What are GxPs?

GxP refers to a collection of quality guidelines and regulations that are used in highly regulated industries to ensure a product is safe for consumers and meets its intended use. GxP quality guidelines are required in a number of industries, including the pharmaceutical, food, cosmetics, and medical device industries. GxP is an abbreviation, where the “G” and “P” represent “good practice” and the “x” is a variable for various operations within a manufacturers business. Examples of GxPs are shown in the following section.

The implementation and enforcement of GxP compliance standards is overseen by regulatory agencies unique to the country of operation. In the United States, the enforcement of GxP guidelines is undertaken by the FDA, while in Europe they are enforced by various National Regulatory Agencies. Due to the fragmented nature of GxP compliance enforcement, different guidelines for the implementation of various GxP systems exist from country to country. However, most guidelines follow the same principles derived from the World Health Organization (WHO) versions of GxP guidelines, and mutual recognition agreements (MRA) exist between regulatory agencies worldwide. These MRAs recognize that country A’s standards for “good practices” meet the standards of country B and that a producer operating in country A, meeting the compliance standards of country A’s regulatory agencies, will automatically meet the standards of country B.

GxP Systems

The core tenants of all GxP systems are traceability and accountability with the ultimate goal of preventing harm to the end-user. GxP quality guidelines span all business units for manufacturers operating in a regulated industries (ie. pharmaceutical, food, etc.). Although the guidelines for each GxP system vary based on geography, the core principles in the context of quality assurance remain the same. An overview of the most prevalent GxP systems is outlined below.

Good Agricultural & Collection Practice (GACP)

Good agricultural and collection practices for medicinal plants are the first step in quality assurance and provide technical guidance on producing high-quality medicinal plant materials for the sustainable production of herbal products. The primary objectives of implementing GACP are to ensure quality is in control and assured throughout the cultivation process to improve the quality, safety and efficacy of finished herbal products, and to encourage sustainable cultivation and collection practices that support the conservation of the environment. The leading authority on GACP is the World Health Organization which developed the Guidelines on good agricultural and collection practices (GACP) for medicinal plants in an effort to guide the formulation of national and/or regional GACP guidelines.

Good Manufacturing Practice (GMP)

Good manufacturing practice guidelines integrate with GACP guidelines for the subsequent steps in the production of goods in regulated industries. The rules that govern each regulated industry are slightly different, however, all GMP guidelines provide the minimum requirements that a manufacturer must meet to assure that their products are high in quality and are consistent from batch to batch. The purpose of applying good manufacturing practices is to ensure there is no adulteration of the product. The application of good manufacturing practices must be enforced by the manufacturer and all the participants in the supply chain to ensure appropriate levels of compliance are met. The primary components of all good manufacturing practices include ensuring the end product is free from contamination, that it is “in control” (meeting product specification), that its manufacture is traceable through documentation, that personnel are well trained, and that the product has been assessed against quality metrics throughout the production process. These aspects are ensured through the use of a quality management system (QMS). The most commonly enforced GMP guidelines include the U.S. Food and Drug Administration’s (FDA) “current good manufacturing practices (CGMP)” under Title 21 CFR, EuGMP practices outlined in “EudraLex – Volume 4 – Good Manufacturing Practices Guidelines”, and the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) Guide to GMP.

Good Documentation Practice (GDP or GDocP)

Documentation is a critical tool for ensuring GxP adherence. In the world of GxP production, there is a common saying: “if any aspect of the manufacturing process hasn’t been documented, then it didn’t happen”. Creating the necessary documentation is the only way to prove that your processes – and your products – meet industry standards and legal requirements for safety, efficacy, and product quality. Good Documentation Practice describes the standard by which documents are created, updated, and maintained. Maintaining records using Good Documentation Practice is an essential component of the quality management system, representing the only official documented record of processing a batch, the final decision to release (or reject) a batch or product, the evidence for corrective or preventive action and that a product meets its product and quality specifications. Good Documentation Practices are enforced by regulatory agencies in the respective country of operation, such as the FDA (US), TGA (Australia), EMEA (European Union), Health Canada (Canada) or WHO (Global Standard).

