I. Equipment Principles
What should be considered regarding equipment principles? Based on pharmaceutical GMP practices, the principles are evaluated as follows: General Provisions—Equipment design, selection, installation, modification, and maintenance must align with the intended use (minimizing risks of contamination, cross-contamination, mix-ups, and errors; facilitating operation, cleaning, and maintenance; and allowing for disinfection or sterilization when necessary—Article 71 of the 2010 revision of GMP for Pharmaceutical Products);
Procedures—Standard operating procedures (SOPs) for equipment use, cleaning, maintenance, and repair must be established, and corresponding records maintained (Article 72); Documentation—Documents and records regarding equipment procurement, installation, and qualification must be established and maintained (Article 73); Previous Version—Equipment design, selection, and installation must meet production requirements (easy to clean, disinfect, or sterilize; convenient for production operations and maintenance; capable of preventing errors and reducing contamination—Article 31 of the 1998 revision); Assessment—Equipment design, selection, and installation must meet production requirements (easy to clean, disinfect, or sterilize; convenient for production operations and maintenance; capable of preventing errors and reducing contamination—GMP Certification Inspection and Assessment Standards); Sterilization Cabinets—Sterilization cabinets used for sterile drug production must feature automatic monitoring and recording devices (capacity must match production batch sizes—GMP Certification Inspection and Assessment Standards). In summary, there are six key aspects to consider: intended use, risk reduction regarding contamination, operating procedures and records, documentation for procurement/installation/qualification, ease of cleaning and disinfection, and automatic monitoring for sterilization cabinets.
II.
Requirements for Contact Surfaces
What should be considered regarding contact surface requirements?
Based on GMP practices, contact surfaces are evaluated according to these criteria: Core—production equipment must not adversely affect drug quality (surfaces in direct contact with the drug must be smooth, clean, easy to clean or disinfect, corrosion-resistant, and must not chemically react with, adsorb, or leach substances into the drug; Article 74); Materials—equipment, containers, utensils, piping, valves, and pumps in contact with the drug solution must be made of high-quality, corrosion-resistant materials (piping installation should minimize welded joints; 2000 Supplementary Notice on License Renewal); Utensils—avoid using utensils that are fragile, prone to shedding particles, or susceptible to mold growth during production (measures must be in place to prevent contamination caused by screen breakage when using sieves); Filtration—filter media must not adsorb drug solution components or release foreign matter (use of asbestos-containing filter media is prohibited); Food—inner surfaces of production equipment and utensils in direct contact with food must be corrosion-resistant, non-toxic, and harmless (Article 15, Detailed Rules for Review of Production Licensing for Foods for Special Medical Purposes; equipment performance and precision must meet processing requirements; periodic calibration or verification of measuring instruments and key gauges, Article 14); Surfaces—food-contact surfaces must be corrosion-resistant (made of non-toxic materials; designed to withstand the intended use environment and the effects of the food; 21 CFR Part 110)—Six criteria for contact surfaces: smooth/clean/easy to clean; corrosion-resistant/non-reactive/non-adsorbing; high-quality corrosion-resistant materials; avoidance of fragile/shedding utensils; non-adsorbing/non-leaching filtration; non-toxic/harmless inner surfaces for food contact—compliance is achieved when these six criteria are met.
III.
Cleaning Standards
What to look for in cleaning standards.
In accordance with GMP practices, consider cleaning from these perspectives: Procedures—production equipment must be cleaned according to detailed operating procedures (these must specify comprehensive cleaning methods; equipment or tools used; names and preparation methods of cleaning agents; methods for removing identification from the previous batch; methods to protect cleaned equipment from contamination prior to use; maximum storage duration for cleaned equipment; methods for verifying cleanliness before use; and instructions enabling operators to clean various types of equipment effectively and reproducibly; Article 84); Disassembly/Assembly—if equipment requires disassembly or reassembly, the sequence and methods must be specified (Article 84); Cleaning Protocols—cleaning protocols for facilities, equipment, and containers must be established for all pharmaceutical production workstations, based on production requirements and air cleanliness classifications (content should include cleaning methods, procedures, intervals, cleaning or disinfecting agents used, and the cleaning methods and storage locations for cleaning tools; GMP Standard Encyclopedia); Contamination Prevention—pharmaceutical manufacturers must implement sanitary measures to prevent contamination (establishing hygiene management systems with designated personnel responsible); Areas—non-production items and personal belongings must not be stored in production areas (production waste must be disposed of promptly); Packaging—inspections must be conducted before packaging begins (ensuring the workspace, packaging lines, printing machines, and other equipment are clean or ready for use, and are free of products, documents, or materials from the previous batch or unrelated to the current batch; inspection results must be recorded; Article 203)—Six Key Aspects of Cleaning: comprehensive cleaning methods, cleaning agent names and preparation, removal of batch identification, maximum storage duration, workshop-specific protocols, and pre-packaging cleanliness checks—forming a closed-loop system for cleaning management.
IV.
Qualification and Validation
What to look for in qualification and validation.
