On the Proposed Deletion of the EP Monograph for Highly Purified Water
Background
The European Pharmacopeia (EP) Commission recently announced the planned suppression of the monograph for water, highly purified (1927). The notification, which can be found here, was a published summary of the outcome of the 160th Session of the EP Commission dated April 5, 2018. The change is expected to be promulgated with EP 9.7 which has a planned adoption date of April 1, 2019.
Reasoning for the elimination of the #EPHighlyPurifiedWater Monograph was based on the premise that the recent modification to the EP Water for Injections (WFI) monograph made the two classifications redundant.
The EP Highly Purified Water monograph was adopted in 2002 and was often misunderstood in the pharmaceutical water industry. United States Pharmacopeia (USP) does not, nor has it ever had, a monograph for highly purified water. At the time, the formation of the EP HPW monograph appeared to be counterproductive to the efforts to harmonize global pharmacopeia water standards. It was based on the premise that reverse osmosis (RO) and other technologies lacked the “robustness” of distillation. While there is certainly merit to this claim, the argument surfaced that limiting production of WFI to a single process curtailed new technology and innovation in the pharmaceutical water industry.
HPW Applications
Over the last seventeen years, the actual number of systems validated as EP HPW Systems has been limited compared to Purified Water and WFI; likely the consequence of the fewer number of applications. Common applications for the use of EP HPW include:
Opthalmics
Inhalents
Nebulizers
Open wound topicals
Bulk intermediates for ultimate use in parenteral products
Other applications where product has indirect route to the blood stream
However, there are many validated pharmaceutical water systems that exist now or prior to the creation EP HPW monograph that had the exact or similar quality requirements as EP HPW. Most were classified as Purified Water with additional or tighter specifications or as non-compendial water systems. Among the designations used in the industry are:
Low Endotoxin Water
Endotoxin Reduced Water
Pyrogen Free Purified Water
Purified Water with Endotoxin Control
Water for Bulk Sterile Operations
These designations were commonly adopted since no USP monograph for HPW existed, and it would be a misnomer to classify them as #WFI since they were not used in parenteral applications. The justification to classify waters as non-compendial is that the monograph requirements represent the minimum requirements and that additional quality attributes should be assigned or tighter specifications adopted if it is warranted by the process. As such, non-compendial systems such as those listed above must be designed and commissioned in accordance with cGMPs and operated in a continuously validated state.
Existing HPW Systems
The European Directorate for the Quality of Medicines (EDQM) recently noted that the EP WFI and HPW monographs were redundant in terms of their quality requirements and production methods. Obviously, the application of the two is different as one is prescribed specifically for parenteral applications. Assuming the suppression of the EP HPW monograph is implemented, what is the fate of all of the existing validated HPW systems?
One possible solution would be to grandfather all of the existing EP HPW Systems so that they would not need to be revalidated or forced to update documentation or records. This is the most logical approach to deal with the existing, validated systems.
Another option would be for the EP Commission to maintain the current EP HPW Monograph and have two water classifications with the same quality and production requirements, but that are used for two distinct applications. This is less likely to occur in an industry desires pharmacopeial harmonization.
When the EP HPW Monograph is ultimately eliminated, future processes requiring water meeting the HPW standard could be classified as WFI or a suitable non-compendial. They certainly would not have to be classified as WFI. The most logical, non-compendial designation would be highly purified water (not to be confused with EP Highly Purified Water), although any of the others listed above would also be appropriate. It should be interesting to discuss the semantics of a name change as this plays out.