cGMP FDA 483 COMMENTS
The cGMP FDA 483, Comments, are a bit disjointed, however they are judged to be of great importance and have generally come from FDA 483's, cGMP's or company audit reviews. If you have an interesting snag or cured an interesting and difficult problem, how about sharing it with your peers. Some of the problems listed below cost companies million of dollars to find and rectify. You could be the white knight. We will follow you wishes and publish your input with or without atribution, exactly as you instruct. Cick on the link below and let us have details. cGMP FDA 483 inspection No. 113, Comments, cGMP FDA 483 inspection. Biometrics and Computer Security Is biometrics the answer for computer log-on and or server room security? The subject has often been raised by clients. My take has always been, when they steal your password you have the option to change it, if they steal your biometrics !! So it was with interest I watch a (Discovery Channel) program, in which they attempted to fool an expensive complex biometric lock. The makers claimed the lock had never been beaten and that it was foolproof, since it: a) Mapped your fingerprint pattern. b) Measure your skin temperature. c) Measured your skin resistance. d) Measured your pulse. That looks pretty convincing, until you consider b, c & d, are variables. They vary all the time, so the lock can only be sensing if they are present, not what value they are. You could therefore be reasonably safe in assuming that any normal human finger is going to satisfy these requirements. After many complex efforts at transferring someone else’s fingerprint, they obtained a finger print quite conventionally, from a glass sheet (could be window / door / machine part), enhanced it with the normal dusting powder, photographed it and printed out the photograph onto standard office paper. They then trimmed, neatly, around the finger pad area and glued this photocopy of the authorized persons finger print, onto their own index finger pad. This is really low tech stuff, but it opened the door every time. Now, would you like to be the person who had just convinced management to installed hundreds of expensive, high security biometric locks. cGMP FDA 483 inspection No. 112, Comments, cGMP FDA 483 inspection. Cold Chain Insurance Two words that are beginning to have a lot of significance. Clinics around the world are now reading about vaccines that were damaged during storage by being stored in faulty refrigerators. Now the regulators are demanding temperature history documentation for vaccines and other temperature sensitive drugs, from manufacture to use. The regulations are there for all to review, so do not be surprised when you are asked to produce them. In the UK thousands of people are being re-injected to try and ensure protection. What will happen when a protected person becomes infected by the very infection they are supposed to be protected from? Who will carry the can, who can prove that they are not the weak link in the cold chain. cGMP FDA 483 inspection No. 111, Comments, cGMP FDA 483 inspection. US 500 million in Fines. Just when people are relaxing, thinking regulatory pressures are easing, old sores are highlighted again. Question are being ask about improvements since the acticle below was published, and no improvements can be found. Expect new pressures from the legislators to the regulators. In September 2003, The Wall Street Journal published an article informing all that pharmaceutical “manufacturing techniques lag behind those of potato-chip and laundry-soap makers.” The same article correlated the rise in recalls with quality problems and noted that despite fines in excess of US$500 million for manufacturing failures, acceptable levels of quality were not being achieved. cGMP FDA 483 inspection No. 110, Comments, cGMP FDA 483 inspection. Serious Product Contamination. The normal requirement in designing equipment installation is that all powered valves must fail into a safe condition. So with a loss of power (pneumatic or electric) a : -
cGMP FDA 483 inspection No. 109, Comments, cGMP FDA 483 inspection. 21 CFR Part 11, applies to electronic records and signatures. If we consider the records aspect, then 21 CFR Part 11 does not apply to electronic raw data, this is not considered to be a record. If data is held in a none editable format, Part 11 does not apply. Once the data is stored in any format that can be accessed, it must be protected against illegal access and must be compliant with Part 11, to prevent adulteration. A Validation Risk Asseement (VRA) must be carried out to ascertain the regulatory requirements of the data. The VRA outcome must determine the level and scope of validation required, for the raw data generation and handling equipment, and the data record keeping equipment. cGMP FDA 483 inspection No. 108, Comments, cGMP FDA 483 inspection. Ensure you have a plant maintenance schedule and all critical plant equipment is listed. Ensure their maintenance frequency is documented and justified, . cGMP FDA 483 inspection No. 107, Comment cGMP FDA 483 inspection. Ensure you have a plant calibration schedule and all critical instruments are listed. Ensure their calibration frequency is documented and justified. cGMP FDA 483 inspection No. 106, Comment cGMP FDA 483 inspection. Do not over validate; over validation is very expensive and may cost you your job or your reputation, or both. Do not under validate; under valuation could loose your company the right to produce its product(s). Use your risk assessment to justify the extent of your validation. Do not have multiple levels of validation, settle for what you can handle. Generally three levels;
