VALIDATION ONLINE BLOG.

Double Click on any word to have it defined

SUMMARY: The Food and Drug Administration (FDA) is withdrawing a direct final rule that it published in the Federal Register of December 4, 2007 (72 FR 68064), to amend certain regulations as the first phase of an incremental approach to modernize or clarify some of the current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, as well as harmonize some of the CGMP requirements with those of other foreign regulators and other FDA regulations. The comment period closed February 19, 2008. FDA is withdrawing the direct final rule because the agency received significant adverse comments.
FDA will consider the comments received under our usual procedures for notice and comment in connection with the notice of proposed rulemaking that was published in the Federal Register of December 4, 2007, as a companion to the direct final rule (72 FR 68113).

DATES: The direct final rule published at 72 FR 68064 on December 4, 2007, is withdrawn as of April 4, 2008.

Validation Online Blog News. If you have a piece of equipment that your risk assessment has decided requires validation in accordance with cGMP requirements. It is mandatory that if that validation status is altered in any way, then the equipment must be revalidated. You cannot pick and choose, you must follow through the requirements of your own risk assessment. However you can use this risk assessment to set the scope of validation required.

Anyone who thinks they can move computer equipment around with no regard to the new location, is a person of very limited experience and little or no engineering knowledge. Radio Frequency Interference (RFI) is a serious problem in industry, and all validated equipment installations must be verified as immune to RFI, emitted from other equipment, that may be used in the installation area (electric motors – intermittent electric supplies - mobile phones - hand held radio’s used by security/maintenance/contractors - local transmitters taxis/police/firemen).

Out of laterally hundreds of cases here is just two, for this Validation Online Blog;
On the final tests at Sizewell B nuclear power station, we found that as soon as you keyed one of the maintenance hand-held UHF radios, the carrier signal switched the main emergency battery bank to maximum charge, and tried to cook them. When all else has failed this battery bank is there solely, to close down the reactor safely. The charging system controls had to be completely redesigned.

Two years ago we attended Jesus College in Cambridge regarding data corruption in one of the labs. This corruption had been investigated by literally dozens of electrical companies. After listening to the history we decided to install electrical supply and gauss monitors throughout the lab. After a week the records were analysed – everyone was stunned by the findings. We went on to analyse all the rooms that were in use, then marked-up the building drawings and the room doors as to their suitability for computer use. 15% of the rooms were condemned. The regulators are well aware of these problems, subsequently, they do expect RFI studies to have been carried out on all validated electronic equipment installations, and this is not the only requirement they expect.

Positioning of the thermocouples in any temperature mapping exercise is down to judgment. A judgment that must be documented and justified.

In the case of an autoclave, heat is added in the form of pressurized wet steam, anything that can affect the distribution of the incoming steam, can affect uniformity of temperature. Conversely anything that can take heat away from the chamber can affect temperature uniformity.

Lets me say in this VALIDATION ONLINE BLOG, this stage if you want to be pedantic and put tc’s down the drain, the mapping exercise will probable fail. However you are there to verify that product will be sterilized, and product is never placed in the drain. Only the designated product containment area has to be verified.

If this is new installation then get hold of the FAT. In the FAT the chamber is subjected to detailed temperature transfer studies.

Even distribution of the in coming steam can be verified by placing a thermocouple sensor (tc) in each corner of the autoclave (8 tc’s).

Cooling due to heat loss will be maximum the further away you are from the steam inlet and the closer you are to metal that will conduct heat out of the chamber. That is usually, the door, or doors if double sided. If not double sided, then the end wall, and last but not least, the drain. The drain is a big source of heat loss. A tc should be placed as close to the drain, as product would be when the autoclave is in normal use. This gives us an additional 3 tc’s, bringing the total for a standard sized autoclave to 11 tc’s.

I have always considered this sufficient for 1.5 to 2.5 m3 autoclaves. Any bigger and I would concentrate on heat loses i.e. add tc’s to the top and bottom of the doors and or end wall.

It is most important to understand that it is impossible to validate an autoclave while using none validated steam.Your steam must be validated for – superheat – dryness – none condensable gases.

Make certain you do a pre and post mapping calibration, using instrumentation traceable to national standards.Happy mapping.