The Indian pharma industry lags when it comes to implementing pharmacovigilance. Yet, it can play a pivotal role in addressing issues of drug safety and assuring quality
Quality assurance (QA) in pharmaceuticals is a wide concept covering all matters that individually or collectively influence the quality of a product. It ensures that pharma products are of certain required quality for their intended use. QA is also a part in pharmacovigilance (PV), which is concerned with identifying the hazards associated with pharma products and with minimising the risk of any harm to patients. A robust PV QA department in place can increase the overall growth of the pharma company. Global players like the US and the EU have made rapid and far reaching progress, whereas, Indian pharma industry is lagging behind. Indian mid segment/ generic pharma companies started late with their PV set ups and few of the companies are still contemplating. With the newly drafted Good Pharmacovigilance Practice (GPVP) guidelines for Indian pharma industry by Central Drugs Standard Control Organization (CDSCO), it is expected that PVQA in India would be more heard of and/or practiced, in India in the near future.
Is quality assurance system in place?
The quality of medicine has been a major concern in the pharma industry. There has been a growing awareness on the significance of quality of pharma products. QA plays an important role in the development of products and services in pharma and biotech, as part of GMPs (Good Manufacturing Practices).
Dr J Vijay Venkatraman, MD and CEO, Oviya MedSafe, speaking on the concept of QA in pharma industry says, “There is no doubt that the pharma industry is growing by leaps and bounds. However, I feel that the domain of QA and its capability to augment the industry’s success is not well-understood. Rather, the rest of the industry tends to consider that adherence to quality norms lessens their speed and cost-effectiveness, without realising that having a robust QA department in place will be the first step to protect the organisation and in turn the whole industry in the long run.”
Unfortunately, the term QA is considered with regulatory compliance. While QA deals with regulatory compliance, compliance is just a part of QA. If QA activities are performed as a mere compliance exercise, the purpose of QA is defeated. Another problem is that the needs of QA departments are often treated as low priority and are the first to get impacted during cost-cutting initiatives.
Explaining the current scenario of PV QA, Dr Venkatraman further says, “QA plays a very important role especially in PV. However, PV QA departments, on an average, are prepared to cope with favourable outcomes only. There is an unreasonable fear of negative outcomes and due to it, a professional approach to put up Corrective And Preventive Actions (CAPAs) is lacking. Added to it is the fact that QA is seen not as a ‘need to have’ part of the process but as a ‘good to have’ one. Having said so, the awareness of these findings is much better than before and I feel it can only bring us more progress.”
Dr Ranjana Pathak, Global Head, Cipla believes, “QA in PV is still in its infancy stage. It will soon become an integral part of the PV process. As expectations of the regulators keep increasing, the industry has to step up and match the expectations if they want to stay relevant in the industry.”
Moin Don, President and CEO, PVCON says, “QA is a very broad field, encompassing all GXP (GMP,GLP.GCP, GVP,GDP etc.) domains. While QA has been always an evolving and dynamic science, I would like to restrict myself to my area of expertise that is PV and GPvP.
The Indian generic pharma companies always (erroneously) considered PV obligations to be responsibility of multinational innovative companies. In addition, the PV set up has been always considered as ‘Cost centre’ without ‘Return On Investmant (ROI) by the senior management and never got the type of support, it required.”
PV practice
Recently, the health ministry has mandated pharma companies to set up PV department to monitor the safety and quality of authorised pharma products. The Pharmacovigilance Programme of India (PvPI) has been very successful in bringing about a sea change in the PV scenario in India. Due to PvPI, India became the seventh largest contributor to the Uppsala Monitoring Centre’s (UMC) drug safety database (Vigibase). But, what was more important was that PvPI demonstrated appreciable quality in terms of completeness of the Individual Case Safety Reports (ICSRs) reported to UMC (0.94 out of 1). In fact, PvPI has a separate quality review panel in addition to the signal review panel and core training panel.
“PvPI has recently launched the Pharmacovigilance Guidance Document for Marketing Authorization Holders (MAH) of Pharma Products in India which has a dedicated module for quality management system. It provides exhaustive information on PvPI’s expectation in terms of quality from a MAH. Moreover, PvPI conducts skill development programmes for their staff as well as for interested professionals which is a very important step towards better QA of drugs in India,” says Dr Venkatraman.
