[et_pb_section fb_built=”1″ admin_label=”section” _builder_version=”4.16″ global_colors_info=”{}” theme_builder_area=”post_content”][et_pb_row _builder_version=”4.27.4″ _module_preset=”default” custom_padding=”2em||0px||false|false” global_colors_info=”{}” theme_builder_area=”post_content”][et_pb_column type=”4_4″ _builder_version=”4.27.4″ _module_preset=”default” global_colors_info=”{}” theme_builder_area=”post_content”][et_pb_post_title meta=”off” featured_image=”off” _builder_version=”4.27.4″ _module_preset=”default” global_colors_info=”{}” theme_builder_area=”post_content”][\/et_pb_post_title][et_pb_post_title title=”off” meta=”off” _builder_version=”4.27.5″ _module_preset=”default” custom_margin=”1.5rem||||false|false” custom_padding=”||||false|false” hover_enabled=”0″ custom_css_free_form=”selector img {|| object-fit: cover;||}” global_colors_info=”{}” theme_builder_area=”post_content” sticky_enabled=”0″ module_id=”article-hero-image”][\/et_pb_post_title][et_pb_divider color=”#2A3B47″ divider_weight=”2.5px” _builder_version=”4.27.4″ _module_preset=”default” height=”0px” custom_margin=”3rem||3rem||true|false” global_colors_info=”{}” theme_builder_area=”post_content”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.27.4″ _module_preset=”default” custom_padding=”0px||0px||true|false” global_colors_info=”{}” theme_builder_area=”post_content”][et_pb_column type=”4_4″ _builder_version=”4.27.4″ _module_preset=”default” global_colors_info=”{}” theme_builder_area=”post_content”][et_pb_heading title=”Hybrid facilities provide necessary flexibility to biologics manufacturing” _builder_version=”4.27.4″ _module_preset=”default” title_level=”h3″ global_colors_info=”{}” theme_builder_area=”post_content”][\/et_pb_heading][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” custom_margin=”||2rem||false|false” global_colors_info=”{}” theme_builder_area=”post_content”]<\/p>\n
We\u2019ve compared advantages for single\u2011use plastic and multi\u2011use stainless steel bioreactors over a series of blogs. Here, we\u2019ll look at use cases for both single\u2011use and multi\u2011use skids in biologics manufacturing and discuss how they can be used cooperatively in hybrid facilities.<\/p>\n
[\/et_pb_text][et_pb_heading title=”What is a hybrid facility?” _builder_version=”4.27.4″ _module_preset=”default” title_level=”h3″ global_colors_info=”{}” theme_builder_area=”post_content”][\/et_pb_heading][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” custom_margin=”||2rem||false|false” global_colors_info=”{}” theme_builder_area=”post_content”]<\/p>\n
A hybrid facility uses a combination of single- and multi\u2011use skids to produce drugs, whether large\u2011molecule biologics or small\u2011molecule APIs. While nearly every facility uses at least some disposable components, not even state\u2011of\u2011the\u2011art manufacturing technology can use 100% disposables (especially when operating at scale). In reality, almost every manufacturing site is a hybrid facility, whether scale\u2011up, clinical, or commercial.<\/p>\n
[\/et_pb_text][et_pb_heading title=”Advantages of single- and multi-use skids for biologics manufacturing” _builder_version=”4.27.4″ _module_preset=”default” title_level=”h3″ global_colors_info=”{}” theme_builder_area=”post_content”][\/et_pb_heading][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” global_colors_info=”{}” theme_builder_area=”post_content”]Single\u2011use advantages<\/p>\n
[\/et_pb_text][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” custom_margin=”||2rem||false|false” global_colors_info=”{}” theme_builder_area=”post_content”]<\/p>\n
Multi\u2011use advantages<\/p>\n
[\/et_pb_text][et_pb_heading title=”Complementary, not competing” _builder_version=”4.27.4″ _module_preset=”default” title_level=”h3″ global_colors_info=”{}” theme_builder_area=”post_content”][\/et_pb_heading][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” custom_margin=”||2rem||false|false” global_colors_info=”{}” theme_builder_area=”post_content”]<\/p>\n
Single\u2011use skids achieve higher yields than multi\u2011use skids in equivalent volumes, but they are primarily available for small bioreactor volumes and have capacity limitations. Stainless steel bioreactors can often be used in cases where single\u2011use skids are limited, such as for large batch sizes.<\/p>\n
The optimal mix of stainless steel and single\u2011use skids and components will depend on whether the facility is used for scaling, clinical, or commercial production. Both the batch size and the lifecycle costs will vary based on the setting.<\/p>\n
