The pandemic has undoubtedly had a detrimental impact on the pharmaceutical and healthcare industries. Brexit has rubbed salt in the wound, making it increasingly difficult to gain regulatory approval for clinical trials. However, this cycle of events has arguably opened an opportunity for change within pharma, leading companies to consider options to combat rising costs and further complexities.
Clinical trials present costs associated with patient grant, site management, labour, and additional technologic measurement. Many pharma companies have downscaled their clinical trials in order to save money, which has led to increased outsourcing – as this enables them to pass over in-house work to academic and private contract research organisations (CROs). Speaking to Anju Life Sciences Software, writer Esther Landhuis says, “Nearly anything that a pharmaceutical, biotechnology, or medical device business needs to do – from designing assays to planning and running clinical trials – can and may be outsourced to CROs.”
Outsourcing involves reaching out to external companies for help with internal affairs or activities, involving numerous business functions including clinical data management, site management (for trials), and human resources. This relationship opens the door to an array of benefits for pharma companies, particularly those who are struggling to maintain their research and development levels. As operating costs can be extortionate, outsourcing could save billions and could also offer a broad range of services for smaller and underfunded biopharmaceutical companies as well.
Why outsource in clinical trials?
Currently, pharma companies rely heavily on R&D to develop new drugs. J&J spent $82.6 billion in R&D in 2020 while MSD, Merck’s EU outlet, laid out 28.3% of its revenue on R&D in the same year. Outsourcing research activities to CROs also allows pharma companies to compete with a world of exponentially growing knowledge, technologies, and an unpredictable economic climate.
Pharmacovigilance (PV), in particular, is an area in clinical trials that has been severely impacted by Brexit, as the UK is now a separate entity with its own legislation. There is still a dependency on EU infrastructure to ensure the safety of medicines in the country. The UK is also a major contributor towards the establishment of PV across the EU. High costs in the pharma industry are associated with emerging provisions in good pharmacovigilance practices (GVP), due to the demand for specialised PV resources for risk management activities and audit of computerised systems. Flexible outsourcing offers a solution to these rising costs, and adapting to PV resources can be simpler in practice.
Pharmacovigilance in-house is too expensive, and outsourcing provides access to competent, trained personnel, access to state-of-the-art technologies, and rapid standardisation.
Pharmafocus spoke to Esther Poole, Management Consultant – Clinical Safety at Arriello, about the importance of outsourcing in PV. Esther comments: “Patient safety should always remain at the heart of clinical research, and outsourcing pharmacovigilance enables access to the specific safety expertise needed to ensure full compliance. Throughout the clinical development process, a sponsor’s clinical trials can become increasingly complex. A clinical safety vendor can therefore offer the specialist knowledge needed to both manage a product’s safety profile, and to navigate the associated regulatory framework.”
For small pharma and biotech companies with less financial support, outsourcing clinical trials is less of an option and more of a necessity. These companies are less likely to have therapeutic expertise and lack the resources needed to develop a product.
Choosing the right CRO
CROs play a critical role as a service provider. Many often insist on inflexible contracts for pharma and biotech companies, which can lead to high staff turnover rates. Evaluating the qualification of a CRO is based on various criteria, and this is why it is important for companies to choose the right provider to meet their needs, expectations, and budget.
Sponsors can start by compiling a list of CROs specialising in bioavailability (BA)or bioequivalence (BE) research. CROs with extensive expertise performing BA or BE studies, and meeting the deadlines of their sponsors, should be prioritised. CROs that offer all services must also be high on the list. Above all, the CRO should have a credible track record of conducting studies with proper clinical conduct and quality outputs which are delivered on time.
Do they have the capacity to recruit patients for a range of trial sizes? How much experience do they have in assessing drug metabolite? These are the questions that need to be asked when choosing the right CRO to outsource to.
What are the advantages?
Outsourcing reaps numerous benefits. Poole says, “Outsourcing is efficient and budget driven, and it can be beneficial to embed safety into outsourcing arrangements from the beginning. Knowledge is key, and access to revelant safety expertise supports clinical trial efficiency, without which can lead to unexpected increases in a sponsor’s clinical safety budget. Outsourcing is also more cost-effective when maintaining a global safety database. The ultimate aim of clinical development is to get new drugs to market, and partnering with a pharmacovigilance provider who offers both clinical safety and post-authorisation services can make this transition much smoother.”
