GxP Primer: Where Do Good Practices Come From and Why Do We Need Them?

When legislators write laws and regulations for the life sciences industry—for example, the Code of Federal Regulations (CFR) Title 21, which pertains to food and legal pharmaceutical drugs—they are written in broad terms. Global health regulators interpret those laws and regulations and issue guidelines for the industry.

More specific and actionable than the regulations themselves, the guidelines inform life sciences organizations of what they need to conform to and how they’ll be measured against those laws and regulations.

These guidelines are known as Good x Practices (GxP) and the global health regulators that issue them include:

• The International Society for Pharmaceutical Engineering (ISPE)
• The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH)
• The U.S. Food and Drug Administration (FDA)
• The Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom
• The European Medicines Agency (EMA) in the European Union
• The Therapeutic Goods Administration (TGA) in Australia
• The Pharmaceuticals and Medical Devices Agency (PMDA) in Japan

Harmonization efforts aim to reduce regulatory barriers while maintaining high standards of product quality and safety. The ICH has global representation and the ISPE offers specific and widely accepted actionable frameworks that are aligned with regulatory guidances. Therefore, the ICH and ISPE frameworks are virtual global standards that can generally be applied with confidence in many locations.

GxP Guidelines in Action

While specific requirements may vary from country to country, the principles of GxP are consistent: ensuring quality, safety, and efficacy throughout the lifecycle of regulated products.

For example:

• Good Manufacturing Practice (GMP) are guidelines for the manufacture and sale of food, drug, and active pharmaceutical products to ensure they are high quality and don’t pose a risk to the consumer or public.
• Good Clinical Practice (GCP) is an international quality standard for clinical trials involving human subjects.
• Good Laboratory Practice (GLP) guidelines apply to non-clinical studies that assess the safety and efficacy of chemicals for humans, animals, and the environment.

GxP guidelines emphasize:

• Traceability: using documented records to verify the history, location, or application of a product, device, or medicine throughout the supply chain.
• Accountability: taking responsibility for organizational activities through relevant processes and procedures.
• Data integrity: ensuring the accuracy of information by adhering to the principles of ALCOA to confirm that data is attributable, legible, contemporaneous, original, and accurate.

Procedures for critical processes in every life sciences organization must be consistent, current, clearly written, and well-documented. To ensure that procedures are followed correctly, employees must be trained on their responsibilities. Equipment should have established maintenance schedules and records. Products should have specifications for testing, sampling, status control, and records.

How a QMS Supports GxP

Multinational life sciences organizations must ensure compliance with GxP standards in multiple jurisdictions, which requires quality management systems (QMSs), comprehensive documentation, and regular audits to demonstrate adherence to applicable requirements.

A quality management system documents processes, procedures, and responsibilities for achieving quality policies and objectives. Its purpose is to control four managerial functions: quality planning, quality assurance, quality control, and quality improvements.

The FDA and other regulatory authorities work to harmonize global GxP practices with the QMS standards set forth by the International Organization for Standardization (ISO). As a result, GxP practices are integrated with ISO standards in guidance documents from the ICH.

ISO and ICH QMS requirements apply across all product classifications, including drugs, biologics, medical devices, and combination products.

A well-designed QMS improves safety, supports continuous process improvements, and enables regulators to assess your organization’s compliance with GxP requirements.

What Happens if GxP Guidelines Aren’t Followed?

During audits and inspections, regulatory authorities like the FDA and EMA cite companies for failures in data integrity and data controls. For example, the FDA will issue:

• Form 483 – a written report of significant findings and concerns that the investigator found to be objectionable conditions or practices. It’s delivered at the end of the inspection. Companies are encouraged to respond in writing with their corrective action plan and implement their plan expeditiously.
• Warning letters – are issued when responses to Form 483 are inadequate. A company must respond to a warning letter within 15 working days with a plan to resolve the findings and how they plan to prevent future occurrences.
• Establishment Investigation Report (EIR) – is issued in addition to the Form 483. It specifies No Action Indicated, Voluntary Action Indicated, or Official Action Indicated.
• Consent decree – a legal agreement that’s issued when the FDA identifies serious violations of regulatory requirements. It outlines actions the company must take within three to five years to address the violations and comply with regulatory standards.

Citations sometimes result in fines or prosecution and may cause sites to be closed down until remediated. Corrective and preventive actions (CAPA) are put in place to address complaints, nonconformances, recalls, and deviations.

To prevent non-compliance, phase-appropriate QMS practices ensure that your products meet safety and quality standards throughout their lifecycle. As your processes scale up and the product lifecycle matures, QMS practices streamline regulatory compliance.

Elements of a successful QMS implementation include:

• Applying change management to facilitate continuous improvement
• Providing assurance that there are no unintended consequences of changes
• Managing and monitoring process performance and product quality throughout the lifecycle to maintain a state of control

How to Operationalize Your GxP Data

While you’re staying on top of those GxP regulations, don’t be too risk averse. It’s never too early to start driving business value with your data. A short list of examples includes:

• Data lakes to break down silos to automate compliance reporting.
• Data orchestration that takes information from multiple storage locations, organizes it, and makes it available for analysis.
• Cloud technologies to enable platforms for innovation and new business models.
• Security and governance that are built into cloud-based GxP solutions.

Future-Proof Your Quality Processes

The FDA’s Computer Software Assurance (CSA) methodology encourages the use of automation and new technologies to help shift the focus from mere compliance to superior quality. USDM uses the CSA methodology, pairs it with exceptional domain expertise, and delivers a true risk-based approach for process and product quality.

Additionally, integrated GxP compliance is a managed service from USDM that embraces cutting-edge technologies to help future-proof your quality processes. It incorporates digital quality to reinforce quality standards in your organization and incorporates:

• Quality by design. Whether your organization is in the biotech, pharma, or medical device space, quality by design helps you create products that meet customer needs for safety and efficacy while mitigating risk. USDM employs advanced technologies to automate quality control, handle repetitive and error-prone tasks, and ensure consistency.
• Vendor partnerships. USDM partners with technology vendors in the life sciences industry to enable efficient and effective digital transformation. Among these strategic partnerships are Cloud Assurance Certified vendors that are trusted to meet GxP quality and compliance demands and give you a competitive edge.
• Risk management. Automated workflows and testing are two valuable contributors to risk mitigation in your business. The USDM Integrated GxP Compliance approach amplifies digital quality in your systems and data to minimize compliance-related risks and fuels continuous improvement throughout your organization.
• Quality documentation. Good Manufacturing Practice (GMP) requires comprehensive documentation for things like manufacturing processes, quality control tests, and maintenance logs. ProcessX, a proprietary software solution from USDM, automates manual processes and workflows to help you address critical GMP areas of your business.
• Simplified compliance. Create forward-thinking processes and efficiencies that defend against complex quality requirements. USDM Cloud Assurance as a Platform  delivers end-to-end GxP compliance that enables a continuously compliant tech stack so you can focus on life-saving work.

Whether you are new to the industry or just want to better understand technologies that support your QMS and operationalize your GxP data, contact USDM. We’ll help you reduce manual efforts with automation, streamline processes and procedures, and drive data-based decision-making.

We also offer GxP training and education and deliver full-service computer software, equipment, and process validation in regulated life sciences environments.