Market Place
Now that it has been
established that the novel coronavirus is going to globally impact the drug
supply chain, it becomes imperative to analyze the extent of the impact.
Since the outbreak of
the novel coronavirus — COVID-19 — in December, PharmaCompass has been constantly reaching out to
manufacturers around the world to assess the current state of the drug supply
chain. This week, we share our preliminary analysis based on the feedback we
have received from drug manufacturers around the world.
Drug shortages are
for real
Last week, the US
Food and Drug Administration (FDA) announced the first human drug shortage
as a result of the coronavirus outbreak. In addition, the FDA announced it was
tracking 20 drugs that could face shortages. Some generic drugmakers are predicting shortages
as early as in June or July, due to the novel coronavirus.
The FDA did not disclose the name of the drug in shortage or the 20 drugs it is tracking, as this is considered ‘confidential commercial information’.
In India, a committee constituted by the country’s Department of Pharmaceuticals started monitoring the availability of 58 active pharmaceutical ingredients (APIs) to take preventive measures
against illegal hoarding and black-marketing in the country.
According to a report published in The Economic Times, after
reviewing the list of drugs, 34 were found to have no alternatives which
include critical and essential drugs like potassium clavulanate, ceftriaxone sodium sterile, piperacillin tazobactam, meropenem, vancomycin, gentamycin and ciprofloxacin.
This was immediately
followed by the Indian government restricting the exports of 13
APIs along with some of their finished formulations. The list includes paracetamol, tinidazole, metronidazole, acyclovir, vitamin B1, vitamin B6, vitamin B12, progesterone, chloramphenicol and neomycin. For most
of the products on this list, India is a net importer, as there is little
domestic manufacturing of these APIs.
COVID-19 is also
likely to impact bottomlines. Leading generic drugmaker Mylan said it expects the coronavirus outbreak to impact its financial results
while some of the largest drugmakers — including AstraZeneca, Merck and Pfizer — have said that the coronavirus outbreak could affect their supplies or sales.
Paracetamol
affected; prices double in less regulated markets
The decline in industrial activity in China is certainly taking its toll, as drugs which are on the World Health Organization’s Model list of Essential Medicines are beginning to face significant price increases in the wake of disruption of key starting raw materials for bulk drugs.
The export
restriction out of India on commonly used analgesic, Paracetamol — sold under the brand names such as Tylenol (in the US), Panadol (in the UK), Dafalgan (France) and Crocin
(India) — is not surprising as the API has witnessed almost doubling of prices in less regulated markets because exports of its key building block para-amino phenol (PAP) have dramatically reduced from China.
While there are only
a few manufacturers who produce paracetamol without being dependent on Chinese
PAP, a few major manufacturers in India depend almost completely on Chinese PAP
for their paracetamol production and usually only keep three to four months of
inventory.
By the end of
February, their inventory stockpiles had halved and in the event of a continued
supply disruption, their entire inventory pipeline is likely to dry out. In
addition, Chinese paracetamol manufacturers, who export a significant amount of
their bulk ingredient production globally, including to India, are also
currently unable to export. This is beginning to create the potential of panic
among sourcing executives across the world.
Several
antibiotics also in danger of acute shortages
While paracetamol was listed on the API watch list circulated by India’s Department of Pharmaceuticals, our survey has revealed that other products on the list like ciprofloxacin, amoxicillin and azithromycin are also facing severe raw material
shortages. As a result, the prices of these bulk drugs have also increased
sharply.
In a statement to The Economic Times, leading Indian generic manufacturer Mankind Pharma’s chairman and managing director said
amoxicillin is the most commonly used API to manufacture antibiotics and the
company has invested Rs 1 billion (US$ 14 million) in placing irregular orders
with vendors to try and address the potential shortage that is expected. He
went on to say that if the situation continues until April, there will be an
acute shortage.
In a statement to the US House of Representatives last October, Janet Woodcock, the FDA’s Director of Center of Drug Evaluation and Research, said the FDA has determined that there are three WHO Essential Medicines whose API manufacturers are based only in China. The three medicines are: capreomycin, streptomycin (both indicated to treat Mycobacterium
tuberculosis) and sulfadiazine (used to treat chancroid and trachoma).
