Market Place
While the world feels the heat of the Covid-19 pandemic with the global pharmaceutical supply chain getting impacted, normalcy is returning
to China. According to new reports, the production of drugs and APIs in China is also returning to normal.
In a press conference held by top Chinese officials this week, the country’s ministers highlighted that as of March 28, the average operating rate of industrial enterprises across China had reached 98.6 percent and the production of some key vitamin, antibiotic and analgesic raw material drug companies had returned to normal with yields of major products reaching above 80 percent.
Officials had paid heed to resumption of production
The officials
highlighted that during the critical period of epidemic prevention and control,
the Chinese government had paid close attention to the resumption of production
of API companies. After receiving reports that some companies in Hubei had not
resumed work, which would impact the supply chains of products like metronidazole, ibuprofen, and taurine, the
authorities urgently coordinated with the relevant departments of Hubei, other
provinces, cities and counties to carry out key scheduling for some API
manufacturers and actively organized employees to return to work.
However, despite
these initiatives, due to the impact of the epidemic, wherein some enterprises
had stopped production and subsequently faced challenges with logistics and
transportation difficulties, there was a shortfall in supply.
The export
volume of APIs did decrease this year compared with the same period last year
and the officials estimated that most products witnessed a drop of about 10 to
20 percent, and in some cases the decline of individual varieties had reached
30 percent. Repeated communications between the officials and these
companies revealed that the main contributor to the decline in exports was sea
freight, as international shipping had greatly reduced, and transportation
costs have also increased.
Although
international transportation has become a bottleneck for the supply of some
APIs, the press conference highlighted that the output of other APIs had
exceeded the level of the same period last year.
China to meet global demand for chloroquine
The officials
made a special mention of medications like chloroquine phosphate which have
received significant attention as a potential treatment of the novel
coronavirus. After chloroquine phosphate was identified as a potentially
effective treatment, the government worked with the two major API manufacturers
in China to organize the companies to meet international demand. For example, Chongqing Kangle Pharmaceuticals exported 4.9
tons of chloroquine APIs within five days.
This news from
China is encouraging to the global supply chain as following the rising interest in a chloroquine analog — Hydroxychloroquine (HCQ) — the
Indian government issued a directive which
prohibits the export of HCQ API and formulations made from HCQ. The directive
did, however, offer exemptions to exports from special economic
zones/export-oriented units and in cases where export is made to fulfill an
export obligation under any advance license issued on or before the date of the
notification.
Last week, Hungary, which is also one of the world’s largest exporters of HCQ, also banned the commercial export of the ingredient and the
United Kingdom (UK) banned the export of finished formulations of HCQ as part
of a list of 135 medicines posted that cannot be exported from the UK
because they were needed for the UK patients.
In early
March, the Indian government had also restricted the exports of
13 APIs along with some of their finished formulations. The list included paracetamol tinidazole metronidazole acyclovir vitamin B1 vitamin B6 vitamin B12 progesterone chloramphenicol and neomycin.
However, a recent report published in The Economic Times highlighted that out of 13 drugs whose exports were restricted, the government is likely to lift the ban on the following five APIs — paracetamol, tinidazole, metronidazole, ornidazole and azithromycin. There were
also reports of significant pressure from the US on the Indian government for products
like paracetamol and the officials expect the ban to be lifted in the coming
days.
The Chinese
officials further went on to provide assurances that the supply of chloroquine phosphate can be increased in accordance with international market demand and that China’s Ministry of Industry and Information Technology will also organize the implementation of monitoring and production scheduling of key products, coordinate and solve the export transportation difficulties encountered by enterprises and strengthen communication.
Our view
The press
conference highlighted that China attaches great importance to the safety of
the global pharmaceutical industry supply chain and President Xi Jinping had
promised at the G20 summit of member states on March 26 that China will
increase its efforts to supply APIs to the international community.
The Chinese
government is working earnestly to implement the commitment to maintain the
production of API manufacturers and ensure the safety and stability of global
industrial chain supply, the statement emerging out of the press conference
said.
