Tim Sandle

Tim Sandle
The University of Manchester · School of Pharmacy and Pharmaceutical Sciences

PhD
Interests: Disinfection, Microbiology, Contamination Control, Risk Management, Healthcare.

About

867
Publications
1,985,431
Reads
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2,085
Citations
Introduction
Dr. Tim Sandle is a chartered biologist and holds a first class honours degree in Applied Biology; a Masters degree in education; and has a doctorate from Keele University. Dr. Sandle works at BPL. He is a tutor with the School of Pharmacy and Pharmaceutical Sciences, University of Manchester for the university’s pharmaceutical microbiology MSc course. He is also a visiting lecturer at University College London.
Additional affiliations
January 2002 - present
Pharmig
Position
  • Communications lead
Description
  • Communications lead, newsletter editor, and presenter (conferences and webinars) for Pharmig (Pharmaceutical Microbiology Interest Group).
Position
  • Researcher
September 2006 - present
University of Manchester
Position
  • Visiting tutor
Description
  • Tutor in Pharmaceutical Microbiology
Education
January 2005 - March 2010
Keele University
Field of study

Publications

Publications (867)
Article
Full-text available
Cleanroom microflora are of importance for microbiologists and quality control personnel in order to assess changes in trends. Shifts in the types of microflora may indicate deviations from the "norm" such as resistant strains or problems with cleaning practices. Given the few published studies of the typical microflora, this paper uniquely reviews...
Article
Full-text available
Aims: To examine for psychrophilic or psychrotolerant micro-organisms in pharmaceutical cold rooms (in relation to numbers, incidents and species) and to determine, where such micro-organisms are present, whether standard microbiological environmental monitoring regimes require modification. This is presented as a case study. Methods and results:...
Article
Full-text available
Cleanroom wipes, saturated with disinfectant, are commonly used within pharmaceutical grade cleanrooms as part of contamination control programmes. Whilst standards are in place for the testing of wipes for particle shedding, there is a limited data relating to the particle generation from wipes when they are used in practical conditions. This pape...
Article
Full-text available
Whilst the pharmaceutical microbiologist now faces a somewhat bewildering array of different test systems, once the selection has been made it is important, from a GMP perspective, that the system is validated. For this, both the United States Pharmacopeia and European Pharmacopeia offer some guidance. In general, the two approaches share more simi...
Data
Full-text available
The aim of this study was to describe the incidence of contamination of pharmaceutical products by melanized fungi and to consider control measures in relation to bioburden and cleanrooms. This study reviews and analyses pharmaceutical product recalls and offers incidence rates of fungal detection from a typical cleanrooms. The recalls include some...
Article
Biological printing (bioprinting) is a form of additive manufacturing that utilizes living cells, proteins, and nutrients as the basis of raw materials for manufacturing biomaterials for medicine and samples for the use in pharmaceutical development. A future goal is to use it to create entire organs for transplants, since 3D bioprinted models can...
Article
Full-text available
When does fluid mechanics meet microbiology? An important fusion is with understanding water systems and contamination control. One of the important design considerations for pharmaceutical and healthcare facility water systems is the velocity of the water flowing through pipework. Specifying the flow is an important contamination control measure,...
Preprint
Full-text available
Actually, liver pathologies pley a central role in medicine. So are differents studies in this research direction. In liver pathology, including liver cirrhosis, during illnes status, are implied three cytochrome P450 (P450 or CYP). In this direction play a role also gene families CYP 1, CYP2 and CYP3. Liver diseases are associated with metabolic a...
Article
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ISO 9001: 2015 is a process-focused quality management system (QMS) standard that requires all quality system processes to be measured, monitored, controlled, and improved. To comply, both business and quality objectives need to be established for relevant functions at appropriate levels, and these objectives need to be measurable. When objectives...
Article
Full-text available
CBiol, FIScT | EJPPS | 294 (2024) | Click to download pdf Back to Journals | Article | Summary | References | Author There are different factors that influence the accuracy of light-scattering particle counting within the cleanroom. There are variations between different instruments in terms of their collection efficiency, such as the effect of coi...
