-dose toxicity studies in mice and rats when administered intranasally. In single-dose studies, higher than normal doses of the vaccine were given to animals and they were observed for 14 days for toxic effects. No vaccine-related untoward effects were found in animals receiving SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) In repeated-dose toxicity studies, three doses of higher than normal doses of the vaccine were given intranasally to animals on day 0, 7 and 14 and were subsequently sacrificed. Necropsy was done to assess adverse effects on any organs. No vaccine-related adverse effects were found in the study animals receiving SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) PHARMACEUTICAL PARTICULARS 6.1. List of excipients SII Influenza vaccine (human, live attenuated) Pandemic, Freeze dried contains the following excipients: INGREDIENT CONCENTRATION Partially hydrolysed gelatin 2.5% Sorbitol 5.0% L-Alanine 0.1% L-Histidine 0.21% Tricine 0.3% L-Arginine hydrocloride 1.6% Lactalbumin hydrolysate 0.35% Phosphate buffer saline Base 6.2. Incompatibilities In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products Shelf-life Shelf life for vaccine will be nine months. For diluent it will be 24 months for 5 dose in a glass vial and 36 months for 1 dose in a plastic ampoule. Page 7 of 8

8 6.4. Special precautions for storage Vials of SII Pandemic influenza vaccine (human, live attenuated) A (H1N1) 2009 must be transported and stored between 2 to 8 C Nature and contents of the container SII Pandemic influenza vaccine (human, live attenuated) A(H1N1) 2009 is supplied as a vial containing lyophilized cake in a 40mm height and 16.5 mm diameter USP type 1 glass vials with 13 mm bromo butyl rubber stoppers and 13 mm orange colour aluminium flip-off seals. For 1 dose, an ampoule containing 0.5 ml sterile water for inhalation as diluent is also supplied along with the vaccine. For 5 dose, a vial containing 2.5 ml sterile water for inhalation as diluent is also supplied along with the vaccine. 1 dose: Each vial of Influenza vaccine (human, live attenuated) Pandemic, Freeze dried after reconstitution with 0.5 ml of sterile water for inhalation contains 1 dose of 0.5 ml, containing not less than EID 50 of the live attenuated influenza virus reassortant of the pandemic (H1N1) 2009 virus: A/California/7/2009 (H1N1) like strain. 5 dose: Each vial of Influenza vaccine (human, live attenuated) Pandemic, Freeze dried after reconstitution with 2.5 ml of sterile water for inhalation contains 5 doses, each of 0.5 ml, containing not less than EID 50 of the live attenuated influenza virus reassortant of the pandemic (H1N1) 2009 virus: A/California/7/2009 (H1N1) like strain Instructions for use and handling and disposal The vaccine should be allowed to reach room temperature before use. Shake gently to assist dissolution and allow it to stand. Verify that the contents form a clear liquid. Discard the vaccine if any particulate matter is seen. Once Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal has been administered, the sprayer should be disposed of according to the standard procedures for medical waste (e.g., sharps container or biohazard container). Manufactured by: Serum Institute of India Ltd, 212/2, Hadapsar, Pune India. Page 8 of 8