Tuesday, June 15, 2010

Do I want my drugs to be delievered using nanoparticles?

As you may be aware of there is increased focus on the safety of nanoparticles. Googling 'nanoparticles, safety' will get you get more than ½ million hits. Add the term 'FDA' and this is reduced to just under under 200.000 hits. This and the fact, that my son, who is a Ph.d.-student at DTU-Nano this past weekend told me, that appearantly nanoparticles ones the enter the body don't get out again, is why today I have been attending a one-day seminar on “Polymers in Drug Delivery” arranged at IDA by the Danish Society for Polymer Technology.

The seminar opened with a state-of-the-art presentation by Jean-Francois Lutz of the Fraunhofer Institute for Applied Polymer Research in Germany. He first outlined the avenues of drug delivery: oral, intravenous, transdermal, regulated pumps, aerosols or suppositories. He started by stating, that the first polymer used for drug delivery was discovered in 1929 and during the following 80 years this has resulted in more than 20.000 publications by only 5-6 products on the market. I am talking about PEG or polyethyleneglycol, which is uncharged, water soluble and also soluble in many organic solvents. There are 4 types of ways of using polymers in drug delivery: Prodrugs – polymer drug conjugates of which paclitaxel is a samle product, micelles – no products yet, but a japanese researcher have 10 in clinical trials, capsules – microobjects eg encapsuable ipoprofen crystals, and hybrid nano particles – examples are gold nanoparticles surrounded by citrate. A new area is viral gene carriers – again with no products.

Next Kenneth Howard from iNANO at Århus University toke the stage. He described delivery of gene silencing therapeutics including results of tests on animals using chitosan and siRNA, which self assemble into nanoparticles for treatment of radiation induced flammation (RIF) and rheumatism. There is no know treatment for RIF, and rheumatism often affect women in their early 40's with – as far as I know – just pain relief as a possibility.

Then Michael Stolzenburg was supposed to talk about PLA-PEO vesicles for drug delivery. Shortly after starting his presentation he felt sick and left the room. Quite some time elapsed before the meeting chairman left to see how Michael was doing. However, the audience was not informed about his condition. I guess the message from this seminar management was “the show must go on”, since a colleaque of Michael completed the presentation, at the end of which the chairman remarked 'it is very nice to have a back-up'. I was very happy to chat with Michael during the afternoon coffee break, but a bit asammed, that I did not take action.

During the day I also learned about smart hydrogels for drug delivery, and medical chewing gum (you properly know the once smokers use to stop smoking?). Finally I learned about spray dried siRNA loaded PLGA nanoparticles and supercritical carbondioxde for making silocone based medical devices. Really a very good learning experience about something I did not know much about, and which could possibly affect us all.

Now to the question of the day: Would I take drugs using nanoparticles? Before I give the answer you have to understand, that nanoparticles ones they enter your body does not seem to leave it again. So one shold not overlook the fact, that nanoparticles could accomulate in my body, and that we really have no knowledge of the long term effects. Yes, I properly would take such drugs. If I had RIF and was offered one of the describe drugs I would consider the risk of the drug lower than the risk of untreated RIF. I have taken such decisions before in my life. Some years ago I toke arenesp to stimulate my bone marrow. Unfortunately I was a slow responder, so before my system responded I was taking rather larges doses of arenesp. Unknown at the time was, that large dosis of arenesp increases your risk of blood clouths. Eventually, I got a blooth clouth in my left leg and also in both lungs. I was lucky, and survived. Using modern medicine will always be a tradeoff between the benefits of the drug and its known or unknown side effects. At the time I started taking arenesp the side effect, which hit me was not known.

Process safety is much like deciding whether to take a new drug or not. A differnet chemical route may avoid a very toxic intermediate, but could involve more severe process conditions. Trade offs cannot be avoided.

Tuesday, June 08, 2010

Loss Prevention 2010 Continues in high Gear!

