GMP: the growing issue of theft
The quality, safety and efficacy of medicinal products depend on a whole range of different factors, among which two of the most important factors are that medicinal products have been manufactured and distributed in a compliant manner. The patient is not always able to judge these things properly, which is why they must rely on all stakeholders involved in the manufacturing and distribution chain. Obvious transport damage is easy to detect, whereas inappropriate storage may not be identified easily. Drug theft is an increasing issue here, as well.
Nowadays, drug products as well as active substances are traded globally. They often change hands several times. Besides the related dangers such as mix-ups, wrong storage or improper transport, the danger of theft is also growing. This is a matter of financial loss at first, but the stolen drugs often also find their way back into the supply chain. Meanwhile, storage and transport are not controlled. And due to the original packaging, this is hard to detect.
This was one of the main reasons for the revision of the EU GDP Guidelines in 2013. In Section 3.2. "Premises", it says: "Unauthorised access to all areas of the authorised premises should be prevented. Prevention measures would usually include a monitored intruder alarm system and appropriate access control. Visitors should be accompanied." Furthermore, there are strict rules in section 5.2. "Qualification of suppliers" which are to prevent drug products from illegal sources from entering the legal supply chain.
Thefts show just how important these regulations are time and again. For example, various drug products by the companies CSL Behring, Pfizer and Galderma Laboratorium had been stolen from the logistics service provider Thermomed GmbH in late 2015. The "Bundesvereinigung Deutscher Apothekerverbände e. V." (the German Federal Union of German Associations of Pharmacists; ABDA) commented on this in their AMK News on 30 October, 20151; since it could not be ruled out that there would be attempts to bring the stolen drugs (amongst which were products that require refrigeration) into the supply chain, they asked pharmacies for an increased level of attention.
Another example from 2015 underlines the necessity for a higher level of transport security: Police in Belgium found a trailer carrying $7.82 million dollars' worth of pharmaceuticals in a warehouse in Opglabbeek, located in the east of the country, after it was stolen several days earlier. The driver of the vehicle left the trailer unattended over a weekend in the town of Peer, also located in eastern Belgium, and returned to find it had been stolen. The trailer was carrying a refrigerated load of insulin and other unspecified medicines. Police are still searching for the thieves.
The lack of awareness of secure parking locations plus an insufficient number of secure sites in the right locations continued to have a major impact on crime statistics in EMEA. According to the annual report 2016 of the Transported Asset Protection Association (TAPA), 40.7% of all cargo thefts occurred when trucks stopped at unsecured parking locations.2
Migrant movements through illegal means along the Calais-Dover route to enter UK has also increased and detected in pharmaceutical shipments in recent years, where illegal migrants have broken into trucks when parked en-route to Calais border control and has sought refuge inside the consignment in transit. Some medicinal packs were stolen in the process. This has resulted in full medicinal consignments to be discarded due to increased risk of contamination and suspected damage.
The issue of falsified medicines entering the legal supply chain through stolen goods has therefore already reached Europe. This is also demonstrated by the case of the HIV medicine Viread (Tenofovir) in Germany3 and the theft of Herceptin in Italy4 in 2014. This case hit the headlines due to various attempts by forgers to re-enter Herceptin into legal sale.
The US Food and Drug Administration FDA reported on a theft of more than 16,000 packages of the hormone preparations "Gonal-f RFF Redi-ject" and "Gonal-f Multi-Dose", which also took place in Italy5. The goods, which had been stolen in May 2018, had been intended for shipping to the US. The crime took place near the town of Bari in Italy, where a delivery truck was hijacked. US authorities had been warned that there could be illegal deliveries now to the United States.
Over the course of several years, cytostatic drugs had been stolen from Greek hospitals and resold illegally. Most of these preparations must be refrigerated, during storage as well as during transport. That was very likely not the case here. The goods had been stored in private homes and apparently also on a fish market. There is also an interesting television report on this (in German)6. A German company had bought a large part of the drugs and sold it to various pharmacies.
