Market Place
We usher in 2023 with the key highlights of the US Food and Drug Administration’s December 2022 list of Off-Patent, Off-Exclusivity (OPOE) Drugs with No Approved Generics. With this list, the FDA hopes to bolster competitiveness
in the generics market.The OPOE list gets updated every six months. Such updates are a part of FDA’s initiative to improve transparency and encourage the development and submission of abbreviated new drug applications (ANDAs) in markets with little competition.Since 2017, the FDA has been publishing the OPOE list of drugs without an approved generic. For a year now, the FDA has been publishing two versions of the OPOE list — one for prescription drug products and one for over-the-counter (OTC) drug products that are approved and marketed under a new drug approval (NDA).View FDA's 2022 List of Off-Patent and Off-Exclusivity Drugs (Free Excel)Four
new applications added to Dec 2022 list; 96 first generics approved last yearWhile the FDA’s June 2022 list of OPOE Drugs with No Approved Generics had 98 new applications for prescription drugs, the December 2022 list saw a sharp decline — only four new applications were added during this period. We had witnessed a similar trend in 2021 — the December 2021 list had only 16 new applications as
opposed to 35 new applications in the June 2021 list.The four new applications were for diclofenamide (a drug to treat glaucoma), ephedrine sulfate (a drug used to treat asthma and
heart failure that also acts as a central nervous system stimulant), meloxicam (an arthritis drug) and pemetrexed (a chemotherapy medication). In
May 2022, the FDA approved the first generics for pemetrexed injection
developed by several companies, including Accord Healthcare, Fresenius Kabi, Apotex, Qilu Pharmaceutical, Biocon, Dr. Reddy’s Laboratories and
Zydus, to treat non-small cell lung cancer (NSCLC) and mesothelioma. Almost one-third of the prescription products – 184 out of 505 – are drug products delivered as injectables, and 68 entries are for oral solid dosage forms (such as tablets, capsules and modified release forms).In the June 2022 list, a total of 60 OTC
drug products were listed. This time too, the same number of OTC drug products
figured in the OPOE list. These include antiseptic agent chlorhexidine gluconate,
non-steroidal anti-inflammatory drug ibuprofen, anti-allergy drug loratadine and painkiller acetaminophen. Of these, 19 are delivered as
oral solid dosage forms (such as
tablets, capsules and modified release forms).In 2022, the FDA approved 96 first generics. This is slightly higher than
the 93 approved by the agency in 2021.As the name suggests, “first generics” are the first approvals handed by the FDA to manufacturers to market a generic product in the United States. The agency considers first generics to be important to public health, and prioritizes review of these submissions.View FDA's 2022 List of Off-Patent and Off-Exclusivity Drugs (Free Excel)AbbVie’s Humira, Novartis’ Entresto to finally face generic competitionAbbVie is facing one of the steepest patent cliffs in the industry’s history, with Humira slated to face the onslaught
of eight biosimilars this year. The blockbuster drug had generated US$ 21.2 billion in 2021. Amgen’s Humira biosimilar – Amjevita – will hit the market this month. The other Humira
biosimilars that will be launched this year include Abrilada (Pfizer), Cyltezo (Boehringer), Hadlima (Samsung Bioepis), Hyrimoz (Sandoz), Hulio (Viatris) and Yusimry (Coherus BioSciences). In mid-December, Fresenius Kabi became the latest
company to win US approval for its Humira copycat — Idacio.Novartis’ heart failure drug Entresto will also go off patent this month. The blockbuster drug had generated US$ 3.5 billion in 2021.View FDA's 2022 List of Off-Patent and Off-Exclusivity Drugs (Free Excel)Our viewIn our previous OPOE drug listing, we had talked about FDA’s intent to bring down drug prices, with the agency putting 98 new applications of prescription drugs in the OPOE list for June 2022. That intent has only become stronger with the US Patent and Trademark Office (USPTO) and the FDA joining hands to promote
competition. The two bodies are working towards improving the patent system in an effort to stop its misuse through “patent thickets”, “evergreening” and “product-hopping”. With this clear intent to lower drug prices in the US, the OPOE lists for 2023 and beyond are likely to get more interesting. For now, all eyes are set on what generic competition will do to blockbusters like AbbVie’s Humira and Novartis’ Entresto.
