GxP Compliance for the Pharmaceutical Industry

October 02, 2020

Regulation is an unavoidable fact of life for the pharmaceutical industry. The consequences of a manufacturing or distribution error for most industries are limited and largely financial. However, for pharmaceutical manufacturers, errors can have a widespread impact on the health and wellbeing of the population. To protect against errors happening, and to ensure that they can be properly identified and understood when they do, the FDA maintains a regulatory framework that governs how pharma companies do business.

The goal of the FDA is always to protect the consumer. Once a drug receives approval, the FDA must be able to ensure that standards are being maintained. Naturally, this is difficult to do at scale, so they rely on audits and investigations into errors to protect against similar issues arising in the future. This is why at the core of the FDA’s pharmaceutical regulatory framework are ‘Good Practice Standards’ or GxP.

What is GxP?

The “x” in GxP is a placeholder for a number of areas in the pharmaceutical research, manufacturing, and distribution process where Good Practices must be applied. Essentially, GxP or cGxP (Current Good Practices) is an umbrella term to describe the regulations and guidelines provided by them which define how a drug should be researched, manufactured, distributed, and most importantly - how that should all be documented.

The two central goals of GxP standards and regulations are introducing accountability and traceability to every project being undertaken by pharmaceutical companies.

Accountability

Achieving accountability requires pharmaceutical companies to maintain an accurate, auditable record of who was involved in the production and distribution of a drug, what their role was, and what all their contributions were to the project.

Traceability

Traceability refers to the ease with which a drug’s creation, and any errors that may have been introduced during that process, can be audited. A project which has followed GxP should be able to trace any issues back to the exact moment that they happened so that the correct people can be held accountable and changes can be implemented to remove the risk going forward.

What is GxP Compliance?

GxP compliance entails implementing a rigorous system of documentation and records management that provides the FDA with a clear path for auditing the manufacturing and distribution process of a drug, from start to finish. More specifically, it means meeting the guidelines outlined in the CFR 21 Part 11 regulation, which was put in place and is enforced by the FDA.

CFR 21 Part 11 specifically deals with the creation, management, and destruction of electronic records and signatures. As most pharmaceutical manufacturers now maintain the lion’s share of their records electronically, CFR 21 Part 11 has become the primary piece of regulation for which pharma companies must meet compliance requirements.

While CFR 21 Part 11 (rightly) puts in place highly-stringent requirements for the management of electronic records, it does not need to be a major drain on resources and time. Naturally, manually implementing GxP standards for pharmaceutical companies would be incredibly difficult. Thankfully, there are excellent pharmaceutical records software solutions that are CFR 21 Part 11 compliant, and that seamlessly implement guidelines for you, making GxP compliance something which is built into the system itself. And, furthermore, compliance will both protect companies from hefty fines and financial losses and result in a more streamlined process overall.

GxP Systems Validation Process

While implementing a GxP compliance IT system does greatly reduce the cost and effort of meeting GxP standards in the pharmaceutical industry, it is important to note that compliance also requires regular validation of those systems. Thankfully, good GxP-compliant software platforms make validation easy. On top of that, there are helpful guidelines published by the International Society of Pharmaceutical Engineering (ISPE) which detail the correct GxP systems validation process.

GxP Assessment Questions

While GxP compliance IT and records management systems should always be validated by experts, anyone involved in the implementation of a system aimed at GxP compliance should be aware of some basic GxP assessment questions. These questions are designed to determine whether or not a software system has a direct impact on GxP.

  1. Is the system used to monitor or control a manufacturing, packaging, or distribution process that is subject to GxP?

  2. Does the system have the potential to affect product quality, safety, identity, or efficacy?

  3. Does the system produce data or reports that are necessary for the GxP audit process?

  4. Is the system used for GxP batch sentencing or batch records?

What is the Difference Between GxP and GMP?

You may have heard the term “GMP”, or “Good Manufacturing Practice”. This is one of the most crucial and widespread iterations of GxP, meaning that sometimes one is used in place of the other. While they are occasionally used almost interchangeably, GxP refers more broadly to the concept of “Good Practices”, encompassing a long list of industry’s and activities. Some of these guidelines are provided by different agencies and regulations, making some more essential when it comes to compliance.

