As many biopharma and life sciences companies have experienced a sharp increase in demand for new products and technologies in 2020–2021, our blog series “Challenges of Rapid Growth” explores common growing pains and provides helpful CQV tips.
Variables to Consider When Scaling Up
Scaling up can often come with setbacks, but with thoughtful planning around validation, these setbacks can be reduced or even eliminated. There are many areas to consider that will keep your scale-up plan running smoothly. Remember, process validation is no longer a singular finite activity; it is a continuous activity that must be managed at every part of the scale-up phase.
Planning is the foundation to responding to all potential variables in your scaling up process – a key to delivering on-time and on-budget. Without thoughtful planning in place, it’s impossible to predict which equipment or processes need to adjust to meet regulatory standards.
Our experts have four key considerations to maintain validation while scaling up your projects.
Starting with a plan is critical to determining how your scale-up will run and, ultimately, to ensuring success. A few pillars that you need to have in place during the planning process include:
- An agreed upon project plan and scope
- Comprehension of the FDA’s 2011 Process Validation: General Principles and Practices
- A regulatory filing strategy
- A ready-to-respond, cross-functional team of experts
Proper planning also allows your company to facilitate a realistic approach to how and when the scale-up needs to happen and each validation process that needs to take place.
In addition to ensuring your project starts off strong with proper planning, a team of commissioning, qualification, and validation experts will also be able to proactively predict and address potential process validation hurdles throughout your project.
2. Compliance and Regulatory Strategy
As part of the planning process, you’ll need to layout a compliance and regulatory strategy, which should include:
- Internal controls
- A way to document to prove your processes (protocols, reports, and procedures)
- Risk assessments
- Identified hold times and processing times
- Repeat studies
- Documented regulatory requirements
- A validation strategy
Having a compliance and regulatory strategy can help you plan for process validation challenges that come with increasing capacity and output, often impacting things like:
- Fill/finish batch sizes
- Compounding, mixing or homogenization capacity
- Processing times
- Bioreactor volume
- Flow rates
Documenting your compliance and regulatory strategy will show evidence of how your facility is moving from phase to phase during scale-up.
3. Facility Fit
Without a doubt, equipment is the costliest consideration when it comes to scaling up. Many things will need to be modified as you transition from small batch to commercial production, or as you ramp your commercial efforts to a larger scale.
You will certainly have to modify or bring in new equipment to meet your needs, but consider facility fit as well. Is your facility large enough to accommodate the new equipment? Are structural adjustments required? Do you also need to scale up your utilities?
Having a seamless validation process that addresses all equipment and utilities associated with sterilization, cross-contamination prevention, processing times, fill/finish, modifications, and safety can reduce rework, save time, and keep production on track.
One way to ensure your facility can better handle a scale-up is by leveraging current trends like modular pods and equipment.
4. Quality-by-Design (QbD)
Having QbD in place from the start can give you a leg up in terms of validation. This means using a process development plan, an engineering plan, and a strong data integrity process as the roadmap to your scale-up’s success.
The QbD concept is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management [ICH Q8 (R2)].
Working with a qualified partner is a great way to ensure your cGMP documentation systems and standards are compliant.
You will only be ready for scale-up if you are actively planning, recording, and documenting your work to prove validation and compliance along the way. At the end of the day, you need to have evidence for every phase of the process.