Impressions: 2571
https://www.pharmacompass.com/radio-compass-blog/fda-s-list-of-off-patent-drugs-suggests-higher-approvals-of-first-generics-in-2022
#PharmaFlow by PHARMACOMPASS
05 Jan 2023
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Acquisitions and spin-offs dominated headlines in 2019 and the tone was set very early with Bristol-Myers Squibb acquiring
New Jersey-based cancer drug company Celgene in a US$ 74 billion deal announced on
January 3, 2019. After factoring
in debt, the deal value ballooned to about US$ 95 billion, which according
to data compiled by Refinitiv, made it the largest healthcare deal on
record.
In the summer, AbbVie Inc,
which sells the world’s best-selling drug Humira, announced its acquisition of Allergan Plc, known for Botox and other cosmetic
treatments, for US$ 63 billion. While the companies are still awaiting
regulatory approval for their deal, with US$ 49 billion in combined 2019
revenues, the merged entity would rank amongst the biggest in the industry.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
The big five by pharmaceutical sales — Pfizer,
Roche, J&J, Novartis and Merck
Pfizer
continued
to lead companies by pharmaceutical sales by reporting annual 2019 revenues of
US$ 51.8 billion, a decrease of US$ 1.9 billion, or 4 percent, compared to
2018. The decline was primarily attributed to the loss of exclusivity of Lyrica in 2019,
which witnessed its sales drop from US$ 5 billion in 2018 to US$ 3.3 billion in
2019.
In 2018, Pfizer’s then incoming CEO Albert Bourla had mentioned that the company did not see the need for any large-scale M&A activity as Pfizer had “the best pipeline” in its history, which needed the company to focus on deploying its capital to keep its pipeline flowing and execute on its drug launches.
Bourla stayed true to his word and barring the acquisition of Array Biopharma for US$ 11.4 billion and a spin-off to merge Upjohn, Pfizer’s off-patent branded and generic established medicines business with
Mylan, there weren’t any other big ticket deals which were announced.
The
Upjohn-Mylan merged entity will be called Viatris and is expected to have 2020
revenues between US$ 19 and US$ 20 billion
and could outpace Teva to
become the largest generic company in the world, in term of revenues.
Novartis, which had
followed Pfizer with the second largest revenues in the pharmaceutical industry
in 2018, reported its first full year earnings after spinning off its Alcon eye
care devices business division that
had US$ 7.15 billion in 2018 sales.
In 2019,
Novartis slipped two spots in the ranking after reporting total sales of US$
47.4 billion and its CEO Vas Narasimhan continued his deal-making spree by buying New
Jersey-headquartered The Medicines Company (MedCo) for US$ 9.7
billion to acquire a late-stage cholesterol-lowering
therapy named inclisiran.
As Takeda Pharmaceutical Co was
busy in 2019 on working to reduce its debt burden incurred due to its US$ 62
billion purchase of Shire Plc, which was announced in 2018, Novartis also purchased
the eye-disease medicine, Xiidra, from the Japanese drugmaker for US$ 5.3 billion.
Novartis’ management also spent a considerable part of 2019 dealing with data-integrity concerns which emerged from its 2018 buyout of AveXis, the
gene-therapy maker Novartis had acquired for US$ 8.7 billion.
The deal gave Novartis rights to Zolgensma,
a novel treatment intended for children less than two years of age with the
most severe form of spinal muscular atrophy (SMA). Priced at US$ 2.1 million,
Zolgensma is currently the world’s most expensive drug.
However,
in a shocking announcement, a month after approving the drug, the US Food and
Drug Administration (FDA) issued a press release on
data accuracy issues as the agency was informed by AveXis that
its personnel had manipulated data which
the FDA used to evaluate product comparability and nonclinical (animal)
pharmacology as part of the biologics license application (BLA), which was
submitted and reviewed by the FDA.
With US$
50.0 billion (CHF 48.5 billion) in annual pharmaceutical sales, Swiss drugmaker
Roche came in at number two position in 2019
as its sales grew 11 percent driven by
its multiple sclerosis medicine Ocrevus, haemophilia drug Hemlibra and cancer medicines Tecentriq and Perjeta.
