Sunday, 24 June 2018

Report on the International API inspection programme published

As part of the Certification of Suitability procedure, the EDQM runs an inspection programme for API manufacturers and is committed to optimise the inspection resources as much as possible. Therefore it has been an active member of the International API Inspection Programme since its creation back in 2008, together with the EMA, several European Union national authorities and international partners.

The report can be accessed here: EDQM

Posted by Dr. Tim Sandle

Saturday, 23 June 2018

MHRA VHP (Vapour Hydrogen Peroxide) Fragility

The MHRA have recently written about the sterility assurance concerns of hydrogen peroxide, especially around the issue of hydrogen peroxide vapour not being a penetrative method.

This is in keeping with a point I’ve made in my book “Sterility, Sterilisation and Sterility Assurance for Pharmaceuticals”, which is available for review or purchase here.

The MHRA post has been written by Andrew Hopkins and it reads:

I have been the chairperson for the revision of Annex 1 of the EU and PIC/S GMPS for the manufacture of sterile medicinal products for a couple of years now. As such I engaged with stakeholders and other regulators to understand their wishes and concerns. One particular topic that has come up as a discussion point at a number of the more recent conferences that gives me great concern, and this is around how to sterilise direct and indirect product contact items in an isolator. I therefore felt it was time to go into print regarding the agency’s view.

A number of manufacturers are looking at isolator technology in new or existing facilities, which is great to hear, but the fly in the ointment, is that the consideration of how to sterilise direct and indirect contact parts does not always form part of the design process. But before I go further I will clarify what I mean by indirect and direct product contact parts:
Indirect product contact parts, as the name implies, are equipment parts that come into contact with items and components, such as stoppers. So, although the equipment itself does not contact the product the items that are “processed” by the equipment do.
Direct contact parts are those that the product passes through, such as filling needles or pumps.

The issue that is arising is that a number of manufacturers are not including robust systems of sterilisation, such as autoclaves, dry heat or offsite irradiation in their facility designs. This leaves a situation where the Agency is being asked, why Vapour Hydrogen Peroxide (VHP) cannot be used for “sterilisation” of these direct and indirect product contact parts. After all, pharmacopeias refer to VHP as a sterilising agent. However, our concern is that although under ideal conditions, VHP can achieve a reduction of biological Indicator spores of up to 6 logs, the process itself is incredibly fragile.

If we cast our minds back a number of years, when VHP was being used to decontaminate the internal surfaces of isolators (not the indirect or direct contact parts) there were a number of issues seen with biological indicators failing the process due to clumping of spores at a microscopic level. This led to a number of papers being written (such as “Biological indicators don’t lie, but in sporicidal gassing disinfection cycles do they sometimes confuse the truth?”, European Journal of Parenteral & Pharmaceutical Sciences 2009; 14(1): 5-10 © 2009 Pharmaceutical and Healthcare Sciences Society) that justified biological indicator failure at one or two locations based on statistical analysis. The papers also recommended that a number of indicators (usually 3) be placed at each location to demonstrate a 3 log reduction (which is not a sterilisation process). This, along with other evidence, such as VHP failure due to very minor occlusion, even to the degree that fatty acids from a fingerprint may “protect” contaminating organisms from the VHP demonstrate the true fragility of the process as a sterilant.

If we then consider the design of some of the indirect and direct product contact parts, we find that a number of them are either difficult to achieve VHP penetration, or, damage and wear and tear can leave surfaces that lead to difficulty to clean and therefore potential occlusion.

VHP, when well controlled and validated, is a useful method for the decontamination of the surrounding workspace, e.g. an isolator environment. However, given the above concerns, our current stance is that VHP cannot be used to sterilise critical items. Even if some of the concerns can be removed by well thought out processes, this still leaves the sterilisation at risk of the vagaries of manual process during set up. For instance, how many of us see ‘human error’ as a high percentage of root cause errors during deviation investigations? Therefore, it would be a high risk option and potentially leave the patient at risk from such a fragile process.

