Monday 27 January 2020

Integrating Good Distribution Practice into the QMS

Good Distribution Practice (GDP) concerns the distribution processes for pharmaceutical products that results in medics and patients obtaining access to the medications required. For the pharmaceutical organization, the distribution process occurs both upstream and downstream. Upstream are the suppliers who create goods and services used in a manufacturer’s own operations, such as raw components or materials. The downstream supply chain efficiently distributes a company’s products or services to its customers. Each stage, both upstream and downstream, needs to be proactively managed to minimize quality, as well as financial, confidentiality, operational, reputational and legal risks.

Here is an extract:

These distribution processes concern supply chain, including cold supply chains (where required), and the tracking and tracing of medicines. Traceability includes ensuring that the required environmental controls are met, and that tampering or fraudulent activities are avoided, to the level that each induvial item can be traced from the completion of manufacture to its arrival with the end user (Marucheck et al, 2011). The distribution network for medicinal products is invariably complex and it involves many different parties at different stages. In addition to the challenges associated with this complexity and with protecting the product from being affected by environmental conditions, damage, or loss, there is also a threat from criminal activities centered on seeking to introduce falsified medicines into the supply chain (Bruinsma, and Bernasco, 2004).

GDP requirements are designed to codify and to structure the processes. These requirements bear close similarity to the requirements set out in Good Manufacturing Practice (GMP) regulations. The primary difference is that GDP covers the wholesale distribution of medicines, whereas GMP covers their manufacture.  There overlap between the two rest with the need to maintain product quality after a batch has been released from the manufacturing site, as well as the necessity to monitor and control complaints, address problems, and have a system in place to enact a recall.

In assessing the requirements for GDP, there are different national and supranational standards. In the US GMP is based on the Code of Federal Regulations 21 CFR 210/211, with additional guidance contained within USP chapter 1079 “Good Storage and Distribution Practices for Drug Products.” (USP, 2018) There is an additional USP chapter of interest, chapter 1197 “Good Distribution Practices for Pharmaceutical Excipients” (USP, 2018b). For Europe GDP is based on the Directive of the Board of the European Community 92/25/EEC regarding the wholesale distribution of drugs for human consumption, supported by guideline 2015/C 95/01 (European Commission, 2015), and the Falsified Medicines Directive (European Commission, 2011), which requires a unique identifier and an anti-tampering device to allow the verification of the authenticity of medicinal products. With the World Health Organization, the applicable text is Annex 5 of the WHO recommendations “good distribution practices for pharmaceutical products.” (WHO, 2010a) One commonality through these regulations and following on from items raised during pharmaceutical organization inspections, is with a focus on serialization. This has required for new strategies, processes, and technologies that allow for a business to, at any time, pinpoint the location and origin of any single drug.

A weak GDP system is one where there is a key disconnect between the manufacturer and the process that occurs once the product leaves the facility (Rees, 2013). An overarching area of regulatory concern is with the effectiveness of the incorporation of GDP into the Quality Management System (QMS), a system that applies for both wholesaler and broker. This chapter looks at Quality Risk Management in relation to GDP, covering areas like good distribution principles, the necessity of having Quality Technical Agreements in place, and measures to take appropriate corrective and preventative actions should deviations occur.

The reference is:

Sandle, T. (2019) Integrating Good Distribution Practice into the QMS. In Schmitt, S. (Ed.) Good Distribution Practice: A Handbook for Healthcare Manufacturers and Suppliers, Volume 1, DHI/PDA Books, River Grove, IL, USA, pp241-272

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday 25 January 2020

Four-level food web for gut microbes discovered

A new computational model suggests that the food web of the human gut microbiome follows a hierarchical structure similar to that of larger-scale ecosystems.

In the human gut, hundreds of species of microbes exchange nutrients in a complex food web. Large-scale food webs, such as those of tropical forests, typically follow a hierarchy in which energy flows from plants, to herbivores, to carnivores. Wang and colleagues wondered if the gut microbiome could be considered to follow a similar hierarchy, from microbes that consume nutrients in food eaten by the human host, to those that eat nutrients produced by the first microbes, and so on.