Given the global pharmaceutical supply chain’s overwhelming dependence on China, the nation’s return to normalcy is a positive sign for countries across the world. For the time being, the pandemic has only increased the world’s dependence on China. All countries that want to reduce their reliance on China will take time not just to build capacities, but also to emerge out of the Covid-19 crisis.
Impressions: 1617
https://www.pharmacompass.com/radio-compass-blog/chinese-industrial-activity-revival-at-98-6-percent-officials-assure-of-api-supplies
#PharmaFlow by PHARMACOMPASS
02 Apr 2020
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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: 8182
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
This week, Phispers brings to you the latest news from the world of pharma where Merck was found lying under oath, Mylan’s “exceptionally large” drug price hikes reignited the price-gouging debate and data integrity issues surfaced in China. And, a lot more.Dr. Reddy’s acquires products from Teva; but faces penalties in the USThis has been a mixed week for Dr. Reddy’s Laboratories. The company has signed a deal
with Israeli drug maker Teva to acquire a portfolio of eight abbreviated
new drug applications (ANDAs) in the US for US $ 350 million. In April 2015, Teva
had entered into a deal with Allergan
to buy its generics products for US $ 40.5 billion, soon after it failed in its
bid to buy Mylan.
On the flip side, the US Consumer Product Safety Commission
(CPSC) has sought civil penalties against Dr. Reddy’s for failing to report problems with packaging of several medicines. In a 4-1 vote held two weeks ago, CPSC said Dr. Reddy’s knowingly violated federal law as issues with child-resistant blister packs for five prescription drugs were not reported within the mandated 24 hours. The violations had occurred between 2002 and 2011.
After antibiotics in Chinese rivers, it’s metformin in American watersIn June last year, we reported on how antibiotics were found
in the rivers
of China. This week, a
new study has found traces of the widely-used diabetes drug – metformin – and other medicines in dozens of streams throughout southeastern United States. The survey was done on 59 streams and it found an average of six different drugs. The findings suggest the cause of contamination was
unrelated to discharges from wastewater treatment facilities. Metformin
appeared in 89 percent of the samples and 97 percent of the sample sites. Researchers also found traces of tramadol (opioid);
carbamazepine
(anti-seizure drug) and Allegra (antihistamine). At some of the sample sites,
the concentrations of these medicines are expected to affect aquatic life. There was also some good news about metformin this week. Research
has suggested that metformin may exert a long-term protective effect against
neurodegenerative diseases, including Alzheimer's and Parkinson's. Court overturns US $ 200 million jury award; says Merck ‘lied under oath’A federal judge in San Jose found Merck lied
to a business partner and to the court. As a result, the judge threw out a
patent infringement judgment Merck had won against Gilead
Sciences. He also overturned a US $ 200-million jury award. This judgement is considered a landmark one, considering it involves Gilead’s blockbuster drug Sovaldi, a treatment for the hepatitis C virus, and Merck – the world’s fourth-largest drug company. “Merck's misconduct includes...misusing Pharmasset's confidential information..., and lying under oath at deposition and trial,” the federal judge, Beth Labson Freeman, said. This news comes at a time when a review by the US Food and
Drug Administration (FDA)
staffers questioned whether an experimental Merck drug is effective in
treating Clostridium difficile, or C. difficile, the most common cause of
infectious diarrhea in hospitals and nursing homes. Mylan’s ‘exceptionally large’ drug price rise brings pricing debate back in focusPrice gouging has been plaguing the global pharma industry
for quite some time now. During the week, there was news about Mylan and Pfizer
increasing prices. Over the last six months, Mylan
has raised prices by more than 20 percent on 24 products. Meanwhile, Pfizer was in news for increasing the list prices
of its medicines in the US by an average of 8.8 percent. This is the second
time this year that Pfizer
