Pharma Uptoday Monthly Magazine Volume 12; Issue Mar 2015

VOLUME: 12 - ISSUE: MAR 2015 |
PHARMA UPTODAY
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Inside this issue
3 News Uptoday
47 New Guidance
56 Audit Findings
483 Observations
- India's Lupin says FDA raises concerns over plant at Pithampur
57 Warning Letters
- Micro Labs Limited, Bangalore
- Apotex Research Private Limited
- Oregon Compounding Centers, Inc. dba Creative Compounds
- Cantrell Drug Company
- Warning Letters on Data Integrity: What does the FDA expect
from Third Party Auditors and Consultants?
63 Regulations of the Month
- § 211.194 Laboratory records (a)(5)(6)(7)(8) & (b)

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News Uptoday
Drugs of seven Indian pharma firms in EMA's suspension list
Several drugs manufactured and marketed by as many as seven Indian generic pharmaceutical
companies have been recommended for suspension by the European Medicines Agency (EMA) in its
orders issued on January 23, 2014, after questions were raised over the integrity of clinical research
data generated at a site operated by Hyderabad-based GVK Biosciences.
The European drug regulator, however, maintained that there was no evidence of harm or lack of
effectiveness with any of the medicines linked to studies conducted by GVK Bio.
While the list of suspended medicines comprise the names of several major global generic drug players,
including Teva and Mylan, at least a dozen drugs marketed by Indian companies and their subsidiaries
have also been figured in this list. These companies are Dr Reddy‘s Laboratories Limited, Ranbaxy
Laboratories, Lupin, Torrent Phama, Alembic Pharma and Glenmark.
Earlier last year, French medicines agency (ANSM) said it had found evidence of manipulation
of electrocardiograms related to the conduct of studies on some of these generic medicines at GVK‘s
Hyderabad site. Subsequently, EMA‘s Committee for Medicinal Products for Human Use (CHMP) looked
over 1,000 pharmaceutical forms and strengths of medicines at the GVK site and recommended for
suspension of close to 700 of them for lack of data from other sources. For the medicines that are
considered critical, the manufacturers are given 12 months to submit additional data.
In the UK, the anti-epileptic drug Levetiracetam, anti-diabetic drug Pioglitazone among other drugs of Dr
Reddy's Laboratories, ulcer drug Pantoprazole of Lupin, Alendronic acid of Ranbaxy, a product used to
treat bone diseases, anti-hypertension drug Irbesartan by Torrent Pharma figured in the list of medicines
recommended for suspension by EMA.
Some of these and other types of drugs were recommended for suspension in other European countries
including Romania, Sweden and the Netherlands.
―As Europe is a small market for many of these Indian companies such as Dr Reddy's and Lupin, the
suspension of drugs from the markets of individual European countries will not have any significant
impact on the revenues,‖ Sarabjit Kour Nangra of Angel Broking, who tracks the pharma sector, told
Business Standard.
Last week, Dr Reddy‘s also maintained that it was not going to be impacted by the EMA‘s decision. The
anti-epileptic drug marketed in Germany by the company‘s German subsidiary Betapharm has also been
figured in the list.
The review was covered nationally authorised medicines whose marketing authorisation applications
included clinical data from studies conducted by GVK Biosciences site in Hyderabad, according to EMA.
―The review was initiated at the request of the European Commission in relation to findings by the
French medicines agency of non-compliance with good clinical practice (GCP) at GVK Biosciences site,‖
the agency said.

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Mylan to buy Famy Care's female healthcare businesses for $800 mn
Mylan Inc's Indian subsidiary Mylan Laboratories has signed a definitive agreement to acquire certain
female health care businesses from Famy Care Ltd, a specialty women's health care company with
global leadership in generic oral contraceptive products (OCPs), for $750 million in cash plus additional
contingent payments of up to $50 million. The transaction is expected to close in the second half of
2015, subject to regulatory approvals and certain closing conditions.
The acquisition will build on Mylan's existing partnerships with Famy Care in North America, Europe and
Australia, and provide Mylan with an enhanced and now vertically integrated platform that will accelerate
the company's growth in the important global women's health care space.
Under the proposed transaction structure, Famy Care will spin off its female health care businesses
under a court approved scheme of demerger. Post demerger, Mylan will acquire the shares of the new
resulting company.
Centerview Partners and Goldman Sachs & Co. are serving as financial advisors to Mylan and Cravath,
Swaine & Moore LLP and Luthra & Luthra are acting as legal advisors. Credit Suisse is serving as
financial advisor to Famy Care and Covington & Burling LLP and AZB & Partners are acting as legal
advisors.
This transaction especially complements Mylan's pending acquisition of Abbott's non-US developed
markets specialty and branded generics business, which also includes a women's health care portfolio
and sales and marketing capabilities. Additionally, the acquisition of the Famy Care businesses will
make Mylan a hormonal contraceptives leader in high-growth emerging markets around the world.
The acquisition is expected to be immediately accretive to Mylan's adjusted diluted earnings per share
and growth profile upon closing.
Mylan CEO Heather Bresch commented, "In 2008, Mylan established a partnership with Famy Care,
significantly enhancing its presence in the women's health care segment in the US and other developed
country markets. With today's acquisition, we are building on this successful partnership and further
accelerating our global growth in this important therapeutic area. We see many opportunities to tap the
large women's health care market in Europe, particularly through our pending Abbott deal; the prospect
of driving additional value from this business in North America; and exciting growth potential in emerging
markets. Finally, we are excited to welcome Famy Care's more than 900 employees to the Mylan family
and look forward to their contributions to our mission of providing the world's 7 billion people access to
high quality medicine."
Mylan president Rajiv Malik added, "By adding this vertically integrated business and globalizing our
women's health care platform, we are creating the right foundation to become a leader in this growing,
attractive sector. Famy Care brings us a broad portfolio, strong technical capabilities and dedicated
hormone manufacturing, which complement Mylan's powerful global commercial footprint and supply
chain infrastructure. In addition to the opportunities we see in North America and Europe, Famy Care's

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businesses will strengthen our position in emerging markets, where we can build upon and leverage our
existing capabilities, including the strong presence we have established through our antiretroviral
business and our track record of success in competing for tenders in these markets. Finally, we see
opportunities for generating more front-end sales, in addition to Famy Care's successful partnering
strategy, as a result of our exceptional global infrastructure."
Commenting on the transaction, JP Taparia, non-executive chairman of Famy Care, said, "This
transaction represents a significant milestone for Famy Care and its employees, who have created a
world-class women's health care franchise. We foresee significant opportunities in the women's health
care business across developed and emerging markets, and the proposed transaction provides an
opportunity for our team to capture the opportunity in an even more effective manner. Famy Care and
Mylan have shared a very strong partnership since 2008, and the Famy Care team looks forward to
taking our vision and ambitions to the next level within Mylan. In 2010, we started the process of
transitioning from a family-owned business into a meaningful institutional player in the global
pharmaceutical industry by enlarging our shareholder base with the investment by pan-Asian private
equity firm, AIF Capital Ltd. Their involvement and support for Famy Care have been very helpful in the
company's achievement of critical corporate milestones over the last four years. Shareholders of Famy
Care will evaluate and pursue other opportunities in the residual Famy Care business outside of
women's health care segment."
Famy Care, headquartered in Mumbai, India, offers a comprehensive range of women's health products
including oral and injectable contraceptives, intra-uterine devices (IUDs), tubal rings and hormone-
replacement therapy products. More than 15 per cent of the world's women using oral contraceptive pills
today use a Famy Care product. It is the world's largest producer of generic OCPs, with four high quality
manufacturing facilities in India, two of which have been approved by the U.S. Food and Drug
Administration (FDA) and the European Union.
Famy Care is the first generics company to have received prequalification from the World Health
Organization for hormonal contraceptives. This manufacturing base represents one of the lowest cost
and largest dedicated to OCPs globally, and brings Mylan strong capabilities in OCP cycles, injectables,
IUDs and tubal rings.
Famy Care has a strong presence in the private, institutional and non-governmental organization sectors
and markets its products in more than 90 countries around the world.
Famy Care also has strong research and development capabilities in the women's health care segment,
including in the development of hormonal and high-potency formulations. The company's R&D and
regulatory affairs team, comprising more than 100 professionals, has a strong track record of bringing
products to market, with approximately 600 product registrations in approximately 90 countries and a
pipeline of more than 200 filings, including more than 100 filings for the developed markets.
Mylan and Famy Care have an exclusive partnership dating to 2008, under which Famy Care develops
and supplies OCP products to Mylan for distribution to customers in the U.S. and certain other markets.
In the U.S., Famy Care and Mylan have a portfolio of 12 approved products, with abbreviated new drug
applications pending FDA approval for 30 products.

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The global women's health care market is growing at a compound annual rate of approximately 62 per
cent, with hormonal contraceptives representing the largest and fastest growing products in the
segment. Lower oral contraceptive penetration rates in emerging markets represent an important growth
opportunity, and this opportunity is supported by global initiatives, such as Family Planning 2020, which
provide funding for contraceptive access in these markets.
Under the terms of the transaction, which has been unanimously approved by both companies' boards
of directors, Mylan will acquire certain female reproductive health care businesses from Famy Care for
$750 million in cash at closing, subject to certain adjustments, plus an additional payment of up to $50
million, contingent upon achievement of certain development and regulatory milestones. Mylan expects
that its financial leverage will not be materially altered as a result of this transaction.
Sun Pharma gets US FTC clearance for Ranbaxy acquisition
Sun Pharmaceutical Industries has received US Federal Trade Commission (FTC) clearance for
acquisition of Ranbaxy Laboratories. The US FTC has completed its review of the proposed acquisition
of Ranbaxy by Sun Pharma and has granted early termination of the waiting period under the Hart-
Scott-Rodino Antitrust Improvements Act of 1976 (HSR Act).
The early termination of the waiting period under the HSR Act satisfies one of the essential conditions to
the closing of the Ranbaxy acquisition.
Sun Pharma and Ranbaxy also announced that the FTC accepted a proposed consent agreement
pursuant to which, Sun Pharma and Ranbaxy have agreed to divest Ranbaxy‘s interests in generic
minocycline tablets and capsules to an external third party.
Sun Pharma and Ranbaxy are working closely towards completion of the transaction and will comply
with the conditions laid down in the FTC consent agreement within the specified time.
IPA demands setting up of Dept of FDA under health ministry for better implementation of food &
drugs laws
The Indian Pharmacist Association (IPA) has asked the Central government to create a new Department
of Food and Drug Administration (FDA) under the ministry of health and family welfare on the lines of
Gujarat, Maharashtra and Goa for better coordination with agencies dealing with food and drugs laws.
In a letter to Prime Minister Narendra Modi, IPA president Abhay Kumar said that creation of a separate
department of FDA in appropriate ministry and similar structures should be made mandatory in all states
and Union Territories for uniform implementation of food and drugs laws throughout the country.
Kumar in his letter said that at present Gujarat, Maharashtra, Goa and recently Punjab government have
created the FDA department with food and drugs divisions functioning effectively under a senior level
secretary.
At present, the food law is implemented Food Safety and Standards Authority of India (FSSAI) under the