Streptomycin is also on the watch list published by India’s Department of Pharmaceuticals along with commonly used anti-hypertensives like losartan, valsartan, telmisartan and olmesartan and diabetes treatment metformin.
Intermediates
becoming a problem for generic drugmakers
PharmaCompass’ discussions have also revealed that in many cases while API manufacturing factories in China have returned to work, there are disruptions in the availability of raw materials and/or logistics at sea ports and airports which have led to unavailability of supplies.
While the FDA has a
list of the number of API facilities in China which are in a position to supply
to the United States, Woodcock said in her statement that the FDA “cannot determine with any precision the volume of API that China is actually producing, or the volume of APIs manufactured in China that is entering the US market.”
This visibility
reduces drastically when one has to assess the dependence of each API
manufacturer around the world on China for intermediates. Our discussions have
revealed that it is these intermediates which are becoming a problem for most
API manufacturers, even those based in India.
It was worth
highlighting that a manufacturing process change at an intermediate stage of
commonly used blood pressure medicine valsartan resulted in the recall of
millions of pills as it was found to contain a cancer causing impurity above
acceptable levels. Similarly, in 2008, the adulteration of heparin in China,
which killed 81 people and left 785 severely injured, was an outcome of the
subcontracting of precursor chemicals of Heparin.
Our view
The over-dependence
on China for key starting materials has been the subject of discussion ever
since we launched PharmaCompass. Rosemary Gibson explored this subject
in detail in her book China Rx: Exposing the Risks of America’s Dependence on
China for Medicine.
The restrictions imposed on industrial activity and transportation in China in the first two months of this year has resulted in NASA’s satellite images showing a decline in pollution levels over China.
While China works
towards getting its industrial and transportation engine up and running to 2019
levels, the outbreak has spread to other countries which will further increase
the demand for drugs to fight the virus.
This is a time when
the pharmaceutical industry needs to act responsibly and make decisions which
are in the best interests of patients globally.
Sharing information is one such step — it will allow for drug stockpiles and inventories that exist to be re-distributed to areas which need them most. For, in the event of an urgent need, drugs will become available to those who are most in need.
Impressions: 8185
https://www.pharmacompass.com/radio-compass-blog/covid-19-india-restricts-drug-exports-amid-rising-prices-of-essential-bulk-drugs-fda-announces-first-drug-shortage
#PharmaFlow by PHARMACOMPASS
04 Mar 2020
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This week, Phispers brings you the
latest on the Ranbaxy-Daiichi and Merck-Gilead cases. There is also news on
Medtronics, which faces a whistleblower lawsuit. And Valeant, which has come
under the scanner for allegedly defrauding insurers. Our compliance roundup
updates you on companies across the world that faced regulatory action
recently. Singapore court’s 373-page order reveals how Ranbaxy withheld information from DaiichiLast week, a report in The Indian Express brought to light how Ranbaxy deliberately withheld information from Japan’s Daiichi Sankyo in the Ranbaxy-Daiichi case. The information was based on a copy of the Singapore International Arbitration Centre’s (SIAC) order, passed in April 2016. The former owners of Ranbaxy – Malvinder Singh and Shivinder Singh – face a penalty of Rs 35 billion (US $ 523 million) and have until August 22 to challenge the SIAC order. The information implicates the Ranbaxy top brass in a “in a slew of irregularities, from fraud to falsehood.” In over 373 pages, the SIAC order lays out what it calls “the path of deception that Ranbaxy took and how it kept Japan’s Daiichi Sankyo — which bought Ranbaxy in 2008 for Rs 198 billion (US $ 2.96 billion) — in the dark even a year after its purchase”. The SAIC order was based on a 2004 Self-Assessment Report (SAR) prepared by the then head of research and development of Ranbaxy, Rajinder Kumar, for the company’s internal use. The contents of an internal report were not shared with Daiichi. The SAR listed
over 200 drugs, including antiretroviral drugs for treating AIDS patients, for
which Ranbaxy allegedly used fabricated data to bag approvals from regulators
and authorities of more than 40 countries. Compliance roundup: Chinese, Indian, American and Spanish firms in compliance troubles Notice of non-compliance to Artemis Biotech: Artemis
Biotech, a division of Themis
Medicare in India, received a notice
of non-compliance from European regulators. According to the regulators,
