Tuesday 31 March 2015

Alternative methods for control of microbiological quality

The European Pharmacopeia is to completely revised the chapter “Alternative methods for control of microbiological quality”. This is chapter 5.1.6 and is the chapter relating to rapid and alternative methods. A draft has been published in the current edition of Phareuropa and it is available for public comment.

The introduction to the revised document reads:

“The objective of this chapter is to facilitate the implementation and use of alternative= microbiological methods where this can lead to efficient microbiological control and improved assurance for the quality of pharmaceutical products. The microbiological methods described in the European Pharmacopoeia have been used for over a century and these methods for detecting, enumerating and identifying micro-organisms still serve microbiologists well. Over the years, these methods have been invaluable for the production of microbiologically safe pharmaceutical products. However, conventional microbiological methods are slow, and in the case of sterility tests, results are not available before an incubation period of 14 days. Consequently, the results from these conventional methods seldom enable proactive corrective action to be taken.

Alternative microbiological methods for the control of microbiological quality have been introduced in recent years, and some of these methods have shown potential for real-time or near real-time results with the possibility of earlier corrective action. These new methods, if validated and adapted for routine use, can also offer significant improvements in the quality of testing. Alternative methods may be used for the application of Process Analytical Technology (PAT) to in-process samples of pharmaceutical products and for environmental monitoring, thereby contributing to the quality control of these products.”

The revised chapter includes sections on:

  • General critical aspects of methods based on early detection of growth
  • Electrochemical methods
  • Measurement of consumption or production of gas
  • Bioluminescence
  • Turbidimetry
  • Growth detection using selective and/or indicative media
  • Solid phase cytometry
  • Flow cytometry
  • Direct epifluorescent filtration technique (DEFT)
  • Autofluorescence
  • Phenotypic techniques
  • Genotypic techniques
  • Validation of alternative microbiological methods
The chapter is available for review via Pharmeuropa. You will need to register in order to comment.

Pharmeuropa is a free online EDQM publication. Draft monographs are published in Pharmeuropa for public enquiry, which lasts for three months. Comments received are processed by EDQM, at this stage the draft can be amended and republished. If no further revision is required the draft monograph is proposed to the European Pharmacopoeia Commission if adopted an implementation date is given and this is about one year after the adoption of the monograph. The monograph is then published in the European Pharmacopoeia (or supplement). The monograph is published about 6 months after adoption. Therefore draft text appearing in Pharmeuropa may not become official for up to 2 years. Those monograph’s adopted will be highlighted in reviews of the European Pharmacopoeia or supplements

Posted by Tim Sandle

Monday 30 March 2015

Impending New Child-Friendly TB Treatments

TB Alliance has announced a new partnership with the U.S. Fund for UNICEF that will dramatically increase the scope and impact of child and maternal health programs around the world to include the diagnosis and treatment of pediatric tuberculosis (TB), a significant cause of child mortality.

“Pediatric TB has stayed in the shadows for far too long,” said Caryl Stern, President and CEO of the U.S. Fund for UNICEF. “We are thrilled to be working with TB Alliance to deliver new treatments that children around the world so desperately need and that will help us improve child survival.”

The collaboration will help elevate childhood TB as a priority issue to improve child survival and integrate TB within UNICEF’s child health services around the world. It will also facilitate the uptake of the first appropriate, child-friendly TB treatments that TB Alliance and its partners are developing, as part of a broader partnership with the World Health Organization (WHO), and which correspond to WHO’s recommended treatment guidelines.

“Today, there are no appropriate TB treatments for children,” said Mel Spigelman, MD, President and CEO of TB Alliance. “The partnership with the U.S. Fund for UNICEF will help ensure the new treatments coming to market can reach sick children, who can then be treated and cured.”

TB Alliance, in concert with other partners, has been working to better understand the burden of disease in children and address other issues that prevent access to TB treatment. Current estimates highlight that at least 550,000 children suffer from TB and as many as 53 million are latently infected.

UNICEF, TB Alliance, and WHO will now work together to facilitate uptake of the new child-friendly TB treatments, which are expected to reach the market in 2016. The new treatments are expected to be included in the UNICEF supply chain, one of the world’s largest purchaser and supplier of medicines and vaccines for children. The partnership will also connect the health providers in UNICEF’s global network with better educational tools and information on pediatric TB with the goal of integrating TB into existing initiatives that address maternal and child health and pediatric HIV/AIDS.

