market landscape: sourcing, partnering, …€¦ · — market landscape: sourcing, partnering, and...

— MARKET LANDSCAPE: SOURCING, PARTNERING, AND COMPLIANCE IN 2016A special report from CPhI and Newport™, Cortellis™ and Bioworld™.

TABLE OF CONTENTSWELCOME TO CPHI WORLDWIDE! 3

GPHA SHINES LIGHT ON SHADY REMS AND DISTRIBUTION PRACTICES 4

CADILA WARNED FOR GMP FAILURES 5

INSECTS LEAD TO RECALL 6

INDUSTRY TO INDIAN GOVERNMENT: BULK UP ON API CAPABILITIES 7

U.K.’S NHS WIDENS BIOSIMILARS USE PLANS 10

BRAZILIAN PHARMA REGISTERS FIRST API BASED ON BIODIVERSITY 13

TACKLING COUNTERFEIT DRUGS, INDIA BOLSTERS TRACK-AND-TRACE EFFORTS 15

CHALLENGES IN IMPLEMENTATION 15

CFDA ZEROES IN ON QUALITY, BUT CONDUCTED FEWER GMP INSPECTIONS IN CHINA 18

ACTIVITY, OPPORTUNITY PICKING UP FOR JAPAN’S BIOSIMILAR MARKET 21

KOREA’S HANMI INVESTS $200M IN CHINA-BASED MANUFACTURING PLANT 24

ADVICE FOR BIOPHARMAS IN CHINA? MIND THE GAP 26

CLEAR CONSTRAINTS 26

EMCURE’S WARNING LETTER HIGHLIGHTS ONGOING DATA INTEGRITY ISSUES IN INDIA 28

‘WE DO HAVE A QUALITY PROBLEM’ 28

PERU’S PHARMA GUILD EVALUATES GUIDELINES FOR BIOSIMILARS 31

ABOUT THE PRODUCT 33

WELCOME TO CPHI WORLDWIDE!CPhI, the global pharma platform, is pleased to join forces with Newport™, Cortellis™ and BioWorld™, leading sources of intelligent information for pharma professionals around the world, on this co-branded special report, Market Landscape: Sourcing, Partnering, and Compliance in 2016. The report was developed from a series of articles over the course of the year on CPhI themes written for BioWorld Today, the global biopharma news service.

CPhI and Newport, Cortellis and BioWorld believe that through knowledge-sharing our industry develops as a whole, opportunities arise and new horizons are uncovered. We see this report as a great way to kick off the conference, along with its exciting co-located events, ICSE, InnoPack, P-MEC and FDF. Articles in Market Landscape: Sourcing, Partnering, and Compliance in 2016 focus on manufacturing and distribution practices, generics finished dose trends, biosimilars strategies, API capabilities, business development and more. The stories were written from eight different countries.

This report is part of a continuing collaborative effort between CPhI and Newport, Cortellis and BioWorld. Join us on this learning journey as all together we drive the industry forward.

MARKET LANDSCAPE: SOURCING, PARTNERING, AND COMPLIANCE IN 2016 PAGE 4

GPHA SHINES LIGHT ON SHADY REMS AND DISTRIBUTION PRACTICESTaking advantage of the spotlight of public ire over escalating drug prices, generic drugmakers have joined forces with pharmacists and others to illuminate, and end, what they consider a shady practice to protect brand therapies from follow-on competition.

The Generic Pharmaceutical Association (GPhA) and 10 other groups, including Express Scripts and the Academy of Managed Care Pharmacy, are urging the U.S. Senate Special Committee on Aging to support The Fair Access for Safe and Timely (FAST) Generics Act, H.R. 2841, to prevent brand drugmakers from using risk evaluation and mitigation strategies (REMS) to deny generic and biosimilar sponsors access to drugs for development purposes.

The problem extends beyond REMS, the organiza-tions said in a recent letter to the Senate commit-tee, which held a hearing last month to scrutinize a recent spate of over-the-top price hikes for off-patent small-molecule drugs. In addition to REMS, “brand firms are using restricted distribution networks to deny manufacturers of generics and biosimilars access to product samples they need to obtain FDA approval and market entry,” according to the letter. (See BioWorld Today, Dec. 11, 2015.)

“These abuses are growing, and the resulting delay in generic and biosimilar competition is costing patients, the federal government and the health care system billions of dollars annually,” the letter continued.