Roche’s newly introduced medicines generated US$ 5.53 billion (CHF 5.4 billion) in growth, helping offset the impact of the competition from biosimilars for its three best-selling drugs MabThera/Rituxan, Herceptin and Avastin.
In late 2019, after months of increased
antitrust scrutiny, Roche completed
its US$ 5.1 billion acquisition of Spark Therapeutics to strengthen its presence in
gene therapy.
Last year, J&J reported almost flat worldwide sales of US$ 82.1 billion. J&J’s pharmaceutical division generated US$ 42.20 billion and its medical devices and consumer health divisions brought in US$ 25.96 billion and US$ 13.89 billion respectively.
Since J&J’s consumer health division sells analgesics, digestive health along with beauty and oral care products, the US$ 5.43 billion in consumer health sales from over-the-counter drugs and women’s health products was only used in our assessment of J&J’s total pharmaceutical revenues. With combined pharmaceutical sales of US$ 47.63 billion, J&J made it to number three on our list.
While the sales of products like Stelara, Darzalex, Imbruvica, Invega Sustenna drove J&J’s pharmaceutical business to grow by 4 percent over 2018, the firm had to contend with generic competition against key revenue contributors Remicade and Zytiga.
US-headquartered Merck, which is known as
MSD (short for Merck Sharp & Dohme) outside the United States and
Canada, is set to significantly move up the rankings next year fueled by its
cancer drug Keytruda, which witnessed a 55
percent increase in sales to US$ 11.1 billion.
Merck reported total revenues of US$ 41.75 billion and also
announced it will spin off its women’s health drugs,
biosimilar drugs and older products to create a new pharmaceutical
company with US$ 6.5 billion in annual revenues.
The firm had anticipated 2020 sales between US$ 48.8 billion and US$ 50.3 billion however this week it announced that the coronavirus pandemic will reduce 2020 sales by more than $2 billion.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Humira holds on to remain world’s best-selling drug
AbbVie’s acquisition of Allergan comes as the firm faces the expiration of patent protection for Humira, which brought in a staggering US$ 19.2 billion in sales last year for
the company. AbbVie has failed to successfully acquire or develop a major new
product to replace the sales generated by its flagship drug.
In 2019, Humira’s US revenues increased 8.6 percent to US$ 14.86 billion while internationally, due
to biosimilar competition, the sales dropped 31.1 percent to US$ 4.30 billion.
Bristol Myers Squibb’s Eliquis, which is also marketed by Pfizer, maintained its number two position
and posted total sales of US$ 12.1 billion, a 23 percent increase over 2018.
While Bristol Myers Squibb’s immunotherapy treatment Opdivo, sold in partnership with Ono in Japan, saw sales increase from US$ 7.57 billion to US$ 8.0 billion, the growth paled in comparison to the US$ 3.9
billion revenue increase of Opdivo’s key immunotherapy competitor Merck’s Keytruda.
Keytruda took the number three spot in drug sales that
previously belonged to Celgene’s Revlimid, which witnessed a sales decline from US$ 9.69 billion to US$ 9.4 billion.
Cancer treatment Imbruvica, which is marketed
by J&J and AbbVie, witnessed a 30 percent increase in sales. With US$ 8.1
billion in 2019 revenues, it took the number five position.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Vaccines – Covid-19 turns competitors into partners
This year has been dominated by the single biggest health emergency in years — the novel coronavirus (Covid-19) pandemic. As drugs continue to fail to meet expectations, vaccine development has received a lot of attention.
GSK reported the highest vaccine sales of all drugmakers with
total sales of US$ 8.4 billion (GBP 7.16 billion), a significant portion of its
total sales of US$ 41.8 billion (GBP 33.754 billion).
US-based Merck’s vaccine division also reported a significant increase in sales to US$ 8.0 billion and in 2019 received FDA and EU approval to market its Ebola vaccine Ervebo.
This is the first FDA-authorized vaccine against the deadly virus which causes
hemorrhagic fever and spreads from person to person through direct contact with
body fluids.
