Pharmaceutical manufacturing professionals should expect a surge in high defect rates as soon as the U.S. Food and Drug Administration (FDA) addresses its massive backlog of safety and quality inspections. Focusing on calibration and validation is vital to improving quality control in time to face regulators’ heightened scrutiny.
Why Focus on Improving Calibration and Validation?
As manufacturing costs rise and regulations tighten, many pharmaceutical manufacturers have outsourced production. In doing so, they have substantially reduced their effective oversight of quality control. This lack of visibility comes at an inopportune time, as the FDA is making progress on its backlog of inspections.
Around 42% of the plants registered to produce drugs for the U.S. — nearly 2,000 facilities — are overdue for a post-pandemic review. Many of these uninspected manufacturers are located in India and China since pharmaceutical companies outsourced work to produce low-cost prescriptions.
According to FDA guidelines, overdue facilities are considered a significant risk and must be prioritized when selecting plants for mandatory inspections. However, the agency’s staffing shortage has put it in a difficult position, so it has yet to reach nearly half of the registered places that have gone without review since 2019.
The FDA will likely seek to make an example out of any noncompliant facilities to incentivize others to remain compliant despite its inadvertent lack of urgency surrounding inspections. Prioritizing calibration and validation is essential for pharmaceutical manufacturers if a regulatory crackdown is on the horizon — whether they are domestic or abroad.
The Importance of Proper Calibration and Validation
Good manufacturing practice (GMP) regulators like the FDA and the European Union’s European Medicines Agency are still recovering from pandemic-induced developments that forced them to postpone in-person inspections. As such, they are undergoing changes, focusing more on design instead of prioritizing testing for quality assurance.
The GMP regulators’ burgeoning interest in a quality-by-design system necessitates a renewed focus on compliance throughout the life cycle of drugs. Strict adherence to regulations throughout planning, development and quality control may soon be essential to remain compliant with rapidly evolving standards.
Proper calibration and validation play a central role in meeting GMP guidelines for pharmaceutical manufacturing. They ensure processes consistently produce desirable results and equipment remains highly accurate, guaranteeing drug safety, efficacy and quality. These systemic methods are arguably the most critical aspects of compliance.
These methods also provide vital documentation, enabling business leaders to generate accurate, timely reports for GMP regulators. At the very least, they are fundamental to visibility during production. Without proper calibration and validation, pharmaceutical manufacturers risk heightened defect rates.
The Consequences of Lackluster Quality Control
Professionals who do not consistently ensure output aligns with predetermined specifications risk experiencing major and critical defects. Manufacturing mistakes can produce errors that are up to 100 times the size of the instrument’s inaccuracy. The importance of adequate, frequent calibration cannot be overstated.
The efficacy and safety of drugs become ambiguous when discrepancies go unnoticed, meaning injury, illness or death are probable outcomes. Legal issues will follow, with regulatory agencies and affected individuals seeking litigation for restitution. At the very least, public backlash is likely.
Once the general public realizes individuals were harmed or killed by a production line mistake, they will turn their ire to pharmaceutical manufacturing. Even if their attention is fleeting, reputation damage is all but inevitable. Simultaneously, regulatory agencies will be increasingly strict in the future.
Drug development and production are costly — can facilities afford failure? Manufacturing plants already experience upwards of 25 hours of downtime monthly, so experiencing more due to preventable quality control errors is unacceptable. Leaders should do everything possible to lower their rejection rate and acceptable quality limit (AQL).
How to Lower Defect Rates in Drug Manufacturing
According to ISO 2859-1, the AQL should not exceed 4% for minor defects, 2.5% for major defects and zero percent for critical defects. Plants should be nowhere near these figures, as they are considered the worst acceptable quality level for drug products during a random sampling of a production batch.
To avoid putting consumers at risk and to preserve companies’ reputations, the pharmaceutical manufacturing sector must prioritize validation, qualification and calibration. Doing so will improve quality control and lower defect rates and AQL. There are several ways they can approach this issue.
Calibrate and Validate Frequently
How often should manufacturing plants calibrate and validate their equipment and systems? In addition to periodic checks, noncyclic inspections are necessary when unforeseen circumstances arise. For example, if a worker notices a discrepancy or a particularly important batch is expected, they should initiate nonscheduled audits.
Select Reputable Outsourcing Partners
How much trust should business leaders place in their outsourced partners? In 2023, the FDA rejected a drug based on deficiencies it discovered during a safety and quality inspection at a third-party manufacturing plant. Sometimes, the agency does not catch the issue in time, which has resulted in injury and even death.
Convincing the pharmaceutical manufacturing sector to abandon outsourcing is nonsensical, as this approach is incredibly cost-effective. Instead, companies should develop a rigorous selection process to ensure they only work with reputable facilities. Third parties should have an excellent compliance history and consistently provide detailed documentation.
Invest in Automation Solutions
Automation can help manufacturing professionals streamline the bulk of tedious, repetitive calibration and validation processes, enabling skilled workers to focus on high-risk or value-adding tasks. Possible solutions include artificial intelligence, computer vision systems, robot process automation or robotics.
Preserving Quality in Pharmaceutical Manufacturing
Preserving quality control in pharmaceutical manufacturing is about more than remaining compliant — people’s jobs and lives are on the line. Decision-makers must carefully consider the consequences of neglecting calibration and validation processes, understanding that inaction could result in detrimental outcomes.
