Process Optimization

Introduction

While the United States continues to vaccinate and protect its citizens from Covid-19, new variants of the disease continue to pop up around the world. In addition to costing millions of lives (Google states nearly 3.3 million in 220 countries and territories worldwide as of May 7, 2021, which includes 579,000 in the US alone), problems caused by the disease are wreaking havoc with the pharmaceutical supply chain.

Among the short-term effects cited in a July 3, 2020 article on Springer are:

• Demand changes leading to shortages caused by panic-buying oral home-care medications.
• Supply shortages of active pharmaceutical ingredients (APIs) and finished products, especially those coming from China and India.
• Shifting communications and promotions to telecommunication and tele-health, such as 70 – 80 percent drop in visits to physician offices and clinics.
• Changes in the focus of research and development programs to dealing with Covid-19.

Long-term effects on the pharmaceutical industry cited in the Springer article include:

• Delayed approvals for non-Covid-related pharmaceutical product, partly caused by the closure or semi-closure of regulatory agencies.
• Self-sufficiency and lower demand for APIs and finished products made in China and India caused by individual countries and organizations such as the European Union looking at the health needs of its citizens.
• Slowed growth resulting from economic slow-downs in economies around the globe.
• Ethical issues caused by poorly researched clinical therapies.
• Consumption changes of health products by consumers.

By the Numbers

• A 2-fold increase in investigational treatments in the U.S.
• 100% – 700% increase in the use of medicines to treat Covid-19 in U.S. hospitals (January-July 2020).
• 7 million excess prescriptions for hypertension, 6 million for mental health, 5 million for respiratory problems, 4 million for diabetes and 2 million for anxiety in the U.S. alone.
• 156 clinical trials for Covid-19 in the Middle East and 140 in the EU.
• 70%-80% reduction in patient visits to doctors’ offices in the EU.
• 23% of patient interactions in the EU are done online.

Supply Chain Effects

Deloitte produced its “Covid-19 Response for Pharma companies: Respond. Recover. Thrive” report. Among the report’s sections is a look at Supply Chain Management.

Key risks in procurement cited by Deloitte are:

• Quality checks of received materials. Mitigation measures include increasing warehouse space for quarantining shipments from China.
• Shortages of raw materials, APIs and solvents due to dependency, inadequate materials to complete BOMS/batch size processing. Mitigate by boosting stocks of critical inventory, evaluating alternate sourcing of impacted materials and using government support policies when looking at investments in production plants.
• Shutdowns of vendor plants. Mitigate by identifying shutdowns from remote (i.e., Asian) sources and pressure test supply chains for various scenarios.

Key risks for planning include:

• Expiration of materials and monitoring for reassessments and quality certificates. Mitigate by submitting studies to the FDA with the longest agreeable expiration date.
• Shutdowns of contract manufacturers. Mitigate though communication regarding their ability to deliver products.
• Quality control checks at contract manufacturers or traded goods for contamination issues. Mitigate by having quality control personnel on-site and thoroughly sanitizing all in-bound products, employees and equipment.
• Contamination after final packaging. Mitigate by disinfecting shipments before delivery and providing photographic proof.

Logistics and transportation risks cited by Deloitte include:

• Non-availability of local transportation to move raw materials and finished goods. Mitigate by locating alternate partners and getting approval to move essential drugs should a lockdown occur.
• Contamination issues from transport vehicles. Mitigate by disinfecting all vehicles, planning to store temperature-sensitive products and arranging warehouse space.

Export risks are:

• Contractual compliance. Mitigate by ensuring the person(s) collecting the order is aware of any regulatory restrictions.
• Contractual terms with domestic and export customers. Mitigate by seeking advice from insurance brokers and engaging early with clients to determine what could work if supply chain challenges or personnel issues occur.

Continuing Effects

Disposable components for single use systems are being shunted to Covid programs at the expense of other critical programs. This is one of the continuing effects on the supply chain cited by Contract Pharma in its Covid-19 Impact Report.

Kay Schmidt of Catalent said finding vaccines and target therapies for Covid-19 has boosted demand for its services. The increased demand “has led to greater collaboration and innovation between partners, regulators and throughout supply chains to meet key milestones” plus internal and external management, planning and communication to ensure resource allocation for multiple programs.

James Rogers of Sterling said, “The impact of the global pandemic has exposed the fragility of the pharmaceutical supply chain.” He predicts that supply chain resilience and reliability will be given the same importance as price when developing future supply strategies.

Danita Broyles of U.S. Pharmacopeia is quoted by Contract Pharma as saying, “The decrease in on-site inspections has the potential to increase quality risks to the global supply chain,” adding pressure to manufacturers and suppliers to ensure the quality of their products.