cGMP FDA 483 inspection No. 105, Comment cGMP FDA 483 inspection. The overarching philosophy articulated in both the cGMP and in robust quality systems is: Quality must be built in to the product, the critical variable characteristics for all inputs must be adequately controlled, and, although clearly required by cGMP, representative sample testing alone cannot be relied on to guarantee product quality. cGMP FDA 483 inspection No. 104, Comment cGMP FDA 483 inspection. In the IQ and OQ, there are sections that call for descriptions of;
Remember that these are included purely to indicate to the regulator /reviewer / approver, where, in the manufacturing process the equipment is used, and what functionality is used (and hence must be qualified). You are not validating you’re descriptions. You validate the equipment against the official documentation package (engineering drawings, design specifications, URS, cGMP, VMP, VP etc). The system interface with utilities and other equipment must all be detailed in the VP. The IQ and OQ are directed purely at the equipment given in their title. The required description should be brief and preferably plagiarized from other official documents: - process description from process SOP. Equipment functionality from manufacturers / operators manual. cGMP FDA 483 inspection No. 103, Comment cGMP FDA 483 inspection. Watch your dates (regulators and reviewers are trained to). Start with your VMP and cascade down through the VP to IQ to OQ to P1Q to P2Q; make sure your dates for execution, review and completion approval, cascade. Make certain that all your supporting documents are approved and dated in accordance with requirements given in the VP. Double check on calibration certificates for equipment, utilities, facilities and all test equipment used, that they are in date, before allowing protocol execution to commence. All testing carried out using a sensor that does not have a current calibration certificate detailing that the standards used for calibration are traceable to national standards, will be considered adultered. Which means all subsequent testing is meaningless. Any product produced, would be deemed adultered, and use of it would be considered a serious violation of cgmp. cGMP FDA 483 inspection No. 102. During FDA and MHRA audits, regulators are asking for a written justification for the HEPA clean-filter pressure drop (PD). This clean-filter PD is added to the filter working range (supplied on filter certification) to calculate the change dirty-filter PD. Without calculating this clean-filter PD, you cannot know what the dirty-filter change PD is. In a non auto-compensating HEPA flow regime, a new filter, as it works, slowly clogs-up. This progressively reduces the airflow through the filter. This can resultant in insufficient air flow to protect staff and or the product, it can be dangerous for both, it also takes you out of the validated state. If you started with an actual flow that was only 70% of the rated flow, the filter would be seriously blocked before you reached the un-corrected dirty filter change PD. This would seriously compromise your room / equipment pressure regime, and could render your product as adultered. This is why regulators will ask for the filter clean DP justification. Have you have got this in place? It is most advisable to do so now by downloading this Method Statement. cGMP FDA 483 inspection No. 101. The client nearly always insists on reviewing and approving consultant prepared documents, prior to their use. These tasks are the most consistently under manned tasks in projects. After many project disputes about what were or are the actual choke points in project progress, we started to advocate that a simple progress plan was set out to display, to all, the time involved in this task. Use a planning tool such as Microsoft Project. Meet with the client or your peers, and jointly agree that the times allowed for the various tasks, is a time they can and will work to. Agree how often a document should be reviewed (is each person going to review concurrently, consecutively or is every one circulated and given a set time to return document with their comments), all commenting must be complete within a set number of reviews. The number of reviewers must be as low as possible, three being the acceptable limit. A small project may involve (just for discussion) 20 items requiring validation. That is, 20 (IQ's)(OQ's)(PQ's), that have to be authored, reviewed (once), approved for use, and reviewed for final approval. We now know the reviewers have to review, 60 documents 3 times. A total of 180 reviews, if we have 10 reviewers (an extreme, but has been so), that comes to a total of 1800 reviews. If each document lies on a reviewers desk for 4 days this could be 7200 days. Now allow for the documents that will get lost (miss-filed, tea spills etc), and it quickly becomes evident that unless this side of the validation effort is very rigorously controlled, anarchy will prevail. It is at this stage that we learned to construct a simple plan for Document Review Manpower Requirements. The manpower required always amazes the client, however, once they agree the parameters and have been served with the documented forecast, the onus is on them to perform to the parameters they agreed, or provide additional resources. cGMP FDA 483 inspection More Being Added Daily, If You Would Like to Add To This Page, Please Use The 'Submit Query' Form.
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