[\/et_pb_text][et_pb_heading title=”Contract manufacturers have a different set of priorities” _builder_version=”4.27.4″ _module_preset=”default” title_level=”h3″ global_colors_info=”{}” theme_builder_area=”post_content”][\/et_pb_heading][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” custom_margin=”||2rem||false|false” global_colors_info=”{}” theme_builder_area=”post_content”]<\/p>\n
The considerations of an engineer at a contract manufacturer are entirely different than those of an in\u2011house manufacturer at a pharma company \u2014 regardless of the scale of operation.<\/p>\n
The key reason is that contract manufacturers<\/a> require a higher level of flexibility at their facilities than traditional pharmaceutical setups. Whereas pharma companies tend to be dedicated to a single drug, a contract manufacturer must be ready for rapid changeovers between campaigns. (As a side note, it will be interesting to watch if this changes over the next several years for pharma companies moving from solely focusing on blockbuster drugs to developing orphan drugs, genetic therapies, and other treatments requiring only small batch sizes).<\/p>\n This is likely why CMOs were early adopters of single\u2011use bioprocessing technologies: they were able to increase batch success and minimize contamination risk, while also achieving savings to the bottom line from reduced cleaning requirements. Further, this meant fewer processes to be validated.<\/p>\n [\/et_pb_text][et_pb_heading title=”Designing a hybrid facility” _builder_version=”4.27.4″ _module_preset=”default” title_level=”h3″ global_colors_info=”{}” theme_builder_area=”post_content”][\/et_pb_heading][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” custom_margin=”||2rem||false|false” global_colors_info=”{}” theme_builder_area=”post_content”]<\/p>\n Optimal facility layout and automation strategies are specific to the types of equipment used. A\u00a0roundtable<\/a>\u00a0published in American Pharmaceutical Review strongly recommends first choosing the production volumes necessary for each manufacturing step, and then moving on to determine the optimal solution for each skid or piece of equipment. Footprint constraints, connectivity, and specific skid preferences all play a role in determining the best solution.<\/p>\n Example considerations for a hybrid approach<\/p>\n [\/et_pb_text][et_pb_heading title=”Switching to hybrid” _builder_version=”4.27.4″ _module_preset=”default” title_level=”h3″ global_colors_info=”{}” theme_builder_area=”post_content”][\/et_pb_heading][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” custom_margin=”||2rem||false|false” global_colors_info=”{}” theme_builder_area=”post_content”]<\/p>\n There is no standardized method for integrating single\u2011use and stainless steel into the same facility. That being said, if moving toward a hybrid solution seems advantageous, there are certain skids which may be easier to transition away from stainless steel.<\/p>\n Media mixing and buffer prep equipment is generally simple to transition from stainless steel to plastic, single use. The single\u2011use equipment mirrors the reusable equipment fairly closely and can therefore drop into existing setups relatively easily. The frequent changeovers required by these skids also mean that switching to single use increases uptime and availability by eliminating cleaning steps.<\/p>\n Bioreactors are also fairly simple to transition between stainless steel and plastic. Most early challenges with single\u2011use control systems have been overcome, and single\u2011use systems provide flexibility to move toward perfusion setups and continuous manufacturing that steel cannot achieve. And, as discussed earlier, it is not uncommon for a single\u2011use seed reactor to feed a stainless steel production reactor.<\/p>\n As the biologics and overall pharmaceutical industry has begun operating by the principles of quality by design and are thinking about validation<\/a> early on, hybrid facilities are proving to be quite advantageous. Hybrid setups allow for a mix of customization, flexibility, and off\u2011the\u2011shelf validation, while balancing lifetime costs, quality, and availability to your biologics manufacturing process.<\/p>\n [\/et_pb_text][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” text_font=”|700|||||||” custom_margin=”||2rem||false|false” global_colors_info=”{}” theme_builder_area=”post_content”]Learn more: How do you know when it\u2019s time to switch to single\u2011use? \n