Ben Wylie of ChargePoint Technology said that, “many governments are now pushing the industry to rethink its model to safeguard drug production.” He cited a program in India to reduce reliance on China for critical drugs and APIs.

Covid-19’s Impact on Regulatory Practices

Covid-19 will have an ongoing impact on regulations in the areas of clinical study trial design, clinical trial study development and post-clinical trial regulatory submissions, Dr. Ronan Brown of IQVIA wrote in an article on European Pharmaceutical Review.

Among the changes forced on drug makers is a more decentralized approach to collecting patient information and rapid access to regulators, Dr. Brown said. This includes pre-investigational new drug meetings with the FDA now granted in less than 30 days. The FDA has also taken steps to accelerate the review and start of new studies. Flagging potential obstacles and safety concerns during these early meetings lets pharmaceutical companies move faster into human trials, he explained.

Decentralized clinical trials, which he expects will ultimately cost about the same as the traditional versions, will offer greater diversity in terms of patient cohorts along with increased mobility and convenience.

At a Glance

• The pharmaceutical and life sciences sectors have relied on conventional batch manufacturing methods as a trusted model for production requirements. For faster, more dynamic manufacturing, pharma companies like CDMOs are turning to continuous manufacturing.
• While continuous manufacturing offers more flexibility and agility, there are a number of practical and financial aspects that pharma companies need to take into consideration while making the partial or complete transition.
• Transitioning from batch manufacturing to continuous manufacturing requires pharma companies to be equipped with the right tools and technologies. For many, partnering with experts to seamlessly drive the transition and ensure employees are well-trained is essential.

For years, CDMOs have made do with solutions focused on batch manufacturing. Fast forward to today, however, and the world is changing rapidly, with newer more efficient technologies being introduced for more dynamic process management. While the pharma sector might seem hesitant to let go of batch manufacturing, more and more companies are slowly transitioning to continuous manufacturing.

The global pharmaceutical continuous manufacturing market is predicted to grow with a CAGR of 8.2% over the forecast period of 2018-2024.– Researchandmarkets.com

With a growing number of benefits, including shorter production cycles, no equipment-stop requirements, and reduced risk for things like manual errors; continuous manufacturing is being viewed as the next big step in pharmaceutical manufacturing. In addition to the benefits, however, businesses need to expect any financial, practical, and behavioral hurdles that might arise.

This article aims to highlight these hurdles for organizations comparing batch vs. continuous manufacturing in order to gauge respective pros and cons.

Continuous Manufacturing and Its Impact on the Pharma industry

Continuous manufacturing is a highly streamlined ecosystem where multiple stages and discreet testing across various facilities are not required. For pharma companies, this can mean avoiding excessive downtime or closures of production units in the event of a faulty batch, saving manufacturers thousands of dollars previously dedicated to these types of tasks.

Continuous manufacturing is more flexible and dynamic in nature, allowing manufacturers to introduce changes with ease and efficiency. In comparison, batch manufacturing in the pharmaceutical industry has always been highly restrictive in nature. Continuous manufacturing enables pharma companies to lower their carbon footprint, reducing any harmful emissions released into the environment and does not require the longer ‘hold times’ familiar to batch manufacturing, where between every stage materials need to be tested for quality. The transportation and storage of these samples (which are often in bulk) require both high costs and a planned holding time. These hold-ups and more can be mostly mitigated with continuous manufacturing. Companies can also significantly reduce the manufacturing lifecycle, including time to market for a drug. The single production line model found in continuous manufacturing works well to save time, leverage process flexibility, and enhance resource utilization.

3 Hurdles Implementing Continuous Manufacturing

With so many apparent benefits, it’s still a question of why the pharma industry hasn’t gone all out when it comes to continuous manufacturing. The answer lies in understanding the hurdles involved in implementing continuous manufacturing. Listed below are 3 common hurdles to consider when moving to continuous manufacturing.

The Right Path for the Pharma Industry

With so much impact and so many possible benefits, the application of continuous manufacturing will continue to rise for businesses in the pharma sector. Going forward, precision medicine, personalized care, and agile transformation will continue to be of utmost importance for CDMOs and pharma giants. While these goals and more can be met by embracing continuous manufacturing, in order to achieve these targets, pharma companies will need to be willing to make necessary changes to their infrastructure in order to make a smoother transition to continuous production.

Key Takeaways

• The pharmaceutical industry can take advantage of numerous benefits and opportunities with continuous manufacturing vs older batch manufacturing processes.
• While continuous manufacturing is on the rise in the pharma sector, companies need to plan appropriately to ensure a smooth implementation/ transition.
• Pharma companies need to be open to changes in infrastructure and mindset to take full advantage of a continuous manufacturing model.