In July 2018, 25 packages of Certican® (Everolimus) had been stolen from an importer7. It cannot be ruled out that there had been attempts to re-enter the stolen drugs into the legal supply chain in this case, either. How the medicinal products are stored and transported is uncertain.
In a blog8, the British Medical and Healthcare Product Regulatory Agency (MHRA) reported on illegal attempts to enter a warehouse. In detail, the entry spoke of two robberies of wholesalers. Goods had been picked up from warehouses by people who pretended to be authorised customers. In both cases, legitimate pharmacy customer details were used by the criminals. The MHRA emphasized the importance of affirming the legitimacy of the recipient. Appropriate processes must be established. Ideally, a contract or technical agreement is set up before a customer may obtain medicinal products.
Prevention Measures in Transport
There are many security mandates enforced in company security policies to combat theft, diversion and dealing with incursion from intruders during border-crossing. These measures are put in place independently and in conjunction which aid to secure transport.
Lock and Seal mechanism
The locks listed below are currently considered suitable by a pharma company and to be fitted to doors that give access to the load area of a vehicle or trailer:
- Container/trailer doors lock system tying both doors together. As a minimum, the case must be made of hardened steel and be 6mm or 0.25 inch thick x 75mm or 3 inches wide. The system must be equipped with a lock providing sufficient protection against tampering (i.e., drill and pick resistant).
- An electronic slam-lock system.
- A padlock with the minimum shackle (locking bar) diameter of 11mm or 0.4 inch and which should comply with internationally recognised standards. Where possible, the shackle should be enclosed.
One obvious step taken by some hauliers is to restrict access to keys. In some cases, they have fitted a combined electronic seal and lock which can be locked and unlocked by keying in a pin.
For High Security Vehicles, companies are going one stage further and the doors are locked and unlocked remotely by the monitoring centre, only unlocking them if there is an emergency or once you are sure the truck has reached its destination. With this system, every door opening is captured as part of an audit trail which can be uploaded to a remote server automatically. An alert can be triggered if the opening is unauthorised.
It is also enforced by some pharma companies to apply only Metal Security seals, uniquely numbered and strongly recommended to meet ISO 17712 standards for shipments. When the seal is removed at the eventual destination, the seal must be retained until the shipment is accounted for. If you rely on a plastic seal instead, there is always the risk that it will be carefully glued back together if a door is opened illicitly and the seal is broken.
GPS and Alarm Systems
It is also mandated by some pharma companies that the vehicle must have an engine immobiliser fitted and a 'Silent Panic' button in the truck (with an audible/visual alert at monitoring centre). These devices must be linked to an active monitoring service to allow for monitoring and remote stop of the engine. A satellite and/ or GPS tracking system must be permanently fitted on the trailer and/or the tractor. Remote monitoring must be performed by a dedicated monitoring centre which can guarantee 24/7 monitoring. Such monitoring must enable automatically triggered alarms to be followed up on in real-time. The tracking system is fitted also ensures that the monitoring centre can keep tabs on the trailers when they are uncoupled from the tractor unit.
GPS tracking system is also utilized by some companies to create "Geofences" with "triggered alerts". Geofences are designated areas that are defined on a map. They can either be a certain radius around a single point, or any shape that is created from several points. Geofences can be created around neighbourhoods that must be avoided, customer sites, or any other area that needs to be monitored. Triggered alerts allow to monitor activity in a more passive manner. Rather than watching the real-time map, the system simply gets alerted whenever a geofence is crossed. You can also use geofences with date/time stamps so previous activities can be viewed any time. Should there be any breakdown or be involved in an accident, the system will be alerted and the relevant authorities can be contacted promptly.
Companies using curtain-sider trailer rather than box bodied trailer is arguably more of a challenge to keep secure. One option taken by companies is to reinforce the curtains with an anti-slash backing to up to half their height. It uses Kevlar material which can be heatwelded to the inside of the curtains either as a retrofit or when the truck body or trailer is first constructed. Available at heights of up to 3m, one of its big advantages is that it does not make it more difficult to open or close the curtains. Reinforced curtains can be supplemented by a secure TIR cord. One end is plugged into the trailer's air system, the other into a security seal and, if the cord is tampered with, an alarm sounds in the cab. An alert can be sent straight to the operator.
