Pharma Focus Asia

UNIFYING DRUG SAFETY

The significance of harmonisation in pharmacovigilance

Nikesh Shah, VP and Global Head, Safety and Pharmacovigilance, Indegene

Dr. Siva Kumar Buddha, Director - Safety and Pharmacovigilance, Indegene

In the world of pharmaceuticals, harmonisation in pharmacovigilance is paramount. Organisations such as ICH have standardised regulations, streamlined drug submissions, and improved adverse event reporting. Harmonisation involves aligning regulations, data collection, and reporting standards across countries and regions. This enhances the sharing of adverse event information, streamlines drug monitoring, and ensures patient safety through consistent, evidence-based decision-making in the pharmaceutical industry. The interview will uncover the nuances of Harmonisation in Pharmacovigilance.

1. Could you explain what harmonisation in pharmacovigilance means and why it is important in the context of global drug safety?

In pharmacovigilance, harmonisation refers to the collaborative effort among regulatory authorities, pharmaceutical companies, and stakeholders to standardise and align processes, regulations, and standards related to drug safety monitoring and reporting on a global scale. It ensures consistent and uniform practices across different regions and countries. This consistency simplifies the exchange of critical information regarding adverse events, allowing for earlier detection and response to potential safety issues, which can improve patient safety. In addition, harmonisation enhances the efficiency of new drug applications and regulatory submissions, reducing duplication of efforts and expediting the approval process. This, in turn, accelerates patients' access to new and potentially life-saving medications. Moreover, harmonisation promotes transparency and collaboration in the pharmaceutical industry, fostering the sharing of best practices and the pooling of resources to improve overall drug safety. It also facilitates international research collaborations, leading to a more comprehensive understanding of drug risks and benefits. Organisations such as the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the Pan American Network for Drug Regulatory Harmonisation (PANDRH) are working towards bringing together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of pharmaceuticals and develop guidelines. ICH has been around since 1990 and has grown to include more members and observers from around the world. ICH aims to create global guidelines for the pharmaceutical industry so that safe and effective medicines are developed, registered, and maintained in the most efficient way possible. ICH's guidelines are used by many countries to assess new medicines. Currently, it includes 21 members and 36 observers, representing regulatory authorities, pharmaceutical companies, and other stakeholders from around the world.

2. How does the global regulatory landscape impact the need for harmonisation in pharmacovigilance practices?

The global regulatory landscape has a significant impact on the imperative for harmonisation in pharmacovigilance practices. This globalisation of the pharmaceutical industry necessitates a unified approach to drug safety. The European Medicines Agency (EMA) especially in the EEA regions has been very instrumental in harmonising at the European Union (EU) level from lab to patient activities concept.

Several key factors highlight the impact of the global regulatory landscape on pharmacovigilance harmoni sation. Some countries have unique pharmacovigilance regulations, such as REMS in the USA, Analysis of similar events requirements for SUSARs in the USA and a few other countries, and French imputability for causality for cases submitted to ANSM, to name a few. There are still differences in guidelines pertaining to definitions, causality scales, frequency of the literature search, and signal statistical method for quantitative analysis etc.. Asia is the most populous continent with nearly 60 per cent of the world's current population; yet, there is no centralised data system, PV regulations and harmonised reporting rules. This heterogeneity creates challenges for pharmaceutical companies, which must navigate a complex web of regulations to ensure compliance. This also increases their costs in maintaining compliance with diverse regulations. The primary objective of pharmacovigilance is to safeguard patient health. Global harmonisation consistently ensures that drug safety data is collected, analysed, and acted upon, regardless of geographic location. This uniformity is crucial in promptly identifying and mitigating potential safety concerns. With the globalisation of clinical trials, often conducted in various countries, harmonisation becomes a logistical necessity. It streamlines the process of reporting adverse events and standardises the evaluation of safety data. The COVID-19 vaccine situation is a good example where the safety data published from other countries were taken into consideration by the public to make decisions on the choice of the vaccine.

3. What are the key benefits that pharmaceutical companies and regulatory authorities can gain from harmonised pharmacovigilance processes?

