Sudhanshu Pandey, Joint Secretary, Department of Commerce, Ministry of Commerce & Industry, Government of India takes some tough questions from Viveka Roychowdhury on the sidelines of the recently held iPHEX 2016. Now in its fourth edition, the trade show, conceived by his Ministry and Pharmexcil, as a platform to burnish India Pharma Inc’s global image, saw regulators from countries as diverse as Ghana, Nigeria and Ukraine, to name just three countries, hold discussions and decide to work towards harmonisation of regulations. Edited excerpts from the interaction
Sir, there is no escaping the fact that the slew of 483s, warning letters, and batch recalls against pharmaceutical manufacturing plants in India over the past few years have damaged Brand India Pharma. What is your ministry’s strategy to address this perception?
Firstly, if you undertake a comparative analysis of 483s issued on a global basis, the ratio of 483s issued to India-based plants is not disproportionate. Secondly, the quality or safety of the end product has not been the issue at all in any of the cases. The inspection procedure has become too process driven. For instance, if an inspector notices scope for improvement in a particular process, it does not necessarily mean that the process is wrong, his interpretation is that since there is a gap, there is a possibility of manipulation, so it deserves a 483. But, the same inspector could have advised the company to further improve the process.
We are engaging with overseas regulators on these aspects but I want to reiterate that the companies who export must comply with the regulations of the importing country and I believe 100 per cent in this.
What can industry and the Indian regulatory system do to plug these gaps?
One major gap during the inspection process is that staff at the middle and lower levels may not speak fluent English or understand the accent. Inspectors coming from non-English speaking countries might not speak fluent English as well.
Many inspectors have started speaking to the shop floor level staff during the inspection, instead of talking to the management. These staff get nervous and scared during these interactions, because in the Indian culture, an inspection has a negative connotation and is considered an examination or a punishment instead of being seen as a normal part of the production process.
So, the plant worker has trouble understanding the query of the overseas inspector, and mumbles a reply, then contradicts his own statement because of lack of clarity caused by the language barrier. The inspector will issue a 483 simply because there is a mismatch between the statements of the senior management and staff, even though there may be no evidence that the process was indeed compromised. Is this an evidence-based approach?
I believe a simple solution to the language barrier is to have inspectors take translators with them as is being done by them in China. In fact, this is one of the suggestions we have presented to overseas regulators. These discussions do seem to be bearing fruit. One overseas regulatory body has reportedly started a week-long orientation programme for inspectors before they depart for India, so that they can correctly interpret some of the cultural responses. We are stressing that the inspector’s evaluation should be totally evidence-based.
Do you see any improvement in the situation?
Yes. Indian pharma’s regulatory woes have attracted a disproportionate level of negative press. But the positive side is that our pharma companies have started investing in training and capacity building of their own employees at all levels, which is the long term answer.
The government is also investing in human resources. The Ministry of Health & Family Welfare is recruiting more inspectors to build muscle. Both my department, the Commerce Ministry, and the Health Ministry, are interfacing more regularly with the state governments to convince them to invest more in the drug regulatory system within states. The number of federal drug inspectors has already increased from 30 to 183, and this number will further increase. I estimate that the combined regulatory staff, at federal and state levels, including inspectors, would be around 1500 today.
This number is far from sufficient, considering that India has almost 10,000 pharma manufacturing facilities. Contrast this with the fact that the US has 15000 regulatory staff for 3000 pharma manufacturing facilities. We do have a long way to go.
But can a country like India afford it? Either the tax payer, the industry or the end consumer would have to pay. The US chose to increase inspection fees [via the Prescription Drug User Fee Act (PDUFA)] which has been in place for over two decades and the more recent Generic Drug User Fee Amendments of 2012 (GDUFA) and the result is that patients in the US have had to pay more for medicines.
Ultimately, the bottom line is, can you give the developing world, the quality desired by the developed world, at developing world prices? Quality does come at a cost. The question is, who will bear this cost? This is the challenge.
Therefore, I believe that we have to strike our own balance, deciding the optimum level of quality so that human health is not compromised. As long as there is enough oversight, sincerity and commitment during the manufacturing process, chasing the state of ‘zero possibility of error’ would be a questionable investment.
This is the point I made at a session I chaired at IPHEX, which had regulators from Ghana on the dais as well. Firstly, developing countries would have to find their own optimal levels of quality. Secondly, there has to be a system of harmonisation because if the same process is repeated in multiple countries, the cost will go up. If there is mutual trust in each others’ quality system, then there is no need to replicate the process. Today, even if you are a member of one of the PIC/S countries where you have invested a lot in all the three stakeholders (regulator, government and industry) there is still no guarantee that your dossier will be accepted in another PIC/S country as they may decide to apply their own national laws. (PIC/S refers to the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme, a movement started in October 1970 by the European Free Trade Association (EFTA) to harmonise GMP regulations)
Developing countries need to come to this mutual understanding because they have no choice but to consider healthcare as a national priority. Else the demographic dividend will not be an asset but a liability, a demographic disaster. It will not happen overnight but this narrative has to start.
So, what is the solution? Do you envisage different groupings of nations, along the lines of the G8-G20 situation?
I would not advocate a G8-G20 divide, but rather allow countries to choose the methods as per their national health requirements, which might be common among some countries. PIC/S is one convention, we could have another. If we can achieve the same quality with different processes and methods, thus reducing costs, why not? Of course, vaccines and complex molecules for cancer, etc. do need to follow set processes and methods as they need higher quality standards. But we can follow this for simple, easy-to-handle molecules, where the risks are minimal.