Five-Point Checklist for Pharmaceutical Scale-Up

Posted by David Watt and Norm Fong

Scale-Up Blog Series, Part 3

[Editor’s note: Scale-up is an inevitable part of the product life cycle of every successful drug, and each time it is required, a meticulous process must be followed to ensure that the end result is identical to the product formulation as originally devised. This is part 3 of an in-depth, multi-part series on product scale-up. Visit our blog page to read parts 1 and 2.]

A successful drug product may go through a scaling process several times during its life cycle. The laboratory-scale batches used in clinical trials that expand to pilot-scale and finally to commercial-scale production may be just one iteration in a product’s evolution. Popular products may also expand production to other facilities or even other countries. Conversely, when demand inevitably begins to shrink, a similar process will be used in scaling down production to appropriate levels.

As the owner of a drug, you’ll want to carefully plan each of your technology transfer and scale-up events with your contract manufacturing organization (CMO). Here’s a checklist of the key considerations:

1. The Right People

Start by ensuring the CMO tech transfer team has the right experience and expertise in the technology you are transferring. You’ll need to be able to define the target product profile as it relates to quality, safety and efficacy, as well as the route of administration, dosage form, bioavailability, dosage and stability. The team will also need to identify critical quality attributes to be tracked during the scale-up process — including attributes of the drug substance and excipients — and select an appropriate manufacturing process. Requesting the CVs of the CMO team members may help determine if they are the right fit.

Assuring-Pharmaceutical-Technology-Transfer-Success-eBook2. The Right Equipment

The CMO scale-up team should prepare a SUPAC (Scale-Up and Post-Approval Changes) comparison of the scale-up process, comparing the donor site equipment train, process and parameters with those of the objective volume of production. To scale effectively, you’ll need equipment with directly comparable capabilities. In practical terms, this means that if your process utilized a particular brand of a high-shear mixer granulator for development work, it’s advisable to use the same brand for the scaled-up granulation process. The SUPAC report should demonstrate that all the pertinent equipment is within the scale for commercial viability.

3. The Right Systems

From a regulatory standpoint, the scale-up process is carefully defined. Before manufacturing registration batches, the CMO should challenge and optimize the existing manufacturing process by making additional development batches at laboratory-scale, pilot-scale and possibly even at production-scale. This effort provides the basis for justification that scale-up can be achieved without a consequential loss in quality and provides the link between formulation and process development, pilot-scale manufacture and eventual commercial production. The CMO should have the proper quality and regulatory systems and personnel in place to ensure compliance throughout the process.

4. The Right Price

Sometimes initial quotes are missing key information. As part of the scale-up process, pharmaceutical and biotech companies should ensure that all costs are shown up front and that there are no hidden expenses that may lead to scope creep and extra charges.

5. The Right Location

One aspect of moving from laboratory-scale to commercial production that is often overlooked is logistics. Especially with temperature-sensitive drugs and biologics that must utilize a cold chain, the expense of moving a drug from manufacturing to market is one that must be considered.

Conclusion

Strategies for product development, including scale-up and scale-down, can vary from company to company and from product to product. You’ll need to choose a flexible, experienced CMO whose capabilities match your manufacturing, packaging and distribution needs, striving to control timelines and costs throughout the product life cycle.

Learn how we applied this checklist to prepare products for commercial-scale production.

Read Our Case Study >>

Topics: CMO Partner, excipients, scale-up, Process Development, SUPAC, Registration Batch

David Watt is the Technical Director in the Business Development Department at WellSpring, and has over twenty years of pharmaceutical GMP experience in technical definition and evaluation of Contract Development and Manufacturing projects, both from provider and client perspectives. David has previously worked at Valeant, Medicis, Patheon and Syntex Pharmaceuticals. David is responsible for overseeing all technology transfer activities in the organization.

Norm Fong is the technical transfer manager, business development, for WellSpring. He has over 21 years in the pharmaceutical manufacturing industry and has held development, transfer and commercial manufacturing positions over the course of his career with Patheon, Global Pharm (formally Pharmacia Upjohn) and Genpharm (owned by Merck). Norm is responsible for overseeing technology transfer and all validation activities in the organization.

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