Friday 30 September 2016

Preparing for ISO 13485:2016

The new ISO 13485 revision is here and, for medical device manufacturers, this is significant news.

ISO 13485:2016 provides an international standard that can be truly harmonized across multiple regions and regulatory requirements. But it also introduces notable QMS changes, particularly in the area of risk management. In this 16-page white paper, we answer your biggest questions about ISO 13485:2016, including:
  • Overview of the update to the new standard
  • Breakdown of what has changed in each section
  • Guidelines on how to prepare for the new standard
  • Deadline for recertification
  • Requirements for recertification
  • Considerations for timing the update and recertfication

With this, Emergo has issued a white paper, which introduces the standard. It can be accessed here.

Posted by Dr. Tim Sandle

Thursday 29 September 2016

Draft PIC/S guidance on data integrity

PIC/S has issued a new draft document relating to data integrity, titled “Good practices for data management and integrity in regulated GMP/GDP environments.” (PI 041-1 (Draft 2)).

According to the document:

Good data management practices influence the integrity of all data generated and recorded by a manufacturer and these practices should ensure that data is accurate, complete and reliable. While the main focus of this document is in relation to data integrity expectations, the principles herein should also be considered in the wider context of good data management.

Data Integrity is defined as “the extent to which all data are complete, consistent and accurate, throughout the data lifecycle” and is fundamental in a pharmaceutical quality system which ensures that medicines are of the required quality. Poor data integrity practices and vulnerabilities undermine the quality of records and evidence, and may ultimately undermine the quality of medicinal products.

Data integrity applies to all elements of the Quality Management System and the principles herein apply equally to data generated by electronic and paper-based systems.

The draft can be accessed here.

Posted by Dr. Tim Sandle

Wednesday 28 September 2016

New EMA draft guideline on sterilisation of the medicinal product

Given the importance of sterile products, in providing both a therapeutic medicine and with regards to the necessity of being free from viable microorganisms, pyrogenic substances and visible particulates, no new guidance has been issued by a regulatory authority in recent years. This has changed with a new draft guidance document from the European Medicines Agency. Issued in April 2016 for public comment, the document is titled Guideline on the Sterilisation of the Medicinal Product, Active Substance, Excipient and Primary Container.

The key points are reviewed in an article for GMP Review by Tim Sandle. The reference is:

Sandle, T. (2016) New EMA draft guideline on sterilisation of the medicinal product, GMP Review, 15 (2): 6-8

For further details, please contact Tim Sandle

Posted by Dr. Tim Sandle

Monday 26 September 2016

Improving bioburden testing

Tim Sandle has written an article for European Pharmaceutical Review about improving assurance in relation to microbial bioburden assessments. This relates to the use of biocontainer bags, designed to reduce the chance of false positives occurring.

Assessment of microbial levels in (and on) samples is an important part of pharmaceutical process control. Samples are drawn from intermediate product at defined stages (ideally based on risk assessment) and these allow for the microbial levels to be tracked from upstream processing to downstream processing (with an expectation that the microbial levels decrease, or at least remain unchanged provided they are below an acceptable action level). For aseptically products, European guidelines require a certain bioburden to be met at the point that a bulk product passes through a sterilising grade filter.

Due to the relatively low specification – of 10 CFU/100mL – pharmaceutical manufacturers need to ensure that false positive results are avoided (as might arise from extraneous environmental contamination). False positives can result in batch rejection. A key innovation, in recent years, is the biocontainer sampling bag. This item of irradiated plastic is in keeping with moves towards single use, sterile processing technology.

The article examines the importance of bioburden testing, particularly in relation to aseptically filled products, together with the most important criteria for sampling bags.

Sandle, T. (2016) Improving microbiological assurance for bioburden tests, European Pharmaceutical Review, 21 (3): 41-44

The article can be viewed via the European Pharmaceutical Review website.

Posted by Dr. Tim Sandle

Sunday 25 September 2016

Mitigating Risks in Aseptic Manufacturing

The aseptic drug manufacturing sector has been under scrutiny following product recalls due to quality and manufacturing failures that threaten patient safety.

A new e-book has been issued by Pharmaceutical Technology. The book outlines the key issues of glass delamination and extractables and leachables are examined, as well as advances in blow-fill-seal technologies that can avoid manufacturing issues traditionally associated with aseptic fill processes.

For further details see: PharmaTech

Posted by Dr. Tim Sandle

Friday 23 September 2016

EU GMP Annex 17 ‘real time testing’

The EMA has published responses to the public consultation on EU GMP Guidelines, revised Annex 17 on the Real Time Release testing.

