Indian pharma generics companies account for around 30 percent (by volume) and about 10 percent (value) in the US$ 70-80 billion US generics market.

In the last two years, a large percentage of warning letters of all the FDA’s warning letters were issued to worldwide pharmaceuticals companies for failing to meet data-integrity standards. Data Integrity issues can put a brake on all growth engines of a pharmaceutical company. Any serious violation concerning data integrity may lead to severe regulatory actions like the ban on drug export or delay in approval to ANDAs.

Regulatory agencies are also evolving the new ways to test the data in pharmaceuticals against all requirements which are necessary to keep the integrity of data 100% intact. In the last couple of years, the Indian pharma companies have faced a lot of challenges with the US FDA due to data integrity issues in their environment.

The top management of all pharma companies in India shall build and cultivate a strong culture of data integrity. The culture of the company should help employees to understand the impact of data integrity issues on company operations, damage to reputation, differences between “errors” and “falsification’ etc.

The IT Team can play a vital role in ensuring 100% data integrity by helping employees to understand the complete data lifecycle, discovering all leak points which offers possible falsification/manipulation/change in data and controlling them by implementing the right set of custom and off the shelves IT tools and applications.

Ensuring Integrity in Data Lifecycle

It is very important to understand the complete life cycle of data in pharmaceuticals. Data in no stage should be left orphaned. It should always be under monitoring of an electronic surveillance ecosystem. The sophisticated IT tools should be implemented and shall record each event happening on a set of data. Who, what, when and why happening on data shall be recorded without fail. The crux of validation of data life cycle in pharmaceuticals revolves around one equation which is "The authentic validated data from source" will feed into a validated custom made or OEM prebuild "Algorithms" and a desired "output data" will be received. The "output data" may be processed further, then locked up to avoid further processing.  Later backed up and subsequently preserved/archived.

Organizations shall put equal emphasis on all phases of data lifecycle while implementing the IT surveillance tools and processes should be

I think, having stringent processes to close all possible leak points in the data lifecycle will be treated as a unique capability that will differentiate the leaders of tomorrow in pharma.

Real-time availability of data integrity status

Apart from implementing the conventional approaches like access protection, manual/paper-based review of the audit trails to ensure data integrity, having a real automated inspection software which detects each change made to the data in real-time can play a key role in maintaining the 100% data integrity at any point of time. All changes made to access permissions, shared logins, data at rest, data in motion, audit trail, old archival, etc. should be detected and record in real-time. This change data should be quick to retrieve in a report format anytime whenever it is needed. This is only possible by having a mix of off the shelve IT tools and custom scripts. It also helps the pharmaceutical company to be audit-ready anytime. Under normal circumstances, the changes made per approved change controls can be verified by performing a checklist based tests. In the absence of an automated inspection software, the changes made to the data after completion of change control will be discovered in later stages. Manual proofreading or inspections are proven to be inefficient and often cannot assure that data is free from any unauthorized changes or any type of error in the data.

Design technical tools and scripts to ensure 100% data integrity

Though there are opportunities available at multiple phases of the data lifecycle, I would like to highlight the few in which the industry faces challenges in ensuring 100% data integrity.

To detect alteration in backup data

Design a procedure to check the integrity of data in SQL and oracle databases with the help of prebuild commands like “backup validate” VALIDATE, “restore validate”, “rman”, “checksum check=true”, “dB check”. SQL, ORACLE also capable to detect block (both inter and intra) corruption, logical block corruption, fractured blocks, etc. Setup a maximum limit for the total number of corruptions permitted in a file via rman backup. Feed a checksum while taking a backup. Try to verify only the backup option before restoring the actual copy.

To ensure no alteration in data while it is in motion

You might be moving the GMP data from one location to another, physical to virtual and vice versa, Tier-1 to Tier-2 storage, from disk to DVD, etc. A sophisticated approach is required to ensure the data is not altered anywhere during motion otherwise it will be extremely difficult to detect the alteration in later stages. Use a validated utility that gives bit by bit audit trails. The usage of MD5 checksum is an extremely effective way to detect any type of alteration. The creation of a validation hash when you burn your optical disks (or put away additive backups on the hard drive) can check on the integrity of all the files by running a hash-checking utility.

Summary

With increasing stringent reviews of the integrity of data in the pharma industry by worldwide regulatory agencies, there is a pressure on organizations to build a robust and flexible framework to prevent and catch data integrity issues. The IT department shall play an essential role in building the technical framework with the help of readily available tools and custom software’s/scripts to prevent integrity issues during the whole life cycle of data