Saturday, 28 May 2016

CBER - Blood and Blood Components

Listed below are the guidances that FDA CBER are planning to issue during the course of the year:

Relabeling of Apheresis Plasma Intended for Transfusion to Concurrent Plasma for Further Manufacture; Draft Guidance for Industry

Recommendations to Reduce the Risk of Transfusion-transmitted Chikungunya Virus (CHIKV); Draft Guidance for Industry

Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion; Draft Guidance for Industry (Revised Draft1)

Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Products; Final Guidance for Industry

Labeling of Red Blood Cell Units with Historical Antigen Typing Results; Draft Guidance for Industry

For more details see: CBER

 Posted by Dr. Tim Sandle

Friday, 27 May 2016

Failure Mode Effects Analysis for Filter Integrity Testing

From a more global point of view, the goal of failure mode effects analysis (FMEA) for filter integrity testing (FIT) is to align the risks as closely as possible with its source. This analysis can identify the root cause of the risk and help the quality assurance staff and operators detect the occurrence of a particular deviation. Additionally, the analysis also helps define the adapted level of training to reduce operator mistakes.

Magnus Stering has written an interesting article for Pharmaceutical Processing about the risk assessment of filter testing.

The article identifies risks for achieving a higher level of FMEA for FIT and for improved quality assurance. It can be accessed here.

Posted by Dr. Tim Sandle

U.S. National Microbiome Initiative

Last Friday the White House announced that it was creating a National Microbiome Initiative to bring together scientists to study microbial diversity associated with the human body and our environment. The move will inject $121 million/year into microbiome projects from federal agencies as well as an additional $400 million from other institutions, including the Gates Foundation. In addition to monetary support, the NMI will foster collaborative studies, interdisciplinary research and comparative studies.

Microbiomes are the communities of microorganisms that live on or in people, plants, soil, oceans, lakes, rocks, and the atmosphere. Recent discoveries have generated a new view of the biological world, one that recognizes that plants and animals are actually meta-organisms containing one or many microbial species. Inanimate surfaces, from rocks to keyboards, are likewise swarming with microbial life.

These microbial communities help define the health and integrity of their living or inanimate hosts. Microbiomes influence the behavior of diverse ecosystems, with effects on human health, climate change, food security, and other factors. Imbalanced microbiomes have been associated with human chronic diseases such as obesity, diabetes, and asthma; local ecological disruptions such as the “dead zone” in the Gulf of Mexico; reductions in agricultural productivity; and disruptions in weather and atmospheric conditions related to climate change.

Despite the exciting progress that has already been made in microbiome science, the knowledge and tools necessary to manipulate microbiomes in a directed manner are lacking. The NMI will focus on comparative study of microbiomes across different ecosystems to seek organizing principles that shape all microbiomes. Understanding these principles are necessary to develop approaches to reliably alter microbiomes to benefit individuals, communities, and societies.

Specifically, the NMI will have three goals, which were developed through a year-long fact-finding process that involved Federal agencies, non-government scientists, and a broad community of citizens. These goals are:
  1. Supporting interdisciplinary research to answer fundamental questions about microbiomes in diverse ecosystems.
  2. Developing platform technologies that will generate insights and help share knowledge of microbiomes in diverse ecosystems and enhance access to microbiome data.
  3. Expanding the microbiome workforce through citizen science and educational opportunities.
See: Announcing the National Microbiome Initiative

Posted by Dr. Tim Sandle

Thursday, 26 May 2016

New National Quality Standard for Healthcare Associated Infection (QS 113)

A new standard has been issued for U.K. health services. This quality standard covers organisational factors in preventing and controlling healthcare-associated infections in secondary care settings.

Organisational factors include management arrangements, policies, procedures, monitoring, evaluation, audit and accountability.

Secondary care settings include hospital buildings and grounds; inpatient, day case and outpatient facilities and services; elective and emergency care facilities; and hospital maternity units and services.

For further details on the revised standard, see NICE.

Posted by Dr. Tim Sandle

Wednesday, 25 May 2016

FDA - Labelling for Biosimilar Products

The principal components of therapeutic biological products are large, complex molecules like monoclonal antibodies and cell signaling proteins. The nature of biological products creates unique challenges that generally do not exist with small molecule drugs. For instance, unlike small molecule drugs made through chemical synthesis, biological products are produced in living systems, such as microorganisms, plant cells or animal cells.

In relation to these products, the U.S. FDA has issued new guidance on how they should be marketed and labelled.

A draft guidance for industry has been produced, which can be accessed here

Posted by Dr. Tim Sandle

9th Edition European Pharmacopoeia - available

The 9th edition of the European Pharmacopoeia, is now available for order.

Each format allows direct access to the EDQM Online Knowledge database. The database provides information on a given substance or general method of analysis and also contains information such as: the monograph’s revision history; the chromatogram in pdf format; the links to the reference standard catalogue number; the trade names of some reagents, such as chromatography columns and biological kits; and access to the list of Certificates of Suitability to the monographs of the European Pharmacopoeia (CEPs) that have been granted for this substance.

