Objectives

Within bioprocess engineering research for industrial related processes also quality management implementation is provided. In this respect, different concepts are developed according the industrial needs and the quality planning principles (Figure 1).

Figure 1: Quality planning concept

According to the GMP regulations, several risk management-based plans and strategies need to be implemented. Although, this concept is indented to be applied to manufactures, we have recognized that for process development in applied research, process transfers and our BioIndustrial Pilot Plant environment an additional value is gained. The establishment of risk management concepts as well as quality plans for room monitoring are developed.

Risk management concepts are developed according to the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines.

A quality plan is a consisting a document, or several documents, that together specify quality standards, practices, resources, specifications, and the sequence of activities relevant to a particular product, service, project, or contract.

Quality plans are characterized by objectives to be attained (for example, characteristics or specifications, uniformity, effectiveness, cycle-time, costs, resources, utilization, yield, dependability, and so on). Allocation of responsibilities, authorities, and resources during the different phases are also addressed as documented standards, practices, procedures, and instructions. A documented procedure for implementation, changes and modifications as well as the measuring of the achievement are included. At the highest level, quality goals and plans should be integrated with overall strategic plans of the organization. At lower levels, the quality plan assumes the role of an actionable plan. Such plans may take many different forms depending on the outcome they are to produce. Quality plans may also be represented by more than one type of document to produce a given outcome.

  • Quality planning
  • Quality control
  • Quality improvement

Through these criteria, knowledge is used achieving an optimized risk-benefit ratio for the critical process attributes, for implemented control strategies, equipment exchanges and environmental monitoring (Quality Planning). Quality is controlled by multitude of analyzers (quality control), which should improve the process quality and stability (quality improvement). It is also aimed that the results directly improve existing processes, allocate process development and process adaptation and are transfer from more inflexible towards more flexible processes with enlarged operation space.

Implementation

Integration of quality planning with risk management is conducted according the current ICH-Q9 guideline (Fig.2). ICH Q9 has provided the pharmaceutical industry and regulators alike with a common framework for applying Quality Risk Management (QRM) principles in their work. However, despite the guideline being in place for almost 15 years, the benefits of QRM, as envisaged by ICH Q9, have not yet been fully realized. Revision to ICH Q9 hopefully will help provide consistency and clarity, helping to improve quality manufacturing [Final Business Plan, ICH Q9(R1) - Quality Risk Management, Endorsed by the Management Committee on 26 October 2020].

Figure 2: Overview of a typical quality risk management process according to ICH-Q9.

Based on the above mentioned strategies, several applications for risk assessment integration were performed (Table 1).

Project

Objectives

Achievements

Analysis of microbial contamination risk for our multi-purpose BioIndustrial Pilot Plant

Failure Mode Effects Analysis (FMEA) for all process-steps;

Quality plan for environmental monitoring

Implementation of an appropriate concept

Training-plan implementation

Self-inspection plan installed

Single-use process verification strategy

Risk assessment for process switch from stainless-steel  towards disposable equipment

Assessment of the critical control points

Quality plan for continuous monitoring

Criticality of relevant process parameters were identified

Further risk management concepts are provided

Recommendations for quality control chart implementation

Risk Assessment for cleaning validation of a multi-purpose liposome facility

Suitable cleaning validation Assessment of potential risks and their criticality

Quality plan for sampling and suitable analyzers

Implementation of cleaning validation strategy

Establishment of an applicable HACCP* concept

Road model for the cleaning validation

Risk Management implementation for R&D continuous integrated bioprocess

Implementation of risk management early in the process development

Implementation of management tools for continuous production

Flexible concept for R&D and manufacturing

Implementation of SWIFT#,

Bow Tie§ and FTA$ analysis for the development phase

Adaptation of risk management concept for continuous bioproduction

Quality plan for risk communication

Table 1: Overview of representative QM-projects

* Hazard Analysis Critical Control Point
# the structured what-if technique
§ risk management tool
$ Fault tree analysis