The benefits of knowing the differences between specified & objectionable organisms<\/li>\n<\/ul>\n<\/p>\n
What Is A Specified Organism?<\/h3>\n
A specified organism is one that according to the pharmacopeia, cannot be present in a sample (usually 10g). These microbes are specified either as they may be an indicator organism (a microbe where its presence may indicate a pathogenic microbe could be present) or they may actually pose product safety concerns (whether by reducing the efficacy or posing a risk to the end user).<\/p>\n
USP <1111> Microbiological Examination of Nonsterile Products<\/i> lists several organisms which, depending on the route of administration, can be objectionable in a drug:<\/p>\n\n- Staphylococcus aureus<\/i><\/li>\n
- Escherichia coli<\/i><\/li>\n
- Pseudomonas aeruginosa<\/i><\/li>\n
- Candida <\/i>albicans<\/i><\/li>\n
- bile-tolerant gram-negative bacteria<\/li>\n<\/ul>\n
The relevant monographs state when these microbes need to be absent\u00a0\u00a0 When this is the case this is known as a specified microbe.\u00a0 This tends to be logical.\u00a0 For example, Candida albicans<\/em> may be specified for a vaginal application route, E. coli<\/em> and Salmonella sp.\u00a0<\/em> could be specified when the product is ingested.\u00a0 Pseudomonas aeruginosa\u00a0<\/em> and Staphylococcus aureus<\/em> might be specified for topically applied products.<\/p>\nE.coli<\/em> though capable of causing disease on its own is typically used as an indicator organism.\u00a0 The presence of this microbe could mean the product (or sample) has been contaminated with faecal matter.<\/p>\nAs well as these stated microbes, any other microbe recovered might be objectionable.<\/p>\n
What Is An Objectionable Organism?<\/h3>\n
An objectionable organism is one that we do not want to see in product based upon:<\/p>\n
\n- What the microbe is<\/li>\n
- How many microbes were recovered<\/li>\n
- How the product is used<\/li>\n
- Who the end user is<\/li>\n<\/ul>\n
The PDA defines objectionable organism as, \u201cmicroorganisms that, due (their) numbers and pathogenicity can cause infection, allergic response or toxaemia in patients receiving the product\u201d.\u00a0 The PDA also notes that where the product appearance, stability or efficacy can be affected by the microbe, then it is objectionable.<\/p>\n
It can be argued that a specified microbe is not necessarily objectionable. All microbes recovered from any<\/i> TAMC or TYMC test should be identified and examined to determine if they are objectionable.<\/p>\n
The primary difference\u00a0 between specified and objectionable microbes is that a specified microbe MUST NOT be present in any product. An objectionable microbe must also be absent, but it is up to the manufacturer to determine is a recovered microbe is objectionable.<\/p>\n
Determining If A Recovered Microbe Is Objectionable<\/h3>\n
A non sterile manufacturer should be concerned if microbes that are not specified are recovered during the specified test and they should determine if microbes recovered by the TAMC and TYMC tests are potentially objectionable.\u00a0\u00a0 This can be evaluated by reviewing:<\/p>\n
\n- Microbe pathogenicity: what disease is the microbe capable of causing and might this microbe in the product cause disease?<\/li>\n
- Microbe source: where is the microbe found in nature (and in what numbers)?\u00a0 What is the likelihood of this microbe in a product causing disease in a patient who may be immunocompromised?<\/li>\n
- Potential product spoilage: can the microbe by it\u2019s very nature spoil the product or inactivate it?\u00a0 Might the microbe use the product or its components as food? Might the microbe product substances that are toxic or deactivate the active ingredients in the product?<\/li>\n
- Results of the TAMC test: was the specific microbe recovered during the TAMC or TYMC test?\u00a0 The specific test is meant to revive microbes that might not be able to be recovered via the general tests.\u00a0\u00a0 If you recover Staphylococcus aureus <\/i>in the TAMC test and find none in your specific test for this microbe you must investigate why.\u00a0 Was the TAMC test contaminated?\u00a0 Was the specified test conducted correctly?<\/li>\n