The draft expands the concepts of ‘real time’ testing beyond just parametric release and could provide opportunities for the use of new and future technology to improve on-going process control, overall product quality and patient safety.

Such monitoring based on:

Critical Process Parameters: A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality [ICH Q8 (R2)].

Critical Quality Attributes: A physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. [ICH Q8 (R2)]

These comments can be found on the EMA website.

Posted by Dr. Tim Sandle

Wednesday 21 September 2016

Bacterial endotoxin contamination and testing limits in ophthalmics

Endotoxin contamination in ophthalmic pharmaceuticals and medical devices presents a risk to users; moreover, endotoxins can cause acute inflammation of the eye following ocular lens replacement surgery.

A new article reviews the risks and requirements for product testing, together with current regulatory guidances. It further analyses recall data relating to ophthalmic pharmaceuticals due to endotoxin contamination. The article concludes by making recommendations for endotoxin control and sets out appropriate endotoxin test limits for finished ophthalmic products.

The article has been written by R. Vijakumar and Tim Sandle. The reference is:

Vijakumar, R. and Sandle, T. (2016) Bacterial endotoxin contamination and testing limits in ophthalmics, European Pharmaceutical Review, 21 (4): 16-18

For further details, please contact Tim Sandle

Posted by Dr. Tim Sandle

Tuesday 20 September 2016

A Role for Endotoxin in Aggression and Depression

A link between depression and inflammation has been observed in many studies. Aberrant social behaviors, such as aggression, often present with depression and can be indicative of suicidal behavior.

A recent study addressed the association between stress-associated behaviors, such as aggression, and low-level inflammation induced by endotoxin challenge. They found that the addition of endotoxin-induced inflammation exacerbated depression in stress-induced mice but reduced signs of aggression. Specifically, endotoxin caused increases of IL-1β and 5-HT2A mRNA in the brain, increased serum corticosterone and increased TNFα in both the brain and liver. Stress alone did not cause these changes. However, the combination of stress and inflammation resulted in a reduction in the stress-induced changes in 5-HT and IL-1β. These results indicate that low-level inflammation can have significant impact on stress-induced behaviors, specifically reductions in aggression, which can lead to depression.

For further details, see the Journal of Neuroinflammation

Posted by Dr. Tim Sandle

Monday 19 September 2016

Nuovo manuale sul cleaning e la disinfezione

E' disponibile la nuova edizione del manuale "The Cleaning and Disinfection for Cleanroom" (prima edizione 2012), completamente aggiornata ed in linea con gli standard, i regolamenti e le norme di più recenti.

Book1Il manuale è stato scritto per tutti coloro che operano nel campo farmaceutico e sanitario (nei settori di produzione, qualità, medico, ingegneria o servizi generali) ma può fornire preziose informazioni anche ai professionisti, agli studenti e al lettore comune. Il libro fornisce dettagli completi sui diversi tipi di disinfettanti e sulle loro modalità di azione; affronta i problemi legati alla distruzione microbica e al fenomeno della resistenza microbica; introduce le tecniche di pulizia e le più recenti norme di sicurezza; espone l'applicazione del cleaning in ambienti sanitari e farmaceutici, informando sugli attuali standard nazionali e internazionali.
Il libro contiene inoltre indicazioni sull'efficacia dei test sui disinfettanti confontando il punto di vista americano e quello europeo. Capitoli aggiuntivi riguardano l'utilizzo del perossido di idrogeno in forma di vapore negli isolatori, la certificazione dei fornitori di disinfettanti e la garanzia di qualità.
Redatto da esperti professionisti, il volume bilancia concetti teorici con consigli pratici, ed è destinato a diventare uno dei testi definitivi su come tenere sotto controllo la contaminazione all'interno delle aree pulite e degli ambienti controllati.

Il libro è acquistabile direttamente su Amazon (

Posted by Dr. Tim Sandle (source ASCA News)

Cleanroom Microbiology book

A feature about the Cleanroom Microbiology book, including a table of contents.

Posted by Dr. Tim Sandle

Compounded Drug Products That Are Essentially Copies

U. S. FDA has produced a draft guidance document titled “Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act.”

Section 503A, added to the FD&C Act by the Food and Drug Administration Modernization Act in 1997 and amended by the Drug Quality and Security Act in 2013, describes the conditions that must be satisfied for human drug products compounded by a licensed pharmacist in a State-licensed pharmacy or Federal facility, or by a licensed physician, to qualify for exemptions from the FD&C Act.

