GB/T 36036-2018Verify guidance of cleaning and sterilization for pharmaceutical machinery (English PDF)

3.1 Validation file

Verify the master plan, verification plan, verification plan, verification report and verification summary and other relevant documents or materials formed during the verification process. [GB/T 28671-2012, definition 3.8]

3.2 Verification report

A review, review and assessment of the results of the verification plan and the results of the verification test, the missing items and the deviations that have occurred. [GB/T 28671-2012, definition 3.9]

3.3 Challenging trial

Designed to determine a process or a component of a system (such as a device or a facility) that can be set under the harsh conditions Whether to achieve the test of the predetermined quality requirements. [GB/T 28671-2012, definition 3.10]

4.1 Purpose of verification

4.1.1 Verification of pharmaceutical machinery (equipment) cleaning and sterilization in line with the "Good Manufacturing Practices (2010 Revision)", GB/T 36030-2018 and user demand standards to achieve the specified cleaning and sterilization effects.

4.1.2 Verify that the structure of the pharmaceutical machinery (equipment) cleaning and sterilization system meets the requirements of the pharmaceutical production process.

4.1.3 Verify the cleaning and sterilization procedures of pharmaceutical machinery (equipment). The cleaning and sterilization media and operating parameters are correct and effective.

4.1.4 Verify the effectiveness, stability, reproducibility and traceability of pharmaceutical machinery (equipment) cleaning and sterilization.

4.2 Principles of verification

4.2.1 The verification scheme for the cleaning and sterilization of pharmaceutical machinery (equipment) shall be in accordance with the "Good Manufacturing Practices for Pharmaceutical Production (Revised in 2010)", GB/T 36030-2018 and pharmaceutical production process requirements are formulated. There should be a verification scheme for each stage of verification.

4.2.2 The verification plan shall clearly define the purpose of verification, participate in the implementation of the verification department, and personnel responsibilities. The verification content should include cleaning and sterilization methods, wind Risk analysis, residual limit calculation process, test method, qualification criteria, deviation treatment, etc. The verification plan shall be reviewed by the quality management department. Approved.

4.2.3 Verification shall be carried out in accordance with a predetermined and approved plan and documented.

4.2.4 After the verification work is completed, there should be conclusions such as verification report, verification results, evaluations, recommendations, etc., and shall be reviewed and approved; Archive.

4.3 Verification scope

The scope of verification shall be based on the "Good Manufacturing Practices (Revised in 2010)" and the pharmaceutical process for the cleaning and sterilization of pharmaceutical machinery (equipment). Request for confirmation.

4.4 Verification procedure

4.4.1 The verification procedure shall include verification plan, cleaning system structure, pharmaceutical machinery (equipment) cleaning and sterilization verification.

4.4.2 A phased verification report shall be formed in each verification stage. When blind tubes, dead ends, or critical deviations affecting product quality occur, they should not Carry out the next stage of verification.

4.4.3 The verification of the verification data, process data and final report of each stage shall be in accordance with the "Good Manufacturing Practices (Revised in 2010)". File regulations.

4.5 Verification File

4.5.1 Verification Plan

4.5.1.1 Program Content

The plan includes the following.

a) the name of the certified pharmaceutical machinery (equipment);

b) Verification items. such as cleaning and sterilization system structure verification, cleaning, sterilization effect verification;

c) verify the time required and the configuration of the process, manpower and material resources;

d) Verification document change regulations. directly from the quality management department or the project department to change the implementation of the document; from the next feedback file to modify the meaning See the evidence of the practice data and the signature of the manager, from the bottom to the upper level, after approval by the quality department or the project department. carried out.

4.5.1.2 Verification plan implementation

4.5.1.2.1 Review verification procedures, procedures, test items, test methods, test results, compliance with verification documents and related standards during the verification process Quasi-regulation.

4.5.1.2.2 Review the verification plan, process record, whether the test data is signed by the relevant personnel, and the approver's signature is effective.

4.5.1.2.3 Review whether the verification report document is reviewed and the approver signs and confirms.

4.5.1.3 Document Registration Form

The documents formed by the verification process are registered in accordance with Table 1.

Note: No signed documents are not allowed to be archived.

4.5.2 Verification scheme

4.5.2.1 The verification scheme shall be based on the structure of the pharmaceutical machinery (equipment) cleaning system, the nature of the manufactured drug, composition, viscosity, fluidity, adhesion, and resistance. Formulation of characteristics such as heat and pharmaceutical process flow.

4.5.2.2 The cleaning verification plan shall specify the object to be cleaned, the cleaning procedure, the name of the cleaning medium, the preparation method, and the operating parameters to be monitored. Sample location, method and sample identification, residue and microbial limit standards and test methods. For dedicated production equipment and stable product quality The residual acceptable limit standard can be determined by visual inspection.

4.5.2.3 The sterilization verification plan shall specify the object to be sterilized, the sterilization procedure, the location of the cold spot, the biological indicator, the name and quality of the sterilization medium. Requirements, temperature probe and indicator placement, operating parameters to be monitored, sampling position, method and sample identification, sterilization quality standards and inspection method.

4.5.2.4 The verification plan shall be implemented after approval by the quality authority of the user.

4.5.2.5 The verification plan should include the following basic information.

a) The verification plan cover should include the verification project name, file number, version number/revision number, etc.;

b) Header and footer information. file number, version number/revision number, file title, page number;

c) the name, department, position, title and other information of the drafter, reviewer and approver, as well as the signature and date;

d) verification plan revision history, including revision date, revision number, revision content, revision person signature, auditor signature, etc.;

e) Verification team registration form, including name, department, position, division of labor, etc.

