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Lean Principles for Viral Vector Vaccine Process Development

February 10, 2021

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Before COVID-19, the typical best-case scenario for vaccine process development would take several years from the start of process development to full production ramp-up. But the urgency of the novel coronavirus, SARS-CoV-2, and the impact it has had on the world so far, have resulted in a resounding call across the globe that there is no time to spare.

 

As we conclude our rapid vaccine development series, in which Clive Glover, Director of Cell and Gene Therapy, discussed the importance of a platform approach and how a consortium vaccine project achieved process development times as short as 8weeks, we take a final look at how how Pall Biotech leveraged the six lean product and process development principles (LPPD principles) to transform the process development and commercialization timeline.

 

A Challenging Situation

 

By the middle of March 2020, the pandemic was in full swing across the globe and the University of Oxford, funded by the UK government, pulled together a consortium of organizations to work on the large-scale manufacturing of the vaccine.

 

Pall Biotech was honored to have the opportunity to participate in this consortium to develop and deploy a full manufacturing process for the viral vector vaccine candidate (CHAdOx1nCov-19/AZD1222) under development by the University of Oxford and AstraZeneca.

 

As part of this consortium, Pall Biotech was issued with two important tasks: 

 

  • Developing the manufacturing process that could shorten the timeline by 80% (compared with standard 40-week lead time) – Through a collaborative and transparent platform approach leveraging a decade of internal innovation and conceptualization, the development work was able to be done in just eight weeks – an industry first.
  • Ensure that the process could be scaled and deployed across sites to produce millions of doses of the vaccine when ready – This includes securing the supply of the equipment and consumables for manufacturing of the actual vaccine to the broad range of contract manufacturing organizations (CMOs) implementing the process that was developed.
 
To achieve these challenging tasks, Pall Biotech aligned parent company Danaher Business System (DBS) tools with the six recently introduced LPPD Principles compiled by Jim Morgan, senior advisor at the Lean Enterprise Institute:
 
  1. Understand before you execute
  2. It is a team sport
  3. Synchronize workflows
  4. Build-in learning and knowledge re-use
  5. Create new value streams
  6. It is a people-first system
 
Applying the LPPD Principles
 

1.    Understand before you execute means to deeply understand your customer and their context to identify and focus on your unique value proposition for them before you start the detailed development work. 

 

Eighteen months prior to the COVID-19 pandemic, Pall Biotech had already begun developing standard but flexible process platforms based on customer needs, including one for viral vector manufacturing. This allowed Oxford’s lab-scale production solution to be transferred to the Pall Process Development Services (PDS) laboratory in Portsmouth, UK, where it was scaled up from 3 L to 200 L.

 

At the 50 L scale, Pall involved the Process Engineering and Project Management teams within its Biotech division to design the industrialized and scalable process solution that would be deployed to CMOs. Technical gaps in the standard process map for the Oxford/AZ project vaccine candidate were identified and a risk assessment conducted to mitigate risks. Access to these kaizen standard process platforms significantly acceleratedthe development process.

 

2.    It’s a team sport means that you need design, engineering, manufacturing, installation, and many more functions to work together effectively to maximize the value you are creating for your customer. Within the consortium, real trust was built quickly, by harnessing technical competency and the intense desire to defeat SARS-CoV-2.

 

Pall Biotech had a cross-functional team of more than 20 highly dedicated people co-located during the critical design phases. Hundreds of additional Pall Biotech team members supported other portions of the process development work. Having a clear focus and target helped align the team to deliver amazing results in eight weeks, versus the normal 40 weeks. 

 

3.    Synchronizing workflows means coordinating workflows across the entire organization, or in this case, the consortium.

 

Collaborating and doing the technical work required Pall to align internal functions, external customers, and the extended supply base of more than 20 CMOs. Daily visual management, an integral part of Pall’s business strategy, enabled significant time reduction on long lead-time items, such as critical new equipment that had normal lead-times of 12 weeks. Early and frequent communication allowed the consortium partners to adjust quickly to tackle several technical issues that arose.

 

4.    Build-in learning and knowledge re-use involves sharing learnings and the knowledge of how to apply them to new systems with the rest of the organization and is essential to great product and process development. For this project, Pall shared its standard platform for viral vector manufacturing, a template with 80% standard and re-usable elements and the other 20% customizable based on each specific case.

 

5.    Creating new value streams means that instead of products in isolation, it is critical to focus on lean product and process development. Pall had to understand and design an end-to-end value stream for large-scale production of the Oxford/AZ vaccine, including the processes, the equipment, and the consumables to support production of billions of doses. Using the standard template,the team was able to configure standard bioprocess equipment solutions and manifold designs with proven capability, without the need for lengthy validation of new designs – thus reducing time and risk. 

 

The standard platform simplified and compressed end-to-end value stream design and supply-chain planning and re-ordering. Pall Biotech also created an extended value stream replenishment model to support continuous supply to the CMOs as they quickly ramp up to the vaccine production volumes required.

 

6.    People-first is woven throughout a lean development system, which should be designed to engage and challenge people and to help them to do and be their very best. Leveraging the prior viral vector template standardization work freed up technical resources and allowed the team to focus more time and energy on the critical, detailed process development work to provide value during this global health crisis.

 

Successful Process Transfer

 

The developed process – including the equipment and consumable list and all the settings required to run the equipment – was initially transferred to three CMOs that began to run the process as quickly as possible.

 

As of the date of this blog, 20 CMOs are now able to run the process across the globe. Collectively, this network has the capacity to generate more than two billion doses by the end of 2021 – a feat that once would have seemed impossible.

 

To read more on the lean approach of the consortium, please read the full article here.

 

Discover more vaccine blogs by Pall experts here

 

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Clive Glover – Director, Cell & Gene Therapy

Dr Clive Glover is the Director of Cell & Gene Therapy at Pall Biotech. Clive holds a PhD in Genetics and has over 15 years of experience in cell and gene therapy. His work has been published in numerous scientific journals and he has presented at many conferences.
Dr Clive Glover is the Director of Cell & Gene Therapy at Pall Biotech. Clive holds a PhD in Genetics and has over 15 years of experience in cell and gene therapy. His work has been published in numerous scientific journals and he has presented at many conferences.
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