Market Place
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: 54752
https://www.pharmacompass.com/radio-compass-blog/top-drugs-and-pharmaceutical-companies-of-2019-by-revenues
#PharmaFlow by PHARMACOMPASS
29 Apr 2020
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Data
integrity continued to be a hot topic in the pharmaceutical industry through
2017. According to a recent analysis by GMP (good
manufacturing practices) intelligence expert, Barbara Unger, approximately 65
percent of all US Food and
Drug Administration (USFDA) warning letters
issued in FY2017 (October 1, 2016 until September 30, 2017) included a data integrity component.
However, in the previous year, this number was even higher — at 79 percent — implying there has been a decline in non-compliance incidents pertaining to data integrity in 2017.
Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE!
2017’s recurring concern – a failure
to thoroughly investigate problems
In PharmaCompass’ 2016 compilation, serious charges of blatant data manipulation surfaced at organizations around the world.
In 2017, we witnessed a reduction in data-integrity violations
uncovered at pharmaceutical manufacturers due to the absence of audit trail
software in quality control testing equipment.
However, the implementation of audit trails has resulted in the emergence of a new failing – the improper handling of out-of-specification (OOS) results.
Failure “to thoroughly investigate any unexplained discrepancy or failure of a batch” became a recurring theme in concerns highlighted at major generic players like Mylan, Fresenius, Teva, Dr Reddy’s, Hetero Labs and Lupin.
In the case of Fresenius’ oncology API plant in India, USFDA investigators found employees had halted and invalidated
HPLC (high-performance liquid chromatography) analyses nearly 250 times when they
believed the tests were going to end with OOS results.
The
USFDA warned Fresenius SE after the company’s Indian plant that makes cancer-drug ingredients for the US market aborted hundreds of drug-quality tests.
Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE!
The situation at Lupin wasn’t much better as the warning letter issued to its formulation manufacturing facilities in Goa and Indore (Pithampur Unit II) said the company failed to “thoroughly review any unexplained discrepancy” as Lupin invalidated approximately 96 percent of all OOS results obtained at Pithampur and over 75 percent of them in Goa.
Failure to resolve
recurring problems also led the USFDA to tell Meridian Medical
Technologies, a division of Pfizer that
makes the EpiPen injector
device (sold by Mylan NV), that serious component and product failures had
been associated with patient deaths.
In its warning
letter, the USFDA said the Pfizer unit failed to adequately investigate
problems at its manufacturing facility in Brentwood, Missouri. It also did not
take appropriate corrective actions before a USFDA inspection earlier this
year.
Meridian had received hundreds of complaints that
the EpiPen device, which is used to combat serious allergic reactions,
failed to operate during life-threatening emergencies.
Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE!
Non-compliances at
finished drug producers
outnumbered those at API facilities
During 2017, the
number of finished pharmaceutical companies cited for compliance concerns
significantly outnumbered the number of active pharmaceutical ingredient (API)
producers.
While the FDA issued 48 warning letters to drug product manufacturers, API producers received only 18 warning letters. The actions by the European regulators was similar — 15 non-compliance certificates were issued to finished drug producers, as compared to only two API manufactures who were found lagging behind in compliance standards.
China, India and the
United States continued to lead the countries where regulators found most
shortcomings.
As compared to the
previous year, in 2017 regulators issued fewer non-compliance certifications as
the FDA had
been hampered by staffing shortages. As a result, the FDA’s inspections in India “dropped 27 percent in fiscal 2017 from a year earlier, to 185 from 252.”
Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE!
In 2017, EU and
FDA started their mutual recognition program. But will it work?
2017 was also a
landmark year for the US and European regulators as the USFDA and the European Medicines Agency (EMA) announced their program
for mutual recognition of inspections of drug manufacturers, which
became operational on November 1, 2017.
The FDA will now recognize eight EU drug regulators – from Austria, Croatia, France, Italy, Malta, Spain, Sweden and the UK – as capable of conducting inspections of manufacturing facilities that meet the USFDA requirements.
This is an unprecedented move — prior to this, the USFDA had never recognized another country’s inspectorate.
As
part of the agreement, the European Commission (EC), the US FDA and the EMA signed a confidentiality commitment that allows the USFDA to share non-public
and commercially confidential information, including trade secret
information relating to inspections with European regulators.
As the mutual
recognition of inspections program goes live, there were examples of many
companies that were found to be consistently out of compliance by both the FDA
and regulators from the EU. Yet, there were cases where the regulators came to
different conclusions about the state of a particular facility they had
inspected.
While
European regulators had raised compliance concerns at Biocon, the company went ahead and got an FDA nod
for its biosimilar of Roche’s blockbuster cancer drug — Herceptin.
Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE!
The case of Qinhuangdao Zizhu — when WHO and FDA differed
In
another case, an inspection conducted by the USFDA at Qinhuangdao Zizhu Pharmaceutical from November 28 to December 1, 2016 uncovered
significant data integrity concerns and failures in the level of adherence to
current good manufacturing practices (cGMPs) for APIs.