Pfizer and Sanofi also reported an increase in their vaccine sales to US$ 6.4
billion and US$ 6.2 billion respectively and the Covid-19 pandemic has recently
pushed drugmakers to move faster than ever before and has also converted
competitors into partners.
In a rare move, drug behemoths — Sanofi and GlaxoSmithKline (GSK) —joined hands to develop a vaccine for the novel coronavirus.
The two companies plan to start human trials
in the second half of this year, and if things go right, they will file
for potential approvals by the second half of 2021.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Our view
Covid-19 has brought the world economy to a grinding halt and shifted the global attention to the pharmaceutical industry’s capability to deliver solutions to address this pandemic.
Our compilation shows that vaccines and drugs
for infectious diseases currently form a tiny fraction of the total sales of
pharmaceutical companies and few drugs against infectious diseases rank high on
the sales list.
This could well explain the limited range of
options currently available to fight Covid-19. With the pandemic currently infecting
over 3 million people spread across more than 200 countries, we can safely
conclude that the scenario in 2020 will change substantially. And so should our
compilation of top drugs for the year.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Impressions: 54226
https://www.pharmacompass.com/radio-compass-blog/top-drugs-and-pharmaceutical-companies-of-2019-by-revenues
#PharmaFlow by PHARMACOMPASS
29 Apr 2020
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: 1579
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
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: 8004
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
Pharmaceutical companies often lose sleep over compliance-related issues. But three accidents, in as many weeks, have impacted GlaxoSmithKline’s (GSK) global manufacturing operations and highlight how safety requires the same level of focus as compliance. Trouble in China,
Belgium and America Take the case of explosions at a chemicals warehouse in the port
of Tianjin in China earlier this month. The blasts were so large that they
registered seismic activity in China. As per news reports, scientists were alarmed by the scale of explosions – the shockwaves from the first explosion were equivalent to detonating three tonnes of Trinitrotoluene or TNT; while the second explosion, which occurred 30 seconds later, was seven times more powerful (and equivalent to 21 tonnes of TNT).The damage caused by these explosions was catastrophic, as
they claimed
at least 121 lives. But these explosions also impacted GlaxoSmithKline
(GSK), which has two joint ventures in the Tianjin industrial area. Though GSK has not
revealed which drug products have been affected, this is the third
consecutive bad week for the pharma giant. Earlier this month, a boiler
explosion at GSK’s vaccine plant in Belgium killed one person. The following week, GSK had to temporarily shut
down its facility in United States after testing at a cooling tower found
bacteria that causes the deadly Legionnaire's disease. We look at different kinds of accidents that have impacted
pharmaceutical companies across the world. Boiler blowups are
not uncommonGSK’s accident in Belgium isn’t an isolated incident of a boiler explosion in the pharmaceutical industry. In 2012, a fire at Sandoz Canada’s Boucherville (Quebec) plant temporarily halted
production of about 90 per cent of injectable drugs used in Canada, squeezing
the supply of vital anesthetics, painkillers and antibiotics. Hospitals were
left scrambling to implement contingency plans in the face of a cross-country
shortage of injectable drugs. In India, last year, a worker was charred to death when a
boiler in the factory of Malladi Specialties in Thiruvallur burst accidentally. When dry powders explodeNormally explosions are associated with the presence of liquids
and fire. However, there are multiple examples where dry powders generate
enough static that a tiny electric spark is enough to trigger an explosion.In October 2007, a fire at Cambrex
Corporation’s drying department in Charles City, Iowa, injured
six people. And in March 2012, a fatal blast and fire at a Pliva plant in
Zagreb, Croatia, killed one worker and injured 16. Pliva is owned by Teva
Pharmaceuticals. The fire at the Pliva plant is said to have been started by a static electric short circuit that caused a spark, which in turn ignited the powder used in the production of a Paracetamol-based tablet product. Chemical explosions can
be fatalAccidents due to chemical explosions are far more common. A
little more than a year after the Pliva accident, a possible malfunctioning in a reactor plant in Teva’s operations in Israel caused an explosion, killing one person and injuring 30 people.In 2012, four
workers were burnt alive in a major fire that broke out after two blasts
occurred in the reactors at a subsidiary of India’s Ind-Swift
Laboratories – Dashmesh Medicare – in Mohali. While there is a long list of accidents involving chemicals that
have occurred in the manufacturing operations of pharmaceutical companies, not
all accidents involve activities related to production. For instance, Biotech giant Amgen reported
two accidents within a span of nine months at its laboratory, where flammable
materials exploded due to improper handling. The real reason
behind explosions at Tianjin port The port contained hazardous and flammable chemicals,
including calcium carbide, sodium cyanide, potassium nitrate, ammonium nitrate
and sodium nitrate. While the exact cause is unknown, it is common knowledge that
calcium carbide reacts with water to create highly explosive acetylene.
