Analysis of key points for verification of automatic control systems in pharmaceutical factories

In the strictly regulated pharmaceutical industry, automatic control systems are not only a tool to improve production efficiency and stability, but also a key element in ensuring that drug quality meets GMP (Good Manufacturing Practice) requirements. The "verification" link of the system is the core process that proves that it can operate continuously and stably in accordance with established standards, and is directly related to the production licensing and market access of drugs. However, many pharmaceutical companies often face challenges such as complex document systems and disconnection from production reality when verifying their automatic control systems.

This paper focuses on the particularities of the pharmaceutical industry, analyzes the verification points and common problems of the automatic control system at all stages from design to operation and maintenance, and provides practical reference for the engineering and quality departments of pharmaceutical companies.

Design confirmation stage: Lay a good foundation for compliance. DQ is the first step in verification and aims to demonstrate that the system is designed to comply with User Requirements (URS) and GMP regulatory requirements. Common misunderstandings are that URS are written too generally, or that the design does not match the actual production process requirements.

Key point analysis: URS must be jointly formulated by the production, process, equipment, quality and self-control departments, and the content should be specific, measurable and verifiable. For example, for temperature control of fermentation tanks, URS needs to clarify the control accuracy (such as ±0.5℃), recording frequency, alarm upper and lower limits, etc. During the DQ stage, the design documents provided by the service provider (such as functional design descriptions, hardware configuration diagrams, and software structure diagrams) need to be reviewed item by item with the URS. A technical partner who has served the pharmaceutical industry for a long time, his team understands GMP's requirements for computerized systems and can integrate compliance elements such as audit trails, electronic signatures, and data integrity into the system architecture during the design stage to reduce subsequent verification risks from the source.

Installation and Operational Qualification Phase: Ensure that hardware and software are in place. The purpose of IQ and OQ is to prove that the installation of system hardware and software meets design specifications and can operate normally within the specified operating range. This stage can easily become a formality and become a simple "check-off" checklist without fully exposing potential problems.

Key point analysis: IQ should record in detail the models, version numbers, installation locations and network topology of all major hardware and software to form an accurate "system snapshot". OQ needs to test key functions based on risk assessment, such as sensor calibration verification, control loop debugging, alarm function testing, user rights testing, etc. The test should be carried out in a simulated or actual production environment and cover the upper, lower and typical values of the normal operating range. During the project construction of a biopharmaceutical base in Southwest China, the technical service provider assisted the customer in formulating a detailed OQ test plan, and strictly tested and recorded hundreds of control parameters related to product quality, ensuring that the system is fully compliant. The status of compliance enters the next stage.

Performance Qualification Phase: Simulate real production challenges. PQ is the "ultimate test" of verification, which needs to prove that the system can continuously and stably produce products that meet quality requirements under expected process conditions and production environment. The biggest challenge is that the PQ test plan needs to be closely integrated with the specific production process.

Key point analysis: PQ usually requires more than three batches of production operation testing in succession. The verification plan must clarify key process parameters and their acceptance standards, and collect complete production data and automatic control system operation data for analysis and comparison. For example, for the environmental monitoring and automatic control system of the aseptic filling line, PQ needs to continuously monitor and prove that under dynamic production conditions, the suspended particles, microorganisms, temperature and humidity and other parameters in the clean room always meet Level A or Level B standards. This requires the automatic control system itself to have extremely high reliability and data accuracy. The value of a professional automatic control technology service provider lies not only in system construction, but also in its ability to provide full-process technical support and documentation services throughout IQ, OQ, and PQ, helping pharmaceutical companies efficiently pass regulatory reviews.

Continuous verification and change management: throughout the life cycle. Verification is not once and for all. Any changes to the system (such as hardware replacements, software upgrades, control logic modifications) must be evaluated and appropriate change control and re-verification implemented.

Key points: Establishing a sound change management process is the key. The service provider shall be able to provide systematic maintenance support, including regular calibration, backup management, fault log analysis, and test and verification services after change implementation. The in-depth cooperation with well-known automation brands in Hangzhou and other places has enabled some technical service providers to obtain stable product support and compliance upgrade paths, which is crucial to ensuring the compliance of pharmaceutical factory automatic control systems throughout the life cycle.

All in all, the verification of pharmaceutical factory automatic control systems is a rigorous and systematic project that connects engineering technology, production processes and quality regulations. Successful verification is inseparable from the close cooperation of multiple departments within pharmaceutical companies, as well as the professional, compliant, and full-process technical support provided by external technical service providers. Choosing a partner who understands the essence of GMP, has rich experience in implementing pharmaceutical projects, and can provide long-term stable services will become a solid backing for pharmaceutical companies to ensure production compliance and improve quality control levels.