EMEA Guideline on Water for Pharmaceutical Use Revised

EMEAGuideline on Water for Pharmaceutical Use Revised

 
At the beginning of 2001, the draft of the "Note for guidance onquality of water for pharmaceutical use" was published so that theindustry could comment on it (see GMPNews of 2 July 2001). The revised draft was adopted by CPMP/CVMPin November (GMPNews of 8 January 2002) and came into operation on 1 June 2002.

Upon requests on the part of the industry, some changes were made tothe tables 3 and 5 (marked in orange) even after the adoption byCPMP/CVMP.

In table 3, regarding the manufacture of non-sterile APIs that are intended for use in asterileparenteral product, the requirement of 'highly purified water' wasreplaced by 'purified water with an endotoxin limit of 0,25 EU/ml andcontrol of specified organisms'.

In table 5 titled 'Water Used for Cleaning/Rinsing', some modificationswere made in connection with sterile products. Now the CIP (Cleaning inPlace) procedure is also listed. For the initial rinse, only the waterquality 'purified water' is now required; higher qualities are notmandatory any more.

For the final rinse of sterile parenteral products, the water qualityWFI is still required. However, the water quality 'highly purified water'can be used in case a subsequent depyrogenisation step is applied and theuse of 'highly purified water' is justified through validation data.

Water Present as an Excipient in the FinalFormulation

Table 1: Sterile Medicinal Products

Table 2: Non-sterile Medicinal Products

*In certain disease states e.g. Cystic fibrosis, medicinal productsadministrated by nebulisation are required to be sterile andnon-pyrogenic. In such cases WFI or sterilised HPW should be used.

** For some products such as veterinary teat dips it may be acceptableto use potable water where justified and authorised taking accountof the variability in chemical composition and microbiological quality

Water Used During Manufacture of APIs andMedicinal Products 
Excluding Water Present as an Excipient in the Final Formulation

Table 3: Water Used During the Manufacture of APIs (Revised)

* Purified Water should be used where there are technical requirementsfor greater chemical purity.

** The Applicant would need to demonstrate that potential variations inthe water quality, particularly with respect to minimal composition, wouldnot influence the composition of the extract

Table 4: Water Used During Manufacture of Medicinal Products Which IsNot Present in the Final Formulation (Revised)

* For some veterinary premix products e.g. Granulated concentrates itmay be acceptable to use potable water where justified and authorisedtaking account of the variability in chemical composition andmicrobiological quality

Table 5: Water Used for Cleaning/Rinsing of Equipment, Containers andClosures (Revised)

In general, the final rinse used for equipment, containers/closuresshould use the same quality of water as used in the final stage ofmanufacture of the API or used as an excipient in a medicinal product.

* CIP = Cleaning in Place

** Some containers, e.g. Plastic containers for eyedrops may not needan initial rinse, indeed this may be counter-productive since particulatescounts could be increased as a result. In some cases e.g. Blow-fill-sealprocesses rinsing cannot be applied

*** If equipment is dried after rinsing with 70% alcohol, the alcoholshould be diluted in water of the same quality as the water used for thefinal rinse
 

**** Where a subsequent depyrogenisation step is employed the use ofHighly Purified Water may be acceptable subject to suitable justificationand validation data

 
Author:
Dr Andreas Mangel
CONCEPT HEIDELBERG