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Sunday, 24 December 2017
Wednesday, 20 December 2017
Draft EU GMP Annex 1 released
The PIC/S Secretariat has notified that the revised EU-PIC/S GMP Annex 1 on the Manufacture of Sterile Medicinal Products has reached Step 2 of the revision process and on 20 December 2017, the PIC/S and EMA published the draft revision of Annex 1 for public consultation.
The consultation period will last 3 months and run from 20 December 2017 to 20 March 2018.
The revised Annex 1 has been prepared in co-operation with the EMA, World Health Organization (WHO), and PIC/S in order to maintain global alignment of standards, and provide assurance of product quality. The document is subject to parallel public consultation by the European Commission (EC), WHO and PIC/S.
Key changes from the earlier PIC/S Annex are:
- Introduction of new sections: scope, utilities, environmental and process monitoring sections and glossary.
- Introduction of the principles of Quality Risk Management (QRM) to allow for the inclusion of new technologies and innovative processes.
- Restructuring to give more logical flow.
- Addition of detail to provide further clarity.
The draft has been formatted with prescribed line and page numbers to support a joint international consultation within TGA, PIC/S, WHO and the EC.
Posted by Dr. Tim Sandle
2017 Author of the Year – Journal of GXP Compliance
Biodecontamination of Cleanrooms and Laboratories Using Gassing Systems V21 #1
Matrix Approach for the Qualification of a Pharmaceutical Facility Autoclave V21 #4
Pharmaceutical Microbiology: Current and Future Challenges V21 #4
Tuesday, 19 December 2017
How the immune system identifies invading bacteria
The
body's homeland security unit is more thorough than any airport checkpoint. For
the first time, scientists have witnessed a mouse immune system protein
frisking a snippet of an invading bacterium. The inspection is far more
extensive than researchers imagined: the immune system protein, similar to those
in humans, scans the bacterial protein in six different ways, ensuring correct
identification.
See:
Monday, 18 December 2017
How to gown properly for cleanrooms
As shown below, three videos showing how to gown properly when entering cleanrooms.
Practical workshop on good cleanroom gowning from Simon Fiala – Key Account Manager, COMPREI Reinraum.
Posted by Dr. Tim Sandle
Practical workshop on good cleanroom gowning from Simon Fiala – Key Account Manager, COMPREI Reinraum.
Posted by Dr. Tim Sandle
Saturday, 16 December 2017
Strain Collection for Improved Expression of Outer Membrane Proteins
An
article of interest in Frontiers in Cellular and Infection Microbiology. Here
is the abstract:
Almost
all integral membrane proteins found in the outer membranes of Gram-negative
bacteria belong to the transmembrane β-barrel family. These proteins are not
only important for nutrient uptake and homeostasis, but are also involved in
such processes as adhesion, protein secretion, biofilm formation, and
virulence. As surface exposed molecules, outer membrane β-barrel proteins are
also potential drug and vaccine targets. High production levels of
heterologously expressed proteins are desirable for biochemical and especially
structural studies, but over-expression and subsequent purification of membrane
proteins, including outer membrane proteins, can be challenging.
Here,
we present a set of deletion mutants derived from E. coli BL21(DE3) designed
for the over-expression of recombinant outer membrane proteins. These strains
harbor deletions of four genes encoding abundant β-barrel proteins in the outer
membrane (OmpA, OmpC, OmpF, and LamB), both single and in all combinations of
double, triple, and quadruple knock-outs. The sequences encoding these outer
membrane proteins were deleted completely, leaving only a minimal scar
sequence, thus preventing the possibility of genetic reversion.
Expression
tests in the quadruple mutant strain with four test proteins, including a small
outer membrane β-barrel protein and variants thereof as well as two
virulence-related autotransporters, showed significantly improved expression
and better quality of the produced proteins over the parent strain.
Differences
in growth behavior and aggregation in the presence of high salt were observed,
but these phenomena did not negatively influence the expression in the
quadruple mutant strain when handled as we recommend. The strains produced in
this study can be used for outer membrane protein production and purification,
but are also uniquely useful for labeling experiments for biophysical
measurements in the native membrane environment.
Friday, 15 December 2017
How Helicobacter pylori causes gastric cancer
Gastric
cancer is one of the five most fatal types of cancer. According to the
statistics of the World Health Organization (WHO), about 750,000 patients die
each year after developing the disease. The main cause is thought to be the
bacterium Helicobacter pylori (H. pylori). At present, there are no effective
therapies for gastric cancer and growing spread of antibiotic resistances is
further complicating treatment of the infection. Researchers at
Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have now identified two
mechanisms through which this bacterium can cause gastric cancer. Their
findings could result in the development of new therapeutic approaches.