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health ministry and drug laws like D&C Act, DPCO, Pharmacy Act are implemented by different
ministries. He further suggested that the implementation of the food and drugs laws should be handed
over to professionally trained personnel who can efficiently manage, as there is no dearth of manpower
from the food and drugs sectors.
In the states and Union Territories the food and drug laws are by and large enforced by directorate of
health services with poor infrastructure and lack of professionally trained enforcement personnel, results
in poor implementation of these laws. In most of the states even the full time regular drugs inspectors
who are the main instrument for implementation of Drugs and Cosmetic Act 1948 are not posted and the
drugs control department runs on ex-officio staffs.
Further, he expressed the need to create a new department independent from health department with
inter-sectoral coordination especially with health, agriculture, veterinary, consumer affairs, fertilizers,
chemical departments/ministries, which can function as an apex body of the food and drugs authorities
under the ministry of health and family welfare or under appropriate ministry.
Centre to augment compliance of India pharma with recent slew of regulations: Dr BR Jagashetty
Union government will now augment the compliance records of the Indian pharma industry with its slew
of recent regulations, said Dr BR Jagashetty, National Advisor, (Drugs Control), and Project in-charge
for the implementation of two schemes of Central Drugs Standards Control Organization (CDSCO).
The regulations covering Uniform Code for Pharma Marketing, Formation of Task Force to formulate
Bulk drug policy, Medical devices policy, creation of Price Monitoring and Resource units in the state
drugs control department and the Draft Amendment to the Drugs & Cosmetics Act 2015 would
strengthen the Indian pharmaceutical sector, he added.
―These regulations signal the opportunity of Indian pharma sector across the large, medium and small
industries to succeed in a stringent and competitive market conditions globally, stated Dr. Jagashetty.
The draft Drugs & Cosmetics Act (Amendment) Bill 2015 is a chance for the industry to comment and
deliberate about the said norms.
Among the interesting inclusions in the draft Drugs & Cosmetics Act (Amendment) Bill 2015 is the
penalty clauses. ―The penalties indicate that both pharma industry and pharmacy trade will not be able
to exploit and embark on unfair practices. It will also bring in transparency and accountability,‖ said Dr
Jagashetty.
Another key aspect of the draft Drugs & Cosmetics Act (Amendment) Bill 2015 is the introduction of
Central Licencing Authority (CLA) along with State Licencing Authority (SLA) for Schedule III. The CLA
now replaces the Central Licensing Approval Authority (CLAA). We now need to see how the state
drugs control departments accept the CLA, he said.
Commenting on the Medical Devices Policy, Dr. Jagashetty said that it was vital to include the same in
the draft Drugs & Cosmetics (Amendment) 2015 because it was related to patient care. The recent

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foreign direct investments (FDI) policy permits 100 per cent FDI in medical devices sector through the
automatic route. This mandates monitoring sale and manufacture of medical devices in the draft Drugs,
Cosmetics and Medical Devices Act (Amendment) 2015, he said.
The enforcement of a Uniform Code of Pharmaceutical Marketing Practices (UCPMP), issued by the
Department of Pharmaceuticals beginning this year, would thwart unethical practices of bribing medical
practitioners by the pharmaceutical companies, said Dr. Jagashetty.
The price monitoring and resource units (PMRUs) in States and Union Territories to successfully track
violations of drug prices fixed by National Pharmaceutical Pricing Authority will now put in place a
mechanism for price audits, he said.
The Indian bulk drug industry also needs a dedicated policy and this is because active pharmaceutical
ingredients (APIs) are core of any formulation. Therefore formation of a Task Force to formulate a policy
is a step in the right direction by the government, said Dr Jagashetty.
Pharmaceuticals is a priority sector for the country. The government recognises that this industry is
among its key growth propellers and went ahead to unveil the much wanted regulations, noted Dr
Jagashetty.
FY 2015 First Quarter OGD Stats are Published – Picture is Not Rosy
Well, we now have the actual numbers for various input and output metrics for FY 2015‘s 1st quarter
that speaks to the current level of productivity at the Office of Generic Drugs (OGD). I know that there
are training issues that drain resources for new and existing staff. I know that there are tremendous
policy issues that must be addressed. I know that there have been problems with the new IT platform.
I know that the learning curve relative to coordination of reviews from the various disciplines is steep
and, with the number of moving pieces associated with an ANDA review, it is difficult at best to bring an
ANDA approval or Complete Response Letter (CRL) in for a landing. I know all these things, but I also
know from the calls I receive that industry is not particularly happy. I also know that, because of these
bumps in the road, enthusiasm for GDUFA is waning, which may make for some interesting and
contentious negotiations for GDUFA II.
So, let‘s look at some of the numbers. FDA has hired 923 new GDUFA employees as of October 2014
(that number alone is close to 3 times the OGD staff pre-GDUFA and that number is also about 6 times
the number of staff OGD had [155] when I left OGD at the end of 1994). To be fair, these new
employees have been spread out over various components of the Agency, but it also does not include
the number of staff already in the programs that contribute to the ANDA review and approval process.
Here are some specific numbers for the first three month of FY 2015 and a comparison to FY 2013 and
2014.

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Item FY 2013 FY 2014 FY 2015*
CRL** avg/mo/FY 104 105 71
CRL** 1st QTR 127 116 71
DMF CA/mo/FY 142 142 83
DMF CA 1st Qtr 143 73 83
ANDA Rec’ed /mo/FY 81 133 38
ANDA Rec’ed 1st Qtr/mo 108 98 38
Control Corres/mo/FY 80 90 90
Approvals/mo/FY 37 34 34
Approvals 1st Qtr/mo 36 30 34
*- Represents first three month of FY 2015
**- Complete Response Letters
So, what do we see so far this FY? CRLs have decreased by about 1/3 so far this FY and, for the first
quarter same period over the last three years, it is well over a 33% decrease over same quarter for the
last two prior FY. DMF complete assessment numbers have declined, but this is an expected figure
since the number of new DMFs submitted or first time reviews have already been completed in year 1
and 2 of GDUFA.
Original ANDA receipts are down substantially over the first quarter FY 2015. This is good news for
OGD. There was not the ―big‖ December numbers that we usually see primarily because the pipeline of
ANDA submission was likely depleted by the huge number of submissions in the first half of June 2014,
as firms sought to beat the new stability requirements. On the approval side of the coin, things seem
pretty constant over the last three fiscal years. This is one area where the numbers must be
substantially improved if industry is to begin smiling again and if OGD is ever going to get out of the
staggering backlog of original ANDAs it has to deal with.
Controlled correspondences seem to be on par with each of the last two years of GDUFA, but the
numbers still show that industry has a lot of questions to ask, and now, with the limit on what is classified
as a controlled correspondence and who can submit them under the GDUFA metrics, the FY 2015
numbers may actually reflect an increase in actual industry drug development questions.
The numbers are one thing concrete to evaluate performance and, while numbers can sometimes lie,
what are we hearing from our colleagues in industry should concern us all. Here are some snippets.
 We have had a good record with our submissions at OGD with maybe 5-10 deficiencies and minor
status of the CRL. Now we are seeing 20-40 deficiencies and it appears like we all of a sudden don‘t
know what were are doing. Senior management is questioning our effectiveness.
 We received two CRLs with minor questions, and then out of the blue, when we were expecting final
approval, we received a major amendment CRL.
 We have been working with FDA on a difficult ANDA issue and thought we were circling in on approval
based on our last response to a CRL letter, then we got a Biodeficiency letter from FDA that they never
got around to sending us (was not in the last CRL) and were told to hold off until we get additional CMC
comments. The FDA said whoops we forgot to send the BE comments.

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These are just a few of the issues we have heard from industry over the last few months. Is this part of
the learning curve? If it is, then industry hopes the curve levels out soon. One other general issue that
we hear all of the time ever since the inception of GDUFA is that we have no idea who to call at OGD if
we have a real problem.
FDA invites Indian regulators to join inspections
The US Food and Drug Administration (FDA) India Office has invited officials of drug regulatory body,
both at Central and State Government levels, to accompany its team inspecting pharmaceutical units in
the country.
This is subsequent to a memorandum of understanding that the two countries inked during the visit of
US FDA Commissioner to India in February 2014, according to Soloman Yimam, Assistant Country
Director, US FDA India Office.
―Based on that MoU whenever we do GMP (Good Manufacturing Practice) inspections we invite DCGI
(Drug Controller General of India) officials and State regulators to accompany us on the inspections,‖ he
said on Wednesday. Mr. Yimam, speaking on the sidelines of the BioAsia 2015 event here, was
responding to a query on whether Indian government had made requests to allow its officials to be
present during inspections by the FDA. Many in the pharmaceutical industry also favour this.
On whether the agreement was being practiced, Mr. Yimam said: ―There might be some glitches here
and there, but it is something we always strive for - to bring them [Indian officials] on board. We want
them to come with us, do the inspection, observe so that they can learn from our processes.‖
Mr. Yimam, who addressed sessions at the Bio Asia on Tuesday as well as Wednesday, said that the
US FDA in India operates out of New Delhi and Mumbai. It was looking to increase the headcount to 19.
On what is the number now, he said probably 9-10 officials, but did not reply on whether more officials
would mean more inspections.
The number of inspections, he added, was based on the marketing applications filed by pharma
companies seeking to take its products to the US. On whether it pursues a target regarding the number
of inspections, he said it was dependent on how many companies produce products meant for sale in
the US.
FDA Explains its Definition of "Drug Shortage"
Tell me how FDA defines a drug shortage
We define shortages as a period of time when the demand or projected demand for a medically
necessary drug in the United States exceeds its supply.
Explain “projected demand”
Based on health data, information from suppliers, and by evaluating information from U.S. healthcare
transactions, we can anticipate demand and determine if available drug products can meet that
projected demand.

