Regulatory Decision Summary for Panenza (Haemagglutinin-Strain A (H1N1))

The purpose of this New Drug Submission (NDS) was to seek marketing authorization for the non-adjuvanted preparedness vaccine Panenza, for the prophylaxis of influenza in an officially declared pandemic.

Health Canada has authorized the preparedness vaccine Panenza (Pandemic Influenza vaccine, split virion, inactivated), for the prophylaxis of influenza in an officially declared pandemic situation. Panenza is intended for individuals 6 months of age and older who wish to receive a non-adjuvanted vaccine.

Panenza is a non-adjuvanted monovalent vaccine as part of the preparedness strategy to have pre-authorized vaccines with established quality and safety profiles in case of an influenza pandemic. At the time of the future pandemic, the vaccine will be updated with antigen of the influenza virus. The safety and immunogenicity profile of Panenza containing the new virus will then be confirmed in post-authorization studies.

Influenza disease is an acute viral respiratory infection characterized by fever, sore throat, runny nose, cough, headache, muscle pain and fatigue that usually resolve within a week. Severe cases of influenza may lead to pneumonia as well as affect internal organs that last for several weeks.

The emergence of a influenza virus is potentially more virulent and life-threatening in humans due to a lack of immunity, and may spread rapidly among human populations around the world in a pandemic situation.

Vaccination is the best preventive treatment against influenza infection and disease complications. A two-dose schedule three weeks apart is recommended with Panenza for all age groups. In infants and toddlers from 6 months to 35 months of age, half-doses are given three weeks apart.

During the 2009 influenza pandemic, Panenza was shown to induce an adequate immune response (antibody titers) against the H1N1 virus strain in three studies. One study evaluated 101 adults aged 18 to 60 years and in 45 elderly participants aged over 60 to 85 years. The other two studies evaluated 52 adolescents aged 9 to 17 years, 52 children aged 3 to 8 years, 50 toddlers aged 12 to 35 months and 51 infants aged 6 to 11 months. In addition, several post-authorization studies confirmed the vaccine’s safety and efficacy profile during the 2009 H1N1 pandemic.

Panenza contains the antigenic components of inactivated virion particles such as hemagglutinin which do not cause influenza. The non-adjuvanted vaccine is manufactured by the same process as for the company’s other inactivated split virion vaccines that have an established safety profile for over twenty years of marketing experience. The update of Panenza with the novel virus strain is not expected to significantly alter the benefit-risk profile of the vaccine. There is nonetheless uncertainty with Panenza in the expected protection and potential adverse events associated with the new pandemic influenza vaccine, which will require clinical trials and market surveillance during the influenza pandemic. As with any vaccine, some individuals may not be fully protected against the influenza strain contained in Panenza.

Panenza was shown to have an acceptable safety profile in individuals 6 months of age and older, based on the three pivotal clinical trials and from worldwide market experience. In addition, a large post-authorization safety study was conducted in 3934 participants in all age groups and in at-risk individuals, such as healthcare workers, pregnant women and individuals with health conditions. In the three pivotal clinical trials, known adverse reactions were monitored following each administration of the vaccine including injection site reactions (pain, erythema, swelling, induration, bruises) and systemic reactions (malaise, shivering, fever ≥ 38°C, headache, muscle pain). Systemic reactions were observational in small children aged 6 to 35 months (fever, vomiting, crying abnormal, drowsiness, appetite lost, irritability). Participants were followed-up for any adverse event up to twelve months after receiving two dose of Panenza.

Overall, serious adverse reactions were rarely reported with the use of Panenza, and most severe adverse reactions reported in a few participants generally resolved spontaneously, or after medication particularly in children. None of the participants in the clinical studies were withdrawn from the study due to an adverse event related to the vaccine.

The benefit in the use of Panenza is considered favorable over the risks, with risk mitigations described in the Product Monograph (PM).

An updated Risk Management Plan (RMP) for Panenza was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Panenza has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

A Notice of Compliance was recommended.

For further details about Panenza, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.