Looking into the OSD Crystal Ball: Industry Experts Reflect on Opportunities & Challenges in '23 & Beyond
The Future of Quality in Manufacturing
The next decade will see pharmaceutical companies change their manufacturing ecosystems with emphasis on product quality, speed to market, efficiency, waste reduction, cost containment and skill retention to meet regulatory and consumer demands. To achieve this, companies are embarking on a digital transformation journey towards a new manufacturing strategy, a concept called Pharma 4.0., to achieve their competitive advantage.
The term Pharma 4.0 is a pharma industry interpretation of Industry 4.0—aimed at adopting innovative methods to deliver higher quality products to the market faster and more efficiently. The Pharma 4.0 concept focuses on connecting every segment of the manufacturing value chain to create new levels of transparency with real-time resolution, adaptability, speed from supply, manufacturing, laboratories, quality, distribution. The use of AI technology, data analytics, process analytical testing (PAT), not only provides real time data that quality can review immediately, but insights needed to optimize production, reduce deviations, ensure the right CAPA are implemented, improve metrics, and accelerate product release. While there has been much focus on ICH guidelines such as Quality Risk Management, (ICHQ9), Pharmaceutical Quality Systems (ICHQ10), Technical and Regulatory Considerations For Pharmaceutical Product Lifecycle (ICHQ 12), Validation 4.0, 21CFR Part 11 and Annex 11 in relation to software and data Integrity, it’s notable that these are foundational principles to the implementation of Pharma 4.0 and should not be overlooked.
To understand why there is a focus on the Pharma 4.0 concept, it is important to review the critical issues that many organizations are facing. It is not new that market changes, increased competition, increased compliance requirements, scientific innovation of complex products—such as mRNA vaccines as an example—have led to increased manufacturing complexity.
The reality within organizations is that once approval has been sought for a new product, or product change, the focus is on speed to market. The lack of robust quality processes, systems and teams connecting and aligning each part of the manufacturing environment, such as supply, manufacturing, quality, and distribution, leads to cumulative quality issues, which can snowball into equipment downtime, deviation setbacks and trends. In addition to this, the time taken for quality to review batch records, analytical data and resolve and document deviations, out-of-specification results at the end of the process doesn’t help either. Thus, organizations find themselves achieving the opposite of that which they set out to achieve and end up delaying product to market. With the focus on speed to market, many of the critical proactive quality steps are not completed thoroughly at the start of the process, by understanding:
- Risk Assessment & Mitigation (ICH Q9)
- Capabilities of the entire value stream including product/ process/equipment/software/connected systems. Reference Validation 4.0
- Continuous improvement strategies to enhance the entire value stream. Reference ICH Q10 and ICH Q12
- Individual and team strengths across the value stream. Retain, train and re-train
Risk assessment of each part of the process from supply of ingredients to distribution of final drug product is critical to identify effective mitigation steps should issues or deviations occur. Similarly, knowledge of process/product/equipment capabilities supports good root cause identification and critical quality attributes support risk-based decision making.
Skill competency within the manufacturing environment also warrants consideration. The onboarding, training, and retention of highly skilled personnel in manufacturing should not be taken lightly. While there are many academic courses available in the quality and regulatory field, the same opportunity is not available in the manufacturing/operational fields. Experience is usually earned after years working in manufacturing with knowledge lost once key personnel leave the organization.
The concept of moving from a reactivate approach to quality to a proactive approach to quality and compliance is a key takeaway from the Pharma 4.0 concept. The ability to use data for predictive and proactive purposes will be a must-have for the Quality/Manufacturing teams of the future. This concept will support an organization aligned, connected, motivated with one common goal and that is to provide a safe, quality product, fit for intended use and on time to the customer.
Siobhan Ashmore, VP of Quality & Regulatory, Life Science Solutions LLC
More Automation in Testing
The pharmaceutical industry is constantly evolving and seeking new ways to improve the efficiency and accuracy of its testing processes. One area in which automation has become increasingly important is in the testing of drugs and other pharmaceutical products. Automation can help reduce the risk of errors, increase the speed of testing, and improve the overall reliability of results.
The growing complexity of testing procedures is one driver behind robust automation in the pharmaceutical testing space. As the science behind drug development becomes more advanced, the testing protocols used to evaluate the safety and efficacy of new products become increasingly complex as well. Automation can help streamline these processes, allowing faster testing, with fewer errors.
