Data integrity issues is proving to be the Achilles heel for future of Indian generic industry. For reasons varying in their severity, many Indian companies have fallen on the wrong side of FDA compliance. While some companies are knowledgeable and well managed, they will make corrections, while others may find it very difficult to gain back the trust. It is an uphill and a long drawn process.

Many Indian officials have come to the defence of Indian pharma by stating ‘Indian companies are being judged based on Western requirements’-This makes us weaker especially when issues like ‘data integrity’ are cited. These are basic requirements and are nothing to do with any evolving requirements.

Basically, if we want to do business in developed countries, we need to fall in line with the developed country’s requirements.

It is possible that you as a reader may consider my thoughts as being ‘un-patriotic’. Actually it is the ‘patriotism’ which is making me think of the urgent need for correction/remediation before it is too late.

Track record of Indian pharma-past & present
India between 1990-2000: Built up the infrastructure. Indian pharma was known for its very good facilities. There were many plants built during the 90s and had the second largest scientific manpower.

India between 2000-2010: Gained label as the best destination for generic formulations and clinical research.

India between 2011- 2014: Collapse of clinical research industry and brakes put on its generic drugs following many import alerts.

In the US, currently it is quite common that pharmacists get a request ‘not to dispense drugs manufactured from India’. Many experts are questioning ‘Do Indian companies have a chronic data falsification problem?. Some of the regulatory agencies are providing specialized training to inspectors sent to inspect Indian companies. This trend is not good for Indian pharma. It is also true that some Indian companies have demonstrated that it is possible to maintain highest standards for data integrity in India.

This abrupt change in scenario may be surprising to some and hence we see defensive comments. As a reaction to many Indian companies being in the news during the past 3-4 years, has forced Indian bureaucrats to come out with defense stating ‘Indian generic companies have been targeted’. This is not a good approach when there have been failings for data integrity. This is not to be defended. Instead, we need to understand the basic essentials.

Companies exporting drugs to the USA get inspected by US FDA. The inspectors record all non- compliances and issue Form 483s. In the event, the observations are of serious nature or the explanation/corrective action is not adequate, the company is issued a warning letter/import ban.

It is very costly to land up with 483 or import bans. In addition to the loss of product both manufactured and work in process, the other costs such as delays/rejections in approvals, fines, litigations, loss of market etc, are at least 100 fold. One should also be aware that most of the developed countries are of very highly litigatory in nature. Most defaulters get punished heavily.

The actual cost of failures is yet to be fully realized by the effected companies by the regulatory actions in the recent past. One of the estimates puts it at at least 4 billion dollars which is equivalent to 4 months supply of medicines for 1150 million population of India. The value of opportunity lost is very high and keeps growing every year.

It is unfortunate that Indian pharma has landed into this unfortunate situation despite the great reputation it had during 1990’s.

It is critical to fully understand that attributes like ‘data integrity’ is not an evolving concept. It is a basic ingredient without which no Regulatory system can reliably depend.

It is important to note that the business of Indian generic companies drastically grew in developed countries. India exports at least 50% of the generics to the US. Hence, getting noticed when in limelight should be expected.

However, for some people like me, who have worked in both countries India and US, know the expectations/practices of these developed markets, the writing was clear on the wall. This prompted me to publish an article on ‘data integrity’ during 2010.

What is required is ‘soul searching’. We got to ‘improve’. We got to understand the differences in standards in Data integrity and expectations on levels of hygiene.

The perceptions of ‘data integrity’ in India and developed countries are very different. These differences are evident and as an analogy, they are similar to adherence levels of traffic lane discipline in the two countries. In developed countries 95% fall in line, whereas, only 5% of road users in India fully respect the lane discipline norms. This indifference to norms is tolerated in India, but punished in developed countries.

We also need to thoroughly convince ourselves to be compliant if we want to do business in developed markets. This is the only choice, but the challenge of becoming ‘compliant’ means each and every person connected should sing the same song and leave no stones unturned in this pursuit.

In a manufacturing activity, it is not a crime to make a mistake. The mistake can always be mitigated. Once a mistake is noticed, it is important that co-workers, supervisor or quality groups should detect the mistake and take necessary action to prevent the same in future. Data Integrity is a combined failure of a number of people and systems. In pharma, every unit dose cannot be tested, the testing is based on statistical sampling and hence it is the trust and reliability on documentation and systems which can give a sense of assurance. If such failures in good documentation practices are detected by inspecting authorities, the entire precipice of ‘quality and trust’ gets destroyed.

