On March 7, 2013, the revised “Guidelines on Good Distribution Practice for Medicinal Products for Human Use” (2013/C68/01) were published by the EU authorities [1]. These guidelines describe the requirements for procuring, holding, supplying and exporting prescription-based and prescription-free medicinal products. These new 14-page revised guidelines differ considerably from the 4-page version of the guidelines (94/C63/03) published in 1994 [2].
This article discusses the new trends in the EU GDP, the most important changes versus the draft version of July 15, 2011, and a risk mitigation approach to safely identify and classify modes of transport according to the new EU GDP.
Globalization Calls for Clear Guidelines
Over the last decades, healthcare has evolved into a global industry. This globalization has a significant impact on the supply chains of medicinal products. Supply chains are getting longer and more susceptible to seasonal variations during the storage, transport and distribution of goods.
In addition, the availability of expertise, infrastructure and equipment for temperature-controlled storage, transport and distribution can differ significantly between countries and continents. These new variables increase quality and safety risks for medicinal products in the supply chain.
To guarantee a consistent quality and safety of medicinal products throughout the entire supply chain, clear guidelines and adequate controls are necessary. Such guidelines help prevent adulterations, mix-ups and temperature deviations of products, and they help prevent theft and falsified medicines entering the supply chain.
The new revised EU GDP, which provide regulatory guidance for the pharmaceutical industry in Europe, together with other mandatory standards and industry best practices such as IATA standards and PDA technical reports, help safeguard the quality and safety of medicinal products.
Genesis of the EU Good Distribution Practice
On July 15, 2011, the EU authorities published a first version of the revised EU Good Distribution Practice (EU GDP). This version was open for public debate. Remarks, changes and observations could be sent to the EU before the end of 2011. Those changes were evaluated by the EU authorities and the final EU GDP was published on March 7, 2013. The guidelines will become effective on September 8, 2013.
The updated guidelines are aligned with the GMP Good Manufacturing Practice. They are structured around 10 chapters. These chapters describe the requirements for all the activities related to the procurement, holding, supply and export of medicinal products – both prescription-based and prescription-free products.
Changes to the Revised EU Good Distribution Practice
Due to the number of remarks made during the public debate in 2011, the new EU GDP include the following changes compared to the draft version from 2011:
- In the draft version, the use of hubs for in-transit storage during transport was limited to 24 hours. In the new EU GDP this has been replaced by “minimize the duration of temporary storage while awaiting the next stage of the transportation route” (GDP 9.2) [3]. The strict limitation of 24 hours has disappeared and it is the responsibility of the pharmaceutical industry to evaluate any risks by means of a risk assessment of the transportation route.
- The notion of "transport according to label claim" in the draft version has been replaced by “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 package.” (GDP 9.2) [3]. Here too, a strict limitation (of the “label claim”) was replaced by a more general phrase so that it is possible to use the available stability data as an input for the transport requirements.
- The notion of "The availability of the responsible person" has been changed and is now described as “The responsible person should be continuously contactable and he may delegate some duties but not his responsibilities” (GDP2.2) [4]. This means that the responsible person does not need to do everything by himself, but that he stays responsible for the work done.
We can conclude that the updated version of the EU GDP is less strict than the draft version. This way the EU authorities have provided guidelines that leave room for interpretation, but that support and do not hinder everyday operations.
New Trends in the Revised EU Good Distribution Practice
- The EU GDP is about “good storage and distribution practices” at various temperatures. The guidelines are no longer limited to the cold chain +2°C to +8°C range. Guidelines for handling ambient temperatures in the +15°C to +25°C are also included.
- The emphasis in the EU GDP is on quality management throughout the entire supply chain, from the manufacturer to the patient. The following new trends can be found in the new EU GDP:
- As a result of the complexity of this process we need a network of quality agreements and service level agreements to defi ne the roles and responsibilities of each partner.
- Risk assessment is to be used to define the necessary preventive measures to guarantee the quality and integrity of the distributed pharmaceutical products.
The remainder of this article illustrates the application of the new EU GDP regarding risk assessment. In addition, a risk mitigation approach that can be used to identify and classify modes of transport according to the new EU GDP will be discussed.
Risk Assessment and Risk Mitigation According to the New EU GDP
Risk management, which consists of risk assessment, risk identification and risk mitigation, is a very important topic in the new EU GDP. The new EU GDP requires that every quality system includes a procedure for dealing with risk management.