Harmonised pharmacovigilance processes offer pharmaceutical companies and regulatory authorities several key benefits. Mainly, the harmonised processes streamline drug safety reporting and data exchange, reducing administrative burdens and ensuring consistent, efficient operations. In addition, harmonisation enhances global collaboration, enabling quicker detection and mitigation of safety concerns, and ultimately safeguarding public health.

Additionally, it expedites the regulatory approval process, accelerating patients' access to safe medications while reducing costs for pharmaceutical companies. Furthermore, standardised practices foster transparency and trust, promoting industry compliance and regulatory confidence. Overall, harmonised pharmacovigilance not only improves patient safety but also enhances operational efficiency and regulatory effectiveness for both pharmaceutical companies and regulatory bodies.

4. How does harmonisation in pharmacovigilance contribute to enhanced patient safety and better healthcare outcomes?

Standardising safety-monitoring practices globally ensures timely and consistent reporting of adverse events, enabling rapid identification of potential risks associated with medications. Early signal detection can prompt regulatory agencies and pharmaceutical companies to take prompt actions to mitigate and safeguard patients. It also brings more transparency in the safety data, which can enable better benefit-risk analysis. Streamlined processes can give patients quicker access to new medications through faster regulatory approvals. This also contributes to better health outcomes via optimised treatment plans, and reduction in medication errors, therefore building patient trust and compliance.

5. In what ways does harmonisation streamline reporting and data management processes, leading to more efficient resource allocation?

Currently, there are multiple reporting rules like timelines, formats, criteria (seriousness, listedness, country, etc.,) and medium for submission of the individual cases. This causes a lot of administrative burden and additional resources to manage and monitor. This can lead to multiple chances of missing the timelines and reporting as necessary, leading to diminished visibility of the risk profile of the drug for the regulators. This burden can also cascade to the downstream activities where the requirements like aggregate reports submission timelines and medium of submission are different. Harmonisation initiatives need simplification and centralization of reporting rules at a global level. This can reduce the administrative burden and allow resources to be redeployed for more important activities like signal and risk assessments. Centralisation of data leads to more efficient data management, making it easier to identify safety signals and trends. Not only this the collaboration on harmonisation initiatives encourages knowledge sharing among pharmaceutical companies and regulatory authorities.

6. How does harmonisation influence the submission of safety data to regulatory authorities? Are there specific requirements or guidelines that companies should be aware of?

Harmonisation in pharmacovigilance significantly influences the submission of safety data to regulatory authorities. It promotes a standardised and streamlined approach to reporting, ensuring consistency in the information provided to regulatory agencies across different regions. Most of the time the regional PV guidelines are built based on the ICH PV guidelines (E2A to E2F), which promotes some sort of standardisation. These guidelines cover aspects like ICSRs, periodic safety update reports (PSURs), Pharmacovigilance Planning and Developmental safety update reports (DSURs). Adhering to these standards simplifies the submission process, as companies can follow a single set of guidelines for multiple markets. This alignment reduces the burden on pharmaceutical companies, allowing them to efficiently compile and submit safety data while ensuring compliance with global regulatory expectations. Recently, TransCelerate Biopharma Inc., which is funded by 20 organisations dedicated to making research and development, including pharmacovigilance monitoring and reporting, published an article on ICSR replication with different health authority databases and its impact on the quality analysis of the safety information. They have found that the average ICSR is replicated 3 times. However, some ICSRs are replicated in 10 or more databases leading to inconsistencies in the data and the exposure data inaccuracy. There is an opportunity for implementing a centralised database with integration between multiple databases to avoid them. On similar lines, MSSO MedDRA is based on a terminology belonging to the Medicines and Healthcare Products Regulatory Agency (MHRA) of the UK; this was developed using the ICH process by the ICH partners, including WHO to facilitate a standardised medical terminology. This has very much helped to maintain consistency in the coding of adverse events, medical history, drug indications, lab tests etc.; recently they have also mapped the ICD-10 with MedDRA, which also gives room to integrate the real-world data into the safety analysis.

7. What are some of the challenges or barriers that companies may face when attempting to implement harmonised pharmacovigilance practices?