In
the warning letter issued to the firm, the laboratory analysts admitted to the FDA inspectors that they had been “setting the clock back and repeating analyses for undocumented reasons.”
At
Qinhuangdao Zizhu, “initial sample results were overwritten or deleted” and the company “reported only the passing results from repeat analyses”.
In addition to not having effective measures to control data within their computerized systems, the FDA investigators found that the firm “relied on incomplete information” to determine whether Qinhuangdao Zizhu’s drugs met established specifications.
The investigators found “a recurring practice of re-testing samples until acceptable results were obtained” and that batch production records “contained blank or partially completed manufacturing data”.
On
March 8, 2017, Qinhuangdao Zizhu Pharmaceutical was placed on import alert
by the USFDA.
Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE!
Almost
a year prior to the USFDA inspection, in October 2015, the company had been
inspected by a WHO Prequalification Team (PQT) for levonorgestrel, mifepristone and ethinylestradiol APIs. The inspection found “five major deficiencies including data integrity issues and several minor deficiencies”.
The
WHO, however, went ahead and closed its inspection as compliant, based on
corrective and preventive actions (CAPAs) provided by the manufacturer.
In
view of the USFDA actions, and the fact that Qinhuangdao Zizhu Pharmaceutical
is the only WHO-PQT prequalified source of levonorgestrel API (as was seen in a similar case at Mylan), the WHO approach towards the compliance position was to
focus extensively on product quality.
READ: FDA and EU differ on cGMP standards at the same facilities: How will they mutually recognize inspections?
Our view
As the US regulators push hundreds of new generic drugs to market
in an effort to drive down prices of generic drugs in the United States, the
industry should get ready for an increasing number of inspections in the coming
years.
Our compilation indicates that in 2017, while most companies had installed the infrastructure necessary to combat issues related to data-integrity, there were problems that were systemic in nature. These ‘systemic problems’ remain, and the industry must get ready as the FDA and European inspectors join hands to crack down on them.
PharmaCompass’ 2017 Recap of FDA Warning Letters, Import Alerts & EU Non-Compliances is an easy way to evaluate companies that have run into compliance challenges so that appropriate risk mitigation strategies can be adopted.
Impressions: 9112
https://www.pharmacompass.com/radio-compass-blog/2017-recap-of-warning-letters-import-alerts-and-non-compliances
#PharmaFlow by PHARMACOMPASS
11 Jan 2018
In our continuous endeavor to share business intelligence that can help grow your pharmaceutical business, PharmaCompass had introduced PharmaFlow last month — a monthly roundup of deals and investments
from across the globe.
By
tracking investments and M&As in the global pharmaceutical
industry, we hope to provide our readers with an insight into the breakthrough
technologies and business trends of the future.
In
September, Teva continued to divest in order to reduce
its US$ 35 billion debt burden incurred last year due to the acquisition of the
generics division of Allergan. Meanwhile, the world of pharmaceuticals
saw deals in the medical devices space, and the Chinese drug industry continued
to expand its global footprint.
Click here to view the major deals in September 2017 (Excel
version available) for FREE!
Teva’s disinvestments lead the deals in September
Debt-laden Teva Pharmaceuticals, the world’s leading generic drug manufacturer, continued to look for divestiture opportunities and sealed three separate divestments that together fetched US$ 2.48 billion. The Israeli drugmaker, which also got a new CEO (Kåre Schultz) last month, announced it would use the proceeds to repay its term loan debt.
Capital Partners Fund VI acquired a portfolio of products from Teva’s global women’s health business, spanning contraception, fertility, menopause and osteoporosis for US$ 703 million in cash. The portfolio of products, marketed and sold outside of the US, includes brands such as Ovaleap, Zoely,
Seasonique,
Colpotrophine
and Actonel.
Combined annual net sales of these and other products within this portfolio for
2016 were US$ 258 million.
Teva has also entered into an agreement under which Foundation Consumer Healthcare will acquire Plan B One-Step and Teva’s value brands of emergency contraception (Take Action, Aftera, and Next Choice One Dose) for US$ 675 million in cash. Combined annual net sales of Plan B One-Step, Take Action, Aftera, and Next Choice One Dose were US$ 140 million in 2016.
Click here to view the major deals in September 2017 (Excel
version available) for FREE!
Teva also entered into a definitive agreement with CooperSurgical, under which the latter will acquire Paragard (intrauterine copper contraceptive), a product within its global women’s health business, for US$ 1.1 billion cash. Paragard posted revenues of approximately US$ 168 million for the trailing 12 month period ending June 30, 2017. This transaction also includes the sale of Teva’s manufacturing facility in Buffalo, New York, which produces Paragard exclusively.
M&As in the next generation medical
devices space
NeoTract acquires Teleflex: September also saw the acquisition of NeoTract by Teleflex Incorporated. NeoTract is a privately-held medical device company that has developed and commercialized the US FDA-cleared UroLift System — a novel, minimally invasive technology for treating lower urinary tract symptoms due to benign prostatic hyperplasia, or BPH. Performed primarily through a transurethral outpatient procedure, the UroLift System delivers permanent implants that hold open the urethra, reducing the prostate obstruction without cutting, heating, or removing prostate tissue. Teleflex saw significant potential in NeoTract’s technology and acquired the company in early September, in a transaction valued up to US$ 1.1 billion.
