GMP LOGFILE: Lead Article

3 min. reading time | by Petra Rempe, PhD

In its GSDP Guideline published in 2020, the WHO summarizes current requirements for the storage and transport of medical products and at the same time attempts to harmonize international requirements. This guideline also contains an annex with recommended temperature and humidity limit values for storage and therefore also transportation temperatures.

Read a short summary of the guideline below.

6 min. reading time | by Fritz Röder

Pharmaceutical water occupies a unique position in the pharmaceutical industry. Raw materials and excipients are normally only used after quality control and subsequent release. Pharmaceutical water, however, is always used immediately after it has been produced because microbiological approval can take several days. For this reason, pharmaceutical water is regarded as being extremely critical, and there are many specifications in the pharmacopoeias and GMP regulations.

5 min. reading time | by Martin Mayer

The introduction of the ICH guideline Q9 ‘Quality Risk Management’ in 2005 was crucial for the introduction of QRM approaches in the pharmaceutical regulatory framework. However, over the years, regulators and industry have realised that the QRM principles were not being applied and used as intended. Therefore, the Q9 guideline was revised and published in version (R1) in 2023. The basic principles and concepts of the original 2005 version have been retained but supplemented to achieve the intended clarifications.

6 min. reading time | by Christian Gausepohl, PhD

Quality oversight at the operational level offers many advantages. The company’s quality culture can be positively influenced through close integration.

But what is the best way to implement Quality Oversight directly at the shop floor level?

7 min. reading time | by Joachim Ermer

Important aspects in the implementation of regulatory requirements

The ICH guideline contains general requirements and some recommendations for basic statistical performance parameters and experimental approaches. However, this should not be understood or misused as a checklist. The responsibility of the user to adapt to the task is explicitly pointed out: "It is the responsibility of the applicant to choose the validation procedure and protocol most suitable for their product". Validation that is not tailored to the specific test procedure and its intended use is, at the very least, a waste of time and resources, as the suitability cannot be reliably assessed.

7 min. reading time | by Joachim Ermer

Proof of the suitability of analytical test methods is a general GMP requirement. While the EU GMP Guideline Part I generally requires "validated test methods", Part II refers to the ICH guidelines with regard to the content of method validation. 21 CFR Part 211 also requires in §194(a)(2) that the suitability of the test methods must be verified.

5 min. reading time | by Doris Borchert, PhD

Supply shortages for pharmaceuticals are a serious problem for the public security of drug product supply. At the 30^th GMP Conference, Dr. Josef Landwehr (PTS), Thomas Brückner (Bundesverband der Pharmazeutischen Industrie e.V.) and Andrea Schmitz (Pharma Deutschland e.V.) discussed the background, possible solutions and foreseeable developments in this area.

We have summarised the most important questions and answers for you.

5 min. reading time | by Ruven Brandes and Fritz Röder

How can the quality of pharmaceutical water be monitored?

The quality of pharmaceutical water is defined by a large number of specified parameters. Monitoring is required to ensure that this quality is maintained dur­ing operation of the water system. This includes regular physical measurements as well as chemical and microbiological tests. The European Pharmacopoeia spe­cifically mentions microbiological monitoring and the testing of TOC and con­ductivity.

5 min. reading time | by Richard Denk

Looking at Annex 1, the use of barrier systems such as RABS or isolators is very common. Since Contamination Control Strategy (CCS) requirements are an important part of selecting the appropriate barrier technology, closed RABS or isolators should be preferred.

5 min. reading time | by Andreas Nuhn

Filters in safety cabinets

The filters are the most important part of a safety cabinet. To ensure comprehensive protection of the product and personnel, HEPA filters of at least class H13 must be used, usually H14 filters are used.

7 min. reading time | by Ruven Brandes

When establishing the basic design of equipment, containers, components and machines for pharmaceutical use, a wide variety of materials is required. These are typically subdivided into materials of construction and adjuvants or production aids.

7 min. reading time | by Florian Sieder, PhD

General Requirements

The current Annex 1 of the EU GMP Guide provides guidelines and minimum requirements for the manufacture of sterile products. Some of the requirements contained therein are also relevant for the manufacture of non-sterile products, where the control and reduction of contamination is important.

7 min. reading time | by Sabine Paris, PhD, and Thomas Peither

The 33rd Annual PDA/FDA Joint Regulatory Conference was held in Washington from September 9-11, bringing together over 900 participants. It was a great opportunity for knowledge sharing, connecting theory with real-world practice, and plenty of networking.

We attended the event as representatives of GMP-Verlag and have highlighted some of the key takeaways in this article. The full report will soon be available on our online GMP knowledge portal, the GMP Compliance Adviser.

3 min. reading time | by Raimund Brett

Between rooms of different cleanliness grades, it is required to establish a pressure cascade to prevent cross contamination. Annex 1 of the EU GMP Guide requires a pressure difference of at least 10 Pascal between two different cleanliness classes. These pressures can be achieved if the structure (walls, ceiling, windows and doors) is tight. The pressure level is usually controlled in such a way that the supply air is kept constant, and the exhaust air is controlled via volume flow controllers to maintain the corresponding pressure difference. The pressure differences in a manufacturing area for sterile pharmaceuticals must be continuously measured and recorded. If a pressure drop occurs, an alarm must be triggered. This also applies to the airlocks.

5 min. reading time | by Xenia Dimont

The term "PUPSIT", which stands for the Pre-Use Post-Sterilization Integrity Test, has been included in the revised Annex 1. While the term is new, the requirement to check the integrity of a sterilizing filter after it has been sterilized and before it is used for sterile filtration is not new. This has been included in Annex 1 since 1998.

5 min. reading time | by Thomas Peither

In-house logistics encompasses all the processes required to manage and transport materials within a company. This is particularly important in the pharmaceutical industry, where not only efficiency but also compliance with safety and quality standards are crucial. Efficient logistics can help streamline production, cut costs, and ensure legal compliance. The provision of safe and effective medicines relies on pharmaceutical companies prioritising material management and flow. It ensures the availability, quality, and compliance of materials.

5 min. reading time | by Christine Oechslein, PhD

Carrying out quality testing internally may be a complex process, but it also has many advantages. A solid knowledge of product properties, stability and degradation products is built up over time in a laboratory and can be particularly valuable when carrying out quality risk analysis. However, some tests can be outsourced to external partners.

5 min. reading time | by Doris Borchert, PhD

When was the last time you went to a concert? What images have stuck? The conductor guiding his orchestra through the repertoire with grand gestures and high commitment? The first violin, connecting conductor and orchestra? Or the musicians working as a coordinated team, bringing the music to life? Either way, hopefully it was an amazing experience.

7 min. reading time | by Sabine Paris, PhD

In 2015, with the revision of Chapters 3 and 5 and Annex 15 of the EU GMP Guide and with the publication of the EMA PDE Guideline a paradigm shift occurred in the setting of limits for the validation of cleaning processes. Instead of the previously used criteria, such as 10 ppm or 1/1000 of the therapeutic dose of the foregoing product, the only acceptable criterion is now a toxicological risk assessment based on PDE values.

5 min. reading time | by Harald Flechl

Both of the terms "clean up period" (Annex 1) and "recovery time" (ISO 14644-3, informative part B.4) are often used to describe the same procedure but they are completely different from each other. These test methods have no validity with respect to the airborne microbes, which depend greatly upon the number of persons in the room as well as their clothing and activity.