This week too, Phispers brings you an update on the novel coronavirus.
While China is trying to curtail the impact of Covid-19 on its economy, the developed world is looking at how to protect its drug supply chain from such adversities.
Sanofi is spinning off six of its API production sites to create a new company that will strengthen the bulk drug supply chain in Europe and reduce dependence on India and China.
The US saw the first non-statin cholesterol pill being approved by the FDA in 20 years.
The FDA issued warning letters to a US-based generic drug maker and to a Chinese crude heparin manufacturer.
The agency also revoked a ‘Voluntary Action Initiated’ status issued to Aurobindo Pharma’s plant in Hyderabad, while also unveiling the first version of its searchable online database of biological product information, known as the Purple Book.
Sanofi to spin
off six API units in Europe into standalone company
French drugmaker Sanofi saidit plans to create a major European drug company
that will produce and market active pharmaceutical ingredients (APIs) to third
parties.
The project
consists of creating a standalone company which would combine Sanofi’s API commercial and development activities with six of its European API production sites — Brindisi (Italy),
Frankfurt (Germany), Haverhill (UK), St Aubin les Elbeuf (France), Újpest (Hungary) and Vertolaye (France). These six production sites serve 600 customers outside Sanofi. These would be spun off to create the new company, which doesn’t have a name as yet.
With this new company, Sanofi hopes to expand into a market currently dominated by firms in China and India. Sanofi plans an initial public offering for the new firm, which will be based in France. The new company, which would rank as the world’s second-largest API company, is projected to have sales of US$ 1.08 billion (€1 billion) in 2022.
Sanofi CEO Paul
Hudson said the need for such a company was brought about by outbreaks of a
novel coronavirus that threaten pharmaceutical supply chains.
“The industry needs to be able to make active pharmaceutical ingredients in Europe,” Hudson said. “And
if you’re
going to do it, let’s do it properly.”
The new firm will
employ 3,100 people. Sanofi would keep 30 percent stake in the new business,
and also remain its most significant customer, Hudson added.
Covid-19
update: World studies impact on drug supply chain; China limps back to business
The novel
coronavirus has now infected over 80,000 people across the world (with 78,159
in China alone) and killed more than 2,700. However, in Mainland China, fewer
confirmed cases have been reported of late. Confirmed new coronavirus cases,
according to the National Health Commission of China, stood at 409 on Sunday, down
from 648 reported a day earlier. The number of new deaths, however, rose to 150
from 97 over the same period, it said in a statement.
“The outbreak of novel coronavirus pneumonia will inevitably have a relatively big impact on the economy and society,” China’s President Xi Jinping said, adding that the impact would be short-term and controllable.
China is trying to
curtail the impact of Covid-19 on its economy. The country is relaxing criteria for
factories to reopen. Top leaders in China have urged businesses to work to
prevent an economic slump. Large parts of China relaxed curbs on
transport and travels. However, analysts say the country is risking a renewed
spread of the coronavirus.
Economists estimate China’s gross domestic product growth to slow down to possibly 3 percent or even lower in the first quarter of 2020, from 6 percent in the last quarter of 2019.
FDA identifies
20 APIs sourced solely from China:
The FDA has identified 20 drugs that
are made in or produced solely from APIs sourced from China.
FDA spokesperson
Stephanie Caccomo said the agency has been in contact with the companies that
make the 20 products and “none of these firms has reported any shortage to date.”
Caccomo also said
the FDA has been in contact with more than 180 manufacturers to remind them of
their responsibility to notify the agency of anticipated supply disruptions and
has asked them to review their supply chains for APIs and other components
sourced from China.
“At this time, no firm has reported a shortage is anticipated for any drug due to Covid-19,” Caccomo said.
The FDA statement came after news website Axioscarried a
report on how about 150 prescription drugs — including antibiotics, generics and some
branded drugs without alternatives — are at risk of shortage if the coronavirus outbreak in China
worsens.
Meanwhile, White
House trade adviser Peter Navarro advocated bringing home more of the American
pharmaceutical supply chain amid the coronavirus crisis in China.
“We’ve offshored far too much of our supply chain, not just for corona, but also for the essential medicines we need,” Navarro said.