In transport, the following three questions are key to performing a thorough risk assessment:
1. Know your product
It is important to know how stable and robust your product is. What are the specific requirements and the stability data of the product? What are the characteristics of the primary and secondary packaging? Does the product require special transport packaging? Chapter 9 (9.1. principle) [5] of the new EU GDP describes that you should use good product knowledge to identify, assess and mitigate risks when planning the transportation of medicinal products.
2. Know your transport route and mode
In order to ensure good risk management, it is important to map your entire transport process. As such you can accurately define the different steps, handover points and modes of transportation during the entire route.
Chapter 9 (9.1. principle) [5] of the new EU GDP describes the requirement for a process map that identifies all the critical steps during transportation. This process map is elementary for a documented risk assessment of the delivery routes.
3. Know the capabilities of your partners
Chapters 9 (9.2) and Chapter 7 of the new EU GDP describe the importance of defining all the expectations of each partner in the transportation process [6, 7]. The roles and responsibilities of each partner should be described in a quality or service level agreement.
Evidently, a risk assessment is not an individual exercise but the result of a team effort. All involved parties need to take part in the risk assessment, from manufacturing and logistics teams to transportation and quality assurance partners.
Different Risk Assessment Techniques with One Goal
There are various techniques to perform a risk assessment. Wellknown techniques include the fishbone technique or the Failure Mode and Effects Analysis (FMEA). Once you have mapped your entire process in detail you can score the risks in each step of the process according to the probability of happening and the severity of the risk.
The probability of a risk can be influenced by many variables including stability data, weather conditions, transport mode and protective packaging. The severity of a risk should not be limited to patient risk; it should also take regulatory risk and business continuity into account. By multiplying the probability scores with the severity scores you get a risk score for a certain product or product group for a specifc transport route.
Risk scores can (and should) have an influence on the transport strategy of your company. A good transport strategy must include risk identification and risk mitigation. From the design phase onwards, risks must be under control as much as possible. Risk scores can help to define the selection of the right distribution and logistics partners or the optimal packaging design of the shipping containers.
To keep up with the defined transport strategy clear choices must be made. Examples of such choices can be: only use temperature-controlled vehicles for road freight within Europe, only use reefer containers for ocean freight, only use validated passive shippers and only use temperaturecontrolled equipment for temperature sensitive products. Using such equipment also implies qualification of this equipment (EU GDP chapter 9 – 9.4) [8].
A Challenging Opportunity
The globalization of the pharmaceutical industry has a significant impact on the supply chains of medicinal products. Supply chains are getting longer and more susceptible to seasonal variations.
To guarantee a consistent quality and safety of pharmaceutical products, clear guidelines and controls are necessary. The long awaited EU GDP help us to safeguard the quality and safety of our supply chains.
Important trends in the new EU GDP are the change from cold chain to temperature-controlled, including ambient products and the focus on quality management, service level agreements and a risk based approach.
It will be very interesting to see how all involved partners translate the EU GDP into their operations during the upcoming 6 months and how the health authorities will handle these interpretations during their inspections.
References
- Guidelines of 7 March 2013 on Good Distribution Practice of Medicinal Products for Human Use (2013/C 68/01)
- Guidelines on Good Distribution Practice of Medicinal Products for Human Use (94/C 63/03), 1994.
- Guidelines of 7 March 2013 on Good Distribution Practice of Medicinal Products for Human Use (2013/C 68/01), 9.2 Transportation, page C68/10
- Guidelines of 7 March 2013 on Good Distribution Practice of Medicinal Products for Human Use (2013/C 68/01), 2.2 Responsible person, page C68/3
- Guidelines of 7 March 2013 on Good Distribution Practice of Medicinal Products for Human Use (2013/C 68/01), 9.1 Principle, page C68/10
- Guidelines of 7 March 2013 on Good Distribution Practice of Medicinal Products for Human Use (2013/C 68/01), 9.2 Transportation, page C68/10
- Guidelines of 7 March 2013 on Good Distribution Practice of Medicinal Products for Human Use (2013/C 68/01), 7 Outsourced Activities, page C68/9
- Guidelines of 7 March 2013 on Good Distribution Practice of Medicinal Products for Human Use (2013/C 68/01), Transportation, page C68/10-11
Luc Huybreghts is a Senior Consultant Pharma Services with Pauwels Consulting. He has been working in the pharmaceutical industry for 30 years. As a subject matter expert for temperature-controlled storage, transport and distribution, Luc now uses his experience to develop strategies and implement qualified solutions for top clients in Belgium and beyond.
Luc is a regular invited speaker at pharmaceutical conferences around the world.