2019 is set to be an important year for the pharmaceutical industry. Implementation of new regulations, such as the EU’s Clinical Trials Regulation and Falsified Medicines Directive, Brexit and the emergence of revolutionary technology look set to change the landscape significantly.

Consolidation vs specialist providers in a growing market
The demand for contract research organization (CRO)-conducted clinical trials has been and will continue to rise in 2019. In 2016, the overall bio/pharmaceutical outsourced development spend was $26 billion and is expected to reach $31 billion in 2019, while the market for CRO-conducted clinical development in 2015 was $25.7 billion and is expected to increase to $36.7 billion by 2020.

This trend is being driven by the increased outsourced clinical activities to CROs in response to the ever-increasing size, complexity, duration and cost of clinical trials.

Intense competition in this growing market has led CROs to seek advantages wherever they can and consolidation has been the only answer for some as they look to build a more comprehensive portfolio of service offerings. While consolidation may serve a purpose, it has several drawbacks: less competition and less choice for sponsors forces them to work with organizations that may offer the scale but not the in-depth knowledge or focused services available elsewhere with niche providers. In 2019, we’ll see a clear divide emerge between generic ‘one-size-fits-all’ solutions and more client-centric service providers.

Data quality oversight
As the pharmaceutical industry embraces new technologies and innovations, including electronic record keeping, the volume of information collected before, during and after clinical trials continues to grow. Similar to the adoption of electronic data capture (EDC) systems, which initially started slow and now is the norm, it could be expected that the same will occur with data quality oversight (DQO) once monitoring efforts are centralized.

Data quality oversight (DQO) involves running statistical analytics and generating reports via CSM to identify outliers and anomalies and improve the quality and integrity of clinical trial data. Monitoring and clinical data management teams can then investigate and resolve these identified potential issues.

In the ICH GCP E6 (R2) addendum the FDA accepted that pharmaceutical companies and their sponsors are under pressure to bring cost efficiencies to their processes. The Addendum gave the green light for new technologies and approaches to monitoring and oversight. It allows for a degree of source data verification (SDV) to no longer have to be done on site, as well as to reduce SDV from 100% where risk permits. This resulted in the acceptable use of risk based monitoring (RBM). The use of RBM has risen over recent years—research has shown that between 2009 and 2013, RBM adoption has risen from 33% to over 50% among industry stakeholders. It also resulted in remote monitoring and centralized statistical monitoring (CSM), which in turn leads to greater importance and value for improved data integrity and data oversight.

Performing DQO during study conduct and improving data integrity—the maintenance of, and the assurance of the accuracy and consistency of, data over its entire life-cycle—leads to improved data quality in the final submission data used to demonstrate an investigational new drug’s (INDs) efficacy and safety. For example, a sponsor is now able to respond to any on-site issues faster by verifying source data remotely. Large trials with multiple centers and manual on-site monitoring via investigators are more time consuming from a cost and clinical research associate (CRA) perspective. It is in the best interest of sponsors to detect such potential issues before regulatory submissions and should see more companies adopting the approach in 2019.

Pharmacovigilance
It is expected that the pharmacovigilance (PV) market will register 10% growth to touch $8 billion by 2024, which makes it an exciting time to be a niche pharmacovigilance service provider. An increasingly comprehensive and complex regulatory framework, investment in exploiting scientific advances made in areas such as oncology, and the emergence of new novel therapies and technologies for rare diseases or other unmet medical needs, overall has led to more demand for specialist support in PV and risk management.

2012 saw the introduction of good pharmacovigilance practices (GVPs) in the European Union (EU) and since then, the industry has experienced a huge amount of change, including the launches of the:

• Medical Literature Monitoring (MLM) service;
• Periodic Safety Update Report (PSUR) repository;
• Extended EudraVigilance Medicinal Product Database (XEVMPD); and
• New EudraVigilance system supporting centralized reporting and ISO-ICSR ICH E2B(R3) format submission and download.

The industry has also seen changes to the Risk Management Plan (RMP), the introduction of PV fees, and stakeholder access to the EudraVigilance Data Analysis System (EVDAS) to support signal detection and assessment activities which remains in its pilot phase.

The developments around EudraVigilance will be followed closely in 2019 by the pharma industry as it seeks to ensure that its new processes meet its requirements.

Brexit
One of the key considerations for the pharma industry when it comes to Brexit is pharmacovigilance (PV). The current situation is that, from 30 March 2019, EU PV activities will no longer be able to be conducted in the UK and vice versa.

There is very little time to prepare for what the pharmaceutical industry will look like post-Brexit and it is likely that it will affect companies and sponsors at a wider business level. As we move forward it is vital that the industry carefully monitors output from the EMA and UK government to guide their strategy.

