After all, from both a patient perspective, and a regulatory perspective, failing to 'get it right' can prove extremely costly. The risk to patients is clear enough, but it is just as true that no company wants to fall foul of the regulators.
Cleaning Validation Training Courses
What is clean?
From the regulatory perspective, there is a lot of documentation needed to demonstrate that cleaning has been carried out effectively, and to satisfy auditors. The cleaning validation training courses offered by RSSL Pharma go into great detail about the documentation requirements as well as the legal and standards frameworks against which pharmaceutical manufacturers are assessed during audits.
However, documentation is only part of the story. After all, there is no point in documenting (and carrying out) a cleaning procedure unless it can be shown to be effective. Hence it is vital to take the time and effort to validate any cleaning procedure. That means sampling and testing the plant following a cleaning procedure to show that it has done the job properly, and to show that the same results will be achieved whenever the same procedure is used.
Issues Surrounding Sampling & Testing
Various sampling techniques have been developed to provide material for testing, such as rinse sampling and placebo testing. The former covers a much larger sample area than any other method, but is roughly equivalent to determining the state of domestic dishwashing by measuring the amount of dirt that is left in the washing up water. i.e. it's not very conclusive. The latter method relies on the risky assumption that any contamination will be evenly spread through the placebo batch. It also dilutes the sample and makes accurate analysis difficult, such that some regulators find it unacceptable.
Swab testing is therefore the preferred method, since it can be used to test the cleanliness of difficult areas and should pick up hard to remove contamination. However, swabbing is a skill in itself, and all attempts to validate cleaning procedures are meaningless if the swabbing is not carried out properly.
The role of the operator is so vital to swab testing that it is essential that proper training is given. Indeed, lack of training is one of the biggest sources of error in cleaning validation, with anecdotal evidence suggesting that more than 50% of those employed in swabbing are not totally skilled at the job. Again, RSSL Pharma's training covers these issues.
Analytical Method Validation
Validating the analytical method is as important as validating the cleaning process. Analytical method validation can be a complex and time-consuming process, and for many pharmaceutical companies, outsourcing this function to a specialist laboratory such as RSSL Pharma, is often preferable to committing in-house R&D expertise to the function. Indeed, an experienced third party laboratory with method validation expertise and testing resources is often well placed to save time and money in method development and routine analysis.
Clearly, there are some issues to address if testing is conducted off-site, most particularly to ensure that the swab is not further contaminated during transit, and that any residual chemicals that need to be assessed are stable enough to be analysed once the sample reaches the laboratory. That said, these are also issues that need to be addressed if testing is conducted on-site.
RSSL Pharma's expertise in method development is well established, as is its ability to investigate and explain any negative results. The chemistry laboratories are well equipped with highly sensitive equipment such as LC-MS and GC-MS, capable of detecting trace levels of chemical contamination. The microbiology laboratories can conduct screening for microbial cleanliness. Both laboratories provide a useful service in helping to validate cleaning procedures.
Society often views cleaning as a job for the low-skilled, but in the world of pharmaceutical production that is the wrong attitude to have. Cleaning is as much a part of the process as the actual manufacture of pharmaceuticals. It is not merely the job that has to be done when the most important task is completed.
The Orange Book 2007 and equivalent FDA guidelines are both very clear in their expectations with respect to cleaning, and both underline that any company that fails to validate its cleaning is at risk of regulatory action.
Whilst validation is often seen as a time consuming and expensive exercise, when done properly, it has the potential for dramatic pay-back. When set against the cost of (unnecessary) testing and the major expense of having to with-hold and destroy contaminated product, the one-off expense of validation is negligible.