The need for reliable results in the pharmaceutical testing space also contributed to automation’s expansion. In the pharmaceutical industry, even small errors or variations in testing results can have significant consequences. Automation helps ensure that results are consistent and accurate, reducing the risk of errors and improving the overall reliability of testing processes. By automating testing procedures, pharmaceutical companies can also reduce the time and resources needed to complete these tasks, freeing up staff to focus on other important areas of the business.
Kevin Whitkanack Senior Director, Pharma Services, Product Development and Marketing, Sotax
Customization is Coming
A shift from “one-size-fits-most” to personalized products (especially in health and wellness) is an opportunity for businesses to provide more custom experiences. However, doing so without increasing cost or complexity can be a challenge.
“One-size-fits-most” has been the guiding principle in medicine, health, and wellness since penicillin was first discovered. The model is based on finding a treatment that brings sick people back to homeostasis more often than not, and it has worked quite well. We’ve eradicated many diseases, extended lifespan and reduced death sentences to mere annoyances. While “one-size-fits-most” has been a boon to humans everywhere, a new trend has emerged, that not only helps bring sick people back up to baseline, but helps healthy people push past normalcy to optimize a healthier longer lifespan we never knew was possible.
The ability to personalize products is the result of a confluence of technologies. First, e-commerce made it possible for consumers to shop for anything they desired with ease. Next, robotic advances increased the ability for manufacturers to delay the differentiation of products until just before shipping—making it possible to create slight variations on common products. We must now take that knowledge and technology and apply it where it makes the most sense—healthcare. Consumers don’t just go to a doctor for generalized treatment, but seek out personalized care that optimize their overall wellness. We have the capability to create more personalization through data from blood work, physical exams, and family history. With the availability of new technologies, it’s become easy to personalize wellness treatments at scale. It’s now easy to do this kind of personalization at scale at home without the need for a doctor for the basic things.
By customizing the product, consumers get the maximum benefit to their overall health and well-being. In the future, emerging technology will further aid in healthcare personalization.
Dr. Andrew Brandeis OK Capsule
A Renewed Emphasis on Sustainability Strategies
2023 will continue to pave the way towards sustainable manufacturing, with a growing number of organizations placing focus on creating long-term solutions.
Now is the time for new manufacturing sites to adopt and implement new technologies; to transform pharma manufacturing from being reliant on costly legacy processes. Digital technology will speed up processes by enabling early detection of wear and tear on machinery lines. It will also help to reduce wastage and recalls by effectively tracking defective batches, allowing for timely interventions.
Placing digital ‘Industry 4.0’ technologies – such as AI, machine learning, IoT, Augmented and Virtual Reality – at the heart of manufacturing can further improve R&D and speed up testing, compliance and efficiency. Adopting Industry 4.0 technology and new delivery models can help to build a more self-reliant and robust pharmaceutical supply chain to keep up with changing and increasingly complex healthcare needs. Our focus is on creating high-performing and quality-driven manufacturing units that can support smart, connected, and intelligent systems. Reams of data converts into actionable intelligence, improving several supply chain aspects such as inventory management, trend analysis, forecasting and predictive equipment maintenance.
The growth of digital health technology and telemedicine will continue to drive healthcare innovations in 2023. Developments such as medical device integrations and software monitoring will be centered around at-home and remote diagnosis, ultimately aimed at improving clinical outcomes and pre- and post-consultation care for more ‘informed’ patients.
Karan Singh Managing Director ACG
Persistent Multiple Cost Pressures
2023 may prove to be one of the more difficult years to predict and forecast. Cellulosic and other excipient capacities remain extremely tight, backed by strong manufacturing demand. This may ease somewhat in 2024 as more capacity comes on line from several global producers, but we expect inflationary pressure to persist. Producers are focusing on high volume, baseline products as a way of both satisfying customer core demand and keeping cost containment. By focusing on the most widely used products, gains are made in operational efficiency to produce at maximum levels. With fewer changeovers to low demand and low-yield specialty products, cost efficiency can be maximized.
This means availability can be addressed at the best cost, but transfers the cost and availability pressure to those specialty and lower-demand products. Manufacturers will face challenges sourcing these specialty grades with limited availability, and thus a higher cost.