Chemical experts suggest an acetylene blast could have detonated the other
chemicals, resulting in a much larger blast.According to a report, shattered glass could be found up to
three kilometres (two miles) from the blast site. An area of more than 1.8
square miles near the blast site was destroyed, leaving 6,000 people homeless. A belated admission from authorities that more than 700
tonnes of highly toxic sodium cyanide was being stored at the blast
site has sparked deep anxiety over the potential of chemical
contamination. Wang Hongjiang, Vice Mayor of the town, claimed 200 tonnes of
sodium cyanide had already been collected as the clean-up operations continued.
Chinese authorities are using small, caged animals to test
the living conditions in Tianjin. Our viewWhile, for the past few years, GSK has been embroiled in a
scandal for bribing doctors and officials in China, the explosion in Tianjin is
another yet setback for GSK and its manufacturing operations in Tianjin that manufacture
pharmaceutical and consumer health products.Since the explosions did not occur at the GSK site, the
company could have done little to prevent the damage. However, recent natural disasters – like the ones in Japan
and Nepal – have taught us that the pharmaceutical supply chain needs to start factoring in the safety and environmental risks in addition to the quality challenges.
Impressions: 7590
https://www.pharmacompass.com/radio-compass-blog/glaxo-s-terrible-august-makes-safety-a-priority
#PharmaFlow by PHARMACOMPASS
27 Aug 2015
Recently the USFDA approved Aprecia Pharma’s SPRITAM® levetiracetam – a drug for epilepsy treatment manufactured by 3D
printing. This approval should encourage other players to pursue drug
development with renewed vigor.
Last week saw a revolutionary approval from
the US Food and Drug Administration (USFDA). For the first time, the USFDA
approved a drug manufactured by three dimensional printing
(3DP) – Aprecia Pharmaceuticals received the USFDA approval of epilepsy treatment SPRITAM® levetiracetam. Leveitracetam
was first approved in 1999.
Revolutionary
formulation & rapid delivery system
Aprecia gained the exclusive licence to 3DP technology
from MIT in the late 1980s, and by 2007 it began developing its proprietary ZipDose technology. But SPRITAM is revolutionary, not just because it is 3D printed, but for other reasons as well. SPRITAM® is a porous formulation that rapidly disintegrates with a sip of liquid. The dispersion is significantly superior to a conventional over the counter fast-melt tablet (watch the video: https://www.aprecia.com/zipdose-platform/zipdose-technology.php).
In fact, the drug is designed to dissolve
in the tongue (rather than swallowed as a whole). The patient experience is
enhanced since SPRITAM delivers an extremely high drug load, up to 1,000 mg in
a single dose. No measuring is needed as each dose is individually packaged,
making it easy to carry this treatment on the go.
3D
printers are not even expensive
For those not familiar with 3DP (or
additive manufacturing), it is a process used to make a three-dimensional
object without the use of dies, molds or machining. Instead, additive processes
are used, in which successive layers of material are laid down under computer
control (watch the video: https://www.youtube.com/watch?v=G0EJmBoLq-g).
These objects can often be of virtually any shape or geometry, and are produced
from a 3D model or another electronic data source. A 3D printer is a type of
industrial robot, and can range from small scale consumer models to large
factory units.
Now for the moot question – why are pharmaceutical companies not developing drugs with 3D printing? In fact, 3D printers are inexpensive, and the ingredients used to produce the drugs are the same that are currently being used and there are multiple candidates, other than those Aprecia is working on which would benefit from this technological revolution.
