Dr J Vijay Venkatraman, MD and CEO, Oviya MedSafe and Karunakaran Shanmugam, QA Associate, Oviya MedSafe, advocate implementing pharmacovigilance in a prudent manner to augment the growth of the Indian pharma industry
Pharmacovigilance (PV) is a scientific discipline that significantly impacts public health. It involves several stakeholders such as the pharmaceutical industry, academia, healthcare professionals, consumers and drug regulatory agencies. Pharmacovigilance is often perceived by pharmaceutical companies as an obstructive regulatory ordeal rather than an integral pre-requisite for marketing their products. The traditional perception that PV is a cost centre that does not generate any return on investment is so deep-rooted in the industry that the title of this article itself may seem oxymoronic to many. However, the practice of performing pharmacovigilance in a prudent manner may rather be an augmenter for the pharma industry, which this article explores in detail.
The World Health Organization (WHO) defines PV as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. The specific aims of PV are to:
The above-said objectives should be considered the cardinal responsibilities of all PV stakeholders who can never be justified in compromising on their duties. As any other PV stakeholder, the pharmaceutical industry is also bound to fulfil these obligations. In fact, patients are entitled, as customers, to expect accountability on the part of pharma companies, in cases of any complaints. But, this has led to the unfortunate interpretation of the pharma industry that PV is a detrimental activity that could challenge their prosperity. However, what has not been realised yet is that PV can also add significant value to the pharma industry beyond its commitment to being the custodian of patient safety.
Value addition is defined as the increase in value of a product or service as it goes through the stages of being developed and produced. Value-added products or services are worth more because they have been improved or had something added to them. In other words, value addition is something that justifies the higher worth deserved by a product or a service which has the value added feature versus a similar product or service that does not have it.
Given this background, adoption of the principles of PV may be considered to add value to the concerned pharma companies by:
Enhancing Corporate Image
Corporate image or reputation denotes the way in which a business house, its activities and its products are perceived by outsiders. Corporate image is a composite psychological impression that continually changes with the company’s circumstances, media coverage, performance, pronouncements, etc. In a competitive business scenario, many businesses actively work to create and communicate a positive image to their consumers, shareholders, regulatory authorities and the general public. A company that allows its corporate image to be messed up is more likely to find itself in a variety of problems. PV is an enhancer of corporate image in the following aspects:
Ensuring financial security
Every pharma company wants to be financially secured by preventing loss due to safety-related product recalls and consumer lawsuits. Such scenarios will also lead to decline in company sales, share prices and erosion of shareholder wealth.
It is a fact that no drug exists without its adverse effects and therefore, no pharma company will be penalised just for encountering an Adverse Drug Reaction (ADR) unless the company does not act on it per the applicable regulatory requirements or conceals safety information from the competent authorities. If such non-compliance is noted and if a lawsuit is in the picture, the Court of Law may question the PV system in the company and, in the worst case, this scenario may lead to heavy penalties or even closure of the company. Therefore, having a proper PV set-up protects pharma companies from litigation-related loss by enforcing and documenting compliance with the regulatory norms. In fact, PV is an insurance policy, the value of which is not often realised until a crisis occurs.
Generic companies often come across scenarios wherein they need to choose a few among many products of comparable revenue potential, for commercialisation. In such situations, it may be advisable to select less risky products in terms of safety. To do so, the activity of assessing the safety profiles of the products in question needs to be performed. A simple global literature search for each revenue-wise comparable product may be enough to stratify them based on their risk profiles and provide evidence-based recommendations to the business decision-makers in this regard.
Envisioning scientific challenges
The PV unit opens up a two-way communication channel between the consumers and the company for discussing any issue involving the company product. During this process, the reporters may share data such as off label use, medication error, product quality defect, etc, which may not necessarily be linked to any adverse event. There is also an opportunity for the company to understand product usage patterns and practical difficulties the consumers face with the company products, which may then be passed on to the respective departments within the company for identification of the root cause and for improvisation of the product.
