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PharmTech.com Trends in Formulation 2022 eBook Pharmaceutical Technology ® 53 Qualit y consider innovative approaches, for example in spray drying, compounding, granulation, or formulation." Anticipating upcoming trends Anderson has seen a lot of trends in facility design come in and out of focus. "Ten to 15 years ago, we used to strip out existing facilities and put in new ones be- cause of cross contamination issues, but we're not see- ing that anymore. Instead, even Big Pharma is keeping equipment, carrying out deep cleans, and testing to ensure that there is no trace of possible contaminants, and revamping manufacturing lines. The envelope will change, or the machines might be upgraded, and new packaging lines might be introduced, but they are still able to achieve cost savings by maintaining the same facility. Historically, manufacturers have tended to favor large-scale batch production, and some of our customers choose to maintain this approach. Other manufacturers are switching to smaller batch sizes in higher value products in order to improve the qual- ity of products and speed up the process times. The market is very diverse, and we get different messages depending which customer we talk to." Looking at a more global perspective, he continues, "In terms of regulations, [Europe's] Annex 1 tells us if we need to do anything different as designers. Some fill areas are under Grade A with Grade D background, and we're now seeing Grade A with Grade C back- ground. Open filling is done in Grade A with Grade B background. This shows that some of the classifica- tions and cleanliness regulations are improving, de- pending on whether or not your process involves open filling, the type of packaging line, and whether it's a tablet or an oral dose." Future proofing design Ali Rajabi-Siahboomi, vice president and chief innova- tion officer from Colorcon outlines a few major trends to be aware of, saying that "new drugs coming to solid dosage formulations are more potent and have chemi- cal sensitivities that require careful handling to ensure safety and overcome the risk of exposure as well as pro- tect from environmental conditions such as moisture, oxygen, and temperature controls. An example is the development and manufacturing of macromolecules for oral drug delivery which require more complex and tightly monitored facilities to ensure safety and quality of the finished product." This thread is somewhat picked up and expanded upon by Anderson, who continues, "From an HVAC and containment, airlocks, fire and safety standpoint— everything must be considered in terms of the rising demand for certain types of solid oral dosage manu- facturing modalities." Dave Di Prospero, associate director, Pharmaceuti- cal Process Technology at CRB Consulting Engineers emphasizes that, "use of airlocks, both material and/ or personnel, in concert with HVAC pressurization schemes, provides for the greatest f lexibility when looking to future proof an oral solid dosage (OSD) man- ufacturing operation. Especially when considering high potent compounds. Airlocks, used as a transition between different space classifications (e.g., Controlled not classified [CNC] to Grade D) is a longtime practice that is well accepted by nearly all international regula- tory agencies. This facility design configuration offers contained and controlled operations and is often the standard for multi-product facilities." Anderson agrees and stipulates that, for "heating, ventilation, and air conditioning (HVAC) designers, the main challenge is containment of powder, as it may be toxic or potentially explosive. Cross contamination is also an issue, and this can be reduced with air handling unit AHU zoning. Humidity control is expensive but a must when dealing with gel products, and new heat recovery systems can help to reduce the high running costs. Ref lecting further on a somber tone." He adds, "In the case of powders, liquids, and any gaseous vapor, it is vital that the substance is contained within the room, to protect both the product and the environment around it. With the clever use of bubbles and sinks, and negative pressure regimes we can minimize the risks while maintaining CGMP [current good manufactur- ing practice] requirements. An analogy is if you have a birthday cake, no matter how hard you try, you can't suck the candles out. Similarly, the way to control pow- ders is to push and pull, so you push by blowing and you pull in the right direction, and it's this push-pull approach that helps achieve containment. Due to the risk of explosion, some products require ATEX (explo- sive)-rated areas in case the ventilation system fails to contain the product. Fire is another potential hazard, and specified fire protection can be achieved through the use of suspended ceilings constructed from white- faced mineral fiber fissured tiles in a lay-in grid, galva- nized-finish column casings, and protective fascias." Picking the right formulation under expedited commercial timelines On this score, Di Prospero, with many years of first- hand knowledge, urges anyone to keep it as simple as possible. He states clearly, "whenever possible, direct compression formulations remain the easiest and quickest processing platform for getting new prod- ucts to market. Direct compression requires the fewest number of unit operations and is the least complex of the typical OSD processing platforms. Ingredients are weigh/dispensed, blended, and compressed. Depend- ing upon the powder properties tablet coating may or may not be needed," he concludes. Rajabi-Siahboomi singles out a need for speed, say- ing "there is more and more emphasis to expedite new