“Bringing together the relevant partners, we have an extraordinary opportunity to tackle the issue of pediatric TB,” said Mario Raviglione, MD, Director of the WHO's Global TB Programme. “We look forward to this expanded collaboration, and the impact it can have on improving TB treatment and reducing childhood mortality from TB.”

In 2013, with support from UNITAID and USAID, TB Alliance and WHO launched an initiative to improve pediatric TB treatment and reduce child mortality. The initiative aims to deliver new, correctly formulated, child-friendly TB treatments, while enhancing the market understanding needed to accelerate the time in which new and better treatments will reach children in need. This new initiative with UNICEF allows the expansion of this work by leveraging UNICEF’s global reach and presence in countries with high TB burdens.

Posted by Tim Sandle

Assessing airborne contamination using a novel rapid microbiological method

The cleanliness of changing rooms used to access pharmaceutical cleanroom facilities is of considerable importance. This ensures that the changing environment and the act of putting on cleanroom suits do not generate high levels of contamination; for such contamination might be carried on personnel leaving changing areas and into the process areas. Furthermore, it is important to avoid the transfer of contamination to the outside of the garment during the gowning process. A study was undertaken to assess the levels of airborne contamination in a changing room during use. 

To assess this, a changing room was examined under different conditions: at-rest; occupied (with different numbers of personnel); and post-use. For the assessment, a novel rapid microbiological method was used. The assessment of microbiological air quality within changing rooms is conventionally undertaken using methods which rely upon microbial growth media. Due to incubation times, several days are required to ascertain the contamination level risk. This paper describes the use of an alternative real-time continuous monitoring system (the BioVigilant IMD-A® System), based on optical spectroscopy. The paper concludes that increasing the numbers of personnel going through a changing room increases the level of airborne biological activity and increases the length of time required for the room to recover. The study also demonstrates the usefulness of the rapid microbiological method.

In relation to this, Tim Sandle and colleagues have written a research paper.

The reference is:

Sandle, T., Leavy, C. and Rhodes, R. (2015) Assessing airborne contamination using a novel rapid microbiological method, European Journal of Parenteral & Pharmaceutical Sciences, 19(4): 131-142

For further details and to view a copy, please contact Tim Sandle

Posted by Tim Sandle

Sunday 29 March 2015

Pharmaceutical Cleaning Strategies

Cleaning is an essential practice for any pharmaceutical activity: it is impossible to manufacture drugs in dirty conditions, even if dirt is not evident. Many aspects need to be considered in setting up a cleaning procedure. This is certainly a multidisciplinary issue that involves various company areas: from “Regulations” to Engineering, from Quality Control lab to Production department. Contributions of all these areas together can lead to a robust and reproducible cleaning process.

M.L. Bernuzzi has written a review of cleaning strategies for pharmaceuticals. The article has been published on Pharmaceutical Online and it can be accessed here.

Posted by Tim Sandle

Saturday 28 March 2015

European Pharmacopeia updates

Some updates of interest in relation to the European Pharmacopeia:

European Pharmacopoeia 8th Edition - Supplement 8.4 (implementation date 1st April 2015)

General Chapters

The following general chapters are being revised: Materials based on plasticised poly(vinyl chloride) for containers for human blood and blood components based on plasticised poly(vinyl chloride) for tubing used in sets for the transfusion of blood and blood components

3.1.10  Materials based on non-plasticised poly(vinyl chloride) for containers for non-injectable, aqueous solutions

3.1.14  Materials based on plasticised poly(vinyl chloride) for containers for aqueous solutions for intravenous infusions

3.2.1    Glass containers for pharmaceutical use                                            

It has been decided to further emphasise the need for control of specific components that may be toxic for chronic use and for vulnerable patient groups. The statements in the definition section of Parenteral preparations (0520), in chapter 3.2.1. Glass containers for pharmaceutical use and in chapter 3.2.2. Plastic containers and closures for pharmaceutical use have therefore been supplemented.