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How does an FDA partner, such as the American Society of Health-System Pharmacists define a
drug shortage?
Both FDA and ASHP closely follow drug shortages however, there are some differences in how we track
and report this information. ASHP considers a drug product to be in shortage once the shortage is
verified with manufacturers, regardless of whether the product is or is not medically necessary. They
also consider a drug to be in shortage when supply issues affect how a pharmacy prepares or dispenses
a drug product, or influence patient care when prescribers must use an alternative therapy.
Do the differences in these definitions impact the availability of drugs for consumers?
No – the differences affect how we each define availability and report shortages, but don't affect the
availability of drugs for consumers. For example, ASHP may decide to post on their website when one
manufacturer‘s product is unavailable; while FDA would only post if the total demand is not able to be
met by the current manufacturers, regardless if one manufacturer is "down" or currently not producing.
FDA receives information from manufacturers about their ability to supply a product for the market. A
product is only listed on FDA‘s drug shortage website when it has been confirmed to be unable to meet
current demand (i.e. – the quantity of drug available from all manufacturers does not meet the current or
projected demand). We do not consider a product to be in shortage if one or more manufacturers are
able to supply enough of the product to meet the demand.
In contrast, ASHP‘s drug shortage website provides information about which manufacturers have a drug
available and which ones do not. If a product is listed on ASHP‘s website, it is likely that a consumer will
still find the product available from other manufacturers. The numbers and information from ASHP are
valid; they track availability -- but they do not serve the same purpose as FDA.
Regardless of the differences between FDA and ASHP, we provide the most updated information
possible on our websites about shortages and availability.
Overall, does FDA consider drug shortages a high priority?
Drug shortages are a top priority for FDA. They are a significant public health issue in the United States
and we use every tool in our toolbox to find solutions including working with manufacturers to help
prevent shortages from occurring or lessen the impact of shortages that cannot be prevented. We have
issued a long-term strategic plan that outlines our priority actions, and actions drug manufacturers and
others can take to prevent drug shortages.
Our comprehensive strategy recognizes the importance of addressing the underlying causes of
shortages, including sustaining manufacturing quality. For example, the plan calls for improving data and
response tracking, so we‘re working to clarify the roles and responsibilities of manufacturers. We are
constantly exploring actions the agency can take alone and in collaboration with other groups to reduce
the impact and number of drug shortages.
Why are drug shortages still a critical issue in the United States?

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Health care professionals caring for patients need the right drug, for the right patient, at the right time.
We want to ensure this important tenet of health care - and not having a product available can be a
major road block to treatment. Until drug shortages cease to occur, we will continue to be vigilant in our
efforts to prevent them.
What is the major reason for these shortages?
There are a number of reasons why drug shortages can occur. Over half of all drug shortages are due to
quality or manufacturing issues, such as the presence of particulates or endotoxins. Production delays
at the manufacturer or delays obtaining raw materials and components from suppliers can all cause
shortages. Sometimes companies stop producing a drug to make newer, more profitable drugs. With
fewer firms making sterile injectable drugs, there are fewer production lines and in this case a shortage
can occur if even one of these lines becomes unavailable. Seven manufacturers produce most of the
sterile injectable drugs on the market. When one company has a problem or stops making the drug, it is
difficult for the remaining companies to increase production quickly and shortages can occur.
Why can’t we just say to industry, “make more of product X?”
It doesn‘t work that way – although it would be a lot easier if it did! FDA cannot require a company to
make a drug. We can‘t tell a company to make more of a drug. We can‘t tell them how much of a drug
should be distributed, nor can we tell manufacturers where a drug should be distributed. But if a
shortage is imminent, we can work with companies to try to minimize its impact. Early and open dialogue
between FDA and manufacturers is critical to our success.
How does the agency resolve shortages?
We have a carefully developed process we follow to identify the sources of the shortage and what can
be done to prevent or minimize the impact of the shortage. To address the underlying causes, we work
with the company to help resolve manufacturing or quality problems. The problems can be what we term
―low risk‖ such as the wrong expiration date on a package. High risk problems can include foreign
particles in the drug or sterility issues. We decide how to best address each situation based on its cause
and the public health risk associated with the shortage. We work with other firms still able to make the
drugs that are in shortage to help them ramp up production, if they are willing. Like I said, we can‘t order
them to increase production. If needed, we expedite approval of new production lines or new raw
material sources. If U.S. manufacturers can‘t resolve a shortage immediately and the shortage involves
a critical drug, we may look for an international firm that is willing and able to redirect the product to the
United States.
How has the Food and Drug Administration Safety and Innovation Act (FDASIA) enhanced our
ability to prevent and mitigate drug shortages?

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The biggest impact is the requirement that manufacturers must report shortages to us. This has resulted
in additional early notifications to the FDA about potential shortages, and we have used that information
to prevent shortages. FDASIA has detailed a list of prescription drug and biologic products for FDA to
monitor, and requires all manufacturers of these products to notify us of a permanent discontinuance or
temporary interruption in manufacturing. The Act also requires FDA to send a noncompliance letter to
firms that fail to notify the agency. Other FDASIA requirements involve improving our internal and
external communications; improving communication between FDA and the Drug Enforcement
Administration regarding shortages of controlled substances; and developing a strategic plan to enhance
FDA‘s response to preventing and mitigating drug shortages.
How can the public access the latest information on drug shortages?
FDA is working hard to communicate effectively to the public about shortages to provide the most up to
date information possible. To enhance communications we launched a new searchable format for FDA‘s
Drug Shortage website. This should help the public and health care professionals quickly identify drugs
in shortage and find information on availability. Additionally, the FDA website now provides sections for
new and updated drug shortages, and a listing of drug shortages by therapeutic categories.
We now also have the ability to report a shortage via a web form, and sorting functions to find drug
shortages by generic name or status. This is an exciting development. We hope it will increase public
access to drug shortage information and lessen some of the frustrations. We are also working on a
mobile app that will help communicate drug shortage information to the public in real-time, as well as
provide an additional means for the public to notify us about potential shortages.
The number of reported drug shortages has decreased in recent years. How do you think the
efforts of FDA and its partners have helped create this trend?
The decrease in shortages has definitely been a combination of our efforts and the work of our partners
– particularly the increased number of notifications we receive from manufacturers and health care
providers. While our goal is to prevent all shortages, we‘re not there yet. The downward trend in
shortages, the uptick in notifications, and the increased focus on manufacturing quality are all things we
hope will continue.
We are pleased to have seen a great decrease in new drug shortages over the last few years, however,
more work needs to be done. Although last year there were less shortages, the United States
experienced several critical shortages, like IV saline (intravenous saline solution used to give patients
necessary fluids for hydration and other conditions). We will continue to work with industry and other
stakeholders to address the root causes of shortages and do what is necessary to prevent them from
occurring.

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Pfizer To Acquire Hospira
 Transaction will significantly enhance Pfizer’s Global Established Pharmaceutical (GEP)
Business
 Transaction valued at $90 per Hospira share, for a total enterprise value of approximately
$17 billion
 Expected to be immediately accretive upon closing; $0.10-$0.12 accretion expected in first
full year after close with additional accretion anticipated thereafter
Pfizer Inc. (NYSE:PFE) and Hospira, Inc. (NYSE:HSP) today announced that they have entered into a
definitive merger agreement under which Pfizer will acquire Hospira, the world‘s leading provider of
injectable drugs and infusion technologies and a global leader in biosimilars, for $90 a share in cash for
a total enterprise value of approximately $17 billion. The Boards of Directors of both companies have
unanimously approved the merger, which is expected to be immediately accretive upon closing,
accretive by $0.10 - $0.12 per share for the first full year following the close of the transaction with
additional accretion anticipated thereafter.
―I want to recognize and thank our 19,000 employees around the world for their tireless efforts to deliver
more affordable healthcare solutions, increase patient access to high-quality care and drive sustained
growth for our shareholders.‖
―The proposed acquisition of Hospira demonstrates our commitment to prudently deploy capital to create
shareholder value and deliver incremental revenue and EPS growth in the near-term,‖ said Ian Read,
Chairman and Chief Executive Officer, Pfizer. ―In addition, Hospira‘s business aligns well with our new
commercial structure and is an excellent strategic fit for our Global Established Pharmaceutical
business, which will benefit from a significantly enhanced product portfolio in growing markets. Coupled
with Pfizer‘s global reach, Hospira is expected to drive greater sustainability for our Global Established
Pharmaceutical business over the long term.‖
This strategically complementary combination will add a growing revenue stream and a platform for
growth for Pfizer‘s GEP business. The expanded portfolio of sterile injectable pharmaceuticals,
composed of Hospira‘s broad generic sterile injectables product line, including acute care and oncology
injectables, with a number of differentiated presentations, as well as its biosimilars portfolio, combined
with GEP‘s branded sterile injectables, including anti-infectives, anti-inflammatories and cytotoxics, will
create a leading global sterile injectables business. The combination also reinforces GEP‘s growth
strategy to build a broad portfolio of biosimilars in Pfizer‘s therapeutic areas of strength through the
addition of Hospira‘s portfolio that includes several marketed biosimilars. Pfizer will also use its existing
commercial capabilities, global scale, scientific expertise and world class development capabilities to
significantly expand the reach of Hospira‘s products, which are currently distributed primarily in the
United States, to Europe and key emerging markets, where GEP has a significant presence.
―The addition of Hospira has the potential to fundamentally improve the growth trajectory of the Global
Established Pharmaceutical business, vault it into a leadership position in the large and growing off-
patent sterile injectables marketplace by combining the specialized talent and capabilities of both