Click here to view the major deals in September 2017 (Excel
version available) for FREE!
Under the
terms of the agreement, Teleflex will acquire NeoTract for an upfront cash
payment of US$ 725 million, and will pay up to an additional US$ 375 million
upon the achievement of certain commercial milestones related to sales through
the end of 2020.
In 2016,
NeoTract reported 178 percent year-on-year growth as its revenues grew to US$
51 million compared to approximately US$ 18 million in 2015.
Shandong Weigao acquires Argon Medical
Devices: In another major medical device deal announced in September, China’s Shandong Weigao Group Medical Polymer agreed to buy closely held Argon Medical Devices for US$ 850 million. Argon, which posted revenues of US$ 225 million last year, makes devices including biopsy products, drainage catheters and systems that remove blood clots. Once the purchase is complete, Argon will become one of Shandong Weigao’s “core platforms” for overseas expansion.
Chinese companies carry
on with their global acquisition spree
Shandong Weigao isn’t alone as according to Bloomberg data, Chinese companies had announced
US$ 4.3 billion in US health-care deals until September, more than double the
US$ 1.9 billion in purchases for the same period in 2016.
Chinese deals in Canada, US: In January this year, Chinese conglomerate Sanpower Group had acquired Valeant Pharmaceuticals’ Dendreon cancer business for US$ 819.9 million. Dendreon makes the prostate cancer vaccine — Provenge.
In June this year, Chinese contraceptives maker Humanwell Healthcare Group agreed to
buy US-based RiteDose for about US$ 605 million by becoming a part of a joint stock company.
Fosun resurrects India deal: In September, Shanghai Fosun Pharmaceutical Group resurrected its deal to overcome concerns raised by the Indian
government, by scaling down the stake it proposed to purchase in Gland Pharma from 86 percent to 74 percent. Fosun now proposes to pay US$ 1.1 billion for the 74 percent stake. The acquisition will give Fosun access to the Indian drugmaker’s portfolio of generic injectable medicines that are primarily exported to the US.
Zai Lab’s US IPO: Last month, China-based Zai Lab — a Chinese biotech focused on oncology,
autoimmune and infectious diseases — raised US$ 150
million in its US IPO after the company increased the size of the offering to 8
million shares, from the originally proposed 5.8 million shares. Demand for the
shares was strong, and Zai's stock opened 50 percent above the IPO price
valuing the company at US$ 1.4 billion.
Click here to view the major deals in September 2017 (Excel
version available) for FREE!
Aspen
acquires another portfolio of drugs from Big Pharma
Last year, Italian antitrust authorities fined South Africa-based drugmaker Aspen Pharmacare nearly US$ 5.5 million for halting supplies of
several cancer drugs. This was seen as a negotiating tactic designed to hike
drug prices by as much as 1,500 percent.
The
products whose supplies were halted were: Leukeran 2 mg (chlorambucil); Alkeran 50 mg / 10 mg powder and solvent (melphalan); Alkeran 2 mg (melphalan); Purinethol 50 mg (mercaptopurine); and Thioguanine 40 mg (thioguanine).
The
price-gouging episode began after Aspen purchased the drugs from GlaxoSmithKline. It then began negotiations with the Italian
Medicines Agency over pricing for the cancer medicines. According to the
Italian Competition Authority, Aspen also used the threat of a shortage to
achieve the high prices it had sought, because the drugs temporarily
disappeared from the market.
Last
month, as part of its continued drive to purchase a portfolio of products from
major pharmaceutical companies, AstraZeneca announced that Aspen Global Incorporated (AGI)
will acquire the residual rights to the established anesthetic medicines
comprising Diprivan, EMLA, Marcaine, Naropin, Carbocaine, Xylocaine/Xylocard/Xyloproct, and Citanest.
AstraZeneca had entered into an agreement with AGI in June 2016, under which AGI had gained
exclusive commercialization rights to these medicines in markets outside the
US. Under the terms of the new agreement, AGI will now acquire the remaining
rights to the intellectual property and manufacturing know-how related to the
anesthetic medicines for an upfront consideration of US$ 555 million.
Additionally, AGI will pay AstraZeneca up to US$ 211 million in
performance-related milestones based on sales and gross margin during the
period September 1, 2017 to November 30, 2019.
Click here to view the major deals in September 2017 (Excel version available) for FREE!
Major CDMOs continue to expand manufacturing footprint
Contract
development and manufacturing organizations (CDMO) continued to bulk up their
manufacturing capabilities. First, Catalent announced it would purchase Cook Pharmica in a transaction valued at US$ 950
million. Catalent
intends to use the acquisition to invest aggressively in Cook Pharmica and
create a biologics development and manufacturing center of excellence.
Another CDMO — Avara Pharmaceutical Services — had acquired a Pfizer facility in Italy in August. Last month, Avara entered into an agreement with GSK to acquire a GSK consumer
healthcare manufacturing facility in Aiken, South Carolina. The terms of the
agreement were not disclosed.