- The product’s target user and mode of application:\u00a0 is the user sick or healthy? Was a potentially pathogenic skin microbe found in a topical cream? Was Burkholderia<\/i> cepacia<\/i> or a Pseodomonad found in an inhaled product?\u00a0 If so, there is a potential to infect your end users so you should investigate.<\/li>\n<\/ul>\n
Ideally we should be identifying all<\/i> microbes recovered from both<\/i> the TAMC, TYMC and specified microbes tests and determine if they are objectionable. Enumerating microbes and identifying non typical colonies may not capture all the microbes present within a sample.<\/p>\n
A good reference here is the US FDA\u2019s Bad Bug Book along with the Internet, Bergry\u2019s and you and your company\u2019s product knowledge.<\/p>\n
Risk Assessment Considerations<\/h3>\n
When you recover a microbe your training and experience will give you a good idea if the microbe might cause issues.\u00a0 As part of your risk assessment and investigation you need to consider such things are:<\/p>\n
\n- Recovered microbe count<\/li>\n
- Preservatives and antimicrobials in the product<\/li>\n
- Validation data<\/li>\n
- Intended use of product<\/li>\n
- Where the recovered microbe typically causes disease<\/li>\n
- Historical data of product<\/li>\n<\/ul>\n
A lot of what we do is based on risk.\u00a0 How comfortable we are with risk, the risk to the company, the risk to the product, the risk to your customers.<\/p>\n
Recovered microbe count: Is the count above your alert or action level?\u00a0 Are the number of microbes likely to cause product spoilage?<\/p>\n
Preservatives and antimicrobials in the product: Expand on the last slide and in combination with the numbers and types of microbes recovered they could proliferate in the product causing spoilage by using up or deactivating the preservatives.\u00a0 It is also possible high number of microbes could result in reduced potency of an antimicrobial product.<\/p>\n
Validation data: Were the microbes recoverable during the product\u2019s validation studies?\u00a0 If no, then finding the microbe during testing should cause you concern as how did it get there?\u00a0 This should be investigated.<\/p>\n
Intended use of product and Where the recovered microbe typically causes disease – as discussed in “Determining If A Recovered Microbe Is Objectionable” section.<\/p>\n
Historical data of product:\u00a0 An examination of historical data can show what is typically recovered and incapable of being recovered in a product.\u00a0 If you suddenly start recovering a genus or species that has never been recovered, it may represent a loss of control in your process, something amiss with the product or stating materials or something even more interesting.\u00a0 A brand new microbe in your product is certainly notable and it might be objectionable.\u00a0\u00a0 An examination of historical data is also important from a risk perspective as it will give you and indication of the likelihood of undetected contamination in past batches and whether or not future batches are at risk of the same contamination.<\/p>\n
The Benefits of Knowing The Differences Between Specified & Objectionable Organisms<\/h3>\n
Being aware that any microbe recovered during testing potentially objectionable is important as people tend to assume specified = objectionable and all other microbes are acceptable.<\/p>\n
By examining microbes recovered during TAMC or TYMC testing, one may determine if they are detrimental to the product or patient. This ensures quality products are released to the market that do not have unexpected (or negative) impacts to the manufacturer or the customer.<\/p>\n
Basically, if you recover a microbe that is not a specified microbe, be it from your specified microbe or count testing, based on the microbe, how many there are, your product and the intended user, the microbe might be objectionable.<\/p>\n
Conclusion<\/h3>\n
You will now know the following:<\/p>\n
\n- What a specified organism is<\/li>\n
- What an objectionable organism is<\/li>\n
- How to determine if a microbe is objectionable<\/li>\n
- Some things to consider as part of your risk assessment<\/li>\n
- The benefits of knowing all of the above<\/li>\n<\/ul>\n