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companies, including enhanced manufacturing, and advance its goal to be among the world‘s most
preeminent biosimilars providers,‖ said John Young, group president, Pfizer Global Established
Pharmaceutical business. ―We‘re excited to combine Hospira‘s expertise and key talent with that of
Pfizer to create a leading global business that will deliver an even broader portfolio of important and life-
saving sterile injectable medicines to patients around the world.‖
―The Pfizer-Hospira combination is an excellent strategic fit, presenting a unique opportunity to leverage
the complementary strengths of our robust portfolios and rich pipelines,‖ said F. Michael Ball, Chief
Executive Officer, Hospira. ―I want to recognize and thank our 19,000 employees around the world for
their tireless efforts to deliver more affordable healthcare solutions, increase patient access to high-
quality care and drive sustained growth for our shareholders.‖
Both sterile injectables and biosimilars are large and growing categories. The global marketplace value
for generic sterile injectables is estimated to be $70 billion in 2020. The global marketplace for
biosimilars is estimated to be approximately $20 billion in 2020.
Pfizer expects to finance the transaction through a combination of existing cash and new debt, with
approximately two-thirds of the value financed from cash and one-third from debt. In addition, Pfizer
anticipates the transaction to deliver $800 million in annual cost savings by 2018.
The transaction is subject to customary closing conditions, including regulatory approvals in several
jurisdictions and approval of Hospira‘s shareholders, and is expected to close in the second half of 2015.
Pfizer‘s financial advisors for the transaction were Guggenheim Securities, J.P. Morgan and Lazard, with
Ropes & Gray LLP acting as its legal advisor and Clifford Chance LLP advising on international
regulatory matters. Morgan Stanley served as Hospira‘s financial advisor, while Skadden, Arps, Slate,
Meagher & Flom LLP & Affiliates served as its legal advisor.
About Pfizer:
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly
improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and
manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the
world's best-known consumer health care products. Every day, Pfizer colleagues work across developed and
emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases
of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical
companies, we collaborate with health care providers, governments and local communities to support and expand
access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a
difference for all who rely on us. To learn more, please visit us at www.pfizer.com.
About Hospira:
Hospira, Inc. is the world's leading provider of injectable drugs and infusion technologies, and a global leader in
biosimilars. Through its broad, integrated portfolio, Hospira is uniquely positioned to Advance Wellness™ by
improving patient and caregiver safety while reducing healthcare costs. The company is headquartered in Lake
Forest, Ill. Learn more at www.Hospira.com.

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Wockhardt says resolved US facility compliance issues
Drugmaker Wockhardt on Wednesday said that the company has resolved its compliance related issues
at its Morton Grove facility in the US for which it received a Form 483 from the
US Food and Drug Administration (FDA).
The company also posted 14% year-on-year increase in its net profit to Rs 347.25 crore during the
quarter ended December 2014.
Last year, the US FDA has raised as many as 12 procedural lapses against generic drugmaker
Wockhardt's Morton Grove facility in Illinois, post which it issued a Form 483 to the company.
A Form 483 is a letter which detail unsatisfactory results of manufacturing facilities made by FDA
inspectors for compliance with the current good manufacturing practices (cGMP).
FDA officials carried out the inspection at the company's US unit between January 22 and March 26,
2014. While the company's top management, during the earnings call on May 27, said that the
observations made may not be "very negative", the document provided on the agency's website pointed
out too many lapses in the production process. The facility accounts for over 50% of its sales in the US.
On Wednesday, Wockhardt chairman Habil Khorakiwala told mediapersons that his company has
resolved all issues related to Form 483 at its Morton Grove facility satisfactorily.
Wockhardt has reported a 12% rise in total income from operations of Rs 1,382 crore for the quarter
under review. It increased its research spend significantly, which is at Rs 119 crore was 8.6% of sales
during the quarter, and including capital expenditure is 8.9% to sales.
The India business recorded a growth of 15% during the third quarter of the current fiscal while the
emerging markets business grew 28%. Wockhardt's international business contributed 79% of the total
revenues during the quarter.
The UK business grew 141% in the third quarter (in British pound terms 130%). The Irish business,
however, declined 37% during the period (in euro terms 36%). Wockhardt's US business fell by 48% in
the third quarter and contributed 20% of the global revenues for the company in the last quarter.
Khorakiwala said the growth numbers were boosted by the UK business. He said the UK drug regulator,
Medicines and Healthcare Products Regulatory Agency, gave clearance of complete good
manufacturing practices compliance over its Chikalthana facility.
FDA Commissioner Margaret Hamburg to Resign Next Month
Margaret Hamburg, one of the longest-serving commissioners in US Food and Drug Administration
(FDA) history, plans to announce her resignation tomorrow, FDA officials have confirmed to Regulatory
Focus.
Hamburg's final day at the agency will be in late March 2015, Hamburg wrote in an email. She will be
succeeded on an acting basis by Stephen Ostroff, FDA's chief scientist since January 2014.

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A Long Tenure
Hamburg's resignation brings to an end one of the longest tenures as FDA commissioner of food and
drugs in the agency's history. According to data analyzed by Regulatory Focus, Hamburg will be the
sixth-longest serving FDA commissioner in history, the longest-serving (and only the second) female
commissioner in the agency's history, and the second-longest-serving commissioner of FDA's modern
regulatory era.
Assuming Hamburg leaves office on 28 March 2015, she will have served in office for 2,140 days. She
was sworn into office on 19 May 2009, and had been the only FDA commissioner to serve under
President Barack Obama.
An Agency in Flux
Hamburg's tenure as commissioner has been marked by a number of high-profile changes, struggles
and scandals.
She was brought on in the early days of Obama's push for the Patient Protection and Affordable Care
Act (PPACA), which established a regulatory pathway for biosimilar products. In 2011, tensions flared
between her and Department of Health and Human Services (DHHS) Secretary Kathleen Sebelius after
FDA's approval of an over-the-counter birth control product was overturned for reasons that appeared to
be more political than scientific.

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Hamburg has also overseen massive legislative changes at FDA. The 2012 passage of the Food and
Drug Administration Safety and Innovation Act (FDASIA) created hundreds of new obligations for the
agency, and also established several new pathways for approvals, such as the breakthrough therapy
designation. The 2013 Drug Quality and Security Act gave the agency broad new powers to ensure the
safety of the pharmaceutical supply chain and of compounded pharmaceutical products.
Drug and device approvals also saw marked improvements under Hamburg's tenure, with new drug
approvals experiencing perhaps their best year for approvals ever in 2014, and device approvals making
slow but steady improvements.
Hamburg also oversaw scandals and problems at FDA during her tenure. FDA was chastised for its lack
of oversight of the pharmaceutical compounding industry, for allegedly spying on some members of its
medical device review divisions, for its approach to regulating painkillers, and for its regulation of various
products and areas.
What's Next?
Hamburg's departure comes at a particularly tricky time for FDA.
Both the House of Representatives and Senate are pursuing new legislation aimed at expediting the
processes FDA uses to approve most drugs, and particularly those for patients with rare or life-
threatening diseases. The legislation could have a massive effect on the way in which FDA regulates
almost every medical product it oversees.
In addition, the agency is preparing to enter into negotiations with the pharmaceutical and medical
device industries regarding user fees. Under various pieces of legislation—the Prescription Drug Use
Fee Act, the Medical Device User Fee Act, the Generic Drug User Fee Act and the Biosimilar User Fee
Act—FDA collects fees from pharmaceutical and medical device companies to help it hire more staff and
review new product applications more quickly. In return for that money, FDA is supposed to adhere to
specific timelines for reviewing products.
The negotiations, which notably do not involve Congress, are meant to ensure FDA gets sufficient
funding to make improvements, and that industry is assured its funding—which now makes up more
than half of all funding at FDA—is actually resulting in more efficient regulatory reviews.
Who's Next?
But even more important than what's next is the question of who's next.
Ostroff, who will serve as acting commissioner upon Hamburg's departure, is a relatively little-known
regulator outside FDA circles. As of January 2014, he was the chief medical officer of FDA's food
science division, the Center for Food Safety and Applied Nutrition (CFSAN), and an advisor to FDA's
Office of Foods and Veterinary Medicine.

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Given Congress' focus on medical products at the moment, legislators might instead push for someone
who is able to focus more on reforming and accelerating medical product approvals at FDA.
In a statement, Rep. Fred Upton, who is leading the House's effort to reform FDA, said he is looking
forward to leadership to "ensure we are firmly on the path to cures." Sen. Lamar Alexander, who is
leading the FDA reform effort from the Senate side, said he "hopes the president nominates an FDA
Commissioner who will work closely with Congress on finding ways to get safe medical treatments,
devices and drugs to patients more quickly."
Even Obama might be unlikely to appoint an FDA commissioner who is focused on the regulation of
food. As reported by Regulatory Focus last week, Obama has proposed stripping FDA of its authority to
regulate food products, which would instead be transferred to a new "Food Safety Administration."
So who might succeed Hamburg? If rampant speculation is any guide, the agency may already have
hired its next commissioner. Last month, FDA announced it had hired world-renowned
cardiologist Robert Califf to a top role within the agency: deputy commissioner for medical products and
tobacco.
Califf has been considered for the role of FDA commissioner on two separate occasions.
In appointing his next choice for FDA commissioner, Obama will also have to grapple with a Republican-
controlled House and Senate, both of which might complicate the confirmation process. Hamburg, in
contrast, was appointed when both chambers of Congress were overwhelmingly controlled by
Democrats.
CDSCO working to bring in new norms related to online medicine sales: Dr Jagashetty
Central Drugs Standards Control Organization (CDSCO) is now working to bring in new norms related to
online medicine sales that is being undertaken by scores of pharmacists across the country, Dr BR
Jagashetty, National Advisor, (Drugs Control), and project in-charge for the implementation of two
schemes of CDSCO, said.
Keeping pace with the information technology, internet and cell phones, pharmacy trade is seen to be at
the cusp of change as online drugs purchases come to the fore. Efforts are on to introduce new
standards of pharmaceutical sales in the Drugs and Cosmetics Rules, Dr Jagashetty told.
With the Medical Council of India‘s new norms on prescription format mandating doctors to indicate the
generic drug name along with an identical medication with the same dosage strength and form, also
calls for the need to revise Rule 65 in the present D&C Rules, he added.
With the advent of technology, there is need to update and formulate new set of laws to prevent
violations. We would also be insisting on doctor‘s registration number among other details to be
indicated to the online pharmacy transactions. This is the only way to create transparency, said Dr
Jagashetty.

