A BioPharma product may go through a scaling process multiple times during its life cycle. The product owner may decide to either select a Contract Manufacturing Organisation (CMO) to manufacture a product or manufacture in-house. The first batches manufactured in a small-scale laboratory may be scaled-up to produce larger batches for clinical trials. Following this, a further scale-up process is typically needed to progress to pilot-scale and ultimately to full-scale commercial production scale for market entry. Quantities manufactured during the early laboratory development are typically 100 to 1,000 times smaller than the amounts produced during the pilot and final production stages. It is essential that an organisation places emphasis on making optimal strategic decisions from an early stage in the scale-up process to facilitate successful product entry to the market. Here are four key considerations during the scale-up process:
1. Are you choosing the best location?
With global economic and political uncertainties, as well as ever-changing regulatory environments, it is imperative to ensure the optimal location is selected to manufacture your products on a commercial scale. Irrespective of whether products are being manufactured in-house or outsourced to a CMO, selecting a problematic manufacturing location can have a detrimental impact on an organisation. Transferring from laboratory-scale to commercial production also brings to the fore the area of logistics that may not have been previously considered in-depth. Especially with temperature-sensitive drugs and biotechnologies, the expense of transporting between manufacturing sites and from manufacturing to market could be very significant and pose extra risks to supply chain security.
2. Are you selecting the right partners?
Scaling-up to commercial production typically means new partnerships will be formed to support the manufacturing and distribution of your products. Partners may be required to support several aspects of the production, such as manufacturing, packaging, analytical testing, stability testing, transportation and/or distribution. Start by assessing whether your partners have the right expertise and capabilities to meet product requirements. You may want to prevent your partners from further outsourcing activities they cannot complete themselves as this can bring an extra layer of complexity and new challenges to market entry. If you chose to select a CMO for commercial production, have clearly defined agreements in place that outline quality, safety and efficacy expectations, as well as a transparent legal and financial breakdown. Critical quality attributes for the product should be identified and agreed upon internally before being shared with your partners. How will you communicate with your partners and ensure everyone is streamlined?
3. Is the required equipment available?
When it comes to biopharmaceutical scale-up, the ultimate goal is to mass-produce a product that is consistent in quality, safety and efficacy for supply to patients. Assessing and confirming that your processing equipment is fit-for-purpose is essential to ensuring the scale-up process is efficient and robust. The end-to-end scale-up process must be validated every time the process is scaled-up by a factor of 10 or more according to the FDA’s Scale-Up and Post-Approval Changes (SUPAC) guidelines. It is recommended that the team involved in scaling-up a new product(s) from clinical batches to full scale commercial production assess the equipment intended to be used, including line capacity, speed, size and more. Calibrated equipment that has been qualified for use will help with ensuring a smooth transition during the scaling process. If outsourcing to a CMO, will the equipment be shared with other products? If so, what impact may this have on your product? Employing equipment that excels at yielding tightly controlled particle size distributions (PSDs), regardless of batch sizes, is highly beneficial in comparison to the use of unsuitable equipment that does not truly meet product expectations and may result in quality concerns and yield loss.
4. Have you assessed ‘Robustness’ of the product, processes and systems?
During small-scale laboratory production, you may have carefully refined processes so they are efficient, repeatable and high quality. Are these processes scalable? A key consideration here is the ability of a process to demonstrate acceptable quality and performance, while tolerating variability in inputs. Before scaling up, a cross-functional team should meet to discuss formulation and process design to ensure controls are in place over the variability of parameters. Verification is needed that the defined parameters in early stage product development will stay within the determined design space post scale-up. In addition to this, proactive process monitoring and implementing continuous improvements approach can allow for robustness to be maintained following scale-up.
Operating internationally, HiTech Health supports healthcare companies from the development to the launch and supply of products. At HiTech Health, we are uniquely positioned to offer services and technologies from a multi-disciplinary team during the scale-up process. We can help you select optimal partners to maximise growth ensuring that you bring products to market successfully with security of supply. For more information about HiTech Health’s solutions, call or email us today!