Monday 30 September 2013

Cannabinoid receptors and anorexia nervosa

There could be a connection between anorexia and cannabinoid receptors, according to a new research report by Cindy Casteels, a Post-Doctoral Researcher of the Division of Nuclear Medicine and Molecular Imaging at Katholieke Universiteit Leuven, located in Leuven, Belgium. Cindy's PhD thesis was in Molecular imaging of the type 1 cannabinoid receptor in movement disorders, under supervision of Prof. K Van Laere.

Anorexia nervosa is an eating disorder characterized by food restriction and irrational fear of gaining weight, as well as a distorted body self-perception. Cindy's focus on anorexia is due to the significant impact that the disease has on the lives of many people.

As well as psychological factors, some medics also think that there is a physiological consequence for anorexia. Specifically, there could be a connection between a dysfunctional endocannabinoid system (ECS) and eating disorders. The ECS is a term given to a group of lipids and receptors that are involved in a variety of physiological processes. Cindy explains the significance of the ECS: "The endocannabinoid system (ECS), a major neurotransmission system, is involved in numerous physiological processes often related to homeostatic balance but also in neuro-protection, motor behavior, memory regulation, addiction and cognition. It consists of a family of naturally occurring lipids, the endocannabinoids, of degradation proteins and of cannabinoid receptors."

These receptors are found in the brain, organs, connective tissues, glands, and immune cells, and they are produced naturally by the body. One function of the ECS Cindy explains, is "as an important component in many different homeostatic processes in living organisms, including food intake, energy metabolism and reward processing. It is therefore a potentially interesting therapeutic target in eating disorders such as anorexia and bulimia nervosa, but also in obesity."

Specifically, in relation to body health, the ECS helps to control the way the body reacts to certain foods and the feeling that people get from eating food (what are termed the ‘hedonic aspects’ of eating). One type of receptor, found as part of the ECS, called CB1, is part of the brain region that control food intake, reward and energy balance.

Another function of the ECS is mediate the psychoactive effects of marijuana. This is because marihuana contains phytocannabinoids. These are plant substances that stimulate cannabinoid receptors, such as the Delta-9-tetrahydrocannabinol (THC), which is the most psychoactive of the marijuana cannabinoids. Phytocannabinoids help to stimulate the endocannabinoid system, and also influence the production of receptors. The ECS receptor that is stimulated is CB1, the same receptor that is linked to food intake and food enjoyment.

Cindy surmises: "Regarding food intake, animal studies showed that CB1 knockout mice are leaner than control mice due to reduced food intake, and the same mice are resistant to diet-induced obesity when subjected to a highly caloric diet without their energy uptake being reduced."

To explore this further Cindy Casteel's research team undertook studies on rats (rodents are good candidates for studying eating disorders). In the study, one group of rats were bred to be anorexic and were placed in cages with running wheel; another group were also bred to be anorexic but they were not given a running wheel; a third group were fed a normal diet and were given a running wheel and a final 'control group' were fed normally but they did not have a wheel to exercise on. These various groups were designed to mimic all variables of anorexia nervosa in rats.

For the simulation of anorexia, animals are food restricted (only allowed access to limited amounts of food for short periods) and are given unrestricted access to a running wheel. This is designed to reproduce both the behavioral and neurophysiological conditions of anorexia nervosa. To model anorexia Cindy explains that "the target weight was ~85% of initial weight."

The investigation into the effect of cannabinoids on the rats was shown by an advanced nuclear imaging technique called positron emission tomography (PET). The imaging was designed to look at cannabinoid receptors inside the rats. The researchers scanned the rats for CB1 receptor availability during the anoreix nervosa condition, when they gained weight again.

The study's results have been published in the European Journal of Nuclear Medicine and Molecular Imaging.


According to Cindy: "Future studies simultaneously measuring brain endocannabinoid levels and CB1 receptor binding are needed to further clarify this issue. Of special interest, we have observed a similar finding of a widespread increase in female anorectic patients, suggesting validity of our animal model to mimic human CB1 receptor alterations in anorexia nervosa."

Sunday 15 January 2012

Clean Room Technologies


Advances in cleanroom technologies (new article Sandle and Saghee #1)

In collaboration with Madhu Raju Saghee, the India based GMP expert, we have written an exciting new article examining the more recentadvances in cleanroom technologies. The article is published on-line for 'Express Pharma', the journal for pharmaceutical professionals (Home Page).

The introduction to the article reads:

There have been a number of advances in new cleanroom technologies, which have helped to both reduce the risk of contamination and to streamline process operations. The majority of these technological developments have been orientated towards the manufacturing of sterile products, particularly aseptically filled products. Tim Sandle, Head of Microbiology, Bio Products Laboratory, UK and Madhu Raju Saghee, Corporate Quality Assurance, Gland Pharma review some of the more significant advances in cleanroom technology.