5.12     Reference standards                                                                          

General revision to update chapter to reflect recent advances in pharmaceutical reference standards, including harmonisation with the specifications and definitions of the corresponding ISO Guides (i.e. ISO Guides 30 and 34) and introduction of:

- the definition of international standards based on WHO Technical Report Series 932,
- herbal reference standards (HRS),
- biological reference preparations (BRP) and chemical reference substances for biologicals.

Posted by Tim Sandle

Friday 27 March 2015

Porphyrin synthesis test explained

The porphyrin synthesis test is used to identify haemin producing Haemophilus species. It avoids the problems of red cell carry over associated with tests for X and V dependence. The porphyrin test is considered to be the definitive method for the differentiation of Haemophilus species.

Haemophilus species are not readily distinguishable by their colonial morphology or gram stain appearance. Oral flora grown from routine sputum cultures often contains organisms which resemble Haemophilus species. H. influenzae, which is the principal human pathogen, can be distinguished from other Haemophilus species and oral flora by determining the need for essential factors for growth, specifically Haemin (X factor) and Nicotinamide-adenine dinucleotide (NAD/V factor). H. influenzae requires both factors for growth where as some of the other species require only one. The requirement for one or both of the growth factors nicotinamide adenine dinucleotide (NAD or V factor) and haemin (X factor) is used to characterise Haemophilus species.

Strains which produce their own haemin possess the enzyme porphobilinogen synthase which can convert d-aminolaevulinic acid (ALA) to protoporphyrin and ultimately haemin.
This test demonstrates the ability of a bacterium supplied with d-aminolaevulinic acid to synthesise and excrete porphobilinogen and other porphyrins, indicating that they are not X dependent.

In relation to the porphyrin synthesis test, Public Health England has issued a technical report, including safety information. The report can be accessed here.

Posted by Tim Sandle

Thursday 26 March 2015

Proteins pull together as cells divide

Cell division is how new cells form, both during development and throughout an organism's life.  Successful cell division requires the formation of a dip called a cleavage furrow, a process that has remained complex. Now, researchers have found that no single molecular architect directs the cleavage furrow's formation; rather, it is a robust structure made of a suite of team players.

For information about the new research, see:

Vasudha Srivastava, Douglas N. Robinson. Mechanical Stress and Network Structure Drive Protein Dynamics during Cytokinesis. Current Biology, 2015; DOI: 10.1016/j.cub.2015.01.025

Posted by Tim Sandle

Wednesday 25 March 2015

The first X-ray portraits of living bacteria

Researchers have captured the first X-ray portraits of living bacteria. This milestone is a first step toward possible X-ray explorations of the molecular machinery at work in viral infections, cell division, photosynthesis and other processes that are important to biology, human health and our environment.

The experiment took place at SLAC's Linac Coherent Light Source (LCLS) X-ray laser, a DOE Office of Science User Facility. The experiment focused on cyanobacteria, or blue-green algae. The cyanobacteria were passed into an ultrabright, rapid-fire LCLS X-ray pulses, producing diffraction patterns recorded by detectors.

The diffraction patterns preserved details of the living cyanobacteria that were compiled to reconstruct 2-D images. Researchers said it should be possible to produce 3-D images of some samples using the same technique.

The technique works with live bacteria and requires no special treatment of the samples before imaging. Other high-resolution imaging methods may require special dyes to increase the contrast in images, or work only on dead or frozen samples.

The technique can capture about 100 images per second, amassing many millions of high-resolution X-ray images in a single day. This speed allows sorting and analysis of the inner structure and activity of biological particles on a massive scale, which could be arranged to show the chronological steps of a range of cellular activities.

van der Schot, G. et al: For further details see: Imaging single cells in a beam of live cyanobacteria with an X-ray laser. Nature Communications, 2015; 6: 5704 DOI: 10.1038/ncomms6704

Posted by Tim Sandle

Tuesday 24 March 2015

New insight into Yersinia pestis

Researchers discover that the accepted theory of how Yersinia pestis bacteria travel from fleabite to lymph node is off base. Most bacteria get trapped in a bottleneck and never make it to the lymph node, where infection takes root. Finding out why could lead to new ways to stop the pathogen.

