Not only has Covid-19 tragically killed more than 300,000 people worldwide, it has had a severe impact on businesses, small and large, and, is likely to have a significant long-term impact on the global economy.
The pharma industry has been faced with its own challenges during this pandemic, which centre around supply chain and clinical trial disruption. This situation has led to concerns about the global nature of active pharmaceutical ingredient (API) and generics manufacturing, which was impacted when countries like India and China went into lockdown early in the pandemic.
An early move towards a national, rather than global, approach to generics manufacturing in the future is US President Donald Trump’s move, with the administration spending $354m on a four-year contact with Virginia-based Phlow Corp to manufacture medicines and APIs in the US.
Despite these challenges, the pharma industry has stepped up to repurpose medicines, as well as develop novel drugs and vaccines against Covid-19 and the coronavirus that causes it, SARS-CoV-2. Generics manufacturers are contributing to resolving the coronavirus pandemic by producing existing medicines to support clinical trials and emergency use in hospitals.
European generic medicines manufacturer Accord Healthcare’s vice-president and head of scientific affairs Dr Anthony Grosso discusses the challenges facing the generics industry in the pandemic, as well as how generics companies can step up and collaborate to find solutions to both the current public health emergency and potential future crises.
Allie Nawrat: How has the pharmaceutical industry, and particularly generics companies, been disrupted by the Covid-19 pandemic?
Anthony Grosso: The initial challenge has been to meet this unprecedented surge in medicines, particularly in relation to Covid-19. In parallel to that, we’ve had to ensure and maintain the supply of other essential medicines that are non-Covid-19-related to ensure that we didn’t just completely focus on medicines [for Covid-19] and leave the other ones neglected.
A second initial challenge was around the way the pandemic played out. In Europe, for example, it was Italy first, and then the likes of Spain and countries such as the UK were in lag. The challenge we had as a pan-European supplier was with the finite stocks that were in place; we didn’t want to just exhaust them and send them all to the early wave countries and then leave the other countries dry. We had to think ahead and not just blindly provide these medicines to who was shouting the loudest for them.
The last point is around the supply across borders. It’s a challenge under these conditions to ensure that we could get the medicines transported in a timely manner. We got there in the end, but from a logistics perspective, it was much more challenging and difficult than pre-pandemic.
AN: How can generics companies support the fight against Covid-19?
AG: Ideally the solution to the pandemic is going to be a vaccine, [but] we’re very mindful that that will take time and, as was announced by the UK’s chief scientific officer Sir Patrick Vallance recently, a vaccine might never become available. So, the industry needs to not just sit back and do nothing until a vaccine comes to change the trajectory of the disease.
Similarly, we should not be idly waiting around for novel treatments, as these take longer to trial because you don’t have the longer-term established safety assurances that you might have with existing medicines.
The generics industry has an opportunity to look at what’s already available in its locker – aAt Accord we have over 10,000 marketing authorisations in Europe – to see what could be repurposed in three major domains. If any are shown to be effective, these could likely be scaled up and rolled out much more quickly [than investigational medicines].
First, can any approved medicine fight the virus itself? Can a drug reduce its contagiousness or inhibit its replication to effectively render it much more treatable by the immune system?
Second, a significant issue in some patients with severe Covid-19 is the dysregulation of the immune system, and there’s a lot of treatments out there that could potentially mediate and modulate a cytokine storm effect.
Third is supportive care, and in particular ICU [intensive care unit] medicines. Covid-19 has caused an unprecedented demand on ICU capacity and in particular a requirement to utilise mechanical ventilation as a late-stage consideration. However, it is critical to understand that you cannot initiate or maintain a patient on a ventilator without a necessary cocktail of specific medicines such as strong analgesics and sedatives.
AN: Partnership has been a core theme of pharma’s response to the pandemic. How can the generics industry support researchers in clinical development?
AG: When we were analysing all of our existing compounds, we had a list of thousands. So, in the early stages, we had to go through this list to find what potentially had a good fit in terms of mechanism of action, or interesting in vitro data, that could hint towards potential value in this novel disease.
An early agent that we identified was chloroquine, and then hydroxychloroquine, which is very similar. We took a risk in starting to manufacture that prior to getting a marketing authorisation.
People started to construct clinical trials [of these products], but commonly in the severe end of the disease. [However,] my view was that a repurposed compound was unlikely to make significant gains in late-stage disease as a lone agent. There was one trial, led by the Mahidol Oxford Tropical Medicine Research Unit– the COPCOV study – which was seeking to investigate chloroquine as a prophylactic. We proactively reached out to the lead investigator and offered a related compound, hydroxychloroquine, and scientific support to the study.
[This trial is now underway with first UK participant enrolled, making this] the largest prospective interventional Covid-19 clinical trial, which is [specifically] looking to test the value of these agents as a prophylactic in front-line health workers.
To make this trial a reality, the generics industry had to make a significant investment, and importantly, be proactive; having that availability of supply is essential to try and get these key questions answered.
[Update 28/05/20: the UK Medicines and Healthcare products Regulatory Agency (MHRA) has now paused the COPCOV trial due to safety concerns around the use of these drugs against Covid-19].
AN: What lessons can the generics industry learn from the challenges of this pandemic to date?
AG: The most important thing is that no-one can solve such a problem in isolation; partnerships and collaboration are absolutely essential.
When we were looking at the huge demands likely to be placed on key classes of medicines, there was a question about will we have enough of these medicines over the coming weeks and months to meet the anticipated demand? Since we don’t supply all of these medicines, we realised that we needed to collaborate with others in the generics industry and with branded pharmaceutical companies to answer that key question.
Hence the importance of the work led by [generic/biosimilar trade association] Medicines for Europe. Also, [we needed to] involve the competition authorities to gain their support to allow us to work in this way. This kind of collaboration would not be allowed under normal competition rules, [but] everyone was very pragmatic and understanding of the public health need to work together.
AN: What impact do you think this pandemic will have on the future of generics manufacturing, particularly the global nature of this industry?
AG: This is the first time everyone has had to work in this way. It takes time to set up and go through your internal processes to gain approval to share some key confidential information, but if we all had to do it again, then I expect everyone would be able to do it even more expediently.
Also, I think the pandemic is going to create a much greater focus, awareness and appreciation of our industry.
Key learnings from this pandemic may lead to a call for increased investment into this industry, in order to ensure we don’t sail as close to the wind going forward. The pandemic will likely improve supply resilience. We need to ensure we have more manufacturing hubs so we can ramp up production quicker and have supply contingencies.
I think it is legitimate to have plans in place to ensure that supply can be maintained during a pandemic scenario, however I do not think that equates to a universal move away from global supply.
We don’t know what size the second peak may be or if there will be mutant strains coming through, or whether there will be subsequent pandemics, but we have to be prepared for these possibilities.