So, what are we expecting?

Our expectation is that the contact parts (direct and indirect) are sterilised using a robust sterilisation method that meets the current requirements of annex 1. This means that:

The sterilising agent reaches all of the critical surfaces in a consistent and repeatable manner, typically requiring processes such as moist or dry heat sterilisation.
The item is unloaded from the sterilisation process either wrapped in integral covering or container, or is transferred under grade A conditions, such as a transfer isolator into the manufacturing isolator.

We also expect that the parts are not exposed to the isolator environment until the isolator has been closed and after completion of the work zone decontamination VHP cycle.

We continue to move increasingly into a pharmaceutical world governed by the principles of quality risk management. We are unable to say that VHP will never be an acceptable approach. However, manufacturers who are considering a different approach to sterilisation, or to any other GMP requirement, seek a dialogue with the agency at an early stage. This may save on costly modification later on in the project and who knows, you may even receive some useful help!

The MHRA post can be found here.

Posted by Dr. Tim Sandle

Friday, 22 June 2018

MHRA on Brexit

MHRA update to pharmaceutical companies on exit preparations. MHRA is aware that companies who market pharmaceuticals in the EU and UK will need to plan and make decisions in advance of the UK’s departure from the EU in March 2019.

The UK’s intention remains to secure an implementation period based on the existing structure of EU rules and regulations as quickly as possible, and to agree a deep and special future partnership. MHRA will continue to advise businesses on the basis of the UK position and will continue to work with the EMA in planning for the UK’s withdrawal from the EU and future relationship.

Companies have been asking for detail about UK legislative requirements in different scenarios. MHRA has been working closely with industry associations and other stakeholders and further details on all these issues and more – both Day One and longerterm proposals – will be published when appropriate.

The UK intends to agree a time-limited implementation period with the EU, and both parties have recognised its importance. Should however there be no implementation period,
MHRA’s approach would be in line with the following principles:

The European Union (Withdrawal) Bill will convert the existing EU legislative framework into UK law at the moment of exit, so there would be no sudden changes to the UK regulatory framework.

MHRA would be pragmatic in establishing UK regulatory requirements. We would give adequate notice and ensure that companies had sufficient time to implement any changed requirements.

Where possible, MHRA would be making use of the information it already has to complete administrative tasks for continuity of work and licences.

MHRA would ensure the minimum disruption and burden on companies as the UK exits the EU, while building on the existing relationship between MHRA and firms.


Posted by Dr. Tim Sandle

Thursday, 21 June 2018

First Ph. Eur. monograph on a monoclonal antibody

The European Pharmacopoeia Commission has achieved an important milestone in the field of biotherapeutic products with the adoption of the monograph for Infliximab concentrated solution (2928).

The Ph. Eur. Commission embarked upon the setting of public standards for therapeutic monoclonal antibodies (mAbs) in 2014 with a pilot phase and following extensive consultation with its stakeholders.


Posted by Dr. Tim Sandle

Wednesday, 20 June 2018

Good Design Practices For Pharmaceutical Water Systems (webinar)

Water-borne microorganisms are ubiquitous and varied in their ability to survive and grow under different conditions. Therefore, an out-of-control water system can cause harm to the patient or adulterate pharmaceutical products. Purification of water is required to prevent interaction with drug substances or other ingredients in the product formulation. Water must also be microbiologically controlled and monitored. This webinar from Tim Sandle will assesses some of the requirements for good design, together with the control measures necessary to maintain effective microbiological control in pharmaceutical facility water systems. See:

Posted by Dr. Tim Sandle

How 'microbial axolotl' repairs itself

In a new study, researchers report new insights into the regenerative capabilities of Stentor, a single celled model organism for regeneration biology. The study used novel gene expression methods that allowed the researchers to identify over one thousand genes that are involved in the regeneration process of individual stentor cells.

