Raw materials: Cell and gene therapy critical starting material: a discussion to help establish release specifications for plasmids and the bacterial master cell banks used to produce them

Plasmids release specifications are critical to the manufacture of many cell and gene therapy products. These specifications exist, but there is unlikely to be alignment between different companies. What is needed is a common language and the ability to reference a shared platform that will increase the confidence, speed and efficacy of data gathering and collaborations. The platform should also help shape future guidelines and regulations issued by agencies such as the US Pharmacopeia, with whom BioPhorum has a working relationship.

This is why BioPhorum Cell and Gene Therapy is asking for your help – and is giving you the opportunity to have a say in a scientific community discussion that will influence its suggested testing practices for plasmid release specifications. The team is proposing a platform framework for testing plasmid master cell banks and plasmid DNA.

This article’s scope is strictly limited to plasmid E. coli master cell banks and plasmid DNA used to manufacture cell and gene therapies. This includes, for example, using plasmid DNA in the manufacture of viral vectors (such as an adeno-associated virus) or the manufacture of lentiviral vectors for cell therapies (such as a CAR-T).

The article includes a table that sets out an approach to platform testing, which is similar to that presented in USP <1047> Gene Therapy Products.

Feedback please

The team welcomes feedback on the key questions included in the article:

  1. Do you agree with the ambition of a platform approach for plasmid testing and release?
  2. Do you envisage a phase appropriate plasmid sourcing strategy?
  3. How do you manage the stability of the master cell bank and the plasmid?

There are also more detailed questions, such as ‘Are any attributes missing, e.g. potency, contaminants, or residuals?’ and ‘What is the best practice for the number of timepoints and temperatures to be tested?’.

Professionals from member and non-member companies are invited to share their opinions and thoughts via a confidential online survey OR as a downloadable pdf document that can be returned to info@biophorum.com. Representatives of member companies can also share their thoughts through BioPhorum group meetings.

The team recognizes that the proposed approach is a work-in-progress. It understands that many of you are doing some very innovative work – so this is a chance for you to use your voice to produce a standardized approach, a baseline of tests and the agreed methods that should be followed for the acceptable specification ranges for a plasmid.The team has spent an enormous amount of effort drafting the platform testing table, including a blinded survey to enable the sharing of data and opinions. The final proposals are a combination of thoughts, suggestions and questions from more than 20 companies.


An agreed framework for plasmid testing and release has many benefits. It will give you confidence that your actions are aligned with those of your peers. The alignment will also bring reliability and consistency to the manufacturing process as everyone is meeting the same standard for a particular material.

It also means that manufacturers, suppliers and clients can use the same language and refer to the table and the testing. Importantly, when you come to file with regulatory authorities, you will have a data pack that covers what they will expect to see and that demonstrates you are managing and controlling that material appropriately.

Nobody has tried to define the plasmid release testing needed for cell and gene therapy processes, so the BioPhorum approach is an industry first. With the explosive growth of the cell and gene therapy industry, the need for these release specifications is loud and clear. What do you think?

If you would like to help shape an important part of the cell and gene therapy industry, please share your thoughts in BioPhorum group meetings, complete the confidential survey or return the downloadable pdf to info@biophorum.com





Attached Files

CGT critical starting material - discussion release spec for plasmids & MCB Dec 2020.pdf
Release specifications for plasmids and master cell banks survey November 2020.pdf
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  • Create Date 27th November 2020
  • DOI https://doi.org/10.46220/2020CGT005
  • Last Updated