To qualify for exemptions under section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act or the Act), a drug product must be compounded by a licensed pharmacist or physician who does not compound regularly or in inordinate amounts any drug products that are essentially copies of a commercially available drug product, among other conditions. This guidance sets forth the FDA’s policies regarding this provision of section 503A, including the terms commercially available, essentially a copy of a commercially available drug product, and regularly or in inordinate amounts.

The document can be found here: FDA

Posted by Dr. Tim Sandle

Sterility Testing Book

A feature about the comprehensive Sterility Testing book, including a table of contents
Posted by Dr. Tim Sandle

Pharmaceutical Microbiology book feature

A feature about the new Pharmaceutical Microbiology book

Posted by Dr. Tim Sandle

Risk Assessment and Management for Healthcare Manufacturing: Practical Tips and Case Studies

For further details and to order, see the PDA Bookstore.

Posted by Dr. Tim Sandle

Sunday 18 September 2016

Characterizing the gut microbiome

Clostridium difficile infection (CDI) is a major cause of healthcare-associated infections worldwide. CDI can cause symptoms from mild diarrhea to life-threatening toxic megacolon. Antibiotics disrupt the normal intestinal microflora enabling C. difficile to proliferate in the colon and produce toxins. Currently, restoring the gut microflora through methods such as fecal microbiota transplantation is one of the most effective approaches for the treatment of CDI (read the review). Determining which components of the gut microbiota are required for protection against CDI remains unclear.

Posted by Dr. Tim Sandle

Saturday 17 September 2016

Liquid Dose Trends

Pharmaceutical Manufacturing has issued an e-book of interest – ‘Liquid Dose Trends’.

Parenteral drugs are taking a strong position alongside the more established oral solid dose forms and are quickly coming into their own. This eBook will discuss:
  • New challenges faced by parenteral drug manufacturers
  • How equipment manufacturers are meeting the filling needs of biopharma
  • How to choose the right automated system for vaccine monitoring
  • Five questions to ask biopharma CMOs

For details see: Pharma Manufacturing

Posted by Dr. Tim Sandle

Friday 16 September 2016

The Patient Safety Atlas

In March of 2016, in an effort to prevent healthcare associated infections (HAIs), the Centers for Disease and Prevention (CDC) issued a request for all healthcare providers and healthcare facilities to make three critical efforts to further this cause. The CDC also launched the online Patient Safety Atlas in an effort to control the rising threat of resistant bacterial infections.

The following guidelines are succinct and offer very clear advice:

1) Prevent infections related to surgery or placement of a catheter.
2) Prevent spread of bacteria from spreading between patients.
3) Improve antibiotic use.

There are six antibiotic resistant bacteria that are particularly dangerous and are considered urgent or serious threats by the CDC. They are:

  • MRSA (methicillin-resistant Staphylococcus aureus)
  • CRE (carbapenem-resistant Enterobacteriaceae)
  • ESBL-producing Enterobacteriaceae (extended-spectrum ß-lactamases)
  • VRE (vancomycin-resistant enterococci)
  • Multi-drug resistant Pseudomonas
  • Multi-drug resistant Acinetobacter

Infections caused by these organisms could lead to sepsis or even death. C. difficile infections are the most common HAI found in hospitals, and in many cases, lead to death. However, it is not antibiotic resistant like the others listed above.

Surgery and Catheters: The recommendation for preventing infections from catheters and after surgery include using catheters only when needed, following recommendations for safer surgery and catheter insertion and care, and removing catheters from patients as soon as they are no longer needed.

Patient Isolation: For preventing C.diffficile, it is recommended that healthcare providers are consistent and follow these actions for every patient without exception. When it is appropriate, patients should be isolated, and providers should know antibiotic resistance patterns in their facility and area.  In order to prevent dangerous bacteria from spreading, it is recommended that hand hygiene be improved and that gloves, gowns, and dedicated equipment be used for patients who have antibiotic resistant infections.

Antibiotic Use: Finally, to improve antibiotic use, it is recommended that cultures be obtained and antibiotics started promptly and reassessed 24 to 48 hours later, especially in cases of sepsis. Cultures should be used to reassess the need for antibiotics and to stop treatment as soon as they are no longer needed. Antibiotics should be used appropriately according to the type of infection and in the proper dosage, frequency, and duration.

The Patient Safety Atlas: A patient safety atlas (PSA) was created by the CDC and is a public portal that allows heathcare providers and the greater public to visualize and download data that is based on four years of surveillance (2011-2014) by 4,403 healthcare facilities. These include general acute care hospitals (n=3,676), long term acute care hospitals (n=506), and free-standing inpatient rehabilitation hospitals (n=221).