If intruders manage to get into the cargo area then they need to be spotted as quickly as possible. Onboard CCTV, combined with CO2 monitors, infra-red monitors are also supplementary tools installed to detect such eventualities.
Some companies also opt for additional escort vehicles with the consignment for safety during transit through high risk areas and markets.
However, all these devices and mitigations may end up proving valueless if drivers fail to adopt a few basic security measures. They should always drive with the cab and load area doors locked, remember to take keys out of the ignition and lock the vehicle when they are refuelling at a service station or making a delivery. If they believe they are being followed then they should alert home base / monitoring centre and, if necessary, call the police. If they have to park somewhere over-night, then ideally they should do so at a secure truck stop. If they have no other option, they should park in a well-lit area where other trucks are present. Parking back-to-back ensures that thieves cannot access either set of rear doors. Ensure that all corporate clothing, keys and identity cards are handed back when a driver leaves the company's employment. And check licences, CVs and references when hiring new drivers.
Prevention Measures in Warehouse
Measures to prevent unauthorised access to the warehouse are as mentioned in the GDP Guideline, Section 3.2 intruder alarm systems and appropriate access control, visitors should be accompanied. The challenge in warehouse management is not only to accompany visitors, but furthermore to monitor drivers during loading and unloading procedures, as well as for technical staff during maintenance and cleaning personnel. Clear procedures like using Log-Books for visitors are necessary including regular security training and personnel checks by external authorities (e.g. police) of every person allowed to have unattended access to the warehouse.
These organizational measures are supplemented by further infrastructural measures. The warehouse should be surrounded by gates and fences with a 24/7 presence of gatekeepers or at least CCTV with direct alarms to site security services or a contracted security company. An electronic access control system keeps doors of the warehouse locked for unauthorised persons. To prevent uncontrolled use of emergency exits, escape door guards are commonly used as well as intrusion detection systems and glass break detectors. These systems also require communication in the event of a break-in attempt to internal security and local police.
The highest level of security brings the additional installation of video surveillance. Some countries like Germany used to be reluctant in the use of CCTV due to concerns regarding the protection of personal rights. In the meantime video surveillance for receiving and shipping docks, inspection areas and all personnel access portals has become more and more common for pharmaceutical warehouses.
Adequate lighting also outside the facility including entrances, exits, cargo handling areas, fence lines and parking areas also provides a higher level of security.
TAPA offers for their members the certification of facility security as well as trucking security and as a new campaign a self-certification program.9
For most of the pharmaceuticals warehouses, TAPA standards are helpful as an orientation, but are not implemented to its full extend.
... is Operations Director and organises and conducts courses and conferences on behalf of the ECA Academy in the areas QA and GMP.
Dr Martin Egger
... is Managing Director of Pharmaserv and responsible for the brand Pharmaserv Logistics.
... is Senior Manager Quality for Distribution & Cold Chain Management Vaccines, Quality Assurance Shared Services at GlaxoSmithKline, U.K.
1https://www.abda.de/themen/arzneimittelsicherheit/amk/amk-nachrichten/ (in German)
2 TAPA Incident Information Service (IIS) – Annual Report 2016
3https://www.deutsche-apotheker-zeitung.de/news/artikel/2015/04/09/Importware-von-Viread-zuruckgerufen (in German)
4https://www.pei.de/DE/infos/presse/pressemitteilungen/archiv-pressemitteilungen/2014/07-krebsarzneimittel-herceptin-gefaelschte-flaeschchen-im-handel.html (in German)
5https://www.gmp-navigator.com/gmp-news/hormonpraeparate-in-italien-gestohlen (in German)
6http://www.daserste.de/information/politik-weltgeschehen/kontraste/videosextern/gefahr-fuer-patienten-102.html (in German)
7https://www.deutsche-apotheker-zeitung.de/news/artikel/2018/07/26/warnung-vor-gestohlenem-certican-in-der-legalen-lieferkette (in German)