Loophole in GDP Legislation puts Medicinal Products at Risk

Recommendation

17/18 April 2024
Hamburg, Germany

The Responsible Person for Good Distribution Practice (GDP)

The GDP guidelines (EU Good Distribution Practice Guidelines) are especially important to all parties involved in the supply chain, such as manufacturers, wholesale distributors and transport service providers. One requirement is that storage conditions generally have to be maintained during transport, as well (§9.2 Transportation: "The required storage conditions for medicinal products should be maintained during transportation within the defined limits as described by the manufacturers or on the outer packaging."). The objective is that medicinal products reach the customer (patient) without being exposed to negative quality influences. The problem is that online pharmacies in most member states are not directly bound to those guidelines (EU GDP guidelines don't apply to (online) pharmacies and national regulations for pharmacies mostly only contain the storage, not the shipment). This is surprising indeed since shipments by pharmaceutical wholesalers usually arrive in a matter of some hours, whereas there are longer delivery times to be expected in online trading. Many customers aren't aware of that fact when they place an order online (e.g. at an online pharmacy).

The European Institute for Pharma Logistics (EIPL) now conducted a field study on this - with some alarmingly results.

How was it done?

To comprehend the temperature conditions during transport via parcel services, two approaches were chosen:

1. In January/February of 2017, EIPL ordered various drugs from seven different online pharmacies. The aim was to compare what measures the online pharmacies took in order to protect temperature sensitive goods on the transport route. For instance, they ordered:

• Paracetamol oral suspension for children ("do not store at less than 8°C. Do not refrigerate or freeze.")
• Bromelain hysan tablets ("refrigera te. May be kept outside of the fridge for up to 4 weeks, but not above 25°C.")
• Mutaflor suspension ("refrigerate at 2°C to 8°C")
• Lamisil spray ("do not store at over 30°C. Do not refrigerate or freeze.")

2. The institute shipped 100 test parcels, equipped with temperature sensors, with five different parcel services used regularly by online pharmacies. A cold week in January 2017 was chosen for this. The parcels were sent to fake recipients, hence the parcels were returned to EIPL GmbH as undeliverable. The objective was to comprehend the temperature conditions occurring during shipment with the service providers.

According to the press release and the EIPL study available to CONCEPT Heidelberg, the results of the temperature study are "alarming". Here are some examples:

Study approach 1:

• Due to the addition of cold packs by the online pharmacies, the medicinal products had, on top of the cold outer temperatures, been carelessly exposed to additionally extreme temperature conditions inside the parcel. A paracetamol suspension, which may not be stored (and therefore transported) at less than +8°C according to the manufacturer and package leaflet, had been put directly on a frozen cold pack for shipment.

Fig. 1: paracetamol suspension with other (refrigerated) medicinal products and a cool pack (Source: EIPL GmbH)

• Some deliveries (in standard shipping cartons) had been placed on the cold ground by the front door at cold outdoor temperatures.
• In one delivery, the medicinal products "had been wrapped in old newspaper, air cushions without air, plastic bags - basically waste". A cold pack had been added to the standard shipping carton, in which all drugs had been shipped together.

Fig.2 : Packaging (Source: EIPL GmbH)

• Five out of seven online pharmacies didn't ship the refrigerated drugs separately from the not refrigerated drugs.
• Temperature sensitive medicinal products had often been shipped in standard shipping cartons and therefore insufficiently protected from too low or too high temperatures.

Fig. 3: temperature sensitive medicinal products in a standard shipping carton (Source: EIPL GmbH)

Study approach 2:

• The evaluationof the parcels fitted with a sensor showed that the temperature requirements cannot be complied with in many cases. In some cases, the temperature in the parcels sank under 0°C:
  
  

  Transport Service Provider	Average Temperature during transport
  A	3,51°C
  B	3,19°C
  C	1,36°C
  D	2,84°C
  E	-0,22°C

Average temperatures - period: start of the processing till delivery, without return way (Source: EIPL temperature study)

• The highest measured temperature was 35,9°C, the lowest was -12,5°C. On average, the parcels were outside the temperature range of 2-8°C for more than half of the transportation time.
• Many of the test parcels were handed over to other recipients, six of the 100 parcels were lost completely.
• To an inquiry to all five service providers about the possibility of a tempered transport, EIPL didn't receive a feedback until several days later: "An annual volume of more than 1000 parcels is necessary for tempered shipment."
• Another service provider replied to EIPL only after several active inquiries were made, that "tempered transport was not part of their portfolio."

Which conclusions can be drawn from the data?

• Medicinal products requiring tempered transport are often transported in regular vehicles without active temperature control. Although according to a study, about 20% of all OTC drugs require storage at a defined temperature range, e.g. 2-8°C or 15-25°C.
• Cold-sensitive drugs are often packed up and delivered together with refrigerated drugs.
• The focus is on cost: "From our point of view, the field test shows that the concept of online pharmacies doesn't work out. With the current transport methods via the usual parcel services, transport quality and hence patient safety is clearly neglected", cautions EIPL-CEO Christian Specht. "Therefore, we want to state clearly that the transport route of online pharmacies has to meet GDP requirements, as well. We ask the legislator to fix this loophole and issue a clear regulation in regards to the distribution by online pharmacies."