Technology transfer of tablet production: Quality by Design ("QbD") in GMP-compliant consulting for the pharmaceutical industry

Background to technology transfer

Technology transfer in the pharmaceutical industry, especially in tablet manufacturing, can be challenging. Knowledge about production is often not fully documented, but is based on the experience of individual employees. This leads to relevant knowledge not being taken into account or overlooked when transferring older products. Considerable problems can arise at a new location with different production conditions and new employees - as we all know, the devil is in the detail.

Current status at our new customer

In our current project, the production process of a tablet manufacturer is to be transferred from one contract manufacturer to another. Unfortunately, an earlier internal transfer attempt has already failed because the originally selected contract manufacturer was not prepared to invest further in this process. He considers the product to be non-transferable.

Negative effects of the non-optimal transfer

The central problem lies in the release profile of the coated tablets, which could not be achieved despite numerous production trials. The original manufacturer apparently did not disclose all "production secrets". The product was on the market for years without any known production problems and the license holder has now been "out of stock" for a year, resulting in significant financial losses. The total loss is now in the seven-figure range.

Objectives of the customer in the context of technology transfer

The customer's goal is clearly defined: The production process and technology are to be transferred to a new contract manufacturer, with the quality problem finally being resolved. This is crucial for high production quality and for the product to be available on the market again.

Our consulting solution in the area of Quality by Design (QbD)

The identification of a suitable contract manufacturer is followed by crucial implementation steps. Before new production trials are undertaken, it is essential to determine the causes of the problem. Only then can a small trial be carried out in the laboratory and the production method scaled up. The production steps are described relatively precisely in the dossier, so the scope is limited.

Root cause analysis and risk analysis in technology transfer

With our extensive experience in coating tablets and capsules, we start with a brainstorming session to identify and assess potential problems in the coating process. Instead of an extensive, 100-page risk analysis, we focus on a clear technical assessment to determine whether a problem is likely or unlikely. The aim is to identify 5-8 critical parameters, which are then examined in more detail.

Quality by Design (QbD) as a strategic method

The Quality by Design (QbD) method plays a central role in our approach. It is crucial not only to identify the problem, but also to consider the relevant boundary conditions at the new contract manufacturer, such as occupational safety, batch sizes and control options. Our aim is to select all tests and trials in such a way that the results are also useful in the future when the production process is changed at a later date.

By experimentally developing the most important process parameters and testing possible parameter ranges in the laboratory and technical center, we create a reliable space for production.

Advantages of Quality by Design (QbD) in detail

Quality by Design (QbD) is a structured and systematic concept that is used in the pharmaceutical industry and other areas of product development. The aim is to integrate the quality of a product into the development process right from the start instead of checking it afterwards. The advantages of QbD are multifaceted and decisive for the success of product development.

Proactive quality assurance:

• QbD promotes a preventative approach to quality assurance by identifying and addressing potential problems and risks during the development phase. This reduces the likelihood of subsequent complications and rework.

Optimization of processes:

• Processes can be optimized through an in-depth analysis of manufacturing methods and critical quality characteristics. QbD makes it possible to develop efficient and reproducible production processes that meet product quality requirements. This leads to better control of production conditions and reduces variability.

Increasing product consistency:

• By defining and controlling the relevant parameters, QbD ensures that the end product is of the same high quality in every batch. This is particularly important in the pharmaceutical industry, where consistency determines safety and efficacy.

Reduction of business and market risks:

• With QbD, potential risks can be identified and minimized at an early stage, resulting in a lower likelihood of recalls or regulatory issues. A solid quality basis minimizes the likelihood of unexpected problems and associated financial losses.

Regulatory acceptance:

• Regulatory authorities such as the FDA (Food and Drug Administration) and the EMA (European Medicines Agency) are placing increasing emphasis on the QbD approach. Products that are developed according to QbD principles are often more likely to be accepted for approval, as they are based on clear and comprehensible quality assurance.

Integration of data and knowledge:

• QbD promotes the collection and analysis of data throughout the entire development process. This knowledge can be used to improve future projects and drive innovation. Each project contributes to the knowledge database, which is of great benefit for future developments.

Improved collaboration between stakeholders:

• Thanks to the structured approach of QbD, various specialist departments (e.g. research and development, quality assurance and production) are more closely involved in the development process. This promotes communication and collaboration, which leads to a better overall understanding of the requirements for the product.

Customer satisfaction:

• A product that has been developed with a focus on quality from the outset will better meet customer expectations. Ensuring consistent product quality strengthens trust in the brand and customer satisfaction, which promotes long-term customer relationships.

Efficient use of resources:

• QbD leads to fewer inefficiencies and less waste, as processes are optimized and potential errors are detected at an early stage. This contributes to a reduction in production costs and more efficient use of resources.

Flexibility for product changes:

• If a need for change arises during the production phase (e.g. due to new findings or innovations), the QbD documentation makes it easy to adapt the processes. As all critical parameters and their interrelationships are known, the product can be modified more easily without jeopardizing quality.

To summarize

it can be said that Quality by Design (QbD) not only improves the quality of products, but also increases the efficiency and flexibility of development and manufacturing processes. This leads to a stronger market position and long-term success for companies in the pharmaceutical industry and beyond.

Results and benefits of optimized technology transfer

• The new contract manufacturer can produce the product successfully and to a high quality.

• All critical parameters are clearly identified and quantified, which underpins the validation of the production runs.

• The risk assessment, which is based on quantitative data from the laboratory and pilot plant, is more solid than pure risk assumptions.

• Production can be optimized to specific specification parameters, which increases efficiency.

• Future new developments or product variations can be considered theoretically. For example, it is possible to check in advance what changes need to be made if the batch size is increased.

• There are no losses due to ineffective production trials.

• A digital model enables precise predictions to be made about successful production variants.

• Production becomes more efficient, without faulty batches.

Through this comprehensive approach to technology transfer and the consistent application of Quality by Design (QbD), we ensure not only the quality of the products, but also compliance with GMP (Good Manufacturing Practices) standards. Our consulting services in the pharmaceutical sector are based on fair and transparent procedures in order to provide optimal advice and achieve long-term success for our customers.