Making 3D printed drugs is really not that complicated or expensive. A recently published paper by researchers at the University College of London (UCL), “Effect
of geometry on drug release from 3D printed tablets” produced different shaped tablets using 3D printing which would be otherwise difficult to produce using traditional methods.
Simple
guide to make 3D printed drugs
The researchers simply purchased water-soluble PVA filament from MakerBot (not currently
available but other
PVA filaments are available on Amazon for under US $ 50), along with widely
used pain reducer and fever reliever, Paracetamol (also known as Acetaminophen)
and salts. They cut the filament into small pieces (approximately 2mm in
length), basically turning the spool of filament into pellets. This was
followed by mixing in the Paracetamol, and extruding the mixture from a Filabot filament extruder (it
costs US $ 949) at 180 degrees C. What came out of the printer was a 3D printed
drug.
PharmaCompass’ potential candidates for 3DP
Staying focused on opportunities where an extremely high drug load – up to 1,000 mg – has to be delivered in a single dose we ran a search on the PharmaCompass
database to find a few potential candidates for 3D printing.
Drug Name
Therapeutic Indication
Aminocaproic
Acid
Bleeding disorder treatment
Sucralfate
Ulcer medication
Cefadroxil
Antibiotic
Colestipol
Hydrochloride
Lipid lowering
Metformin
Hydrochloride
Diabetes
Methenamine
Hippurate
Urinary Tract Antiseptic
Ranolazine
Chronic Angina
Valacyclovir
Hydrochloride
Viral Diseases
Icosapent
Cholesterol reduction
In addition to these products, there are
multiple other possibilities which can get created by producing combination
drugs using 3D printing.
Overcoming
the challenges of slow 3D printing
With nearly three million people in the United States diagnosed with active epilepsy, Aprecia Pharmaceuticals’ revolutionary form of Levetiracetam clearly has a very large market need to address. However, the problem with 3D printing is that it is exceptionally slow when compared with conventional production methods for tablets.
Anticipating the problems, Aprecia
Pharmaceuticals announced on Feb. 23, 2015, that the company will open
a new manufacturing facility in Ohio that will use its powder–liquid three-dimensional printing (3DP) technology.
With plans to invest $25 million in a
190,000-ft2 facility, the new facility will be in addition to the
company's existing manufacturing and R&D facility in New Jersey.
Disrupting
healthcare in 3D
In the healthcare industry, 3D printers are
used by dentists to create
replicas of jaws and teeth as well as some finished dental implants and
orthopedic surgeons have tested them to make customized hip replacements.
In 2012, a two-year-old girl in Illinois,
born without a trachea, received
a windpipe built with her own stem cells.
British scientists have also used 3D
printing to create personalized replica models of cancerous parts of the body
to allow doctors to target tumors more precisely.
Our
View
The current way of consuming tablets can
definitely undergo a serious overhaul. With 3D printing technology rapidly
evolving and already inexpensive, there is little reason for the industry not
to pursue this area of drug development with greater vigor.
In addition, if we can measure our blood sugar levels using diagnostic kits at home, is it unrealistic to imagine a day when we’ll start printing our own medicines in 3D?
