Transitioning to integrated continuous downstream bioprocess for vaccine manufacturing

Project description

Advances in the field of vaccines have transformed the prevention of many health conditions and helped in improving quality of life. For example, HPV vaccines such as Gradasil® (Merck & Co) has reduced the probability of precancerous abnormalities by 34% in young adults (20-24 years). However, the cost associated with such sophisticated healthcare (Gradasil® costs ~US$ 360 for three-course vaccination) increases the financial burden on patients and healthcare systems, particularly in low-income regions. On a compassionate basis, Merck is selling Gradasil® to GAVI at a break-even cost of US$4.50/dose to reach low-income countries. However, for affordable and sustainable vaccination, studies indicate that the per-dose cost should be as low as US$1- 2.

In the need for a long-term strategy to provide affordable vaccines, implementation of continuous processing can lead to faster and more efficient utilization of chromatographic matrices, thereby lowering the cost of goods (COGs). Implementation of process analytical tools (PAT) for monitoring process variations and evaluate its impact on product quality attributes will ensure the robustness of continuous operations and reduce the chances of failure at the manufacturing scale.

Project: Development of PAT based control strategies.

• Development of online/at-line tools.
• Evaluate the feasibility of implementation at manufacturing scale.
• Create process controls for implementation of vaccine manufacturing.

Outcomes

Research Impact:

• Increase biologics availability: Reducing time to market with safe, efficient and consistent quality is often a challenge for biologics manufacturers. The pressure to reduce time to market results in insufficient process development leading to late-stage product failures. The projects will aim to develop a robust and flexible platform approach to strike a balance between time to market and sufficient process optimization. Improved predictability and consistency of a platform process can reduce the time and resources required to move from clinical development to commercial
  production.
• Affordable biologics: As part of a long-term strategy to provide affordable biologics, implementation of continuous processing can lead to faster and more efficient utilisation of chromatographic matrices, thereby lowering the cost of goods (COGs). The development of membrane separation technologies offers an opportunity to increase productivity and reduce capital expenditure. Although the cost of single-use membranes may increase COGs, the overall process economics is expected to be improved by eliminating cleaning costs.
• Quality control and assurance: Implementation of PAT for monitoring process variations and evaluation of its impact on product quality will ensure the robustness of continuous operations and reduce the chances of manufacturing failure. Such real-time quality control and assurance capabilities will be beneficial for biopharma industries in both nations.

Deliverables/Outcomes

Project-2
2019
Location IIT-D

Activities:

• General skills in protein characterization.
• Identify critical quality attributes (CQA) for the vaccine candidate under consideration.
• Identification of potential PAT tools based on literature search.

Outcomes:

• Review paper (literature on PAT applications in vaccine manufacturing).
• PhD candidature confirmation milestone.

2020
Location UQ

Activities:

• Training specialised characterization tools for vaccine candidates.
• Evaluate the feasibility of specialised vaccine characterization tools as PAT.

Outcomes: Research paper-1

2021
Location IIT-D

• Activities: Finalize PAT tools for different process steps
• Develop correlations for relating PAT tool measurements and CQA

Outcomes:

• Research paper-2
• International conference presentation
• PhD mid-candidature review milestone

2022
Location IIT-D

Activities:

• Integrate the developed PAT tools in the optimized process developed in project-1

Outcomes:

• Research paper-3
• PhD thesis review milestone

Essential capabilities

• At least one high quality research publication or 2 years of relevant industry experience;
• Excellent academic performance evidenced by a high Grade Point Average (GPA).

Desireable capabilities

Background in bioprocessing, chemical engineering, protein purification or protein chemistry is desirable.

Expected qualifications (Course/Degrees etc.)

1. First Class Masters degree or equivalent.
2. Must fulfil the PhD admission criteria for UQ and IIT-D, including meeting English language requirements.
3. Demonstrating excellent capacity and potential for research.

Candidate Discipline

Chemical Engineering.