Article
Full-text available
Validation is a well-established concept in the pharmaceutical manufacturing industry. One of the early definitions used by the US FDA still holds true, presenting the validation concept as “establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determin...
Article
Full-text available
Sterile single-use disposable technologies present considerable advancements for pharmaceutical manufacturing, improving process design and reducing turnaround times. These technologies will have described chemical, toxicological, physical, morphological and mechanical properties. Despite their many advantages, there are also potential draw backs w...
Article
Full-text available
A biotechnology company has sought to re-invent how biologic drugs are invented by using patented technology to adapt the food algae spirulina to deliver therapeutic proteins1. Spirulina (Arthrospira platensis (Nordstedt) Gomont, formerly Spirulina platensis and Spirulina maxima) is a species belonging to the Cyanobacteria class that lives in fresh...
Chapter
One of the most urgent healthcare needs facing society is antimicrobial resistance, creating a pattern whereby diseases that were once straightforward to treat are becoming increasingly challenging. The situation requires smarter approaches to treatment and the generation of new antimicrobials. These processes involve shifting through millions of c...
Article
Dr. Tim Sandle discusses some of the common issues encountered in the sterilisation of surgical instruments, using autoclave technologies. He argues that to make a thorough evaluation of sterilisation, reliance cannot be restricted to chemical or biological indicators, and a complete understanding of hazards and physical operating parameters is req...
Article
In recent years, novel medical technologies like cell and gene therapies have demonstrated significant promise for treating a range of diseases like cancer and heart disease. Other advances in medicine have focused on repairing or promoting the natural repair of internal injuries. Several of these potential breakthroughs have been hampered by a lac...
Article
Full-text available
Academic writing is distinct from personal writing. Firstly, some kind of structure is required, such as a beginning, middle, and end. This simplified structure varies between the ‘report’ and the ‘essay.’ In this article, some tips are presented for approaching both academic reports and essays. Sandle, T. (2024) Tips for approaching academic writ...
Article
Full-text available
Mycoplasmas are very simple bacteria. They have a minimalist genome and no protective cell wall (due to the absence of peptidoglycan). In fact, mycoplasmas possess the smallest genomes of any organism able to replicate itself. Mycoplasma genitalium is said to be the world's smallest free-living bacterium with only 525 genes, as opposed to the 4,288...
Article
Full-text available
The revision to EU GMP Annex 1, in August 2022, updated the requirement for Grade A environments used during sterile manufacturing. This was the change in acceptance criteria to ‘no growth’ (from the previous value of 1 CFU). This change not only paves the way for alternative microbiological methods it signalled the shift in regulatory thinking tow...
Preprint
Full-text available
A specific key point in liver cirrhosis is the decreased metabolic capacity for drugs. So medicines which are metabolized by oxidative biotransformation play a great role in liver pathology. Responsible for the drug metabolism that takes place in liver during illnes, are three cytochrome P450 (P450 or CYP) gene families in liver microsomes (CYP 1,...
Article
Full-text available
Wastewater treatment plants are present within many pharmaceutical facilities, due to the scale of operations and to ensure that the pollutant concentrations in the treated wastewater comply with the local and/or national regulations regarding disposal of wastewaters into community treatment plants or into rivers, lakes or oceans¹. Due to pollution...
Presentation
Full-text available
When it works well, hydrogen peroxide in vapor or areolized form can be an effective means of ‘no-touch’ biodecontamination. However, operational limitations can create technical challenges for industrial‐scale adoption and inconsistency in the method of delivery can sometimes lead to fragility affecting the reproducibility of cycles. This present...
Preprint
Full-text available
HIV infection is a nowadays pathology that affect persons from all of the world. Pathogenesis of the HIV-infection and cancer is a great problem, with a complexity directions in research. More important in HIV infection to patients, is also to take into consideration others things, such as prevention, diagnosis, monitoring, treatment, including con...