Our view
Our technology of the month for August 2017 — CAR-T therapy for cancer — got another boost as Gilead (which had acquired Kite Pharma for US$ 11.9
billion in August) received approval last week for Kite’s most advanced CAR-T therapy candidate — axicabtagene ciloleucel (axe-cel). Gilead has announced a price significantly lower than the launch price at which Novartis
is selling its CAR-T treatment (Kymriah).
While the man who led CAR-T therapy program at Novartis — Vasant Narasimhan — went on to become the Swiss drugmaker’s CEO last month, its ex-CEO Joe Jimenez told Forbes magazine in an interview that he is “ready to return to Silicon Valley.”
In his interview, Jimenez, 57, indicated what he
thought he could be doing next.
“When I think of what really excites me, it’s where biology comes together with technology, like when you think about what’s happening right now in the Valley in California,” Jimenez said.
According to the interview, Jimenez is not ruling out joining another big company. He is fascinated by more entrepreneurial startups, and “sees an opportunity for those who understand healthcare to bridge the gap between brilliant techies and a broken system”.
He got a glimpse of this potential, he says, from Novartis’ efforts with Verily, the life sciences arm of Alphabet (formerly Google). The companies have been working on smart ocular devices, a contact lens that can monitor the sugar levels of diabetics
through their tears. Jimenez says there is a prototype of this lens, which
showed him that engineering could benefit from healthcare knowhow.
Jimenez isn’t alone in banking on biotech. In September, two former GSK executives — its former CEO Andrew Witty and its one-time research head Moncef Slaoui — announced their moves into the biotech, venture
capital space.
Our view is that large pools of capital combined
with the finest talent would certainly lead to some breakthrough technologies
in the pharmaceutical industry in the near future. Watch this space for more.
Click here to view the major deals in September 2017 (Excel version available) for FREE
Impressions: 2597
https://www.pharmacompass.com/radio-compass-blog/pharma-deals-investments-and-m-as-in-september-2017
#PharmaFlow by PHARMACOMPASS
23 Oct 2017
Last year, data
integrity was a hot topic of discussion in the pharmaceutical industry.
According to a recent analysis by GMP (good manufacturing practices)
intelligence expert, Barbara Unger, approximately 80 percent of all FDA warning
letters in 2015 and 2016 included a data integrity component, and approximately
70 percent of the published European GMP non-compliance reports cited similar
shortcomings.
With a little over
half the year gone, PharmaCompass analyzed the regulatory action for
current GMP (cGMP)
non-compliance to evaluate how things are looking so far in 2017.
Click here to access the compilation of all 2017 non-compliances (Excel version available) for FREE!
As
per our analysis, of all the non-compliance actions taken by the US and
European regulators, India and China continue to see the highest level of
activity, followed by the United States.
While most of the companies in the list are less known
pharmaceutical players, inspections uncovered deficiencies at leading companies
like Pfizer,
Teva,
Mylan
and B Braun.
Data integrity violations continue to remain high
The US Food
and Drug Administration (US FDA) and EU inspections continued to uncover data
integrity issues across countries such as India, China, Italy and Japan.
In a warning letter posted earlier this year, for a January 2016 inspection, FDA investigators uncovered data-integrity violations at ACS Dobfar’s Italian drug manufacturing facility — FACTA Farmaceutici SpA. At FACTA, for multiple lots of sterile drug product, the
original data showed failing results. However, the final data reportedly showed
passing results.
The company was found storing original data in an “unofficial” and uncontrolled electronic spreadsheet on a shared computer network drive. The analyst told investigators that original data was first recorded in the “unofficial” spreadsheet and later transcribed to an “official” form.
Investigators
also documented that employees at FACTA used paper shredders to destroy
critical laboratory and production records.
During an
inspection performed exactly at the same time, FACTA’s EU GMP certification was renewed by the Italian regulators!
Click here to access the compilation of all 2017 non-compliances (Excel version available) for FREE!
Discrepancies
in conclusions drawn by regulators
This year,
while the United States and the European Union (EU) finally announced that they will be able to utilize each other’s good manufacturing practice (GMP) inspections of pharmaceutical manufacturing facilities, the road ahead looks uncertain as, in addition to incidents like FACTA, there have been multiple instances of discrepancies in the conclusions arrived at by regulators.
This year saw
the WHO grant an all clear for a Mylan facility
where the FDA had data-integrity concerns and a
similar situation arose at an active pharmaceutical ingredient (API) facility
in China.
An
inspection conducted by the USFDA at Qinhuangdao Zizhu Pharmaceutical from November 28 to December 1, 2016
uncovered significant data integrity concerns and failures in the level of
adherence to cGMP for APIs.
Click here to access the compilation of all 2017 non-compliances (Excel version available) for FREE!
In
the warning letter issued to the firm, the laboratory analysts admitted to FDA inspectors that they had been “setting the clock back and repeating analyses for undocumented reasons.”