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Through online pharmacy trade, chemists and druggists are looking to offer efficient customer service
and there is an increase in online prescriptions which are being scanned or typed and mailed to the
outlets‘ email IDs. The advantage here is that medicines are dispatched to the doorstep of the
consumers saving time and providing instant sales. The regulators need to arm themselves to scrutinize
the kind of drugs and its quality that are being sold by the pharmacy trade. There is need to keep a
watch if the drugs listed under Schedule H, H1 and X are sold with prescriptions.
The European Union in its Falsified Medicines Directive has mandated a common logo for legally
operating online pharmacies/retailers in the EU Member States as per its guideline 2011/62/EU.
Subsequently it implemented Regulation 699/2014 which mandated use of common logo to identify the
legally operating pharmacy retailers. The global regulatory authority viewed the usage of a common logo
one of its measures to fight against fake medications. The implementation of a common logo would
ensure technical, electronic and cryptographic requirements for verification of its authenticity of the
online pharmacy provider.
With Indian pharma reported to be third in volume, and 14th in value, there is need for a system to be
put in place to audit pharmacy outlets that offer online medicines in a bid to thwart illegal sale of
medicines and related products, pointed out Dr Jagashetty.
India may finally usher in pharma data protection
US President Barack Obama‘s recent visit to India has brought the focus back on data protection (DP)
and patent linkage (PL) — two areas where Washington, at the behest of Big Pharma, has for several
years been nudging the government here, albeit with little success.
With the government‘s change of stance, according to sources, the PMO and the department of
industrial policy and promotion are weighing the option, the easiest of the available, of telling the health
ministry to direct the central and state drug controllers to implement DP and PL. This doesn‘t involve
immediate changes in the relevant laws/rules, which, the sources said, could, however, be thought of
later.
Simply put, the move would mean patent holders could face much less threat from the country‘s nimble-
footed generic companies and enjoy their exclusive marketing rights peacefully and, maybe, for longer
periods.
Data protection, arguably a legal obligation on member nations that are signatories to the multilateral
TRIPS agreement, ensures non-reliance by the drug regulator (Drugs Controller General of India in
India‘s case) on test data of originator companies (usually patent holders) while approving same (bio-
equivalent) generic drugs of the second and subsequent applicants.
The idea is to avoid potential ―unfair commercial use‖ of the data of new chemical entities (NCEs),
created with much effort and at often at huge costs by conducting animal toxicity studies and human
trials.
Patent linkage would ensure patent controllers and drug regulators coordinate so that a generic versions
of a patented product are not approved by the latter during the term of a patent.
While NCE-related data submitted to DCGI for marketing approvals are not disclosed by the regulators

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to others even now, the regulator relies on the same for vetting bio-equivalent generic drugs, resulting in
huge savings for the generic companies and allowing them to launch generic versions as soon as
patents expire. If the regulator doesn‘t rely on the innovator data for approving generics, then entry of
generics could be delayed and be costlier. The generic companies allege that ―non-reliance‖ by the
regulator could give the patent holder the option of making incremental changes in the patented product
and extending the patent protection, a process called ever-greening of patents.
While a high-level committee had in 2007 recommended fixed-term Data Protection for five years (from
the date of filing for marketing) for NCEs with safeguards like an assurance that the DP won‘t exceed
the term of the patent, it never got implemented due to protest by domestic drug companies, NGOs and
sections within the government, including the health ministry. Data protection for agrochemicals was
however given.
The committee headed by Satwant Reddy, then secretary to government, had also said the government
could waive ‗data protection‘ norms in case of national emergency and if the protected product is priced
too high.
To buttress data protection (even now, various domestic laws allow Trade Secret form of protection, the
government needs to amend the Drugs and Cosmetics Act (DCA) to include fixed period data protection
with non-reliance clause. The sources, who wished not to be identified, said this was still perceived to be
a tough option, given the need for Parliamentary approval. The other option is to change the Rules
under the DCA through an executive order, but even here, it would require the health ministry to put up
the amendments for around 40-45 days in public domain for comments from stakeholders, they added.
Sources said prior to Obama‘s visit, the Big Pharma had met the then Indian Ambassador to the US
(current foreign secretary) S Jaishankar to represent their concerns on Indian IPR regime and their
demands on data protection and patent linkage.
Those who favour legally enforced DP argue that it would facilitate early entry of newer (patented)
medicines into the Indian market, project India as a country which encourages innovation and help
attract more FDI in drug manufacturing and research. The counter view is that it could be temporary
barrier for early entry of generics. Also, prices of the pioneer drugs could remain high during the period
of protection.
Fixed period of data protection is provided to pharmaceutical and agro-chemical NCEs by the US, WU,
Canada, China and Brazil, among other countries.
India had a few years ago provided data protection for agro-chemicals through an internal notification
that amended the Rules framed under the Insecticide Act.
Flaying the government‘s move on DP and PL, DG Shah, secretary general of Indian Pharmaceutical
Alliance (IPA) that comprises large domestic drug companies said that the PMO has erred on
committing to the US Trade Representative for changes in India‘s Intellectual Property regime, ―without
consulting the ministries dealing with the subject‖ and ―not disclosing to the nation the commitments
made‖ and ―miscalculating their impact on the economy at large and the public health in particular.‖

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According to Article 39.3 of the TRIPS Agreement, ―Members when requiring, as a condition of
approving the marketing of pharmaceutical or of agricultural chemical products which utilize new
chemical entities, the submission of undisclosed test or other data, the origination of which involves a
considerable effort, shall protect such data against unfair commercial use. In addition, Members shall
protect such data against disclosure, except where necessary to protect the public, or unless steps are
taken to ensure that the data are protected against unfair commercial use.‖
Japan Plans to Suspend Novartis From Doing Business in the Country
Japanese regulators have notified Novartis Pharma K.K., the Japanese arm of the Swiss drug giant, that
they are planning to temporarily suspend the firm from doing business in the country.
Novartis acknowledged receiving notice of the planned suspension, but declined to elaborate on the
reasons for it. Japanese media reports say the move by the government is punishment for the company
failing to report thousands of side effects associated with its drugs, and that the suspension will likely
last 15 days.
The proposed suspension must be approved by the health ministry, and the company will have an
opportunity to defend itself before it is imposed.
Novartis spokeswoman Julie Masow said the drugmaker will be able to handle the financial impact of the
suspension and is making plans to help its patients avoid any problems stemming from the interruption
of business.
Novartis‘ recent history in Japan has been shaky. Early last year, Japan‘s Ministry of Health, Labour and
Welfare filed charges against the company for using falsified clinical data to support marketing for blood
pressure drug Diovan (valsartan), marketed as Valturna in the U.S.
Shantha Constructs Insulin Facility in India
Shantha, a Sanofi Company, began construction of an insulin manufacturing facility near Hyderabad,
India, the company announced in a Jan. 29, 2015 press release. The facility is located in
Muppireddipalli, in the state of Telangana, and will help address local and international demand. Sanofi's
existing plant for its Insuman branded product is in Frankfurt, Germany. Sanofi will invest INR 460 crores
(nearly 75 million USD) in the facility in India, and the site should be fully operational by 2019.
―I am delighted that Sanofi has decided to manufacture Insuman insulin in Telangana state, so that it
helps the 65 million diabetics in India have better access to affordable insulin," said Honourable Chief
Minister Shri K Chandrashekar Rao, according to the press release. "We are shortly going to launch a
new industrial policy that will fast track projects and make Telangana one of the most favored
destinations, for investments, in the world.‖
―Laying the foundation stone for the Insuman insulin manufacturing site is an important milestone in our
journey, at Shantha, to improve public health in India," said Harish Iyer, CEO of Shantha Biotechnics, in
the press release. "For the first time, we will be able to manufacture insulin, in cartridges, here. The new
high technology facility will benefit from our existing biotechnology production expertise. This state-of-

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the-art facility will have the capability to ramp up manufacturing volumes to 60 million Insuman
cartridges per year, within two to three years of commercial manufacturing.‖
Sanofi Launches first Inhalable Insulin in the US
Sanofi announced on Feb. 3, 2015 that it launched FDA-approved Afrezza (insulin human) Inhalation
Powder, which is now available for prescription in US retail pharmacies for the treatment of type 1 and
type 2 diabetes. Afrezza is a rapidly absorbed, short-acting dry formulation of human insulin delivered
from a small and portable inhaler to control blood sugar in diabetes patients. Administered at the
beginning of a meal, Afrezza can help control high blood sugar, but should not be used in patients with
chronic lung disease such as COPD or asthma.
Mannkind Corporation developed Afrezza and can expect an upfront payment of $150 million, with
potential milestone payments up to $775 million, with 35% of future profits. The inhalable version will be
available for $7.54 per daily dose for 12 units, which is $4.40 (per dose or per unit?) more expensive
than Sanofi‘s injectable equivalent, Apidra (insulin glulisine [rDNA origin] injection), according
to Reuters. The company‘s press release lists one of the ―limitations of use‖ as the need to continue
long-acting insulin in combination with Afrezza for patients with type 1 diabetes, meaning the inhalable
product cannot replace other forms of insulin for some patients.
Sanofi‘s diabetes division is responsible for $7 billion in sales annually. In 2014, Sanofi noticed a drop in
sales for its diabetes treatment Lantus, contributing to CEO Chris Viehbacher‘s termination, according
to Forbes. To make matters worse, Reuters reports that the Lantus insulin patent is due to expire this
year, meaning Sanofi expects little to no sales growth through 2018. Introducing the first FDA-approved
inhalable insulin may up the game for Sanofi, securing its hold on the diabetes market.
However, Reuters continues by mentioning that industry analysts expect sales of only approximately
$182 million per year by 2019 given previous inhalable insulin commercialization attempts by Pfizer that
were unsuccessful.
Thermo Fisher Scientific Acquires Advanced Scientifics
Thermo Fisher Scientific Inc. announced on Feb. 5 that it has acquired Advanced Scientifics, Inc. (ASI),
a global provider of single-use technologies for customized bioprocessing solutions, for $300 million in
cash.
ASI designs, manufactures and delivers customized single-use systems and equipment for the
preparation, processing, storage and transportation of biopharmaceuticals. The company has 380
employees and operations in Pennsylvania and Mexico.
Advanced Scientifics had approximately $80 million in 2014 revenue and will be integrated into Thermo
Fisher‘s Life Sciences Solutions Segment.

