Temperature control in the logistic chain (as strong as the weakest link) Mark Roemers AntTail GMP Driedaagse April 2016 Nijkerk
Apr 11, 2017
Temperature control in the logistic chain
(as strong as the weakest link)
Mark Roemers AntTail
GMP Driedaagse April 2016 Nijkerk
Market Characteristics
• Pharmaceuticals supply chains are typically long and fragmented, thus vulnerable to temperature variation and counterfeiting.
• Every hand-over is a potential risk
Market Characteristics
• Cost of non-compliance for your companies reputation is hard to estimate but it can ruin a carefully constructed corporate image in minutes
• Current temperature monitoring systems only deliver part of the puzzle. The full view from manufacturing to patient is not available.
Legislation changed in 2013
• New GDP in Europe and USA incorporates 15-25 °C full monitoring requirement in stead of only 2-8 °C . This is an increase from 5% to almost 100% in volume of shipments.
• This GDP is an increase of handling cost for low price products because of high human involvement in current monitoring solutions.
• Next GDP change is foreseen in 2017 for anti-counterfeiting measures.
Common problems
• All parties in the Pharmaceutical supply chain only have local temperature records, making it impossible to review and analyse data on an aggregated level.
Common problems
• Data is often incomplete and not timely available to the Responsible Person in case of an excursion.
• Incomplete and untimely information equals to non-compliance.
Common problems
• Most commonly used sensors are not reusable. This produces an enormous pile of chemical waist.
• Some sensors are good for 2 - 5 years. They store all data for the lifetime. Cost per shipment (at 1 shipment per month) or per month gets well below €2 per month for the hardware use.
• All sensors can be refurbished. Only the battery is added to the waste. The sensor is factory tested and after approval is released for a second or third life.
• Important item on the Corporate Social Responsibility Annual report.
Stability Data, alarm profile
• Storage and logistics: 2-8 or 15-25, alarm after 30 minutes
Research results LAST MILE
• Storage at patients home’s is not compliant (B. van den Bemt SAT0161) July 2015
• Results: 338 patients (mean age 52.4 (SD 13.5), 54.4% female) received 1309 temperature loggers in total. 278 (82.2%) patients (mean age 52.9 (SD 13.4), 52.0% female) returned in total 756 temperature loggers (57.8%). The majority (95.7%) of the patients were treated with etanercept or adalimumab.
• 79 patients (28.5%) stored their bDMARD within the SmPC recommended temperature range without excursions longer than 48 hours below 2°C or above 8°C (Figure 1).
• 23.4% of the patients stored one or more bDMARD packages for more than 2 hours consecutive time below 0°C (per package – frequency: 4 times [IQR 1 – 14], median longest duration: 7.2 hours [IQR 4.3 – 21.3], maximum duration: 46 days).
• 1.8% of patients stored bDMARDs above 25°C for episodes longer than 2 hours consecutive time (per package – median frequency: 1 time [IQR 1 – 2], median longest duration: 10.9 hours [IQR 6.1 – 33.9], maximum duration: 16 days).
• 6.7% Stored within limits of 2 - 8 Celsius.
Research results LAST MILE
• Storage at patients home’s is not compliant. M. de Jong: MUMC from 3-2015 until 11-2015
• In total, 56 patients (46.3% male, mean age 52.3 ± 13.8 years) received 299
injectors with temperature sensors that generated 2,716,584
measurements. • Figure 1 shows that 9.4% of the biologicals were stored within the
recommended temperature range. • Of the remainder, 12% were stored more than 30 minutes
below 0˚C and 30% were stored longer than 7 days above 8˚C. • Of all patients, 95% would appreciate an alarm
when the biological is not stored under the right
conditions, and also 95% is willing to accept
unused medication when product quality
is ensured.
Research results USA
• Department of Health and Human Services USA, VACCINES FOR CHILDREN PROGRAM: VULNERABILITIES IN VACCINE MANAGEMENT (OEI-04-10-00430 ) June 2012
• The Centers for Disease Control and Prevention’s (CDC) Vaccines for Children (VFC) program provides free vaccines to eligible children through a network of 61 grantees and 44,000 enrolled providers. In 2010, approximately 82 million VFC vaccine doses were administered to an estimated 40 million children at a cost of $3.6 billion.
• A sample of 45 VFC providers from the 5 grantees with the highest volume of vaccines ordered in 2010.
• We also independently measured these providers’ vaccine storage unit temperatures for a 2-week period.
• VFC vaccines stored by 76 percent of the 45 selected providers were exposed to inappropriate temperatures for at least 5 cumulative hours during that period.
Conclusion: we could all have a big problem
• What can we do to minimise our risks?
Audits for GDP as a means to ensure product quality
• Audits are a way to ensure a supplier follows correct procedure, a vital piece of the puzzle
• CAPA system gives insight in excursions or omissions in supplier execution
• Temperature monitoring records provide insight in maintaining correct storage conditions at supplier’s facilities
Audits pitfalls
• SOP’s can be correct. But management has to enforce them
• Loading and unloading is always a risk
• Acceptance and storage of cold-chain products on arrival is very time critical
• Transport is (should be) temperature monitored. How?
The Pharmacy is the last stop in the GDP The Gatekeeper for Patients
• Pharmacies do not execute Audits at their suppliers locations often (enough)
• How can you be sure that what your supplier has received was stored and shipped properly -> Audit
LAST-MILE delivery to patient
• LAST-MILE (to patient) is not part of GDP
• Packing is passive coolers is a critical proces and leads to incidental freezing if not done properly. Use a dedicated patient medication cooler.
Static storage, warehouse or fridge
• What to measure
• Where to measure
• Importance of mapping, what is mapping
• Winter and summer validation? Why?
• To calibrate or not to calibrate?
• Redundancy and power failure
Transparency in the Supply chain
Test for a month, get a report and analysis Insights in process and quality Demonstrable improvement actions
Apply for the free trial: [email protected]
Take the test and improve the ChainFrom sensor to Service:
• Where do we get excursions? • What are our hystereses and fluctuations? • Do “Hand-overs” cause quality issues?