Annex 1 Capping Environments – A Pleasant Surprise?
After my recent three part blog on the PIC/S interpretation of Annex 1, I’ve had reason to revisit the recommendation at some length. During this process I had a moment of clarity regarding capping environments that had escaped me previously.
Section 120 of the Annex states that capping can be performed as either an aseptic process, or as a clean process outside the aseptic core. However, if uncapped vials are to be removed from the aseptic core, the Annex specifies that a “Grade A air supply” must be maintained until the vials are capped.
While the original intention for this section undoubtedly was in consideration of transfer tunnels and similar apparatus which connect the aseptic core to a separate capping area, it starts to become ambiguous when applied to transfer by hand or on open conveyers.
Remarkably, the Annex provides no definition of “Grade A” air supply, making the interpretation even more difficult. Thankfully, the revision of the PIC/S interpretation (PI032-2), defines a Grade A air supply as:
“a supply of air which is HEPA filtered, and at the point of supply meets when tested, the non-viable particulate requirements of a grade A area, as defined in paragraph 4 of the revised Annex 1.”
Additionally, it provides qualification and monitoring requirements for such areas:
· Qualified “at-rest” only. No requirement for “in-operation” qualification
· Qualification requires non-viable counts only
· Particle counts to be conducted “at the point of supply of the filtered air”
· Unidirectional (laminar) air flow is not required, but smoke tests should demonstrate absence of air entrainment from surrounds
· Air velocity limits should be justified (but don’t need to meet Grade A conditions)
· Monitoring for both viable and non-viables should be defined through risk assessment.
The wording of the interpretation refers to transfer tunnels, and it is clear that most, if not all of the thinking for this subject has focussed on this type of arrangement.
So that still leaves the issue “what does this requirement mean for (for example) a small company who transfers fully stoppered vials from an aseptic filling station to a “clean” capping station manually?
Well, on review, it turns out that Grade A air supply is perhaps not as big an issue as it may have seemed. Applying the definition and qualification requirements, it seems clear that any well designed Grade B zone (and probably most Grade C zones) will meet the requirements of a Grade A air supply! Remember, Grade B non-viables limits at rest are almost identical to Grade A.
So don’t panic, you may not need to spend thousands of dollars upgrading air systems after all. Having said that, there are still two significant implications which manufacturers need to consider.
· Have you fully validated your stoppering process so that you can be confident that 100% of your vials are fully stoppered? If you cannot be certain that every vial coming out of your aseptic area is fully stoppered, you are likely to require not only grade A air supply, but fully Grade A and aseptic conditions until the completion of crimping.
· And whatever your transfer process, you need to be able to prove that it does not pose additional risk to your products, so the method of transfer will come into question just as much as the environment in which it is conducted.
Now, transferring a tray full of stoppered vials through a Grade B area from filling to capping; that seems like an excellent candidate for Grade B continuous monitoring … but that’s another blog!
Add comment February 4th, 2010