For more details see: EDQM

Posted by Dr. Tim Sandle

Tuesday, 24 May 2016

European food microbiology legislation scheme

The European food microbiology legislation scheme is designed for laboratories that examine foods for compliance with Regulation (EC) 2073/2005 and subsequent amendments.  It has recently been updated.

The European food microbiology legislation scheme assesses the participants’ ability to:

Test and interpret laboratory results in accordance with EU food safety
Process hygiene criteria

The samples are simulated foods to be tested for compliance with either the food safety or the process hygiene criteria.

A list of the updates can be found at the Public Health England site here.

Posted by Dr. Tim Sandle

Monday, 23 May 2016

Pharmaceutical Facility Sanitization: Best Practices Considered

Cleanrooms and clean areas must be regularly cleaned and disinfected. This is normally undertaken using a detergent step, followed by the application of a disinfectant. It may be necessary to remove the residue of the disinfectant using water. Cleaning and disinfection should also extend to equipment. Furthermore, with personnel, sanitization is important in relation to glove hands.

In relation to this, Tim Sandle has written an article for American Pharmaceutical Review which reviews the key points to consider for the practical application of a cleaning and validation program within a pharmaceutical facility, with a focus on disinfectant selection.

The reference is:

Sandle, T. (2016) Pharmaceutical Facility Sanitization: Best Practices Considered, American Pharmaceutical Review, March 2016, pp1-5

For a copy, please contact Tim Sandle

Posted by Dr. Tim Sandle

Sunday, 22 May 2016

Pertussis (whooping cough) immunisation information

Public Health England has updated its information for public health professionals relating to pertussis (whooping cough).

Whooping cough     is a highly infectious disease that is usually caused by Bordetella pertussis. A similar illness is caused by B. parapertussis, but this is not preventable with presently available vaccines.

There is an initial catarrhal stage, followed by an irritating cough that gradually becomes paroxysmal, usually within one to two weeks. The paroxysms are often followed by a characteristic ‘whoop’ or by vomiting. In young infants, the typical ‘whoop’ may never develop and coughing spasms may be followed by periods of apnoea. The illness often lasts for two to three months. In older children and adults, the disease may present as persistent cough without these classic symptoms and therefore not be recognised as whooping cough.

Pertussis may be complicated by bronchopneumonia, repeated vomiting leading to weight loss, and cerebral hypoxia with a resulting risk of brain damage. Severe complications and deaths occur most commonly in infants under six months of age. Minor complications include subconjunctival haemorrhages, epistaxis (nosebleeds), facial oedema, ulceration of the tongue or surrounding area, and suppurative otitis media.

Transmission of the infection is by respiratory droplet, and cases are most infectious during the early catarrhal phase. The incubation period is between six and 20 days and cases are infectious from six days after exposure to three weeks after the onset of typical paroxysms.

The update takes the form of a revision to the ‘Green Book’ and it can be accessed here.

Posted by Dr. Tim Sandle

Saturday, 21 May 2016

ISO standard for robots and robotic devices

A new ISO standard of interest has been issued. This is ISO/TS 15066:2016 Robots and robotic devices -- Collaborative robots.

Collaborative robotics is when automatically operated robot systems share the same workspace with humans. It therefore refers to a system or application rather than a particular type or brand of robot.

ISO/TS 15066 provides guidelines for the design and implementation of a collaborative workspace that reduces risks to people. It specifies:
  • Definitions
  • Important characteristics of safety control systems
  • Factors to be considered in the design of collaborative robot systems
  • Built-in safety-related systems and their effective use
  • Guidance on implementing the following collaborative techniques: safety-rated monitored stop; hand guiding; speed and separation monitoring; power and force limiting.

For further information, see ISO.

Posted by Dr. Tim Sandle

Friday, 20 May 2016

Objectionable Microorganisms

An objectionable organism is one which can either cause illness or degrade the product thus making it less effective. But how to define what is an objectionable organism?

Microbiologics have an interesting discussion paper on the subject. Here is an extract:

A manufacturer can detect objectionable organisms in its product by:

1.Performing tests for specified microorganisms as described in USP <62>.
2.Identifying all suspicious colonies growing on agar plates used in microbial enumeration tests. To find out more about microbial enumeration tests, see USP <61>.
3.Performing a risk analysis to determine which organisms would be objectionable and then devising a plan for detecting the organisms.

To access the paper, see Microbiologics

Posted by Dr. Tim Sandle

Thursday, 19 May 2016

Should You Try New Approaches to Instrument Calibration?

Validation and instrument calibration are a necessity in every manufacturing and production unit. Calibration procedures have witnessed some changes and new techniques have been introduced. New approaches such as instrument diagnostics and calibration analysis have significantly improved efficiency. Read on to know more.


It is essential that instruments and devices used in your company are routinely calibrated to ensure that you get accurate measurements. However, it should be noted that not all instruments need to be calibrated at the same time or with the same frequency. Instrument diagnostics is the practice of analyzing the level of calibration different instruments require and which instruments can be shifted from periodic schedule to on-demand calibration.

