Drug Safety Monitoring
Drug safety monitoring and overdose prevention
This is part of the overdose statistics blog series (overdose awareness and overdose prevention articles).
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).
Click here for PQS/QMS templates.
Why is drug safety monitoring so important?
For two key reasons:
- 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:
- personnel, contractors, and suppliers have appropriate GMP/GxP compliance training
- 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
Download the latest Australian overdose statistics report (2023-24)
*Australian Overdose Report publication date: 31st of August 2023.
Drug safety monitoring and pharmaceutical overdose risks
Industry expectations that help reduce pharmaceutical product overdose risks
Three (3) key components of effective drug safety monitoring programs include:
- GMP training of employees, contractors and suppliers
- Qualifying and approving suppliers and maintaining an Approved Supplier List (ASL) – and quality testing incoming products
- Good recordkeeping/ALCOA+ as well as batch tracing systems, Pharmacovigilance systems/complaints handling, ADE/SAE reporting, etc.
Let’s review these 3 components of drug safety monitoring in the pharmaceutical sector.
GMP training in the pharmaceutical industry
Personnel/contractor qualifications and training
- Ensuring personnel, contractors, maintenance workers, vendors and suppliers are appropriately trained in GMP compliance (initial and ongoing training)
- Ensuring adequate numbers of personnel to fulfil GMP requirements
- Ensuring personnel have appropriate qualifications, skills, and compliance training in relation to their role responsibilities/product risks
Examples of GMP/GxP compliance training sessions
Examples of online GMP/GxP training
Approved Supplier List (ASL) requirements in the pharmaceutical industry
Supplier qualifications, API testing, other quality management systems
- Risk-based management and auditing of suppliers of raw materials and other products
- using only qualified and approved suppliers
- maintenance of an Approved Suppliers List (ASL)
- ensuring deliveries are actually from the approved supplier; consist of the materials ordered (quantity/type), and meet specifications (quality)
- quarantining and testing incoming materials/APIs before they are released for use in manufacturing
- Quality and testing procedures to ensure medicinal products meet expected quality standards.
- Batch-tracing recordkeeping.
- Records that meet ALCOA+ requirements as well as data integrity requirements (e.g. risk-based data governance systems and data security/record storage).
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.
Other GMP/GxP requirements can be found in industry-specific training packages, the FDA’s CFRs, the TGA’s guidance documents, and PIC/s guidance documents.
Drug safety monitoring programs must take a holistic approach.
There are additional GxP guidelines and PQS requirements in addition to the drug safety monitoring listed above.
Ongoing current GMP training is a crucial component of drug safety monitoring and quality controls; sadly, gaps in cGMP training records are a frequent audit finding.
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.
Case study: Missing safety warnings (Purdue Pharma/McKinsey Group’s marketing materials & sales strategies)
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.
Overdose Awareness and Prevention Resources and Research
Overdose Awareness and Prevention Resources and ResearchPlease support the research of the Penington Institute.
Download the latest Australian overdose statistics report (2023)
*2023 Australian Overdose Report PDF version – 31st of August 2023.
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
Pharmacovigilance systems, as part of GxP, can help manufacturers:
- recognise product risks, such as the habit-forming nature of using opioids
- 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)
- help warn patients, doctors, and other community members of the risks of an opioid dependency and/or symptoms of an overdose reaction
- help educators and researchers with community-wide education efforts to warning people of the dangers of non-medical use of prescription medicines, polysubstance use, and other drug-drug interactions
This information reminds pharmaceutical manufacturing organisations of the importance of complying with GMP/GDP regulations, data integrity requirements, and the FDA’s CFRs.
Pharmacovigilance requirements/online training.
And it reminds ALL of us – as individuals and businesses – to support overdose prevention initiatives such as International Overdose Awareness Day.
- Read the blog on 2021 overdose statistics
- Download the latest Australian overdose statistics report (2023)
- *Australian Overdose Report publication date: 31st of August 2023..
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
FDA = Food & Drug Administration (USA)
TGA = Therapeutic Goods Administration (AUS)
SAE = Serious Adverse Event
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.
Read the blog on 2021 overdose statistics.
Please FOLLOW US on LinkedIn and/or return to these is blog pages for the additional blogs on pharmaceutical safety and accidental drug overdose awareness and prevention.
