What is meant by Good Engineering Practice in the Pharmaceutical Industry?

Good Engineering Practice (GEP) is the foundation of pharmaceutical equipment technology. Good engineering is indispensable for any functioning production environment, especially for all equipment in the GMP environment.

GEP covers the entire equipment layout, design, construction, commissioning and maintenance. GEP-compliant equipment is a prerequisite for GMP, but it does not replace GMP. Only equipment that meets GEP principles makes GMP possible. GEP itself is based on the current state of the art.

GMP requirements and GEP standards

GMP as Good Manufacturing Practice is a legal requirement and is monitored by the pharmaceutical authorities. It demands functioning, qualified and documented systems. The focus of GMP is to ensure product quality and the safety and efficacy of products for patients. GEP deals with the technical systems and ensures that they are designed, procured and installed in a technically sound way. Errors in GEP inevitably lead to problems in qualification, later operation and maintenance. While GMP stipulates what must be ensured in the regulated environment, GEP describes how technical equipment should be designed, built and operated. GEP is therefore not a regulatory construct, but a "good practice" standard that has evolved over decades from engineering, standards, manufacturer guidelines and industry experience. More and more companies understand GEP as a strategic tool: the more cleanly and consistently GEP is implemented in the early project phase, the leaner and more robust qualification will be later on.

In contrast to GMP, GEP is not laid down in law, but is closely aligned with technical standards such as ISO and VDI standards, GAMP 5, ISPE Good Practice Guides and thus with the current state of the art. Explicit examples here include the ISPE Good Practice Guide: Good Engineering Practice as well as the freely available Equipment Design Guide of the ECA, which describes requirements for equipment design. The transition between GMP and GEP is fluid. For example, in order to meet GMP requirements (such as "good cleanability of equipment"), GEP identifies and describes technical options.

In the engineering process, GEP already begins in the concept phase with the creation of clear User Requirements Specifications (URS), a structured risk assessment, the selection of suitable technologies, materials and suppliers, as well as traceable technical specifications. The URS is both a GEP and a GMP document. EU GMP Annex 15 requires the URS as the first GMP document. Already in this early phase, risk minimisation for product quality must be built into the equipment design. Of course, depending on the company, the term URS can be defined more broadly and GEP aspects can also be included in the URS.

Technical project execution should be documented, structured and standardised - for example through design reviews, functional descriptions, P&IDs or flow diagrams, calibration concepts, automation architectures and hygienic design.

Testing in GEP

Factory Acceptance Testing (FAT) and Site Acceptance Testing (SAT) play a particular role in GEP in this context. FAT is carried out at the manufacturer's site and serves to test machines and equipment under controlled conditions before dispatch. The specific tests to be performed are usually contractually agreed. Typically, FAT includes functional tests, safety checks, software tests and verification against the URS and technical specifications. A well-executed FAT identifies technical errors, reduces rework on site and shortens commissioning. SAT, on the other hand, takes place at the installation site and checks whether the equipment functions correctly in its final environment - including utilities, building services and automation. Both steps are regarded as classic GEP activities: they ensure technical functionality but are not yet part of GMP qualification. However, FAT and SAT results can be incorporated into qualification in order to avoid duplicate testing. This is possible if the approach is already foreseen in the qualification plan and both execution and documentation are carried out in a GMP-compliant manner. However, there is also equipment (for example HVAC systems) or catalogue equipment for which FAT or SAT is of little practical use and therefore not carried out.

Commissioning and Qualification

Commissioning and qualification should be clearly separated. Commissioning is a GEP process in which the equipment is technically tested, adjusted, parameterised and made ready for operation. It serves technical verification and is documented accordingly. Qualification, on the other hand - consisting of URS, DQ, IQ, OQ and PQ - is a GMP process which, according to Annex 15, must demonstrate that the equipment is suitable for its intended purpose and operates reproducibly under GMP conditions. Well-designed commissioning activities can (as mentioned above) be integrated into or credited towards qualification activities, for example within the framework of an integrated C&Q model in line with the ECA Good Practice Guide: Qualification and Validation (available free of charge in the ECA website members' area) and the ISPE Baseline: Commissioning & Qualification. This avoids duplicate testing and accelerates qualification. The precise requirements for such integration are bindingly specified in Annex 15.

GMP and GEP documents

GEP documents and GMP documents differ in their purpose and therefore also in the type and depth of documentation. GEP documents originate from technical engineering and primarily serve to plan, build and commission equipment safely. They follow technical standards and include technical specifications, P&IDs, functional descriptions, software design, FAT and SAT protocols or technical test reports. These documents must be correct, complete, traceable and up to date, but they are not yet subject to the stringent requirements for data integrity and formal control that apply in the GMP area. Rules for signatures, audit trails or a fully documented approval structure are usually simpler in the GEP environment.

GMP documents, on the other hand, serve regulatory purposes and must therefore satisfy particularly high standards. They must not only be technically correct, but demonstrably comply with the requirements of the EU-GMP Guide, Annex 11, Annex 15 or 21 CFR 211. This relates in particular to formal control: version control, traceable changes, audit trails, controlled archiving, qualified transmission routes, ALCOA+ compliance and defined roles for drafting, review and approval. Whereas GEP documents primarily demonstrate technical functionality, GMP documents must ensure regulatory compliance and product safety.

Fulfilling GMP requirements through GEP

A clear example of how GMP requirements are practically fulfilled through Good Engineering Practice is temperature control in an autoclave. GMP, according to Annex 1, requires that sterilisation processes run reproducibly under controlled conditions and that temperature and pressure sensors operate reliably and are calibrated over the entire working range. In order for these regulatory requirements to be demonstrated later during qualification, GEP and GMP already begin at the engineering stage: in the initial URS document, not only the requirements for process parameters are defined, but risks of malfunction are also minimised. As a result, the autoclave is specified, designed and documented in such a way that qualification is possible in the first place - for example through chamber design, suitable temperature and pressure sensors, traceable automation concepts, complete technical specifications and a sufficient number of measurement ports for qualification sensors.

During FAT at the equipment manufacturer and SAT on site, the equipment is then functionally tested so that technical faults are identified and corrected at an early stage. Commissioning ensures that all processes, safety devices and utility connections function correctly. Only on this basis can qualification demonstrate that the autoclave operates in compliance with GMP, because all technical functions are stable and reproducible.

Post-commissioning GEP

However, GEP does not end with commissioning. During routine operation, it encompasses maintenance strategies, spare parts management and checking the consistency of the technical documentation. Here too, the following applies: stability and reproducibility in GMP operation are only achievable if the technical basis is properly structured and managed. As a rule, pharmaceutical Quality Assurance is not involved in GEP processes, which are carried out under the independent responsibility of engineering.

Conclusion

In summary, Good Engineering Practice is the technical backbone of GMP-compliant production and technology. It creates the conditions under which equipment can be qualified and operated in a technically robust, safe and efficient manner.

Please also note the training opportunities on technical issues in the GMP environment.