Article
Full-text available
This article considers the necessary steps to be undertaken for the design, construction and certification of cleanrooms used in pharmaceutical manufacturing environments. The article focuses on the engineering aspects relating to airflow and air filtration designed to achieve contamination control. In considering modern approaches, the article add...
Preprint
Full-text available
Pathogenesis of the connection of HIV-infection and cancer is a nowadays problem for research. More important is also to take into consideration a complexity of abordasions, such as prevention, diagnosis, monitoring, treatment, including control measures. These should be supported by statistical studies that report on restricted or extended geograp...
Article
Full-text available
Where there are people there is a risk of contamination. Part of developing a successful contamination control assessment is identifying this risk, whether that is through inadvertent touching and transferring contamination or simply the shedding of skin detritus. Here Dr Tim Sandle explains why understanding our own microbiomes are key to this pro...
Article
Full-text available
Some proteins and many cell cultures are infected with viruses. Should a virus survive the manufacturing process, it presents an impurity with the ability to risk patient health. For this reason, biopharmaceutical manufacturers need to invest and develop virus clearance approaches. At least two viral clearance steps that either remove or inactive...
Article
The range of sampling methods for the environmental monitoring of cleanrooms has included swabbing for several decades. It has long been accepted that the use of swabs leads to a relatively low recovery of microorganisms from surfaces. However, the recovery from swabs can be improved by selecting flocked swabs over plain swabs and with fine tuning...
Article
Full-text available
This article looks at the use and control of reference standards, including what constitutes reference materials and areas of their application. Different categories of reference materials are outlined, together with the methods for their preparation and assessment. The article also looks at the different standards for the use and preparation of re...
Article
Full-text available
Maintaining compliance for the sterility test, demonstrating the validated state, enabling testing consistency, and showing traceability of consumables-each an important component of laboratory data integrity-has been made easier through the introduction of Merck's M-Trace ® system. This article looks at the importance of sterility test compliance...
Article
Full-text available
As rapid microbiology methods continue to develop, many exciting technologies are starting to emerge. This article presents areas for consideration when looking to select a method and design a business case. The aim is to offer general advice to those tasked with making the selection and undertaking the work required to qualify the method so that i...
Article
Fungal contamination in pharmaceutical products represents a potential hazard for two reasons. First, it may cause product spoilage; the metabolic versatility of fungi is such that any formulation ingredient may undergo chemical modification in the presence of a contaminating organism. Spoilage not only affects the therapeutic properties of a produ...
Article
Ideas for extending automation to the endotoxin test has primarily been approached through machinery, to improve assay precision, and through other forms of automation to improve data integrity in terms of sample traceability (including data transfer to laboratory information management systems) and to enable the assessment of data patterns and tre...
Chapter
AI/ML is predicted to be the top technology investment for 60 percent of life sciences companies over the next two years, according to a recent survey from the Pistoia Alliance. In this chapter, advances of AI within the field of microbiology are considered, focusing on technologies that are enhancing the governance of contamination control and w...
Article
Full-text available
The new Annex 1 places even more emphasis on the risks of cross-contamination within aseptic production areas. Not surprisingly, it offers several specifications about the transfer of materials: the use of material pass-boxes with integrated biodecontamination systems, as well as airflow trolleys, becomes essential.
Article
All microorganisms require some amount of water in order to reproduce. Microorganisms take up water by moving it through their cell membranes. This is why, even with all the necessary growth factors, water is proportionately the largest ingredient within culture media. Water is required for metabolic activity and as a biophysical factor. The amount...
Article
Full-text available
There are different factors which influence water system contamination. Good design features are concerned with generation processes, keeping organisms out of water systems and having in-built controls to reduce the possibility of survival. One factor that influences the potential for microbial survival is the presence of organic material – signifi...
