Regulatory requirements for upstream bioprocessing are tightening - and the consequences of getting it wrong are significant. In this interview, Stanley Tan, Director of Regulatory Affairs, and Holly Astley, Project Manager in Revvity's Bioproduction team, share what compliance-ready bioprocessing looks like in practice: from qualifying suppliers to managing change and preparing documentation that holds up under regulatory scrutiny.
Holly Astley, Project Manager: Holly is a Project Manager in Revvity's Bioproduction team, where she has a particular focus on regulatory support and documentation for the CHOSOURCE™ platform. With a PhD in Plant Molecular Biology from the University of Cambridge and more than 15 years at Revvity spanning scientific and client-facing roles, she brings a broad and grounded perspective to the regulatory realities of upstream process development.
Stanley Tan, Director of Regulatory Affairs: Stanley Tan is Director of Regulatory Affairs at Revvity, with over 15 years of experience in pre- and post-market quality and regulatory compliance across diagnostics and life sciences. He holds a BSc in Biochemistry from UCLA, an MBA from USC's Marshall School of Business, and a Regulatory Affairs Certification (RAC) through RAPS.
Key takeaways:
- Regulatory compliance needs to be a priority from the very start of upstream process development, not an afterthought
- Involve quality and regulatory teams during critical decisions like reagent selection and process scale-up to build in compliance from the ground up
- Establish a robust change control process and continuously monitor evolving global regulations to keep your process futureproof
- Prioritize documentation quality and submission-readiness at every stage - it's far easier to maintain than to reconstruct under pressure
Q: What are the most common regulatory challenges teams encounter during upstream process development?
Stanley: Smaller biotech companies often lack dedicated regulatory expertise, which leads them to make supplier decisions based solely on technical performance and cost, without evaluating regulatory support capabilities. They discover mid-development that their supplier can't provide the documentation regulators now routinely demand, forcing costly supplier changes and bridging studies. Larger biopharma companies face a different problem: global regulatory divergence.
Despite substantial harmonization through ICH guidelines, FDA, EMA, and other health authorities differ in how they interpret expectations around raw material sourcing, documentation, lifecycle management, and post-approval changes. Managing those differences requires upfront planning. The underlying trend driving both challenges is regulators' heightened focus on supply chain transparency and continuous supplier monitoring.
Holly: The most common challenges involve ensuring process robustness, managing traceability, and introducing quality-by-design principles as early as possible. These apply to both small biotechs and established biopharma. Smaller companies can struggle with limited regulatory expertise and resources; larger organizations often face challenges tied to organizational complexity and inertia. In all cases, the key is to embed regulatory thinking into process development from day one.
Q: When selecting reagents or consumables for upstream work, what regulatory considerations do teams most often overlook?
Holly: Teams frequently assume vendors will provide adequate regulatory support documentation without verifying this upfront. Details of what documentation will be provided should be discussed early in supplier negotiations, and quality and regulatory teams should be involved during reagent selection, not after purchase orders are signed.
Raw material traceability is also consistently underestimated, particularly for animal-derived components requiring TSE/BSE documentation. Teams need to maintain detailed records of every material lot used not just in manufacturing, but throughout the entire history of cell line generation: from initial transfection and selection through to Master Cell Bank creation. Regulators will ask for this provenance data, and gaps discovered late can be impossible to fill retrospectively.
Stanley: Two specific areas get overlooked most often: supplier change control processes and Drug Master File availability.
On change control, ask directly: "What is your advance notification timeline for manufacturing changes?" and make sure that timeline gives you adequate time to assess impact and file required regulatory updates. On DMFs, ask: "Do you maintain a Drug Master File with FDA, or equivalent documentation in your target regulatory regions?" A supplier with a current DMF significantly reduces your regulatory submission burden. These two questions can reveal a supplier's true regulatory readiness.
Q: How do risk-based approaches to quality translate into practical decisions when qualifying upstream bioprocessing materials?
Stanley: USP General Chapter <1043> on Ancillary Materials provides exactly that structure. It categorizes materials based on the manufacturer's intended use, what the supplier designed and labeled the product for. That intended use is a key factor in determining risk classification, alongside how you actually use the material in your process.
USP <1043> describes a tiered approach: GMP materials manufactured specifically for therapeutic drug or biologic production carry the highest built-in quality assurance. Reagent-grade materials are categorized as moderate-risk and require additional qualification if used in GMP biologic manufacturing. The practical rule: choose materials whose manufacturer's intended use aligns with your application. Attempting to "up-qualify" reagent-grade or non-GMP materials for GMP applications places the entire regulatory burden on you.
