COVID-19: A Year of Unprecedented Change

Contributors:

Marijn Verhoef, Engagement Manager at the Access to Medicine Foundation

Kelly Boyer, Vice President – Film Coating at Colorcon

Mark Quick, Executive Vice President, Corporate Development at Recipharm

Jonas Mortensen, VP Business Development, Almac Pharma Services

How did you initially respond to the pandemic?

Marijn Verhoef:  Though COVID-19 has sent shockwaves through the industry, in a way, we were all anticipating it. At the Access to Medicine Foundation, we’ve been studying what we call Disease X – an unknown threat – for quite some time now. So, though we were asking ourselves what this unknown pathogenic challenge would be, the fact that it was a coronavirus wasn’t a total surprise; coronaviruses had already been identified by WHO and others as a priority for industry to investigate, and the Access to Medicine Index assesses how companies were working on pandemic preparedness. Would they be able to manage supply chain threats? Would R&D continue as normal under the pressure of a pandemic?

There have certainly been challenges for us all to deal with, but the situation has proven how adaptable pharma is and, in recent months, we’ve seen increased collaboration between small and large companies to find solutions as quickly as possible.

Mark Quick: As Marijn says, we’ve certainly had to make rapid adjustments to deal with the changes. When the first wave of the pandemic hit, India and Northern Italy emerged as two of its epicenters – areas where Recipharm has significant operations. It was crucial for us to respond quickly. We implemented a business continuity plan to overcome the operational challenges and to mitigate the supply chain disruption caused by the global lockdown. Importantly, we also had to consider how we would protect the wellbeing of our colleagues operating production lines. 

Boyer: In response to the growing spread of COVID-19 around the world, in March 2020 Colorcon implemented its existing formal, documented Business Continuity Management (BCM) system. This system is comprised of a long-established Business Continuity Plan (BCP) and a series of Disaster Recovery Guidelines that are an integral part of our global business strategy and day-to-day activities. We have seven film coating production plants at locations around the world – all of which can produce equivalent products. And that helped our response to the worsening situation as we were able to manage levels of raw material inventory, continue to manufacture, and mitigate supply disruption. To support the continuity of our operations around the world, like many companies, we implemented a remote work policy, embraced digital communication platforms, and are taking extra precautions in our production facilities to protect our employees and support manufacturing continuity.

Mortensen: As the other contributors have mentioned, Almac has taken steps to ensure continued operations Our global facilities have remained open and operational, without interruption, since the initial outbreak, and we have continued to ship and receive material globally. We’ve done this, in part, by maintaining a centrally managed, country-by-country approach, which ensures we follow best practices and government guidance in each of our global locations. By doing this, we can act as an advisor to clients on how to manage supply chain considerations to ensure that studies and projects are not disrupted. In many cases, this included a shift to a flexible supply strategy.

At the core of our response effort was our robust business continuity framework, which includes a provision for facilitating lines of decision-making through two tiers of command leadership, to ensure reliability and consistency across our organization. This tiered leadership system includes our main board of directors and executive directors, who continually assess the impact of the crisis on our employees and our assets; and other members of our senior team who execute new processes across facilities, and provide feedback from a regional perspective. Lastly, the implementation of communication platforms has ensured collaboration and teleconferencing capabilities across the globe. We’ve had to embrace digitization in other ways as well, such as rolling out a virtual auditing solution to confirm our ongoing site compliance with GMP.

What vulnerabilities has the pandemic highlighted?

Verhoef: I think it’s fair to say that supply chains haven’t always held during the pandemic. We’d already experienced drug shortages in 2018 and 2019, but COVID-19 has exacerbated the problem. Several governments have at times even mandated the domestic production of drugs, which has resulted in a concentration of manufacturing in specific geographies – and placed additional stresses on many companies.

But, in my opinion, rather than vulnerabilities, I think that new opportunities are opening up for the industry; we’ve all seen an unprecedented level of solidarity between industry players. By the same token, it is also becoming clear that the governments of some wealthier nations are blocking equitable access to emerging COVID-19 therapeutics through pre-orders. I think that pharma companies have a role to play in stopping this. They are the ones that control manufacturing and supply, so they should be able to ensure equitable distribution of COVID-19 related products as and when they receive approval.

Quick: The pandemic has highlighted vulnerabilities in the industry’s highly globalized supply chain. During the first wave of the outbreak, for example, the shortage of APIs caused by the closure of Chinese factories had to be managed and mitigated to maintain the international supply of vital medicines. As a result, many governments are now encouraging their local pharma sector to localize supply chains – or at least diversify them – to safeguard against disruption during future economic shutdowns. For example, the US, under President Trump, enacted an “America First” policy to on-shore API supplies, although there is uncertainty around the future of this approach as Biden takes over. The Indian government has also recently launched a scheme to incentivize the country’s pharma industry to source APIs and other key ingredients from Indian suppliers. With manufacturers in India currently depending on China for 70 percent of their API supply, they were particularly impacted during the first lockdown. 