The second day of the triannual process safety conference in Bruges started with two plenary presentation. The first titled "Challenges and needs for process safety in the new mellennium" was given by Sam Mannan from Mary Kay O'Connor Process Safety Center at Texas A&M University in USA. He introduced the terms NIMBY - Not In My BackYard and BANANA - Build Absolutely Nothing Anywhere Near Anyone, and immediately rejected both ideas. In stead he argued for continued learning and improved communications. In passing he incorrectly stated, that several layers of protection failed at Bhopal in 1984, which is only true if incorrect management decisions can be considered a failure of a protection layer. He also argued for increased research in process safety and development of technology for deep water drilling. I am not sure that is the correct medicine. If one reviews the major negative events in the process industry over the last quarter century, Then a surprising large number them are caused by some failure of management. This was the case in Bhopal in 1984, when management without proper review removed and/or in other ways disabled 3 systems, which could have mitigated the catastrofic release of MIC. No failure of technology was involved in that watershed event!

The second plenary was by Vincent Tam from Centre for Fire and Explosion Studies at Kingston University in London. His presentation "The Buncefield Accident: Why is the Explosion so Severe?" attempted to give a scientific explanation for the severe explosion damage observed on buildings and cars around the Buncefield Oil Depot after the explosion and fire in December 2005. Both this mornings speakers pointed out, that Buncefield was not a one of a kind event, but had happened before, and also since. This points to the disturbing fact, that learning from accidents are not really taking place unless goverments institute additional regulations.

After the plenaries I chaired another session about human factors and safety management systems. Today with a clear focus on the former. The first presentation by Ronny Lardner from the Keil Centre in Edinburgh described how they had reduced errors in electrical isolation work on one of BP's platforms in the North Sea by looking closely at performance shapping factors, such as no independent review, unnecessary interruption of critical tasks, and workload. They destinguished between intensional and unintensional errors.By removed interruptions during execution of critical task the number of unintensional errrors on the platform was reduced by almost 2/3.
The second presentation titled "Procedural Controls for Major Incident Hazards" and given by Paul Delanoy, who is a chemist and chemical engineer with The Dow Chemical Company at King's Lynn in the UK. This work focused on task decomposition - an idea central to the work on MFM by Morten Lind at DTU-Elektro.
I think these two papers are some of the best I have heard at this years Loss Prevention symposium, and I hope these results will be published to benefit a larger audience.

The mornings third presentation was by Xavier Cricl from Fire Protection Consultants in Antwerpen. It was titled "Unified Emergency Management in the Port of Antwerp", and described a web-based system for communication between different actors at different levels during an emergency. I believe, that such systems take too much for granted. What means of communication do the stakeholders have in an actual emergency, which could include a complete power outtage in the city of Antwerpen? I also did not feel comfortable about their attention to ensuring the availability of communications lines in case of an emergency by daily testing, as is done by CVECO in Sarnia, Canada. I also wonder about where their emergency centers were, and if they had a mobile emergency operations center, as in Sarnia.

Af lunch I gave a short presentation titled "25+ years after Bhopal - Have we learned the lessons? Properly NOT!", The point of the presentation was that governments continue ot create new regulations for the industry, because the industry does proactively do that on its own either through organisations such as Responsible Care or CEFIC or ACC, There was standing room only in the auditorium for this presentation.

Later in the afternoon the Chemical Safety Boards was awarded the EPSC Process Safety Award for their excellent series of free videos produced sinde the BP Texas City explosion. After this the EPSC showed the 7½ minutes management video developed in collaboration with the WP Loss Prevention based on a suggestion from Peter Schmelzer from Bayer 4 years ago.

Many conference attendees finished the day by enjoying a mediaval dinner at a former church in the center of Bruges. The show was impressive and the food was extremely tasteful.

The symposium finish with a half day of presentations tomorrow.

Monday, June 07, 2010

Loss Prevention 2010 off to a Good Start!

This morning the Loss Prevention 2010 international symposium in Bruges, Belgium opened with a keynote address by J.M. Jaubert from Total titled “Safety Expectations versus Field Achievements: Bridging the Gab”. The background was that Total in 2009 after several good years experienced 4 fatality events. The company board in august of 2009 started a detailed review of process safety, which resulted in many recommendation: 15% of recommendations related to process technology, 40% related to human factors, and 45% related to organizational issues. Total for several years have had a safety culture program. I guess they forgot to audit the quality of the program.