In the article we examine clean-air devices, isolation technology, RABS, weighing stations, clothing, disposable single use technology, aseptic connections, filling machines and more.

To read the article go toAdvanced cleanroom technology

We would welcome your comments. Please also let us know if you would like us to contribute any articles or technical papers.






Paper reference:

Sandle, T. and Saghee, M.R. (2010): Advances in cleanroom technologies, Express Pharma16th-30th September.

Pharmig Training CDs

 Pharmig have issued two training CDs ("electronic packs"), designed to promote best practice in microbiology laboratories. They are designed to act as training guides for new laboratory mangers and supervisors and to provide a way for established laboratories to benchmark their systems against current industry standards. The CDs contain notes, presentations and a wealth of forms and templates. The CDs are:
  • Best Practices in Microbiological Documentation
  • Setting up and managing an effective training programme in the microbiology laboratory
The contents of each CD runs (see below):


Pharmig Electronic Pack 1: Best Practices in Microbiological Documentation
Folder
Contents
Notes
A: Introduction
Introduction to the Good Documentation Practice and the contents of the CD

B: General Documentation
B1. A. Confidentiality agreement
B2. Technical agreement
B3. Quality manual
B4. SOP template
B5. Document change form
B6. Internal audit report
B7. Training worksheet
These documents provide examples of the general laboratory documentation required. These are: confidentiality agreement (a pre-requisite for a contract test laboratory to have with its clients); technical agreement (typically drawn up between the client and the test laboratory); the quality manual, required by all GMP inspectable organisations; a generic SOP template, detailing each of the required headings; an example of a form used to request changes to documentation; an example of an internal audit report, as an example of best practise; and an example of training documentation.
C. Equipment Documentation
C1. New equipment approval form
C2. New equipment risk assessment
C3. User requirement specification
C4. Validation master plan
C5. DQ protocol
C6. IQ protocol
C7. DQ/IQ combined template
C8. OQ protocol
C9. PQ protocol
C10. Validation of equipment risk assessment
C11. Validation report
This section of the CD contains eleven documentation examples and templates relating to equipment validation. This consists of a template for approving new equipment and for the related risk assessment for the introduction of a new item of equipment. The form for the user to define the equipment requirements (URS) and an example of a validation master plan. There section includes the various qualification templates for equipment validation: design qualification (DQ), installation qualification (IQ), plus an example of how these two stages can be combined; operational qualification (OQ), performance qualification (PQ), validation of equipment risk assessment, and a generic validation report.
D. Laboratory Documentation
D1. Document distribution form
D2. Document read list
D3. Document reconciliation form
D4. Document request form
D5. Document review form
D6. Document signature list
D7. Equipment clearance certificate
D8. Stability study test protocol
This part of the pack contains the basic laboratory documentation, centred on documentation control. This includes example documentation for distributing documentation between staff, reading lists to demonstrate training compliance, forms of the reconciliation of documentation and review and signature lists. Also include is a template for an equipment clearance form (required for external examination or calibration of equipment) and an example laboratory protocol relating to a stability trial.
E. Laboratory Test Documentation
E1. Request for analysis form
E2. Additional sample request form
E3. Laboratory validation protocol
E4. Laboratory test sample plan
E5. Autoclave log book
E6. Media QC logbook
E7. Equipment log folder
E8.Example of a test work sheet
E9. Balance logbook
E10. Change control form
E11. Deviation report
E12. Bacterial Endotoxin test method
E13. Sterility test method traceability
E14. Total viable aerobic count method
E15. Out of specification form
E16. Laboratory report template
This section of the pack contains the essential test and analysis documentation for the laboratory. This includes forms for requesting samples for analysis; a template for devising a laboratory validation protocol and a laboratory sample plan. The section also includes example equipment log folders and logbooks (including an autoclave and balance). Other aspects of documentation are covered through change control, deviation reports and out of limits forms. Also included are examples of general test paperwork relating to areas like endotoxin and sterility testing.
F. Electronic Data Management Systems
PowerPoint slides
This section contains a set of PowerPoint slides on the subject of Electronic Data Management Systems and the design of documentation management systems. Reference is made to Good Automated Manufacturing Practice.
G. Documentation Non-Conformances
PowerPoint slides
This section contains a set of PowerPoint slides written by Tim Sandle on the subject of non-conformance relating to documentation. Coverage is given to issues raised by regulatory authorities and to the concept of human error.