In accordance with GMP practices, “confirmation” entails the following six aspects: **Qualification**—the enterprise’s facilities, utilities, equipment, and testing instruments must undergo qualification (production operations and testing must utilize validated processes, operating procedures, and test methods, and a state of validated control must be maintained; Article 139); **Risk**—the enterprise must determine the scope of qualification or validation activities required (to demonstrate that critical elements of operations can be effectively controlled; the scope and extent of qualification or validation must be determined through risk assessment; Article 138); **Records**—documentation and records regarding qualification and validation must be established (Article 140); **Automation**—equipment and instrument parameters may be connected to validated computerized systems (such as DCS or PLC systems) to facilitate data transmission and recording (Guideline on Inspection of Continuous Manufacturing of APIs); **In-line**—in-line monitoring systems (if applicable) must undergo appropriate validation (confirming strategies for data storage, backup, etc.); **Interlocks**—alarm and interlock settings for production line control parameters must be established based on process requirements (confirming effective feedback on parameter deviations during the process; automatic control systems governing diversion mechanisms and disturbance adjustment functions must be validated; Guideline on Inspection of Continuous Manufacturing of APIs). In summary, the six key areas for confirmation are: qualification of facilities and equipment; validation of processes, procedures, and methods; scope determination via risk assessment; maintenance of qualification and validation documentation/records; validation of computerized systems;
and verification of alarms, interlocks, and in-line monitoring systems.
V. Utility Systems
What to look for regarding utility systems.
In accordance with GMP practices, the system is evaluated based on the following aspects: Water Treatment—the design, installation, operation, and maintenance of water treatment equipment and distribution systems must ensure that pharmaceutical-grade water meets established quality standards (equipment operation must not exceed design capacity; Article 97); Materials—materials used for storage tanks and distribution piping for purified water and water for injection must be non-toxic and corrosion-resistant (tank vents must be fitted with hydrophobic, non-shedding, sterilizing filters; piping design and installation must avoid dead legs or blind ends; Article 98); Circulation—systems for the generation, storage, and distribution of purified water and water for injection must prevent microbial proliferation (purified water systems may utilize circulation; water for injection systems may utilize circulation maintained at temperatures above 70°C; Article 99); Lubrication—lubricants and coolants used in equipment must not contaminate the drug product or containers (Article 77); Weighing/Measuring Instruments—weighing scales, measuring tools, instruments, and gauges with appropriate ranges and precision must be provided (Article 75); Cleaning Equipment—appropriate cleaning equipment must be selected, and measures taken to prevent such equipment from becoming a source of contamination (Article 76); Piping—major piping connected to equipment must be labeled to indicate the material contained and the direction of flow (Article 33, 1998 Revision). In summary, utility systems are evaluated against six criteria: compliant water treatment; non-toxic and corrosion-resistant tanks and piping; avoidance of dead legs and blind ends; circulation maintained at 70°C; prevention of contamination by lubricants; and appropriate range and precision of weighing/measuring instruments.
Compliance is determined by meeting these six criteria.
Conclusion
What are the GMP standard requirements for non-standardized assembly lines? The conclusion is that they are defined by five dimensions: principles, contact surfaces, cleaning, qualification, and system integrity.
Principles—Equipment design, selection, installation, modification, and maintenance must align with intended use (minimizing risks of contamination, cross-contamination, mix-ups, and errors; facilitating operation, cleaning, maintenance, disinfection, and sterilization; establishing SOPs and maintaining records; ensuring documentation for procurement, installation, and qualification; complying with Articles 71–73 of the 2010 GMP revision). Contact Surfaces—Production equipment must not adversely affect drug quality (surfaces must be smooth, clean, easy to clean/disinfect, and corrosion-resistant; materials must be high-quality and corrosion-resistant, non-reactive, non-adsorbing, and non-leaching; designs should minimize welds and avoid materials that are brittle, prone to shedding particles, or susceptible to mold growth; filtration media must be non-adsorbing and non-leaching). Cleaning—Detailed SOPs are required (cleaning methods, names and preparation of cleaning agents, removal of batch identification, maximum hold times for cleaned equipment, pre-use inspections, disassembly/reassembly procedures, workshop cleanliness-level protocols, and checks on cleanliness/readiness status prior to packaging). Qualification—Facilities, equipment, and testing instruments must undergo qualification (validation of process procedures and test methods; maintenance of a validated state; scope determination via risk assessment; documentation of qualification and validation records; validation of PLC/DCS computerized systems; validation of in-line monitoring; verification of alarm and interlock settings).
Systems—Water treatment equipment must meet standards (storage tanks and piping must be non-toxic and corrosion-resistant; vents must feature hydrophobic sterilizing filters; dead legs and blind pipes must be avoided; purified water systems should utilize circulation, while Water for Injection systems require circulation maintained at 70°C; lubricants and coolants must not cause contamination; weighing instruments, measuring tools, and gauges must have appropriate ranges and accuracy).
In summary, GMP requirements can be distilled into a single phrase: equipment must be suitable for its intended use with low risk, feature smooth and corrosion-resistant contact surfaces, utilize reproducible cleaning procedures, and undergo continuous qualification and validation—master these four aspects, and GMP compliance is assured.
