Conference report on the ECA GMP & GDP Forum (Part 2)
The second GMP & GDP Forum from June 20 to 22, 2023 took place as an on-site event. This provided the opportunity for face-to-face discussions with other participants and speakers and to learn more about the current challenges facing the pharmaceutical supply chain.
Day 1 of the event was dedicated to GMP, day 2 was a combination of GMP and GDP, and the last day focused on GDP topics only. A summary of the first two days can be found in the previous article.
The third day started with a presentation by Alfred Hunt, who is Chairman of the European GDP Association1 in addition to being a consultant (Hunt Pharma Solutions Ltd, UK). Under the title "GDP Update & Outlook", he gave an overview of the latest developments in good distribution practice and current trends, both in Europe and in the USA.
In addition to the topic of GDP for veterinary medicinal products, which was discussed in detail in the following presentation by Dr Kahlich, Mr. Hunt addressed the following subject areas:
- The extension of GDP certificates in light of difficulties to conduct on-site inspections due to the COVID-19 pandemic,
- Medicine shortages,
- Consequences of Brexit,
- the integration of EudraGMDP into the EMA's Organization Management Service (OMS),
- new documents of the Pharmaceutical Inspection Co-operation Scheme (PIC/S): Aide-Memoire on GDP inspections (PI044-1) and a Q&A document (PS/INF 22/2017).
He concluded his presentation by addressing the new Annex 21 on the import of medicinal products. In this context, he explained that although Annex 21 only relates to the physical import of products, knowledge of the financial supply chain is equally important.
The second presentation was dedicated to the topic of GDP for veterinary medicinal products. With Regulation (EU) 2019/6 on veterinary medicinal products, which has been in force since January 28, 2022, the European Union has restructured veterinary medicinal products legislation. Specific requirements for veterinary medicinal products are set out in Implementing Regulation (EU) 2021/1248 of July 20212 and, in the case of GDP for active substances used as starting materials in veterinary medicinal products, in Implementing Regulation (EU) 2021/1280 of August 20213.
Dr Rainer Kahlich, who works as an inspector at the Leitstelle Arzneimittelüberwachung at the Regierungspräsidium Tübingen, first gave an overview of the legal framework and explained the background and purpose of the new regulations.
After discussing the general differences and similarities between the requirements for GDP for veterinary medicinal products and for medicinal products for human use, he examined certain aspects in detail. He based this on the chapter structure of the new regulations. He also pointed out overlaps with other regulations, e.g. ICH Q9 and the WHO Guidances on storage and transportation.
- As a result, Dr Kahlich came to the conclusion that the GDP requirements for veterinary and human medicinal products are essentially identical. In his view, the most important aspects are:
- Ensuring product quality through suitable temperature conditions during storage and transportation (all parties involved should know exactly what the requirements are for their products and not just specify the storage/transport conditions for reasons of convenience).
- Qualification of suppliers as a crucial and critical step for the integrity of the legal supply chain.
- Careful selection and qualification of transport service providers.
The subsequent paper entitled "Disruption of the Global Supply Chain: How to still be able to be GDPcompliant" was presented by Peter Flury, Head Transportation Management EMEA at CSL Behring AG in Switzerland.
Logistics in transportation has become a key strategic component in ensuring the timely and GDP-compliant distribution of medicines to patients worldwide. Under the subheading "The New Normal", Mr. Flury first pointed out the increasingly unpredictable availability of mode of transport, equipment, carriers and capacities as well as the possible interruption of trade/supply routes "overnight" against the backdrop of the COVID-19 pandemic and global political instabilities.
The main part of his presentation dealt with strategies for coping with and controlling this new normality. Among other things, Mr. Flury outlined criteria for selecting transport service providers that can be used to take into account the risk-based approach to transport planning required in Chapter 9.1 of the EU GDP Guidelines. He also discussed the use of Open Source Intelligent (OSINT). This involves using freely accessible mass media (print media, radio, television), the internet and web-based applications, scientific publications and also commercial data in order to gain usable insights from their analysis.