At Qinhuangdao Zizhu, “initial sample results were overwritten or deleted” and the company “reported only the passing results from repeat analyses”.
On
March 8, 2017, Qinhuangdao Zizhu Pharmaceutical was placed on import alert
by the USFDA.
Almost
a year prior to the USFDA inspection, in October 2015, the company had been
inspected by a WHO Prequalification Team (PQT) for levonorgestrel, mifepristone and ethinylestradiol APIs. The inspection concluded with “five major deficiencies, including data integrity issues and several minor deficiencies”.
The WHO went ahead and closed their inspection as ‘compliant’, based on corrective and preventive actions (CAPAs) provided by the manufacturer.
In view of the US FDA actions, and the fact that Qinhuangdao Zizhu
Pharmaceutical was the only WHO-PQT prequalified source of levonorgestrel API, as in the case of Mylan, the WHO approach towards the compliance position was focused extensively on product quality.
In Japan, at Sato Yakuhin Kogyo, FDA investigators found analysts
performed testing in duplicate without scientific justification, while in
China, the French Ministry of Health found manipulation, backdating and falsification
of GMP documents such as batch manufacturing records, GC (gas chromatography)
and HPLC (high performance liquid chromatographs) chromatograms at Chongqing
Succeway Pharmaceutical.
Click here to access the compilation of all 2017 non-compliances (Excel version available) for FREE!
Heparin makes
headlines again in China; Indian firm fakes strike
This year, concerns
over the testing of Heparin in China re-emerged when FDA issued a warning letter to a contract testing laboratory — Shandong Analysis and Test Center. However, the activities at these companies to deceive inspectors paled in comparison to Vikshara Trading in India where the company faked a strike to prevent an FDA inspection.
When the FDA
inspection finally occurred, the FDA obtained evidence that the firm actively
manufactured numerous products at the time of the supposed strike.
Concerns over
product quality in the United States
In a warning letter
issued to ChemRite CoPac in the US, the FDA found that the company was manufacturing oral drug
solutions using the same equipment that was being used to manufacture numerous
non-pharmaceutical materials including an industrial car care product. The car
care product being made was paraffin-based and carried labels such as “harmful or fatal if swallowed” and “keep out of reach of children.”
The ingredients of
these non-pharmaceutical products were extremely difficult to remove from the
manufacturing equipment, and could contaminate the drug products, the FDA said.
At Raritan Pharmaceuticals, a company that makes teething tablets, the FDA found the drug contained ingredients, such as belladonna, which could pose potential toxic effects for its consumers — infants and children under two years of age.
Click here to access the compilation of all 2017 non-compliances (Excel version available) for FREE!
Sterile drug
manufacturing continues to be a global challenge
Non-compliant
operations uncovered at Sato Pharmaceutical (Japan), Euro Far Allergi (Spain), Tubilux (Italy), Biocon (India), Nova DFL Industrie (Brazil), Pfizer’s US operations (ex-Hospira) show that aseptic sterile drug manufacturing continues to
be a global challenge as companies struggle to get into compliance.
In February
2015, Pfizer acquired a site in McPherson, Kansas, through its US$ 17 billion acquisition of Hospira. Pfizer was aware of Hospira's manufacturing record
when it struck the deal, as the company was issued FDA warning letters in four of the seven continents — Europe, North America, Asia and Australia.
Approval of two drugs have been held up this
year due to compliance concerns at McPherson.
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The USFDA also warned manufacturers of non-sterile, water-based drug products of Burkholderia cepacia
complex (BCC or B cepacia) contamination, as there were product recalls due to
this and other water-borne opportunistic pathogens found in pharmaceutical
water systems.
The regulator’s warning stemmed from a multi-state outbreak of infections. In March this year, Phispers had carried a news item on Badrivishal Chemicals & Pharmaceuticals,
a manufacturer of docusate sodium. It had been placed on FDA’s import alert list in December last year.
Concerns over
water systems were also mentioned in the warning letters issued to Humco
Holding Group in the United States and Resonance Laboratories in India.
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Omitting names of
original suppliers; shipping drugs from banned API makers
The USFDA
investigators found companies in India (Sal Pharma) and China (Suzhou Pharmaceutical Technology and Lumis Global Pharmaceuticals)
omitting the name and address of the original API
manufacturers on certificate of analysis and declared themselves to be the
manufacturers. In the case of Suzhou, one of its suppliers
was placed on FDA’s import alert list.
However, the company shipped API
manufactured from the banned supplier by providing misleading declarations.
Last year, PharmaCompass
had reported on Teva’s newly built sterile manufacturing facility in Godollo, Hungary, and the issues
highlighted by the FDA in its warning letter and the product recalls from this unit. As part of its global restructuring, while Teva is now winding up its sterile injectables plant in Godollo, it remains to be seen what decision
will be taken on its API manufacturing facility in Hangzhou (China), where the FDA had
highlighted concerns over process capability and the resulting impact on
product quality.
Wockhardt’s global compliance problems also continued with its manufacturing facility in the United States — Morton Grove Pharmaceuticals — receiving a warning letter.