To address this question, the researchers developed a computational model that uses the known species of microbes in a person's gut to predict microbial metabolites -- the substances the microbes generate as part of their biological activities, and which may serve as nutrients for other gut microbes. The metabolite predictions generated by the model are in line with experimental data, providing support for its accuracy.

The new model indeed predicts a four-level hierarchy for the food web of the gut microbiome. This suggests that species composition systematically changes along the length of the gut. Near the entrance to the lower gut, one might find bacteria from the highest hierarchical level -- those that consume nutrients in food eaten by the human. Near the end of the gut, one might find bacteria from the lowest level.

The researchers are now working to refine their model by using a machine-learning approach to infer important competitive relationships between gut microbes. Doing so could improve the model's accuracy, potentially reducing the need for expensive measurements of metabolic profiles in research on gut function.

Journal Reference:

Tong Wang, Akshit Goyal, Veronika Dubinkina, Sergei Maslov. Evidence for a multi-level trophic organization of the human gut microbiome. PLOS Computational Biology, 2019; 15 (12): e1007524 DOI: 10.1371/journal.pcbi.1007524

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

Friday 17 January 2020

Ancient feces reveal how 'marsh diet' left Bronze Age Fen folk infected with parasites

New research published today in the journal Parasitology shows how the prehistoric inhabitants of a settlement in the freshwater marshes of eastern England were infected by intestinal worms caught from foraging for food in the lakes and waterways around their homes.

The Bronze Age settlement at Must Farm, located near what is now the fenland city of Peterborough, consisted of wooden houses built on stilts above the water. Wooden causeways connected islands in the marsh, and dugout canoes were used to travel along water channels.
The village burnt down in a catastrophic fire around 3,000 years ago, with artefacts from the houses preserved in mud below the waterline, including food, cloth, and jewellery. The site has been called "Britain's Pompeii."

Also preserved in the surrounding mud were waterlogged "coprolites" -- pieces of human faeces -- that have now been collected and analysed by archaeologists at the University of Cambridge. They used microscopy techniques to detect ancient parasite eggs within the faeces and surrounding sediment.

Very little is known about the intestinal diseases of Bronze Age Britain. The one previous study, of a farming village in Somerset, found evidence of roundworm and whipworm: parasites spread through contamination of food by human faeces.
The ancient excrement of the Anglian marshes tells a different story. "We have found the earliest evidence for fish tapeworm, Echinostoma worm, and giant kidney worm in Britain," said study lead author Dr Piers Mitchell of Cambridge's Department of Archaeology.
"These parasites are spread by eating raw aquatic animals such as fish, amphibians and molluscs. Living over slow-moving water may have protected the inhabitants from some parasites, but put them at risk of others if they ate fish or frogs."

Disposal of human and animal waste into the water around the settlement likely prevented direct faecal pollution of the fenlanders' food, and so prevented infection from roundworm -- the eggs of which have been found at Bronze Age sites across Europe.

However, water in the fens would have been quite stagnant, due in part to thick reed beds, leaving waste accumulating in the surrounding channels. Researchers say this likely provided fertile ground for other parasites to infect local wildlife, which -- if eaten raw or poorly cooked -- then spread to village residents.

"The dumping of excrement into the freshwater channel in which the settlement was built, and consumption of aquatic organisms from the surrounding area, created an ideal nexus for infection with various species of intestinal parasite," said study first author Marissa Ledger, also from Cambridge's Department of Archaeology.


Marissa L. Ledger, Elisabeth Grimshaw, Madison Fairey, Helen L. Whelton, Ian D. Bull, Rachel Ballantyne, Mark Knight, Piers D. Mitchell. Intestinal parasites at the Late Bronze Age settlement of Must Farm, in the fens of East Anglia, UK (9th century B.C.E.). Parasitology, 2019; 1 DOI: 10.1017/S0031182019001021

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday 13 January 2020

Audit and Control for Healthcare Manufacturers: A Systems-Based Approach

Compliance is an affirmative indication or judgement that the supplier of a product or service has met the requirements of the relevant specifications, contract or regulation; also the state of meeting the requirements. Compliance is something that meets both the text and the spirit of a requirement. A key way to assess compliance is through auditing. For further details, see the PDA Bookstore:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday 1 January 2020

Happy New Year!

I'd like to wish all readers a Happy New Year and all the best for 2020!

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

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