As a result of government pressure, it is likely we will see manufacturers around the globe rethinking their supply chains to favor local providers. Ingredient suppliers and CDMOs with a local presence in each of their target markets will be well placed to support these companies.

Boyer: Another area of concern that should be discussed is the sale and distribution of fake and falsified medicines. We know it has been a problem for decades but is spiking now because of COVID-19. The WHO reports that over half of all drugs purchased from online pharmacies are suspected to be counterfeit. And with the number of illegal online pharmacies increasing dramatically since the start of the COVID-19 pandemic, there is a growing recognition that the serialization of medicines through packaging alone will not solve the problems. The Royal Pharmaceutical Society also warns that the UK, in particular, could see “an influx of counterfeit medicines” after the Falsified Medicines Directive ceases to apply at the end of the Brexit transition period.

The COVID-19 pandemic has led to a dramatic rise in online sales. It is estimated that 1 in 4 US consumers now buy their medicines online. But according to the Alliance for Safe Online Pharmacies, a high percentage of online searches to buy medicine return links for illegal pharmacies. These online pharmacies frequently operate without certification, prescribe drugs without adhering to legal guidelines, and may knowingly distribute counterfeit medicines.

Increasingly well-organized counterfeiters backed by sophisticated technologies are continuing to profit from drug counterfeiting at the expense of patients and legitimate companies. They see both Brexit and the pandemic as an opportunity to expand their operations. We’ll all have to closely monitor the situation as we move into the new year.

What positive actions have been driven by the pandemic?

Mortensen: Well before the pandemic became a part of our lives, the clinical trial landscape was shifting – becoming increasingly faster, decentralized, and virtual. The specifics of the trials themselves (size, duration, and number of endpoints) are also changing. Protocols are becoming increasingly more intricate to design and implement given the need to target smaller, more niche populations. Last but certainly not least, there is a growing desire, now compounded by the pandemic, to shorten the timeline between final protocol to first patient visit. Therefore, it is clear that the pandemic has served as a catalyst to naturally implement new tools to support these models and accelerate the adoption of new approaches to increase the speed of drug development. 

Boyer: Even before COVID-19 struck, the industry was already evolving. At Colorcon, we noticed an increasing number of companies were moving away from in-house tablet coating formulations, for example, to a leaner production model using ready-prepared formulations. Such trends continue to accelerate because of heightened concerns about the inherent risk in supply chains. Many companies have long recognized the benefits of newer production models but have feared disruption and so opted to keep existing systems in place. The pandemic has pushed companies to reassess their operations.  

Quick: The desire to end COVID-19 disruption has highlighted the benefits of collaboration, with many companies working together and sharing knowledge. This willingness to collaborate to speed up the development process has filtered down to the commercialization phase as well. Drug developers are seeing the value of working with CDMOs to commercialize and deliver their products to market. CDMOs really do offer a host of benefits for both large- and small-scale developers – they already have the capacity, the in-house expertise, and technical infrastructure in place to manufacture new drugs and vaccines at a commercial scale. This minimizes expenditure on new drug development projects and significantly reduces time-to-market. And global CDMOs often have the local presence to support developers in streamlining and localizing their supply chains. 

Verhoef: Though the collaboration and investment in R&D that we’ve seen in recent months has been positive for the industry, we must ask ourselves what the long-term cost of it will be. We’ve directed both financial and human resources into COVID-19 R&D programs, but how will this affect development for other infectious disease indications? It is likely that staff working on treatments for other infectious diseases have switched focus to work on COVID-19 projects. What then will happen to the programs that they were previously working on? So, although the rapid response to the virus was and is necessary, we must think of the burden that will be placed on patients living with other infectious diseases and the future ramifications for pharma.   

How important is the continued role of small molecules in the pharmaceutical industry?

Quick: There has been a shift in the market in recent years toward innovative biologic and cell and gene therapy products, and many CDMOs are growing rapidly to service this new demand. Nevertheless, small molecules continue to play an important role in the sector and will account for the majority of prescribed drugs for the foreseeable future. As such, they will continue to be a major growth driver for the CDMO market for the next few years. 

With regards to the development of new therapeutics, there remains strong interest in orphan drugs, specialized treatments, and innovative drug products based on existing small molecules to tackle rare chronic conditions, such as Parkinson’s Disease. Small molecules are also being harnessed to develop new multiple-API products designed to boost the effectiveness of existing treatments through delayed or extended dosage. Such products are also ideal for enhancing patient compliance by reducing the number of doses users must take per day. 