For details, see:

Rodrigo J. Gonzalez, M. Chelsea Lane, Nikki J. Wagner, Eric H. Weening, Virginia L. Miller. Dissemination of a Highly Virulent Pathogen: Tracking The Early Events That Define Infection. PLOS Pathogens, 2015; 11 (1): e1004587 DOI: 10.1371/journal.ppat.1004587## Posted by Tim Sandle

Monday 23 March 2015

Italian cemetery provides clues on cholera's evolution

A team of archaeologists and other researchers hope that an ancient graveyard in Italy can yield clues about the deadly bacterium that causes cholera.

Researchers are excavating the graveyard surrounding the abandoned Badia Pozzeveri church in the Tuscany region of Italy. The site contains victims of the cholera epidemic that swept the world in the 1850s, said Clark Spencer Larsen, professor of anthropology at The Ohio State University and one of the leaders of the excavation team.

Archaeologists have spent the past four summers excavating remains in a special section of the cemetery used for cholera victims. Finding traces of the pathogen that caused cholera among the human remains could reveal details about how people lived -- and died -- in this region of Europe.

The bodies of the cholera victims were hastily buried and covered in lime, which hardened like concrete around the bodies. Researchers suspect residents were trying to keep the disease from spreading.

The researchers are of the view that if they find the DNA we could see how cholera has evolved and compare it to what the bacteria is like today. That's the first step to possibly finding a cure.

For further details see: Ohio State University.

Posted by Tim Sandle

Sunday 22 March 2015

Bio Products Laboratory at 60

The U.K.'s Bio Products Laboratory (BPL) recently celebrated 60 years of operating. You can read about the plasma fractional plant's history here.

Posted by Tim Sandle

Saturday 21 March 2015

The remarkable Zymomonas mobilis

The bacterium Zymomonas mobilis can convert atmospheric nitrogen gas into ammonium, researchers at the University of Indiana have found. Their results were published in PNAS this week (February 2).

“It was known already that the Zymomonas genome contains all the genes that are needed, but nobody had checked whether they really are able to fix nitrogen,” said Uldis Kalnenieks of the University of Latvia who was not involved in the research.

“The genes might have been there and annotated in the past, but this [study] now enables perhaps the industrial side to develop it,” said Steve Brown of Oak Ridge National Laboratory in Tennessee who also was not involved in the work. “This opens the door to further studies in this system so I think that’s a pretty exciting result.”

For further details, see The Scientist

Posted by Tim Sandle

Friday 20 March 2015

Optochin test explained.

Susceptibility to optochin is a simple and reliable method of differentiating Streptococcus pneumoniae from other alpha-haemolytic streptococci.

Optochin is a chemical, ethylhydrocupreine hydrochloride and is completely soluble in water. The optochin test detects an organism’s susceptibility to the chemical optochin. The chemical tests the fragility of the bacterial cell membrane and causes S. pneumoniae to lyse due to changes in surface tension.

The optochin test is widely used in the form of filter paper discs, impregnated with ethylhydrocupreine hydrochloride, which are applied directly to inoculated plates before incubation.

The optochin test is less time-consuming than the bile solubility test.

In relation to the optochin test, Public Health England has issued a technical report, including safety information. The report can be accessed here.

Posted by Tim Sandle

Thursday 19 March 2015

ISO 11133:2014

A new ISO standard of interest to those involved with culture media use:

ISO 11133:2014  - Microbiology of food, animal feed and water -- Preparation, production, storage and performance testing of culture media

ISO 11133:2014 defines terms related to quality assurance of culture media and specifies the requirements for the preparation of culture media intended for the microbiological analysis of food, animal feed, and samples from the food or feed production environment as well as all kinds of water intended for consumption or used in food production. These requirements are applicable to all categories of culture media prepared for use in laboratories performing microbiological analyses.

ISO 11133:2014 also sets criteria and describes methods for the performance testing of culture media. It applies to producers such as:
  • commercial bodies producing and/or distributing ready-to-use or semi-finished reconstituted or dehydrated media;
  • non-commercial bodies supplying media to third parties;
  • microbiological laboratories preparing culture media for their own use.

The revised standard replaces ISO/TS 11133-1:2009.#

Posted by Tim Sandle

Wednesday 18 March 2015

Link found in how cells start process necessary for life

Researchers have found an RNA structure-based signal that spans billions of years of evolutionary divergence between different types of cells, according to a new study. The finding could alter the basic understanding of how two distinct life forms -- bacteria and eukaryotes -- begin the process of protein synthesis.

