1、 Continuation of the main normative framework and systematic update of appendices

1. The appendix of medicinal excipients and drug packaging materials has been officially released (Announcement No. 1 of 2025)
   The National Medical Products Administration issued new regulations in January 2025, which for the first time included pharmaceutical excipients and packaging materials in the GMP unified management systemImplemented from January 1st, 2026The core changes include:

   • Deepening risk managementRequire enterprises to establish a full lifecycle quality risk assessment system for auxiliary materials/packaging materials, covering raw material procurement, production process changes, supplier management, and other links, clarifying risk level classification and response measures.

   • Data integrity enhancementEmphasize the traceability of material traceability, change records, and rework management, such as the requirement in the appendix of drug packaging materials for mold number management and retention of rework batch records.

   • Supplier Collaboration ManagementDrug Marketing Authorization Holder (MAH) is required to sign quality agreements with major suppliers and strengthen the review and filing of changes in auxiliary/packaging material production sites and formula processes.

   • Eliminate outdated production capacityGuide enterprises to adopt advanced processes and materials (such as pharmaceutical grade polymer materials), eliminate traditional methods such as manual data recording, and promote the upgrading of the industry towards automation and informatization.

   • Institutionalization of sample retention and quality sampling inspectionFill the previous regulatory gap, clarify the requirements for sample retention, and establish a risk-based sampling mechanism for provincial drug regulatory departments.

2. The draft for soliciting opinions on the appendix of sterile drugs leads the transformation
   The "Aseptic Drug Appendix (Draft for Comments)" released in March 2025 will undergo significant restructuring of the clean area management and validation system

   • Verification of combined dynamic and static airflow patternsRequire air conditioning system validation to shift from a single static mode toDynamic simulation evaluation of operational intervention impact(such as personnel activities, equipment start stop), equipped with visual recording equipment (such as video surveillance) and establishing a standard scene library, the results need to be closed-loop applied to production quality control.

   • Confirm frequency adjustment againThe frequency of reconfirmation for air conditioning systems in Class A/B clean areas has been shortened toOnce every six months， C-level/D-level is conducted once a year, abandoning the extensive model of relying on annual quality reviews and emphasizing the stability of periodic evaluations.

   • Implementation of Pollution Control Strategy (CCS)Introducing the internationally recognized CCS concept, enterprises are required to develop a risk-based full process pollution prevention and control plan, covering optimization of plant design airflow (such as first pass air barriers), dynamic verification of disinfection procedures, and dynamic adjustment of microbial monitoring.

   • Technical Details UpdateThe exposed air ducts must be made of stainless steel material (strengthened by the "Construction and Acceptance Standards for Clean Plants in the Pharmaceutical Industry" implemented in September 2025), and automatic adjustment and traceability of operating parameters are mandatory requirements to prevent manual recording of compliance loopholes.

2、 Core upgrade direction of regulatory requirements

1. Strengthening risk management throughout the entire process

   • The new version of the appendix regards risk management as a core driving element, which runs through material procurement, production processes, facilities and equipment, environmental control, and release decisions. For example, in the appendix of pharmaceutical excipients11 clauses related to risk assessmentEmphasize that change assessment and supplier risk grading review should be based on scientific data support.

   • The Pollution Control Strategy (CCS) has become the core framework for aseptic production, requiring enterprises to dynamically identify pollution sources (such as microorganisms and particles), and reduce the pollution probability of high-risk operations (such as aseptic filling) through engineering control (isolation technology) and monitoring methods (real-time online detection).

2. Upgrade of data integrity and compliance traceability system

   • The appendix of drug packaging materials requires the full lifecycle traceability of materials, rework batches, and production records, and specifies that electronic data must meet the requirementsALCOA+principle(Attributable, clear, synchronous, original, accurate, complete, consistent, and persistent).

   • The validation and operation data of key facilities such as air conditioning systems need to be automatically collected, stored, and associated with operational events, bidding farewell to the elimination of paper-based manual records as evidence of GMP compliance.

3. Deepening the synergy between personnel qualifications and quality system

   • The qualification requirements for key positions (such as production management leader, quality management leader) are refined, for example, the production leader must have a bachelor's degree or above in pharmacy or intermediate professional title+practical experience, emphasizing independent performance authority (not concurrently holding conflicting positions).

   • MAH needs to lead the management of auxiliary/packaging material suppliers, establish a two-way communication mechanism, timely evaluate the impact of changes on drug quality, and update regulatory platform registration information.

3、 Deep integration with international standards

1. Benchmarking PIC/S and EU GMP standards

   • The draft for soliciting opinions on the appendix of sterile drugs introduces the pollution control concept of PIC/S Appendix 1 (such as the application of RABS/Isolator isolation technology), dynamic microbial monitoring (such as tightening the microbial limit to ≤ 1CFU/100mL in high-risk areas such as cell therapy), and process validation innovation (such as mandatory implementation of PUPSIT for filter integrity testing after sterilization).

   • The appendix of pharmaceutical excipients integrates the International Pharmaceutical Excipients Association (IPEC-PQG) guidelines and the EU sterile excipient control strategy to ensure that the production standards of local excipient enterprises are in line with international standards, and to assist in the compliance of drugs going global.

2. Promote mutual recognition of inspections and global collaboration
   China is accelerating its integration into the PIC/S international drug inspection system, and in the future, the compliance reports of GMP certified enterprises can be mutually recognized by member countries, reducing the cost of repeated inspections of exported drugs. Jointly carry out cross-border joint inspection projects with FDA, EMA, etc. (such as Orbis synchronous review), promote the coordination and unity of technical standards, and accelerate the global market launch process of new drugs.

4、 Industry Transformation and Response Suggestions

1. Urgent demand for hardware and technological upgrades

   • Old factory buildings need to evaluate the optimization of air conditioning system airflow organization (such as one-way flow transformation), upgrade monitoring equipment automation (particle counter networking, TOC online detection) to meet the requirements of dynamic and static combination verification and dynamic data acquisition.

   • Encourage the use of advanced engineering control measures such as single use systems (SUS) and isolation technologies to reduce the risk of contamination during aseptic operations, but ensure that supplier quality certification documents (such as particulate matter/TOC control standards) are compliant.

2. Restructuring of Compliance System and Updating of Documents

   • Revise the quality manual, validation plan (such as air conditioning system reconfirmation plan), cleaning and disinfection SOP, and incorporate CCS strategy and risk grading validation (dynamically adjusting sampling frequency based on operational risk) into daily management.

   • Establish a quality file for auxiliary/packaging material suppliers, clarify the hierarchical audit mechanism (such as the frequency of on-site audits for major suppliers), and link it with the change management module to ensure that all changes trigger necessary risk assessments and revalidations.

3. Dynamic Training and Talent Reserve
   Design specialized training courses for the newly added digitalization regulations and pollution control strategies to ensure that operators understand the impact mechanism of airflow intervention on clean areas, and that quality authorized personnel master the new release decision logic (such as the application scenario of conductivity exemption for multiple tests).

5、 Summary: Core of Change and Industry Value

• Dynamic and Static Integration Verification and Periodic EvaluationReplace extensive management and ensure that critical facilities (such as air conditioning systems) are continuously controlled;

• Data electronicization and risk tracingBecoming a compliance bottom line, forcing enterprises to eliminate outdated production capacity;

• Pollution control in line with international standardsPromote technological upgrades in high value-added fields such as sterile drugs and biological products, and enhance global competitiveness.