Whether you are new to pharma, or been around temperature sensitive distribution for some time – there is always something to learn about GDPs.
The EU Good Distribution Practices (GDPs) guidance, including ongoing addendums and Q&A documents have been the basis for many other national GDP documents in other countries. Put simply, the EU has led the way globally on GDPs. However, with the emergence of many other GDPs around the world, practitioners are left wondering how to find common ground and approaches when shipping globally. This, will continue to be ongoing challenge for all of us, for years to come.
What’s new you ask?
Still in 2018, there continues to be further definition of GDPs in Europe, specifically related to temperature control. One such contentious subject or question is:
No. According to the Guideline on declaration of storage conditions (CPMP/QWP/609/96 Rev. 2), Marketing Authorisation Holders have to provide stability data for storage conditions at 25°C / 60% relative humidity (RH), or 30°C / 65% RH (long term) and 40°C / 75% RH (accelerated), in order to justify not including a statement in the medicinal product labelling.
This stability data is generated according to the temperature and humidity conditions of climate zone I (temperate zone) and II (Mediterranean/subtropical zone) in Europe. For more information, see the World Health Organization Expert Committee on Specifications for Pharmaceutical Preparations forty-third report, Annex 2: Stability testing of active pharmaceutical ingredients and finished pharmaceutical products.
No labelling statement means that controls should be in place to maintain conditions relevant to climate zones I and II. Consequently, the temperature should be monitored during storage and transport. Appropriate limits should be set for temperature monitoring to ensure that product stability is not adversely affected.
In an effort to offer practical interpretation of global GDPs, with EU guidance being the basis, ELPRO and PTS Training Service have put together a booklet entitled ‘Compact GDP’ that offers concise explanation of what the GDP requirements are for the areas outlined below, including:
Definitions. GMP vs. GDP
Legal basics (primarily in Germany and Switzerland)
Qualification and Validation
Deviations and Changes
Documentation and records
Warehouses – mapping and monitoring
Counterfeit and recalls
Let’s breakdown and examine some of these important topics.
Qualification and Validation
Qualification (proof of suitability for rooms, systems, facilities) and validation (proof of suitability of procedures, processes and methods) are very important elements of the Good Distribution Practice (GDP).
This also includes the qualification of service providers, monitoring devices, monitoring software and also transport routes.
If deviations occur, for example due to errors, they must be reported immediately and investigated whether and to what extent the deviation has an influence on product quality and patient safety.
Thereafter, follow-up actions are defined (Corrective Actions and Preventive Actions, CAPA) to prevent this or similar errors from recurring in the future. All quality-relevant processes and procedures must be documented comprehensibly.
Qualification and Validation is a critical topic with many facets. The ‘Compact GDP’ booklet goes into deeper detail.
Risk management includes all measures for the systematic identification, evaluation, monitoring and control of risks. After the identification of risks a distinction is made between critical steps, which represent a high risk, (for the quality of the active substance or medicinal product1) and less critical or uncritical steps, which represent only a low risk to the product. Zero risk or 100% security does not exist.
Following the identification of possible risks, the most limited resources (time, money, employees) should be distributed sensibly according to the criticality of the individual steps. This results in a more effective use of resources while maintaining quality. Risk management is an important GDP requirement. The ICH guideline Q9 may be used for the implementation of the risk management measures. During qualification and validation risk assessment is used to define the scope of testing.
Warehouse Mapping Layout
Temperature mapping is an essential part of the qualification of the warehouse. It is usually integrated into the qualification during OQ (operational qualification) in the empty state and in the PQ (performance qualification) under regular operating conditions in summer and winter. The temperature in the warehouse must be monitored continuously in points of maximum thermal fluctuation.
The first step to a mapping layout is the creation of a general grid using empirically established data including grid spacing.
A deviation from these empirically established grid spacings should be scientifically or experimentally justified, for example by comparison with storage spaces of similar construction and comparable air conditioning systems, or by a preliminary thermographic investigation.
The mapping layout is then completed risk-based using the following criteria:
The design of the mapping layout is risk-based, therefore, the structural conditions (windows, doors, etc.), air conditioning technology, infrastructure and storage facilities must be considered.
Only areas in which temperature-specified products are stored (pallet storing positions, reserve storage, transfer areas, incoming and outgoing goods area) need to be mapped.
All regular warehouse operations must be still possible after the installation of the mapping devices.
If measuring points are only used for information (e.g. in addition to roller shutters for determining a door opening or in the outdoor area to determine the infl uence of the outside temperature) it must be noted in the mapping rationale (description of the mapping).
To learn more about GxP Warehouse mapping and qualification, visit ELPRO’s services page.
GDP for APIs and Excipients
In recent years, there has been a spate of new or updated regulatory guidance on GMP and GDP for Active Pharmaceutical Ingredients (APIs) and excipients as well. Due to cases of adulterated ingredients or faulty supply chains, regulators and other industry associations have collaborated to put pressure on suppliers and manufacturers to tighten their processes and carry out the due diligence to ensure quality control of the entire lifecycle and production of medicines.
«Manufacturers need to get ahead of the GDP curve by working closely with their downstream partners to ensure they understand GDP requirements. Often, these partners will not fully understand their obligations. For example, what does it mean to validate a temperature-controlled environment? Simply having a thermostat is absolutely not acceptable», says Mark Paxton, CEO of Rx360.
Read more about GDP for APIs and requirements for API suppliers and pharmaceutical manufacturers.
Stop scratching the surface
Getting GDPs right for your supply chain takes time and research. There is not one right answer for every company or every supply chain. First you must understand the desired outcome of the GDP guidance, i.e. what exactly is the requirement. Then, sit down with your QA and logistics teams to decide how to adapt your current processes, or perhaps consider new technology, that allows your company to meet the requirements.
Expert Knowledge Online
Björn Niggemann regularly writes reports which are published in the journal for pharmaceutical medicine and quality management PM QM.
*please note that the articles are currently only available in German language.
The production and distribution of pharmaceuticals are subject to strict legal regulations in Europe. Production and distribution are audited and inspected by the authorities, points Björn Niggemann (ELPRO Chief Quality Officer) out.
Therefore, the GDP working group of the German Quality Management Association e.V. (GQMA) developed a "Good Distribution Practice (GDP) Audit (Preparatory) Checklist". Read the complete article Pre Audit Questionnaire as a guideline for GDP inspections and audits in the November 2018 issue.
In the March 2019 issue, GDP meets GMP - a "purpose marriage" in the sense of drug safety. It explains that the regulations of Good Distribution Practices (GDP) have meanwhile become just as important as GMP and GLP have been for some time. Read more about this in the article.
About the author
Björn Niggemann has been Chief Quality Officer (CQA) at ELPRO-BUCHS AG since April 2016. In 2004, he was initially commissioned with the development and implementation of GMP parallel to the existing DIN ISO 17025 certification. As part of his Good Quality Practice studies, he and others wrote the brochure "GMP - I am part of it" as a simple training guide explaining the essential components of GMP and the origin of GMP.