How to clean the pharmaceutical equipment validation

Drugs in the production process will form a residue on the equipment, equipment cleaning is to use one or a set of cleaning methods to remove the visible equipment Hangzhou Chuangtian Pharmaceutical Equipment Co., Ltd. and not see the residue and reach the acceptable residue limit, Avoid contamination and interspersed contamination. Clean validation is the choice of chemical experiments and other practices to prove the scientific cleanliness, usefulness, controllability, together with the verification should be completed in accordance with the verification of the establishment of the daytime pharmaceutical equipment to monitor regularly to ensure that the daily production process Usefulness.

Equipment cleaning means that under certain conditions, a Creatine or a set of cleaning methods to eradicate the visible and can not see the process of leaving the product components and reach the acceptable residue limits. Equipment cleaning validation is the process of recognizing the scientific, reasonable and legal (conforming to the cleaning code) draft of the proposed equipment cleanliness protocol.

1 cleaning procedures

1.1 cleaning methods

Process equipment cleaning, generally can be divided into two kinds of craft cleaning and active cleaning. The characteristic of the craft cleaning method is to clean the equipment mainly by the hand-held cleaning equipment. Before cleaning, the general requirement is to disassemble the equipment to a certain degree and transfer to a special cleaning place. The active cleaning is characterized by the initiative and special equipment, Clean process. Compared with the active cleaning, attention is better, but it is necessary to clean the area manually. If there is a difference between the cleaning methods in the production room and the methods used to replace the products, the two should be separated and discussed in the procedure, and the two procedures should be formulated separately if necessary. Similarly, if one approach to cleaning water-soluble residues and another approach to cleaning water-insoluble residues is to separate the two, and define the probable size of each cleaning solution.

1.2 detergent

Detergents should be useful to dissolve the residue, not to corrode the equipment, and should be easily eradicated, as harmless as possible to the environment, or be decontaminated. When cleaning should try to choose a simple composition, clean ingredients clean.

1.3 cleaning procedures

Procedures to detail the cleaning process and each process, each part of the number of cleaning, cleaning level,

1.4 cleaning cycle

Procedures should be rules and verify the longest between the two cleaning time. The longest time from the end of production to the beginning of cleaning, the longest continuous production, the cleaning equipment used for the next pre-production of the longest registration time to make rules.

1.5 cleaning staff and training

Cleaning personnel's ability to operate and its understanding of equipment and processes, work attitude and other crucial role in cleaning. Therefore, it is necessary to train the cleansing staff and make training records.

1.6 Other

For validated cleaning procedures, the key parameters for verification need to be clearly and clearly reflected in the procedure.

2 cleaning verification

Cleaning Validation is a validation of cleaning procedures that provide a scientific means of collecting enough data to demonstrate that equipment that is cleaned according to cleaning procedures consistently arrives at the booked cleaning code.

2.1 plan preparation stage

2.1.1 detergent verification

The verification of the cleaning agent generally includes the adaptability of the equipment and the cleaning agent, whether the sealing ring in the equipment and the pipeline absorbs the cleaning agent, eradicates the cleaning agent after the cleaning, and whether the requirement for defoaming is required. Under normal circumstances should try to use the existing certified cleaning agent.

2.1.2 Sampling and inspection

On the production equipment for a detailed investigation, concluded that a representative, difficult to clean the site as a sampling point. Sampling volume depends on the degree of messiness of the equipment, there are two common sampling methods: direct sampling method and elution sampling method. The direct sampling method is to directly sample the appearance of the equipment to determine whether the equipment is clean or not. The wiping method is a typical direct sampling method. The method can be used for sampling the insoluble material inside the equipment. However, the defect of the wiping method is that it is necessary to disassemble the equipment frequently Can touch the sampling site. Leaching sampling method for the appearance of the plot, can not touch or unpack the system, generally take the final analysis of a sample of eluent, but the law is not suitable for defects in the residue insoluble or piling up and equipment parts situation. So for the specific conditions of products and equipment, if necessary, should be considered together to assess the two sampling methods. Sampling process to be verified, after the recovery experiment to verify the sampling process recovery and reproducibility.

Cleaning verification should be given a detailed analysis of detection residues and contaminants, if necessary, verify the specificity and sensitivity of analysis methods.

2.1.3 Residual solvent limit specification

Organic solvents other than water may be used in the manufacture and cleaning of medicines. International Normative Coordination "residual solvent Raiders" rules: a solvent, two solvents can not be used as a cleaning agent, can not be avoided, the three solvents can be used as a cleaning agent, in the next batch of production allowed solvent residual concentration should not Over 0.5% of initial solvent concentration.

2.2 Verify the implementation of the plan

In accordance with the agreed verification plan to start the experiment, obtain data, evaluate the results, draw conclusions. If the verification shows that the cleaning program can not ensure that the cleaning of the equipment has reached the reservation specification, find the cause, modify the program and verify from scratch until the result is satisfactory. After the verification is completed, the verification statement shall include at least the following contents: ① The description of the implementation of the cleaning procedure, including the original cleaning operation record; ② The inspection result and its evaluation, together with the original inspection record and the laboratory statement; ③ The error explanation, And investigation; ④ verification results, as long as the results of their qualified and unqualified two, not ambiguous.

3 pharmaceutical equipment how to clean validation summary

Cleaning validation First of all, to be clear that the cleaning validation is for a particular product used in equipment cleaning procedures applicable to the product cleaning methods and procedures to verify, and secondly, when more than one product sharing equipment, the production of the product whether the residue into the next batch Another different product, and then affect the safety and effectiveness of another product. If more than one product uses some common equipment and is cleaned with the same cleaning program, representative products can be selected for cleaning verification on demand. Pharmaceutical companies can be based on the solubility of raw and auxiliary information products, activity, toxicity, stability and cleaning the use of detergents and other conditions to be analyzed and selected as the minimum residue of the material and calculate its safety indicators. A small number of organic residues and moisture can promote the growth of microorganisms may occur after a period of time before the product detrimental to degradation products, and therefore, should also be at the right moment after the monitoring of the role of cleaning validation to determine the cleanliness after cleaning can be maintained Long time. The minimum remnant of pharmaceutical equipment specification refers to the status of the effect, quality and safety of the residues (including microorganisms) in the cleaned equipment does not affect the rules of the next batch of products. Due to the fact that there is no uniform rule for the minimum residue standards, enterprises can use the two methods of cleaning and elution methods to verify the more widely used methods. Based on the nature of the products and the actual conditions of production equipment, enterprises can draw up a scientific and rational Achieve and can go through the appropriate measures to check the limits of norms.

In the end, the pharmaceutical products will remain on the equipment during the production process. The cleaning of pharmaceutical equipment is an important measure to ensure the safety of the medicines. The equipment cleaning is to remove the visible and invisible residues on the equipment by one or a set of cleaning methods Reach acceptable residual limits to avoid contamination and interspersed contamination. Cleaning verification is the choice of chemical experiments and other practices to prove the scientific cleanliness, usefulness, controllability, together with the verification should be set according to the analysis method of regular monitoring to ensure the routine production of the usefulness of the process.



Author: A day in Hangzhou Pharmaceutical Equipment Co., Ltd.
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