GMP, however, is just one of those sets of guidelines, referring specifically to manufacturing practices. While it applies to many industries, it is most often used to refer to the pharmaceutical, medical instrumentation, and bio/life science industries. GMP is, in fact, just one of several GxP guidelines that govern the pharmaceutical industry.

Types of GxP for the Pharmaceutical Industry

There are a number of different variations of GxP for the pharmaceutical industry, each one targeting a different stage of the drug development, manufacturing, and distribution pipeline.

Good Manufacturing Practice (GMP)

Arguably the most important of the GxP guidelines when it comes to the pharmaceutical industry, GMP refers to the standards and guidelines which define how a drug or instrument should be manufactured to ensure consistency. GMP, or cGMP, is the foundation of the FDA’s oversight of drugs that are on the market or nearing introduction to it.

Good Clinical Practice (GCP)

GCP applies specifically to clinical trials and the testing of drugs on humans. Defined by the International Conference on Harmonization (ICH), GCP guidelines are designed to protect trial subjects and ensure that drugs and instruments move into human trials only when absolutely necessary.

Good Laboratory Practice (GLP)

Similar to GCP, GLP is the FDA’s set of guidelines for non-clinical trials and testing. Rather than protecting trial subjects, GLP is more focused on ensuring that non-clinical trials are conducted, evaluated, and reported correctly so as to ensure the quality of drugs and instruments in pre-clinical testing.

Good Storage Practice (GSP)

Outlined by the WHO, GSP is the first of the guidelines which deals with the supply chain of pharmaceutical manufacturers. Specifically, it aims to provide guidance on the safe storage of drugs and pharmaceutical starting materials, both during manufacturing and distribution.

Good Distribution Practice (GDP)

Closely related to GSP, GDP deals specifically with ensuring the proper and safe distribution of pharmaceuticals. Housed within the cGMP guidelines laid out and enforced by the FDA, GDP requires the implementation of Quality Management Systems which document every stage of the distribution process.

Good Review Practice (GRP)

The GRP guidelines are published by the FDA and refer to the best practices pertaining to the process, format, content, and management of medical product review.

What is a GxP Record?

The important thing about meeting GxP compliance is not simply that you have the correct processes in place, but also that you fully and accurately document those processes and the actions taken to comply with them. Fundamental to this are GxP records. Unfortunately, there can be some confusion around what exactly constitutes a GxP record, as different regulations and guidelines may define records differently.

For a simple definition, however, we can look to the definition of GMP records as a yardstick. GxP records, then, are any pieces of information that are required by regulations to be preserved as evidence of compliance. These could include everything from emails and other communication to master formulas or batch records.

What is GxP Documentation?

GxP documentation is not only very similar to GxP records, it actually includes it. GxP documentation literally just means any and all pieces of recorded information that are related to the implementation, recording, and communication of GxP compliance. Simply put, not all GxP documentation will necessarily be classified as a GxP record, but all GxP records are also GxP documentation.

What is Non-GxP?

With the understanding that GxP is required by regulators, it might be confusing to encounter the term non-GxP. However, non-GxP does not refer to maverick pharmaceutical companies operating outside the law. Rather, it simply refers to early discovery research that is largely academic in nature and therefore does not require as stringent a set of regulations, which most research institutions and companies argue would stifle the research velocity of their teams.

There is a growing debate around whether GxP should be applied to traditionally non-GxP research environments. Either way though, non-GxP does not mean that projects are managed haphazardly and documentation is not preserved. Large projects require sound records management whether they are aiming to be GxP compliant or not and can still benefit from implementing a robust records management platform.

Summary

When it comes to the research, manufacturing, and distribution of drugs and other medical products, GxP should not just be seen as a set of boxes to check in order to meet compliance. While many of the aspects of GxP are defined and enforced by the FDA and other regulatory agencies, the reason for their existence is as much to streamline and improve the process of drug discovery and development for pharmaceutical companies as it is to protect their customers.

GxP compliance really shouldn’t be seen as a chore that gets in the way of progress. With a modern records management platform in place, there should be no reason for GxP to be a hindrance. Automated audit trails and retention and disposition schedules will allow your organization to benefit from all of the risk mitigation of GxP without any impact on operational efficiency.

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