the company had violated basic principles of data integrity within its instrument
laboratory. And the relevant GMP data was outside the control of the quality
management system. As an outcome of the inspection, the Certificates of Suitability (CEPs) granted for popular cholesterol lowering ingredient – simvastatin – have been suspended. Just three months ago another Indian manufacturer – Krebs
Biochemicals & Industries – had its CEPs suspended for the same product.Alcor found to have unsuitable facilities: A Spanish manufacturer – Alcor SL – that manufactures liquid syrups for use in Spain was found not to have suitable facilities, personnel and materials to ensure proper compliance with GMP during an inspection in June this year. Although the company responded with a corrective action plan, it was found “insufficient”.Claris recalls injections in the UK: Indian manufacturer Claris
Lifesciences recalled
Furosemide
injections in the United Kingdom as they had been inadvertently distributed in
the country. The product was intended for sale in Australia. FDA’s warning letters to Zhejiang Medicine, Concept Products: While
there was activity in Europe, the FDA issued a warning
letter to Zhejiang
Medicine (Xinchang Pharmaceutical Factory), a manufacturer of antibiotics
like levofloxacin,
daptomycin
and vancomycin,
for data integrity violations. Laboratory personnel were found “disguising testing”. The personnel were conducting unofficial testing that was being recorded in separate ‘R&D’ folders before conducting the officially reported sample analyses. Analysts were also found signing
and dating microbiological testing laboratory worksheets five days before the
test results were available and backdating laboratory worksheets for impurities
and content testing by four days.The FDA also issued a warning
letter to a Chinese manufacturer, Concept Products Limited, for “significant violations of cGMP regulations for finished pharmaceuticals”. It placed yet another Indian company Laxachem Organics and Chinese firm Yangzhou
Hengyuan on import alert. Warning letter to Noven: A US-based patch manufacturer – Noven
Pharmaceuticals – received a warning
letter over quality concerns uncovered in its transdermal drug delivery
systems (TDDS) such as Minivelle
and Daytrana.
The FDA expressed concerns over the scientific soundness of the company’s measurement method since the FDA stated that “your unsound methods could be masking product failures” and leading “to product detachment, expose the drug to other people, and other safety issues.” Now, Merck has to pay Gilead’s US $ 200 million legal feeIn March this year, Merck
had won a legal dispute over sofosbuvir,
the API in Gilead's
multibillion-dollar drugs Sovaldi and Harvoni.
The federal jury had ordered Gilead to pay Merck US $ 200 million in damages
for infringing on patents for the hepatitis C drugs. But
in June, the US Dristrict Judge Beth Labson Freeman threw out Merck’s victory and snatched back the US $ 200 million Merck had been awarded. Last week, the same judge added insult to Merck’s US $ 200 million-injury. Freeman said Gilead was entitled to relief from legal fees it had incurred while defending its case.Merck has been handed a US $200
million bill for Gilead's
legal fees. Merck now intends to appeal in the case, saying the judge’s ruling “does not reflect the facts of the case.” FDA launches improved web-based version of its Orange BookThis week, the US Food and Drug
Administration (FDA) launched an improved
web-based version of its Orange Book – a publication on drugs approved on the basis of safety and effectiveness. The Orange Book is widely used by doctors and by the regulatory community for identifying which drug products are substitutable for one another. The improved Orange Book has an updated design and has more user-friendly search optionsFormerly known as the Approved
Drug Products with Therapeutic Equivalence Evaluations, the Orange Book had
first appeared as a published list in 1980. It came online in 1997. Valeant allegedly defrauded insurers, may be under criminal
investigation In one of the most serious probes
faced by Valeant
Pharmaceuticals, the Canada-headquartered company may be under criminal investigation over allegations that it defrauded insurers by hiding its ties with a mail-order pharmacy – Philidor – that boosted its sales. Prosecutors are probing whether
Philidor made false statements to insurers about its ties with Valeant, while
helping patients get coverage for the higher-priced Valeant drugs. According to
a report published in The Wall Street
Journal, criminal charges are likely to be levied against former Philidor
executives and against Valeant as a company. The relationship between Philidor
and Valeant has been under the scanner since October 2015, when questions were
raised about Valeant's accounting. Novartis to expand capacity of monoclonal antibody plant in EuropeNovartis
is investing
US $ 100 million to expand its monoclonal antibody (mAb) capacity at a
