ISPE recently issued the third edition of the Oral Solid Dosage Baseline guide. The guide was revised over a period of time to provide more clarity and definition to the manufacture of Oral Solid Dosage (OSD) Products. Within the body of the guide is a section which provides definition on the risks associated with the manufacturing of OSD products, whether they are tablets, capsules, creams ointments or any of the other varied products which fall under the OSD framework.
There is a significant difference between the manufacturing of OSD products and Aseptic products. Aseptic products are injected directly into the bloodstream, requiring a significantly higher level of cleanliness and sterility in the manufacturing process. OSD products are ingested or directly applied to the skin. The OSD products work through your bodies processes before they can impact your systems, taking an indirect path, as opposed to Aseptic product which takes a direct path.
The baseline guide developed and updated a description of the risk levels that are associated with the manufacturing of OSD products. The levels of risk are focused on maintaining product quality and operator protection. A detailed risk assessment with a risk mitigation plan is critical in assigning the risk level associated with the manufacturing of OSD products.
There are four risk levels described in the OSD guide:
- High(level 3, White, Primary): Open and exposed product, with the purpose of protecting the product, quality
- Medium (Level 2, Grey, Secondary): Process and product is closed, however, there is an opportunity for accidental exposure and cross contamination, with the purpose of controlling the mitigation of product.
- Low (Level 1, Black, Tertiary) Minimal risk of product contact, to provide control and accountability of product.
- Spaces outside of cGMP manufacturing area, the purpose is to support manufacturing.
It is critical to understand that these risk levels are different than the classification descriptions that are associated with Aseptic processing, and should not be compared or associated with those descriptions. The baseline guide suggests that the High, primary zones of an OSD facility meet the ISO 8 “at rest” requirements. There are some countries, primarily China and Mexico, which are moving towards a Grade D, instead of ISO 8, requirement for their High, primary spaces. The complication in moving towards a Grade D classification is the additional burden of managing microbial counts, increasing overall costs for your facility.
In a multi-product OSD facility, there are several opportunities to manage the levels of risk in the facility. They all incur some investment of cost whether they are operating costs, equipment costs, facility costs or consumable costs. The more closed the operation is, though the use of additional equipment cost, minimizes the risk to personnel and product. The use of air locking with pressurization is an additional facility and operating cost that will help manage the risk of cross-contamination.
(Source: IPS – Integrated Project Services, LLC)
