Though technology and research have greatly improved the development process and contract research organization (CRO) and contract development manufacturing organization (CDMO) partners are proving valuable to speed development and production, there is little the industry itself can do to decrease approval times; that means manufacturing improvements and innovations that maintain or improve quality will be crucial to decreasing time to market and remaining competitive while meeting new regulations.
With the continued growth of emerging markets and a rapidly expanding middle class with greater access to treatment and medication options, the global demand for pharmaceuticals continues to grow with the demands and regulations placed on manufacturers following suit. By 2020, global access to medications will be higher than ever, with patients receiving an estimated 4.5 trillion doses, an increase of 24% from 2015.1 With that, spending growth—predicted to increase by 29-32% to $1.4 trillion by 2020, slightly slower than the 35.4% increase from the previous five years—will also continue but is expected to be checked in part by an estimated $90 billion in price reductions, further highlighting the importance of process improvements in manufacturing that could allow for these price reductions without significant profit loses.1
Poised to make great strides
Though packaging, especially secondary packaging, may in the past have been more of an afterthought than a priority, contract services providers have positioned themselves as innovators in this space and are making great strides advancing packaging processes, specifically integrating packaging automation technology that can help companies manage production costs and ultimately, drug pricing.
CDMOs are actively being engaged by pharmaceutical and biopharmaceutical manufacturers for every phase of development; however, outsourcing for packaging specifically is also significant on its own.2 The 2015 Nice Insight Pharmaceutical and Biotechnology Outsourcing Survey found that respondents believed labeling and packaging processes would benefit from technological innovation while 40% of respondents were interested in partnering with a CRO/CDMO that is using technological innovations.3
One year later, The 2016 Nice Insight CDMO Outsourcing Survey revealed that commercial-scale and clinical scale primary packaging services were outsourced by over half of all respondents while labeling and packaging design/development services were outsourced to 48% and 45% of respondents, respectively.2 These numbers become even more pronounced in certain categories with, for example, 78% of emerging pharma/biotech respondents outsourcing clinical scale primary packaging.2
To meet evolving packaging needs, manufacturers find themselves faced with the decision to either expand facilities and operations by increasing resources and upgrading/purchasing equipment or outsource packaging to a CDMO that may already have the necessary expertise and facility arrangements. For many companies, preparing to keep pace with demands, meet all upcoming sterilization and labeling requirements, react to requests from within the retail and healthcare industries and maintain aseptic processing needs can be daunting.4 The cost of upgrades, space limitations in established facilities, and the need to hire and train additional staff is often perceived as a potential barrier that makes CDMO engagement appealing.
Though CDMOs may also face similar challenges in the changing global market, these organizations may be better positioned to adapt and respond to these needs, allowing pharmaceutical/biopharmaceutical companies to focus on drug innovations rather than packaging logistics. Additionally, advancements in packaging to accommodate single doses and the unique needs of biopharmaceuticals have already encouraged many CDMOs to remain at the forefront of changes in this space. With 75% of survey respondents expecting outsourcing expenditures as a whole to rise over the next five years it’s likely that packaging outsourcing will account for some of that increase as regulations continue to develop and manufacturers prepare for the requirements under the Drug Supply Chain Security Act (DSCSA) to gradually take full effect.2
The potential of automation and emerging technologies
The use of automation equipment for both primary and secondary packaging can help manufactures save time, simplify or eliminate training, ensure aseptic manufacturing throughout the entire process, and minimize errors. In the 2015 Nice Insight Equipment Survey, 54% of respondents reported spending $100 million or more annually on equipment with 86% of respondents using packaging equipment and services and 80% using automation equipment and services.5 In an effort to encourage and support the adoption of emerging manufacturing technologies, including packaging and labeling operations, by pharmaceutical manufacturers, the Center for Drug Evaluation and Research (CDER) is developing a program supported by the Emerging Technology Team (ETT), a special team comprised of members from various offices including the Office of Pharmaceutical Quality.6,7 This program is intended to help decrease the risk assumed by pharmaceutical companies looking to adopt new technologies by allowing them to submit proposals regarding the use of specific equipment.6
With 65% of drug shortages caused by manufacturing and quality issues, implementing emerging technology and modernizing pharmaceutical manufacturing can assure drug supply and improve patient safety.7 More specifically, some automation experts believe that robotics may become critical for manufacturers looking to reduce costs and guarantee consistent quality.4 Manufacturers may be hesitant to pursue emerging technology due to perceived high costs and the assumption of complex operations or programing requirements. They may also face more broader concerns regarding delayed approvals because regulators aren’t familiar with new technologies and are unsure how and if they fit into new and existing regulations.4,6 Under the CDER’s new program, the ETT will work with pharmaceutical manufacturers on the submission of their proposals while also helping to identify and facilitate the regulatory review of new manufacturing technology, serving as the lead or co-lead during quality assessments.6
Despite concerns, robotic systems—typically having four or more axes of motion—can be especially useful for packaging due to their flexibility and efficiency, but pharmaceutical manufacturers need to fully understand their sterility requirements with a specific focus on the effecter, or the robot’s gripping mechanism.4 Once in place, these systems can accomplish successive tasks for both primary and secondary packaging (blister packs, boxing, pallet loading, etc.) while also handling multiple packaging configurations on one line (e.g., 60-count and 300-count containers).4 This flexibility is increasingly important as some larger retail outlets demand different packaging with smaller counts to reduce handling errors within pharmacies.4 Fortunately, with robotic systems these changes are often as easy as simply reprogramming rather than adding staff or modifying training, offering a manufacturing cost savings. To further simplify the process, many systems are able to connect to larger IOT networks, allowing for easy access to programing tutorials and streamlined system programming in multiple locations.