Deaths in
Italy, France, Middle-East:
The coronavirus death toll climbed to seven in Italy this
week and the virus is fast spreading in the Middle East, Europe and other parts
of the world. France has also reported two deaths from
Covid-19,
Brazil confirmed
its first case in Latin America, while South Korea on Wednesday said 11 people
have died of the disease there. Iranian state television has reported 19 deaths amid
139 confirmed cases in the country so far. Globally, at least 80,000 people
have been diagnosed with the illness.
In the US, the
Centers for Disease Control and Prevention has warned that it expects the novel coronavirus to
begin spreading at a community level in the United States. A top official said
that disruptions to daily life could be “severe”. There have been 14 cases of the virus diagnosed in the US, all in people who traveled to China recently.
Meanwhile, the WHO has said the
coronavirus outbreak can still be beaten. “The key message that should give all countries hope, courage and confidence is that this virus can be contained, indeed there are many countries that have done exactly that,” WHO Director-General TedrosAdhanomGhebreyesussaid in Geneva.“Using
the word ‘pandemic’ now does not fit the facts but may certainly cause fear,” he added.
The FDA said in a
statement that it is not conducting inspections in China. “While we are not able to conduct inspections in China right now, this is not hindering our efforts to monitor medical products and food safety,” the agency said.
FDA warning
letters reveal data-integrity issues in US; heparin concerns in China
The US Food and
Drug Administration (FDA) issued a warning letter to the US-based generic drug manufacturer —KVK-Tech, Inc. The Pennsylvania-based drug
manufacturing facility was inspected from April 9 to 16, 2019 during which the
FDA highlighted that data generated from the firm’s laboratory testing systems was not
adequately protected from deletion or alteration.
Similar to
observations seen at other sites globally, KVK’s quality assurance employees had
administrator access privileges. They could modify or overwrite data files
without this being captured on audit trails on stand-alone laboratory
equipment. Although the firm had previously committed to the FDA of correcting
its practices, at the time of the April 2019 inspection, the necessary actions
had not been implemented.
The warning letter
also mentions shortcomings in the firm’s analysis methods which resulted in a
failure to detect out-of-specification (OOS) results for at least one lot of
drug product. As a result, a lot of phentermine HCL capsules remained on the market until it
failed stability impurity testing in June 2017.
KVK-Tech also
failed to adequately investigate foreign particles found in methylphenidate oral solution during the filling
process. The firm filtered out the foreign particles, performed visual
inspection, and then released the lot without performing an adequate
investigation into the origin and nature of the particles and their effect on
drug quality.
As a result of the
FDA inspection and subsequent communication with the firm, a recall of the
impacted lot of methylphenidate oral solution was initiated.
Warning letter
to YibinLihao: As FDA
inspections into China have come to a halt due to the spread of the
coronavirus, the agency went ahead and issued a warning letter to Chinese crude heparin manufacturer — Yibin Lihao Biotechnical Co.
The inspection was
conducted between July 31 to August 6, 2019 and during a pre-inspectional call
on July 10, 2019, the firm stated to the FDA that they had not manufactured any
materials for months. At the start of the FDA inspection on July 31, 2019, the
firm stated to the investigator that they were not manufacturing crude heparin.
During a walkthrough
of the company’s warehouse, an FDA investigator observed
a warehouse employee leaving the warehouse with a fiber drum and inquired about
the contents of the drum. Inspection of the drum revealed two batches of crude
heparin manufactured just a few days before the FDA inspection. When asked
about manufacturing and testing records pertaining to the crude heparin
batches, the firm told the FDA that they did not have records for the two crude
heparin batches.
In India, UK’s MHRA (Medicines & Healthcare
products Regulatory Agency) issued a statement of non-compliance with GMP to Bioplus Life Sciences — a manufacturer of finished drug products — for failing to prevent and detect cross-contamination between products. In addition, the statement highlights that integrity of the reported data could not be relied upon and alsomentions the withdrawal of the previous GMP
certificate issued to the firm.
First
non-statin cholesterol pill approved by FDA in 20 years
Last week saw the
first non-statin treatment to be cleared for sale in the US in
nearly 20 years. The drug, bempedoic acid, is made by Esperion Therapeutics Inc. This cholesterol-lowering drug is aimed
at helping millions of people who can’t tolerate or don’t get enough help from widely used statin pills like Lipitor and Crestor.