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Cipla to build a manufacturing plant in Morocco with local partners
Cipla, which has been building beachheads and production capacity in hot spots where most Western
drugmakers are loath to go, will now create a joint venture in Morocco and build a drug manufacturing
facility there.
The Indian company said its U.K. subsidiary will invest $15 million in a JV with Societe Marocaine De
Cooperation Pharmaceutique (Cooper Pharma) and The Pharmaceutical Institute (PHI). Cipla describes
Cooper and PHI as the leading manufacturing companies in Morocco.
"This JV is aimed to strengthen Cipla's presence in Morocco, which is in-line with our global growth
strategy to build front-end presence in key markets," Saxena said."Morocco is an attractive
pharmaceutical market in the African continent," Cipla CEO Subhanu Saxena said in a statement. The
North African country is a constitutional monarchy with an elected parliament and is currently in conflict
with the Islamist group ISIS.
Cipla, Cooper and PHI have had a partnership for 10 years that has allowed Cipla to get established in
Morocco. The joint venture, in which Cipla will hold a 60% stake, will provide what the drugmaker calls a
"front-end presence in Morocco's pharmaceutical market" to sell its products. The JV will start with
respiratory and neurology products but will also build a manufacturing plant in the country to produce
Cipla meds. A spokesperson for Cipla said in an email Tuesday that the company is not yet in a place to
say how large of a plant will be built, or when that might begin.
Cipla is not the only drugmaker making inroads in Morocco. French drugmaker Sanofi has a presence
there, with a program to train health professionals. It followed that up in 2013 with a €20 million
investment to build a 12,000-square-meter logistics operation in Ain Sebâa, Casablanca, from which it
could better distribute its products.
The Morocco deal is one in a series in which Cipla has spread its influence in North Africa and the
Middle East. Last fall, it announced a deal with "its existing Iranian distributor establish a manufacturing
facility in Iran. There were no details, but Cipla reported it would contribute machinery, equipment and
technical know-how over the next three years, an investment it put at about $36.5 million. For that, it
said it will get a 75% ownership in the new operation. Several months earlier, it was a deal in Yemen, in
which it bought a 51% stake in a pharmaceuticals manufacturing and distribution business that it refused
to identify. It said it was paying $21 million up front and then making milestone payments over three
years if sales goals were hit.
China FDA orders respiratory API recalled after 'fur' like impurities found
The China FDA ordered Shandong Qidu Pharmaceutical to recall 21,700 bottles of an
injectable API combination for treating respiratory, urinary and reproductive infections. The agency said
impurities "similar to furs" were found in sampled bottles.
The recalled combination was levofloxacin and sodium, the CFDA said, and the head of the company
was "invited" for a talk, the official news agency, Xinhua, reported. The last name found as the CEO of
the company was Zheng JiaDing.

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The news service said the company, which calls itself one of the top suppliers of IV fluids in China, has
admitted it was negligent and took full responsibility for the problem. The combination drug was sold in
four of China's provinces.
Chinese pharmacies preparing for online sales of pharamceuticals
China Jo-Jo Drugstores, a leading China-based retail and wholesale distributor of pharmaceutical and
health care products through its own online and retail pharmacies, announced that it has entered into a
service agreement with Alibaba Health Information Technology to utilize the electronic prescription
platform in preparing for the upcoming authorization from the China Food and Drug Administration on
the online sales of prescription drugs in China.
Through Alibaba Health's recently launched mobile app, Alijk, patients are able to upload and send
photocopies of doctor's prescriptions to nearby pharmacies so as to check the availability of medicines,
compare the prices and eventually make the payments. Those qualified pharmacies partnering with
Alibaba Health, such as China Jo-Jo, can then fill the orders via in-store purchase or home delivery
service.
"We are very excited to team up with Alibaba Health to build a new future for ecommerce of
pharmaceutical products. Besides assembling a dedicated team to work with Alibaba Health, we have
also been actively focusing on procuring more products and building inventories, as well as recruiting
qualified physicians and licensed pharmacists," stated Li Qi, China Jo-Jo secretary and director. "As
more and more sales of prescription drugs will be shifted from hospitals to both online and offline
drugstores, all of these new initiatives are aim to capture new businesses."
According to industry statistics, the annual Chinese pharmaceutical sales exceeds one trillion RMB (or
$160 billion USD), and 80% of that are from sales of prescription drugs. Until now, the vast majority of
prescription drugs are controlled by state-owned hospitals that rely on pharmaceutical sales for profits.
With little or no competition, prescription drugs sold by these hospitals are overpriced, and doctors tend
to over prescribe. Chinese government, to reform its rigid health care system, is therefore adopting a
zero percent drug markup policy in hospitals and allowing online sales of prescription medicine. The
official policies for online sales of prescription drugs is expected to be released in 2015.
Sun Pharma Declines as Regulatory Issue Puts Pressure on Profit
Sun Pharmaceutical Industries Ltd., India‘s largest drugmaker, fell in Mumbai trading as quarterly profit
came under pressure from efforts to address regulatory issues at one of its factories. Sun Pharma fell as
much as 3.5 percent to 907.30 rupees in Mumbai today before trading at 915.25 rupees at 9:34 a.m.
local time, the biggest decliner on the benchmark S&P BSE Sensex Index. Net income in the three
months ended Dec. 31 fell 7 percent to 14.3 billion rupees ($230 million), the Mumbai-based company
said Saturday, missing the median estimate of 16.5 billion rupees from 31 analyst estimates compiled by
Bloomberg.

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Earnings were hurt by supply constraints arising from efforts to boost compliance at a drug factory in the
Indian city of Halol, the company said. The plant was inspected by the U.S. Food and Drug
Administration last year. Sun Pharma has to make changes to operating procedures and processes to
meet compliance expectations for the plant, Chairman Dilip Shanghvi said on a call with analysts.
―While we do this, the supplies of the facility will be constrained,‖ Shanghvi said. Sun expects to resolve
the constraints in the current quarter.
Ranbaxy Laboratory Ltd.‘s parent Daiichi Sankyo Co. in April agreed to sell its controlling stake in
Ranbaxy to Sun Pharma. The deal came after Tokyo-based Daiichi Sankyo had taken writedowns on
the Indian drugmaker, seen its own share price slide, and failed to raise manufacturing conditions at the
unit to levels that would pass muster with the FDA.
Since then, the FDA has rescinded approvals for two of Ranbaxy‘s products: generics of AstraZeneca
Plc‘s Nexium for heartburn and Roche Holding AG‘s Valcyte. Sun Pharma expects to meet its sales
guidance for the fiscal year ended in March.
Maharashtra has just one FDA officer for 1.35 lakh people
Food and Drug Administration is the only department directly related to the health of a common
man, and yet 31% of the posts in this department are vacant, reveals RTI query
As many as 365 posts of the total 1,176 sanctioned by the Maharashtra government in the Food and
Drug Administration (FDA) are vacant, a query filed under Right to Information (RTI) Act has revealed.
RTI activist Anil Galgali had sought information regarding the total posts that were allotted to FDA, along
with the ones occupied and the ones that have been left vacant.
"31% of the posts have been lying vacant. For a population of 11 crores of Maharashtra, 1,176 posts
that have been allotted for the FDA, only 811 posts have been occupied which means that against 1.35
lakh people, there is only one FDA officer in the state," he said.
According to Galgali, FDA was the only department that is directly related to the health of a common
man.
The headquarters of the department is in the Bandra Kurla Complex (BKC) area of Mumbai along with
divisions at Thane, Pune, Nashik, Aurangabad, Sangli, Satara, Nagpur and Latur comprising 31 districts
of Maharashtra.
In all these offices, only 265 posts of Food Security Officers (FSOs) and 161 posts of Drug Inspectors
have been sanctioned by the government. But 78 posts of FSOs and 37 of Drug Inspectors posts still lie
vacant, the RTI filed this year, revealed.
In the Food Department, 22 Joint Commissioners' posts lay vacant as compared to the 62 posts
sanctioned.

PHARMA UPTODAY
27
In the Drugs Department of the FDA, 13 out of 35 posts that of technical officers, four out of eight senior
Technical Officers, 22 out of 52 posts sanctioned for the Joint Commissioners, nine out of the 12 posts
that of the Administrative heads, 23 out of 60 posts that of Sample Assistants and two out of three Plant
Operators remain vacant, it further said.
GSK acquire vaccine biopharmaceutical company-GlycoVaxyn AG
GSK has acquired GlycoVaxyn AG, a specialist vaccine biopharmaceutical company based in
Switzerland and seems to stregthen their vaccine pipeline. Since forming a scientific collaboration in
2012, GSK has held a minority stake in GlycoVaxyn and has now acquired the remaining shares for US
$190 million (approximately £124 million) in cash to take full ownership of the company.
GlycoVaxyn has developed an innovative biological conjugation platform technology which has the
potential to play an important role in the development of new prophylactic and therapeutic vaccines for a
range of bacterial diseases. This proprietary technology also has the potential to enable GSK to develop
a simplified conjugate vaccine manufacturing process.
Under the terms of the transaction, GSK will additionally acquire a small number of early stage vaccines
in development against bacterial infections such as pneumonia, Pseudomonas, Staphylococcus aureus
and Shigellosis, supplementing the company‘s existing vaccines pipeline.
Dr Moncef Slaoui, Chairman of Vaccines, GSK said: ―This is an exciting opportunity to expand our
research efforts to develop a new generation of vaccines for common and severe bacterial infections, for
many of which there are currently no effective vaccines. It reinforces our commitment to seek out and
invest in great science and complements our proposed transaction with Novartis which will strengthen
our leading position in vaccines.‖
Philippe Dro, Chief Executive Officer of GlycoVaxyn, said: ―At GlycoVaxyn, we are delighted to be
working even more closely with one of the leading vaccine companies in the world on the development
of much needed vaccines.‖
GSK and the GlycoVaxyn management team are committed to an innovative collaboration and will work
together over the next few months to develop ways of working that will maintain the autonomy and agility
of GlycoVaxyn whilst delivering the scale and support that GSK can provide.
After last transaction, GSK has now purchased all shares in GlycoVaxyn, valuing the company at US
$212 million (approximately £139 million). GlycoVaxyn was supported by investments from life science
venture capital firms including Sofinnova Partners, Index Ventures and Edmond de Rothschild
Investment Partners. GlycoVaxyn also received funding from the Wellcome Trust and through a
collaboration with Janssen Pharmaceuticals.

