Contributed Commentary By Marco Anelli

May 22, 2017 | Globalization is undoubtedly having a profound effect on the way life sciences companies manage their regulated activities. For instance, the pharmacovigilance front is seeing greater efforts internationally to improve the management of safety data about medicinal products through more and more standardization with regard to the collecting and sharing of data and information. This is true among both regulatory authorities and companies, though not necessarily with the same perspectives or goals in mind.

For life sciences companies, extension into and the growth of new markets add to safety challenges.

As anybody who follows what’s reported in social networks about drugs can confirm, drugs get used, misused, and abused in different ways from country to country. Further complicating the situation is the fact that, often, product documentation is inconsistent across borders, and what is a known adverse reaction in one country might not be so considered in another, thereby resulting in differences in the ways information gets processed. Another problem often found during inspections and audits at multinational companies is lack of procedural, or even so-called cultural alignment between headquarters and affiliates.

Clearly, regulators would like to see better harmonization. The question is, How should safety alignment be managed?

Is There a Global GVP Convergence?

Strictly speaking, there’s no such thing as global harmonization of good pharmacovigilance procedures, although a recent initiative from the International Coalition of Medicines Regulatory Authorities (ICMRA) demonstrated the organization’s vigorous push towards greater convergence. But there’s growing interest in emulating the European Medicines Agency’s (EMA’s) good-pharmacovigilance-practice (GVP) guidelines, which turns the focus towards transparency, patient empowerment, and gaining better consistency of information across all parts of the submission and product maintenance process. The EMA has said it wants to “harmonize and strengthen the safety and risk–benefit review of medicines across the European Economic Area.”

The US Food and Drug Administration (FDA) has yet to follow the EMA’s lead, but it’s interesting that several of the emerging markets are adopting the EMA’s GVPs—even though it’s with some alterations. For example, both the Middle East and the Eurasian Economic Union have effectively copied the requirements in the GVP modules while adding some of their own regional specifics. Whereas in the past some countries such as China and India invested resources into improving good manufacturing practices and paid less attention to pharmacovigilance, today they’re also getting more serious about safety.

Lesley Wise, managing director at Wise Pharmacovigilance and Risk Management, said a number of markets—especially those that the industry has targeted for growth—are working to improve national pharmacovigilance systems. But, she adds, that doesn’t imply alignment; and each individual regulatory authority will create systems and processes that suit its own country and people.

That’s proving to be true in the Middle East, which has certain complicated variations from the EMA’s GVPs. For example, Julia Appelskog, head of pharmacovigilance at Bluefish Pharmaceuticals, said that although a company submitting a product for registration in Europe would provide a summary of the company’s pharmacovigilance system, in Egypt the company would have to submit the pharmacovigilance system master file summary, as well as the national pharmacovigilance subsystem file and its summary.

A Complex World

There are also areas in which safety requirements diverge significantly. For example, the US FDA is considering setting up what’s called safety committees that would regularly assess unblinded data—and separately from data-monitoring committees. As Wise pointed out, such a move would cut across a lot of the work that is otherwise required for regulatory reporting, and thereby create additional work because the data would have to be reported to some countries but not to others, and an involuntary break in a study’s blinding could jeopardize the results of a whole trial.

Harmonization across the European Economic Area carries many benefits—among them, the fact that the EMA can now carry out single assessments of related periodic safety update reports containing the same active substances or combination of substances as one another. But harmonization carries additional burdens too. For example, David Ferguson, head of international pharmacovigilance at Shire Pharmaceuticals, pointed out that if a company has Europe-wide marketing authorization for a product—applicable in all European Union (EU) member states—the company must have a responsible person for pharmacovigilance in every market, even if it isn’t marketing a single product in some of those EU markets.

There are even greater complexities when it comes to less-developed markets, such as across sub-Saharan Africa, because those markets lack the infrastructure and safety-monitoring capabilities to manage data collection. Yet products for those markets remain essential. One company that has been conducting clinical studies in Africa into an antimalarial drug struggled to collect patient information from even the more-advanced sites. Then the problem grows exponentially once a product is on the market, because gathering patient data from remote communities is extremely difficult.

Organizational Processes

Many regulatory authorities are seeking to strengthen—or, in some cases, introduce—sound GVP principles, but companies’ objectives are also about achieving better knowledge management across the global enterprise and ensuring good-quality data.

With its GVP legislation, the EMA has turned the spotlight on quality, and companies are seeking to improve cross-functional collaboration between pharmacovigilance aspects and quality aspects. But as Lesia Tontisakis of Allergan pointed out, the alignment of pharmacovigilance and quality systems can become complicated in the management of affiliate activities because such alignment requires an additional layer to align quality and safety on a global level as well.

The more strategic role of pharmacovigilance has implications for affiliates—particularly with regard to the ways information gets gathered and communicated back to the centre. Equally, though, pharmacovigilance’s expanding and evolving role requires leaders at headquarters to have strong understandings of pharmacovigilance regulations globally and how those requirements affect the business.

Globalization is just one area wherein pharmacovigilance must adopt new strategies and expand its skills and capabilities. But if companies can better manage their global demands and their safety systems, the complexities of safety regulations, and the connection between global markets and headquarters, they’ll find themselves better placed to make sure their products—and the patients that use them—thrive.

Marco Anelli is R&D Director at ProductLife Group in Italy and is responsible for the coordination of all clinical and preclinical aspects of projects run internally and on behalf of clients. He can be reached at manelli@productlife-group.com.