Future:
Trend in warning letters
Some of the major reasons for warning letters have been inadequate practices/ systems for investigations and Data Integrity. This is a symptom of ‘growing’. Many of the developed markets including the US have gone through such similar problems in the past (1980s).

Generic drug scandal in 1980s and 1990s found some companies to have submitted falsified or inaccurate data to FDA, or to have paid illegal gratuities to FDA officials. As a result of the scandal, the generic drug enforcement Act of 1989 was enacted and FDA’s inspectional program was revised to focus on Data Integrity.

In some countries, the ‘lessons learnt’ were taken seriously and measures were put in place to prevent them in future. There was a ‘cultural adaptation’. This is what India, as a country should embark on. The question is ‘Can Indian pharma learn from this and come out of the shadow it has created’?.

It is important to fully understand the observations and try to figure out the root causes. One of the possible root causes could be ‘price control’ and utilizing ability to ‘manage’ in the price control environment. It may be true that inadequate procedures and improper validation/testing attributes may have crept in due to the ‘cost control environment’ prevailing in India. On the other hand, the expectations are very high in the developed markets. Attempts to ‘manage and bridging the significantly varying levels’ could be one of the strong reasons for data integrity issues. The question of ‘Can we afford to? ‘ may be crossing the minds of many business houses. Instead the question to be asked should be ‘Can you afford not to?’

It is true that exports are not price controlled and should be immune to this effect, but, how can one have ‘dual standards’ in the facility which is manufacturing for both domestic and developed markets?.Assuming that the manufacturing facilities are segregated, but the manpower is transient-hence the problem continues.

In order to achieve uniformity in globally accepted policies and practices, the local price control measures should provide for the necessary ‘quality’ costs. The government authorities have been amenable to enhance approved price, provided it is adequately justified.

Every importer expects the costs to be lower in India. However the expectations of practices are very high.

Indian pharma should resist this temptation of committing to supply at low cost which may result in compromises in quality.

By the way, not many businesses can continue to supply ‘low cost’ products and yet thoroughly implement the ‘best practices’. This is what the importers from regulated markets should reckon and be prepared to pay higher prices for ‘quality products’.

However, irrespective of the pricing aspects, the aspect of failure in data integrity is not a good attribute. Such data integrity issues cited in many companies recently, melts away the critical factor of ‘trust’. Once a problem is noticed in one area, the inspector feels there may be many more and takes the stance of ‘you are guilty until proved otherwise’.

Having confidence and trust in the system is very critical to build the required faith in pharmaceutical business.

Data integrity
According to FDA Glossary, Data integrity is ‘the degree to which data is complete, consistent and accurate’.
In the process of developing and manufacturing drug products, there are thousands of transactions and all of these need to be documented accurately, consistently, completely and preserved in a manner which preserves the authenticity and traceability. This is Data integrity. Even one incident carried out with or without intention diminishes the overall value and is adequate to get this label of ‘failure in data integrity’.
Simple omissions like leaving a box in a document unattended is regarded as a data integrity aspect since the omission can be assumed as intention to ‘fudge’. Selective reporting is also a wrong practice. These are not considered to be major issues in India.

Reasons for failure
It is not that such practices result in cost saving for the companies or have been compelled by the management. In a way, failure in Data Integrity is partially due to ignorance, inadequate training and ability to notice such discrepancies and take such matter seriously when noticed.

The most common reason are that computer systems are not secure. There is resource constraint resulting in using manual systems. Further, there are inadequate procedures and lack of training.

Normally attempts to cover up one mistake or one integrity problem leads to several more. It has a ripple effect like ‘cancer’.

General reasons for Data Integrity issues are due to not recording data in real time, fabricating data, copying pre-existing data as real data and back dating. Other reasons are selective reporting , creating acceptable results without carrying out the tests, testing into compliance-re-running samples without sound scientific justification, forging signatures or using unauthorized signatures, discarding or altering data, reporting inaccurate data-without any back- up data and keeping multiple sets of data or reporting un official data

 Corrective measures
In an attempt to look for primary drivers and corrective measures for such issues, one of the top spots is our ‘education system’.

We should improve the system to ensure engraining the aspects of ‘Good Documentation Practices’ at a very young age in addition to the value system which emphasizes ‘patient safety’ as the main priority even beyond all economical compulsions.