Click here to access the compilation of all 2017 non-compliances (Excel version available) for FREE!
Our view
Earlier this year, a major Indian API manufacturer — Divi’s Laboratories — was placed on FDA’s import alert list. It was issued a warning letter due to a variety of problems which were uncovered at the site. The concerns raised at Divi’s along with other companies indicate a shifting focus on part of the FDA investigators from audit trails as there
is greater depth in the nature of the observations.
To assist the
industry, the FDA has started posting frequently requested Form 483s on a
routine basis which provides insight for the industry to track the new areas of
regulatory focus.
You can find the Form
483s on PharmaCompass at https://www.pharmacompass.com/radio-compass-news/Quality-Alerts
Click here to access the compilation of all 2017 non-compliances (Excel version available) for FREE!
Impressions: 7732
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#PharmaFlow by PHARMACOMPASS
10 Aug 2017
This week in our compliance round up, we look at the continuing problems at Pfizer’s McPherson unit in the US and China FDA’s entry into the ICH as a regulatory member. Yet again, WHO sources API from a plant in China, where USFDA had raised data integrity concerns. Meanwhile, Aurobindo Pharma’s Unit VII clears FDA inspection with zero observations.
Problems continue at Pfizer’s US facility; its sure-shot biosimilar gets rejected
Earlier this year,
Pfizer’s fill/finish manufacturing facility in McPherson, Kansas, received a warning letter from the US Food and Drug Administration (USFDA). The compliance concern was initially revealed in a press release issued by Momenta Pharmaceuticals — a biotechnology company developing a generic version of Teva’s long-acting Copaxone® 40mg/mL (glatiramer acetate injection). Momenta is working in
collaboration with Sandoz, which in turn has tied up with Pfizer as its fill/finish
manufacturing partner.
This week, a month after the FDA staff found that Pfizer’s biosimilar of Amgen’s drug Epogen (epoetin alfa) was nearly identical and an FDA advisory committee followed to recommend approval with a 14-1 vote, the FDA issued a complete response letter (CRL) to Pfizer.
The letter cited
concerns which had already been raised in the warning letter issued on February 14, 2017, following a
routine inspection of the facility.
This development
continues to be positive news for Teva, as Copaxone generated US$ 4.22 billion in sales last year. Continued
compliance concerns at Pfizer indicate that Momenta will still have to wait for
its generic to get approved.
While
previous FDA inspections at the McPherson facility had raised concerns over the assurance of product sterility, no warning letter had ever been issued to this site.
In
February 2015, Pfizer acquired the McPherson site through its US$ 17 billion acquisition of Hospira. Pfizer was aware of Hospira's manufacturing record
when it struck the deal, as the company was issued FDA warning letters in four of the seven continents — Europe, North America, Asia and Australia.
Once again, WHO sources API from Chinese firm where FDA had
raised concerns
Three
weeks after PharmaCompass shared the differences in assessments of the World Health Organization (WHO) and the USFDA over
the observations at a Mylan finished formulation
site in India, a similar situation has arisen at an active pharmaceutical
ingredient (API) facility in China.
An
inspection conducted by the USFDA at Qinhuangdao Zizhu Pharmaceutical from November 28 to December 1, 2016 uncovered significant data
integrity concerns and failures in the level of adherence to cGMP (current good
manufacturing practices) for APIs.
In
the warning letter issued to the firm, the laboratory analysts admitted to FDA inspectors that they had been “setting the clock back and repeating analyses for undocumented reasons.”
At Qinhuangdao Zizhu, “initial sample results were overwritten or deleted” and the company “reported only the passing results from repeat analyses”.
In addition to not having effective measures to control data within their computerized systems, the FDA investigators found that the firm “relied on incomplete information” to determine whether Qinhuangdao Zizhu’s drugs met established specifications.
The investigators found “a recurring practice of re-testing samples until acceptable results were obtained” and that batch production records “contained blank or partially completed manufacturing data”.
On
March 8, 2017, Qinhuangdao Zizhu Pharmaceutical was placed on the import alert by the USFDA.
Almost
a year prior to the USFDA inspection, in October 2015, the company had been
inspected by a WHO Prequalification Team (PQT) for levonorgestrel, mifepristone and ethinylestradiol APIs. The inspection concluded with “five major deficiencies including data integrity issues and several minor deficiencies”.
The
WHO went ahead and closed their inspection as compliant based on corrective and
preventive actions (CAPAs) provided by the manufacturer.
In
view of the USFDA actions, and the fact that Qinhuangdao Zizhu Pharmaceutical
is the only WHO-PQT prequalified source of levonorgestrel API, as in the case of Mylan, the WHO approach towards the compliance position has been
to focus extensively on product quality.
The WHO has requested manufacturers that use levonorgestrel manufactured by Qinhuangdao Zizhu to take “additional measures such as comprehensive testing upon receipt” to help ensure that the quality of all batches of levonorgestrel is assured.
In
addition, the WHO has said that procurement agencies may continue to procure
FPPs that contain API produced at Qinhuangdao Zizhu Pharmaceutical, until
further notice.
