Thursday 29 April 2021

Conducting Compliant Investigations

A new book of interest (edited by Jeanne Moldenhauer), covering different approaches to conducting compliant investigations, where compliant is defined as meeting the requirements of the applicable regulatory documents.

Conducting Compliant Investigations

The information it provides on conducting investigations that will be acceptable to regulatory investigators will be instrumental in helping you to significantly reduce regulatory risk.

Select topics covered in this book include:

  • Why should we perform investigations?
  • What should be determined in the investigation?
  • Detailed background on U.S. FDA 483 and U.S. FDA Warning Letters investigations
  • What types of regulatory actions are taken in response to failure investigations?
  • Chapters on investigating various types of failures (e.g., data integrity, sterility test, media fill, environmental monitoring)
  • Descriptions of appropriate corrective and preventative actions
  • Writing a good investigation report
  • Tracking and trending investigations

The book includes two chapter written by Tim Sandle:

  Sandle, T. (2021) Getting to the heart of the matter: Approaching root cause analysis. In Moldenhauer, J. (Ed.) Conducting Compliant Investigations, DHI/PDA, River Grove, IL, USA pp45-108 ISBN 978-942911-57-9

Sandle, T. (2021) Investigating sterility test failures. In Moldenhauer, J. (Ed.) Conducting Compliant Investigations, DHI/PDA, River Grove, IL, USA pp227-268 ISBN 978-942911-57-9


Conducting Compliant Invest... by Tim Sandle

For details, see the PDA Booksore:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

Wednesday 28 April 2021

Digital Data #2: Digital Search Challenges

Digital research is essential for the modern pharmaceutical or healthcare facility, and this requires the process of undertaking digital searches. This can include specialist software, such as regularly updated pipeline databases to searching specialty journals, or utilizing different online database to obtain data. The search and research process relies on the ability to use online resources to find, assess, and leverage information to inform a decision. Digital online research methods are related to existing research methodologies but re-invent and re-imagine them in the light of new technologies and conditions associated with the Internet, making use of the advantages that digital data presents.

To access the article for free, see:


 Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

Tuesday 27 April 2021

Digital Data #1: Content Creation

In pharmaceuticals and healthcare, the majority of searching and researching is undertaken online. To undertake this effectively requires digitally mediated research methods, which refers to the application of online and other digital technologies, such as online papers, surveys, text messages and interactive voice response systems for research purposes. On the other hand, the digital librarian needs to ensure that digital data has been presented correctly and appropriately indexed. There are a number of digital libraries that researchers in the sector will seek to access. This requires digital archiving. This is the process of the practice of identifying data that is no longer active and moving it out of production systems into long-term storage systems. Archival data is stored so that at any time it can be brought back into service. The activity creates digital repositories. These are online databases of digital objects that can include text, still images, audio, video, digital documents, or other digital media formats. The pharmaceutical industry depends heavily on the integrity and confidentiality of archived records.

This article looks at some examples of how data can best be stored, archived, indexed, and presented. Here the goals of digital archiving can be summarized as: to preserve, contextualize, present, and enable the use of digital resources.

To access the article for free, go to the IVT Network:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

Monday 26 April 2021

Why it’s time to strengthen and widen the microbial test panel

The testing of culture media, and conducting microbiological method suitability studies, disinfectant efficacy studies, Antimicrobial Effectiveness Test (or Preservative Efficacy Test), and associated activities, requires the use of a test panel of microorganisms. These organisms need to be representative of the intended application and be of a suitable range in order to demonstrate that a low level of viable cells can be recovered without any indication of the inhibition of growth or excessive growth-promotion (typically defined as the recovery of between 50 to 200% of the challenge count). This activity provides the basis for the release of culture media or for verifying that a method is suitable for recovering any microorganisms that might be present in a product sample.

This approach has been established for several decades and in many cases, the types of organisms selected for the panel are drawn from guidance presented in the major pharmacopeia. The test panels of organisms recommended by compendia along with specific standards are in place to allow for reproducibility between laboratories. In the case of most standards (such as the disinfectant efficacy norms), these are designed to be multi-industry. Hence the presented organisms may or may not be suitable for the intended application.


In addition, with the compendia, all too often the organisms recommended for, say, the Microbial Limit Test method verification, are applied to the release of all culture media used for all activities, be that the test for sterility or for the recovery of organisms from water systems.

Not only is this inappropriate – for the microbiologist should be reviewing the panel and deciding upon the appropriate organisms – the recommended panels have not kept pace with improvements with our understanding of the types of microorganisms likely to cause contamination. Take, for example, the inclusion of Salmonella in the panel for the recovery of so-called ‘objectionable microorganisms’ for use with the Microbial Limits Test (1). To my knowledge and based on discussions with microbiologists over a couple of decades, no Salmonella has ever been recovered from a raw material.

Equally the selection, especially in relation to the testing of culture media used for cleanroom environmental monitoring, has not moved forwards with the findings from the human microbiome project and the depth of species richness found on the human skin microbiome.

The argument that the test panel quoted in the compendia is representative and thus if culture media release testing can recover such organisms then it can reasonably be assumed that any other similar organisms can be recovered does not really hold up. Unless that is, the only concern is with the recovery of non-fastidious mesophilic organisms.

Instead, I maintain that in terms of the appropriate panel, this should be based on:

  • What is currently being recovered, and 
  • What should theoretically be recovered.

To read the full article, the reference is:

Sandle, T. (2021) Why it’s time to strengthen and widen the microbial test panel, European Journal of Parenteral and Pharmaceutical Sciences, 25 (4):

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

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