The
international team of scientists headed by Dr. Nicole Tegtmeyer of the Chair of
Microbiology at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
investigated how bacteria destroy the stomach's protective layer. This protective
layer is composed of densely packed epithelial cells that protect the stomach
against the effects of gastric acid. The researchers have now discovered that
H. pylori secretes an enzyme, a protease called HtrA, which it uses much like a
weapon to penetrate this protective layer. HtrA cleaves the three proteins
occludin, claudin-8 and E-cadherin, rupturing the layer of epithelial cells. As
a result, the H. pylori bacteria can access deeper, normally pathogen-free
tissue layers, and inflict further damage. This is the first step towards
gastric cancer starting to develop.
This
first phase, however, is followed by one that is even more dangerous, as the
team discovered. Needle-like protrusions, termed type IV secretion systems, are
activated and function as 'molecular syringes'. Using a receptor-dependent
mechanism, these inject a bacterial toxin, the CagA protein, through the
basolateral membrane of the host cells. The injected CagA subsequently
reprograms host cells, making them potentially cancerous. Another effect of
this protein is that it prevents the human immune system from recognising and
eliminating the bacteria -- a crucial mechanism for the long-term survival of
H. pylori in the human stomach.
See:
Posted by Dr. Tim Sandle
Tuesday, 12 December 2017
Novel antibiotic resistance gene in milk
A
new antibiotic resistance gene has been found in bacteria from dairy cows. This
gene confers resistance to all beta-lactam antibiotics including the last
generation of cephalosporins used against methicillin-resistant Staphylococcus aureus. A transfer to S. aureus which is likely according to
the researchers would jeopardize the use of reserve antibiotics to treat human
infections caused by multidrug-resistant bacteria in hospitals.
Macrococcus
caseolyticus is a harmless bacterium naturally found on the skin
of dairy cows which can spread to milk during the milking process. It can also
be present in dairy products made from raw milk like e.g. cheese. Researchers
of the Institute of Veterinary Bacteriology of the University of Bern have
identified a new methicillin resistance gene in strains of M. caseolyticus isolated from milk. Transfer of the gene to Staphylococcus aureus, a bacterium found
on the skin and mucosa of animals and humans, would have dramatic consequences
for public health. This methicillin resistance gene would turn this bacteria
into a hazardous methicillin-resistant S.
aureus (MRSA), which is known to cause difficult-to-treat infections in
hospitals. Acquired methicillin resistance in bacteria is associated with genes
mecA, mecB, or mecC. However, none of these genes were present in the M. caseolyticus strains -- they carried
the novel resistance gene mecD.
See:
Friday, 8 December 2017
Pharmig News #69
A
new edition of Pharmig News has been issued, edition 69. In this issue:
- Industry reflections by David Keen.
- Part 2 of Pharmig’s industry review of culture media practices.
- Review of MHRA deficiencies – trends and topics.
- Regulatory round-up
- New Pharmig courses
- And more…
The
articles by Tim Sandle in the new edition are:
Sandle,
T. (2017) Industry practices relating to culture media use: The Pharmig survey
(part 2), Pharmig News, Issue 69,
pp2-5
Thursday, 7 December 2017
5 Keys To Aseptic Processing Improvement & Efficiency
Today,
life science products should also be affordable to patients and a reasonable
business proposition for manufactures. These objectives can present challenges
to manufacturers as they strive to gain production and process efficiencies.
Hal
Baseman has written an interesting article for Pharmaceutical Online. Here is
an extract:
- Science- and risk-based approaches should be used to obtain information needed to make decisions related to the evaluation, design, qualification, operation, and monitoring of sterile product manufacturing processes.
- Technology should be considered to mitigate or reduce the risk to product quality identified in sterile product manufacturing processes and operations.
- Traditional testing and monitoring methods as control strategies should be challenged to ensure they are the best means for aseptic processes.
- New products, therapies, and technologies will present challenges to traditional and existing methods for development, manufacture, validation, and testing of sterile products.
- Global health authority technical and regulatory guidance and requirements should be harmonized with regard to technical language and definitions.
Wednesday, 6 December 2017
Data-Driven Risk Management For Quality By Design
The main hope of ICH Q8-Q10 pertaining
to operational excellence is to enable (bio)pharmaceutical companies to achieve
product realization. The goal is to do so by establishing and maintaining a
state of control and facilitating continual improvement while responding to
pressures for efficiency and profitability improvements.
Peiyi Ko, Ph.D. and Peter Calcott,
Ph.D. have written an interesting article on the subject for Pharmaceutical
Online. Here is an extract:
“risk management is open to individual
interpretations and at times has varied and been time-consuming and
not-informative for prioritization, re-inventing risk assessments and leading
to wasted resources and unsatisfactory outcomes. Therefore, it is proposed to
use a quantitative approach with probabilistic calculations and monetized harm
to account for occurrence and severity, respectively. Specifically, failure
modes and effects analysis (FMEA) is a classic tool for summarizing the modes
of failure, factors causing these failures, and the likely effects of theses
failures to reduce process complexity for management. It generates a risk
priority score for a failure mode by multiplying the ratings for severity,
occurrence, and detection.”
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