What is GxP compliance?
Industry support of overdose prevention
This is blog 8 of 10 Blogs in the overdose awareness and overdose prevention series.
What is GxP compliance? And how does GMP/GxP compliance help with overdose prevention efforts?
- GMP and GxP are pharmaceutical-industry quality standards and manufacturing guidelines.
- These quality standards apply to the manufacture of pharmaceutical products, medical devices, and veterinarian medicines.
Compliance with manufacturing regulations (GMP/GxP guidelines):
- ensures medicinal products meet safety, quality, and efficacy standards
- provides patients with beneficial pharmaceutical treatment options, without causing preventable harm
- ensures information published by manufacturers and distributors is accurate (e.g. evidence-based dosing recommendations, safety risks, drug-drug interaction warnings, etc.)
Accurate packaging and labelling information can help:
- reduce dosing errors
- reduce unexpected drug-drug interactions
- prevent unintentional overdose toxicity or overdose deaths
Download the latest Australian overdose statistics report (2021)
*Australian Overdose Report publication date: 31st of August 2021.
Illicit supply chains sell unsafe products with contaminants and unpredictable dosing levels
Industry compliance with GxP guidelines also helps to prevent pharmaceutical products from being diverted into illicit supply chains. This includes unauthorised web-based pharmacies.
Unauthorised online distributors are notorious for selling substandard products and counterfeit drugs.
Illicit distributors divert products, mix them with deadly chemicals and contaminants, and advertise fake pharmaceuticals via their online channels or street distribution networks.
A large percentage of online distributors are unauthorised (meaning not confirmed as legitimate sellers, and known to sell fake drugs).
These groups:
- advertise dependency-forming pharmaceuticals using counterfeit labelling (false branding/illegal advertising)
- distribute products that contain substitute APIs (e.g. rat poisons) and/or inconsistent API percentages
- do not comply with batch tracing requirements and have no procedures for recalls when a batch proves deadly
This is in direct — and deadly — contrast with quality-tested APIs produced by GMP organisations that comply with GxP guidelines.
Non-medical use of medicines obtained without a legitimate prescription — and used without Physician supervision — adds to the overdose epidemic. These are potent medicines. In illegal supply chains, they have unknown contents and potency levels; and are often very deadly.
Inconsistent potency levels in illicit products — as well as polysubstance use — can readily lead to unintentional overdose deaths or other patient harms, such as brain damage and organ failures.
Read the blog on factors linked with prescription overdose fatalities.
API supplies are frequently targeted by sophisticated crime gangs.
GxP compliance helps the pharmaceutical industry prevent criminal diversions and associated harms. But logistics teams, and warehouse/distribution personnel, need to be trained. Good Warehouse Practice (GWP) and Good Distribution Practice (GDP) are helpful GxP guidelines for preventing product diversion.
GxP and Overdose Awareness Awareness Day
Where is the link between GMP/GxP compliance, overdose awareness building, and overdose prevention education?
The link is that industry GxP compliance helps prevent product diversions, ensures consistent product quality (dosing), and inform patients and doctors of the RISKS of known drug-drug interactions and of polysubstance use.
GxP can also help ensure labelling contains information on dependency risks and overdose harms.
- Information missing from packaging/labelling and marketing materials was at the heart of the opioid epidemic in the United States
- Overdose death statistics in Australia and other countries reveal a continuing increase in opioid-related overdose deaths
- Highly potent synthetic opioids, such as those used to treat cancer pains, are another reason that overdose risks are elevated
- Diversions of drug supplies include prescription theft and/or non-medical use
Case study about GxP non-compliance (product information/labelling)
Purdue Pharma and McKinsey Group Lawsuits
Read more on the Purdue Pharma/McKinsey legal battles and billion-dollar settlements currently working their way through courts in the USA
Please get involved in International Overdose Awareness Day and other overdose prevention/community education activities.
The opioid epidemic is a clear example of the importance of GMP compliance by pharmaceutical manufacturers and their distribution channels. Marketing information distributed by Purdue Pharma (and the McKinsey Group) was inaccurate in relation to potential dependency risks, overdose risks, and drug-drug interactions for opioid prescription medications.
Recap of overdose prevention efforts and GxP compliance
Industry compliance with GxP guidelines and other GMP regulations and FDA CFRs:
- ensures quality testing to ensure consistent API levels in prescription medicines
- requires proper labelling and packaging for medicinal products
- requires evidence-based medication warnings (e.g. this medication may cause drowsiness and should not be used while operating machinery)
- promotes the safe use of prescription medicines (dosing recommendations, toxicity warnings, drug-drug interaction information)
- requires product security and protection from supply chain diversions (product theft, delivery substitutions, or counterfeit products entering consumer supply chains)
- requires pharmaceutical supply controls via inventory audits, batch tracing and recordkeeping (including serialisation on packaging, where required)
These GMP/GxP requirements can help reduce risks of prescription drug dependencies, non-medical use of prescription medications, and overdose toxicity.
Overdose research resources
Download the 2021 Australian Overdose Report
Watch the < 3 minute video on Australian overdose statistics
Read the other blogs in this overdose awareness/prevention article series.
Recognising the importance of complying with GMP & GxP guidlines reminds us all – as individuals and businesses – to support overdose prevention initiatives such as International Overdose Awareness Day.