This new drug is
to be used as an add-on treatment with statins. It lowers bad cholesterol or
low-density lipoprotein (LDL) by inhibiting its synthesis in the liver. It
targets patients with high cardiovascular risk.
The oral treatment, which will be sold under the brand name — Nexletol — is expected to be priced at around US$ 10 per pill and will be available in the US(through prescription) from March 30, Esperion said. Stifel analyst Derek Archila expects the drug to bring in sales of about US$ 3 billion by 2029 at its peak.
The approval comes
after studies showed an 18 to 28 percent fall in LDL cholesterol, as compared
to a placebo, in patients who were also on statin. High levels of LDL
cholesterol are known to raise the risk of heart attacks or strokes.
Esperion has also
submitted a marketing application for the approval of bempedoic acid in
combination with ezetimibe, another cholesterol-lowering drug. The FDA is
expected to announce its final decision this week.
In January last
year, Daiichi Sankyo Europe had entered into an exclusive licensing agreement with Esperion Therapeutics for Daiichi Sankyo Europe to market bempedoic acid and bempedoic acid / ezetimibe combination tablet in the European Economic Area and Switzerland.
FDA rescinds
VAI status on Aurobindo’s key unit in Hyderabad
In a flip-flop,
the FDA has revoked the ‘Voluntary Action Initiated’ status issued to Aurobindo Pharma Limited’s plant (Unit IV) in Hyderabad two days after
indicating it might not pursue further regulatory action. It told the company
the inspection of the unit remains open and is being
reviewed.
Gurudatta GG of Estima Pharma
Solutions, a pharmaceutical
GMP and regulatory consultancy
told The Economic Times that the FDA may have been in a hurry when it concluded that voluntary action is sufficient. “However, the review process might not have been completed internally and someone might have raised objections with respect to certain serious issues in regard to this injectable facility,” he added.
In November,
Aurobindo’s
Unit IV, a key site for the
Indian generic major which generates between 10 to 15 percent of its revenues,
was issued a 37-page Form 483.
The sterile drug
manufacturing facility was found to have inadequate procedures to prevent
microbial contamination of drug products. The environmental monitoring
activities in the aseptic processing areas were found deficient as were the
systems for maintaining any equipment used to control aseptic conditions.
Aurobindo’s Unit IV also has the largest number of new drug applications pending approval — at about 47 — compared to the company’s total pending applications — at about 150. If these observations escalate to a warning letter or an official action indicated, it could put the spanner in Aurobindo’s growth plans. The company may also
incur higher costs to comply with US FDA regulations due to increasing
scrutiny.
FDA launches
Purple Book and database of drug approvals since 1985
This week, the FDA
unveiled the first version of
its searchable online database of biological product information, known as the
Purple Book.
The database
allows for easier searches and includes information on product names
(proprietary and proper), the type of biologics license application (BLA) that
was submitted, strength of the biologic, dosage form, product presentation,
license status, BLA number and approval date.
“Once the Purple Book database is completed, it will offer information about all licensed biological products, including information pertaining to exclusivity,” FDA said.
Biopharma
companies had requested the FDA to
include exclusivity information in the Purple Book, similar to what’s offered in the Orange Book.
The agency said
the database will be updated with new drug applications that are deemed to be
BLAs on March 23 and will “continue to be updated through August 2020 when all functionality and all BLAs are expected to be available on the new Purple Book online database.”
The Purple Book,
which currently contains 89 entries, will be updated on a weekly basis, FDA
said.
Meanwhile, the FDA also released a dataset containing information
about all new drugs and biologics approved by the Center for Drug Evaluation
and Research (CDER) dating back to 1985.
This will provide
researchers with more accurate and accessible data about historic drug
approvals, the FDA said.
“FDA created the compilation to facilitate data accessibility, transparency, and accuracy when researchers seek information about an approved drug,” FDA said, adding that the compilation should accurately reflect “the state of each application at the time of initial regulatory approval.”
The compilation is
a downloadable and contains information on more than 1,000 new molecular
entities (NMEs) and new biologics approved from January 1, 1985 through
December 31, 2019.
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