Market Place
It has been an
unprecedented week where compliance glitches have emerged from almost all parts
of the globe. This week, PharmaCompass
brings you a compilation of such troubles to give you an idea about the nature
of such compliance issues. And, the problems regulators are facing walking the
tightrope between drug safety and drug availability. Pfizer halts production in India after joint
inspection by four regulatorsPfizer recently halted production at a plant
near Chennai in India, after a PIC/S (short for Pharmaceutical Inspection
Convention and Pharmaceutical Inspection Co-operation Scheme) joint inspection
with regulators from four international agencies, MHRA (Medicines and
Healthcare products Regulatory Agency of the UK), USFDA (United States Food and
Drug Administration), TGA (Therapeutic Goods Administration of Australia) and
Health Canada, found various quality control problems. A Pfizer spokesperson told
The Economic Times: “A holistic plan is being developed to address specific inspection observations and to implement enhancements to site operations.” The plant was
acquired by Pfizer through its US $ 17 billion acquisition of Hospira, which had run into a fair share of manufacturing compliance problems with the FDA. Over the last few years, numerous Hospira plants — including those in the United States, Europe, Asia, and Australia — received warning letters and had to subsequently issue product recalls. The same
facility in Chennai received an FDA warning letter in 2013. Pfizer’s own operations in Asia ran into problems when US FDA investigator Peter Baker uncovered data integrity malpractices at a
finished dosage manufacturing facility in Dalian (China). Teva recalls product exempted from
import alert on Hungarian facilityA little over
two months ago, Teva’s largest sterile medicines plant in Hungary was placed on FDA’s import alert list. When the alert was announced, all drugs produced at the finished dosage forms facility – barring antibiotics Amikacin and Bleomycin – were placed on the import alert list. With a large chunk of drugs and drug ingredients being manufactured outside the US, the American regulator has had to increase its international oversight and ban products manufactured in plants that do not meet the regulatory standards. However, these bans have led to drug shortages. As a result, the FDA has had to (sometimes) exempt products and allow imports from plants that it believes have a poor record. According to the FDA Import Alert records, since 2013 the FDA has allowed eight plants whose products are otherwise banned from the US to go ahead and import some drugs or ingredients in order to avoid drug shortages. Amikacin manufactured at Teva’s Hungary plant was once such drug.However, the FDA’s exemption to prevent a drug shortage suffered a setback when Teva announced
a voluntary recall of seven lots of Amikacin Sulfate Injection due to the potential for the
presence of glass particulate matter. This announcement follows a similar announcement by Teva when one lot of Amikacin was
recalled in March this year. Wockhardt back on FDA’s import alert listJust when it
seemed Wockhardt was getting its compliance act together and putting its problems behind it, its
bulk drug facility got placed on the FDA’s Red List. The bulk drug division in Ankleshwar (Gujarat) is the latest to join FDA’s import alert list, with Wockhardt’s Waluj and Chikalthana (Maharashtra) units already on the list. While
Wockhardt recently said it had received establishment inspection reports (EIR) for the facilities with observations, it also mentioned that the “receipt of EIR does not materially change the status of import alert for the concerned manufacturing units for the US market.” The bulk drug facility in Ankleshwar had received a EU Written Confirmation from the Indian Central Drug Authority for the following seven products – dextromethorphan hydrobromide, adenosine, tamsulosin, nicardipine, cefuroxime axetil, fexofenadine and ceftriaxone sodium. FDA’s warning letter to China’s Xiamen reveals horrific details of GMP deficiencies Chinese drug maker Xiamen Origin Biotech (known
as Attix Xiamen Pharmaceutical in North America) was placed on the
FDA Import Alert list in May 2016. However, it was only recently that its warning letter was put up on the FDA
website, bringing to light the magnitude of GMP deficiencies. According to the warning letter, the company “repeatedly falsified and omitted information on the certificate of analysis (CoA)” issued to customers and went to the extent of fabricating the name of an employee, which was used as a false signing authority on the CoA sent to customers.The company also included an ‘expiration date’ which exceeded the manufacturer’s labeled expiration date without any basis for the extension. In addition, the company made deceptive statements
to the investigator, who also found dirty warehousing spaces and a rodent in
the room adjacent to the warehouse.The FDA’s action in China follows an import alert which was placed on the North American operation of the company – Attix Pharmaceuticals – in Canada in February 2015. The warning letter issued to Attix Canada showed the company was packaging highly potent beta-lactam products “in a facility that is not dedicated to manufacturing beta-lactam drugs”. The practices created “an unacceptable risk of beta-lactam cross-contamination in other beta-lactams and in non-beta-lactam APIs”.An outcome of the North American inspection was a
series of API recalls in both the United States and Canada. Japanese camphor producer refuses inspection; lands up on FDA’s Red ListWhile Wockhardt got placed on FDA’s import alert list as an outcome of an inspection, Nippon Fine Chemical in Japan appeared on the dreaded Red List
for refusing to be inspected.Nippon Fine
Chemical produces pharmaceutical grade Camphor, an active ingredient (along with menthol) in vapor-steam products, such as
Vicks VapoRub. Inno Pharma’s Vitamin D drops with 75 times higher content recalled in DenmarkIn Denmark, Vitamin D drops made by Inno Pharma were recalled recently as the content was “75 times too high”. The product is marketed to infants and pregnant women in Denmark, and sold under the brand ‘Vitamin D3-draber’.The hazardous nature of the drops made the Danish Health Authority (Sundhedsstyrelsen) advise anyone who had taken ‘Vitamin D3-draber’ from Inno Pharma for a week or longer to see their doctor for a blood test to assess the risk posed to them of Vitamin D toxicity. Also known as hypervitaminosis D, this is a rare but
potentially serious condition that occurs when you have excessive amounts of
vitamin D in your body. The main consequence of vitamin D toxicity is a buildup
of calcium in your blood
(hypercalcemia), which can cause poor appetite, nausea, vomiting, weakness, frequent
urination and kidney problems.