“PV in some countries is making in roads and hence not fully understood. However, PV is essential to ensure the safety of the patient particularly in relation with adverse events of a drug/ device on the patient. PV is also going to ensure better and long standing usage of a particular drug on an uncontrolled environment with and without co morbidities etc,” says Pathak.
Speaking on the various initiative taken by PvPI, Don says, “To the credit of PvPI, it must be said that with more than 200 AMCs throughout India, and various initiatives taken, PV is reaching to people/places which was earlier not thought of. The implementation of GPVP guidelines would not only strengthen the PVQA but would also add to the understanding and realisation of MAHs about their ultimate responsibility towards patients’ safety and well being which of course can be achieved through overall robust QA system.”
Challenges
Today’s pharma business is generally global. Hence, having locally acceptable standards alone will not guarantee growth of a concerned organisation. However, there are problems in living up to global standards because there is considerable variation in the standards followed in one region as opposed to another.
“Having a QA system that will serve as a ‘Common Minimum Programme’ in terms of global compliance and therefore global quality. This is one of the primary challenges. In the context of PV, a significant challenge is that there is a lack of expertise in differentiating Product Quality Complaints (PQCs) from Adverse Events (AEs) or Lack of Efficacy (LoE) cases. This is one area where proper understanding of PV and having a proper PV QA system in place will have a direct positive impact on the overall quality of a pharma product manufactured or marketed by a given company. This is a priority area that deserves the attention of the top managements in pharma,” says Dr Venkatraman.
According to Dr Sameer Thapar, Global Pharmacovigilance Director, Oracle Health Sciences Consulting, the greatest challenge is finding suitable auditors for PV QA. It is not enough to convert a former GCP auditor to a GVP one without providing them sometime in a PV operations role. He says, “PV is a process-based domain, where one task can be repeated but with a slight variation each time. Take for instance, the Medical Review function. It is rendering a consistent judgement on subjective criteria. Two judgements may have the same end result, but could be derived from two differing viewpoints. Also, in this process-based domain, checklists, such as ones used for other GXP audits, rarely are beneficial. There are many governing factors on operational decisions, from appeasing regulations to nuances brought by previous external inspections. It is mandatory for anyone entering the PV QA area to realise these criteria and to spent time in or around the operational analytics to fully be able to render a good GVP audit.”
Speaking from the PvPI perspective, which also plays an important role in the quality assurance of the medicine and what are the challenges faced by the sector, Dr V Kalaiselvan, Principal Scientific Officer, Indian Pharmacopoeia Commission says, “Lack of skilled PV manpower is a major challenge faced by the pharma industry. In line with Prime Minister’s Kaushal Vikas Yojana (PMKVY), Indian Pharmacopoeia Commission has started a skill development programme on ‘Basics and Regulatory Aspects of Pharmacovigilance.’” Thus skilled manpower can be utilised for the establishment of a sustainable PV system in pharma industries.
“There are numerous challenges in the industry, from trained people up to clarity with regulations and everything in between. Today’s consumer is much more savvy, they expect more from the manufacturers and technology often is ahead of regulation, for example novel therapies (growing skin, organs etc), the regulations have not been developed as yet,” says Pathak.
Required measures
“A robust PV system needs to be rigorously followed by the pharma industry. We need to have an integrated approach to develop a robust PV system. The pharma industry and regulatory authority must work together for patient safety,” suggested Dr Kalaiselvan.
According to Don, a very stricter /stringent oversight by the regulatory authority and demand for GXP compliance alone would ensure standard quality medicine in the market. Presence of sub standard, adulterated /spurious medicines in the market is well known. With access to advanced technology and processes, this nefarious activity can be significantly curbed given the political will, that is required.
Dr Venkatraman, says, “Quality has to be ensured right from the stage of BA/BE studies in case of a generic product and from the stage of clinical trials in the case of an innovative drug. While clinical trials are quite well-regulated, BA/BE studies are still riddled with questions on their reliability. We may recall that this has led to product withdrawals following analyses of BA/BE data by foreign regulators. Similarly, GMP deviations keep getting identified during regulatory inspections. Therefore, the focus on quality research and quality manufacturing has to be improved.”
He also suggested that doctors and other healthcare professionals need to be motivated to report PQCs and/or AEs without hesitation so that the real adverse effect load of any drug in India can be assessed.
With the launch of the PV Guidance Document for MAHs in India which is to be effective from January 2018, the industry now has a higher level of commitment to patient safety in the form of a governmental obligation. Enforcing rules with proper conduct of PV audits and inspections will be the next level in augmenting patient safety in India.