Article
Full-text available
Microbiological culture media is either a solid, liquid or semi-solid composite designed to support the growth of microorganisms. It is represented as the commonly seen solid agar in a dish (the Petri dish) or liquid broth in a bottle. Liquid media are used for encouraging growth or for continuously maintaining reproduction, as with pure batch cult...
Article
Full-text available
Advanced Therapy Medicinal Products (ATMPs) are gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineered products (1). These therapies, without hyperbole, offer ground-breaking new opportunities for the treatment of diseases and injuries. They are particularly important for severe, untreatable or chronic diseas...
Article
Good contamination control measures include cleaning and disinfection, which play an important function in keeping cleanrooms and equipment sanitary. Such requirements extend to transfer disinfection. The optimal material for the construction of equipment and transfer hatches is electropolished stainless steel due to the minimising of opportunities...
Article
The U.S. FDA has now finalized a guidance document on the immunotoxic potential of pharmaceuticals after issuing the draft guidance in February 2020. The aim is to provide advice in terms of pharmaceutical product development for the purposes of nonclinical evaluation. There are several pharmacological impurities that can appear, through unintended...
Article
Cleaning validation verifies the effectiveness of cleaning processes within pharmaceutical and healthcare facilities. It should be directed to situations or process steps where contamination or the carryover of materials pose the greatest risk to product quality, as evaluated to appropriate limits. To ensure cleaning process robustness, care must b...
Article
While rapid microbiological methods have advanced, most microbiology laboratory tests remain reliant upon assessing microbial growth on agar plates. Discrepancies with plate counting, together with the limitations of human vision, have led to regulatory concerns to the extent that the U.S. FDA Q&A document on data integrity recommends “double plate...
Article
The modern microbiology laboratory is starting to look very different from the laboratory of 10 years ago, and in the next few years, the microbiology laboratory is set to appear different from the laboratory of today. The work will still involve assessing microbial numbers, determining susceptibility, and identifying organisms, and there will cont...
Article
There are the fungal organisms that pose the greatest risk to human health worldwide. In all, fungi form the World Health Organisation (WHO) priority pathogens list (FPPL). One of the aims is to help to direct global health efforts to research into methods to tackle fungal pathogens, considering that many of the fungi and the diseases they causes r...
Article
An important component of pharmaceutical products and medical device research and development is a focus on the users of the device. Developing an effective device or medication can be easily undone if it is not used correctly, and errors made by patients or clinicians are often a direct result of design limitations.1 Weaknesses can be overcome by...
Article
Full-text available
On the basis of Food and Drug Administration (FDA) of United States of America recall data from 2012 to 2022, heterotrophic microorganisms have caused the majority of microbial contamination incidents reported in non-sterile pharmaceutical products. Some of the products impacted are liquids, tablets, capsules, oils, drops, creams and emulsions. The...
Article
Assessing microbiological data and undertaking investigations into the origins of contamination, establishing root causes, and setting appropriate preventative actions constitutes a core part of the contamination control strategy. Despite the importance of this process, regulatory findings frequently cite poor quality microbial investigations. Thi...
Preprint
Full-text available
The study aimed to manage and to analyse the results of the laboratory tests, routinallypractice for hepatitis C diagnosis, using blood tests. Statistical analysis of this study results, was performed using the laboratory informatic system. The results of the study are substantial and intricate reffering to comparision between two methods concretll...
Article
For reworking, a pharmaceutical manufacturer needs to have in place a procedure that includes details on retesting and reevaluation criteria for the nonconforming product after rework. Reworking should be associated with a deviation record (for the original reason to consider rework) and executed under change control. As well as standard product-re...
Article
Full-text available
For several decades isolators, as separative devices, have been commonplace in pharmaceutical and healthcare products manufacturing. Although isolators presented a significant step forward on the contamination control continuum, isolators, if not appropriately operated, can be vulnerable to contamination ingress. The primary mechanism for ingress i...
Article
Full-text available
While these are well-established facts, the ability of M. luteus to survive for prolonged periods within the cleanroom environment is less commonly understood. Excluding endospores, for the common vegetative bacteria, M. luteus displays a level of robustness for prolonged survival within the cleanroom if it is not directly eliminated using a disinf...
