Quality Risk Management: Putting GMP Controls First

Abstract

This paper concerns the need for improvement in the use of risk-based principles and tools when working to ensure that the manufacturing processes used to produce medicines, and their related equipment, are appropriate. Manufacturing processes need to be validated (or proven) to demonstrate that they can produce a medicine of the required quality. The items of equipment used in such processes need to be qualified, in order to prove that they are fit for their intended use. Quality risk management (QRM) tools can be used to support such qualification and validation activities, but their use should be science-based and subject to as little subjectivity and uncertainty as possible. When changes are proposed to manufacturing processes, equipment, or related activities, they also need careful evaluation to ensure that any risks present are managed effectively. This paper presents a practical approach to how QRM may be improved so that it better supports qualification, validation programs, and change control proposals in a more scientific way. This improved approach is based on the treatment of what are called good manufacturing process (GMP) controls during those QRM exercises. A GMP control can be considered to be any control that is put in place to assure product quality and regulatory compliance. This improved approach is also based on how the detectability of risks is assessed. This is important because when producing medicines, it is not always good practice to place a high reliance upon detection-type controls in the absence of an adequate level of assurance in the manufacturing process that leads to the finished medicine.

A failure mode and effect analysis (FMEA)-based approach for risk assessment of scientific processes in non-regulated research laboratories

“…For automotive manufacturing, technical risk analyses are a mandatory part for QMS certification IATF 16949 and the FMEA method is used as a living tool throughout the product/process realization process [26]. Moreover, Quality Risk Management became an integral part for manufacturing and pharmaceutical industry [27][28][29], where FMEA is also the preferable method [30,31]. Even though risk management is not formally required for non-regulated research, it began to capture the attention of researchers for the great possibility to identify and control errors and therefore increase research performance.…”

Manufacturing DTaP-based combination vaccines: industrial challenges around essential public health tools

“…As well as the Good Manufacturing Practices (GMP) and Quality Assurance requirements applicable to all biodrugs and more specifically to vaccines (15)(16)(17)(18)(19), there are numerous manufacturing and quality control specificities and challenges associated with these complex products (20-25, 101,102) compared to traditional pharma products (26) or even to some biological products such as humanized monoclonal antibodies obtained from recombinant technology (27) or ribonucleic acids (28).…”

Analysis of Industrial Practice of Drug Quality Risk Management in Russian Pharmaceutical Enterprises

“…Тем не менее, применение системы управления рисками вызывает у производителей затруднения [6][7][8][9][10]. Так, в базе писем-предупреждений FDA (Food and Drug Administration -Управление США по санитарному надзору за качеством пищевых продуктов и медикаментов) замечания к системе управления рисками встречаются достаточно часто 4 [11]. В реестре отклонений от надлежащей производственной практики Агентства по регулированию лекарственных средств и медицинской продукции Великобритании (MHRA UK) только в 2018 году 5 имеются 74 несоответствия по управлению рисками для качества, из них 54 (почти 73%) оценены как критические или существенные.…”

“…При этом, только в фармацевтической промышленности управление рисками для качества является обязательным элементом фармацевтической системы качества любого предприятия, предусмотренной надлежащей производственной деятельности (GMP) и входит в лицензионные требования 2 . Требования по надлежащему использованию управления рисками для качества лекарственных средств описаны в документах регуляторных органов многих стран, а также международных организаций [3][4][5]. Основополагающие принципы управления рисками для качества на российских фармацевтических предприятиях приведены в Правилах надлежащей про-…”

“…Правила надлежащей производственной практики Евразийского экономического союза, утвержденные Решением Совета Евразийской экономической комиссии от 3 ноября 2016 г. № 77 4. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters Доступно в интернет 30.09.2020 5 https://www.gov.uk/government/statistics/good-manufacturingpractice-inspection-deficiencies Доступно в интернет 30.09.2020…”