4.5.2.6 The verification scheme shall include the following.

a) Pharmaceutical machinery (equipment) cleaning and sterilization comply with the "Good Manufacturing Practices (2010 Revision)", GB/T 36030-2018, Meet the requirements of pharmaceutical production processes;

b) Cleaning and sterilization of pharmaceutical machinery (equipment) basic conditions. including model, name, serial number, equipment P-ID structure diagram, use, structure And characteristics, functions, control devices, main technical parameters, etc.;

c) implementation of standards and specifications;

d) use instrumentation and ancillary facilities registration forms;

e) test records, including test content, requirements, qualification standards, test methods, test procedures, test results, etc.;

f) Deviation from the explanation and conclusion, and signed by the verifier and the reviewer;

g) verification conclusions;

h) Verify the signature and date of signature of the responsible person or relevant responsible person.

4.5.2.7 Verify that the responsibility of the project leader is as follows.

a) The organization develops and approves a project validation plan.

b) Provide regulatory support related to verification, such as GMP specifications.

c) Review and approve verification documents such as cleaning and sterilization procedures.

d) Analytical method validation.

e) The regulatory verification process is implemented as approved.

4.5.2.8 The duties of the person responsible for implementing the verification program are as follows.

a) Confirm equipment cleaning and sterilization procedures.

b) Verify the target active ingredient calculation and selection.

c) Make sure that the steps in the cleaning and sterilization procedures are followed.

d) Assess the impact of the introduction of new equipment on verification.

4.5.2.9 The duties of other verifiers are as follows.

a) Laboratory laboratory technicians should prepare validation reports and reports on relevant analytical methods to perform sample testing.

b) Technical support staff should assess the impact of the introduction of new drugs on cleaning and sterilization verification. Determination of the target active ingredient (residue) Calculate and choose the reason.

c) The verifier should work in accordance with the approval documents and procedures.

4.5.3 Cleaning and Sterilization System Structure Verification (see Appendix A)

4.5.3.1 Structure verification shall include the following.

a) Adaptability of the cleaning system structure and materials to the cleaning and sterilization media and cleaning and sterilization processes; detachable scrubbing pharmaceuticals Adaptability of mechanical (equipment) structures and materials to cleaning and sterilization media and cleaning and sterilization processes;

b) structural safety protection function;

c) Whether the installation environment, location and space of the pharmaceutical machinery (equipment) meet the cleaning and sterilization requirements;

d) whether the process piping meets the cleaning and sterilization process requirements;

e) rationality of the interface between the cleaning and sterilization media and the drain port;

f) Whether the sampling position or sampling point is reasonable, whether there is a graphic or list identification;

g) cleaning device compliance;

h) In-place cleaning and sterilization control procedures. Disassembly and assembly feasibility of the removable parts.

4.5.3.2 Implementation of structural verification. Observe, record and analyze inspections, collect inspection original records and inspection reports, and make structural design inspections Proof of conclusion.

4.5.4 Cleaning and Sterilization Verification (see Appendix B)

4.5.4.1 Verification should include the following.

a) Cleaning and sterilization verification is performed after the structural verification is passed;

b) after using the alternative medicine or the actual production of the medicine according to the pharmaceutical process, and then according to the cleaning and sterilization scheme under actual use conditions run;

c) Feasibility of cleaning and sterilization procedures, including cleaning and sterilizing medium name, type conformity, operational parameter feasibility; cleaning and sterilization Quality compliance;

d) conduct challenging tests where necessary;

e) control accuracy accuracy and safety protection functions;

f) effectiveness and reproducibility of cleaning and sterilization programs;

g) Test the conformity document of the instrument.

4.5.4.2 Cleaning and sterilization verification implementation. Collect test data and data analysis through test observation, recording, sampling and other means to prove Feasibility and stability of pharmaceutical machinery (equipment) cleaning and sterilization procedures. Determine the effectiveness and reproducibility of cleaning and sterilization results.

4.5.5 Plastic ampoules bottle filling and sealing machine in place cleaning and sterilization verification example

See Appendix C.

A.4 Purpose

It is designed to review whether the structural design of the cleaning system complies with the "Good Manufacturing Practices (2010 Revision)" and GB/T 36030-2018. And pharmaceutical machinery (equipment) product standards.

A.6 Implementation standards and specifications

A.6.1 "Good Manufacturing Practices for Pharmaceutical Production (Revised in 2010)" (Ministry of Health of the People's Republic of China).

A.6.2 "Pharmacopoeia of the People's Republic of China (2015 Edition)" (National Pharmacopoeia Commission).

A.6.3 GB/T 36030-2018 "General technical requirements for cleaning and sterilization of pharmaceutical machinery (equipment) in place".

A.6.4 GB 5226.1-2008 "Mechanical electrical safety machinery and electrical equipment - Part 1. General technical conditions".

A.6.5 JB/T 20158-2013 "Pharmaceutical equipment in place cleaning device".

A.6.6 In-place cleaning and sterilization of pharmaceutical machinery (equipment) product standards, should indicate the standard number and standard name.

A.8 Cleaning system structure verification

A.8.1 Structure verification

The main purpose of the verification is to confirm the design, manufacture and installation of the cleaning and sterilization of pharmaceutical machinery (equipment) in accordance with GB/T 36030-2018 or the feasibility of the user's request for operation, the verification content is as follows (see Table A.6).

A.8.2 Functional verification

The main purpose of the verification is to confirm the design function of the pharmaceutical machinery (equipment) to achieve cleaning and sterilization according to GB/T 36030-2018 or users. The feasibility of the operation is required, and the verification contents are as follows (see Table A.7).

A.8.3 Cleaning device verification

The main purpose of the verification is to confirm the function of the cleaning device for cleaning and sterilizing the pharmaceutical machinery (equipment) according to GB/T 36030-2018 or The feasibility of the user's request for operation is as follows (see Table A.8).