Scientists have long thought that the molecular signals that initiate protein synthesis in bacteria and eukaryotes are mutually exclusive. Scientists in Kieft's lab explored whether a structured RNA molecule from a virus that infects eukaryotic cells could function in bacteria. Surprisingly, they found that it could initiate protein syntheses, a process necessary for life.

For details see:

Timothy M. Colussi, David A. Costantino, Jianyu Zhu, John Paul Donohue, Andrei A. Korostelev, Zane A. Jaafar, Terra-Dawn M. Plank, Harry F. Noller, Jeffrey S. Kieft. Initiation of translation in bacteria by a structured eukaryotic IRES RNA. Nature, 2015; DOI: 10.1038/nature14219

Posted by Tim Sandle

Tuesday 17 March 2015

Potassium Hydroxide Test explained

Many Bacillus and Clostridium species organisms that have lost some of the integrity of their cell wall, appear Gram negative on staining resulting in possible misidentification.

The potassium hydroxide test may aid in differentiation between Gram positive and Gram negative organisms and is a useful complement to the Gram stain and the antibiotic disc test. Like the Gram stain reaction, the test is based on differences in the chemistry of the bacterial cell wall.

In the presence of potassium hydroxide, Gram negative cell walls are broken down, releasing viscid chromosomal material which causes the bacterial suspension to become thick and stringy. Gram positive organisms remain unaffected. Hence the alternative name for this procedure, the “String Test”.

In relation to the potassium hydroxide test, Public Health England has issued a technical report, including safety information. The report can be accessed here.

Posted by Tim Sandle

Monday 16 March 2015

Dracunculiasis and the Long Decline of an Ancient Disease

The disease dracunculiasis (guinea worm disease) has ravaged human populations for thousands of years (reference to the disease is documented in the Egyptian medical Ebers Papyrus, dating from around 1550 BC.) Current indications suggest that global incidences of the disease have been rapidly declining due to the concerted efforts of national and international health agencies. Here, only 148 dracunculiasis cases were reported worldwide in 2013 (which represents the lowest annual total ever recorded) and only four endemic countries remain: Chad, Ethiopia, Mali and South Sudan. With these countries, the majority of the cases occur in South Sudan . Nonetheless across these regions the number of endemic villages has declined from the peak of 23,735 in 1991 to 79 in 2013.

Guinea-worm disease is caused by the parasitic worm Dracunculus medinensis or "Guinea-worm". This worm is the largest of the tissue parasite affecting humans. The adult female, which carries about 3 million embryos, can measure 600 to 800 mm in length and 2 mm in diameter. The parasite migrates through the victim's subcutaneous tissues causing severe pain especially when it occurs in the joints. The worm eventually emerges (from the feet in most of the cases), causing an intensely painful oedema, a blister and an ulcer accompanied by fever, nausea and vomiting.
To find out more about this disease and why a decline has occurred, Tim Sandle has written a review paper for the journal Journal of Ancient Diseases & Preventive Remedies.

The reference is:

To view a copy, please contact Tim Sandle.

Sunday 15 March 2015

ICH Q3D Guideline on Elemental Impurities

The ICH Q3D Guideline on Elemental Impurities reached Step 4 of the ICH Process in December 2013 and now enters the implementation period (Step 5). This new guidance has been developed to provide a global policy for limiting metal impurities qualitatively and quantitatively in drug products and ingredients. The existing ICH Q3A Guideline classifies impurities as organic, inorganic, and residual solvents. The Q3A and Q3B Guidelines effectively address the requirements for organic impurities. An additional Guideline Q3C was developed to provide clarification of the requirements for residual solvents. The new Q3D Guideline would provide similar clarification of the requirements for metals, which are included in the ICH inorganic impurities classification.

For further details, see: Q3D guideline

Posted by Tim Sandle

Saturday 14 March 2015

FDA - cGMP requirements for combination products

The FDA has issued a new draft guidance.

This guidance describes and explains the final rule on CGMP requirements for combination products. Prior to issuance of the final rule, although CGMP regulations were in place to establish requirements for drugs, devices, biological products, and Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), there were no regulations to clarify and explain the application of these CGMP requirements to combination products. The final rule was intended to provide such clarification and specify how compliance with applicable CGMP requirements may be demonstrated.