Good Distribution Practice (GDP)

The implementation of rigorous quality standards in highly regulated industries extends beyond the manufacturing of said products. The distribution of products requires similar levels of security and quality control that are defined by Good Distribution Practices. Ultimately, Good Distribution Practice defines the minimum standards a wholesale distributor must meet to ensure that the quality of products isn’t adversely impacted throughout the supply chain. This includes that products are authorized within the country of origin and consumption, products are stored in conditions optimized for their preservation, contamination is avoided, adequate turnover of stored products takes place, and the correct products reach the correct consumers. Good distribution practice also extends to the sourcing, storage, and transportation of APIs used in the production process which highlights the importance of implementing a product tracing system. Similarly to other GxP systems, Good Distribution Practice is enforced by regulatory agencies in the respective country of operation, such as the FDA, TGA, EMEA, Health Canada, and WHO.

Good Clinical Practice (GCP)

Good Clinical Practice is an international quality standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials. Good Clinical Practice ensures that clinical trials are conducted ethically using a scientific method that produces credible clinical trial data. Clinical trials are an integral part of pharmaceutical development, however, without adherence to Good Clinical Practices, the safety and wellbeing of the trial subjects cannot be protected, and the credibility and accuracy of results cannot be validated. GCP typically follows the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, which governments can then transpose into regulations for clinical trials. The enforcement of Good Clinical Practice differs globally; in the European Union, GCP is regulated by formal legislation contained in the Clinical Trial Directive (Directive 2001/20/EC), while in the United States, ICH GCP guidelines are recommended by the FDA, however, are not statutory.

Good Laboratory Practice (GLP)

Good Laboratory Practice is a quality system used by research laboratories and organizations operating in regulated industries to ensure that experimental (non-clinical) research studies are executed in a manner that assures uniformity, reliability, reproducibility, and quality. Good laboratory practice defines a set of quality standards for study conduct, data collection, and results reporting that validate a study has been conducted according to its study protocol. GLP does not, however, prove that a study actually addresses the scientific hypothesis. A key component of Good Laboratory Practice is the definition of roles and responsibilities within a study. GLP work requires a Study Director (oversight and execution), an analyst (execution), and a QA auditor (monitor study conduct and verify procedure). GLP principles cover all aspects of a laboratory’s daily activity, such as the layout of testing and storage areas to prevent contamination, cleaning and calibration of equipment, and recording and archiving test results. Good Laboratory Practice regulations are outlined by the FDA in the United States under Directive 21CFR58, and for the European Union via the Organization for Economic Co-operation and Development (OECD) under Directive 2004/10/EC.

Other GxP systems include, but are not limited to, Good Auditing Practice (GAP), Good Pharmacovigilance Practice (GVP), Good Regulatory Practice (GRP), and Good Safety Practice (GSP).

GxP in the Cannabis Industry

Each of the GxP systems included in the previous section are relevant to the medical cannabis industry and constitutes “Good Cannabis Production Practice”. Although each of the GxP systems outlined above apply to the cannabis industry, there is currently no universally accepted guidelines for Good Cannabis Production Practice, therefore licensed producers are forced to identify, interpret, and apply the aforementioned guidelines published by regulatory agencies in the country of operation or distribution. Typically, each country outlines the compliance standards that must be implemented in order to operate or sell a product in their jurisdiction. Despite the fragmented implementation of quality standards throughout the world, each quality system is applied to the same production processes in a cannabis operation. The areas covered by each GxP system, as applied to the cannabis industry, are outlined below:

1.     Good Agricultural and Collection Practice

1. Plant propagation
2. Cultivation
3. Collection and Harvest
4. Cutting and Drying

2.     Good Manufacturing Practice

1. Drying
2. Comminution, extraction from plants, fractionation, purification, and concentration
3. Expression from plants and distillation
4. Further processing into a dosage form including packaging as a medicinal product

3.     Good Documentation Practice

1. Records
2. Standard Operating Procedures
3. Work Instructions
4. Specifications

4.     Good Distribution Practice

1. Distribution of herbal cannabis, extracts, APIs, and final product forms

5.     Good Clinical Practice

1. Clinical trials and clinical practice, including pharmacy dispensing

6.     Good Laboratory Practice

1. Analytical testing of herbal cannabis, extracts, APIs and final product forms