plant in Europe. The Swiss drugmaker has committed about US $ 1 billion to
boost its biosimilar production in order to emerge a leading player in
biosimilars. Novartis is beginning work on the mAb project that will boost
capacity by 70 percent at the Novartis biotechnology center in Huningue,
France. Meanwhile, the company has
acknowledged that employees in South Korea may have been involved in rebate
trickeries. But it says an investigation of similar accusations
in Turkey uncovered no problems. In Turkey, Novartis considers the matter
closed.In April, a prosecutor in Turkey
had reportedly opened an investigation after receiving a copy of an email sent
by an anonymous whistleblower to Novartis CEO saying the unit there paid
consultants US $ 290,000 in 2013 and 2014 to win about US $ 85 million in
business from government hospitals.Matters in South Korea are a lot serious. In South Korea, prosecutors want the government to suspend the company’s operations there after they indicted half-dozen executives for issuing improper rebates. German watchdog criticizes efforts to accelerate new drug approvalsGermany’s cost-effectiveness watchdog – the German Institute for Quality and Efficiency in Health Care – has criticized
an effort by European regulators to accelerate approval for new medicines
based on limited evidence. These concerns come at a time when regulators on both
sides of the Atlantic are looking for new approaches to fulfill unmet
medical needs through faster approval of drugs.Adaptive pathways approach is a term
used to describe a method for jumpstarting drug approvals for select patient
populations. Two years ago, the European Medicines Agency (EMA) had launched a
specific pilot program in this direction. However, the German watchdog
maintained that the EMA failed to make its case that this approach for
approving drugs can make a demonstrable difference. Medtronic faces
whistleblower lawsuit for using devices under false pretensesMedtronic, a major medical device manufacturer, is facing a whistleblower lawsuit that claims it sought FDA approval for its devices under false pretenses. The devices were being regularly used for a purpose they weren’t intended to be used by the regulators.According to Dr. Vikas Saini, president of the Lown Institute, a Boston healthcare think tank, who has been following the case, the devices had been labelled ‘not for cervical spine use’. “Yet, in everything about them, including emails from their marketing folks, it makes clear that they were meant to be and were used in the cervical spine,” Saini said.Medical devices are lightly regulated by the FDA. Once
cleared by the FDA, physicians used medical devices however they deem fit. Questions being
raised on health of Clinton, Trump Donald Trump and Hillary Clinton are two of the oldest presidential candidates in the US history. While Clinton’s doctor certified that she “is in excellent physical condition” and Trump’s physician declared he would be “the healthiest president – ever”, these testaments are not being taken seriously in the absence of detailed medical records. Both Trump’s and Clinton’s doctors released brief
assessments of their health recently. Television host Sean Hannity has aired a series of segments on Fox that cast doubts on Clinton’s health. Democrats, on the other hand, have been questioning Trump’s mental health. One congresswoman recently suggested he should undergo a “mental fitness test.”
Impressions: 5118
https://www.pharmacompass.com/radio-compass-blog/ranbaxy-s-path-of-deception-revealed-in-singapore-court-order-chinese-indian-american-and-spanish-firms-in-compliance-troubles
#PharmaFlow by PHARMACOMPASS
18 Aug 2016
Peter J. Werth, President and Chief Executive Officer, ChemWerth, a US-headquartered full-service generic active pharmaceutical ingredient (API) development and supply company providing cGMP quality APIs to the regulated markets, is a proponent of removing data to a data-integrity (DI) file from data history, if it isn’t linked to product quality. According to Werth, FDA is unnecessarily obsessed with data integrity issues, and pharma companies have begun to fear FDA inspections. This needs to change, Werth tells PharmaCompass.
Excerpts from the interview.
Can you tell us about your journey in the world of
pharmaceuticals?
I
began by supplying generic cough and cold APIs by setting up a chemical
business back in 1975. There was a small group of companies (first generic companies)
that mainly sold cough and cold products. These companies wanted to sell patent-expired
generics and we developed select APIs for them. There was no real FDA (US Food
and Drug Administration) approval process involved.
By 1982, I realized the generic industry would be big business and API sourcing was key to success. Since I knew the API business, my wife and I formed ChemWerth – a company that supplied generic APIs.
By
1988, ChemWerth was working with 10 American and three Chinese manufacturers.