It's also worth noting that cell substrates, such as CHO host cell lines, are not the primary focus of USP <1043> and require extensive characterization under ICH Q5A and Q5D.
Q: What should teams look for when evaluating a supplier's regulatory readiness - beyond certifications on a website?
Holly: The answer depends on the type of material.
For consumable materials like culture media or transfection reagents, start by evaluating quality agreement flexibility: can the supplier accommodate your specific documentation needs and audit rights? Ask directly about their customer communication process during recalls and deviations as well as examine their track record on that front.
For a strategic, one-off purchase, like a platform host cell line that will underpin your entire cell line development program, the considerations are different. Given the criticality of that decision to your pipeline, and the fact that you'll rely on that cell line across multiple clinical programs over many years, the level of regulatory support the supplier is prepared to offer becomes a critical selection criterion. Can they help you respond to agency questions down the line? Will they still be around and invested in supporting you five or ten years from now?
Stanley: Regardless of material type, two additional layers of regulatory readiness are frequently overlooked. First, understand which GMP framework the supplier manufacture is under (pharmaceutical GMP or medical device GMP) because each has different expectations for environmental control, traceability, and documentation.
Second, verify their regulatory inspection track record. Ask directly whether they've been subject to FDA, EMA, or other agency inspections, and request the outcomes. That information gives you a far clearer picture of a supplier's quality assurance than any certification on a website.
Q: What are the key regulatory considerations when selecting and qualifying a CHO host cell line?
Holly: Track record is the most important factor. If the supplier can demonstrate that the cell line has been used to produce biopharmaceuticals, ideally multiple products, that have progressed through clinical testing and received market approval in your target geographies, that gives you strong confidence that regulators are comfortable with the available documentation.
If that track record isn't there, you need to examine the documentation thoroughly: raw material traceability throughout the cell line's development history, and a detailed account of how that development unfolded.
Beyond that, having access to starting vials from a cGMP-compliant cell bank that has already passed all relevant adventitious agents testing is a significant advantage. It reduces the risk of unexpected findings when you complete that same testing on your producer cell line banks.
From a practical standpoint, if the supplier has consolidated all of that traceability and safety documentation into a Drug Master File lodged with the US FDA, or equivalent documentation filed with regulators in other regions, that meaningfully reduces the burden on your regulatory team. Rather than incorporating all of that information directly into your own submissions, you can simply cite the DMF.
Stanley: ICH Q5A and Q5D provide the framework regulators use to evaluate cell substrate documentation. ICH Q5D covers cell line characterization, provenance, and cell bank qualification; ICH Q5A addresses viral safety and adventitious agent testing. A supplier who has packaged this documentation in line with ICH Q5A and Q5D into a DMF provides a significant regulatory asset.
Beyond the technical requirements, evaluate whether the supplier can provide regulatory support during submissions, including responding to agency questions and providing updated documentation
Q: What is the best strategy for staying ahead of regulatory changes that could impact upstream processes?
Stanley: Build regulatory intelligence into your development process from day one, not as a last-minute compliance check. That means two things: establish regulatory monitoring systems, and choose regulatory-ready partners.
On monitoring: assign someone on your team to track FDA, EMA, ICH, USP, and other relevant guidance updates. Review warning letters in your therapeutic area for early signals of inspection focus areas and participate in industry working groups. Regulatory changes rarely come out of nowhere; there are usually signals months or years in advance.
On partners: prioritize suppliers who demonstrate regulatory awareness, maintain Drug Master Files to support your submissions, and can provide regulatory support during your filing process. Teams that take this proactive approach don't get caught off guard because they've built regulatory intelligence into their processes and partnerships from the start.
Q: If you could give one piece of advice to a team building an upstream process today, what would it be?
Holly: Document everything with regulatory submissions in mind from day one, not just what you did, but why you did it, and any deviations or changes along the way. Save that documentation in a way that is easy to identify and follow. Five years from now, when regulators ask questions, you won't remember the details and you may have moved on, leaving colleagues to depend on your good practices.
The time invested in rigorous documentation today will save months of scrambling, and potentially costly delays, later.
Stanley: Choose your suppliers based on their regulatory documentation quality and support capabilities, not just technical performance and price. When you're facing a regulatory inquiry 12, 18, or 36 months from now asking for detailed documentation on raw material sourcing, manufacturing process, and quality control, your supplier's regulatory readiness becomes the difference between a 30-day response and a 6-month delay.
Prioritize regulatory readiness in your supplier selection process, and you'll future-proof your upstream workflows against the evolving expectations we've discussed.
The CHOSOURCE™ platform is available for research, clinical, diagnostic, and commercialization applications, including services, under specific licenses from Revvity.