The WHO-PQT is planning to conduct an on-site inspection of
Qinhuangdao Zizhu Pharmaceutical and also plans to work with finished
pharmaceutical products manufacturers to identify additional sources for
levonorgestrel.
China
FDA approved as an ICH member
In a major boost to China’s pharmaceutical growth plans, the International Council for Harmonization (ICH) Assembly approved the China Food and Drug Administration
(CFDA) as a new Regulatory Member. This decision was taken during a meet in
Montreal, Canada, from May 31 to June 1, 2017.
While compliance concerns linger over some pharmaceutical factories in the country, China’s acceptance of this membership indicates that the country is prepared to bring its drug manufacturing and testing practices in line with international quality standards.
ICH was created in
1990 to bring regulatory authorities and the pharmaceutical industry together
in order to discuss scientific and technical aspects of drug registration. Over
the last 25 years, ICH has worked on achieving greater global harmonization so
that safe and effective drugs are developed and registered in the most
resource-efficient manner.
In India, Aurobindo’s Unit VII gets zero observations; Lupin founder passes away
Indian pharmaceutical industry lost a
veteran this week. Desh Bandhu Gupta, the founder chairman of Lupin and a self-made billionaire, died in Mumbai at the age of 79.
Five years back, he had handed over the reins of Lupin to his eldest daughter Vinita
Gupta and son Nilesh Gupta.
Desh Bandhu Gupta, or DBG as he was
known, was a deft businessman who founded Lupin in 1968 with just Rs 5,000
borrowed from his wife. Prior to this, he was the professor of chemistry at the
Birla Institute of Technology and Science, Pilani. He went on to become India’s 20th richest person with an estimated net worth of US$ 5.1 billion (according to the 2016 Forbes India Rich List).
While much of the industry abandoned making anti-TB drugs, given the low margins and the government's price controls, Lupin remained consistent as the world’s largest supplier of anti-TB drugs. DBG forged global alliances to develop new medicines to fight tuberculosis.
Meanwhile, another Indian company — Aurobindo Pharma — sailed through a USFDA inspection with zero observation. Aurobindo Pharma’s Unit VII is a formulations manufacturing facility and one of the
largest facilities for the company from which has filed the maximum ANDA
applications to the FDA.
According to a recent company presentation to investors, the company has filed 158 ANDAs (abbreviated new drug application) from this facility, of which 88 drugs received final approvals and 20 drugs have tentative approvals and 50 are currently under review.
Impressions: 4004
https://www.pharmacompass.com/radio-compass-blog/fda-problems-at-pfizer-s-us-facility-continue-china-fda-joins-ich
#PharmaFlow by PHARMACOMPASS
29 Jun 2017
GSK, Google form first bioelectronics firm; 11 generic companies benefit from the Teva Allergan deal
This week,
Phispers brings to you the details of the bioelectronics firm formed by GSK and
Google. There is also news on companies like Teva, Takeda, Jinan Jinda and Eli
Lilly, besides two other news snippets pertaining to the FDA -- while the first
one pertains to generic approvals, the other one relates to an additional black
box warning on a few antibiotics. GSK and Google
join hands to form first bioelectronics startupGlaxoSmithKline and Google’s parent company – Alphabet – have joined hands to create a new company that is focused on fighting diseases by targeting electrical signals in the human body. This way, GSK and Alphabet’s life sciences unit – known as Verily Life Sciences – will be jump-starting a new field of medicine known as bioelectronics.Verily Life
Sciences and GSK will together contribute US $ 715.12
million
over seven years to the startup Galvani Bioelectronics. The startup will develop
miniature electronic implants for the treatment of asthma, diabetes and other
chronic conditions. The
implantable devices developed by Galvani, which is owned 55 percent by GSK and
45 percent by Verily, can modify electrical nerve signals. The aim is to
modulate irregular or altered impulses that occur in many illnesses.The
new company
will be based at GSK’s Stevenage research center north of London, with a second research hub in South San Francisco.The announcement comes just weeks after GSK had said it was going to use Apple’s HealthKit to conduct clinical trials.Three years ago, GSK had first unveiled its ambitions in bioelectronics in the journal – Nature. Bioelectronic remedies attach battery-powered implants the size of a grain of rice (or even smaller) to individual nerves to correct faulty electrical signals between the nervous system and the body’s organs.GSK believes altering these nerve signals could open up the airways of asthma patients, reduce inflammation in the gut from Crohn’s disease and treat patients with a range of other chronic ailments such as arthritis. So far, the implants have only been tested on animals but the aim is to produce treatments that will supplement or replace drugs that often come with side-effects.GSK
has been working on bioelectronic medicines since 2012 in a push to develop new
patentable treatments, since its Advair respiratory treatment faces competition
from generic versions. It has invested US $50 million in a venture capital fund
for bioelectronics and provided funding to scientists working in the field. Teva divests 79
products to 11 generic players to close Allergan dealTeva
Pharmaceutical Industries – the world’s largest generics drug company – won a US
anti-trust approval to purchase Allergan's generics
