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Publicação
Qualificação da Inspeção Visual para Validação da Limpeza na Indústria Farmacêutica
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Resumo(s)
A inspeção visual tem sido amplamente utilizada pela indústria farmacêutica após a
limpeza para libertar equipamentos ou dispositivo, uma vez que é uma etapa crítica para con-
firmar a eficácia do processo de limpeza. As propostas para o seu uso como método analítico
para validação da limpeza têm aumentado nos últimos anos.
Neste sentido, este estudo tem como objetivo desenvolver um protocolo para a qualifi-
cação dos operadores na inspeção visual da limpeza de equipamento no Departamento de
Líquidos da Hikma Farmacêutica S.A., bem como discutir o seu uso como critério na validação
da limpeza.
Para tal, determinou-se os limites de limpeza dos produtos de base oleosa, onde foi ne-
cessário calcular o Maximum Allowable Carryover (MAC) com base no Acceptable Daily Exposure
(ADE) e determinar os produtos pior-caso. Posteriormente, elaborou-se um protocolo para a
qualificação da inspeção visual onde os produtos pior-caso determinados anteriormente, fo-
ram depositados aleatoriamente num único ponto de cada coupon através de uma micropipeta
e deixou-se secar ao ar durante um período de 72h. Foi ainda realizada uma análise de risco
do tipo Failure Mode and Effect Analysis (FMEA) às qualificações da inspeção visual do equipa-
mento, onde foram identificados os modos de falha e foram sugeridas melhorias.
Foi concluído que para o produto 5 e para o agente de limpeza, todos os operadores se
conseguiram qualificar sendo o Visual Residue Limit (VRL) de 61 μg/25cm2 e de 5 μg/25cm2,
respetivamente. Para o produto 7, apenas cerca de 84% dos operadores conseguiram qualifi-
car-se na inspeção visual não tendo sendo possível determinar o VRL.
Para ambos os produtos que foi possível determinar o seu VRL, a avaliação da detetabi-
lidade demonstrou que os limites de deteção se situam apenas a uma ordem de grandeza de
0,3 abaixo do limite de aceitação de limpeza estabelecido, concluindo-se que não será prudente
utilizar a inspeção visual como método exclusivo da validação de limpeza, podendo induzir a
problemas graves como a contaminação cruzada.
Visual inspection has been widely used by the pharmaceutical industry after cleaning to release equipment or devices, as it is a critical step in confirming the effectiveness of the cleaning process. Proposals for its use as an analytical method for cleaning validation have increased in recent years. In the same way, this work aims to develop a protocol for operator qualification in visual inspection of cleaned equipment in the Liquid Department of Hikma Pharmaceutical S.A. It also discusses its use as a criterion in cleaning validation. To achieve this, the cleanliness limits of oily base products were determined, where it was necessary to calculate the Maximum Allowable Carryover (MAC) based on Acceptable Daily Exposure (ADE) and identify the worst-case products. Subsequently, a protocol for the qualification of visual inspection was developed, where the previously determined worst-case products were randomly deposited at a single point on each coupon using a micropipette and allowed to air dry for a period of 72 hours. A Failure Mode and Effects Analysis (FMEA) was also performed on the equipment visual inspection qualifications, identifying failure modes and suggesting improvements. It was concluded that for product 5 and the cleaning agent, all operators were able to qualify, with a Visual Residue Limit (VRL) of 61 μg/25cm2 and 5 μg/25cm2, respectively. For product 7, only about 84% of operators were able to qualify in visual inspection, and it was not possible to determine the VRL. For both products were the VRL could be determined, the detectability assessment showed that the detection limits were only 0,3 order of magnitude lower than the established cleaning acceptance limit. It was concluded that relying solely on visual inspection as the ex- clusive method for cleaning validation would not be prudent, as it could lead to serious issues such as cross-contamination.
Visual inspection has been widely used by the pharmaceutical industry after cleaning to release equipment or devices, as it is a critical step in confirming the effectiveness of the cleaning process. Proposals for its use as an analytical method for cleaning validation have increased in recent years. In the same way, this work aims to develop a protocol for operator qualification in visual inspection of cleaned equipment in the Liquid Department of Hikma Pharmaceutical S.A. It also discusses its use as a criterion in cleaning validation. To achieve this, the cleanliness limits of oily base products were determined, where it was necessary to calculate the Maximum Allowable Carryover (MAC) based on Acceptable Daily Exposure (ADE) and identify the worst-case products. Subsequently, a protocol for the qualification of visual inspection was developed, where the previously determined worst-case products were randomly deposited at a single point on each coupon using a micropipette and allowed to air dry for a period of 72 hours. A Failure Mode and Effects Analysis (FMEA) was also performed on the equipment visual inspection qualifications, identifying failure modes and suggesting improvements. It was concluded that for product 5 and the cleaning agent, all operators were able to qualify, with a Visual Residue Limit (VRL) of 61 μg/25cm2 and 5 μg/25cm2, respectively. For product 7, only about 84% of operators were able to qualify in visual inspection, and it was not possible to determine the VRL. For both products were the VRL could be determined, the detectability assessment showed that the detection limits were only 0,3 order of magnitude lower than the established cleaning acceptance limit. It was concluded that relying solely on visual inspection as the ex- clusive method for cleaning validation would not be prudent, as it could lead to serious issues such as cross-contamination.
Descrição
Palavras-chave
Limpeza Contaminação-Cruzada Inspeção Visual Qualificação VRL FMEA