Drug safety monitoring is an important part of GMP/GxP compliance.
Drug safety monitoring includes pharmacovigilance as well as supply chain protection. These safety measures can help prevent product diversions, and reduce product overdose risks, and are key components of an effective Pharmaceutical Quality System (PQS).
To ensure products are safe and effective to use and that ‘safety signals’ are recognised in a timely manner.
To prevent diversions of quality-checked products into illicit drug supply chains where quality becomes compromised (such as online pharmacies selling counterfeit or substandard products will fake branding/packaging).
As noted in other blogs written to support overdose prevention education, products sold by illicit distributors (online or by ‘street-level dealers’) are often made by mixing various chemicals under unsanitary conditions (e.g. in filthy drug labs). These illicit products are based on dilution of diverted products and mixing them with other chemicals of unknown potency/drug effects (such as mixing these with rat poison or bleach). Not only do these products have wildly varying potency levels — a serious risk for overdose reactions — they have various other active ingredients and contaminants.
Inconsistent batches – and products that are not being manufactured and not being quality checked according to GMP requirements, will lead to dosing inconsistencies.
Dosing inconsistencies — and unpredictable amounts of active ingredients — often lead to overdoses.
And overdoses often lead to death.
Drug safety monitoring and related quality controls can assist other overdose education/overdose prevention efforts.
Drug safety monitoring programs require the following compliance measures and quality controls.
We’ll discuss the importance of establishing an effective Pharmacovigilance system, below, but first, let’s look at the essentials of Good Manufacturing Practice (GMP) and GxP guidelines.
GMP regulations reduce overdose risks by requiring pharmaceutical manufacturers to ensure:
suppliers meet quality standards and clearly defined product specifications
product packaging and labelling information is accurate (this includes the manufacturer’s online content/website content)
drug safety monitoring systems are in place (pharmacovigilance systems) and are being monitored for effectiveness
complaints from patients/medical professionals are recorded, properly categorised, and appropriately handled
adverse drug reactions/serious adverse events are reported to the Regulatory Authorities within the required time frames
product security and data integrity are maintained throughout production to help prevent diversion for non-medical use purposes or illicit supply chains
other measures to ensure safe, quality, effective medications
Good Documentation/Good Record-Keeping Practice in the pharmaceutical industry
Record-keeping, data integrity/data governance, and product information (packaging/labelling)
Maintenance of batch tracing records throughout the product lifecycle, through distribution to patients.
Ensuring accurate information on packaging and labelling regarding safe use instructions, potency/dosing recommendations, and product risks including product-use contraindications.
The list above reminds us of the BENEFIT of compliance with GMP/GxP guidelines, to promote the safe use of pharmaceuticals (and medical devices) and help reduce overdose risks.
Of note are GMP requirements for accurate packaging and labelling – which includes manufacturer website content in relation to their products.
Materials warning patients and doctors of drug dependency risks and overdose risks relating to certain types of medications, such as opioids and synthetic opioids, was a key compliance gap in the United State’s opioid overdose epidemic.
It was Purdue Pharma’s non-compliance with industry requirements for accurate product information (e.g., appropriate packaging/labelling on habit-forming medications) that contributed to the opioid crisis.
*Australian Overdose Report publication date: 31st of August 2021.
The value of Pharmacovigilance systems and overdose prevention efforts
Product Safety Monitoring
A manufacturer’s responsibility includes ongoing pharmaceutical product safety monitoring requirements.
GMP, QRM, and batch traceability requirements continue through the delivery of the medicines or medical devices to patients (or for veterinarian medicines, through delivery and administration to animals).
It doesn’t stop there, however.
GMP/GxP compliance includes post-delivery “product safety monitoring” – otherwise known as Pharmacovigilance.
GMP/GxP compliance involves ongoing monitoring of product quality and the effectiveness of the PQS (Pharmaceutical Quality System).
Product safety complaints monitoring
Pharmaceutical product safety signals and trends analysis requires:
Investigation of product deviations (CAPA)
Monitoring of product complaints
Classifying, tracking, reporting and analysing ‘drug safety signals’ and complaint trends
appropriate reporting of adverse drug reactions (ADRs) and SAEs within legally required timeframes
Alerting distributors, manufacturers, Regulators, and medical professionals of potential issues with certain medications
These responsibilities fall under ‘Pharmacovigilance’ system requirements as part of the PQS/QMS.
Pharmacovigilance responsibilities help Pharmaceutical Manufacturers, as an industry, reduce overdose risks.
Industry drug safety monitoring and overdose prevention
better understand the overdose toxicity risks that occur when patients use certain medicines in higher doses (than recommended), for longer periods of time, and/or with other substances (drug-drug interactions)
*Australian Overdose Report publication date: 31st of August 2021.
In summary, PQS systems need to include post-marketing drug safety monitoring (Pharmacovigilance systems).
These systems help reduce overdose risks while promoting overdose prevention information and education.
Further reading and information
Definitions/terms
GMP = Good Manufacturing Practice
GxP = Guidelines and specific components of Good Manufacturing Practice
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