A CDMO's Checklist - Part Two | Data & Documentation

A CDMO’s Checklist For Prospective Clients – Part Two

This is Part 2 of our checklist series; you can review Part 1 here.

In summary, we are reviewing what a CDMO wants to see in a client, a checklist that will provide some insight into what CDMOs are looking for out of a partnership with a client. Part 1 focused on the element of a transparent process; Part 2 will discuss other areas of transparency.

Analytics

It is fairly common for the analytical package to be incomplete at the time of tech transfer for early-stage programs, but the CDMO needs to have a complete picture of the analytical development status.

  • Identity and Purity – these are often the most well-understood assays, but even these seldom have specifications prior to tech transfer. What should be disclosed is:
    • How many assays and of what type (i.e., three color flow panel)
    • If the assays need further development/optimization
    • The type of equipment that has been used to run the assay in the past
    • If the assays have been qualified
    • If you are open to change if the CDMO sees issues with the current assay (and if not, why?)
  • Residuals – for early-stage trials most residuals are calculated by wash volumes. However, at times, cells carry proteins or other materials over and the wash calculations don’t tell the entire story. It is always good to discuss ancillary materials that may need to be assessed at the end of the process; these usually include any material that could cause an allergic reaction (e.g., BSA), immunomodulatory materials (e.g., cytokines or antibodies), or toxins. The key is to have the discussion up front about what you have done, what you have not, and any concerns you have.
  • Raw Materials – like residuals, testing of raw materials is usually minimal for early-stage trials. However, some critical raw materials may require more than a simple CofA check. If you have concerns about any raw material, make sure you discuss this with the CDMO before the proposal is written, as this will need to be included in the scope of work.Potency – of course, this is the assay that is typically most challenging in cell therapy. Often before a first-in-human trial, this has not been considered (again, that is ok). But it is good to discuss if you have given this thought. If you have four different ideas you would like to test, let the CDMO know. Last-minute surprises in the analytical package are bound to cause delays and create issues. Remember, we’re keeping transparency in mind.
  • Potency – of course, this is the assay that is typically most challenging in cell therapy. Often before a first-in-human trial, this has not been considered (again, that is ok). But it is good to discuss if you have given this thought. If you have four different ideas you would like to test, let the CDMO know. Last-minute surprises in the analytical package are bound to cause delays and create issues. Remember, we’re keeping transparency in mind.

Documentation

Do you have draft batch records? Standard Operating Procedures? Analytical Test Methods? As they say in GMP – if it wasn’t documented, it didn’t happen. Getting the documentation written, reviewed, and approved correctly prior to GMP manufacturing is crucial. So, how much of a head start can you provide the CMDO? Have you worked with another CDMO? Can you transfer batch records, or are most of your procedures written on the back of a napkin? Understanding not only how mature the processes are, but also how well the procedures are documented, is a great way for a CDMO to better understand the maturity of the overall program.

Raw Material and Equipment Selection

This may seem fairly straightforward, but it is not uncommon for a process to come to a CDMO where both raw materials and equipment are not solidified. Again, it is ok, but it needs to be discussed early. Do you need a new process for cell isolation? Are your ancillary materials GMP-grade, or will some need to be either transitioned to GMP-grade or qualified in if no GMP option exists? You don’t need a locked down BOM before transferring a process, but it should be understood how close it is and if you require the CDMO to finalize selection of any equipment or material.

Timelines

This also seems very obvious, but unfortunately it is an area that often creates tension and issues down the line. If you have promised investors a certain timeline or have clinical sites on standby, but don’t align the CDMO to the same timeline, it is a disaster waiting to happen. Don’t think this happens? I can assure you it does. Rule of thumb – anytime you provide a date or timeline to anyone associated with the product or trial, make sure the CDMO is in the loop. Nothing is worse for a CDMO than to have to accelerate a timeline because of a commitment made by the sponsor where the CDMO was not informed. Better yet? Ask the CDMO if the timeline change is achievable prior to making the commitment!

Regulators

Ever sign up a CDMO for something in an IND and not tell the CDMO about it? Yes, this happens too. Please, before you tell the FDA that your CMDO is going to be your Phase 3 manufacturer, make sure the CDMO is aware and has agreed to it. Going back to the timeline, make sure they agree to the timeline you are providing the FDA as well. This should be a partnering discussion to ensure everything has been addressed. In that timeline, did you leave adequate time for method validation? Did you ensure no new raw material testing would be required? As you progress through clinical development, stringency is raised, so ensure you are regularly talking to your CDMO about how this progression changes requirements and the requisite time and cost for those changes.

Miscellaneous

I have often been told that a good question to ask someone in an interview is “What is a question I should have asked you but didn’t?” Same thing goes here. The CDMO will ask a lot of questions, but they may miss something key. If that is the case, volunteer the information. If you are conducting an allogeneic trial, but treatment will only be an option with a 4 of 6 HLA match or better – let them know. If you are making a master cell bank for use in a US based trial but want the cell bank to be created to also be used in Europe at some point – inform them. If you discuss that 40% of your runs fail but don’t tell them it was only the runs where the apheresis was 18 hours or older at start – they may spend valuable time chasing down false leads. In general, inform the CDMO. You may be divulging some items that you think are not important, but in this case “too much information” is better than “not enough”.

No one likes a change order, as on top of the change to the budget and often the timeline, they create churn and stress on both parties. The more we get right up front – which is dependent on our understanding of the process, analytics, and everything else above – the fewer change orders will be required over the life of the relationship.

Explore the other entries in our Checklist Series:

Part One

Part Three

Learn More