How smart is your operation? Have you got smart equipment, smart processes, smart operators, smart suppliers and smart distribution? Having a network of connected devices in pharmaceutical manufacturing facilities means remote access to equipment, proactive maintenance of equipment based on actual logs and analytics, real-time plant floor visibility, 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.
Challenges in the Indian pharma sector
India’s pharmaceutical sector has seen unwavering growth in the past few years, going up to 23 billion US$ in 2012, from 23 million US$ in 2002. Various industry reports suggest that the pharmaceutical sector in India has been growing consistently at the rate of 13-14% every year since the last five years. According to the consulting firm McKinsey & Company, India’s pharmaceutical sector will touch 55 billion US$ by 2020.
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 pharmaceutical exports over the next four years, says a new study. The annual growth rate in pharmaceutical exports may almost halve to 7.98% by 2020 from 14.77% 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 pharmaceutical products from India to the US is definitely declining, mainly due to increasing US Food and Drug Administration (FDA) scrutiny on the quality of pharmaceutical products, coming from drug manufacturing plants located in India. As per the reports, in order to boost the growth rate of exports to the US, Indian companies will need to leverage their compliance to US FDA regulations. Also, closer to home, the domestic sector registered the slowest monthly sales growth in March for 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 (a pharmaceutical market research company) estimated that the ban could result in the loss of `3,049 crore to the Indian pharmaceutical industry annually.
Scaling up solutions
In 2016, three Indian companies got US FDA warning letters—IPCA Silvasa on January 29, 2016; Emcure Pune on March 3, 2016 and Poly Drugs Sewri on April 14, 2016 – each one for GMP violations w.r.t data entry & documentation. So, three issues are clear: our (major) market is abroad; we must leverage our compliance to the US drug regulations and we still have issues of compliance in terms of data entry & documentation. 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 – deliberate manipulations and human error. 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. Also, 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 a drop in profit margins. In the worst case scenario, it could be a global fine, in millions of dollars, collapse of reputation or even bankruptcy and jail terms if drugs are found harmful to patients. Therefore, speed to market with precision is critical. Delayed time to market or reduced time in market erodes strategic positioning and profitability.
The Technology Ladder
You can start at the bottom of the ladder and make sure that you progressively go up the ladder. As per the figure, 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 & capture the process electronically as a record. The next rung is the topmost 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.
Accuracy in operations
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 greenfield 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, re-work, and injuries & poor customer retention.
Companies like Apple and Google have a full-time in-house training set-up. GSK had professors from Duke’s University come to Singapore for training of the Asia Pacific staff. Moreover, Electronic Batch Record Systems (EBRS) are a perfect solution for the pharmaceutical industry. Through a user-friendly Graphic User Interface (GUI), EBRS could 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 audits an 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 and strong electronic record controls.
In today’s regulatory environment, GMP and DI is expected from the entire pharmaceutical 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.
Imagine a system, such as the one depicted in the figure. Here, the operations from order placement, receipt, sampling/testing, issue to manufacturing, actual processing, again testing & finally into the warehouse for distribution is all wired and captured electronically.