Pharmig Electronic Pack 2: Setting Up & Managing an Effective Training Programme in the Micro Laboratory
Folder
Contents
Notes
A: Introduction
Introduction to the Best Microbiology Laboratory Training

B: Induction material
B1. Induction Programme
Induction
 B2. Training Programme
Induction
B3. Probation Review
B4. Job description
B5. Abbreviated CV
This file contains examples of the important forms required for new starter induction, including the training programme.
Also included in this section are a draft job description for a microbiology technician and an abbreviated curriculum vitae.
C. Employee development
C1. Personal development review plan
C2. Personal development review plan continued
C3. Personal development review plan continued
C4. Personal development review plan continued
C5. Personal development review plan for learning and development
C6. Personal development review plan for performance objectives
C7. Personal development review plan for manager and staff review
C8. Personal development review plan for establishment of development needs
C9. Personal development review plan for progress review

This section contains a variety of materials geared towards the new employee induction and development, including the mechanism for capturing and identifying training needs.
The section also includes employee performance objectives.
D. Employee appraisal
D1. Self appraisal form
D2. Appraisal interview summary

This section contains a basic appraisal system framework for both running the review and for the employee’s own self assessment
E. Good Manufacturing Practice
E. Introductory GMP training questions
This section contains examples of GMP training questions, both of a general nature and in relation to microbiological practices
F. External training
F. External Training and Development
This form is a useful one for capturing the external training that  anew employee has been on and for facilitating feedback and learning outcomes
G. Measuring training
G1. Personal and Development Training
G2. Personal and Development Training SOP
G3. Company training worksheet example 1
G4. Company training worksheet example 2
This section contains the paperwork required for reviewing, measuring, recording and trending training against SOPs. It contains several useful reconciliation tools. This section is presented as an example of best practice.
H. Training in microbiological techniques
H1. General Microbiology
H2. Gram Staining
H3. Aseptic Techniques
H4. Media QC
H5. Environmental Sampling
H6. Sampling & Plate Counting
H7. Identifications
H8. Microbial Limit Tests
H9. Endotoxin Testing
H10. Sterility Testing
H11. Cleaning & Disinfection
This section contains several examples of training in microbiological techniques. This includes the practical areas to be assessed and the types of questions required for assessment and the means to measure competency.
I. Training Non-Conformances
PowerPoint slides
This section contains a set of PowerPoint slides written by Tim Sandle on the subject of non-conformance relating to training issues. Coverage is given to issues raised by regulatory authorities.
J. Train the Trainer
PowerPoint slides
This section contains a set of PowerPoint slides written by Brian Alexander on the how to make a good trainer and the type of training needed for a microbiology trainer.
K. Training matrix
J1. SOP defining the training matrix
J2. Example of a training matrix
This section examines how training can be tracked across the laboratory using a training matrix and how different levels of training, from beginner to expert, can be defined.

The CDs have been written and produced by Tim Sandle and Brian Alexander.

The full references are:

Sandle, T. and Alexander, B. (2011). Electronic Pack 1: Best Practices in Microbiological Documentation, Pharmaceutical Microbiology Interest Group, Pharmig: Stanstead Abbotts, UK

Sandle, T. and Alexander, B. Electronic Pack 2: Setting up and managing an effective training programme in the microbiology laboratory, Pharmaceutical Microbiology Interest Group Pharmig: Stanstead Abbotts, UK

The CDs cost £75.00 ($130) for Pharmig members and £99.00 ($175) for non-members.
For details: Pharmig CDs

Monday 21 November 2011

Pharmig Training Packs

Pharmig Training CDs

Pharmig have issued two training CDs ("electronic packs"), designed to promote best practice in microbiology laboratories. They are designed to act as training guides for new laboratory mangers and supervisors and to provide a way for established laboratories to benchmark their systems against current industry standards. The CDs contain notes, presentations and a wealth of forms and templates. The CDs are:
  • Best Practices in Microbiological Documentation
  • Setting up and managing an effective training programme in the microbiology laboratory
The contents of each CD runs (see below):

Sunday 13 November 2011

Pharmig 2011 Conference

The UK and Ireland Pharmaceutical Microbiology Interest Group (Pharmig) are holding their 19th conference on Wednesday 16th and Thursday 17th November 2011. The event is open all.

