Gopal Nair, Director, ISPE India Affiliate, elaborates on the challenges in the Indian pharma sector and details strategies to make pharma organisations smart
Indian pharmaceutical industry is truly at cross roads today. On one side, the domestic prices are being regularly cut by the government thereby reducing the profit margins. On the other hand, the more profitable export market has seemingly suddenly thrown up hurdles in the form of tougher regulatory action thereby delaying or stopping exports. The important aspect that seems to be missed is that drugs are being made for the patient whether domestic or foreign and as such the ‘Standards’ of these drugs should not differ! And here lies the nub. Many in this industry still find it difficult to grasp that these ‘standards’ like meticulous documentation or OOS investigations, to name just two, really contribute to product quality!
The message now is loud and clear – If you want to stay in this game you better comply with all standards.
No one wants to be taken out of play or be ‘eliminated’ from the game. Pharmaceutical operation is not a game but is serious business; it is a business of wellness, of patient’s safety and one of compliance to standards.
So how ‘smart’ is your operation? How ‘wired’ is your operation?
I am not, here, discussing concealed wiring! I am asking these questions: Have you got ‘smart’ equipment? Smart Processes? Smart Operators? Smart Suppliers? And Smart Distribution?
Having a network of connected devices in pharma manufacturing facilities means remote access to equipment, proactive maintenance of equipment based on actual logs and analytics, real-time plant floor visibility, the ability to recognise and respond to compliance issues immediately, and the ability to monitor and control serialisation. The resulting analytics from these connected devices can be used to avoid compliance issues and hence audit failures.
But perhaps I am getting ahead of myself. So let me start with our (Indian pharma’s ) problems.
India’s pharma sector has seen unwavering growth in the past few years, going up to $23 billion in 2012, from $23 million in 2002. Various industry reports suggest that the pharma sector in India has been growing consistently at the rate of 13-14 per cent every year since the last five years. According to the consulting firm McKinsey & Company, India’s pharma sector will touch $55 billion by 2020 (http://info.shine.com/industry/pharma/2.html)
Tighter scrutiny of Indian manufacturing sites by US drug regulators, increased competition and weaker currencies in key markets such as Africa and Russia are likely to slow down the growth of Indian pharma exports over the next four years, says a new study. The annual growth rate in pharma exports may almost halve to 7.98 per cent by 2020 from 14.77 per cent CAGR during 2010-2014, according to a joint report on Intellectual Property Rights (IPR) by TechSci Research and industry chamber Assocham.
The growth rate for exports of pharma products from India to the US is definitely declining, mainly due to increasing US Food and Drug Administration (FDA) scrutiny on the quality of pharma products coming from drug manufacturing plants located in India
“In order to boost the growth rate of exports to the US, Indian companies will need to leverage their compliance to US FDA regulations,” the report added.
Closer to home, the domestic sector registered the slowest monthly sales growth in March for financial year 2015-2016, primarily hit by the government’s recent decisions to ban 344 combination drugs and bring nearly 800 essential medicines under price control. AIOCD AWACS estimated that the ban could result in the loss of Rs 3049 crore to the Indian pharma industry annually.
In an interview with a leading financial daily, DG Shah, Secretary General of Indian Pharmaceutical Alliance, had this to say:
Problems for Indian pharma companies started a year-and-a-half ago. FDA issues keep on cropping up now and then. How do companies tackle this? Why is it happening?
DG Shah: These large companies have come together and formed a quality forum and we are taking the best available consultants in the world including the regulators both MHRA/ EDQM and US FDA to address these issues. There are several industries we need to look at. Take steel, automobile, airline, which have been ranked as complying with the best quality standards, so it is not that that we do not have capability or we cannot do it. It is a question of focus and that focus has come back about 12 months ago and the results will take some more time. So, I am absolutely confidant and determined we will resolve these issues. For some companies it maybe earlier, for some it may take a little longer. But the market is the US and nobody would want to leave that market.”
This year itself, three Indian companies got US FDA warning letters – IPCA Silvasa on Jan 29 2016; Emcure Pune on March 3 2016; Poly Drugs Sewri on April 14 2016 Each one for GMP violations w.r.t data entry & documentation.
So three issues are clear
- (Major) market is abroad;
- We must leverage our compliance to the US drug regulations
- We still have issues of compliance in terms of data entry and documentation.
