APR January/February 2022 - 16

»
MICROBIOLOGY
»
The reader would be most familiar, due to parenting, with use of
the binding gels for pre-natal sonograms, which with non-invasive
procedures such as transthoracic echocardiograms, bladder and
vascular scans are low risk procedures. Higher risk procedures include
those with mucous membrane contact such as trans-esophageal
echocardiograms, and trans-vaginal ultra-sonograms to the highest
risk with invasive procedures such as trans-rectal prostate biopsy,
thyroid biopsy, epi-aortic ultra-sonograms, and stereotactic breast
biopsy (Olezkowicz et al, 2012; Rutala and Weber, 2019)
In terms of risk mitigation, invasive procedures should employ singleuse
sterile ultrasound gel. Other risks include failure to sanitize
ultrasound probes between use, replenishing non-sterile ultrasound
bottles from a bulk gel container, and using readily contaminated
water baths to warm the gel to body temperature.
Use of Immunosuppressive Agents, Corticosteroids
More emphasis should be given to the specific drug, dosage level and
duration of treatment in terms of possible promotion of microbial
infection. This is well described for corticosteroid usage (Fardet et al,
2016). A recent publication highlighted that low-dose glucocorticoid
treatment in patients with rheumatoid arthritis increased infection
rates (George et al, 2020). In addition, drugs that repress gastric acid
secretion, i.e., e., proton pump antagonists, are an additional risk for
oral dosage forms taken with these products because microorganisms
are not destroyed by the low pH in the stomach (FDA Drug Safety
Communication 2017) and immunosuppression drug use to prevent
organ transplant rejection reduce the immunological response to
infection (Fishman, 2017). Does the use of the newer monoclonal
antibodies, gene and cell therapies, and inflammation-suppressing
drugs change the risk of infection? Probably this is so.
The Presence of Disease, Wounds, Organ Damage
What are the diseases with increased rate of infection? Are common
diseases like cancer, heart disease, diabetes, rheumatoid arthritis,
asthma, and chronic obstructive pulmonary disease associated with
increased risk? Are they all associated with immunosuppression or are
there other risk factors? When is a non-sterile drug product targeted
for a specific patient population in contrast to the general population
is the risk increased? Can this be identified? Is the effect of organ
damage on infection rates well established?
Additional Questions
The author believes that setting microbial limits, screening for specified
microorganisms, and excluding objectionable microorganisms by
route of administration does mitigate risk by rejecting non-sterile drugs
contaminated with objectionable microorganisms. Unfortunately,
many drug manufacturers release non-sterile drugs continuant on
meeting the narrow compendial requirement overlooking there are
not different microbial requirements based on the medical status of
the recipient of the non-sterile drug. Should there be so?
16 |
| January/February 2022
Should the risk assessment go beyond genus and species to strain,
antibiotic resistance, and other genotypic and phenotypic features?
This approach is being taken by the USP <64> Probiotics Tests with the
identification of lactobacilli and bifidobacterium strains in probiotics
and could be taken to good advantage with microbial contamination
of non-sterile drugs. For example, although Escherichia coli is used
as a pathogen indicator organism not every member of the genus
Escherichia and species E. coli are pathogenic and they are part of
the normal human intestinal microbiotia (Yu et al, 2021). With Gramnegative
bacterium associated with opportunistic bacterial infections
those species and strains with resistance broad-acting antibiotics are a
more serious public health threat.
Should additional risk factors be added to the list? For example, risk
associated with invasive surgical procedures, the immaturity and/or
malfunctioning of the microbiome, emerging medical treatments, and
organ and medical device transplant.
Other Pertinent USP Chapters
Other than the general microbiological requirements recommended
in USP <1111>, where does the USP address specific non-sterile
dosage forms? The pertinent sections of the following chapters are
quoted and the content analyzed.
USP <2> Oral Drug Products-
Product Quality Tests
Microbial Content
The chapter states: " The presence of certain microorganisms in
non-sterile preparations may have the potential
to reduce or
even inactivate the therapeutic activity of the product and has a
potential to adversely affect the health of the patient. Some liquid
oral products can be subject to extreme microbiological control,
and others require none. The needed microbial specification for a
given liquid oral product depends on its formulation and use and is
indicated in the monograph " .
This position is consistent with ICH Q 6a Specifications: Test procedures
and acceptance criteria for new drug substances and new drug products
Decision Trees #6 and 8 and USP <1112> Application of Water Activity
Determination to Non-sterile Pharmaceutical Products.
As aqueous, multiple-use, oral drug products may contain Burkholderia
cepacia that may overcome the antimicrobial preservative system, the
newer chapter Test for Burkholderia cepacia complex <60> should be
cited in <2>.

APR January/February 2022

Table of Contents for the Digital Edition of APR January/February 2022

APR January/February 2022 - Cover1
APR January/February 2022 - Cover2
APR January/February 2022 - 1
APR January/February 2022 - 2
APR January/February 2022 - 3
APR January/February 2022 - 4
APR January/February 2022 - 5
APR January/February 2022 - 6
APR January/February 2022 - 7
APR January/February 2022 - 8
APR January/February 2022 - 9
APR January/February 2022 - 10
APR January/February 2022 - 11
APR January/February 2022 - 12
APR January/February 2022 - 13
APR January/February 2022 - 14
APR January/February 2022 - 15
APR January/February 2022 - 16
APR January/February 2022 - 17
APR January/February 2022 - 18
APR January/February 2022 - 19
APR January/February 2022 - 20
APR January/February 2022 - 21
APR January/February 2022 - 22
APR January/February 2022 - 23
APR January/February 2022 - 24
APR January/February 2022 - 25
APR January/February 2022 - 26
APR January/February 2022 - 27
APR January/February 2022 - 28
APR January/February 2022 - 29
APR January/February 2022 - 30
APR January/February 2022 - 31
APR January/February 2022 - 32
APR January/February 2022 - 33
APR January/February 2022 - 34
APR January/February 2022 - 35
APR January/February 2022 - 36
APR January/February 2022 - 37
APR January/February 2022 - 38
APR January/February 2022 - 39
APR January/February 2022 - 40
APR January/February 2022 - 41
APR January/February 2022 - 42
APR January/February 2022 - 43
APR January/February 2022 - 44
APR January/February 2022 - 45
APR January/February 2022 - 46
APR January/February 2022 - 47
APR January/February 2022 - 48
APR January/February 2022 - 49
APR January/February 2022 - 50
APR January/February 2022 - 51
APR January/February 2022 - 52
APR January/February 2022 - 53
APR January/February 2022 - 54
APR January/February 2022 - 55
APR January/February 2022 - 56
APR January/February 2022 - 57
APR January/February 2022 - 58
APR January/February 2022 - 59
APR January/February 2022 - 60
APR January/February 2022 - 61
APR January/February 2022 - 62
APR January/February 2022 - 63
APR January/February 2022 - 64
APR January/February 2022 - 65
APR January/February 2022 - 66
APR January/February 2022 - 67
APR January/February 2022 - 68
APR January/February 2022 - 69
APR January/February 2022 - 70
APR January/February 2022 - 71
APR January/February 2022 - 72
APR January/February 2022 - 73
APR January/February 2022 - 74
APR January/February 2022 - 75
APR January/February 2022 - 76
APR January/February 2022 - 77
APR January/February 2022 - 78
APR January/February 2022 - 79
APR January/February 2022 - 80
APR January/February 2022 - 81
APR January/February 2022 - 82
APR January/February 2022 - 83
APR January/February 2022 - 84
APR January/February 2022 - Cover3
APR January/February 2022 - Cover4
https://www.nxtbookmedia.com