The concerns surrounding Brexit and its impact on the industry mean that it will be all too easy for companies to take their eye off the ball when it comes to ensuring they meet the new PV regulations. It’s vital to ensure the necessary changes are made.

What that means regarding the licensing of medicines and alignment/cooperation on a range of PV factors is still unknown. Clarification on the following EU-led initiatives will need to be considered in the negotiations between the EU and UK:

• EudraVigilance;
• The use of single assessment for Periodic Safety Update Reports (PSURs) and Risk Management Plans (RMPs); and
• The role of the Pharmacovigilance Risk Assessment Committee (PRAC) and Qualified Person Responsible for Pharmacovigilance (QPPV).

It is almost certain that after Brexit, marketing authorization holders (MAHs) will have to put in place a UK-based QPPV, as well as a EU QPPV based in the remaining EEA region to continue distributing drug products in both markets, although draft legislation issued by the UK government indicates that there may be a transitionary period of 21 months for establishing a UK QPPV, even in the event of a no-deal Brexit. Specialist PV providers in the respective regions are likely to be heavily relied upon in the coming years to ease the burden on pharma companies.

Machine learning and artificial intelligence
Artificial intelligence (AI) and machine learning (ML) is generating a lot of interest in the pharmaceutical industry at the moment with AI in drug discovery companies emerging. From a drug development and clinical data perspective however, it seems AI and ML could just be a fancy term for automation with few ‘real’ AI solutions in place.

At industry events such as PhUSE conferences, both pharmaceutical and clinical research organizations (CROs) are currently working to facilitate AI solutions and working parties have been formed for joint collaboration. AI and ML has the potential to bring increased efficiencies to the statistical analysis and programming of clinical data and with the increasing costs of drug development, it’s easy to understand the appeal for pharmaceutical companies to create such solutions. However it seems only a handful of Pharma companies are championing this while others are trying to get up to speed. As a data focused CRO, Quanticate is developing some AI solutions that are more than automation and advanced programming, such as tools to make intelligence decisions based on historical data, another to help compare outputs across different datasets, and finally an AI based approach for knowledge sharing and training.

With advances in technology in this AI space, and Pharma companies increasingly expecting service providers to have solutions in development, AI is expected to be “table stakes” in the industry by 2020.

More orphan drugs
There are estimated to be around 7,000 known distinct rare diseases that affect 350 million people worldwide, and approximately 80% of those rare diseases are caused by faulty genes. Scientific advances such as the CRISPR/Cas9 genome-engineering system have simplified the pharmaceutical and biotech industry’s ability to develop gene therapies, especially for single gene mutation disorders. The FDA now has more than 700 active Investigation New Drugs (INDs) for gene and cell therapies, and in 2017, approved two cell-based gene therapies (chimeric antigen receptor T-cells [CAR-T]) as well as the first gene-therapy product to be administered in vivo. Collins and Gottlieb, of the NIH and FDA respectively, have stated that, “it seems reasonable to envision a day when gene therapy will be a mainstay of treatment for many diseases.”

Not only is there the satisfaction of being behind a ‘miracle cure’ and the varied and interesting and challenging science behind the rare disease trials, there are also financial incentives for pharmaceutical companies to step into this area. The U.S. Orphan Drug Act EU Regulation on Orphan Medicinal Products facilitate tax incentives, enhanced patent protection, and marketing rights and clinical research subsidies for companies developing orphan therapies.

Orphan drugs then may help companies reduce the impact of revenue loss caused by patent expirations of blockbuster drugs as the incentives to help them with the development of rare diseases.
Once successfully authorized, a rare disease drug can be purchased for a considerable amount, and research shows firms with marketed orphan drugs are more profitable than those without. It is fair to predict that more and more pharma companies will start working in the area of rare diseases and CROs will do well to have a good understanding and area of expertise in this field. 

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David Hukin is managing director at QVigilance. He has 15 years’ experience in the pharmaceutical industry, with more than 14 years working in the pharmacovigilance sector. David has worked in small, medium-sized and large specialty pharma/biotech companies and has gained pre- and post-marketing experience in a range of therapeutic areas including gastroenterology, hepatology, neurology, oncology and psychiatric conditions as well as advanced therapy medicinal products (ATMPs) and orphan drug indication products for rare diseases. Since 2015, David has worked in the specialist pharmacovigilance service provider sector, leading multiple large teams responsible for clinical and post-marketing for customers ranging from small pharma/biotech to large specialty and generic companies.

Thomas Underwood is marketing manager at Quanticate where he has over 10 years’ experience. Originally working in operations in both clinical data management and programming, Thomas moved into the organization’s commercial division and has been in his current role for over eight years. An integral part of Thomas’s role is product development which has involved extensive research into industry regulations and the resulting technology and services these influence such as Risk Based Monitoring, Data Quality Oversight and Centralized Statistical Monitoring.