Introduction
Selecting a contract development and manufacturing organization (CDMO) is one of the most consequential early decisions a sponsor will make in the development of AAV gene therapy. The appropriate partner depends on the sponsor's program goals, timeline, budget, indication, and internal capabilities. This section is intended to help sponsors frame their own due diligence by outlining areas of consideration and illustrative questions that have emerged from BGTC project team experience. It is not intended to be prescriptive or to favor particular CDMOs or business models.
Vector and plasmid
A useful starting point for due diligence is understanding the CDMO's experience producing AAV biotherapeutics intended for IND-enabling and clinical use. Sponsors may want to explore the CDMO's track record across serotypes relevant to their program, the range of scales at which they have operated, and the number of regulatory submissions their work has supported. It can be valuable to understand whether those activities can be performed at the same CDMO or will require coordination across multiple partners, and what that implies for technology transfer, comparability, and timelines.
Questions sponsors may consider:
How many regulatory submissions has this CDMO been involved in?
Are materials being produced outside of the US?
If yes, what are the additional considerations for shipping to the US?
Is the CDMO able to construct both GMP vectors and plasmids?
Batch grades
As noted in the Overview of manufacturing batches section terminology for non-GMP material (research, toxicology, pilot, engineering) is not standardized, and CDMOs apply these terms differently depending on their facilities, equipment, and procedures. Understanding how a prospective CDMO defines and produces each batch grade offers a window into the CDMO’s overall manufacturing capabilities – including how documentation is generated, how equipment / facility space are allocated, and how quality oversight / monitoring are applied across batch grades. It may also be worth understanding how each batch grade is intended to be used, particularly the progression from early development material through to GMP, and how different batches are expected to support analytical activities at different stages (e.g., analytical method development vs. method qualification or validation). Aligning on these definitions and expectations upfront supports more effective communication with the CDMO.
Questions sponsors may consider:
How do you define and differentiate non-GMP batches (e.g., research, toxicology, pilot, engineering) with respect to scale, materials, quality oversight, and documentation?
What are your capabilities for developing and manufacturing each batch grade?
What documentation (batch records, Certificate of Analysis, Certificate of Testing) is generated for each batch grade?
How does your process knowledge and documentation carry forward as material progresses from early development batches toward GMP?
What grade of lab or manufacturing space will our batches be produced in (basic lab, controlled environment, or classified suite)?
For a Process Development (PD) run, are reactors and equipment shared or dedicated? Are personnel dedicated to our program?
What environmental monitoring and quality oversight are applied at each batch grade?
Timeline coordination
Coordinating manufacturing timelines and cost with a CDMO requires careful consideration and planning around schedule, budget, and interdependencies with downstream activities such as GLP toxicology studies and CRO engagements. Sponsors typically make contractual commitments to secure manufacturing slots and timelines. Manufacturing delays have the potential to cascade beyond the CDMO.. The considerations below are drawn from BGTC project team experience and are intended as a starting point for planning discussions rather than prescriptive requirements.
Ways of working with CDMO
Establishing effective ways of working with a CDMO early in the relationship helps keep programs on track. A CDMO's communication style and project management approach shape how smoothly a program progresses and how sponsors plan and allocate their own resources. Understanding how a CDMO operates and manages relationships gives sponsors a fuller picture when selecting a partner suited to their needs. While project management is typically included as part of the service, the degree of dedicated support across the full project lifecycle can vary. Consistent reporting and a dedicated project manager provide sponsors with clearer visibility into timelines and earlier awareness of potential delays or other impacts. The level and continuity of that support can influence how much project oversight a sponsor needs to provide on their own side, and how experienced that internal support should be.
The considerations below are drawn from BGTC project team experience and are intended as a starting point for planning discussions.
Questions sponsors may consider:
What is the CDMO's communication plan, and how proactive will they be in raising delays, deviations, or timeline changes?
Will there be dedicated project management support from the CDMO?
Does the sponsor have resources to actively manage the CDMO and maintain visibility into timelines?
Who is the single point of contact on each side (sponsor and CDMO), and what is the escalation pathway when issues arise?
What documents will the CDMO make available for review (e.g., batch records, analytical data, protocols, reports)?
How much time will sponsors have to review materials before turning them around, and is that workable given our internal review process?
Quality assurance (QA) agreements
The QA Agreement defines the quality responsibilities, documentation, and review rights shared between a sponsor and a CDMO. A key risk to manage is scope: QA agreements may default to covering only GMP batches, which can leave sponsors without documentation they need for non-GMP material (e.g., as toxicology batch records). By gaining clarity early and ensuring the agreement captures every document the sponsor needs to review and approve, teams can mitigate the risk of gaps that tend to surface later in development. The considerations below are drawn from BGTC project team experience and are intended as a starting point for discussion.
Questions sponsors may consider:
What is in scope, and how comprehensive is the QA agreement?
Does the agreement cover non-GMP material (e.g., toxicology batch records, blank and executed batch records), or only GMP batches?
Which documents will the sponsor have the right to review and approve?
Are these documents sufficient for the program’s needs (e.g., reporting requirements)?
What batch records are documented, and for which batch grades?
How are batch records documented (e.g., electronically)?
How are batch records shared (e.g., shared file system vs email)?