Impressions: 4582
https://www.pharmacompass.com/radio-compass-blog/fda-approved-first-3d-printed-drug-is-no-fad-but-a-technology-you-can-easily-develop
#PharmaFlow by PHARMACOMPASS
13 Aug 2015
With Novartis shutting two plants in Germany and one in India by 2016-end, the global reliance on China for bulk drugs has increased even further, raising serious concerns over safety, supplies and national security. Which
plants? Last week, Novartis announced it will be shutting three plants of its generic business – Sandoz – by the end of 2016. The first plant is in India and the other two are located in Germany, in Gerlingen and Frankfurt. Frankfurt,
manufacturer of a key antibiotic intermediateThe Frankfurt plant is where Sandoz manufactures
7-ACA
(7-aminocephalosporanic acid), the core chemical structure (building block)
for producing a whole host of cephalosporin antibiotics. The reason given for closure -- prices of the cephalosporin active pharmaceutical ingredients (APIs) and intermediates have collapsed as Asian competitors have dumped excess capacity on the market. The shutdown of the Frankfurt facility
means that the global reliance on China for APIs, used to produce antibiotics
(such as cephalosporin) and especially
7-ACA, will increase only further. Chinese
APIs are already a security threat for India India produces a third of the world's
medicines, mostly in the form of generic drugs. However, according to an Oct 2014 report
by a Boston Consulting Group (BCG) and Confederation of Indian Industry (CII), more
than 90 percent of the key raw materials (intermediates and APIs) that go into
making at least 15-odd essential drugs come from China.The drugs listed include the most commonly used painkiller such as paracetamol, aspirin; antibiotics such as amoxicillin and ampicillin, cephalexin, cefaclor, ciprofloxacin, ofloxacin, levofloxacin; first line diabetes drug metformin; and antacid ranitidine. There are no domestic producers left for many drugs such as penicillin-G, and its derivative 6-aminopenicillanic acid, or 6-APA.Since India is still receiving a large quantity of 7-ACA from Germany (confirmed by the import statistics available on the PharmaCompass database), 7-ACA and its derivatives were not mentioned in this report.As per news reports, the Indian government
is now worried about over-dependence on imports from China. "Any
deterioration in relationship with China can potentially result in severe
shortages in the supply of essential drugs to the country. Additionally, China
could easily increase prices of some of these drugs where it enjoys virtual
monopoly," said Bart Janssens, partner, BCG, in a news
report published in The Economic Times. Recognizing the national healthcare
security challenge facing India, the Department of Pharmaceuticals (DoP) has
decided to declare the year 2015 as ‘Year of Active Pharmaceutical Ingredients.’ As part of this initiative, the Indian government intends
to build
cluster parks to boost India’s self-reliance on Chinese imports. Quality,
environmental concerns over Chinese AntibioticsChinese supplies of 7-ACA have been plagued
with multiple issues in the past. In 2012, for instance, several Chinese drug
companies were accused of manufacturing 7-ACA using contaminated ‘gutter oil’, instead of more
expensive soybean oil. Gutter oil is reprocessed oil manufactured from waste oil and animal fat collected from restaurants’ fryers, drains, grease traps and slaughterhouses. Chinese restaurants can get through a lot of cooking oil and this waste oil fuels a highly profitable gutter oil black market as there are few other outlets, such as biofuel production, for this by-product.Similarly, antibiotic pollution in the rivers of China is a serious cause of concern for the Chinese. Our previous analysis, “Antibiotic
resistant superbugs: deadlier than cancer and closer to you than you think” provides a detailed overview regarding the challenge being faced. However, with growing focus on antibiotic pollution in China, a shutdown of factories failing pollution norms would be a severe setback for the global antibiotic supply chain. In addition to these challenges, quality concerns have been raised during international regulatory inspections of some of the leading antibiotic producers in China, like Zhuhai
United and North
China Pharmaceutical Company. South
African stock outs of essential drugs a global concernThe outcomes of these challenges are already being felt in countries such as South Africa which are facing an acute shortage of critical drugs. According to a report
published in Groundup, drug shortages in South Africa’s health facilities have become a crisis. The story mentioned the situation in a hospital (Stanger Hospital) in Ilembe District KwaZulu Natal, where 200 products were out of stock. These included various doses of morphine, some antibiotics and antiretrovirals, especially paediatric ones, used to treat HIV. “About a hundred patients per week are going without ranitidine which prevents stomach ulcers. Several Ilembe facilities are even out of stock of paracetamol tablets,” the Groundup report said. There are multiple reasons for the drug stock
outs. However, unprofitability because old, off-patent products are being sold by
manufacturers at prices very close to the cost of production has played a major
role. Firms are abandoning such products and seeking higher return
alternatives. In addition, due to quality failures suppliers are unable to provide lifesaving medications to the South African population. Our
ViewThe problems of stock outs and quality concerns in South Africa can easily expand across the world and can’t be addressed until the global pharmaceutical industry reduces its reliance on China for bulk drugs and intermediates. It remains to be seen if the threat to the global supply chain will make Novartis reconsider its decision or drive a national government to buy the Frankfurt facility.
