On 10 August 2004, EMEA published Annex 2 to the Note for Guidance on Process Validation. This annex is planned to come into force in January 2005.

The new annex, which comprises not more than 3 pages, can only be read together with the main document, the Note for Guidance on Process Validation (CPMP/QWP/848/96 or EMEA/CVPM/598/99), which came into operation in September 2001. The Note for Guidance had been created in order to define in which cases information on process validation has to be handed in together with the dossier for a marketing authorisation. Apart from that, it specifies the range of data that have to be provided. Both the relevant directives (Annex I to Directive 2003/63/EC and Directive 2001/82/EC) and the above-mentioned Note for Guidance on Process Validation refer to "non-standard methods of manufacture." The new Annex 2 now regulates the validation of non-standard processes and defines which processes are to be subsumed under the term "non-standard methods of manufacture."

In the definition of "non-standard processes" the text gives examples where "production scale validation data" have to be handed in as early as during marketing authorisation or - as the original text states not quite clearly - "might need to be provided" during this phase.

When looking at these examples, one is surprised how many processes are considered to be non-standard. On the whole, 4 criteria are mentioned:

1. The manufacture of specialised pharmaceutical dose form
2. The incorporation of some new technology into a conventional process
3. (Highly) Specialised processes involving new technologies or an established process known, or likely, to be complex and therefore to require particular care
4. Non-standard methods of sterilisation

Annex 2 gives lyophilisation as an example for item 3 and aseptic processing as well as parametric release for item 4. Also the further points mentioned in the text lead to the fact that a number of methods are classified as "non-standard processes" and therefore production scale validation data have to be provided at the time of submission. 
  

 
You can download Annex 2 to the Note for Guidance on Process Validation if you click here.

Please click here if you would like to download the main document of 1 March 2001.