Section II of the guidance provides the definition of a combination product, an overview of the final rule, and the role of the lead center and other agency components with respect to combination product CGMP issues.

Section III addresses certain general considerations for CGMP compliance for combination products, and Section IV presents the purpose and content of specific CGMP requirements addressed in the final rule, and Section V analyzes hypothetical scenarios intended to clarify how to comply with certain CGMP requirements addressed in the final rule. Throughout this guidance, the agency also refers to existing guidance and additional sources of information that address CGMP requirements for drugs, devices, biological products, and HCT/Ps, to further inform combination product manufacturers on how to comply with CGMP requirements.

For further details, see FDA.

Posted by Tim Sandle

Friday 13 March 2015

GMP data integrity definitions

Data integrity is fundamental in a pharmaceutical quality system which ensures that medicines are of the required quality.

In a new document, the U.K. MHRA provides guidance on GMP data integrity expectations for the pharmaceutical industry. This guidance is intended to complement existing EU GMP, and should be read in conjunction with national medicines legislation and the GMP standards published in Eudralex volume 4.

The data governance system should be integral to the pharmaceutical quality system described in EU GMP chapter 1. The effort and resource assigned to data governance should be commensurate with the risk to product quality, and should also be balanced with other quality assurance resource demands. As such, manufacturers and analytical laboratories are not expected to implement a forensic approach to data checking, but instead design and operate a system which provides an acceptable state of control based on the data integrity risk, and which is fully documented with supporting rationale.

Data integrity requirements apply equally to manual (paper) and electronic data. Manufacturers and analytical laboratories should be aware that reverting from automated / computerised to manual / paper-based systems will not in itself remove the need for data integrity controls. This may also constitute a failure to comply with Article 23 of Directive 2001/83/EC, which requires an authorisation holder to take account of scientific and technical progress and enable the medicinal product to be manufactured and checked by means of generally accepted scientific methods.

For details, see MHRA

Posted by Tim Sandle

Thursday 12 March 2015

Clostridium antitoxins – monographs withdrawn

From Jan 1 2015 the monographs (0339, 0340 & 0341) for three Clostridium antitoxins for veterinary use will cease to form part of the European Pharmacopoeia.
  • Clostridium novyi alpha antitoxin for veterinary use (0339),
  • Clostridium perfringens beta antitoxin for veterinary use (0340),
  • Clostridium perfringens epsilon antitoxin for veterinary use (0341)

For further details see: Ph. Eur.

Posted by Tim Sandle

Wednesday 11 March 2015

Antibiotic bacteria lurking in rivers

Rivers appear to be a significant source of antibiotic resistant bacteria, and have a consequential impact on the environment. New research into the river Thames has found numbers to be higher near waste water treatment works.

In 2013 Digital Journal reported that antibiotic-resistant bacteria had been isolated in specific spots along the Hudson river, from the Tappan Zee Bridge to lower Manhattan. The cause was linked to raw sewage being pumped into the water. Now similar research has uncovered the same trend in the U.K.

The finding is the outcome of a joint project between microbiologists working at University of Warwick's School of Life Sciences and the University of Exeter Medical School.

The research into the river Thames has discovered high numbers of antibiotic resistant bacteria and has shown that the numbers of such bacteria are highest close to water treatment facilities. Many of the bacteria recovered are from the class Enterobacteriaceae, a grouping that includes many human gut pathogens like Escherichia coli.

For the study, the microbiologists analysed water and sediment samples from 13 sites across the Thames river catchment and developed detailed models to predict the distribution of antibiotic resistant bacteria.

This supports the theory that high numbers of antibiotic resistant bacteria are released into the environment through human and agricultural use. With agriculture, the situation arises because of the administration of antibiotics to farm animals. This is done to increase the quality of meat. However, it is hard to avoid animal slurry from entering rivers, especially during times of heavy rain.

The results are important due to the concerns with the rise in antimicrobial resistant bacteria and the risks these organisms pose to human health (especially with those receiving hospital treatment.)

In terms of waste water treatment, it was found that not all water processing plants are the same. Those that use a third phase of sludge treatment (tertiary plants) tended to pump out lower numbers of bacteria (and hence lower numbers of antibiotic resistant bacteria.)