Some animals, such as the axolotl salamander, can regrow new body parts in a process that involves the generation of new cells. The damaged cells will die off and the limb will regenerate through cell division, which creates new tissue. Single-celled organisms however cannot utilise this strategy, as they only comprise a single cell -- hence upon significant damage, they usually die. Yet, some single-celled organisms, such as the giant ciliate Stentor, have the rare ability to repair themselves when damaged, in a process referred to as 'self-repair' or 'self-regeneration'. Whereas the ability of Stentor to self-regenerate has been known for some time, detailed knowledge about which genes play a role in this process has thus far been lacking. Now, a research team from Uppsala University has identified over a thousand genes that are involved in rebuilding a fully-fledged Stentor cell after being cut into two halves.

The Uppsala research team focused their study on the Stentor polymorphus, a trumpet-shaped ciliate which they could isolate from a pond nearby the laboratory.


Henning Onsbring, Mahwash Jamy, Thijs J.G. Ettema. RNA Sequencing of Stentor Cell Fragments Reveals Transcriptional Changes during Cellular Regeneration. Current Biology, 2018; DOI: 10.1016/j.cub.2018.02.055

Posted by Dr. Tim Sandle

Tuesday, 19 June 2018

Guidance for pharmaceutical companies to prepare for UK’s withdrawal from EU

The European Medicines Agency (EMA) and the European Commission have updated their guidance to help pharmaceutical companies prepare for the United Kingdom’s (UK) withdrawal from the European Union (EU).

Updates to the questions-and-answers document are marked ‘NEW’ and include information on how the UK’s withdrawal will affect the status of inspection outcomes by the UK national competent authority and batch release processes for medicines that are subject to Official Control Authority Batch Release (OCABR) and Official Batch Protocol Review (OBPR). The document also clarifies how scientific opinions of the Committee for Medicinal Products for Human Use (CHMP) for ancillary medicinal substances in medical devices requested by UK notified bodies will be affected. In addition, it includes new information on back-up arrangements for Qualified Persons for Pharmacovigilance (QPPVs) and on marketing multi-country packs of medicines, where one of the countries in which the packs will be sold includes the UK.

The Agency has also published an updated version of its practical guidance for industry which outlines the steps that companies should follow to make sure that necessary changes to their marketing authorisation are made by the end of March 2019, to allow for the continued marketing of their medicine in the Union after Brexit. The document should be read in conjunction with the updated questions-and-answers document. All updates are marked ‘NEW’.

Companies are reminded to plan for the UK’s withdrawal from the EU on 29 March 2019 in order to avoid any impact on the continuous supply of medicines for human and veterinary use within the EU and are advised to regularly check EMA’s dedicated webpage on the consequences of the UK’s withdrawal from the EU.

Posted by Dr. Tim Sandle

Microbiome project to launch for International Space Station

Northwestern microbiome project to launch June 29 for International Space Station. Studies of twin mice and twin men aim to discover effects of space on body’s microbiome

Twenty laboratory mice are poised to play an important role in preparing humans to go to Mars. A Northwestern University-led study of the microbiome in space is one of five science investigations scheduled to launch Friday, June 29, on board the SpaceX Dragon and head for the International Space Station (ISS).

Scientists Fred W. Turek and Martha H. Vitaterna are leading the project. They and seven team members will attend the early morning launch at Cape Canaveral Air Force Station. The team will be in Florida by June 18 to begin preparations.

The researchers want to learn how the microgravity environment of space affects the community of thousands of microorganisms in the gastrointestinal tract, or microbiota, and how space affects circadian rhythms and other physiological systems.

The mouse study complements the Northwestern team’s previous study of identical twin astronauts Scott and Mark Kelly, one of 10 NASA-funded groups studying the twins to learn how living in space for a long period of time affects the human body.