There are also advantages to clinical trial outsourcing which extend beyond just cost effectiveness and flexibility. It provides the ability to rapidly scale up and down, because it makes resources easier to maintain. Managing resources in house can come with all sorts of difficulties, including internal legislation and labour laws, among others.
The benefits of outsourcing are also determined by qualitative factors, such as feedback from working partners on how the relationship is progressing. Outsourcing relationships have evolved over the last 10 years, and digital innovation has made communication more plainsailing. There has also been a change in the style of outsourcing relationships – Colin Mackay, founder and CEO of Symbiosis, says: “There has been significant consolidation in the contract manufacturing sector, meaning that the industry is less fragmented with fewer service providers. This reduces the choices available to drug developers when selecting partners to work with to develop their promising molecules. As a result relationships seem to be a lot more about strategic partnerships and less about straightforward, operational outsourcing.”
What is needed for an effective CRO-sponsor relationship?
For outsourcing to work effectively, CROs need to operate according to the quality systems of the sponsor organisations that hired them. In the US, this is a necessity for compliance with FDA regulations. This quality system should also include an agreement between sponsor and CRO, underlining the responsibilities of both parties to ensure effective communication, and successful collaboration. Lines of communication should also be as clear as possible, and information overload should be avoided.
Effective communication is also mandatory, and this means ensuring fast response times, and leaving no room for assumption. CROs and customers should also work together as a single team as much as possible to develop a shared understanding of the end goals of their partnership. The more effectively sponsors and partners can communicate, the more they will get out of their strategic collaboration. A strong working relationship is crucial, and by following clear guidelines, both parties can make the most out of the outsourcing partnership.
What are the challenges and complexities?
The pandemic has opened up the possibility of remote working options, highlighting the increasing importance of virtual presence for the pharma industry, and it is vital for companies to use this to their advantage. However, this emphasises the need for technical skills and enhanced data security, which many companies do not have access to in house. Outsourcing to CROs can reduce the weight of some of these responsibilities. Poole continued, “Although geographical location is still crucial for regulatory aspects of clinical trials, inspectors and auditors who previously carried out audits on site are working virtually.
Due to the evolving nature of post-Brexit requirements, the long-term impact on outsourcing also remains to be seen. From a PV perspective, it is vital that pharma companies and sponsors remain on top of new requirements, for example introduction of regulatory reporting via the MHRA Submissions Portal. Navigating new legislation and understanding the practical implications for clinical trials requires collaboration from all areas of the pharma industry, including pharmacovigilance providers.”
Outsourcing in clinical trials also does not come without the danger of safety oversight and poor planning, which can result in greater costs. However, many CROs do not include formal safety provisions in their outsourcing services, adding a limitation to what they can offer in clinical trials. Failure to ensure clinical safety could lead to potential non-compliance and other inefficiencies.
There is also the risk of non-compliance of regulatory requirements, and CROs and their partners should make sure that they are following the requirements of the relevant regulatory body. Marketing Authorisation Holders (MAH) need to effectively demonstrate to the regulatory body that an appropriate oversight programme is in place for outsourced activities. However, there are also challenges associated with applying the same level of oversight to all outsourced activities, so sponsors should work with CROs to develop an oversight programme that works best for that particular trial.
Investing in CRO management also comes with its challenges, and is considered a highrisk investment. Speaking to Labiotech, Richard Scaife, Managing Director at OM360 Outsourcing Consultancy and Chairperson at PCMG, said: “Managing CRO outsourcing is a complicated task, intensive task. Once you have made your selection, there’s not enough time or budget to change your mind when projects are underway.”
The ethical implications must also be considered, the most controversial of which is the wellbeing and safety of its participants. Participants need to be fully aware of the trial they are participating in, and no information can be withheld from them. CROs and their customers therefore need to ensure that they have the full informed consent of their participants. Despite these issues, it is important to note that these ethical issues are present in the process of clinical trials, regardless of whether outsourcing is involved or not.
To summarise, clinical trial outsourcing has an array of benefits for pharma and biotech companies, ranging from cost effectiveness, to efficiency, to scalability. These can be enjoyed by not only the largest companies, but also smaller and less established organisations as well. Although outsourcing offers a more simplified process, there are still measures that need to be taken in order to ensure the most efficient and fruitful collaboration possible.
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