PHARMA UPTODAY
28
Requirements for Risk Analyses in the Regulatory Submission Dossier: EMA's and FDA's
Recommendations
The EMA has published a new question & answer-(Q&A) paper together with the FDA at the end of
2014. This document answers questions on detailed requirements in connection with the documents
concerning regulatory submissions. Among other things it answers questions on the topic risk analysis.
To the question "What types of risk assessments can be included in a regulatory submission?" the
document provides a very pragmatic answer: It is up to the applicant himself to determine this. But it is
stated explicitly that this information can be useful to aid the assessor/reviewer for determining how the
applicant selected the specific formulation, manufacturing process and controls. The document mentions
that the Agencies have seen risk assessments that have been used for the selection of in-process
controls for example.
The question "What level of detail should be considered for a risk analysis related to process design in a
regulatory submission?" is answered more precisely in the document. In the beginning the answer is
rather general: The level of detail should be commensurate with the significance of the outcome of the
risk analysis to the commercial manufacturing process and to the control strategy. Taking the example
of a critical process step the document gives more concrete information. This information should contain
the following:
 A statement of which risk analysis tool was used. If a novel risk analysis tool was used, a
definition of this method along with an example of its use should be included.
 A comprehensive qualitative or quantitative summary of the outcome of the risk analysis (e.g. the
risk priority number).
 The threshold value for the risk priority number (and an explanation for why such a threshold was
chosen) leading to the selection of variables/parameters that warranted further study.
 A list of all risk priority numbers.
 Information on the way in which risk assessment activities were used to determine which process
parameters and quality attributes are to be considered critical or non-critical.
Interestingly, the document also contains a notice to the regulators themselves. These should take the
following into consideration before requesting additional details regarding a risk analysis: complexity of
the dosage form, the commonality of the risks identified relative to products of the same type, and the
amount of commercial scale manufacturing data available.
The answer to the question "What level of detail should be considered for a risk analysis related to
product design in a regulatory submission?" is similar to the answer to the question on process design:
The level of detail should depend on the risk presented by the formulation and dosage form. In the case
of the product design, however, the topic "misuse" should also be taken into consideration. As an
example a solid modified release oral formulation for an opioid is mentioned.

PHARMA UPTODAY
29
Supply Chain: A Series of new Regulations in Force
The new EU Directive 2011/62/EU and its delegated acts keep on changing the pharmaceutical supply
chain. The directive introduced numerous Delegated Acts with different time schedules and had some
impact on revisions of several chapters of the EU-GMP Guidelines.
Here is the status quo of the Directive and the delegated acts:
Already in 2011, the European Commission published Directive 2011/62/EC, the so called Falsified
Medicines Directive (or FMD).The main goal was the fight against counterfeit medicines. In 2014 the
technical characteristics of one key requirement were defined, the unique identifier delivering the
possibility of verification of the authenticity of single folding boxes. This will be a 2D barcode (data
matrix). As this new requirement will become active in 2018, it is time to start defining strategies for both
technical implementation and change control strategy.
The new EU GDP Guidelines have been effective since 2013 (2013/C343/01). These requirements
highlighted the need for an effective quality management system supported by risk assessment and
appropriate controls in the distribution chain.
The new GDP Guidelines apply not only to the wholesalers and manufacturers of pharmaceuticals; they
also incorporate the specific requirements for the Brokers dealing with pharmaceutical products. The
responsibility for the product during storage and distribution will remain with the manufacturers up to the
point of sale, where wholesale dealers will take ownership of the products. It is clear that those playing a
role in the pharmaceutical supply chain now have to comply with these requirements, therefore the
service providers such as transportation companies and logistic service providers need to gain good
understanding of what is required to be able to provide appropriate service to their clients.
In 2014, the Pharmaceutical Inspection Co-operation Scheme PIC/S has published a PIC/S Guide to
Good Distribution Practice for Medicinal Products (PE 011-1). This Guide is based on the EU GDP-
Guidelines (2013/C 343/01) and quotes the EU Guide almost completely.
However, EU specific references have been deleted and the term "must" is often replaced by the term
"should". A dedicated Responsible Person is not introduced by the PIC/S document. It talks about
"designated responsible person(s)" or "designated person(s)". Chapter 2.2 "Responsible person" of the
EU GDP Guide is not quoted in the PIC/S document.
GDPs for APIs are still on their way. The "Guidelines on the principles of good distribution practices for
active substances for medicinal products for human use" were published for consultation by the EU early
2013. The new guidelines address distribution organisations and distributors involved in procuring,
importing, exporting, holding or supplying active substances.
GMPs for APIs: Whereas for medicinal products a GMP Directive (Directive 2003/94/EG from 8
October 2003) and detailed guidelines (Part I of the EU GMP Guide) have been existing for many years,
there has been no equally binding act in all the EU members states for APIs. Only the detailed
guidelines as Part II of the EU GMP Guidelines are in place. This has now been caught up on. On 25
November 2014, the "Commission Delegated Regulation (EU) No 1252/2014" was published in the

PHARMA UPTODAY
30
Official Journal of the European Union. As the subtitle shows, this regulation is to be seen as
"supplementing Directive 2001/83/EC... with regard to principles and guidelines of good manufacturing
practice for active substances for medicinal products for human use".
Now, the set of rules for APIs is complete: the new regulation provides the necessary legal framework of
GMP principles for APIs; the long existing Part II of the EU GMP Guide delivers further concretisation of
these principles.
EMA has published a template for the QP's declaration concerning GMP compliance of the API used
as starting material and verification of its supply chain called "The QP declaration template":
The QP Declaration should be provided in support of an application for a new marketing authorisation,
variation or renewal of a medicinal product(s) authorised in the Community, using EU or national
procedures within the scope of the respective Directives.
With this document, the Qualified Person confirms that an API used in manufacture of a Medicinal
Product submitted for approval meets EU GMP standards. It includes all sites of full or partial
manufacture of the API and the confirmation has to be based upon an audit of the API manufacturer(s).
In 2013, hardly any other topic was as extensively discussed in the pharmaceutical environment as the
so called Written Confirmation (confirming the GMP compliance of an API / of the API manufacturer).
Since 2 July 2013, all APIs manufactured outside the EU have to be accompanied by a Written
Confirmation, issued by the Competent Authority of the exporting country. Without this confirmation
there is almost no possibility to import an API into the EU. However, one alternative to a Written
Confirmation is the admission to the list of "Third Countries" with comparable inspection standards.
Authorities from countries on that list do not have to issue Written Confirmations. Countries currently on
the list are Australia, Japan, Switzerland and the USA. Countries under assessment are Brazil, Israel,
Singapore and New Zealand.
Matrix compares old vs new EU GMP Guide Part I, Chapter 8 - effective as of 1 March 2015
Starting with the 1 March 2015 the revised EU GMP Guide Part I, Chapter 8 (Complaints, Quality
Defects and Product Recall) becomes effective (see also our GMP News from 23 September 2014).
Until then the version with the validity date 1 February 2006 is still applicable.
The following matrix provides you with a compact overview of the changes. It allows you to quickly
compare it with an existing QM system and can thus be used for a "GAP" analysis, a self inspection or
for audits.
EU GMP Guide Part I, Chapter 8
Version effective as of 1 March 2015
(new version)
EU GMP Guide Part I, Chapter 8
Version effective until 28 Feb. 2015
(old version)
Principles
(supplemented by:
- QRM requirements
- Reference to chapter 1
Principles

PHARMA UPTODAY
31
- Reference to competent authority
- Reference to chapter 7)
Personnel and Organisation -
8.1
(supplemented by:
- Independence of Marketing and sales
- Emphasizing Training)
8.1
8.2 -
8.3 -
8.4 -
Procedures for handling investigations of
complaints including quality defects
Complaints
8.5 8.2 (partly)
8.6
(supplemented by:
- Special focus on falsification)
8.7
8.7 -
8.8
(supplemented by:
- Focus on adverse event)
Comparable to 8.4
8.9
(supplemented by:
- Investigation procedures described in detail, e.g.
CAPA)
Comparable to 8.2
Investigation and decision making -
8.10
(supplemented by:
- QRM requirements
- QC not mentioned any longer)
8.3/8.5
8.11
(Rework not mentioned any longer)
8.4
8.12 Comparable to 8.6
8.13 -
8.14
(supplemented by:
- Early phases of investigation
- Decision making process
- Risk reducing actions)
Partly 8.5
8.15
(Counterfeits not mentioned)
8.7
Root Cause analysis and CAPA -
8.16 -
8.17 -
8.18
(supplemented by
Comparable to 8.6

PHARMA UPTODAY
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- CAPA and effectiveness monitoring and
assesment)
8.19
(supplemented by:
- Trending)
Comparable to 8.6
Product recalls and other potential risk reducing
measures
Recalls
8.20
(supplemented by:
- Risk reducing actions)
8.10
8.21 -
8.22
(supplemented by:
- Recalls prior to a root cause analysis)
8.11
8.23 8.13
8.24 -
8.25
(supplemented by:
- Scope of recall regarding the distribution network
- Missing recall due to short shelf-life products)
8.12
8.26
(supplemented by:
- Need for recall prior to information of authority
- Cooperation with competent authority)
8.12
8.27 -
8.28
(supplemented by:
- Details regarding Rework)
8.14
8.29 8.15
8.30
(supplemented by:
- Mock recall)
8.16
8.31 -
QRM: Quality Risk Management, QC: Quality Control, CAPA Corrective And Preventive Action
IPEC raises concerns over FDA guidance related to inactive ingredients
The International Pharmaceutical Excipients Council of the Americas (IPEC) is raising concerns
with the US FDA over ANDA (abbreviated new drug application) guidance related to excipients.
Based on the final Refuse-to-Receive (RTR) Standards Guidance for Industry related to ANDA
submissions, IPEC says that ―some information pertaining to inactive ingredients contradicts with
ongoing long standing work between IPEC- Americas and key stakeholders from the Office of Generic
Drugs Expert Working Group.‖