business, after agreeing to divest 79 generic drugs to rival firms. This was arrived
at to settle Federal
Trade Commission (FTC) charges that its proposed US $ 40.5 billion acquisition of Allergan’s generic pharmaceutical business would be anti-competitive. The remedy requires Teva to divest the drug portfolio to 11 firms, and marks the largest drug divestiture order in a FTC pharmaceutical merger case.The Teva-Allergan deal, which was announced in July 2015, solidifies Teva’s position as the world's largest maker of generics while freeing Allergan to focus on branded drugs.The
companies that
have acquired
the divested products are Mayne Pharma
Group, Impax
Laboratories, Dr Reddy’s Laboratories, Sagent
Pharmaceuticals, Cipla Limited, Zydus Worldwide
DMCC, Mikah Pharma, Perrigo Pharma
International, Aurobindo
Pharma USA,
Prasco and 3M Company. Eli Lilly CEO
steps down; company under probe by US Justice Department Eli Lilly CEO John
Lechleiter has stepped down after steering the pharma company through long R&D droughts. The company’s president David Ricks will move up to the top spot. And after a brief spell as executive chairman, Lechleiter will leave the company next spring.Lechleiter
has been the company's CEO since April 1, 2008, and the chairman of its board
of directors since January 1, 2009.The
announcement has come at a time when Eli Lilly has been asked by the
Justice Department to disclose information on relationships with pharmacy benefits
managers (PBMs), the companies that negotiate prices and set reimbursement
conditions.It
has not been clear what exactly the department of justice is looking for. In
the past, drug makers such as Novartis and AstraZeneca have agreed to
pay fines and penalties to settle allegations pertaining to PBMs. FDA continues
to race ahead with generic approvals The
American regulator has reduced its pile of ANDA (abbreviated new drug
applications) by about 500
applications in the first six months of 2016. The FDA has also approved 315 more ANDAs over the same time period and has sent 66 more complete response letters — or rejections — to drug makers.This
news comes after Bloomberg reported
last month that the FDA has become ‘something of a bogeyman’ for India’s stock markets by approving generic drug applications from India at a record place. Similarly, PharmaCompass
had reported last week that Indian
companies have been fixing compliance issues. China’s Jinan Jinda fails another EDQM inspection; compliance troubles in Denmark In
regulatory news from across the world, Jinan Jinda, a Chinese API
manufacturer that had failed an inspection by Italian regulators in June 2015,
had more bad news awaiting it a year on. In
a June 2016
re-inspection, this time by the Spanish Health Authority, the regulator maintained the ‘facilities non-compliance standing’ since two critical observations were made and the corrections from the previous inspection “were found as not having been implemented in a satisfactory way”. And critical deficiencies were found on raw data.In
the June 2015 inspection, the critical observation was related to an unofficial
and non-controlled storage area containing mainly raw materials and finished
products which had been made
inaccessible to inspectors as the door had been removed and replaced with a panel fixed with
screws to the wall.Meanwhile,
the FDA issued an untitled letter (dated July 15, 2016) to Danish allergy
immunotherapy company ALK-Abelló (ALK) over manufacturing and quality control issues at its Horsholm, Denmark facility. The letter comes after a 12-day inspection of the facility in March 2016. During the inspection, the FDA had cited ALK for four “significant deviations” from cGMP requirements. Another black
box warning added to antibiotics like Cipro and LevaquinThe
FDA has upgraded
warnings on
certain antibiotics, such as Johnson & Johnson’s Levaquin, Bayer’s Cipro
extended-release tablets and Merck’s Avelox. The FDA had
added a black box warning in 2008 about the increased risk of tendinitis in
which the tissue connecting muscle to bone becomes inflamed. In
May this year, the FDA had advised restricting the use of fluoroquinolone antibiotic for certain uncomplicated
infections and had warned about the disabling side-effects of the drug.The new warning talks about long-term risks to the drugs’ current black box warning. The agency also advised using the drugs only for serious infections. Manufacturers of fluoroquinolone have faced thousands of lawsuits from patients who claim that their injuries were caused by the drugs. J&J alone faced 3,400 lawsuits over Levaquin’s links to tendon problems and has also settled many of those cases. Takeda to
overhaul R&D, downsize operations in the UKTakeda Pharmaceutical of Japan has
said it plans to build a new pipeline of drugs. It plans to revamp its
research operations at the cost of around US $ 727 million.. The
company also plans to close some of its R&D operations in the UK. Takeda is
beginning the first ‘consultation stage’ of the layoff process in the UK, which hosts a pre-clinical R&D operation in Cambridge as well as a development center headquarter with facilities in the UK, Switzerland and Denmark.Under the revamp, Takeda’s R&D activities will be concentrated in Japan and the US, the 235-year old drug company said in a statement. Takeda plans to now focus on the three therapeutic areas of oncology, gastroenterology and the central nervous system.“We need to first build new capabilities and embrace new ways of working,” Andy Plump, Takeda’s chief medical and scientific officer, said in the statement.
Impressions: 2757
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#PharmaFlow by PHARMACOMPASS
04 Aug 2016
