Nowadays there are more and more pharmaceutical corporations producing highly active medicine, it's very normal to see that the utilization of airtight equipment in the production process of highly active productions. However many companies are still confused about the airtight performance test of this type of equipment and how to conduct the risk assessment of the test process. Therefore, this article will pay attention to the introduction of how to conduct airtight performance test and risk assessment of airtight equipment used in the production process of highly active medicine. Hoping relevant pharmaceutical corporations can be enlightened from it, and making the production and verification of highly active drugs more standardized and scientific
1. Visão Geral
In this article, "highly active drugs" refers to the general term for drugs with high activity, high toxicity, high allergenicity, and high risk.
O artigo 28 da BPF chinesa de 2010 mencionava que o trabalhador da área de operação de alto risco (por exemplo: a área de produção de alta atividade, alta toxicidade, alta infectividade, materiais de alta alergenicidade) deve ser aceito em treinamento especializado; o artigo 46 mencionava que a produção de medicamentos com propriedades especiais, como medicamentos altamente alergênicos (como penicilinas) ou produtos biológicos (como BCG ou outros medicamentos preparados com microrganismos ativos), deve utilizar plantas, instalações e equipamentos de produção dedicados e independentes . Este é um requisito especial para esta classe de medicamentos.
De acordo com os requisitos da China GMP, o escopo e a extensão da confirmação ou verificação devem ser determinados pela avaliação de risco. O teste de desempenho hermético do equipamento hermético utilizado na produção de medicamentos altamente ativos também requer uma avaliação de risco.
2. The elements may influence the equipment's airtight performance
2.1 Pessoal
Se os funcionários foram treinados e têm experiência relevante. E cuidado do pessoal durante a operação, a amplitude de movimentos, etc. tudo pode afetar os resultados do teste de desempenho hermético do equipamento.
2.2 Equipamento
It's very important for the choose of test instrument. For air sampling, the flow rate of sampling pump is usually set at 2 L/M, and the sampling pump is calibrated with a calibrated flow meter. In addition, sampling pump need to be calibrated before and after test to ensure sampling pump does not change a lot in the test process. The air flow rate is very important, and the relevant information of the pre-calibration and post-calibration should be recorded.
Para amostragem de superfície, os swabs de amostragem não devem soltar impurezas, não devem reagir quimicamente com a substância a ser testada, devem ser fáceis de eluir, armazenar e usar.
2.3 Materiais
In suitable circumstance, the particle airtight performance test of the equipment can use substitute materials instead of actual materials. Test data completed with substitute materials can be used to predict similar operating conditions for actual materials. In some circumstances, using substitute materials may be necessary. For example, actual materials' chemical analysis method is not insensitive, or medicine ingredients are very expensive or medicine components are dangerous. Actual operation may have many kinds of substitute materials can be selected. However its chemical, physical properties and powder characteristics should be considered comprehensively, and should be close to the properties of the actual material.
2.4 Método
Os métodos de amostragem geralmente são amostragem de ar e amostragem de superfície.
Air sampling of personnel usually places the sampling head in the breathing area of the personnel(mouth, nose), this can simulate the total amount of inhalable particles. When sampling in operator breathing area, sampling equipment can't disturb the normal operation of operator. Breathing area sampling is recognized as the sampling method which closest to the actual impact on the operator, because this method considers some relevant elements about operator's activities and actions.
Surface sampling(swab sampling or wipe sampling) also can be used to ensure the equipment airtight property whether meet the requirement. Surface sampling can't adopt the methods of air sampling, such as surface's particulate matter, operators' clothes, or operators' hand/glove.
Comparing with air sampling, the execution of surface sampling should use validated methods and need to consider recovery rate of substitute from specific surface to solvent. The sampling area is specific 100c㎡(10cm10cm), but for the special requirements of geometric or contaminated equipment, in this case, take a specific area.
2.5 Ambiente
O teste de desempenho hermético de partículas de equipamentos herméticos precisa considerar a influência do ambiente de teste para o resultado do teste.
Durante o teste, precisamos registrar e pensar em fatores básicos do ambiente de teste, incluindo qualidade do ar, temperatura, umidade, mudanças de ar e outros fatores.
2.6 Medição
Entrando nas fases de medição após a amostragem com instrumento de amostragem, o processo de medição precisa considerar os erros que podem ser causados pelo processo de análise, o instrumento de teste para análise de amostra precisa garantir seu desempenho estável e confiável. Precisando de um instrumento impecável de procedimentos operacionais para orientar o trabalho relacionado ao pessoal.
2.7 A análise de risco de equipamentos herméticos também deve considerar os seguintes fatores
● Considering any influence for the accuracy of test result of any activities now and before. For example, the presence of contamination residues may affect the results of sample analysis;
● If you want to compare the airtight performance of different sealing equipment, you should concern the change of any system related to sealing equipment, near system or support system. Because these changes may influence the airtight ability of sealing equipment, such as change of air flow in air conditioning system, change of standard operating procedure (SOP), change of equipment itself, and change of sampling equipment;
● If an activity has a potentially significant risk to the accuracy of the test results, remedial measures should be taken to reduce or eliminate the impact;
● Text details should be detailed record;
● If video or photography has no influence to the product or environment, it is a valid method to provide sit recording.
3. Conclusão
The airtight environment required for highly active drugs in the pharmaceutical production process is guaranteed by sealed equipment, equipment also forms the first protective screen for staff. If the airtight performance of the equipment does not meet the requirement, not only the drug's quality will be damaged, but also the operator's health will be influence a lot. Therefor, how to ensure the airtight ability of sealing equipment is a great important question for pharmaceutical companies which produce highly active medicine. This article provides guidance or suggestions for the risk research of equipment airtight capabilities of related enterprises from the perspective of how to identify risks and possible risk points of sealing equipment, in order to bring certain help.