PHARMA UPTODAY
33
IPEC-Americas‘ comments point out the ―contradictory and ambiguous information contained in the
various FDA guidance documents,‖ which ―can only create confusion for excipient manufacturers and
ANDA sponsors.‖
More specifically, IPEC says it‘s concerned that the FDA ―has placed so much emphasis on current data
captured in the IID [the current FDA Inactive Ingredients Database] which contains a lot of inaccurate,
incomplete and missing information.‖ IPEC claims the database has not been updated since October
2013 and that the agency has yet to clarify data requirements for inactive ingredients that exceed the IID
level(s), which ―creates ambiguity for the industry.‖
The final guidance notes that if an inactive ingredient ―is determined to be a novel inactive ingredient for
the corresponding route of administration of the drug product (unless it is a physical mixture of
components found in the IID and within acceptable IID maximum levels), FDA will refuse-to-receive the
ANDA.‖
But IPEC says it‘s unclear to industry ―just how the Agency defines novel inactive ingredient (i.e. novel
excipients). Inactive ingredients with a long prior history of human exposure and safe use in related
applications should not be viewed the same as a new chemical entity (NCE) and these excipient should
not be subjected to an RTR.‖
IPEC also disagrees with the FDA that the use of an excipient that does not have precedence in the
same route of delivery should always be viewed as high risk and subject to ANDA refusal. ―Similarly,
coprocessed excipients where each ingredient may have precedence of use in the IID should not be
viewed as a novel excipient even though co-processed excipients are not simple physical mixtures of
excipients,‖ IPEC states.
Tox Studies
The council also takes a position on toxicology studies related to excipient DMFs (drug master files),
which seem to have been connected to some industry concerns recently. IPEC notes that the ―details of
these studies are considered confidential by excipient manufacturers and are not shared with their
customers.” However, summaries of the studies “have not sufficiently met OGD filing reviewers’
standards recently, as demonstrated by the increased number of Refuse to File letters (due to
insufficient safety data) received by pharmaceutical companies.
―It is our belief that if detailed study information already exists in the excipient DMF, then the FDA OGD
reviewer should be able to review a summary of safety study details along with a reference to the
specific DMF version and section where the full study report(s) can be found rather than asking the
sponsor to provide this information outside of the DMF system where confidentiality is no longer fully
protected,‖ IPEC says.

PHARMA UPTODAY
34
FDA Accepts Apotex's Neupogen Biosimilar Application: Raises Issues of How the Agency Will
Address Exclusivity, Previous Warning Letters to Apotex
Apotex Inc. has announced that as of February 13, 2015, the FDA has accepted for filing the company's
application for filgrastim, a biosimilar version of Amgen's Neupogen. The product was jointly developed
with Intas Pharmaceuticals Ltd. Filgrastim is used to help cancer patients taking chemotherapy to fight
infections and fever by boosting white blood cell count. This is the fifth application submitted through the
351(k) abbreviated approval pathway created by the Biosimilar Price Competition and Innovation Act
(BPCIA), and the second biosimilar submitted by Apotex.
This latest Neupogen biosimilar application is noteworthy for several reasons.
Sandoz’s Neupogen Biosimilar Application Has Already Been Accepted and Recommended by
FDA Advisory Committee
Apotex is a few months late with its Neupogen application on the 510(k) pathway. The FDA accepted
Sandoz‘ biosimilar application to Neupogen last year, and the biosimilar received unanimous support of
FDA‘s Oncologic Drugs Advisory Committee on January 7, 2015.
An important distinction, however, is that the term "interchangeability― is a higher standard than
biosimilarity, and indicates that the biosimilar may be substituted for the reference product without the
intervention of the health care provider who prescribed the reference product. Biosimilars can be
approved as stand-alone products, but the end goal of this biosimilar pathway is interchangeability--
recognition that the new product is essentially "equal" to the original biologic.
The problem is that FDA has not yet released guidance on interchangeability. Apotex‘s biosimilar
application for Neupogen highlights the need for such guidance because the biosimilar pathway
provides exclusivity periods for the first interchangeable biologic product:
(6) EXCLUSIVITY FOR FIRST INTERCHANGEABLE BIOLOGICAL PRODUCT.—Upon review of an
application submitted under this subsection relying on the same reference product for which a prior
biological product has received a determination of interchangeability for any condition of use, the
Secretary shall not make a determination…that the second or subsequent biological product is
interchangeable for any condition of use until the earlier of—
(A) 1 year after the first commercial marketing of the first interchangeable biosimilar biological product to
be approved as interchangeable for that reference product
If Sandoz's biosimilar for Neupogen is indeed approved and found to be interchangeable, what would be
the status of Apotex's product? FDA is planning to release interchangeability guidance later this year.
UPDATED, 2/19/2015, 5:45 pm: Sandoz has highlighted that its current application is for approval
of "EP2006" (their application name for the Neupogen biosimilar) as specifically a biosimilar and
not as an interchangeable biologic. Thus, we will have to wait to see the exclusivity issue play
out and also await future guidance by FDA on interchangeability

PHARMA UPTODAY
35
Looking abroad, it is perhaps unsurprising that Neupogen has multiple biosimilar potentials. Apotex is
one of nine manufacturers that have a filgrastim biosimilar product approved by the European Medicines
Agency, the regulatory body for approval of medicines in the European Unions. There have been 22
total biosimilars approved by EMA, so filgrastim makes up a large portion of available biosimilars
overseas.
View the full list of biosimilars approved in Europe online at GaBi, the Generics and Biosimilars
Initiative.
IPA suggests nine proposals to Union govt to be included in D&C Amendment Bill 2015
While the Union government is preparing for amendment of Drugs and Cosmetics Act and Rules, the
Indian Pharmaceutical Association (IPA) has submitted nine proposals to the department of health and
family welfare to be considered for inclusion in the Draft D&C Amendment Bill, 2015.
While the association puts major recommendations for the growth of Indian pharmacy profession and
public health, it is also concerned about the centralisation of regulatory power by the Union government.
It has said that the provisions proposed in the draft are aimed to centralise the power in the hands of the
Union government or the Central Licencing Authority (CLA) which will undermine the function of state
licencing authorities who have large and capable infrastructure.
IPA argues that the draft contains so many conflicting provisions which if not reviewed, would hinder the
growth of the pharma industry, especially the SMEs. Empowering only CLA to regulate medical devices
and clinical trials throughout the country will seriously hinder proper vigilance leading to significantly
poor compliance of regulatory mandates and ultimately hamper the consumer interests.
The recommendations sent by IPA general secretary, Kaushik Deshai, pointed out that some of the
proposals in the draft bill showed a marked deviation from the recommendation of Parliamentary
Standing Committee (79th report).
The association suggests that the definition of ‗new drug‘ should be in tune with Rule 122E of the Drugs
and Cosmetics Rules, where a specific period has been fixed for a new drug. If the period is not fixed, it
will encourage monopoly of the particular manufacturing company.
The draft replaces the terms ‗drug inspector‘ as ‗drug control officer‘. As per the Bill, the drugs control
officer authorised by CLA has been empowered to inspect any institution conducting clinical trials. He is
also empowered to initiate prosecution under Section 4T.
According to IPA, for effective regulation, state drugs control officers should also be given power in both
Section 4H and Section 4T.

PHARMA UPTODAY
36
While constituting Medical Devices Technical Advisory Board (MDTAB), one expert with pharmacy
education nominated by pharmacy council of India and one pharmacist from drugs control administration
should be included in the Board.
The state licencing authorities should also be empowered to issue licence for manufacture or sale or
distribution or marketing of any medical device. The power should not be vested exclusively with the
Central Licencing Authority, IPA wants.
Robyn Urback: Why is Health Canada still approving make-believe ‘homeopathic vaccines’?
If I were of a more entrepreneurial spirit, I would develop, patent and seek Health Canada approval for
my own particular version of a childhood vaccination. I‘d call it a ―quadrivalent‖ inoculation, effective in
preventing nearly all illnesses that infiltrate the body and spirit, and it would be available for sale by
anyone who considers himself or herself a medical practitioner. Without divulging too many of the
vaccine‘s secrets, I will say that it will be one part borage seeds, one part that special feeling in your
heart, and administered by plucking your thumb against the inside of your cheek and making a popping
sound with your mouth.
This vaccine, the name of which I‘m still working on, would have roughly the same efficacy rate as the
homeopathic vaccines that are currently approved for sale by Health Canada. These homeopathic
vaccines, also known as ―nosodes,‖ are created by taking a small amount of infected material — saliva,
blood, feces for example — and diluting it to the point wherein there is basically no active ingredient left.
The vaccine is then administered to the patient — often in the form of a sugar pill — after which the
individual is said to be protected from measles, mumps, meningitis, polio and more. The belief is that the
nosodes will somehow catalyze an autoimmune response when and if the body ever encounters these
viruses, and act by harnessing the power of make-believe and that aforementioned special feeling in all
of our hearts.
Health Canada has approved for sale around 150 different types of nosodes, though they are not
supposed to be marketed as replacements for conventional vaccines. In fact, packages of homeopathic
vaccines must be labelled with a disclaimer saying the product is ―not intended as an alternative to
vaccination.‖ That disclaimer is nevertheless ignored by plenty of homeopaths and naturopaths across
Canada, as chronicled recently by The Globe and Mail; Little Mountain Homeopathy in Vancouver, for
example, claims on its website that homeopathic vaccines are ―are just as effective or even more
effective than regular vaccines.‖ There are decades worth of medical literature that would dispute that
statement, but Little Mountain can keep selling its magic pills anyway, just as long as it keeps the
disclaimer sticker on the label.
Government of India to come with plans to improve bulk drug manufacturing capacities
The government will shortly come out with strategies to improve bulk drug manufacturing capacity in
India in order to reduce dependence on China for import of bulk drugs.

Pharma Uptoday Monthly Magazine Volume 12; Issue Mar 2015

Pharma Uptoday Monthly Magazine Volume 12; Issue Mar 2015

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Pharma Uptoday Monthly Magazine Volume 12; Issue Mar 2015