Article
A major challenge with antimicrobial drug development is the necessity to test millions of drug compounds in the hope of finding one that will kill a given microbial pathogen. As part of the search for new antimicrobial compounds designed to be effective against emerging drug-resistant bacteria, laboratories are using robotic chemical-synthesizing...
Article
Nanomedicine has advanced considerably in the past five years (as per the OECD nanotechnology R&D intensity measure). Nanomedicine is a broad term, defined as using nanoscale materials, including biocompatible nanoparticles and nanorobots for disease diagnosis, drug delivery, physiological sensing, or for actuation purposes. The innovations in nano...
Article
Full-text available
For effective cleaning validation, appropriate limits need to be set to identify risks of cross-contamination from equipment surfaces, especially where there is shared equipment used across different process streams. To do so requires an understanding of which indirect surfaces pose the greatest likelihood of contamination transfer together with an...
Book
The guide has been completely revised and re-written to provide you with a roadmap to regulatory compliance for cleaning & disinfection. The new text will walk you through the steps needed to design, validate, and implement an effective cleaning and disinfection programme.
Article
For both sterile and non-sterile manufacturing, bioburden control as evidenced by microbial counts is especially important in relation to the quality of the finished product and as an indicator of process control. Samples are drawn from intermediate product at defined stages (ideally based on risk assessment) and these allow for the microbial level...
Article
Rapid microbial tests should be risk-based so the stakeholder can select the preferred technology for their intended use and balance user requirement specifications including time to result, specificity, limit of detection, sample size, and product attributes. Many rapid methods produce signals not based on a colony forming unit (CFU), and that som...
Preprint
Full-text available
Several studies have demonstrated the effectiveness of antimicrobial polymeric flooring (such as the special flooring manufacturing by Dycem). These studies have focused on particulate removal and reductions in microbial levels. What has been less-well studied is the suitability of this type of flooring for the reduction in fungal counts. This arti...
Article
Cleaning validation receives a great deal of attention within the biopharmaceutical industry, not least because of the risks of product adulteration and hence patient harm from improperly cleaned surfaces (notwithstanding additional concerns such as operator protection). Traditionally, cleaning validation efforts focus on direct product-contact sur...
Article
For the past two decades, nanotechnology has promised a revolution in medicine, especially in creating “smart” ways to deliver medicines to specific targets for more effective treatments. Scientists are working on various types of nanoparticles, especially to diagnose and treat cancer. This article considers some of the key innovations within the f...
Technical Report
Full-text available
Anyone working in drug manufacturing knows Dr. Tim Sandle. A microbiologist, author, and science journalist, he is one of the leading experts and figurehead in the field. For this reason, we asked Dr. Sandle for his opinion on the effects of the new ANNEX 1 in the strategies that, with due differences, the entire industry will have to implement: f...
Article
Full-text available
This paper identifies the risks of contamination by viruses in the manufacture of biopharmaceutical products in cleanrooms. Different types of viruses are described with non-enclosed viruses being more resistant to disinfectants. Care should be taken as many common disinfectants are only suitable for bacterial or fungal contamination. A table gives...
Preprint
Full-text available
The study aimed to manage and to analyse the results of the laboratory tests, routinally practice for hepatitis C diagnosis, using blood tests. Comparison of ELISA method results (Enzyme-Linked Immunosorbent Assay) and chemiluminescence methods results. Statistical analysis of this study results, was performed using the laboratory informatic system...
Article
Full-text available
For aseptically filled products, as well as for many terminally filled products, the sterility test is a mandatory product release test. It is, however, statistically poor at detecting anything other than gross contamination (this limitation has been addressed in a number of studies (1)). This limitation relates to the few numbers of articles teste...
