Validation Online Blog.

21 CFR Part 820 and 211 together detail numerous predicate rules that are mandatory for all companies who require to be compliant with FDA applicable rules and regulations for manufactures or processors of drugs and other regulated products.

When a company decides to use electronic means to store, access or retrieve these records, then a requirement for the system to be 21 CFR Part 11 compliant arises. Part 11 compliance is achieved through software functionality and documented procedures in how to use the functionality.

The access to the controlled data is by the use of a user ID, and a password, however when the user has access, and then is called away, how long will the terminal remain active in the un-used state.

The regulators insist that you have a written justification for the duration of this period of time. If you set a random time of five minutes, the regulator might consider that is to long for all the terminals to remain active and unmanned, when the fire alarm goes off (your would-be offender might know it is just fire drill). If you set a time of one minutes, then you end up with an office of people wasting time, by having to continually log back into the system.

This small compact item plugs straight into your USB port and once set up (a simple and quick process) allows you to log into the system with a flick of your finger. You can satisfy the regulators without increasing your staffs work load. Brilliant.

Failure Mode Evaluation & Analysis for Bio-Med.

Validation Online has taken the difficulty out of using a Fault Mode Evaluation & Analysis (FMEA) as a method of analysing risk. All the risk assessment tables are included and referenced and the analysis flow chart is ready to go. All ambiguities and obscurities have been designed out and the tool can be used by first timers with the greatest of ease.

Try it, and find out just how good an FMEA can be at assisting you to anticipate problems and then pre-empt them. This FMEA carries our usual warranty; so if you find it unfit for purpose, your purchase costs will be refunded in full.

Once you start using this method of measuring risk, you really will wonder how you managed before. Regulatory agencies world wide now require documented evidence that processes and techniques have been subjected some form of risk analysis.

Risk assessment is a much discussed subject. Now, in retrospect when you look back over some of the problems we had in the past, you realise that had a Failure Mode and Effect Analysis been carried out prior to accepting the functionality of some process equipment, we could have avoided much heart ache and cost.

Please click here and read the summary of why the FMEA and the VRA are both essential to your validation task.

Please Click here to Purchase FMEA for BIO-Med.

REVALIDATION SCHEDULED

As long as the process operates in a state of control and no changes have been made to the process or output product, the process does not have to be revalidated. Whether the process is operating in a state of control is determined by analyzing day-to-day process control data and any finished device testing data for conformance with specifications and for variability.

REVALIDATION on RELOCATION

When equipment is moved to a new location, installation and operation should be requalified. By comparing data from the original installation and operation qualification (IQ and OQ) and the requalification, the manufacturer can determine whether there have been any changes in equipment performance as a result of the move. Changes in equipment performance should be evaluated to determine whether it is necessary to revalidate the process.

REVALIDATION JUSTIFICATION

Part 820.75 of the QS regulation requires that vaIidated processes be monitored and controlled so that when changes or process deviations occur, a manufacturer will know to review and evaluate the process and perform revalidation when appropriate. 21 CFR 820.75(c ) requires you to have documented procedures in place for evaluating; when revalidation is required.

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.

GAMP 5.

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Unethical or Crooks.

cGMP Defiant or Ignorant

Do You Have to re-validate a computer, just because you have relocated it?

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).

This is a mandatory requirement.

Out of literally hundreds of cases, here are 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.

Temperature Mapping Autoclave and Others

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.

Design Qualification is both an emerging regulatory requirement and a tool for project success. If structured and executed properly, it can help assure the design is robust and complete, giving the project team and QA reviewers a high degree of confidence that every requirement has been factored into the design. - VALIDATION ONLINE BLOG - Finally, DQ cannot be performed without first formally defining requirements. Meeting requirements is the ultimate objective of the project; verifying requirements have been met is the role of qualification. Remember you read this first in the Validation Online Blog.

VALIDATION ONLINE BLOG.