Today begins the World Health Organisation (WHO)’s World Antibiotic Awareness Week, which aims to increase global awareness of antimicrobial resistance (AMR) and encourage the public and policymakers alike to avoid the spread of antibiotic resistance.
The pharmaceutical industry produces these life-saving treatments in use today, through manufacturing and research programmes. When in-PharmaTechnologist (IPT) spoke with Lucas Wiarda (LW), head of the sustainable antibiotics program at DSM Sinochem Pharmaceuticals, he told us that both are under threat.
“The prices [of antibiotics] have been dropping to such an extent that life-saving treatments have dropped below the price of a box of chewing gum. It […] means companies are either stepping out of the area or performing shortcuts [during manufacture],” he explained.
Lack of return on investment has seen major pharma companies, such as AstraZeneca and Novartis, divest their assets in the space – severely limiting R&D in the area.
In addition, the pressure put on pharma to lower the cost of antibiotics has led to manufacturing practices that are now contributing to the rise of AMR.
To find out how companies are balancing the tightrope of producing sustainable antibiotics, Lucas Wiarda explained what actions DSM Sinochem Pharmaceuticalsand the wider industry are now taking.
IPT: What instigated DSM Sinochem Pharmaceuticals's efforts against AMR?
LW: We are one of the biggest manufacturers of antibiotics in the world and, we thought, how are we connected to one of the biggest global threat today? We are one of the bigger, if not the biggest, manufacturers of amoxicillin, which is quite an old antibiotic but is very frequently used. Obviously, if bacteria become resistant against this precious antibiotic then, of course, we will have to wind down and close our factories. So, our efforts have been driven by a major, business concern; I am a father of a son, many of my colleagues are also part of a family, so there is also the human perspective. We are concerned that antibiotics could become ineffective and therefore bacterial infections could become deadly again.
IPT: What are major drivers of AMR and how is the understanding around this changing?
LW: Previously, the focus had always been on the irresponsible use or misuse of antibiotics, by humans and by animals – because we do not finish our treatments or we take too much, or we take them just for a cough. In many countries, they are not subject to prescription so you can just get them over-the-counter.
Another element is the pipeline of new antibiotics that are not coming through. The WHO [World Health Organisation] has published numerous articles in which it shares their concern that there have been no really big breakthroughs in antibiotic treatment in the last 20 to 30 years. It's a huge concern.
Lastly, we looked at our own manufacturing process and we started saying that everyone should manufacture antibiotics responsibly. This was triggered by numerous scientific articles on the high concentration of antibiotics found in Indian waterways; there were abnormally high concentrations in the area where the manufacturers were producing antibiotics. This cocktail of antibiotics form the ideal breeding ground for antibiotic resistance, much the same way as in the human body.
IPT: How has DSM Sinochem Pharmaceuticals reacted to this global threat?
LW: We made all kinds of investments and also improved manufacturing practices to reduce the antimicrobial active waste released into the environment. For instance, we are using our own wastewater treatment plants, which have the right capacity to treat water according to the capacity of our plants. We have also introduced a test that measures the antibiotic activity in our effluent. We were one of the first companies to introduce such practice and, of course, we have tried to make the issue public.
We started to reach out to our customers and suppliers, especially the former, to stress that we, as an industry, could be furthering AMR when our products are meant to fight bacterial infections – this is a contradiction.
IPT: How is the wider industry reacting?
LW: It took a while before everyone started understanding the issue but we managed to submit a white paper, in 2016, where the 13 signatory companies committed to a number of measures to combat AMR.
Number one was concerning reducing the environmental impact of manufacturing antibiotics.
Number two was related to the misuse and stewardship of antibiotics.
Number three was related to R&D.
The fourth one was related to access; of course, you need access to the right antibiotics.
We followed this up with a mechanism to enforce the commitments made, and established the AMR Industry Alliance, with the help of the IFPIA [International Federation of Pharmaceutical Manufacturers & Associations]. We started asking the signatories of the roadmap to report the progress we are making and to do so we have established 'working groups', which were organised around those four pillars. This led to a series of questions that a company had to answer about its progress.
IPT: How will these be measured?
LW: We reached out to the scientific community to develop science- and risk-based tolerance levels for our effluent. As an industry, we could introduce our own standards but obviously many people would say they were not very credible. This led to a list of defined tolerance levels for most antibiotic manufacturers, which we now have to start adhering to. The roadmap companies are now taking measures - so, they will measure the effluent levels based on the scientifically defined method to test effluent. At that point, they will have to determine whether the tests are positive or negative against the tolerance levels.
IPT: What timeframe is industry working towards?
LW: Our intention, within the industry, is that before 2020, we will start measuring and introducing measures to meet the standard. From an industry perspective, this is an enormous commitment but this also shows the serious nature of the issue.
IPT: What is hindering further progress?
LW: There is an issue here that there are only 13 companies. The first declaration on AMR, as an industry-led initiative, was signed by over 200 companies but this latest one only had 13. Nonetheless, we have brought the initiative together with the AMR Industry Alliance and we hope that these 200 companies will start implementing the measure stated in the latest roadmap.
IPT: Why have some companies been reluctant to sign up to the new guidelines?
LW: Most of the companies that signed these white papers are located in the western hemisphere, whereas the majority of the manufacturing takes place in India and China. It's really important that we come up with mechanisms that also make those manufacturers subject to the standards we, as an industry, have to implement. That is a bit cumbersome.
We call on the public sector, whether that is a public organisation such as the WHO, the United Nations or national governments to start defining mechanisms where the public procurement systems will also take into account social and environmental criteria rather than only the price.
IPT: Is making the pricing debate difficult in the current climate?
LW: We understand that it is sensitive because we are aware that healthcare must be affordable and available for all. At the same time, the prices have been dropping to such an extent that life-saving treatments have dropped below the price of a box of chewing gum. It increases the accessibility and affordability of such treatment but that means companies are either stepping out of the area or performing shortcuts, which will harm the standards, social or environmental, that is also undesirable. If there is no fair return on products, it will not help build a sustainable supply chain.
There is a relation between the enormous price hikes, with notable examples seen in the US, and an unsustainable supply chain. The list of product shortages is also growing, which is a result of the value chain. The companies that used to manufacture these products cannot any longer because it's not economically feasible. The parties that then take over the market apply different standards.
There was a case where the last factory in China that produced the ingredients for tazobactam, a last resort antibiotic, had an explosion and there were very severe shortages in Europe. This is very an antibiotic that is very frequently used and from one day to another, it wasn't available anymore. This is all the consequence of a very unsustainable value chain.
IPT: How much does making the products sustainable influence price?
LW: We have shown that making the antibiotics more sustainable does not necessarily lead to higher prices - it could be a few cents. We do hear stories, and we do suffer from, some cases where customers have stepped down and this is not a matter of 1,000% price increases, it is only a matter of a few percentage points.
IPT: What more be done to combat AMR?
LW: If we really want to make a change in fighting AMR then we have to start working together, though this is one of the most difficult things – there is a natural tension between the public and private sector but we have to. We talk about climate change, there is a bigger trend there where the public and private sector can talk to each other. The same needs to happen with this global threat.
After joining DSM Sinochem Pharmaceuticals in 2008, Lucas Wiarda has performed various roles, and is currently business unit director for drug products and head of the sustainable antibiotics program. Lucas played a key role in establishing the Industry Roadmap on Antimicrobial Resistance (AMR) and is a member of the AMR Industry Alliance Board.