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: 1619
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: 8190
After 2 years of sky-high approval numbers, the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research approved 22 novel drugs in 2016, down from the 19-year high of 45 in 2015. The FDA also approved many new dose forms, formulations, combination products and vaccines.
This
week, PharmaCompass, shares its analysis of the new drug approvals by the FDA
in 2016.
Reasons behind the low approvals in 2016
Of the 22 novel drugs approved by the FDA, the FDA approved 9 products with orphan designation, in line with the industry’s recent focus on rare diseases. However, as the industry shifts its focus towards biotechnology, only 7 of the novel products approved were biologic applications.
The 9
orphan designees approved (41% of all new drug approvals) were significantly lower than the 21 (47%) orphan designees approved in 2015 and 17 (41%) in 2014. FDA’s approval of 4 (18%) oncology drugs in 2016, was also down from the 14 (31%) approvals in 2015, 9 (22%) in 2014 and 9 (33%) in 2013.
The
reasons for the low 2016 approval count, have been attributed to the agency
approving five drugs in 2015 that actually had approval action dates in 2016
and an increase in the number of drugs that the agency rejected.
A key reason for the rejections was the sponsors’ failure to comply with good manufacturing practice regulations.
Click here to access our list of all New Drug Approvals (Excel version available) for FREE!
Gilead’s Epclusa, the first
all-oral, pan-genotypic, single tablet regimen for the treatment of adults with
chronic hepatitis C virus (HCV) infection, is expected to become the most
profitable approval of 2016 with expected sales of $ 8.4 billion by 2022.
2016 also saw the FDA’s contentious approval of Exondys 51™ (eteplirsen) under its accelerated approval process. Exondys 51™ treats Duchenne muscular dystrophy (DMD), a rare genetic disease which causes progressive muscle wasting that affects around 20,000 boys and young men in the United States.
Approvals of three biosimilars which
target $ 33 billion in brand drug sales
In a
giant leap for the generic pharmaceutical industry, three biosimilar
applications were approved in 2016 that target brand drugs which generated more
than $ 33 billion in sales last year.
All the three biosimilars approved were tumor-necrosis factor alpha (TNF α) inhibitors used to manage inflammatory conditions.
Pfizer and Celltrion’s Inflectra, a
biosimilar to Janssen’s Remicade® (2016 sales - $ 8.8 billion), was the first to get approval for all Remicade-approved indications, except pediatric ulcerative colitis. Inflectra was launched at risk in November 2016.
After Inflectra’s approval, the FDA approved Sandoz’s Erelzi, a biosimilar to Enbrel® (etanercept – Amgen, 2016 sales - $
9.1 billion).
On Sept. 23, 2016, Amgen’s Amjevita™ (adalimumab – atto), a biosimilar of the world’s best-selling drug by revenue, AbbVie’s Humira®(2016 sales - $ 16.4 billion), was also approved for treating adults with a variety of medical conditions ranging from rheumatoid arthritis, plaque psoriasis, to ulcerative colitis.
Click here to access our list of all New Drug Approvals (Excel version available) for FREE!
Kim Kardashian’s pregnancy drug is now available in a new strength
Diclegis,
a combination of an antihistamine (doxylamine succinate) and a form of vitamin B6 (pyridoxine HCl), made headlines
when the FDA issued a warning letter for the social media promotion of the drug by Kim Kardashain, star of the reality show ‘Keeping Up With The Kardashians’
Duchesnay,
the company which produces Diclegis, got approval for Bonjesta which combines twice
the amount of doxylamine and pyridoxine when compared with Diclegis which contains
10mg of each ingredient.
Indian generic companies get approvals for
differentiated products
As the
generic industry in the U.S. continues to face severe pricing pressure, Indian
generic companies are attempting to overcome these challenges by trying to move
up the value chain by supplying differentiated generic products.
Consistent
with this strategy, the applications of Sun Pharmaceuticals
for a new ophthalmic version of Bromfenac (Bromsite) and Dr. Reddy’s Laboratory
for an injectable version of Sumatriptan (Zembrace™ SymTouch) to treat migraines were also approved.
Click here to access our list of all New Drug Approvals (Excel version available) for FREE!
Pfizer launches an opioid treatment with
abuse-deterrent properties
The abuse
of opioids, including prescription painkillers and drugs like heroin, is
something the United States has struggled with since before the 1900s. Last year, the FDA announced that immediate-release
opioid painkillers such as oxycodone and fentanyl will have to
carry a "black box" warning
about the risk of abuse, addiction, overdose and death.
Pfizer
got approval last year for Troxyca ER a combination containing oxycodone and naltrexone. Troxyca ER has properties that are
expected to reduce abuse when crushed and administered by the oral and
intranasal routes.
In it,
the oxycodone releases slowly over several hours. If the capsules are crushed,
the encased naltrexone mixes with oxycodone, essentially cancelling any euphoric
effects.