Such data is usually received from Patient Support Programs (PSPs) and Market Research Programs (MRPs) in particular. PSPs and MRPs are aimed to help patients and/ or healthcare professionals (HCPs) better manage disease and optimise treatment. Identifying adverse events is not an objective of PSPs and in fact, PSPs are usually not designed to be organised data collection schemes. However, the information obtained from PSPs will provide new scientific insights which may significantly aid product development. PV data can also support product R&D by spotlighting bioavailability/ absorption issues, safety issues associated with impurities/ excipients, formulation-linked safety issues and so on. Several life-threatening drugs which have been withdrawn at various stages of drug development and many drugs which were perceived and subsequently announced unsafe in the past have later re-entered the market with appropriate safety recommendations either for the same or for different indications. Both of these scenarios are results of proper pharmacovigilance being performed. For example, the thalidomide disaster is considered one of the darkest episodes in pharma research history as it caused phocomelia in new born babies, a rare congenital abnormality in which the long bones fail to develop, when the drug was taken by antenatal mothers. More than 10,000 babies with phocomelia were reported in 1961 and the drug was banned the following year all over the world. Over a period of time, the beneficial effects of thalidomide were acknowledged and it is now recommended for the treatment of multiple myeloma, erythema nodosum leprosum, aphthous ulcers in HIV-infected patients, chronic graft-versus-host-disease and a variety of tumours. Today, thalidomide is available even in regulated markets like the US and the UK with appropriate usage restrictions. This has been possible due to the risk management programmes centred on pregnancy which were put in place for the product failing which we would have lost the product forever.
The statin group of drugs which are widely prescribed today were once feared due to rhabdomyolysis associated with their usage. Careful PV activity revealed that rhabdomyolysis was caused only when statins were taken in higher starting doses, especially in Asian patients. Once the root cause was identified, proper warnings were put in place and it resulted in retention of the drug in the market.
Although the mandate of protecting consumers from harmful effects of drugs is a core objective of PV, the above cases have been illustrated to emphasise the fact that PV also protects products from being blindly withdrawn from the market citing safety issues.
PV sometimes opens up new avenues for drug development, often in a hitherto unknown indication. Minoxidil, which was initially approved as an anti-hypertensive drug was later identified to cause hair growth as an adverse effect which resulted in the drug being re-developed for the indication of hair loss. Today, Minoxidil is available over the counter for the treatment of androgenic alopecia, thanks to a ‘beneficial adverse effect.’
Enabling business expansion
A robust PV system is a vital need for pharma companies intending to market their products in developed countries. In fact, the very presence of a product in a developed market is considered as a surrogate measure of safety by many developing countries in which the PV system is passive and still emerging.
Figure 1 outlines the life cycle of a pharma company which begins its business usually as a drug manufacturer. Most of its business could be in contract manufacturing in which scenario it may have little PV liability. As part of its growth, it starts to market its products in its home country and in unregulated markets where PV liabilities may be rudimentary. In the next steps, when it moves into the Rest of the World (RoW) countries which have mandates for PV. Finally, the dream destination for such a company would be to have its own market authorisations in the developed markets like North America and Europe, which have the most stringent PV obligations. It is thus obvious that business expansion is impossible to achieve without investing in PV. However, what needs to be highlighted is that PV requirements have begun to emerge even at a manufacturing stage, in recent times, indicating that PV is necessary even to achieve growth in domestic business.
Further, in the global scenario, many multinational pharma companies with innovative products look at establishing joint ventures with other pharma companies which have better market penetrations in other parts of the world. Obviously, local pharma companies with good PV compliance track records stand better chances to win such business deals, although there may be many other parameters for partnership decisions to be made.
The pressing need of pharma companies to have PV systems in place in order to seamlessly run and grow their businesses have generated quite a lot of demand for PV capabilities. Not all companies are willing and able to set up their in-house PV systems, which has resulted in the evolution of the fast-growing PV outsourcing industry, which is expected to continue its exponential growth for the next decade too.
PV is a cross-functional subject that used to be ignored in the past. But in recent times, PV has asserted itself as a key regulatory obligation for the pharma industry. It is a fact that many pharma companies feel that PV is a speed-breaker, which perception is not entirely untrue. However, all of us will agree that speed-breakers are essential to ensure everyone’s safety when one drives through a crowded street. On the other hand, PV to a pharma company in the growth mode is like a seat belt to a luxury car speeding on a motorway. It would be illogical to assume that PV would be a speed-breaker on a motorway, but this is how PV is seen by many pharma companies. Hence, it is high time for us to realise that the pharma industry cannot safely exist without PV. In fact, PV is an ‘Unsung Hero’ which monitors the benefit-risk ratio of not only the pharma products but also that of the pharma companies that manufacture or market them.
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