But the generic scandal changed everything. My American partner factories gave
up the API business when new
regulations came in. Chemical plants could no longer manufacture APIs. From my
previous 11 years of dealing with China, I knew that almost all of the dosage
form factories also produced APIs. This was especially important for the
injectable grade products. By the early 1990s, ChemWerth was developing APIs
for highly toxic oncology injection drugs and many antibiotics. We successfully
introduced doxorubicin, daunorubicin, mitomycin, bleomycin, etoposide, ifosfamide and several antibiotics such as lincomycin, clindamycin phosphate, amikacin sulfate, tobramycin and vancomycin (all from China).
Today, ChemWerth represents 25 Chinese factories for about 100 products. We still represent one American API supplier along with several Indian manufacturers. We recently expanded to supply veterinary drugs and partnered with a major supplier of polypeptides and a world-class supplier of heparin and related products.
You have been working with China for many years now. When
did you first come to China and how has the Chinese pharmaceutical industry
transformed over the years?
I first went to China in 1979. During that
trip, I realized I could successfully deal with the Chinese. Most of my friends
who went to China said it was impossible to deal with them. I always thought
this gave me an advantage in China. Over the next seven years, I kept in touch
with China, but did very little business.
In 1986, I was running ChemWerth and was a
consultant with a company to help its large pharmaceutical facility produce generic
APIs. We targeted clindamycin phosphate for development, since the product had
good sales, and was off patent. It also had no competition because Upjohn
(an erstwhile US-headquartered pharma company that got merged with Pharmacia in
1995, which in turn got bought over by Pfizer) controlled all the key starting material – lincomycin
hydrochloride. Using my contacts and my ability to deal with Chinese factory directors, I managed to break Upjohn’s stronghold in lincomycin. I convinced three factories to work with me so that I could file a DMF (Drug Master File). Clindamycin became a very good product for ChemWerth and gave me reason to visit China regularly to develop new business.
In those days, factories were generally old and needed upgradation. Documentation was always good, and in detail. However, it was mostly in codes and therefore useless to most others. It was extremely difficult to convince the factory to provide a true and detailed process to ChemWerth to file a DMF with the FDA. There is still a tendency (amid factories in China) to hide important facts. As a result, it takes ChemWerth at least three versions/iterations before we think we have got the right process details.
Today, the hardware in China’s pharmaceutical factories is excellent, and is usually purchased from the best overseas manufacturer. The software is good too and is likely to improve drastically as manufacturers realize software is equally important as hardware.
In view of the current GMP concerns being uncovered at
Chinese companies, are you still focused on China as a source of
pharmaceuticals?
In my mind, and in the ChemWerth representative factories, there are no
GMP concerns, no quality concerns, and no data history concerns. The FDA's
fascination with data integrity focuses on a problem that does not exist in more
than 90 percent of the pharmaceutical factories. There are at least 18 reasons
to remove data from data history. All of these 18 reasons are related to
analyst error and equipment failures (laboratory gross errors) and not related
to quality or GMP manufacturing. (Click here to read Werth’s 18 reasons to remove data).
I agree that gross errors/laboratory gross errors should not be deleted. I also agree that deleted gross errors/laboratory errors not related to quality do not deserve a warning letter.
However, the FDA should also know the main reason data is deleted is because the analyst (often) knows the result is not correct for reasons not related to quality (gross errors/laboratory gross errors). They do not want to conduct an expensive, time-consuming, and cumbersome OOS (out-of-specification) investigation. Therefore, they delete the data, weigh out new samples, fix the problem, analyze, and either receive acceptable results or rejection results.
Today, China has the most modern manufacturing facilities and the money to invest in software to manufacture the highest quality with the best traceable records. The Chinese need to trust the FDA to treat them fairly and not rely on two and three-year-old DI information. They will do the job correctly now and in future. But they cannot change the past. As stated earlier, all DI product-related observations have proven that the product quality and product history were acceptable.
China can only become a stronger API supplier. China’s volumes will increase and costs will decrease, because the domestic market is growing rapidly. The country will have cost/pricing pressures and will need to concentrate more on the difficult products that require expensive equipment. The standards set by the China FDA (CFDA) match the US FDA standards. And this will make it easier to operate under one quality and documentation system. Most importantly, they have the money to invest in the latest technology, best scientists, and equipment.
