Why local knowledge is key to global pharmacovigilance outcomes

By Alex Brenchat and José Miguel Rivas Romero

There is no issue more important to health authorities than patient safety. This has led to pharmacovigilance (PV) being one of the most highly regulated fields, with strict yet often differing expectations from local authorities. At the same time, we are witnessing growing efforts by marketing authorisation holders (MAHs) to standardise their regulated activities with the aim of enhancing processes and outcomes.

The challenge for companies is to ensure their local affiliates meet local PV obligations while staying aligned with global PV requirements. Often, however, companies lack PV expertise at the local level and struggle to achieve a coordinated approach to global PV operations, which results in inefficiencies, delays or non-compliance.

The burden on the local affiliate can be enormous. In smaller markets in particular, local staff often wear many hats, managing regulatory, quality and medical affairs activities as well as meeting commercial objectives. Many lack the level of PV expertise needed and can’t give these activities their full attention.

Often PV management at the central level is not aware of the local requirements, which can vary significantly from one country to the next, even within markets like the EU, or how certain business models might impact local PV expectations.

Lack of standardisation also puts pressure on local affiliates who must comply with global PV standards while also adapting to their country’s regulatory requirements.

In some cases, pharmaceutical companies may rely on third-party vendors to manage local PV activities. Ensuring that these external entities adhere to the same high compliance standards is a significant challenge. Mismanagement by third parties can lead to non-compliance issues for which the MAH remains accountable, as spelled out by regulatory authorities. Companies must therefore ensure they maintain full oversight of the pharmacovigilance system master file (PSMF).

Globalisation has led the industry to expand into many markets, each of which has its own set of PV regulations. These can differ quite significantly in terms of reporting timelines for adverse events, requirements concerning documentation and formats, language requirements and risk management plans specific to local populations. Keeping track of and complying with these points of difference can be challenging.

By way of example, in the Middle East and Africa region there are quite significant differences between countries. PV regulations in countries such as Saudi Arabia, South Africa and Egypt are developed and strict, while some countries have only started their PV journey in the last few years and others have no clear regulations at all.

On the ground expertise can often be a challenge for companies. For example, PV experts on the ground note that Oman requires a Local Safety Responsible pharmacist who resides in Oman if the company does not have a scientific office in the country. But, as our experience has found, most Omani pharmacists are working for the health authority or public institutions, creating a conflict of interest. In other countries, such as Algeria and Tunisia, PV personnel are leaving for better opportunities abroad, regional experts have reported.

In these markets, communications about regulatory updates are not always shared via standard channels such as the regulator’s website. As such, companies need local presence and contact in alternative channels such as personal relationships and WhatsApp groups. This underscores the importance of having expert support to navigate and understand the local requirements.

Regardless of who is handling local PV activities, our experience has been that there are several common problems that tend to arise, particularly in smaller, less well-developed markets.

The first is a resource issue. Companies unfortunately often don’t provide smaller or emerging markets with the resources they need to properly meet their PV obligations, including adequate technology, personnel or operational support. Under-resourced affiliates often struggle to meet regulatory requirements, manage pharmacovigilance effectively and perform key operational tasks.

Another issue often observed is inconsistent monitoring of local affiliates, which can result in companies failing to meet the requirements of health authorities in those markets.

From the local affiliate perspective, failing to maintain strong relationships with local regulatory authorities, either due to resource constraints or oversight, can create issues for companies. As previously noted, it is in fact these relationships that are key to staying on top of local requirements and ensuring expectations have been met.

Furthermore, companies sometimes underestimate the complexity of local regulatory environments, believing that the affiliates will manage compliance.

If those affiliates don’t have adequate resources and oversight and have not maintained a strong relationship with the health authorities, the MAH may not have that important regulatory intelligence that can be key to keeping a product on the market.

There is also an assumption that standard operating procedures (SOPs) that work well at the global level will be sufficient at the local level. But, as our experience shows, this is not necessarily the case. It is important to ensure any SOPs are relevant and make sense to that affiliate office.

To avoid these issues, it is important that MAHs allow sufficient time and resources for training that is tailored to the needs of local staff and not burden them with unnecessary information or complex processes that could be handled more seamlessly.

While demand for PV outsourcing services has risen significantly in recent years, MAHs need to consider these partnerships as well as their own roles and responsibilities carefully. There are several important steps we recommend MAHs undertake when initiating an outsourcing engagement.

While maintaining proper oversight, the MAH cannot expect their partner to take on the responsibility for local PV activities without ensuring they are properly integrated into the business, which includes providing them with access to relevant information and connecting them with the relevant stakeholders from the office. The flipside of that is building the buy-in at the local level by properly communicating headquarters’ intentions to the local affiliates.

Expectations also need to be clearly communicated and properly agreed – and compensated. Service providers are reimbursed for activities performed and expectations beyond these are often unrealistic.

Many of the issues we see with local PV outsourcing arise because adequate information is not shared from the headquarters to the affiliate or to the outsourcing partners, and relationship building is left entirely to the local affiliates. The same is true if the affiliate does not communicate all its processes and local agreements with headquarters. For example, local partnerships with third parties may not always be known at central level. While the local affiliate may prefer local PV agreements to be managed without interference from the headquarters, it is generally expected that PV agreements are reported and that all such contracts are reflected in the PSMF.

Another problem that can arise is if the MAH decides to partially outsource or subcontract PV activities without knowing whether this will be permitted by the country. An example of this would be Brazil, where the authority requires clear and detailed documentation defining those involved in each PV activity and forbids subcontracting. Additionally, some roles in Brazil, including the pharmacovigilance officer (RFV) and the deputy may not be outsourced.

The role of the project manager is often not well understood, which can make ongoing communication problematic. Furthermore, if clear objectives are not set, PV teams can struggle to understand what is expected of them.

Understanding the local needs and expectations, what the biggest time restraints are and where the greatest challenges lie is key to successfully managing local PV activities.

Steps MAHs can take to better manage the relationship, whether with internal teams or outsourcing partners, include clear two-way communication, understanding the nuances to each market, eliminating unnecessary or insufficient processes, carrying out constant monitoring of local performance and emerging risks, and building mutual trust supported by robust PV systems.

References are available on request.

Alex Brenchat is Vice President, Practice Area Lead for Local Pharmacovigilance Services and José Miguel Rivas Romero is Program Manager, Service Line Lead for LPVS and Pharmacovigilance Expert, both at PharmaLex, a Cencora company

Disclaimer: The information provided in this article does not constitute legal advice. PharmaLex and Cencora strongly encourage readers to review available information related to the topics discussed herein and to rely on their own experience and expertise in making decisions related thereto.