Data is at the heart of good quality control but data integrity is increasingly being challenged by the regulatory authorities and failings in this respect can lead to Warning Letters and closure. Rajiv Joshi, Partner, Fraud Investigation & Dispute Services, EY India, looks at the issue
A recent Products Regulatory guidance from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) specifies that data integrity is fundamental in pharmaceutical quality systems to ensure that medicines are of a stipulated quality. The concept of data integrity, or rather issues around it, has seen a noticeable upsurge due to increased harmonisation and co-operation among prominent regulators such as the MHRA, the US Food and Drug Administration (FDA) and others. The ramping up of various guidelines, clarifications, seminars and sessions on data integrity by the regulators and industry experts alike can only be taken as a cue that augmented data integrity compliance is the need of the hour.
Regulatory inspections are a key concern for global pharmaceutical companies because failing to meet requirements could bring untold damage to a business – resulting in diminished customer confidence, low trust by regulators, monetary loss to shareholders and even an adverse impact on any pending and future drug approvals.
Here, prevention is better than cure. Initiating remedial activity post inspection not only sends out the wrong message – that compliance only becomes important with hindsight – but the investment in remediation will also be in direct proportion to the magnitude and expanse of data integrity issues that have already emerged.
However, the industry can circumvent these challenges by conducting proactive data integrity reviews. Periodical surprise reviews conducted at manufacturing sites by independent third parties are useful in managing issues at an early stage. These third parties are non-biased in their approach and provide employees with the opportunity to reveal potential non-compliances (if any) without apprehensions.
These third parties also deploy new methodologies, such as forensic process reviews using forensic technology, so results are fair and accurate. Companies can also conduct a cost-benefit analysis to see that periodical proactive reviews are beneficial compared with a reactive cost of compliance after being hit by an import alert or receiving a statement of non-compliance from regulators.
It is often seen that an oversight by Quality Assurance, although unintentional, becomes an issue leading to breaches of data integrity
According to a recent survey report by EY India titled ‘Analysing the state of Data Integrity Compliance in the Indian Pharmaceutical Industry’, 18% of more than 170 respondents said there was a shortage of QA staff to independently witness and review manufacturing and testing of all manufactured products. Often the increase in personnel with supervisory roles is not matched to the ever-increasing production volume.
The survey also highlighted that at least 57% of the employees had seen work pressure on the manufacturing personnel to meet Key Performance Indicators (KPIs) such as volume of output, low rejection ratio and overall equipment effectiveness. If there is heightened pressure on those doing the activity and their work is not adequately and independently reviewed, there is a high probability of data integrity errors.
It is often seen that an oversight by Quality Assurance (QA), although unintentional, becomes an issue leading to breaches of data integrity. QA staff are entrusted with design, implementation, monitoring, review and revisions in the core quality systems of a drug manufacturing process. They could perform better with the aid of cGMP training for employees, which explains documentary requirements and expectations, with periodical and robust self-inspection programmes, adequately investigated deviations, etc.
A procedural lapse in any of these core responsibilities can bring many challenges that will have an impact upon the prevailing data integrity model. For example, a batch of drugs is released in a rush to meet dispatch timelines without investigating evident deviations. While the timeline might be met, QA’s release of this potentially ailing batch may lead to severe repercussions such as rejection by the customer, market complaints, or worse – a batch recall. Examples such as these may be ignored on a day-to-day operational basis; however, this would rank as a major observation by regulatory inspectors.
In addition, with the advent of electronic records across the drug manufacturing and testing stages, the responsibilities of the QA department have gradually transformed towards a more information technology (IT) driven methodology for monitoring and control. Keeping pace with the technological upgrades has often been perceived as a challenge for the traditional, check-list driven QA department. However, regulatory observations indicate disabled audit trails, deleted test data files, obsolete data backup and retrieval mechanism and uncontrolled access to IT systems are not uncommon.
With the advent of electronic records across the manufacturing and testing stages, the responsibilities of the QA department have gradually transformed towards a more IT-driven methodology for monitoring and control
Data integrity non-compliance can have a detrimental impact on the pharmaceutical industry globally. There is a clear need for immediate and sustained efforts on the part of both manufacturers and the regulators. QA is the quality custodian throughout the lifecycle of drug products and it needs to provide comfort and assurance to patients, regulators and management. Adding to the routine review, an eye toward data integrity will increase regulator confidence.
A focused shift to proactive and periodical data integrity reviews and timely internal self-inspections by adequately trained QA staff is critical to the success of the pharmaceutical industry. Performing a thorough root cause analysis to implement CAPAs for identified gaps and persistent monitoring of controls can prove to be important tools in the drug manufacturer’s arsenal for combating data integrity concerns.
From a long term perspective, generating the need, understanding and value for Quality by Design during the entire manufacturing process is the key for assurance of prolonged data integrity.