“This rodent research mission — just NASA’s eighth since completion of the ISS and the rejuvenation of America’s space biology program — is analogous to the Year in Space human twins study, but we will in effect be working with 10 identical siblings from two different families,” said Turek, the Charles E. and Emma H. Morrison Professor of Biology and director of Northwestern’s Center for Sleep and Circadian Biology. “Because a trip to Mars and back is expected to take several years, we need to determine how the gut’s microbiota might be altered in zero gravity over long timescales.”

The 20 mice aboard the ISS, half of which will spend a record 90 days in orbit, will be complemented by Earth-bound controls in three different groups, including one living in a highly specialized NASA simulator that replicates the exact minute-by-minute conditions — but with gravity — inside the space station.

These findings, as well as the results from the Twins Study, are expected to lead to better protection of astronaut health during long-term space missions. (Results of the Twins Study are scheduled for publication later this year.) Findings from the rodent study also may lead to improved treatment of gastrointestinal, immune, metabolic and sleep disorders in humans on Earth.

“It’s important to understand how space travel may impact the circadian system, since it coordinates so many biological processes,” said Vitaterna, research professor and deputy director of the Center for Sleep and Circadian Biology at Northwestern. “The exertion of liftoff, absence of gravity and confined living arrangement all add to the stress of life in space. The key to adapting may be in the body’s ability to maintain harmony across systems.”

For the first time, NASA will video record the mice in space for 48 continuous hours to help the researchers study the animals’ sleep-wake cycles.

Posted by Dr. Tim Sandle

Monday, 18 June 2018

New USP–NF Online launch date

USP plans to launch the new USP–NF Online product on June 18, 2018

Below is an updated list of new features for the new USP–NF Online:
  • NEW feature: Accelerated Revisions such as Errata, Revision Bulletins, and Interim Revision Announcements (IRAs) are now integrated into the new platform, thereby providing you access to official content in one location. Please note that you can still access Accelerated Revisions on
  • NEW feature: You have access to three publications simultaneously (USP41–NF36, First Supplement to USP41–NF36, and Second Supplement to USP41–NF36) within the new USP–NF Online platform when it launches. You will no longer have to login and logout to view another publication.
  • NEW feature: A “Document Tool” menu allows you to quickly view a specific test or procedure within a document by clicking on a linked table of contents along with a “Support” tab with helpful links.NEW feature: Other features include: bookmark icon, create alert icon, quick list of Reference Standards icon, print icon, email link to document icon, and email link of Reference Standards icon.
Posted by Dr. Tim Sandle

Automated, Digital Colony Counting: Qualification and Data Integrity

Many laboratory managers have given attention to automated, digital devices to streamline the plate counting processes. Such devices have been commonplace to the clinical laboratory for some time; although adoption within pharmaceutical laboratories has been slower. Recent regulatory interest in data integrity and the economic pressures driving the ‘lean’ laboratory, with a focus on cost control, improving sample throughput, and reviewing whether each sample tested adds value or produces meaningful information, may account for the growing interest.

This paper considers the selection and adoption of automated, digital capture colony counters within the pharmaceutical microbiology laboratory. The focus is on how such devices can be qualified (or validated) and how data integrity concerns can be addressed, provided that the former has been appropriately planned and executed.

To understand how these devices work, and how accurate they are, plus how data integrity considerations must be handled, Tim Sandle has written a paper for the Journal of GxP Compliance.

The reference is:

For details, contact Tim Sandle

Posted by Dr. Tim Sandle

Sunday, 17 June 2018

New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States

New program to reduce animal testing relating to toxicology in the U.S.

This strategic roadmap is a resource to guide U.S. federal agencies and stakeholders seeking to adopt new approaches to safety and risk assessment of chemicals and medical products that improve human relevance and replace or reduce the use of animals. This document was developed with input from members of 16 federal agencies, multiple interagency workgroups, and input from the public. As such, it represents a consensus perspective that does not necessarily reflect opinions or policy of any specific agency or workgroup, and should not be taken as a commitment by any federal agency.

