Ensuring Safer Drugs to Market
We report on some of the key debates taking centre stage at the 8th Pharmacovigilance Conference, held recently, including the implications of emerging markets, utilizing new and emerging technologies, risk management strategies, and shifting towards patient-centricity.
Ever since the Thalidomide incident of 1961, where medication taken by pregnant mothers caused unexpected birth defects, the safety of drugs has been a public health priority. Enter pharmacovigilance - the science and activities which relate to the detection, assessment, understanding and prevention of adverse effects of drugs and other drug-related problems. The 8th Pharmacovigilance Conference brought together representatives of pharmaceutical and biotechnology companies, and regulatory and customs agencies to discuss developments in information and communication technology for ensuring the timely reporting of adverse drug reactions, the safety of drugs, and the detection of counterfeit drugs in the market.
Implications of emerging markets
Emerging markets in Brazil, China, India, Indonesia, Mexico, Russia and Turkey have greatly expanded the growth of the global pharmaceutical trade. The value of this market is expected to reach 1.3 trillion USD by the year 2020. However, the growth of the global pharmaceutical trade brings with it the problem of monitoring adverse drug reactions (ADRs) over a large and growing population base in developing markets. The conference focused on identifying risk factors in bringing medicines safely to these emerging markets in order to avoid, or at least minimize, ADRs.
It also evoked discussion on the three key areas which will prove crucial to the detection, analysis and prevention of ADRs - the learning of new and existing pharmacovigilance standards and requirements; improving compliance with these standards and requirements through training; and, avoiding common deficiencies in safety inspections.
Delegates heard presentations and debates from stakeholders in the pharmaceutical industry on updating knowledge of legislation and policies, as well as technology and communication systems. More importantly, the primary focus was to help industry stakeholders develop an approach to pharmacovigilance akin to high-quality risk management.
There is a need to ensure there are no disconnects between prescribing, dispensing and adverse event reporting.”
Catherine Akers, Senior Regulatory Affairs Manager, Amgen, spoke of the need for more intensified monitoring of ADRs, highlighting that drugs are trialled on a limited number of individuals and so the generalizability of the side-effects to the general population is limited. Furthermore, emerging markets present the possibility of unique immune responses and manifestations that can’t be predicted. The severity of the immune responses will vary, as will the tolerability of the drugs.
ADRs can stem from errors in prescribing and dispensing by healthcare professionals and the actual taking of the drugs by the patients or end-users themselves. Akers said, “Amgen believes three levels of traceability for all biological medicines are essential to allow health authorities to track an event to its root cause. There is a need to ensure there are no disconnects between prescribing, dispensing and adverse event reporting.”
Utilizing new and existing technology
The emerging markets are still developing their pharmaceutical regulation frameworks. Information technology can provide useful solutions for pharmacovigilance. Specifically, information technology can assist in collecting, integrating and analyzing safety data from preclinical models. Information technology can also help researchers to access and use data and research sources for a more effective safety analysis. Stakeholders in these developing markets need to increase and enhance their use of automation technologies that can improve the safety of medicines.
Pharmacovigilance databases already exist and are readily accessible. Learning how to use the pharmacovigilance databases in order to facilitate the detection of ADRs is important in generating safety signals. For instance, when there is a report of off-label or unapproved use of certain medicines, information technologies can enhance decision-making on which signals to investigate.
Sophie Molle, from the World Customs Organization (WCO), introduced delegates to an innovative tool being used in the fight against counterfeit drugs. First, however, she offered some shocking statistics on the number of counterfeit pharma products found during interception operations. She reported that over ten days in April 2013, 23 customs administrations inspected a total of 460 containers and intercepted 1 billion worth of fake products; half of these intercepted fake products were pharmaceuticals.
The new tool that it is anticipated will help reduce these numbersis the IPM Tool - the only global anti-counterfeiting tool. This secure online tool allows two-way communication between customs officers and pharma onoperational data concerning products. Molle explains, “Customs officers aren’t experts in pharma, so need help in order to stop fakes.”
