Thursday 20 September 2018

EDQM publishes a new section dedicated to biotherapeutics

As public standards for the quality of medicines in Europe, the monographs and reference standards of the European Pharmacopoeia (Ph. Eur.) play a major role in ensuring the quality of biotherapeutics, thereby contributing to overall patient safety. By providing these recognised common standards for the quality of medicines and their components, the Ph. Eur. promotes public health and ensures the safety of medicines for patients. Ph. Eur. Standards are designed to meet the needs of all stakeholders, including industry, Official Medicines Control Laboratories (OMCLs) and regulatory authorities.

The new biotherapeutics section on the EDQM website summarises Ph. Eur. Commission activities and achievements in this field. In addition to clarification of the role of Ph. Eur. monographs in the biosimilars regulatory pathway, it describes the recently concluded P4-BIO pilot phase and the ongoing pilot phase on monoclonal antibodies (“MAB pilot phase”), explaining the strategy followed by the Ph. Eur. when setting requirements for the quality of this important class of biotherapeutics. It also describes various levels of flexibility integrated into Ph. Eur. texts, including those introduced recently to address the structural complexity, heterogeneity and compound diversity derived from different manufacturing processes of complex biotherapeutics.


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday 19 September 2018

How soil bacteria munch on plastics

Thin mulch films made of polyethylene are used in agriculture in numerous countries, where they cause extensive soil contamination. Researchers have now identified an alternative: films made of the polymer PBAT biodegrade in soils.

Our world is drowning in a flood of plastic. Eight million tons of plastic end up in the oceans every year. Agricultural soils are also threatened by plastic pollution. Farmers around the world apply enormous amounts of polyethylene (PE) mulch films onto soils to combat weeds, increase soil temperature and keep the soil moist, thereby increasing overall crop yields.

After harvest, it often is impossible for farmers to re-collect the entire films, particularly when films are only a few micrometers thin. Film debris then makes its way into the soil and accumulates in the soil over time, because PE does not biodegrade. Film residues in soils decrease soil fertility, interfere with water transport and diminish crop growth.

Researchers at ETH Zurich and the Swiss Federal Institute of Aquatic Science and Technology (Eawag) have now shown in an interdisciplinary study that there is reason to be hopeful. In their recent study, they demonstrate that soil microbes degrade films composed of the alternative polymer poly(butylene adipate-co-terephthalate) (PBAT). Their work has just been published in the journal Science Advances.

In their experiments, the researchers used PBAT material that was custom-synthesised from monomers to contain a defined amount of the stable carbon-13 isotope. This isotope label enabled the scientists to track the polymer-derived carbon along different biodegradation pathways in soil.

Upon biodegrading PBAT, the soil microorganisms liberated carbon-13 from the polymer.

Using isotope-sensitive analytical equipment, the researchers found that the carbon-13 from PBAT was not only converted into carbon dioxide (CO2) as a result of microbial respiration but also incorporated into the biomass of microorganisms colonizing the polymer surface.

The researchers are the first to successfully demonstrate -- with high scientific rigor -- that a plastic material is effectively biodegraded in soils.

Because not all materials that were labelled "biodegradable" in the past really fulfilled the necessary criteria. "By definition biodegradation demands that microbes metabolically use all carbon in the polymer chains for energy production and biomass formation -- as we now demonstrated for PBAT," says Hans-Peter Kohler, environmental microbiologist at Eawag.

The definition highlights that biodegradable plastics fundamentally differ from those that merely disintegrate into tiny plastic particles, for instance after exposure of the plastic to sunlight, but that do not mineralise.

In their experiment, the researchers placed 60 grams of soil into glass bottles each with a volume of 0.1 litre and subsequently inserted the PBAT films on a solid support into the soil.

After six weeks of incubation, the scientists assessed the extent to which soil microorganisms had colonised the PBAT surfaces. They further quantified the amount of CO2 that was formed in the incubation bottles and how much of the carbon-13 isotope the CO2 contained. Finally, to directly demonstrate the incorporation of carbon from the polymer in the biomass of microorganisms on the polymer surfaces, they collaborated with researchers from the University of Vienna.

At this stage, the researchers cannot yet say with certainty over which timeframe PBAT degrades in soils in the natural environment given that they conducted their experiments in the lab, not in the field. Longer-term studies in different soils and under various conditions in the field are now needed to assess the biodegradation of PBAT films under real environmental conditions.


Michael Thomas Zumstein, Arno Schintlmeister, Taylor Frederick Nelson, Rebekka Baumgartner, Dagmar Woebken, Michael Wagner, Hans-Peter E. Kohler, Kristopher McNeill, Michael Sander. Biodegradation of synthetic polymers in soils: Tracking carbon into CO2and microbial biomass. Science Advances, 2018; 4 (7): eaas9024 DOI: 10.1126/sciadv.aas9024

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday 10 September 2018

New PIC/S Guidance Documents

The following new PIC/S Guidance documents have been adopted:

PIC/S Aide-Memoire on “CrossContamination in Shared Facilities” (PI 043- 1).

The purpose of this Aide-Memoire is to assist GMP inspectors in the assessment of the risks to the product from cross-contamination in shared facilities. This document provides guidance for GMP inspectors to use in preparation for, and performance of, inspections. It promotes a risk-based approach.

PIC/S Guidelines on the formalised risk assessment for ascertaining the appropriate GMP for excipients of medicinal products for human use (PI 045-1).

PIC/S Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities (PI 046-1).

PIC/S Guidelines on the principles of GDP for active substances for medicinal products for human use (PI 047-1).

Also, the following Chapters and Annex of the PIC/S GMP Guide have been revised:
  • Chapter 3 on “Premises and Equipment”;
  • Chapter 5 on “Production”;
  • Chapter 8 on “Complaints and Product Recall”;
  • Annex 17 on “Real Time Release Testing and Parametric Release”.
  • The revised Chapters are based on the equivalent Chapters of the EU GMP Guide with some minor differences in terms of language.
See PIC/S:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday 3 September 2018

GMP in Practice: Regulatory Expectations for the Pharmaceutical Industry

The fifth edition of the book "GMP in Practice: Regulatory Expectations for the Pharmaceutical Industry" is now available, at a special introductory price. 

The book is written by James Vesper and Tim Sandle. As companies strive to harmonize global requirements for quality systems, the 5th edition of this text provides an overview of the 34 essential global cGMP requirements that are typically included in a modern pharmaceutical quality system, including data integrity and how they have evolved. Explore risk-related questions, delve into several expectations for each quality system element encompasses, and review real-world examples from cGMP regulations from the US FDA, Health Canada, the European Union, the World Health Organization, and the International Conference on Harmonization (ICH). See:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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