Key initiatives
All the players in the pharma industry have a major role to play in the process of remediating the Data Integrity and other compliance aspect.

Like we, in the industry say ‘Quality’ is everyone’s responsibility’, taking effective remedial measures is the responsibility of all including government, company management and employees. This three-way partnership should have a strong and unanimous objective.

Some of the important aspects for each segment are listed below:
A. Government:

• Value ‘Quality’ and make necessary provisions for product costing in the ‘Drug Price Control Order’.
• Improve the work ethic culture in the young by incorporating concepts of good documentation practices and the Integrity aspects in the primary education system.
• Take steps to curb corruption in all aspects of life.
• Publicize non compliance which helps to improve compliance.
• Bring out changes in laws to facilitate companies to take serious action on erring employees when it comes across data integrity acts. Also amend impractical laws which, in some cases, force companies to commit ‘integrity’ issues (factories/Labor Act for example).
• Insist that every business provides for ‘help line’ to report wrong acts.
• Make inspections and enforcement meaningful, by proper empowerment and then hold the officials accountable
• Bring about transparency in enforcement and
• publicize wrong doers so that the wrong doers are prevented from joining other companies.

B. Company leadership :

• Practice ‘Zero tolerance’ for wrong doings and ‘walk the talk’. Make it clear that there is no ‘second chance.’
• Incentivise employees to ‘see, report and fix problems instead of ‘managing the situation.
• Provide necessary infrastructure (data management systems) to maintain integrity of data and also detect ‘integrity/non compliance’ aspects
• Provide necessary provision in costs for unforeseen expenses like batch failures. This makes un-biased and correct decision making easy.
• Develop appropriate systems to communicate ‘failures’ in project schedules –which is one of the main reasons for failures in ‘data integrity issues’.
• Do not make ‘low cost’ as the unique selling proposition to promote sales. Build in necessary costs for quality, thorough training of personnel.
• Create an environment to encourage reporting of failures and encourage communication of facts.
• Empower quality department should be a part of the management team should have the final say in ‘Quality’ matters.
• Invest in intense training on good documentation practices
• Rely on ‘data’ rather than ‘opinions’ for all actions.
• Make executive managers commit on schedules and costs and hold them accountable instead of business owners making commitments and subsequently struggle to maintain the commitments.
• Avoid mixing business of regulated markets with domestic manufacture if the price control aspect is compelling ‘short cuts’.
• Emphasize on training. Focus on “Performance Improvement” tools and applications that enable our clients to define, assess and measure technical skills within the production and operations areas of the business.
• Invest on systems. Build on reporting tools so that “competency” data is available to both managers and HR teams who can identify “high performers” within the organization, and deliver the appropriate developmental opportunities;

The emphasis should go beyond ‘basic compliance’. The Leadership should build in and develop a ‘culture’ across the board.
The management should ensure the following;

• Instal a robust quality programme which can prevent, detect and mitigate data integrity issues
• Records and data is accurate and protected.
• Routinely review audit trails
• Use trained auditors to detect data Integrity issues.

C. Employees

• Develop ability to say NO- when you are convinced that you are going/ to go against the basic rules.
• ‘Under promise and ultimately perform better’ rather than ‘promising too much’ and then ‘managing’ to achieve the target, thereby failing in the ‘integrity of the data’.
• Accept failures, have the courage to report that something has failed instead of covering up.
• Be thorough and systematic. Avoid ‘band aid approach’ and practice established systems to seek the root cause in trouble shooting.
• Do not compromise. The patient’s safety is ‘supreme’.
• In general, Indian chemists are complemented for our ‘flexibility’. While flexibility Is a good virtue for some industries, flexibility in pharma may lead to short cuts and is a ‘NO-NO’ in developed countries.
• Feel ‘responsible’ to report if others are not complying to the data integrity practices.

This list is not meant to be an ‘all inclusive’ list. Also it is not ‘one tool for all’. The level of emphasis may vary for each Company/situation. The regulatory standards and expectations are evolving and hence we should be cognizant of everything for 100% compliance.

I am confident and hopeful that the Indian pharma will regain its lost glory. Let us make it a way of life so that the efforts will be engrained into the system to make it sustainable and withstand the test of trust and regaining the lost confidence. Let us remember that there is no ‘second chance’ as we are safeguarding precious life, which also has no ‘second chance’.

DISCLAIMER; The views provided here are the views of the author and do not in any way reflect the views of both the present and past employers of the author.