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Maximizing Stability of Newer Vaccines: Approach towards increasing access to Vaccines Dr. Suresh Jadhav Executive Director Serum Institute of India Ltd Pune, Maharashtra, India

The best shot: reaching 22 million missed children A seminar on accelerating access to vaccination MSF Oslo Seminar, Norway, 14th Oct'13

Thermostable Vaccines: a key to improving access to vaccines STORAGE ISSUES

•97% of available vaccines require storage at 2 - 8 C° BUT 75% to100% of vaccines experience “temperature excursions” during shipping, leading to potency loss and potential spoilage.


•Eg. US CDC Federal Vaccines for Children Program: incurs > $20 million USD* in vaccine waste / year (poor refrigeration and exposure to freezing temperatures).


•Bottlenecks and economic losses bigger for countries in Climatic Zone IV. •Even countries with currently well-functioning supply chains could experience bottlenecks when new vaccines (rotavirus, PCV, etc) are introduced.

Need for


*CDC estimates

•Inherent value to manufacturers: improves bulk production efficiencies, reduces risk of recalls (eg cold chain breached), reduces shipping and storage costs. MSF Oslo Seminar, Norway, 14th Oct'13

Strong rationale for producers and purchasers to explore thermostable and/or vaccines with maximized stability.

Improving access to vaccines: logistics Global cold chain logistics market, in USD million


6.9 5.9 2009


+ Cold chain spending will grow faster in the developing world through 2015.

Novel technologies and other approaches to address those costs: • Liquid formulations are preferred form of presentation. Included in Target Product Profile for supply to UN agencies. • Technologies available, but come with challenges: - IP and regulatory issues for newer excipients/technology - Regulatory pathways more complex for developing newer formulations of existing vaccines.

Novel technology: Thermostable vaccines or vaccines with maximized stability •Cost effectiveness •Tools, technologies and expertise available with DCVM •Case study of MenAfriVac

MSF Oslo Seminar, Norway, 14th Oct'13

MenAfriVac: stability Maximizing stability

Stability profile*

Reconstitution studies*

•Carrier Protein: Tetanus a

Stability at 2-8°C

At 2-8°C

relatively stable protein.

•Excellent stability for >42 months

•Inclusion of stabilizing

Stability at 25°C

excipients such as reducing

•Stability at 25°C (Accelerated Stability) for 6 months + extension to 24 months.

•Consistency Batches subjected to Reconstitution Stability study at 2-8°C for 24 hours after reconstitution.

sugars played an important role in maximizing stability. •Novel lyophilization cycle suited to product stability. •Maximizing stability as a goal was one of focus during initial development of product.

subjected to Reconstitution

Stability at 40°C

Stability study at 25°C for 24

•For consistency batches stability at 40°C (High accelerated Stability) for 4 weeks.

hours after reconstitution.

•Lots (consistency batches) stored at 2-8 °C for 36 months and then 40 °C stress stability for 2, 4, 6, 8, 15 week time points. * In all these conditions, the product was found to be within the approved shelf life specifications for free Ps and molecular size

At 25°C

•Batches stored at 2-8 °C for 12 months and subjected to 25°C accelerated stability for 6 months.

MSF Oslo Seminar, Norway, 14th Oct'13

•Consistency Batches

MenAfriVac for CTC • • •

PATH through project Optimize approached SIIL for evaluating Men A conjugate vaccine in CTC Goal: evaluate all available stability data and see if the vaccine can be shipped at 40C° and the time frame. Based on the agreement, stability data was submitted to DCGI and WHO. WHO forwarded the data to Health Canada for evaluation.

To enable all countries across Africa to deliver MenAfrivac - given cold chain challenges: detailed review of the currently available stability data generated by the SII by the BGTD of Health Canada has undertaken a detailed review to determine whether data support the inclusion of labeling information for use of the vaccine in a CTC outside the standard 2-8 °C. The Biologics and Genetic Therapies Directorate (BGTD) of Health Canada

Recommendation of Health Canada after evaluation of stability data •

Stability data evaluated by Health Canada to give the recommendation for ECTC, reconstitution studies at 40°C was suggested.

To comply with above, the same was done and data was submitted to WHO and HC.

MenAfrivac batches at different shelf life were exposed at 40°C for 4 days, followed by reconstitution. The reconstituted product are incubated at 40°C and samples were drawn at 0,2,4,6 and 8 hours and free polysaccharide release was assayed.

The data demonstrated that the vaccine has 2- 4.5 % rise in free polysaccharide and vaccine supports the storage of reconstituted vaccine up till 6 hours.

MSFSerum Oslo Seminar, InstituteNorway, of India 14th Limited Oct'13

WHO’s approval

MSFSerum Oslo Seminar, InstituteNorway, of India 14th Limited Oct'13

Global Expectations Regulatory •

For heat stability: will only be realized after changes are made to storage guidelines. WHO initiatives in this area are encouraging.

Regulatory pathways towards use of Novel (stabilizers / adjuvants / excipients) in vaccines are time & cost intensive and unpredictable. Given such scenario, industry has no option but to stick to approved excipients.

Introduction of novel production processes or novel equipments will necessitate GMP compliance of production facilities.

Approaches to maximize stability of vaccines should be encouraged. Effective stability testing study designs during initial development of product are key for predicting formulation characteristics.

Some current vaccines are sufficiently stable and should be investigated for storage outside the cold chain. Studies to generate safety and efficacy data to support the label claim for allowing storage out of cold chain should be encouraged. (e.g. Hepatitis B, TT, Td, TD, measles, etc). MSF Oslo Seminar, Norway, 14th Oct'13

Global Expectations (cont’d) Technical • •

Formulation development might be complex. Development of Thermostable versions of existing vaccines challenging. Extensive development & testing required, including non-inferiority clinical studies to prove no impact on quality, safety and efficacy of vaccine. Commercial/IP

• •

Lack of commercial incentive for manufacturers to produce improved formulations. IP owners of Vaccine stabilization technologies will have to be convinced about public-sector health priorities i.e. to make available such technologies for making affordable thermostable vaccines.

MSF Oslo Seminar, Norway, 14th Oct'13

Thank You

MSF Oslo Seminar, Norway, 14th Oct'13

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