Source: Hardy Diagnostics

Posted by Dr. Tim Sandle

Thursday 15 September 2016

Inflammatory diseases and the microbiome

Immune-mediated inflammatory diseases (IMID) is a term used to define a group of disorders that share common pathogenic mechanisms. IMID include inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and others. Many studies have linked IMID to dysbiosis (a disruption in the microbiome). Researchers are now investigating whether changes in the gut flora are common between IMID or if specific perturbations are associated with a single disease. A new review explores the current research on the gut microbiota in IMID.

Posted by Dr. Tim Sandle

Monday 12 September 2016

Cardiopulmonary diseases

A new article of interest:

Introduction. Respiratory pathology is commonly associated with cardiopulmonary diseases. For this reason, patients with signs and symptoms belonging to cardiopulmonary diseases frequently seek medical attention in pulmonology health care units searching for specialist´s advice. In this context, it can be stated that cardiopulmonary disorders are frequently intricated with lung diseases.

Methodology. The present study refers to the statistical analysis of two groups of symptomatic patients with known cardiopulmonary disease, who came to the pulmonology specialized medical services for medical consult. As a first investigation, chest radiography was carried out as a standard targeted screening. For this study we randomly chose two groups of symptomatic patients who came for medical consult to the specialized pneumology unit in two distinct calendar periods. The data analysis of this study was done by gender and age group.

Results. The results of the study were plotted comparatively for all patients in the two study groups. The rendering of the results was done using sectorial graphics. Thus, information regarding the vulnerable gender to respiratory diseases was shown, regarding patients who have been diagnosed with cardiopulmonary disease. At the same time, data regarding age groups with known chronic cardiopulmonary pathology vulnerable to lung disease were plotted.
Conclusions. The data presented in this study and the obtained results render information on respiratory pathology associated with cardiopulmonary disease in chronic patients with various cardiopulmonary disease.

The reference is:

Gyurka A. G., Cheşcă S. A., Sandle T. Statistical study on cardiopulmonary diseases, Medicine and Ecology, 79 (2): 95-98

For further details, please contact Tim Sandle

Posted by Dr. Tim Sandle

Saturday 10 September 2016

How ISO 13485:2016 Impacts (medical devices)

ISO 13485:2016 specifies requirements for a quality management system where an organization needs to demonstrate its ability to provide medical devices.

ISO 13485:2016 provides an international standard that can be truly harmonized across multiple regions and regulatory requirements.

To help guide companies through the process, Emergo have produced a useful white paper. With a focus on Quality Management Systems, the white paper looks at:
  • Overview of the update to the new standard
  • Breakdown of what has changed in each section
  • Guidelines on how to prepare for the new standard
  • Deadline for recertification
  • Requirements for recertification
  • Considerations for timing the update and re-certfication
For further details, see Emergo.

Posted by Dr. Tim Sandle

Thursday 8 September 2016

Risk Assessment and Management for Healthcare Manufacturing: Practical Tips and Case Studies

Save 15% on the PDA Bookstore's Newest Publicationthrough Sept. 30, 2016
Risk Assessment and Management for Healthcare Manufacturing:
Practical Tips and Case Studies

Authored by Tim Sandle

Avoidance of hazards and assessment of risks have long been part of the manufacture of pharmaceuticals and healthcare products. A high quality drug product must be free from contamination and reliably deliver the intended therapeutic dose as stated on the label and to achieve this manufactures must always be mindful of risk.
This book is divided into four sections that present a formal approach to risk. The first section provides a look at risk assessments and hazards, exploring the origins, looking at key concepts and philosophies and assessing the regulatory perspective.
The book concludes with an extensive set of case studies to show real-world applications of the tools and techniques presented. The wide range of topics presented throughout the four sections includes risk considerations for aging pharmaceutical facilities, application of quality risk management to cleanroom design and process incident investigation.
Save up to 15% when you purchase your copy of Risk Assessment and Management for Healthcare Manufacturing: Practical Tips and Case Studies by Sept. 30. Enter campaign code RAMHM during checkout. 
Posted by Dr. Tim Sandle

CDC Issues Updated Zika Recommendations

CDC has issued updated Zika recommendations. These are titled “Interim Guidance for healthcare providers caring for pregnant women with possible exposure to Zika virus” and “Interim Guidance for the prevention of sexually transmitted Zika virus.”

CDC updates its interim guidance related to Zika virus transmission and related health effects based on the accumulating evidence, expert opinion, and knowledge about the risk associated with other viral infections. CDC will continue to update this guidance as new information becomes available.

For further details see: CDC

Posted by Dr. Tim Sandle

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