Activities to implement the strategic roadmap goals are already underway. ICCVAM workgroups will develop detailed implementation plans to address roadmap goals, tailored to specific toxicological endpoints of concern.

To expedite the use of 21st-century science to protect and improve public health, federal agencies and stakeholders will work together to build a new framework to enable development, establish confidence in, and ensure use of new approaches to toxicity testing that improve human health relevance and reduce or eliminate the need for testing in animals. The successful development and implementation of these new approaches will require coordinated efforts that address the three strategic goals described below.

(1) Connect end users with the developers of NAMs
(2) Foster the use of efficient, flexible, and robust practices to establish confidence in new methods
(3) Encourage the adoption and use of new methods and approaches by federal agencies and regulated industries

Posted by Dr. Tim Sandle

Saturday, 16 June 2018

Rapid mycoplasma testing method approved

Manufacturers of cell-culture-based therapeutics can now rely on a faster method for detecting mycoplasma contamination. The Applied Biosystems MycoSEQ Mycoplasma Detection Kit is a fully integrated solution for real-time PCR-based mycoplasma detection. Used throughout the bioproduction workflow, the MycoSEQ method is an alternative to costly, time-consuming culture-based tests often done externally by contract labs, which can take up to 28 days.

Following validation, regulatory review, and acceptance, the MycoSEQ assay and method can be used for lot release by manufacturers in different therapeutic modalities including biotherapeutics, cell and gene therapies, vaccines, and other cell-culture-based therapeutics.

To date, nine global manufacturers of therapies subject to U.S. Food and Drug Administration, European Medicines Agency, and/or local regulatory agency review have received regulatory acceptance for accelerated lot release protocols that specify the Thermo Fisher Scientific MycoSEQ method.

See: ThermoFisher

Posted by Dr. Tim Sandle

Friday, 15 June 2018

Suspect Product and Illegitimate Product

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance entitled “Definitions of Suspect Product and Illegitimate Product for Verification Obligations Under the Drug Supply Chain Security Act.” The draft guidance is intended to describe FDA's interpretation of terms used in the definitions of “suspect product” and “illegitimate product” in the Drug Supply Chain Security Act (DSCSA), for purposes of trading partners' verification obligations (including notification). The draft guidance lays out FDA's current understanding of the following key terms for such purposes: Counterfeit, diverted, fraudulent transaction, and unfit for distribution.

For details, see The Federal Register

Posted by Dr. Tim Sandle

Thursday, 14 June 2018

Standardization of Data and Documentation Practices for Product Tracing Guidance for Industry

FDA has issued a new guidance of interest. This guidance is intended to assist trading partners in standardizing the data contained in the product tracing information that trading partners must provide, capture, and maintain…This guidance is also intended to help trading partners understand the data elements  that should be included in the product tracing information, particularly in situations where trading partners are permitted by law to provide other trading partners with product tracing information that omits certain elements that would otherwise be required. In addition, this guidance recommends documentation practices that trading partners can use to satisfy the product tracing requirements.

For details see: FDA

Posted by Dr. Tim Sandle

Wednesday, 13 June 2018

7 Simple Lifestyle Changes That Lead to Positive Health Payoffs

Is your lifestyle costing your health?

According to an article published in the Center for Science in the Public Interest, a sedentary lifestyle and unhealthy eating habits are the leading causes of death in the U.S.

Different types of lifestyle diseases such as heart disease, high blood pressure, chronic liver disease or cirrhosis and cancer have become so prevalent today. But if there’s an upside to this, it’s that many people are now taking strides to change their way of living and diet.

More and more people are also investing in natural wellness products to improve their health and to lower the risk of developing these frightening lifestyle diseases.

Avoiding the Onset of Lifestyle Diseases

To avoid the onset of certain medical conditions, here are some simple lifestyle changes that offer huge health benefits:

1. Drink more water

The average adult human body is made up of 50 percent to 65 percent water. For your body to work properly, every cell, tissue and organ needs the right amount of water. As such, you have to stay hydrated all the time.