Pfizer
also received approval for an extended release form of Tofacitinib (Xeljanz® XR) to treat adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.
Click here to access our list of all New Drug Approvals (Excel version available) for FREE!
A dietary supplement gets approved along with new forms of commonly used drugs
In 2016, Endoceutics
got Intarosa, a once-daily vaginal insert, approved which is the first FDA
approved product to contain prasterone, also known as dehydroepiandrosterone (DHEA).
Although
DHEA is included in some dietary supplements, the efficacy and safety of those
products have not been established for diagnosing, curing, mitigating, treating
or preventing any disease.
Lisinopril, the most commonly used drug
by U.S. Medicare patients, was approved as an Oral Solution for the first time.
Diabetes
treatments, one of the most commonly prescribed drug categories in the U.S., saw
the addition of Sanofi and Novo Nordisk’s fixed-dose,
long-acting insulin and glucagon-like peptide 1
(GLP-1) agonist combinations to the list of options available to treat adult
type-2 diabetes.
Our View
The approval
of new drugs ensures that the world has access to improved healthcare solutions
and breakthrough medical therapies.
With Donald Trump “focused on accelerating the FDA” and an on-going argument that drugs should not have to be proven effective before getting approved, this year looks like the one where the new drug
approval scenario will be shaken up for time to come.
Click here to access our list of all New Drug Approvals (Excel version available) for FREE!
Impressions: 14465
Kim Kardashian who is a model, actress, entrepreneur, socialite and star of the reality show ‘Keeping Up With The Kardashians’, has her posts on social media promoting the drug Diclegis, result in the US Food and Drug Administration (FDA) issuing a warning letter recently.The reality TV star shared
a selfie of herself, on Instagram and Twitter, holding a bottle of Diclegis, a
prescription-only drug used to treat nausea and vomiting during pregnancy. The posts violated FDA’s drug-promotion regulations and the warning letter was issued to Duchesnay USA, the company which produces the drug. The FDA’s warning letter said the media posts did not communicate the
medical risks of the drug. Viral CommunicationKardashian’s posts, told over 40 million followers that Diclegis (doxylamine
succinate and pyridoxine
hydrochloride) made her feel “a lot better” and worked after everything else her doctor recommended had failed to cure her morning sickness. In addition she said, “Most importantly, it’s been studied and there was no increased risk to the baby”.“I’m so excited and happy with my results that I’m partnering with Duchesnay USA to raise awareness about treating morning sickness…,” the post added, and was liked over 450,000 times. Kardashian’s post was pre-approved by Duchesnay, with whom Kardashian “partnered” to raise awareness about morning sickness. What Kardashian
failed to mention“The social media post is misleading because it presents various efficacy claims for DICLEGIS, but fails to communicate any risk information,” says the FDA warning letter. According to its FDA-approved product labeling, DICLEGIS is indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management. The FDA also issued the warning letter for omitting material
facts as the drug has not been studied in certain populations of women.
Diclegis has not been studied in the about 1 percent of women who undergo
dangerously severe vomiting called hyperemesis gravidarum, the condition that made
headlines last year when in Britain, Prince William's wife Kate was briefly
hospitalized.A different version of the drug, Benedictin was taken off
the market in 1983 following a series of lawsuits alleging links to birth
defects. The decision
taken by Merrell Dow Pharmaceuticals, to stop selling Bendectin, was driven
by commercial reasons because the company's insurance premiums had soared to US
$ 10 million a year, only US $ 3 million less than the income from the sale of
the drug. However, subsequent FDA investigations never established any
link between the drug and the reported problems. All in the family The promotion was also a family affair. Duchesnay said Kardashian’s mother, Kris Jenner, also a paid spokeswoman, shared Kardashian’s social media posts on her own accounts. Jenner tweeted, "#SPONSORED Glad @KimKardashian is feeling better, wish I had something like this product during all my pregnancies! (sic)"As an expected corrective action, in the letter sent to the Executive Vice-President of Duchesnay, the FDA has mentioned that “corrective
messaging should be distributed using the same media, and generally for the
same duration of time and with the same frequency that the violative
promotional material was disseminated”.Diclegis has been available
in Canada under the trade name Diclectin® for more than 30 years as the only prescription drug specifically indicated and approved for the management of nausea and vomiting of pregnancy (NVP). The product is a delayed-release combination of an old antihistamine and a form of vitamin B6 (doxylamine
succinate and pyridoxine
hydrochloride) designed to help women take a daily dose before their nausea
sets in.Thankfully, the 34-year-old Keeping
Up With the Kardashians star's doctor had prescribed her Diclegis. Although the FDA may not be happy about the posts, the
advertisements have been a resounding
success. AdWeek assessed
the controversy will help the company in the long run, since more people have
now heard of Diclegis.
Impressions: 3580