Impressions: 7173
https://www.pharmacompass.com/radio-compass-blog/compliance-troubles-emerge-at-pfizer-teva-wockhardt-and-xiamen-origin
#PharmaFlow by PHARMACOMPASS
11 Aug 2016
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New drug development is a series of complex
activities invariably involving tremendous financial investment. The
undertaking, to bring a new drug to market, makes it almost impossible for smaller,
privately held pharmaceutical companies, to even dream of such endeavors.
Is
it possible for companies, lacking the resources of the pharmaceutical majors,
to expand the use of existing drugs, established in some countries but not
marketed in others?
Our PharmaCompass
analysis this week looks at products, which have monographs in the European
Pharmacopoeia but have never been approved in the United States.
Would it surprise you that amylmetacresol, one
of the two active ingredients in Strepsils, one of the world’s largest-selling sore throat product has never been approved for use in the
United States?
-Reckitt Benckiser,
the company that owns the Strepsils brand, markets Cepacol for sore-throat relief in
the United States. While Strepsils contains, amylmetacresol
and dichlorobenzyl alcohol, Cepacol
has a completely different set of active ingredients i.e. benzocaine
and menthol.
-Interestingly, while on the topic of throat relief, pholcodine,
an opioid cough
suppressant, is not prescribed in the United States
where it is a Schedule I drug. However, as a class B substance in the United Kingdom, it can be purchased
over-the-counter (OTC) in most pharmacies.
-Ergometrine, used to facilitate childbirth, while on the WHO’s essential drug list for important medications in a basic health system has
also never been sold in the United States.
-Hypertension and congestive heart failure drug cilazapril is sold across Canada and other European countries. Although cilazapril
is supposed to have limited
advantages over other drugs in the same class, exports out of India to
Turkey, New Zealand and Canada indicate a robust demand in these countries.
-Some molecules, discovered in France like, anti-diarrhoeal drugs nifuroxazide
and racecadotril,
lipid lowering ciprofibrate
or anti-cancer agent buserelin are
used extensively in select countries. However, for reasons unknown, they have
never been approved in other parts of the world.
-Lymecycline, a broad-spectrum antibiotic belonging to the
tetracycline class, is used in the treatment
of acne and marketed by Galderma SA, a completely owned subsidiary of Nestle. Lymecycline is 5,000 times more soluble than tetracycline
base and has unique pharmacological
activity amongst the tetracycline class of molecules. As the product
has been on the market for over a decade, generic versions are now also
available across Europe.
-As antibiotics continue to get increased attention in view of the growing concern of ‘superbugs’, there are antibiotics like roxithromycin
and flucloxacillin, which are sold in the UK and Australia but have never
obtained approval in the United States.
Are
these products safe?
Countries like France, United Kingdom, and
Canada, where many of the above mentioned drugs are marketed, have active
pharmacovigilance programs, which monitor drugs, should there be any serious
adverse events. Continued use for years in well regulated pharmaceutical
markets is usually proof that the products are safe.
However, for the antibiotic flucloxacillin,
concerns have been identified regarding a genetic link associated
with liver injury. While flucloxacillin
has not been approved in the United States, the FDA website does provide details
on this risk.
Liver toxicity concerns have limited the
sales of some commonly used OTC products like nimesulide
and propyphenazone
(brand name: Saridon) in some countries. Yet, there are parts of the developing
world, where the sales continue to increase.
There are graver concerns for products like
cisapride,
which was launched by Janssen
for increased motility of the gastrointestinal tract but was withdrawn, from
the US market, due to concerns of fatalities linked to cardiac arrhythmias.
The product continues to be exported from India to countries like Switzerland,
Thailand, Mexico, China and Canada.
Our
View:
Reviewing the export data out of India, on
the PharmaCompass database, it is
clear that in the markets, where the above mentioned products are sold, there
is substantial demand.
Major pharmaceutical companies have little
incentive in taking old molecules global since there is little intellectual
property protection to assure the profits that they are used to. However, for
others there may be an opportunity worth considering.
Launching a new product is always a
Herculean challenge, but hopefully the successful use in existing patient
populations, is a good starting point.
API manufactures can also review these products
since there may be better margins in these niche molecules when compared with
others, which have become commodities.
Impressions: 3117
https://www.pharmacompass.com/radio-compass-blog/niche-european-molecules-is-there-a-business-opportunity-worth-pursuing
#PharmaFlow by PHARMACOMPASS
11 Jun 2015
