Overview
In the intricate world of drug development, the role of quality cannot be overstated. Ensuring the safety, efficacy, and reliability of pharmaceuticals is a cornerstone of the healthcare industry, as highlighted in the U.S. FDA’s Fiscal Year 2023 Report on the State of Pharmaceutical Quality. This report, a comprehensive analysis of drug manufacturing sites, inspections, and product quality, underscores the critical need for a robust quality system throughout the development phases of a drug product.
Though the FDA report is focused on commercial products, the information also translates to investigation drugs as the same issues exist during drug development. At Syner-G Biopharma, we aim to emphasize the paramount importance of quality with a phase-appropriate, fit-for-purpose approach during drug development.
The Role of Quality in Drug Development
Quality is essential at every stage of drug development, from initial research to final product distribution. For pharmaceutical companies, especially virtual ones relying on contract manufacturing organizations (CMOs), maintaining high standards requires vigilant oversight, careful supplier selection, and periodic requalification. Effective sponsor oversight involves regular audits, detailed quality agreements, and continuous communication with CMOs to ensure compliance with regulatory standards. Ensuring quality is not just about meeting regulatory demands but a fundamental responsibility to protect patient safety and enhance product reliability.
Case Study: Criticality of Attributes
A practical example involves a manufacturer of a drug, where the raw material’s impurity profile could significantly influence the product’s safety profile. Through risk assessment, the residual levels of certain impurities are classified as critical quality attributes (CQAs). The company then tailors its testing protocols to rigorously monitor these impurities during manufacturing.
An example would be the use of lower-grade excipients in dry powder inhalers causing potential safety concerns to the patients. In this case, the manufacturer would be relying on the additional testing during routine manufacturing to ensure excipient quality and patient safety.
Another example would be the use of ethanol in a process step which also includes water. Typically, ethanol would include water content as a quality attribute. However, in this case, the company may choose to not assess the water content of the incoming ethanol because it can be justified as not being critical due to its insignificance relative to the water added during the process step itself.
Key Highlights from the FDA’s Report
The FDA’s FY2023 report reveals critical quality-related issues in the pharmaceutical industry. The agency received 17,086 quality-related reports, marking a 5% increase from the previous year. These reports include 12,549 MedWatch reports, 3,792 Field Alert Reports, 347 Biological Product Deviation Reports, and 398 consumer complaints. Notably, contamination issues accounted for a significant portion of recalls, with contamination-related recalls increasing by 58% from FY2022. Specific types of contamination included sterility assurance issues (38%), foreign material/particulate contamination (31%), microbial contamination (17%), product mix-up/cross-contamination (8%), and chemical contamination (6%).
The report also highlights ongoing challenges with CGMP deficiencies, which were the most common defect group for recalls, representing 52% of all recalls. Additionally, the FDA added 93 companies to import alerts for drug quality reasons, significantly higher than in previous years. These figures underscore the importance of stringent quality controls and continuous monitoring to address and prevent quality issues in the pharmaceutical supply chain.
Why Quality Matters in Drug Development
Quality issues can lead to drug shortages, product recovery/recalls, and, most importantly, pose significant risks to patient safety. The FDA’s report indicates that quality problems remain one of the most common reasons for drug shortages, which can severely impact patient care.
By prioritizing quality, pharmaceutical companies can ensure the following:
- Patient Safety: High-quality drugs reduce the risk of adverse effects and ensure that patients receive the intended therapeutic benefits.
- Regulatory Compliance: Adhering to quality standards helps avoid regulatory actions such as warning letters, import alerts, and recovery/recalls.
- Market Reputation: Companies known for their commitment to quality are more likely to gain the trust of healthcare providers and patients.
- Cost Efficiency: Preventing quality issues early in the development process can save costs associated with clinical trial delays, recovery/recalls, legal liabilities, and lost revenue.
How Can a Sponsor Maintain a High-Quality Standard
Effective sponsor oversight is essential for ensuring that all aspects of drug development adhere to the highest quality standards. Sponsors must take an active role in overseeing their CMOs and other partners to ensure compliance with regulatory requirements and internal quality benchmarks. This involves regular audits, detailed quality agreements, and continuous communication to monitor and manage every step of the process.
- Audits and Inspections: Regular audits and inspections of manufacturing sites, both scheduled and surprise, help ensure that CMOs adhere to Good Manufacturing Practices (GMP) and other regulatory standards.
- Quality Agreements: Establishing comprehensive quality agreements that outline the responsibilities, expectations, and quality standards for both the sponsor and the CMO is critical. These agreements should include procedures for handling deviations, complaints, and recalls.
- Effective Monitoring: Implementing systems for periodic/continuous monitoring of manufacturing processes and product quality helps identify and address issues in real-time, preventing potential quality lapses.
Good Supplier Selection
Selecting the right suppliers is the first step towards ensuring quality in drug development. This process should be thorough and based on a detailed assessment of the supplier’s capabilities, compliance history, and commitment to quality.
- Due Diligence: Conducting thorough due diligence on potential suppliers, including evaluating their quality systems, regulatory compliance history, and financial stability, is crucial.
- Capability Assessment: Assessing a supplier’s technical capabilities, production capacity, and ability to meet specific quality standards ensures that they can reliably supply the necessary materials or services.
- Reputation and Track Record: Considering the supplier’s reputation and track record in the industry can provide insights into their reliability and quality focus.
Supplier Qualification
Once selected, suppliers must be qualified to ensure they meet all necessary quality and regulatory standards. This process involves a detailed evaluation of their systems, processes, and performance.
- Initial Qualification: The initial qualification process should include on-site audits, testing of materials or services, and validation of processes to ensure they meet the required standards.
- Documentation Review: Reviewing all relevant documentation, including quality manuals, standard operating procedures (SOPs), and previous audit reports, helps verify the supplier’s compliance and quality practices.
- Performance Metrics: Establishing key performance indicators (KPIs) to monitor supplier performance on an ongoing basis ensures they continue to meet quality expectations.
Ongoing Oversight
Maintaining high quality standards requires continuous oversight and management of suppliers and CMOs. This ongoing oversight ensures that initial qualifications are maintained and that any emerging issues are promptly addressed.
- Regular Audits and Reviews: Conducting regular audits and performance reviews helps ensure ongoing compliance and quality. These reviews should be based on a risk-based approach, focusing on critical suppliers and high-risk areas.
- Feedback Loops: Establishing feedback mechanisms to communicate performance issues and improvements needed helps maintain a collaborative and proactive relationship with suppliers.
- Risk Management: Developing and implementing risk management plans to identify, assess, and mitigate potential risks in the supply chain ensures continuity and quality of supply.
Conclusion
Quality in drug development is not just a regulatory requirement; it is a fundamental responsibility that ensures the safety and efficacy of pharmaceuticals. For virtual companies and those relying on CMOs, this means rigorous sponsor oversight, careful supplier selection, thorough qualification, and continuous management. By prioritizing these elements, companies can maintain high-quality standards, comply with regulatory requirements, and ultimately deliver safe and effective medicines to patients.
Syner-G Biopharma Group provides comprehensive technical, quality, and regulatory strategic support across all stages of pharmaceutical development ensuring compliance throughout your product’s life cycle.
Reference
FDA Fiscal Year 2023 Report on the State of Pharmaceutical Quality
