Ankura Consulting, a leading global expert services and advisory firm, announced the expansion of its Pharmaceutical and Biopharma Regulatory Compliance offering in India. Amit Jaju, Senior Managing Director, India in an interview with Thomas C Thottathil outlined the steps Indian pharma companies should follow to be compliant with global regulatory requirements

The pharma industry in India has its challenges when it comes to digitization and automation. Covid-19 has forced many of them to move forward quickly in this direction. What should be the approach for Indian pharma companies?

There are a few things to consider when digitizing pharma companies in India. The first is a large number of small companies. A study by IMS found that there are more than 10,000 pharmaceutical companies in India, with only about 30% of them classified as large enterprises. This fragmentation makes it difficult for the industry to implement digitization and automation initiatives.

Another challenge is the lack of technical infrastructure. Only a fraction of Indian pharma companies have access to reliable power and broadband connectivity as many of them have operations in remote locations. This limits their ability to use digital technologies.

Finally, there is the issue of cultural resistance to change. Many Indian pharma companies are comfortable with their traditional ways of doing business and are reluctant to adopt new technologies.

Despite these challenges, there are several ways that Indian pharma companies can digitize their operations. One approach is to partner with larger companies that have the necessary technical infrastructure and expertise. This can help smaller companies overcome the lack of infrastructure and resistance to change.

Another option is to invest in digital technologies themselves. This can be expensive, but it can help companies overcome the challenges of fragmentation and lack of infrastructure.

Finally, companies can also partner with technology providers to get access to needed technologies. This is a less expensive option than investing in digital technologies themselves, and it can help companies overcome the challenge of cultural resistance to change.

India has the highest number of USFDA approved plants and it is in an enviable position as it’s called the pharmacy of the world. However, the question remains is India the `quality pharmacy’ of the world?

India is often hailed as the pharmacy of the world as it is a leading producer and exporter of pharmaceuticals. India's pharmaceuticals and drug exports were worth US $ 24.44 billion in FY 2021. India is the world's 12th largest exporter of medical goods and supplied 58.6 million Covid-19 vaccines to 71 nations as of May 2021. India is the world's largest exporter of traditional medicines, with products sold to more than 200 countries with the United States as the key market. In terms of volume, India is the world's largest provider of generic medicines, owing to 20% of global export in that category.

For India to be called ‘quality pharma’, Indian pharma companies should aim to become the global benchmark of quality by building up a quality culture in the manufacturing and quality unit including providing appropriate training to the employee, following CGMP practices, employee involvement and feedback, implementing a governance model. Further creating a mindset that everybody in the organization, not just the quality controllers, is responsible for quality.

Complying with regulatory guidelines and able to demonstrate quality to the regulators during the inspection

Focusing on data-driven approach as compared to process-driven. Using digital tools is one of the most effective ways to analyse terabytes of data in various processes such as drug discovery, research & development, quality testing and compliance.

Leveraging digital technology to ensure high standards of quality checks and data integrity practices can be maintained throughout day-to-day operations in the manufacturing units and quality labs.

Automating various operations to reduce risk and human error (if any)

Many Indian pharma companies find it difficult to navigate the regulatory landscape in regulated markets and they find it as a challenge. Do you have the tools to help them address these issues?

Keeping up with the regulations is an uphill task for organizations in the highly controlled pharmaceutical industry. One of the areas in which the pharmaceutical industry continues to receive a significant number of observations from regulators is ‘Data Integrity Compliance’. While the companies have the framework for reporting data integrity gaps in place, the nature of the framework is such that it does not monitor and analyse data to identify deviations on a real-time basis, making it a reactive instead of a proactive approach. Preventing data integrity concerns is a worthwhile investment because recovering from them, when they are discovered, is far more expensive than preventing them. Ankura’s Early Warning System (EWS) automated solution can be leveraged to detect and plug any data integrity gaps and serve as a mainstay process to identify any compliance deviations. EWS helps solve the challenge of integrating multiple Quality systems (i.e. CDS, NON-CDS, LIMS) into one platform enabling the quality control department to take advantage of the integrated monitoring capabilities to show alerts for any non-compliant activities from a regulatory compliance perspective. Furthermore, utilizing the technology, any fraudulent or falsification activities can be investigated and addressed rapidly, as human errors and data/procedural gaps are discovered in real-time.

Many Indian pharma companies face data integrity issues and as you mentioned it’s a potential disaster as it’s better to plug the loopholes rather than wait for that warning letter. Is this issue only about Indian companies or are these common challenges for companies serving the regulated markets?