has substantially boosted prices for its prescription drugs. On January 1, Pfizer had raised prices by an average of 10.4 percent. Mylan boosted prices by more that 100 percent on seven other products. Wells Fargo analyst David Maris termed the price hikes as “exceptionally large.” In Europe, the high price of drugs is straining its cash-strapped
health systems and depriving patients of the latest products. Ergo, the European
pharmaceutical industry is considering a radical shift in the way it prices
drugs so that companies are rewarded for the clinical benefit of treatments
rather than the number of pills sold. An internal report prepared by the
European Federation of Pharmaceutical Industries and Association has called for
the removal of external reference pricing and placing curbs on parallel
imports. Interpol’s Operation Pangea IX seizes US $ 53 million worth of illicit medicinesInterpol seized potentially life-threating drugs and goods,
including fake cancer medication, substandard HIV and diabetes testing kits,
counterfeit dental equipment and illicit surgical equipment, through its Operation
Pangea IX. The operation involved targeting illicit online sale of
medicines and medical devices. It involved 193 police, customs and health
regulatory authorities from 103 countries. Operation Pangea resulted in 393
arrests worldwide and the seizure of more than US $ 53 million worth of
potentially dangerous medicines. The operation was supported by private partners from the
Internet and payment industries and saw the suspension of 4,932 websites
selling illicit pharmaceuticals. India’s pharma industry growth dips to two-year lowThe impact of Indian health ministry’s gazette notification banning the immediate manufacture, sale and distribution of 344 fixed dose combination (FDC) drugs has begun to reflect in growth
numbers. The Indian pharmaceuticals market’s growth this May was the lowest in two years, impacted by a drop in sales of FDC drugs, fresh price cuts and a lower than expected uptake, according to pharmaceutical market research company AIOCD PharmaTrack. For May, the pharmaceuticals market grew by 7.7 percent compared to 11.6 percent during the same month last year, reaching sales of Rs 994.76 billion (US $ 14.8 billion) over a 12-month period. India’s FDC market dropped 14.6 percent and is now valued at Rs 1.96 billion (US $ 29.1 million). Valeant may sell stake in Egypt’s largest drug company AmounValeant
Pharmaceuticals International plans to step up its debt-reduction plans and
is considering the sale
of Egyptian drug maker Amoun Pharmaceutical. According to a report, Amoun
may attract drug companies with an interest in expanding in emerging markets.
Valeant is reportedly working with Goldman Sachs Group on the sale. Last year, Valeant had acquired Amoun’s holding company – Mercury Holdings – for around US $ 800 million, along with some contingent payments. Valeant’s intentions at the time were to use Amoun as a platform to further expand in the Middle East and Africa.
GMP problems roundup:
Fresh cases emerge in China, India Beijing
Taiyang Pharmaceutical Industry, a Chinese manufacturer of diphenyhydramine
hydrochloride, a commonly used antihistamine, was placed on the FDA import alert
list in April 2016. Last week, Beijing Taiyang was also placed on Health Canada’s Inspection Tracker List as the regulatory agency evaluated the risk the company’s products posed to patients. The primary reason given for the action was data integrity concerns.
Akums
Drugs & Pharmaceutical Limited is a major Indian contract manufacturer
with nine facilities that mostly supply to the domestic market. Akums’
international expansion plans suffered a setback as its facility in Haridwar (India)
failed its first EDQM (European Directorate for the Quality of Medicines &
HealthCare) inspection. The critical deficiency observed by the
inspectors was the “lack of sterility assurance as there was insufficient
evidence during validation to confirm that all ampoules in the load met the
sterilizing conditions”. There were also deficiencies observed across all
aspects of the quality management system. Akums’ failure is a setback for the Netherlands-based Nordic
Pharma Limited for whom Akums was manufacturing progesterone
injection 50mg/mL ampoules (Gestone). The inspection failure will result in the
recall of four batches from the UK and Ireland and will most likely have Nordic
Pharma retain their existing contract
manufacturer, Hikma
Italia SPA.
Impressions: 4088
https://www.pharmacompass.com/radio-compass-blog/dr-reddy-s-faces-penalties-in-the-us-metformin-found-in-american-waters-interpol-seizes-illicit-medicines
#PharmaFlow by PHARMACOMPASS
16 Jun 2016