After the presentation the Danish safety expert J.R. Taylor asked if part of the problem was management via a large amount of e-mails. To this question Jaubert responded, that part of the problem was lack of regular visits by management to the plant due to pressures with responding to e-mails and creating presentations. I recall having a manager of the Esso Chemical Canada site at Sarnia, Canada, who spent two mornings a week talking to people in the control rooms and the maintenance shows just to keep in touch. Eddy de Rademaker, the chairman of the symposium organizing committee, beat that by stating that in his first job many years ago he had a manager, who each morning toured his plant before he went to his office. Along the same line a Danish refinery a few years ago found, that contractor performance increased in both safety and quality of work, when they assigned employees to keep contact with them on a daily basis.
A representative from the Health and Safety Executive in the UK raised the issued of the impact of available skills as the result of downsizing and outsourcing activities. I did not hear a direct answer to that question.

The triannual 2½ day Loss Prevention symposium is arranged by the EFCE Working Party on Loss Prevention and Safety Promotion. Previous symposia were in Edinburgh (2007) and Praha (2004), and the next one will be in Firenze (2013). The members of the Working Party, who have been appointed by their national engineering organizations, constitute the technical program committee for the symposium. The current chairman of the Working Party is George Suter from Switzerland, and after this symposium Eddy de Rademaker from Belgium will take over as chairman.

After the morning coffee break I chaired a session on Human Factors and Safety Management Systems at which 4 contributions was presented. The first work “Experiences in Assessment of Safety Management System” was presented by Fabrizio Gambetti from ENI in Italy. Fabrizio graduated from Polytechnic of Milano with an aeronautical engineering degree, and is thus another example, that the initial degree may have nothing to do with your current employtment. He is currently safety manager supporting development of the safety management system for Eni owned and operated refineries. In his presentation he touched upon the different views of operators and management on process safety, issues relating to HSE and contractors, and the need for KPI's. Unfortunately questions from members of the audience kept me from asking if his company would be willing to share values of KPI's for the company as a whole or from individual refineries, as part of their communication with neighbours according to Responsible Care.

The second work was “Process Safety Metrics, Diagnosis and Control – Aspects of a Holistic Approach” presented by Bert Knegtering and co-authered by Professor Emeritus Hans J. Pasman currently working at Texas A&M University. Bert in his presentation touched upon the complexity of organizations, occupational safety – as in Shell's Hearts & Minds program – and process safety, and how different layers of protection may shift with time. I need to re-read his paper – and possibly his thesis – in order to understand the implications of this work.

The third presenter was Steve Tanzi, a chemical engineer with PricewaterhouseCoopers, who has worked with Mike Broadribb from B.P. America on a presentation titled “One Company's Experience with Process Safety Metrics”, which of course is linked to the recommendations of the Baker Committee after the Texas City explosion on March 23rd, 2005. The audiences questions the number of indicators proposed – more then 50, and I asked about who had responsibility for acting on an indicator. Steve explained, that in connection with each measure a person responsible for the quality of the measure was apointed, and another person responsible for acting on the indicator, plus to other with other responsibilities relating to the measure. I still tend to agree with Peter Schmelzer of Bayer, that the number of indicators should be drastically reduced – properly to less than 5 – for SME's to cope with them.

The final and fourth presentation was “Governance of Process Safety within a Global Energy Company” given by Mark McBride, a chemical engineer with Centrica. His presentation focused on three areas: leardership, accountability and stakeholder engagement. He questioned whether safety issues at powerplant that fall under the Seveso II directive was any different, than at those that did not. When questioned after the presentation Mark explained than Centrica HSE Committee consist of both directors and board members. I pointed out, that there are companies, who have committee of the board consisting of non-company employees overlooking safety issues at the corporate level.

A very good start on an excellent conference programme on loss prevention and safety promotion.