While some devices have to be calibrated periodically without fail, the less critical instruments can be monitored carefully to observe if they indicate any change that needs immediate attention, which then should be calibrated as per requirement. On-demand calibration will eliminate hundreds of unnecessary calibrations per year. Instrument diagnostics ensure that efficiency is increased by folds, without compromising on the quality.


Calibration was a manual process and so was documenting. With automation, it became possible to achieve paperless calibration where the data pertaining to calibration can be recorded, stored and documented electronically. Paper is completely eliminated which helps in saving money.

The calibration process can be significantly streamlined by optimizing periodic calibration schedules, synchronizing instrument data in the calibration management system and using documenting calibrators. Paperless documentation allows technicians to access the required information and upload calibration results from any location, at any time. Further, it eliminates the necessity for administrative technicians and staff to manually fill out the data which usually takes a lot of hours. Needless to say, paperless calibration is faster, efficient and streamlined.


If possible, the interval between calibrations can be extended to reduce the overall number of procedures that are performed annually. These extensions are done in a manner that they remain in compliance with company regulations and policies. Calibration analysis identifies those instruments that don’t need to be calibrated as often as the others. This is achieved through an on-going, computer-driven analysis of the available historical data.

Calibration analysis includes safety and quality related instruments which need to be calibrated on a schedule but it has to ensure that the calibrations are done on the right schedule. It doesn’t matter if you calibrate some instruments on a yearly basis instead of calibrating every six months, but you have carefully monitor and check if they are performing as designed without compromising or affecting the quality between calibrations.

Results of Practicing New Approaches of Calibration

A number of critical instruments were observed to study if they showed any tendency to under-performed when the calibrations intervals were extended. All the product-related instruments were studied and depending on the result, they were moved into the ‘on-demand’ schedule. It was ensured that none of the instruments were over-calibrated or under-calibrated. Instrument calibration and diagnostics showed promising results and an increased efficiency by facilitating the following:

Reduced the time spent per calibration by at least 15 minutes, which equated to hundreds of hours saved per thousands of calibrations

Thousands of sheets of paper were saved per year
Over 200 hundred calibrations eliminated every year by extending calibrating intervals

A minimum of 500 hours saved per week due to elimination of manual data entry

Reduction in human errors

At least 30% of instruments (not related to safety and quality) shifted from scheduled calibration to an on-demand schedule, annually saving up to approximately 300 hours.

Author Bio:

Edward Simpson is a seasoned Calibration and Technical Engineer working for RS Calibration Inc. Edward has a knack for finding faults in machines and does not rest until they are rectified to perfection. He lives in Pleasanton, CA and can be contacted anytime for matters related to machines on his email He also invites people to visit his company to learn more about the type of calibration work he does.

UHPLC Workflows for Biotherapeutic Characterization

Advanstar have issued a free e-book relating to Biotherapeutic Characterization.

The introduction of UHPLC revolutionized bio/pharma analytical laboratories and advances in technology promise more for the future. In this e-book, experts explain recent advances in UHPLC, and the basics of glycan analysis. Sample preparation technologies that can increase sample throughput and improve data quality for peptide quantitation are explored. In addition, the characterization of intact antibodies using reversed-phase chromatography is detailed.

The e-book can be accessed here.

Posted by Dr. Tim Sandle

Wednesday, 18 May 2016

GMPs for HVAC in non-sterile pharma

The World Health Organization has issued a draft guidance, titled “Supplementary guidelines on Good Manufacturing Practices for Heating, Ventilation and Air-Conditioning Systems for Non-Sterile Pharmaceutical Dosage Forms.”

The scope of the document is:

“These guidelines focus primarily on the design and good manufacturing practices (GMP) requirements for HVAC systems for facilities for the manufacture of solid dosage forms. Most of the system design principles for facilities manufacturing solid dosage forms also apply to facilities manufacturing other dosage forms (such as liquids, cream, ointments) and other classes of products including biological products, herbal medicines, complementary medicines and finishing process steps for APIs.”

In terms of the change process, during the consultation on data management, bioequivalence, GMP and medicines’ inspection held in 2015 the possible revision of the guidance for (WHO Technical Report Series, No. 961, Annex 5, 2011) was discussed with the inspectors. It was suggested that in light of the new developments a draft for revision be prepared. This new proposal for revision was drafted based on the feedback received, the new, current trends in engineering and the experience gained during the implementation of this guidance in inspection.

At the same time, the opportunity was used to improve the graphic images and make them more readable in e-version as well as in print.

The document reference is Working document QAS/15.639/Rev.1, and it is dated May 2016.

The document can be found here: WHO

The closing date for comments is July 12, 2016.

Posted by Dr. Tim Sandle

ISO 14004:2016 - Environmental management systems

The newly revised ISO 14004:2016, Environmental management systems – General guidelines on implementation, provides organizations with support to help with the implementation of an EMS. It is designed to complement, but is not limited to, ISO 14001, ISO’s standard for environmental management systems.

For further details, see ISO.

 Posted by Dr. Tim Sandle