- Read the blog on 2020-2021 overdose statistics
- Download the Penington Institutes 2021 Annual Overdose Report
Further reading for individuals unfamiliar with GMP regulations or GxP guidelines
GxP basics: What does the ‘x’ in ‘GxP’ represent?
The ‘x‘ in GxP is meant to represent a wide variety of GMP compliance guidelines that inform the design, maintenance, and review, of the manufacturer’s Pharmaceutical Quality System (PQS). Guidelines are based on quality risk management principles.
GxP includes collective GMP guidelines used in addition to PIC/s GMP Guide Part I and GMP Guide Part II, product-relevant Annexes, and other pharmaceutical industry publications.
Purpose of GxP guidelines: GxP guidelines aim to ensure appropriate resources are devoted to the manufacture of medicinal products so that these products meet quality, safety, and efficacy expectations.
Application of GxP guidelines: PIC/s GxP guidelines and other GMP guideline publications from Regulatory Authorities apply to:
(1) pharmaceutical medicines including ATMPs/biological medicines,
(2) medical devices, and
(3) veterinarian medicines.
Examples of GxP guidelines: Compliance publications associated with the acronym “GxP” include Good Recordkeeping Practice (GRK), Good Warehouse Practice (GWP), Good Distribution Practice (GDP), other GMP compliance guidelines.
Complying with expected GxP guidelines is an important part of the Pharmaceutical Quality System (PQS).
GxP Compliance: Quality Risk Management responsibilities
What do GMP regulations — and GxP guidelines — actually require pharmaceutical manufacturers to implement, in terms of quality assurance measures?
It’s a complex answer.
- The reason is that there are many different GMP requirements (hence the acronym ‘GxP’); some of which are product-dependent.
- Requirements can also vary slightly depending on the Regulatory Agency, e.g. their current auditing focus and PIC/S guideline interpretations.
That noted, PIC/S, described further below, aims to ensure global consistency in GMP compliance auditing (during inspections by Regulatory Agencies).
Learn the 10 Golden Rules of GMP compliance or take the GMP induction training bundle.
Who publishes GMP regulations and GxP compliance guidelines?
GMP/GxP guidelines are published by various organisations and Government Authorities.
GMP/GxP guidelines are available from PIC/s, the ISPE, and Regulatory Authorities such as the FDA (FDA CFRs), the TGA, the MHRA, the EMA, and other Regulatory Authorities tasked with ensuring the quality and safety of medicines and medical devices in their jurisdictions.
List of Regulatory Authorities and GMP Compliance Auditors.
Clarification of acronym meanings and definitions for “GxP” and “GMP”
To understand GxP guidelines is to first understand current Good Manufacturing Practice regulations (“cGMP”).
- GMP guidelines set quality and safety standards for pharmaceutical manufacturing practices.
- These guidelines apply to a variety of medicinal products, including medical device manufacturers, veterinary medicines producers, and manufacturers/administrators of ATMPS (Advanced Therapy Medicinal Products) and other biological medicines.
The industry’s primary GMP guidelines are published by the Pharmaceutical Inspection Co-operation Scheme or “PIC/S”.
GxP is an acronym that represents a wide range/collection of quality standards and risk-management guidelines applicable to the pharmaceutical industry, including medical devices and veterinary medicines.
In general, GxP guidelines are part of — and closely aligned with — other GMP requirements.
GMP/GxP compliance helps ensure product quality requirements are being met by pharmaceutical industry manufacturers. The two acronyms (GMP and GxP) are often used together – as “GMP/GxP” as well as alone.
GMP Guides, PIC/S Annexes, and other regulatory publications
GMP/GxP guidelines describe the minimum quality management standards that manufacturers are expected to meet to ensure the supply of safe, quality, effective medicinal products for patients and/or for animals.
- Some guidelines (Annexes, for example) are product-specific guidelines for meeting GMP requirements.
- Other guidelines are applicable to nearly EVERY pharmaceutical product or medical device, at an industry-wide level (in other words, they are not product-specific).
Industry-wide GxP compliance guidelines include Good RecordKeeping Practice (GRK), Good Warehouse Practice (GWP), Good Distribution Practice (GDP), and Data integrity/Data governance guidance.
Terminology/acronym use
- The GMP acronym might be used when referring to a primary guidance publication such as the PIC/S GMP Guide Part I and GMP Guide Part II, and relevant Annexes.
- The GxP acronym might be used when referring to a group of guidelines (or ‘collective’ GMP compliance guidelines) — such as when referring to overall GMP compliance responsibilities.
GMP = Good Manufacturing Practice
GxP = Guidelines and specific components of Good Manufacturing Practice
FDA = Food & Drug Administration (USA)
TGA = Therapeutic Goods Administration (AUS)
This information reminds pharmaceutical manufacturing organisations of the importance of complying with GMP/GDP regulations, data integrity requirements, and the FDA’s CFRs.
And it reminds ALL of us – as individuals and businesses – to support overdose prevention initiatives such as International Overdose Awareness Day.
Please FOLLOW US on LinkedIn and/or return to these is blog pages for the additional blogs on drug overdose awareness and prevention, being published daily from 22 August through 31 August 2021 (inclusive).