Issue link: https://www.e-digitaleditions.com/i/1517802
PharmTech.com Quality and Regulatory Sourcebook eBook March 2024 Pharmaceutical Technology ® 21 Aseptic MAnufActuring of the operator's body in a grade-A environment. In an aseptic compounding operation, the risks associ- ated with the aforesaid elements would mostly vary depending on the degree of human exposure to the aseptic operation. This is a function of the existence or lack of a physical barrier from the operator. There- fore, for the purpose of differentiating the risk level based on human exposure, three categories of risks are identified: • i nter vent ions i nvolv i ng exposed produc t or product contact surfaces without any physical separation of the operator in a Grade-A environ- ment, or presence of the operator or a portion of his body parts in such an environment are deemed a greater risk concern • interventions involving closed/wrapped product or product contact surfaces without any physical separation of the operator in a Grade-A environ- ment, or presence of the operator or a portion of their body parts in such an environment are deemed a medium risk concern • interventions involving physical separation of product or product contact surfaces with the op- erator by means of a rigid barrier or glove ports are considered a lower risk concern. The example shown in this article involves an open RABS. However, the IREM model criteria would be true for a closed system as well, such as an isolator where inter ventions may be performed using de- contaminated but not sterilized fixed-port gloves. In these cases, the disruption of first air by a decontam- inated glove could also pose a relative risk. Operator skill/experience. Operator skill/experi- ence is a critical factor in manual aseptic processing. The risk associated with the manual processes var- ies with knowledge of aseptic techniques, familiar- ity with the specific standard operating procedures (SOPs), familiarity with equipment and tools used, ability to recognize potential contamination sources, etc. The amount of practice required to master such aseptic processing skills can vary depending on the individual, their level of experience, and the com- plexity of the interventions. Further, the amount of time it may take for operators to start forgetting the critical aspects of the last performed activity and re- quire retraining can vary depending on several fac- tors, including the complexity of the activities, the frequency of practice, and the individual's level of experience and proficiency. Although operator skills are difficult to measure, it can be proven by success- ful execution of the activities under a review. After a brainstorming session, the team decided to consider if the same product is manufactured by an operator for three to five times in past six months, then this could be a medium-risk scenario. Whereas, if the op- erator manufactured more than five batches in the past six months, then this would be considered low risk; and if the operator manufactured fewer than three similar batches in the past six months, then it would be considered a high-risk concern. The risk levels selected here are purely based on what the team felt in the given scenario in the com- pany with respect to the factors, such as complexity of the operation, general skill level of the employees, the detailing in the batch processing records, and the effectiveness of their trainings. The individual companies are encouraged to choose their own risk categorization based on their specific scenarios. Risk tool development. Similar to the first part of this article, a three-stage table was created to deter- mine intervention risk level. The use of two comple- mentary risk blocks allowed for a simple comparison of five risk factors and to narrow those down to the overall risk level of an intervention. The risk classifications are color coded in Tables I–VI [Click here to view tables]. Numerically, the risk classification number increases as the classification decreases. The assessment steps are as follow: • Step 1. Duration and complexit y risk factors were assessed to create risk class (A) (see Table II) [Click here to view Table II]. • Step 2. Proximit y and human exposure were assessed to arrive at risk class (B) (see Table III) [Click here to view Table III]. • Step 3. The two risk classes (A & B) were assessed for an initial risk categorization (see Table IV). [Click here to view Table IV]. • Step 4. The final intervention risk levels are de- termined by assessing the risk levels from Step 3 with the final risk factor Operators skill level/ Experience on this specific task, expressed as the number of occasions the operator executed same/similar product on that line for a given du- ration (see Table V). [Click here to view Table V]. • Step 5. Risk control/mitigation activities were then assigned based upon the risk evaluation output from step 4 (see Table VI). [Click here to view Table VI]. All factors were weighted equally (i.e., duration was noted to be no more important than complexity or proximity, etc.). This was the result of discussion by the team. They concluded that because the final outcome of this exercise is the relative risk of each in- tervention to others in a given aseptic processing line, unless there is evidence to support weighting one factor more than the others, all should be weighted equally. Further, because each risk factor explained in this article is independently contributing to the final relative risk level of any intervention, and the team did not intend to measure/quantif y the abso- lute risk of any intervention, a differential weightage was not necessary. If the team had concluded that one