This then brings me back to the first question: How wired is your factory? How smart is your operation? The issues of ‘Data entry’ have been given a euphemistic catchy phrase, by the regulators, calling it ‘Data Integrity.’
Issues of data integrity can happen due to two reasons;
- Due to deliberate manipulations
- Due to human error. This article deals primarily with the second reason and how this can be mitigated.
Human beings will make errors and since we are in the business of making life saving drugs ‘human error’ if uncorrected can endanger lives! The only manner in which we can minimise and eliminate errors is to automate as much as possible.
There is a great fallacy in our thinking that labour is cheap and that automation is expensive. In a globalised supply chain scenario, we have not fully grasped the real cost of failure. In the best case scenario, it could be temporary suspension of supplies and drop in profit margins; in the worst case scenario it could be global fines in millions of dollars, collapse of reputation or even bankruptcy and jail terms if drugs are found harmful to patients.
Speed to market with precision is critical. Delayed time to market or reduced time in market erodes strategic positioning and profitability.
So let me introduce to you what I call ‘The Technology Ladder.’ It looks something like this:
You can start at the bottom of the ladder and make sure that you progressively go up the ladder. As depicted in the picture above starting from a simple transfer of liquid by opening a valve to deliver the liquid into a container manually, to the middle rung of having a PLC control the time of transfer, volume/ weight of transfer and capture the process electronically as a record. The next rung is the top most and represents the ultimate ‘smart’ factory with a network of connected devices in the manufacturing facility with remote access to equipment, capability of proactive maintenance of equipment based on actual logs and analytics and real-time plant floor visibility.
Today, there are technologies available that will enable you to retrofit electronic equipment into your old process and have them wired thereby eliminating data integrity issues stage by stage. If you are putting up a new facility in a green field site then it certainly makes for good business sense to start higher up on the technology ladder.
If you are not at the top of the technology ladder make sure you are not on the bottom most rung either. Humans are fallible and errors are to be expected, even in the best organisations. When a deviation occurs, the important issue is not who blundered, but how and why did the defenses fail? Some of the hidden costs to having an untrained and/ or unskilled workforce can include lost production time, inefficiencies, missed deadlines, rework, and injuries and poor customer retention.
IT Companies like APPLE, GOOGLE etc. have full time in-house training set up. GSK had professors from Duke’s University, USA, who went to Singapore to train Asia Pacific staff. Remember that training hours/ budget are also one of the inspection issues by regulatory authorities.
Electronic Batch Record Systems (EBRS) are a perfect solution for the pharma industry. Through a user-friendly Graphic User Interface (GUI), EBRS can provide an efficient way for automatic capturing of data, exchange of batch information, batch production management, report generation and for accuracy of operators.
EBRS would also provide a central storage of data to maintain data security and integrity. By providing functionality for application security, audit log generation, and e-Signature capture, EBRS would ensure that the system becomes completely compliant with the 21 CFR Part 11 regulations.
When the US FDA audit your operation aggressive data experts hunt for common DI deficiencies, including lack of
- GMP knowledge
- Understanding regulatory expectations
- Management interest in compliance reporting,
- Escalation of problems
- Continuous improvement techniques,
- Mature QA oversight,
- Strong electronic record controls.
In today’s regulatory environment, GMP and DI is expected from the entire pharma supply chain. This includes companies responsible for clinical trials, research, manufacturing, and distribution.
For the US FDA, ‘import alerts’ and delaying review of new NDAs and ANDAs are the tools of choice to enforce compliance. Remember that for these auditors you are guilty until proven innocent.
Imagine a system such as the one depicted below. Here the operations from order placement, receipt, sampling/ testing, issue to manufacturing, actual processing, again testing and finally into the warehouse for distribution is all wired and captured electronically.
In conclusion, I would like to quote some famous personalities – starting with Archimedes who said, Give me a place to stand and with a lever I will move the whole world. (Archimedes 12th Century.)
The second quote is from J F Kennedy who said: My fellow inhabitants of this planet: Let us take our stand here in this Assembly of nations. And let us see if we, in our own time, can move the world to a just and lasting peace. (John Fitzgerald Kennedy 1917-1963)
Followed by own plea: “My Fellow Colleagues of this Industry: Let us take a stand at our workplace. And let us see if we, in our time, can move this industry to one of lasting compliance.”