Quality: How serious are we?

The USFDA report of 2019 titled, ‘The State of Pharmaceutical Quality for CDER regulated drugs legally marketed in USA’, rates average compliance score of Indian pharma manufacturers as 6.8 in a scale of one to 10. In fact, amongst all the regions, India ranked lowest in USFDA’s scale of compliance. The highest compliance number, 7.7 was attributed to EU manufacturers followed by the US (7.6) and China (7.3). Even Rest of the World (ROW) scored higher (7.0) than India. While we are justifiably proud that India is nicknamed as the ‘Pharmacy of the World’ and we have the maximum number USFDA inspected facilities outside the US with about 40 per cent of the medicines by volume in the US are supplied by Indian companies, the real picture of India’s quality compliance in the eyes of USFDA is not very flattering. 

No wonder, Indian companies, in the recent past, have been scrutinised intensively by USFDA and if the data is to be believed, Indian companies have miles to go before USFDA considers them as no more the risk of noncompliance. Traditionally, India as a country is not associated with QUALITY outside India, a similar comparison of what Chinese products are considered outside China. Though China has worked hard in past to emerge as an economic powerhouse and the perception of Chinese products and technologies have started to change. To change perceptions about quality one needs to change the total mindset of the manufacturers. Today, Indian manufacturers self -measure quality based on the outcome of USFDA inspection and are not bothered much about quality metrics to holistically measure the status. 

But, an outcome of USFDA inspection can depend on many factors like the type of inspectors performed the inspection, how detailed was the inspection, how many inspectors participated, how effectively the inspection was managed and finally how the company could avoid the “auditors luck”. No two USFDA inspection are the same and no inspection can unearth all the discrepancies. So, entirely depending on the outcome of USFDA inspection to determine quality and compliance status of a company will be completely wrong.  

The story of India emerging as a powerhouse for affordable, generic quality medicines is fascinating. If we investigate the genesis of success of top Indian pharma companies, we will mostly see remarkable stories of first-generation entrepreneurship, of dreams, farsightedness and aspiration. Be it Dr Anji Reddy of DRL, Dilip Sanghvi of Sun Pharma, Dr Hamied of Cipla, DB Gupta of Lupin, Dr Parvinder Singh of Ranbaxy, these are stories of a person’s dream and courage to become successful entrepreneurs. Most of the companies started their journey in the late ’60s or ’70s when starting a new business was a Herculean task. Those were the days of the socialist mindset of industrial license, quota of limit of manufacturing, political influence, power brokers and power of networking wherein the political class determined the success of any entrepreneur. Those were not the days of investors and private equity players investing money to any budding business. All most all of them started modestly, by investing their own or their relative’s money along with loans from government banks. The common traits of all these pioneering entrepreneurs were undaunted aspiration and immense belief on the capability of Indians. 

The real breakthrough and opportunity came when Prime Minister Indira Gandhi brought the Indian Patent Act in 1972, where process patent was acknowledged but not product patent. This decision encouraged these entrepreneurs to venture into bulk drug manufacturing where the process was re-engineered, by passing the patented processes. India already had the talent pool of chemists and technologists who applied their skills in developing unique processes bypassing patented processes, many times far better than original patented processes. This helped the government also to make affordable latest drugs available to its citizens. Over the next decade, India emerged as a major player in bulk drug manufacturing. All these companies, in the beginning, were India-centric and competed to gain market share. So, to gain market share all companies concentrated mainly in R&D and marketing – R&D for developing new products and marketing to gain market share and growth. In the entire value chain of pharma operations, manufacturing, quality and supply chain did not get its appropriate importance. All the companies had ‘star clubs’ for marketing people where the performers were recognised and even taken to foreign countries like Thailand, Mauritius, at the company’s expense for rest and recreation. The performers in R&D were also adequately recognised and rewarded. The logic was quite simple because all these companies were harping on growth which only can come with the introduction of new products and increasing market share. No company ever thought of forming “star clubs” in manufacturing, recognising performers and offering them rest and recreation programmes like those for the marketing people.

In manufacturing, it was important only to manufacture the product and deliver as per the schedule and no importance was given to following standard operating procedures, guidelines, validation or data management and integrity. One of the major drawbacks was also our Drug Control Administration’s inability to administer Good Manufacturing Practices in Indian manufacturing facilities. 

This changed when these companies started first exporting to non-regulated and finally to advanced countries. As India started getting exposed to foreign regulator’s scrutiny, there was an urgent need to strengthen manufacturing and quality functions. The companies started giving importance to quality, manufacturing and regulatory personnel. Many of the companies created a Quality Policy, written down with the help of consultants but there was no focus or rigour of management to implement. Enforcement of regulators like USFDA, MHRA or TGA made all the companies alert to quality, manufacturing and regulatory personnel. Suddenly, management of companies realised that in a market like the US, especially in generic medicines, marketing is not the main challenge, but clean compliance record and cost of products makes all the difference. 

Once a product is approved by USFDA, all generic products are qualitatively the same in the US market – important are the track record of compliance, competitive cost and efficient supply chain performance. In the long journey of pharma business in India, today technical people involved in manufacturing have a lot of importance in the eyes of management, especially for companies actively involved in exporting to advanced countries. 

We all agree that India today needs to focus on quality, but our focus should not be limited to meet only USFDA’s compliance criteria. For example, in the last couple of years, USFDA issued 483s on incomplete and inadequate investigations on issues like OOS, deviations etc. Most of the companies today have focused on improving the quality of investigations. While it is an important step to improve compliance, one question comes to mind that what is prompting investigations in the first place. The answer to this question will lead to some fundamental issues. Issues like unstable and undefined processes, inadequate or ill-defined procedures, unscientific specifications, repetitive mistakes, inadequacy of training, serious market complaints etc., prompted many investigations wasting the valuable, productive time of technical people. Continuing this process is not going to add any value in the overall improvement in our quality journey. 

It is important to focus on the genesis of problems and take corrective and preventive actions. They should encompass all the activities, including R&D, tech transfer, manufacturing and quality. Unless and until we take some very tough decisions on the process of product development, process capability of products and deriving science-based specifications, the problems will continue to occur and we will never be able to come out from this vicious cycle of doing investigations. Our entire focus should be to prevent any incidences compelling us to carry out investigations.

It is also time to compare the performance of pharma industries with other industries in terms of improvement parameters. The pharma industry is comparatively recession-proof and has long enjoyed better EBITDA margins. In the process, where other industries have investigated their performance critically to remain competitive, the pharma industry remained cocooned with inefficient performances for too long. With increasing competition in generic industries and price control, it is now extremely important that pharma industry borrow some tools and techniques from other industries to bring robust efficiency in performance.  

If the quality metrics are defined appropriately and rigour is placed on responsibility and accountability, there is no reason why pharma processes cannot become as efficient as automobile, semiconductor industries. A process capability as high as Six Sigma should be the only criteria for pharma processes whereas most of the processes that traditionally run in the pharma industry are, at best, of three sigma capability. Quality metrics like the cost of quality, customer complaints and return, actual yield vs theoretical yield, overall equipment efficiency (OEE), change over time, throughput rate, defects analysis, supplier quality metrics etc., must be included in the overall appraisal of people and processes. 

The journey of quality is long and arduous. There is no quick fix to achieve quality instantaneously. However, if we remain focused on important quality metrics and compliance, there is no reason why India cannot be regarded as a high-quality medicine supplier to the world in future.