The findings have been published in The ISME Journal. The research is titled “Validated predictive modelling of the environmental resistome.”

Posted by Tim Sandle

Tuesday 10 March 2015

EU GMP Annex 1 – time to comment

The European Medicines Agency (EMA) has issued a concept paper in which it is recommended to revise the current annex 1 of the European GMP Guidelines, on the manufacture of sterile products. A public consultation is now under way on this concept paper, with a deadline of 31 March 2015.

Key proposals include:
  • The revised guideline will clarify to what extent Q9 and Q10 should be followed in the design and implementation of facilities, equipment and processes for the manufacture of sterile medicinal products.
  • Revision to the Ph.Eur. monograph on methods other than distillation for the production of water for injection.
  • Broaden the scope beyond sterile products since guidance on the conditions of the manufacture of some non-sterile finished products and the early stages in the manufacture of a range of products is important.
  • To encourage the use of new technologies to protect sterile products (the proposal states: “embrace the use of new technologies to prevent detrimental impact on product and also to encourage the introduction of new technologies that are not currently covered.”) 

In terms of when the guide is likely to come out, the timetable is: 
  • Preparation of draft concept paper - September 2014
  • Approval of draft concept paper - October 2014
  • Released for consultation – February 2015
  • Deadline for comments – March 2015
  • Discussion in PIC/S Committee – May 2015
  • Discussion in GMDP IWG - June 2015
  • Discussion with other Working Parties - June 2015 – September 2015
  • Proposed date for release of draft guideline - October 2015
  • Deadline for comments - April 2016
  • Re-discussion in GMDP IWG - June 2016
  • Re-discussion in PIC/S Committee – July 2016

The document can be found here.

Posted by Tim Sandle

Monday 9 March 2015

Auditing Cleanrooms

Quality auditing is the systematic examination of a quality system and audits form an important part of Good Manufacturing Practice (GMP). Auditors need to be knowledgeable about cleanroom operations, and have an understanding of microbial contamination as well as being trained specifically as auditors. Ideally, the auditors should have complete independence of the functions they are auditing.

This is the basis of an article by Tim Sandle for Cleanroom Technology. The reference is:

Sandle, T. (2015) Auditing Cleanrooms, Cleanroom Technology, February 2015, pp66-68

For a copy of the article, please contact Tim Sandle

Many aspects of a cleanroom are designed to ensure contamination control, including the control of air movement, air filtration, cleanroom practices, cleaning and disinfection schemes. Tim Sandle discusses how the different aspects are checked and assessed through the audit process.

Posted by Tim Sandle

Sunday 8 March 2015

Bacteriology reference department (BRD): user manual

A guide to Public Health England's bacteriology reference department (BRD), its units, and the tests and services they provide, has been made available.

The document can be accessed here.

Posted by Tim Sandle

Saturday 7 March 2015

Urease Test explained

The urease test is used to differentiate urease-positive organisms (e.g. Proteus) from other organisms. It can also be used to detect the presence of Helicobacter pylori.

The urease test is used to determine the ability of an organism to split urea, through the production of the enzyme urease. Two units of ammonia are formed with resulting alkalinity in the presence of the enzyme, and the increased pH is detected by a pH indicator.

For more about the urease test, see a special technical note from Public Health England.

Posted by Tim Sandle

Friday 6 March 2015

Bacterial crystal structure

Two crystal structures for translocator protein (TSPO)—from the bacteria Bacillus cereus and Rhodobacter sphaeroides—are the latest pieces in the puzzle that is determining the functions of this integral mitochondrial membrane protein. The structures, published in the journal Science, are a match, but they differ from a published murine TSPO.

“Membrane proteins are very difficult to work on . . . so when you have two independent groups actually coming up with seemingly identical or very similar structures, it’s very gratifying,” said structural biologist Chris Tate of the Medical Research Council’s Laboratory of Molecular Biology in Cambridge, UK, who was not involved in the studies.

“This protein is 5 billion years old, so it has been evolving over all that time and has adapted to the various needs of the tissues, cells, and species. . . . It’s not surprising that it may really have diverse roles,” Vasillios Papadopoulos, a professor of medicine at McGill University in Montreal stated.

For more on this interesting research, see The Scientist.

Posted by Tim Sandle

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