USFDA regulatory actions, such as warning letters and form 483, have increased from 2014 to 2019. However, the US FDA sent over 2,700 Form 483 observation letters in 2020, compared with more than 4,700 in 2019, a 42% decrease. The trend is essentially the result of fewer inspections by the regulators due to Covid-19 related challenges but as inspection resumes, Data Integrity Compliance is likely to be the focus area of the regulators to ensure reliability and accuracy of the data. Based on our market research data on regulatory actions, DI violations have also been cited in pharma companies based in China, the USA, Japan, and Europe.

How would you define Industry 4 when it comes to the pharma industry?

Pharma 4.0 is an initiative by the International Society for Pharmaceutical Engineering (ISPE) to envision a digitally mature pharmaceutical industry. It is a framework for adapting digital strategies to pharmaceutical manufacturing in line with the trajectory to Industry 4.0.

In its most simplified form, Pharma 4.0 is the pharmaceutical industry upgrading itself as a smart factory by incorporating digital enablers into the current quality systems. This will enable greater opportunities for process improvements throughout the life cycle of pharmaceutical products. Companies will have a greater degree of connectivity and transparency through automated systems, which will provide control over operations and quality, and allow faster decision-making.

Pharma 4.0 may include:

Elimination of data silos with integrated monitoring across the lifecycle of drugs.

Improved collaboration and productivity in highly regulated facilities

The elimination of paper-based processes

A shift to risk-based regulatory compliance models

Despite the technological progress, pharmaceutical companies still have a long way to go to adopt fully autonomous self-correcting automated systems. However, Pharma 4.0 is a road map for implementing the required first steps, some of which may be taken by most existing facilities. A digital transformation strategy starts with finding small opportunities for improvement which can be scaled up as required. One of the areas which companies can look at as a part of their digital transformation strategy is leveraging the EWS solution that helps move away from manual means of compliance and leveraging the power of automation and system consistencies to address issues proactively.

Are you working with any Indian company at present and what’s your experience globally working with pharma companies?

We are assisting multiple large Indian pharma companies in implementing as well as conducting a feasibility study of an Early Warning System in the quality control lab. The objective is to automate the manual process of data integrity compliance checks performed for quality systems such CDS-Empower. The team has collaborated with the client quality control manager and information technology team to customise the data integrity rules, dashboards and management reporting as per the client’s specific requirements and applicable regulations.

We are also conducting similar engagements with some medium-sized pharma companies in the United States and Japan.

We have experienced after working with pharma companies globally that companies in each region have different characteristics. In some regions, pharma companies tend to be larger and have more resources. They also have a wider reach, selling their products in more countries. Companies in these regions also have more focus on R&D to develop new drugs which have different digitization and compliance requirements altogether. There is a significant focus on the use of forensic technologies to protect trade secrets and prevent data theft.

In other regions, pharma companies are more focused on manufacturing and distributing existing drugs. This difference in focus can lead to different strategies and approaches.

Should Indian drug regulators work with their overseas counterparts to frame regulations that would be compliant with both?

Yes, the Indian drug regulator such as Central Drugs Standard Control Organisation (CDSCO) should consider close cooperation with overseas regulators such as the USFDA. This will bring synergies between both the agencies and will help the USFDA in gaining confidence in CDSCO’s inspection. This needs further exploration as the USFDA is more concerned with the drugs that are made in India but exported to the USA. FDA already has Mutual Recognition Agreements (MRA) with other foreign regulatory authorities such as The EU and The UK which allows drug inspectors to rely on the information from inspections conducted within each other’s borders. But only the USFDA can determine whether those authorities can conduct inspections that will meet their quality requirements and standards.

Such mutual recognition will not only give opportunities for small pharmaceutical companies that are struggling to get their foot in the US market but also open new horizons for big players that are already established.

The USFDA plans to start an unannounced inspection programme in India and China. How will this play out for pharma companies?

Foreign pharmaceutical facilities are given significant time between the time they are notified by the US FDA regulators for a facility inspection and the time the inspections take place whereas the domestic facilities in the US receive short notice or no advance notice before a facility inspection.

In 2014, the FDA ran surprise inspections that led to many companies being served warning letters and alerts. The move led to a 60% increase in regulatory actions against generic companies. Between 2014 and 2015, India’s top five generic companies collectively lost a market cap of ?15 billion.

As per market reports, almost 40% of the generic drugs in the US are imported from India and China. Generic companies with significant US market should evaluate their current practices as per the regulatory guidelines and take corrective actions for any gaps identified. Having a process to identify and overcome any regulatory deviation is a worthwhile investment because recovering from the consequence of deviations when discovered, is far worse than the costs associated with prevention. Hence, companies should leverage experts to implement technology solutions that can monitor quality and compliance on a real-time basis. Such solutions can further strengthen the trust of the regulators as the integrity of data collected and preserved for compliance underscores the sanctity of the process.