Multi-purpose packaging challenges
Primary packaging must maintain product purity, help ensure the sterility of every dose and deliver each dose in a way that’s convenient for both patients and caregivers. Secondary packaging must be shippable, easy to handle and stock and, in the case of OTC medications, stand out on retail shelves. Achieving a balance between the two can be challenging. Accurate labeling, properly measured doses, and easy-to-handle packaging are patient-centric solutions that the industry is already embracing, but traceability requirements that are expanding under the Drug Supply Chain Security Act (DSCSA), Title II of the Drug Quality and Security Act of 2013 (DQSA), are adding an additional layer of patient protection and forcing manufacturers to change and enhance packing processes.8,9
The current, sustained interest in biologics and the potential surge in biosimilars are already helping fuel packaging advancements. But, improving traceability at the package level will require additional design considerations, production procedures and either staff training or the use of automated/robotic systems to ensure that barcodes can be scanned, matched, and packed properly. By 2023, 10 years after the DQSA was signed into law, verification of drug legitimacy, detection and notification of illegitimate products, and the facilitation of product recalls as necessary will all be possible at the package level.9 These requirements are designed to protect patients from unsafe products while protecting manufacturers from illegitimate competition and allowing them to easily notify necessary agencies if issues arise.
All upcoming regulations are intended to improve quality and safety in the market and therefore it will become increasingly critical for manufactures to ensure that all processes, down to sealing and packing the last box or container are as efficient and effective as possible. As robotics continue to improve, the technology will offer round-the-clock manufacturing options, packaging flexibility and more advanced capabilities than ever before, allowing pharmaceutical companies to improve in-house capabilities while CDMOs can further enhance their offerings to become even more attractive industry partners.
- Global Medicines Use in 2020: Outlook and Implications, IMS Institute for Healthcare Informatics, November, 2015 http://www.imshealth.com/en/thought-leadership/ims-institute/reports/global-medicines-use-in-2020
- The 2016 Nice Insight CDMO Outsourcing Survey. January 2016 http://www.niceinsight.com
- The 2015 Nice Insight Pharmaceutical and Biotechnology Outsourcing Survey. January 2015 http://www.niceinsight.com
- Rios, M., Greb, E., “Robots: The Next Phase in Pharmaceutical Automation.” pharmatech.com, September, 2009 http://www.pharmtech.com/robots-next-phase-pharmaceutical-automation-0?id=&sk=&date=&pageID=2
- The 2015 Nice Insight Equipment Survey. January 2015 http://www.niceinsight.com
- “Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base Guidance for Industry.” U.S. Department of Health and Human Services, December, 2015 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM478821.pdf
- Kopcha, M., “Modernizing Pharmaceutical Manufacturing to Improve Drug Quality: Ensuring a Safe and Adequate Supply of Drugs.” FDA Voice, February, 2016 http://blogs.fda.gov/fdavoice/index.php/tag/fdas-emerging-technology-team-ett/
- Haehl, K., “Choosing the Optimal Drug Delivery System to Meet Patient Needs.” Pharma’s Almanac, 2015 http://www.niceinsightcdmo.com/articles.aspx?post=2772&title=Choosing+the+Optimal+Drug+Delivery+System+to+Meet+Patient+Needs+
- “Drug Supply Chain Security Act (DSCSA): Title II of the Drug Quality and Security Act of 2013.” U.S. Department of Health and Human Services, February, 2016 http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSecurity/DrugSupplyChainSecurityAct/
To learn more about Nice Insight contact Emilie Branch, scientific research manager, at firstname.lastname@example.org or visit www.niceinsight.com.