In your view, what can pharmaceutical regulators and the industry
do differently in order to communicate that the product quality is not at risk,
given the environment where data-integrity violations have become commonplace?
The FDA needs to understand that DI has no relationship with product quality. We have two recent examples. In the first case, DI issues applied to 70 batches. All 70 batches were retested and all were found to be in specification. The second case gave the same results – between two inspections over 100 batches were considered potentially fraudulent. All 100 batches were retested and were found to meet the specification. At both the factories, the data history showed all the batches are in specification – this implies 100 percent correlation to quality. The data integrity listed 100 batches and no batch failed specification – this shows 0 percent correlation to quality.
From a DI perspective, FDA inspections in factories that only produce APIs for export should be different from inspections in pharmaceutical companies that export APIs and dosage form. In reality, API manufacturers cannot cheat. They sell their product to dosage form manufacturers, which in turn are responsible for the quality that goes into the dosage form.
Off specification batches will be rejected and returned to the API manufacturer. While inspecting factories’ customer complaint file, it is rare to find batches being rejected and returned to the factory. The same does not apply to pharmaceutical companies that produce both API and finished dosage. They can hide information. Data integrity is more of an issue with companies that manufacture both API and dosage form.
What steps is ChemWerth taking with its partners in China
to improve compliance standards?
ChemWerth is addressing this issue with the FDA and ChemWerth representative factories. In broad terms, data history should be paramount, since it is related to product quality. Data integrity is a part of data history. ChemWerth has prepared a standard operating procedure (SOP) to handle electronic data.(Click here to read ChemWerth’s SOP). A simple version is that when one or both samples are out-of-specification, the analyst’s supervisor (who committed the error) reviews the data with the analysts. If they determine that one of the 18 reasons for analyst error or equipment failure is the cause of the failure, then this is noted. Three new samples are prepared, the error is corrected, and the samples are run and if all samples pass then these results are retained in data history and the product is passed. The previous bad result is documented and removed to the data integrity file. No lengthy, time-consuming, and expensive OOS report is conducted. This makes the procedure factory-friendly.
In the above example, if one of the three new samples fails, then all results are retained in the data history. The batch is rejected for rework or reprocessing.
I believe the present atmosphere between the
FDA and API manufacturers is at an all-time low. The industry feels the FDA
inspectors are looking at mostly irrelevant data to prove that the factory
operates fraudulently. Factories no longer welcome FDA inspections, out of fear
of DI failure. Factories feel the FDA is using DI to point out fraud where
there is none (excluding Hisun
and Ranbaxy).
In the past, we always welcomed FDA inspections as part of doing business. We
need to get back to that time and place.
Impressions: 6149
https://www.pharmacompass.com/radio-compass-blog/data-integrity-has-no-relationship-with-product-quality
#PharmaFlow by PHARMACOMPASS
07 Jul 2016
Researchers at the University of Nottingham’s Centre for Biomolecular Sciences have demonstrated that Bald’s Leechbook, an Old English leather-bound manuscript, has a one thousand year old Anglo-Saxon remedy for eye infections, which can kill the modern-day superbug Methicillin-Resistant Staphylococcus Aureus (MRSA).
The remedy, verified in university labs
in both the United States and United Kingdom, worked better than the current
gold standard for MRSA flesh infections, the antibiotic vancomycin.
With our past analysis varying from ‘APIs urgently needed in US and Canada’ to ‘Are assessments of foreign regulatory (USFDA
& EDQM) inspections fair?’,
one might wonder why focus on spinning tales like Harry Potter... Well, the
answer could be worth $100 trillion!
Antibiotics, those boring commodity
molecules, which humans consumed more than
3 million kg of in 2009, and animals were fed almost 13 million kg in 2010, have
now started gaining global attention due to concerns of antibiotic
resistance.
How
serious is the focus and how bad is the concern?
2012 -
Law passed in the United States, commonly known as the GAIN Act, or the Generating Antibiotics Incentives Now Act, to help stimulate the development of new antibiotics to treat serious or life-threatening infections. Under the GAIN Act, certain antibacterial or antifungal drugs can be designated as “Qualified Infectious Disease Products” (QIDPs), which allows the drug to get priority
review, eligibility for fast track designation and the possibility of an
additional five years of marketing exclusivity.