There is still a lot of cost pressures in the marketplace. Like the ingredient manufacturers, raw material suppliers are approaching manufacturing efficiencies in the same manner – focus on core product in order to maximize output and minimize cost. We are seeing farmers focus on large-volume products like corn, soybean, etc., and less on specialty products, like cotton and sunflower, where they can’t achieve the same level of efficiency per acre. This compounds the availability problem for low volume, specialty products whether it is for the commodity itself, or any specialized versions like non-GMO or organically certified stock.
Along with raw materials, cost pressures still persist across the board. New taxes levied in 2023 on energy will have a big impact in our markets. Logistics issues may have waned in the short term, but diesel prices remain high and have not come down at the same rate as gasoline. Equipment and labor shortages persist and will likely remain in tight supply as states like California reduce the number of old trucks on the road. If recessionary fears manifest to reality, logistics may be one of the few places where demand may drop and cost benefits can be achieved.
If consumers face decisions with discretionary income, transportation may soften due to reduced overall demand, but basic needs like food, medicine, housing and fuel will likely remain constant.
Inflationary pressures will push labor costs up as employees require higher salaries to offset cost increases. The Superfund Chemical Excise Tax re-implemented in mid-2022 will have an enormous impact on processing chemicals. As a result, many basic chemicals used as processing aids doubled, or more, in cost. Labor, oil, and raw materials will also have an impact on packaging so we see cost pressure across the entire supply chain from raw materials, labor, processing, and final packaging.
In the end, with mid-term production capacities fixed, we expect high demand and limited availability. While we may get some short-term relief in logistics, inflationary pressures will continue across all sectors of the supply chain. Core products may see some stabilization, but specialty grades and niche products face limited availability and higher prices.
Ken Seufert President JRS Pharma
Better Tool Management
One of the biggest challenges in tablet manufacture continues to be the pressure on time to get a product to market and reducing costs. At I Holland, we are continually working on innovative solutions to help drive the demand for tablet manufacture. An area where we have seen significant growth, and a trend that we predict will continue to grow, is computer-based Tool Management Systems.
Modern tablet production requires increased capacity, flexibility, rapid response and robust traceability, with the core objective of maximized press uptime. What was once monitored through simple manual methods is not enough in the current culture of high volume, tightly controlled and audited tablet production. To successfully produce tablets, manufacturers must undertake an in-depth analysis of production.
Computer-based monitoring systems can help maximize productivity per punch to meet high-capacity manufacturing requirements. Put simply, a tool management system is a register of all tooling within a site or organization. It fundamentally automates the visibility of what is happening with the tools. Its main objective is to establish compliant, efficient, and accurate maintenance of punches and dies and ensure that the tooling is never a cause for delay in the production schedule.
Within tablet production, it is crucial to have a complete audit trail covering tablet tooling usage and maintenance. Using software that has the capability to track this not only makes sense when it comes to production monitoring and management, but is also an essential regulatory requirement within the pharmaceutical industry.
The data can also provide information to effectively measure performance areas by showing what and how many products have been produced and a summary of any production issues experienced.
By implementing an advanced TMS, problems like wear to punch heads and tips can be detected before they impact production. It can also prompt a call to action highlighting when specific punch and die maintenance actions are required.
Implementing a tool management system is invaluable and will always lead to better results. It enables manufacturers to effectively manage their tooling to produce high-quality tablets in an ordered, auditable, and traceable way. Successful tablet production requires forward thinking. Without investment in innovative solutions like TMS, tablet manufacturers are at risk of stalling company growth.
Andy Dumelow Head of Technical Sales I Holland
Materials-Sparing Formulations Will See Higher Uptake
Materials-sparing formulation development approaches enabled by compaction simulation will be widely adopted. This trend is driven by at least two factors:
- The need for developing a tablet formulation early so that Phase 2 studies can use the intended market dosage fo;
- Wider availability of compaction simulators that can simulate both die compaction and roller compaction.
Rich information on the properties and performance of API and blends can be collected using grams of material on a compaction simulation. Punch sticking, air entrapment, speed effect, tooling design, and other process parameters can be studied to optimize formulation and manufacturing process so that they are amenable for commercial manufacturing. Companies without a compaction simulator can use resources available from universities and CROs with demonstrated expertise.
Dr. Calvin Sun, Professor and Associate Department Head, Department of Pharmaceutics, University of Minnesota