Tuesday, October 5, 2010

Method Validation, Bonsai To Go and Improving GMP compliance

“The country does not matter, either the micro lab works or it doesn’t”

I have audited facilities in many different countries.  China (e.g., Shanghai, Jiangsu, Guangdong , Huizhou, Zhuhai), Taiwan, Thailand, Hong Kong, Korea,  Dubai, Israel, Italy, Canada, and the United Kingdom (i.e., Wales and England).
The regulatory compliance is subject to local regulatory agencies in the country involved, but the microbiology lab answers to a greater authority, the “Science of Life”.  Most labs have some degree of success in performing the testing.  However, I generally find that most labs can improve on the test methodology.   In two words- “Method Validation”.   The tools to measure growth success of different species on the actual test materials in question must be established in order to evaluate the real efficacy of the lab test program.  These tests are called “Microbial Recovery Validations”.   The lab should validate the method works to recover the general types of organisms expected, and especially the restricted organisms specified for the product.  For example, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella spp., Candida albicans, mold and any others specified as restricted for a given product or raw material.  

“100 things can go wrong in the microbiology lab that may give you false acceptable test results.”

I have audited over 60 manufacturer or microbiology lab operations (41 facilities or labs in 11 different countries).  In Asia I found they almost always had the same 17 items that needed correction or refinement before results could be verified.  There was a clear connection with all the failing labs.  The cosmetic industry in Asia, adopted clinical lab testing methods to meet the local government regulations for qualifying the microbiology lab.  A good start but other modifications and verifications are needed.  The methods have been validated to work for standard clinical test materials like blood, urine, and tissue.

However clinical methods are not always appropriate for organisms encountered in  manufactured products.  One reason is the products are at room temperature, not usually at human body temperatures.  A second reason was the clinical strategy of not risking test contaminations from positive controls. Thus the use of positive controls in the lab was considered not necessary.  As a result the labs did not have examples (i.e., stock cultures) of the organisms they were looking for.   Therefore in-line positive controls and media controls were not established to verify test results.   

Another concern is that cosmetic products are usually preserved, unlike clinical samples.  As a result, the test method may not neutralize the anti-microbial components in the test materials and result in false negative test results.

Even if this neutralization was performed as some companies did, the potential toxicity of the neutralizers were not evaluated.  Overuse of neutralizers could also result in no growth and false negative test results.   I can help you develop method validation procedures to verify the method was successful in recovering the microbes that could be present.

I have encounter inappropriate microbial test methods in US operations as well.  In the course of investigating a contamination of a raw material, it was found that the root cause of not detecting the microbes was over-neutralization in the test method .  This yielded false negative test results. We did resolve how to correct the situation by modifying the test procedure.

“Bonsai To Go Society?”

We live in a fast paced world.  Even traditionalists of different cultures have modified the traditional rules to conform to a faster pace.  Traditionalists respect the ancient values of original cultural societies.  However modern people have adopted quicker methods that may arrive at the same objective.  Some better than others and some with definite limitations.

                               Bonsai with 20 years training
The art is to create antiquity in young trees.  [The opposite of the cosmetic industry.]
Different methods are used to imply age.  Traditional methods of pruning over years of training can create a representative of a 100 year old tree with a long history of good and bad times.  

                                  Rapid Bonsai in two hours

 A rapid modern method would be to wire several saplings together and create what appears to be a single branching tree. In a short two hours a bonsai artist may transform saplings into an ancient miniature tree- Bonsai.      

                                  Details of rapid method 
Likewise there are newer rapid microbiological methods that need only be validated for the specific application that could be used for shorter release criteria to decrease manufacturing time.  The limitations need to be evaluated by method validation in order to substantiate quality, regulatory acceptability and practical cost of using a given technology.

Improving GMP compliance for manufacturing of cosmetic SPF products.
Cosmetic manufacturers that make SPF (Sun Protection Factor) products for Europe and non-American markets are not required to meet OTC (Over the Counter Drug) regulations that are enforced in the United States and Canada.  Consequently, they cannot legally manufacture these items for sale in the North American markets.  Compliance with US Federal Code of Regulations and Drug Product registrations are required to compete in this market.  I can audit your facility to determine what controls are lacking and provide a corrective action list to comply with the regulations.  The objective would be to assure the quality and safety of the product.  Consequently, the company should perform well in an official FDA audit.