Based on several case studies presented by Mr. Flury, the previously identified aspects of the selection of transport service providers and the use of OSINT were illustrated using concrete examples.
Peter Flury's presentation was followed by another contribution from Alfred Hunt. Under the heading "Data Integrity in a Hybrid Working Environment", Mr. Hunt addressed the question of how to ensure that good documentation practice and data integrity principles are followed even when staff are in remote locations and validated electronic systems may not be in use. After all, even in such a constellation, signatures must be obtained and hard copies of documents retained.
In such a process, if multiple "approved" copies of the same document are made, unvalidated computerized systems are used and the traceability of the approval is not guaranteed, there is a greater risk of data integrity problems. After recalling the well-known ALCOA+ principle, Mr. Hunt outlined concrete solutions for complying with requirements.
Some "do's" and "don'ts" are clearly shown in the slide from his presentation in Figure 1.
Figure 1
In particular, Mr. Hunt addressed possible problems when scanning documents, the management of scanned documents and the associated paper records, "true copies", electronic signatures and the use of emails and email accounts.
Finally, he summarized the key aspects as follows:
- identify risks to the legibility of documentation.
- ensure that employees are aware of the requirements for the authenticity of copies.
- identify where the original documents are stored - and whether this is validated.
- beware of rescanning!
- ensure that no data is lost during transfers and scans.
- risk assessment of all interfaces where data is generated.
Dr Torsten Schmidt-Bader, Managing Director of moveproTEC - compliance & innovation advisory, focused in his presentation on the validation of computerized systems under GDP. He began by outlining the regulatory requirements and expectations. In particular, he addressed the requirements according to chapter 3.3.1 (computerized systems) of the EU GDP Guidelines and compared these with the requirements from the GAMP Guidelines. This resulted in the following conclusions:
- Validation according to the GAMP requirements is time-consuming, leads to an enormous workload and could be considered "too much" for GDP inspectors.
- The EU GDP Guidelines have a rather unclear approach to validation studies.
- A "lean" validation is possible, but regulatory acceptance may vary.
In the second part of the presentation, under the headline "Golden rules for IT validation", Dr Schmidt-Bader showed how a "lean" GDP validation can be approached, namely through the well-thoughtout selection of CSV requirements from the relevant regulations. A "lean" GDP validation is therefore a practical mixture of different approaches, and the ALCOA+ principles help to define the objectives, acceptance criteria and scope of the validation.
Dr Schmidt-Bader demonstrated that such an approach can be successful using a current case study (validation of a new warehouse and material management system for a wholesaler based in Germany), in which he showed the individual steps in detail. In this example, the time and budget savings compared to a complete GAMP validation were 30-40%.
The third day of the conference, and thus the GMP & GDP Forum as a whole, concluded with a presentation by Saddam Huq, Director, Cold Chain and Logistics at GSK, U.K., entitled "Case study on Thermostability".
The starting point for his considerations was the definition and the resulting requirement for the so-called stability budget from PDA Technical Report No. 53, which states verbatim:
"A stability budget considers the results of long term, accelerated, extreme excursion, and temperature cycling studies to determine the amount of time out of storage that a drug product may experience without any significant risk to its quality."
"Firms have used the idea of a stability budget to assign permissible time out of storage for packaging and labeling operations for refrigerated drug products for some time."
In his presentation, Mr. Huq highlighted the following types of studies:
- accelerated stability studies,
- extreme temperature studies,
- cycling studies,
- long-term stability studies.
The product budget was explained in detail using the example of a drug to be stored under refrigeration conditions. Mr. Huq then went on to discuss the management of temperature deviations and showed how the two terms "excursion" and "deviation" can be distinguished from each other. He concluded his presentation with a few remarks on trend analyses, emphasizing that these should be an essential part of the risk management process.
The GMP & GDP Forum takes place every two years. The next forum is planned for June 2025.
About the Author
Dr Markus Funk joined CONCEPT HEIDELBERG in October 2019 as operational director and is in charge of the topics GDP and analytics.