Article
Full-text available
There are different elements that contribute to good aseptic technique within the cleanroom and the laboratory. One such element is the donning of gloves (1), handling items appropriately, and keeping gloves regularly disinfected (2). Glove disinfection is an essential step for bacteriological control, although how successful control is maintained...
Article
Full-text available
For isolators to be used effectively, they need to be operating to EU GMP Grade A / ISO 14644 class 5. This is achieved through the barrier concept, the maintenance of a positive pressure, the supply of HEPA filtered air and its extraction, and by subjecting the isolator to an automated decontamination cycle. Isolators are most commonly sanitised u...
Preprint
Full-text available
Chronic liver diseases stimulate a degree of hepatocyte injury. This previously mentioned modifications, alters the known liver architecture and finally ends in cirrhosis. Liver pathology as cirrhosis develops after a long period of pathological alterations. The management of this liver pathology, is centred on the treatment of the causes and compl...
Article
Full-text available
The pathology of childhood occurring with increased frequency is tonsillitis. The infection affects both sexes equally, without any association with environmental factors. The symptomatology attracts attention and requires treatment by a specialized medical team. The severity of the symptoms often leads to surgery to remove these formations via a t...
Article
Gene therapy products are required to be safe, stable, of low toxicity, and of a particular cell type specificity. In some cases, viral vectors are engineered to infect a wide range of cell types; in other cases, the viral vector is modified (pseudotyped) to target a specific kind of cell.1 An important step in the development process is assembling...
Article
With dual-incubation regimes, a key variation in practice concerns the starting temperature and order of incubation. Moving from higher to lower temperatures can inhibit the growth of fungal contamination, not only because fungal growth is optimized at low temperatures, but also because high temperatures could damage the lytic cellular enzymes that...
Book
Graphically representing data is more than just creating pretty pictures; proper data visualization can improve the communication of sometimes abstract information to make data accessible, understandable, and usable. Patterns and insights arise during the review process — whether data are intended for internal or external publication or for inclusi...
Article
Cleaning and disinfection are necessary protective and reactive steps to address microbial deposition on surfaces within pharmaceutical cleanrooms. An appropriately designed cleaning and disinfection program plays a central role in a contamination control strategy. There is considerable literature on the importance of cleaning and with disinfectant...
Article
Full-text available
An important objective of hygienic design relating to the pharmaceutical and healthcare sectors is with the avoidance of product contamination by microorganisms, particles and chemicals. When considering cleaning validation, microbial and chemical deposits and their removal require different approaches and they are influenced by different factors (...
Article
Full-text available
Improving the time-to-result and doing so with greater accuracy has become a topic of concern for the microbiology laboratory as much as it has for other economic sectors. Achieving the result early may improve the chances of patient survival or it may help a firm to reduce inventory hold times. There is a wide spectrum of rapid microbiological me...
Article
Late in 2022, the FDA authorized a new vaccine including an adjuvant, available under emergency use authorization to prevent COVID-19 in individuals 12 years of age and older. The important word is “adjuvant,” the use of which is sometimes open to misinterpretation, especially with traditional adjuvants made from aluminium salts. An adjuvant is a...
Article
Scientific data is concerned with measuring and hence data, whether that is qualitative or quantitative. In pharmaceutical microbiology, this could be a number of cells or colony forming units, a series of growth or no growth results; and incidences of microorganisms. Gathering such data allows for trending and enables control to be achieved. With...
Article
Analytical techniques for validating cleaning methods must evolve to match the pace of an increasingly complex manufacturing landscape for new therapeutics. Within the bio/pharma industry, there is a certain expectation for companies to maintain required levels of cleanliness within their facilities to ensure products that are manufactured are at...

Questions

Questions (3)
Question
What are to best websites (or other media) for keeping up-to-date with regulatory developments and standards? It would be useful to develop a list here, as a resource of the RG community.
Question
With quality risk management, are there any suitable tools or assessments for incorporating 'risk acceptance'?
Question
How might artificial neural networks influence the development of microbiology? It will be interesting to gain your thoughts on potential future insights and technologies.

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