April 2014 - WHO’s first
global report on antibiotic resistance in 114 countries reveals a serious, worldwide threat to public health. The loss of effectiveness of antibiotics can create a “post-antibiotic era” in which, common infections could become deadly again.
December 2014 - Former Goldman Sachs chief economist, Jim O'Neill, chairs UK report, which warns that failure to tackle the antibiotic resistance problem, will make it bigger than cancer by 2050 on one hand, will also cost the global economy up to $100 trillion, and could cause at least 10 million extra deaths a year.
March 2015 - The White House releases a five year - $1.2 billion National Action Plan, for combating antibiotic resistant bacteria. The fight is officially declared a “national security priority”.
Recognizing the multiple challenges
faced due to antibiotic resistance, the USFDA & Center of Disease Control
have launched a partnership, the Get
Smart Campaign, which seeks to ensure that patients get the right
antibiotic at the right dose for the right amount of time.
However, studies are now beginning to show
that the problem is spiraling out of control, since it is more than just an
antibiotics prescription issue.
Earlier this month, analysis of urine
samples of almost 60% of over 1000 school children in China, were
found to contain antibiotics. As the tested antibiotics have been clinically discontinued, the most likely source of exposure is the food and the environment.
In addition to the China schoolchildren
study, a Swedish
study around Hyderabad (the heart of the Indian pharmaceutical industry), found a number of drugs contaminating the water, some in concentrations higher than in patients’ blood.
As antibiotic production is heavily polluting,
the residual traces of antibiotics in the waste water are also responsible for
growing antibiotic resistance in many areas.
So while governments continue to battle with the major health challenge of antibiotic resistance, the entire supply chain is currently linked to China, where the environmental concerns are continuing to grab attention of local authorities.
The United States is almost
completely reliant on China for its supply of life-saving antibiotics; India, the world's pharmaceutical factory, imports 80% of its
bulk drugs from China; it is worth wondering how a cooperative, global solution
will be arrived at.
While the Indian government is promoting
self-sufficiency of antibiotic supply, by trying to revive the almost defunct
Hindustan Antibiotics Limited (HAL), the challenges faced are gigantic.
So
how are the scientists and industry helping?
Companies are actively developing
new antibiotics and there are many in the pipeline, however "of the 32
or so companies with antibiotics in clinical development today, only five rank
among the top 50 pharmaceutical companies by sales."
In June 2014, Actavis
acquired Durata
Therapeutics for about $675 million to get their lead product DALVANCE (dalbavancin),
the first drug approved as a QIDP. Merck
followed suit in December by acquiring
Cubist
Pharmaceuticals, a company specializing in developing treatments for
superbugs for $9.5 billion.
The Medicines Company is the only company left with an approved new antibiotic that has not been acquired by Big Pharma. Their antibiotic Oritavancin,
has Orange Book patent expiries starting in 2015 but exclusivities are valid
until 2019.
A team from Northeastern University
along with others, earlier this year, published a paper in Nature on a new
antibiotic, Teixobactin, which has a novel mechanism
of action and is a new discovery technology platform. This is the first big
antibiotic breakthrough in decades. Under accelerated regulatory approval the
molecule will take about five years to reach the clinic.
Our ‘Phisper’:
While everybody is trying new, innovative solutions to address this global problem, you can consider the “Ancientbiotic” way from Bald's Leechbook. It is after all, widely thought of as one of the earliest known medical textbooks, and contains Anglo-Saxon medical advice and recipes for medicines, salves and treatments.
The simple eye salve used by the researchers contains two species of Allium (garlic and onion or leek), wine and oxgall (bile from a cow's stomach) brewed in a brass vessel. The ingredients are pounded together and left to stew for days. The resulting mash kills germs as well as germs that form a sticky mess called a biofilm; modern antibiotics find this difficult to achieve.
If you wish to get ahead, contact Dr
Christina Lee, the Anglo-Saxon expert from the School of English who enlisted the help of microbiologists from the University’s Centre for Biomolecular Sciences to recreate the 10th century science... She is looking for funding support!
Impressions: 3228
https://www.pharmacompass.com/radio-compass-blog/1000-year-old-remedy-maybe-a-solution-to-a-100-trillion-pharmaceutical-problem
#PharmaFlow by PHARMACOMPASS
16 Apr 2015