Impressions: 7274
https://www.pharmacompass.com/radio-compass-blog/novartis-plant-shut-down-creates-urgency-to-find-alternatives-to-chinese-apis
#PharmaFlow by PHARMACOMPASS
30 Jul 2015
Africa represents the last geographic frontier where high growth is still achievable. Over the past two decades, Africa has emerged from a troubled history to become one of the world’s fastest growing economic regions, states a McKinsey report (Africa: A continent of opportunity for pharma and patients). A
quick glimpse of the gold mine in AfricaAfrica has one of the highest number of notified cases for diseases like AIDS and tuberculosis (TB), which provides sizable opportunities for the industry given the enormous size of the patient population. The South African government has plans of scaling
the number of people getting treatment for AIDS from
3 million to 4.6 million by the end of 2016. In December 2014, the government issued an $860
million tender for supply of AIDS drugs and only
four companies were the main beneficiaries! The African’s growthAfrica’s GDP (Growth Domestic Product), already the size of Russia’s, has a working age population, which is already 30% more than that of Europe and the size is expected to double in the next five years. Africa’s pharmaceutical economy has been forecasted to grow at an estimated 9.8% compounded growth when compared with 2% for the United States and 1% for Japan. While the size of the African pharmaceutical economy is significantly smaller than established markets, by 2020 the total size is expected to be between $44 billion and $66 billion.Although Africa is a big continent, McKinsey
simplifies life by suggesting that companies should focus on specific countries,
as more than 2/3 of the African growth has come from just 10 out of 54
countries. - Africa’s top 10: Algeria, Egypt, Kenya, Ivory Coast, Libya, Morocco, Nigeria, South Africa, Sudan, and Tunisia.In addition, the strong support of
governments advocating the use of generic drugs, along with physicians and
pharmacists getting used to prescribing generics, has the industry booming. The
generic business in Algeria and Morocco is forecasted to grow at a minimum growth
rate of 22%. Africa?
How does one get started?South Africa is currently embroiled in an
ongoing political crisis caused by severe drug
shortages. Lifesaving drugs for AIDS and TB along with common antibiotics
like benzyl
penicillin, heart medicine digoxin,
anti-asthma salbutamol
inhalers, anti-epileptic sodium
valproate, vaccines etc., have all encountered shortages.“The shortages at district hospitals have forced doctors to give medication to some patients, leaving others to suffer in agony. Paracetamol, a very basic painkiller, is also in short supply.”, reported news channel,
News24.With over 150
product lines in shortage, the South African government has taken radical
measures like flying
in 20 key medicines, accelerating the approval process and automatically allowing registration of suppliers who are WHO prequalified to overcome the 15 month approval timeline for drug applications. South African regulators will continue to inspect all
local and some international API sites despite relaxing facility assessment
rules last week. Our ViewConcerns
raised by the South African media, regarding API sourcing
constraints, delays in formulation manufacturing or managing changing product
demand can easily be addressed if the pharmaceutical industry decides to
develop their African business.However, not everything will be smooth
sailing since Africa faces challenges of civil unrest, dependency
of countries on oil prices, concerns over non-payment of bills and outbreaks of
epidemics like Ebola. McKinsey also
states that talent is scarce and finding a reliable local partner is critical
to success.Concerns aside, companies like Aspen, Hikma, Mylan, Cipla
Medpro, have already made significant inroads into the African market. While India’s Cipla envisions a billion
dollars from Africa by 2024 and Canada’s Valeant is in advanced talks to acquire Egyptian drugmaker, Amoun
Pharmaceutical Co. for about $700-800 million, the African opportunity has already started getting attention.For those on the sidelines, a lists of
products currently in shortage, is available
online and the only question is who bets bigger on Africa first!
Impressions: 2548
https://www.pharmacompass.com/radio-compass-blog/plan-an-african-safari-to-discover-the-world-s-fastest-growing-pharmaceutical-opportunity
#PharmaFlow by PHARMACOMPASS
18 Jun 2015
Over
700 commonly used generic medicines were
recommended for suspension by the European Medicines Agency (EMA) based on data
integrity concerns, over clinical studies conducted at GVK Biosciences in
Hyderabad, India.What
will be the g