The IPM tool is essentially a database of pharmaceutical information that is available through the internet. This database includes photographs, descriptions, and trace-and-tracking information, as well as reports of lots and batches of medicines that have been reported stolen or missing. This database can then be accessed by customs inspectors through their smartphones.
A customs inspector need only use a barcode scanner application on his or her smartphone to check the barcode or Global Trade Item Number of a particular batch or lot of medicines. The application will then direct the customs inspector to the database, where the authenticity of the drugs being inspected can be confirmed. The customs officer can also obtain information to assist with inspections and help with decisions regarding whether to clear the drugs as authentic or detain them as counterfeit. This can speed up the clearance of authentic drugs through customs whilst also detecting counterfeit drugs.
The IPM Tool was launched in 2011 and was introduced to 60 countries in 2013. By 2014, it was in 80 countries. According to Molle, the aim is to have it in 120 countries by 2017.
Risk management in a "Just Culture"
Dr. Peter-Christoph Schulz, Director of PCS Pharmacovigilance, highlighted the importance of knowing how to analyze data on patient safety. In particular, he proposes a hypothesis-driven approach to the analysis of data to minimize risks to patients, stating, “A hypothesis-driven approach gives a holistic view of everything that could happen and so you can then focus on what is really important for risk management plans.” In other words, risk management strategies should drive the articulation of hypotheses, data collection, and evaluation early in the development program to clearly delineate emerging risks and remaining uncertainty. This data can then be used to inform risk management.
Dr. Brian Edwards, Principal Consultant at NDA Regulatory Science Ltd., built on the importance of risk management with his talk on the role of human factors in pharmacovigilance. Edwards focused on the culture of blame that prevents the accurate and timely reporting of ADRs, proposing that the culture of blame so commonly seen within pharma organizations be replaced with a “Just Culture” - where reporting of errors is encouraged and honest mistakes are separated from intentional mistakes. Indeed, he strongly advocates for a systems approach being taken to error management – mistakes are about the organization rather than the individual.
A "Just Culture" would also emphasize the need to identify problems or errors at a very early stage. The aim is to avoid the errors having the effect of undermining the reporting system and breaking trust in that system. He concluded by saying that errors will always be made - to err is part of human nature – but he also noted that while mistakes can’t be diminished, the way mistakes are responded to can be.
Involving patients in pharmacovigilance
There was a thought-provoking panel discussion between Barbara Dawson (Vice President, EU QPPV at The Medicines Company), William Gregory (Director of Safety and Risk Management, Pfizer, USA), Summit Munjal (Medical Director Lead at Takeda Pharmaceuticals), and Dr. Eszter Teleki (Group Director at Bristol-Myers Squibb Pharma EEIG). Emphasis was placed on a patient-centered focus when monitoring ADRs. Monitoring ADRs eventually translates into value for patients. They proposed that, in order to monitor and report ADRs, there must be close collaboration between patients and prescribers. Communication and collaboration ultimately improves patient safety.
They also proposed that patients themselves could receive training in self-monitoring for ADRs and how to report them. Patients participating in clinical trials could also be given directions as to what ADR information they should tell their doctors about. Patients, after all, are experts in their own condition and so their input in monitoring and reporting ADRs is invaluable.
There needs to be a change in outlook on pharmacovigilance from merely dealing with ADRs as they happen to actively managing that risk.
The overwhelming call of the conference was for change. There needs to be a change in outlook on pharmacovigilance from merely dealing with ADRs as they happen to actively managing that risk. This could be achieved by generating hypotheses about the possible risks of ADRs from available data, as well as utilizing new tools and technologies to enhance pharmacovigilance. This applies to experts investigating counterfeit drugs and involves arming customs inspectors with data and technology so that they can intercept counterfeit drugs before they reach the intended emerging markets.
The need for cultures that enforce pharmacovigilance was also emphasized, with a focus on moving from a culture of blame to a culture of trust. The most pressing message that we were left with, however, was the need to involve not only healthcare professionals but also patients in the monitoring of ADRs.
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