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: info@anttail.com

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?