As with any big change, with the harmonisation of pharmacovigilance processes across the globe, there are also challenges to tackle. Some of them are Data privacy and security issues and laws in different countries, resistance to change within the organisations and regional regulators, cultural differences, data compatibility issues and budget allocation, amongst others. Despite these challenges, the benefits of harmonised pharmacovigilance practices, such as improved patient safety, streamlined operations, and enhanced regulatory compliance, make it a worthwhile pursuit for pharmaceutical companies. Effective change management, strategic planning, and collaboration with regulatory bodies are key strategies to overcome these obstacles and achieve harmonisation successfully.

8. What role does technology play in enabling harmonisation in pharmacovigilance? Are there specific data standardisation initiatives that are particularly impactful?

Yes, technology plays a pivotal role in facilitating harmonisation in pharmacovigilance by enabling streamlined data management and reporting processes. One particularly impactful initiative is the adoption of the ICH E2B (R3) standard for Individual Case Safety Reports (ICSRs). This standard defines a consistent format for reporting adverse events, making it easier for pharmaceutical companies to submit safety data to regulatory authorities worldwide. Furthermore, the use of advanced data analytics and artificial intelligence (AI) contributes significantly to harmonisation efforts. AI can process large datasets and identify safety signals more efficiently, enhancing the ability to detect emerging risks consistently across different regions. Similar to MedDRA, the adoption of WHO DD in pharmacovigilance systems ensures that the names and attributes of drugs are uniform across regions.

9. Can you discuss the importance of global collaboration and knowledge sharing in achieving harmonisation goals in pharmacovigilance?

Global collaboration and knowledge sharing are pivotal in achieving harmonisation goals in pharmacovigilance - for reasons like standardisation of best practices, enhanced patient safety, more visibility for the regulators on the risk profile of the drug, enhanced data analytics application on the centralised data, common goals with common data, consistency in the data standards, early detection of signals with red flags within the system, resource optimization and also room for more real-world data integrations. It promotes transparency, consistency, and collective problemsolving in pharmacovigilance. They not only advance the harmonisation of safety practices but also enhance patient safety by facilitating the early detection and management of medication risks on a worldwide scale.

10. What emerging trends or technologies do you see playing a significant role in advancing harmonisation efforts in pharmacovigilance?

With the proven use cases in other industries and within PV, regulators are also very positive about implementing AI and automation in PV. Newer large language models (LLMs) like ChatGPT and other AI techniques have the potential to analyse vast datasets more efficiently than manual methods through ML and NLP. They can also help integrate the RWD from electronic health records, wearables, and social media, which can provide a broader and more diverse dataset for pharmacovigilance. Particularly in terms of data security and privacy concerns, technologies like Blockchain offer secure and transparent data sharing. Its decentralised nature can simplify global data exchange and enhance the reliability of safety data, promoting harmonisation. In addition, Telemedicine and Remote Monitoring can enable remote patient monitoring, offering a broader view of medication safety and side effects, particularly relevant in the era of decentralised clinical trials. These advancements are integral to achieving global harmonisation in drug safety monitoring and ultimately improving patient health outcomes.

11. Any other comments?

In totality, harmonisation in pharmacovigilance requires collective action and cooperation among regulatory authorities, pharmaceutical companies, vendor companies, healthcare professionals, patients, and international organisations. Vendor companies, in particular, have a crucial role in providing the technological infrastructure and solutions necessary to support harmonised practices in data management and reporting.

--Issue 53--

Author Bio

Nikesh Shah

Nikesh Shah, heads the Safety and Pharmacovigilance business at Indegene. He is also responsible for Marketing, Presales and Strategic Initiatives for the Enterprise Medical Business. Previously, he led the Corporate Strategy function at Indegene. He worked with the CEOs office and the Founding team on identifying and executing strategic initiatives within the organization including M&A, BU strategies and corporate planning initiatives.

Dr. Siva Kumar Buddha

Dr. Siva Kumar Buddha, a medical doctor with an MBA in Leadership and Strategy, possesses over a decade of diverse Pharmacovigilance experience. He is currently working in the capacity of Director, Pharmacovigilance at Indegene. He is a staunch advocate for PV automation and has spearheaded several automation initiatives, underscoring his commitment to innovation in drug safety. He is also a prolific author, trainer, and mentor in the field.

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