Verhoef: Small molecules have always been important to the pharma industry. Long before the introduction of biologics, they were relied upon to treat myriad diseases and continue to play a role in disease management today. Take dexamethasone, for example. The drug has now been repurposed as a COVID-19 therapeutic, but the drug has a broad spectrum of uses across a variety of disease areas. 

In low- and middle-income countries, small molecules improve medicine access as they are usually cheaper and usually don’t require refrigeration. But the role of advanced therapies and biologics is undeniable and governments worldwide should ensure that those in poorer nations can access them in a similar way to the 20 percent of the global population who live in high-income countries.

Mortensen:  The continuing role of small molecules is also evident if we look at recent approvals of new molecular entities. Small molecules dominated new drug approvals by the FDA in 2019, accounting for 79 percent of all NME approvals. What we have noted though is that the type of drug product is changing. We are witnessing a significant growth in developing and manufacturing age-appropriate formulations, especially for pediatrics – mainly multi-particulate formulations, such as mini-tablets filled into stick packs. Potent drug products that require contained processing are also on the rise, together with decreasing batch sizes as medicines targeted towards smaller patient populations in line with the growing trend in orphan and ultra-orphan indications. 

In what ways do you think pharma can be better prepared for the next pandemic?

Boyer: Simply put, we need to focus on supply chains – from raw materials to finished products.Managing raw materials is a critical part of the production process. So, implementing a process to measure how much each raw material contributes to products is key here. But the ability to map supply chains – knowing who makes a particular material, where they are located, how it is transported, and where it is housed – will be essential for dealing with any future crises.

Verhoef: Boyeris right. The crux of the issue is supply chain management – although it should also go without saying that pharma companies must invest in R&D targeting those pathogens that are known to have the potential to trigger a pandemic. Companies need to assess vulnerabilities in their supply network. Single sources of particular ingredients of APIs can hinder manufacturing, so companies need to establishglobal and regional hubs to assure them of security. If one provider of APIs is unable to supply companies with products, another should be able to fill the gap. This will also help to boost local capacity and capability. For example, a hub in any Sub-Saharan country will have the responsibilities of manufacturing and logistics – allowing it to supply the region. This will undoubtedly help if we are faced with another pandemic. Building these robust lines of supply will be our best defense.

Quick: Onshoring and localizing the supply of APIs is one step many pharmaceutical companies are taking to address this issue, encouraged by their governments. This positive measure will help manufacturers protect their supply of raw materials in the event of an economic shutdown in one part of the world during a future pandemic. Those who do not localize will look to diversify to ensure they are not reliant on one market for raw materials.

What do you think the industry’s priorities need to be for 2021?

Verhoef: A key focus for 2021 will be on how companies raise capital to improve access to medicines globally. The industry was making headway with this, but COVID-19 snowed on these developments. We need to get back on track as it will indicate that companies aren’t only thinking of medicines access as a form of philanthropy but an essential part of their business models – this will help allow sustainable access to much-needed medicines in low- and middle-income countries.

COVID-19 has been at the forefront of the industry’s collective mind this year and is guaranteed to impact the sector next year. Hopefully, we’ll see a series of filings for registration and market authorizations for COVID-19 treatments and equitable access to them all. But, to reiterate a point I previously made, if government leaders fail to display solidarity, then the industry should step up to make a difference for patients across the globe. The pandemic will only be over when the majority of the world’s population is immunized and has access to appropriate treatment. I hope we – as companies, organizations, and individuals – can remain engaged in taking appropriate steps to combat the disease until the WHO declares the pandemic over.

Boyer: Having robust business continuity plans in place to ensure continued supply is vital in ensuring the continued safe supply of medicines. But, as also mentioned earlier, we also need to pay attention to counterfeit and falsified drugs – and their prevalence will continue to increase. The growth in the number of illegal online pharmacies (over 600 new sites per month!) is further fuelling the counterfeit fire. Cost-effective and simple to implement technologies are needed more than ever to combat counterfeiting and provide greater security to the supply chain and greater safety for the patient.

Quick: For the next 12 months, it is imperative that the industry continues to use lessons learned from the pandemic (and its impact) to find new ways to ensure their operations and supply chains are more resilient in the future. As many COVID-19 vaccine candidates approach the final stages of development, it is likely we will see a considerable amount of manufacturing capacity devoted to the task of vaccinating the global population. 

Though this is important, we also need to make sure we maintain our focus on existing drug development projects to help the global healthcare sector treat other serious conditions. 

It is also important that we continue to prioritize the development of new drug products, dosage forms, and delivery systems to support patient-centric treatments. In doing so, we can help ease pressure on healthcare providers as they focus on dealing with the pandemic and its fallout.