Speakers and sessions include:
  • Recent issues & observations during EU GMP Inspection by Neil Raw – GMP Inspector, MHRA Sustaining a lean QC Microbiology laboratory – case study by Amy McDaniel – Director, QC Microbiology, Pfizer (USA)
  • Risk based approach for determining objectionable micro organisms by Dr. Stephen Rawlings – Principal Microbiologist, GlaxoSmithKline
  • Regulatory update - items of interest for the microbiologist by Dr Tim Sandle, BPL
  • Advances in Microbial Identification by Sarah Wallis – Registered Specialist Biomedical Scientist, Sheffield Teaching Hospitals NHS
  • Risk management of contamination during cleanroom operations by Tim Eaton – Sterile Manufacturing Specialist, AstraZeneca
  • Sterility Failure – What happens next? by Neil Raw – GMP Inspector, MHRA
  • The manufacturing plant microbiologist – breaking barriers and building relationships by Scott Smith – Microbiology QC Leader, Sanofi-Aventis
  • Best practices for performing contamination investigations by David Keen – Supply Microbiology Manager, Reckitt Benckiser
  • How to justify doing less monitoring, sampling and testing and still pass an inspection by Stewart Green – Managing Director, GXP Consulting
  • Developing a meaningful environmental monitoring programme for sterile/non sterile products by Dr Julia Mottishaw – QP, Teva Runcorn
  • Applications of risk assessment in the microbiology laboratory by Amy McDaniel, Pfizer
  • Cleaning and Disinfectant Validation by Kim Morwood, MGS
  • What is an objectionable organism? by Stephen Rawling, GlaxoSmithKline
  • Method Validation by Julia Mottishaw, Teva Runcorn
The venue is: The Nottingham Belfry Hotel, Mellor’s Way Off Woodhouse Way, Nottingham, NG8 6PY. UK

To read more read the brochure: Pharmig Conference

Pharmaceutical Microbiology Book

THE GOLD STANDARD FOR STERILE MANUFACTURING Injectable product manufacturing is booming because of the growth of new biopharmaceuticals and small molecule anticancer drugs. The requirements for contamination control will become even more stringent than today. Isolators or blow-fill-seal equipment have already replaced the conventional clean rooms and LAF-hoods in many production facilitities. Conventional microbiological monitoring methods, requiring 3 to 5 days of incubation will become inappropriate. Equipment is already available allowing real time, simultaneous viable and non-viable counting. This book is a useful reference guide for the SMB (Small and Medium Business) pharmaceutical sector which does not have the resources to have access to such top-quality information in this field. This book therefore represents an unparalleled and unprecedented text in the field of pharmaceutical and medical device microbiology. Perhaps even more outstanding is the fact that this book not only covers subject matter and technical content which is established as best and expected practice, but also includes content regarded as possible, future and emerging technology or processes.

The results of 45 years of scientific and technological development are laid down in these 33 chapters. These chapters, all written by international experts, give a vivid picture of today s pharmaceutical microbiology. The high standard of the chapters makes it an essential reference guide that should be on the shelf of everyone who is involved or interested in this field. Experts from top pharmaceutical companies like Baxter, Johnson and Johnson, Amgen, Pfizer, Patheon, Sartorious, Gador, Catalent, British NHS, GE Healthcare and many more top experts from industry and academics have come together to create this collection of knowledge of Microbiology as related to Pharmaceuticals, Medical Devices and Biotechnology. The list of authors includes chair and members of USP expert committee on Microbiology and Sterility Assurance, president and senior experts in Parenteral Drug Association, ISPE and ASTM. Foreword by Hans van Doorne, Chair of EDQM, Committee on Microbiology. Contents 1. The Essentials of Pharmaceutical Microbiology by Tim Sandle and Madhu Raju Saghee 2. Relevance of Microorganisms in Pharmaceutical Processing by Ossama M. El-Tayeb 3. Microbial Contamination and Spoilage by David G. Allison 4. Microbiological Considerations in Medical Device Industry by Martell Winters 5. Selection of Microbiological Culture Media and Testing Regimes by Tim Sandle 6. Microbial Identification by Ziva Abraham 7. Microbial Examination of Non-sterile Products by Jaymie Tomes and Florence Wu 8. Practical Approaches to Sterility Testing by Tim Sandle 9. Microbial Aspects in Cleaning Validation by Andrew Walsh 10. Validation of Microbiological Methods by Sandy Rubio 11. Selection and Validation of Disinfectants by Paul Vina, Sandy Rubio and Tim Sandle 12. Auditing a QC Microbiology Laboratory by Andy Martin 13. Quality Assurance in a Microbiology Laboratory by Christophe Barcella 14. Environmental Monitoring by Tim Sandle 15. Microbial Content Testing of Pharmaceutical and Biotechnologically Derived Products by Dilip Ashtekar and Tim Sandle 16. Bacterial Endotoxins Test by Masakazu Tsuchiya 17. Antimicrobial Effectiveness Testing by Scott V. W. Sutton 18. Monitoring of Microbiological Quality Attributes of Water for Pharmaceutical Use by Dilip Ashtekar 19. Investigation of Microbiological Data Deviations by Monica Lagomarsino 20. Alternative Microbiological Methods and New Pharmaceutical Microbiology Curriculum by Claudio D. Denoya 21. The Implementation of Rapid Microbiological Methods by Michael J. Miller Total 33 chapters included in the book.

Complete info at businesshorizonsdotcom