Drinking plenty of water every day offers various health benefits such as:

● Improving digestion and weight loss

● Helping to keep your skin healthy

● Aiding in flushing toxins from the body

● Helping in lubricating joints

● Helping to keep you feeling energized

According to a Food and Nutrition Board report, the average male adult needs about 15.5 cups (3.7 liters) of fluids and the average female adult requires approximately 11.5 cups (2.7 liters) of fluids per day.

2. Get more sleep
Getting proper sleep is crucial to maintaining good mental and physical health.

If you don’t get enough sleep, you are putting yourself at higher risk of developing certain health issues including obesity and heart disease.

In a study published in the Journal of the National Sleep Foundation, health experts recommend that adults get seven to nine hours of sleep every day for normal and healthy living.

3. Minimize or avoid the use of tobacco products and intake of alcohol

Although completely removing the habit of smoking and drinking are not the easiest things to do, you will experience huge and healthy rewards when you are successful in doing so.

Smoking or tobacco use is the leading cause of lung cancer and different types of pulmonary diseases. Once you quit smoking, you will improve your health, reduce your risk of developing chronic diseases, and save money.

Refraining from drinking alcohol altogether or, at the very least, limiting your intake, is also a smart and healthy decision to make. Drinking too much alcohol will have harmful effects on your organs including the liver, kidneys and gastrointestinal system.

It is always best to stop smoking and drinking altogether. But if you can’t, start by minimizing your use of tobacco products and your alcohol consumption. 

4. Eat more healthy foods

It can be hard to stop giving in to your temptations for sweet, salty and fatty foods and sugary drinks. But to have a healthier diet, begin by eating more nutritious, organic foods and less junk food.

This means adding more fruits, nuts and vegetables to your daily diet. In addition, focus on increasing your intake of healthy fats instead of French fries, pizza and other unhealthy fried foods.

5. Choose your supplements wisely
It is best to get all the essential vitamins and minerals from the foods you eat. However, if you don’t eat well-balanced meals daily, you can rely on supplements to get the nutrients you need.

Before buying any supplements, it is best to consult your doctor first. Find out if you will benefit from taking in antioxidant-rich Bio Q tablets for improved cellular health. Just make sure to source your health supplements from a trusted supplier or manufacturer to ensure quality.

6. Be more physically active

Getting enough exercise every week will allow you to reap a variety of health benefits. These include:

● Improved heart health

● Weight loss

● Better muscular tone

● Stronger bones

● Lower risk of cancer and diabetes

● Improved mental health

Working out regularly doesn’t mean you have to sign up for a gym membership immediately or buy some sporting gear. You can get the physical workout you need by engaging in leisure time physical activities you like such as walking, hiking, biking, gardening and swimming.

The World Health Organization (WHO) recommends getting 150 minutes of moderate intensity aerobic physical activities through the week, doing at least 75 minutes of vigorous-intensity aerobic physical activities during the week, or coming up with an equivalent combination of the two to experience various health benefits.

7. Manage or eliminate stress from your life

Lastly, stress has detrimental effects on your body since it disrupts normal hormone production and can affect everything from blood sugar levels to poor sleep quality.

To avoid the negative effects of stress, find ways to properly deal with it. Learn to meditate, practice deep breathing and mindfulness, create a feel-good garden, listen to music, exercise, or spend time with your loved ones and friends – all these can help you deal with and forget your stress. You’ll also be happier and healthier.

If you want to prevent the onset of lifestyle diseases, you have to start making changes in your lifestyle.

But you don’t have to go vegan or hit the gym every day to improve your daily routine. Making some simple, doable changes to your lifestyle can help improve your health and enhance the overall quality of your life.


Gehana Kennedy is the owner of, the go-to source for high-quality wellness products including a range of step-by-step formulated vitamins, fitness supplements and natural skin care products. With innovative ideas and implementation of new technologies, she was able to establish a platform that offers not only quality products but also valuable information for customers.

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