The FAST Generics Act, which failed to see the congressional light of day when it was introduced in 2014, addresses the misuse of REMS and restricted access programs by closing loopholes and making access to competitors a condition of drug approval and biologic licensure. Brand companies violating the act could be subject to antitrust lawsuits with treble damages.

The bipartisan legislation was re-introduced in the House in June and sent to Energy and Commerce’s Subcommittee on Health just as that subcommittee was finalizing the 21st Century Cures Act, with a focus on encouraging and speeding biopharma innovation. As a result, the FAST Generics Act once again languished in the shadows.

But growing congressional and public disgust with inexplicable price hikes for older, off-patent drugs could light the way for approval of the act. In pushing for passage of the FAST Generics Act, the GPhA letter raised the specter of Martin Shkreli, the former CEO of Turing Pharmaceuticals AG, who stepped into the public limelight when his company bought Daraprim (pyrimethamine), a 62-year-old anti-parasitic drug, and promptly jacked the price nearly 5,500 percent and restricted access. (See BioWorld Today, Sept. 23, 2015.)

The letter noted that when Shkreli was asked if he would approve a sale to a generic manufacturer, he responded that he would probably block it. While acknowledging that generic competition

Generic drugmakers have joined forces with pharmacists and others to illuminate, and end, what they consider a shady practice to protect brand therapies from follow-on competition.

Mari Serebov BioWorld

Regulatory Editor


was inevitable, Shkreli said he wasn’t going to do anything to make it easier for Turing’s competitors.

In light of such tactics, “any policymaker seeking ways to lower health costs should consider increasing competition from generic drugs by embracing measures such as the FAST Generics Act,” GPhA President and CEO Chip Davis said this week.

GPhA also is using the intense scrutiny of drug pricing to push for congressional action on other measures, such as:

• Ensuring that the FDA has the resources necessary to handle a backlog of more than 3,800 generic drug applications and to shorten the median generic drug approval times, which currently stand at 48 months—compared with 10 months for standard review of a new drug or biosimilar

• Increasing the use of generic drugs among low-income Medicare and Medicaid populations

• Ensuring that the framework for biosimilars expands and expedites patient access

GPhA also is trying to link a provision of the 2015 Bipartisan Budget Act to the pricing debate, urging its repeal. That section subjects generics to a heftier Medicaid rebate if their price hikes exceed the rate of inflation. Brand drugs already face that consequence. The possibility of an increased rebate for generic drugs “is bad for Medicaid and its beneficiaries, bad for taxpayers, and it should be immediately repealed,” GPhA said.

CADILA WARNED FOR GMP FAILURES

After nearly a year and a half of back and forth with the FDA over good manufacturing practice (GMP) shortcomings at two of its plants in India, Cadila Healthcare Ltd. was hit with a warning letter citing “significant” violations at the facilities.

The Dec. 23 letter, which was posted to the FDA warning letter database Tuesday, cited recurring quality problems with warfarin sodium tablets produced at Cadila’s formulation plant in Moraiya. The company recalled one lot of warfarin tablets in May 2013 because of a failed assay and oversized tablets. Similar out-of-specification issues were noted in inspections later that year and again in 2014.

Following the second inspection, Cadila temporar-ily suspended the manufacture of all strengths of the tablets in September 2014. Two months later, manufacturing resumed after new protocols were implemented. However, the company acknowledged this past June that subsequent lots had failed potency and content uniformity specification tests, the FDA said.

Another problem at the Moraiya facility involved the handling and investigation of complaints from pharmacies and distributors concerning product mix-ups. While Cadila documented that some of the mixed-up drugs were manufactured on adjacent equipment lines, the company didn’t complete a root-cause analysis and failed to file field alert reports with the FDA in eight of nine instances.

“Any policymaker seeking ways to lower health costs should consider increasing competition from generic drugs by embracing measures such as the FAST Generics Act.”— Chip Davis

President and CEO, GPhA


The FDA cited the second facility, an API plant in Zyline, for not identifying the root cause of failed compound analysis results for four API batches and then reprocessing the failed batches without scientific justification. Other violations included failure to restrict access to computerized systems to prevent unauthorized use or deletion of data and to ensure the timely recording of quality-related activities.

For instance, FDA investigators found an “unofficial” notebook in the engineering office and several plastic bags filled with paperwork in the scrapyard. One item in the trash was a torn notebook of deficiencies. But those deviations weren’t indicated in the batch record.

When Cadila informed the Bombay Stock Exchange of the warning letter Dec. 31, it clarified that the API facility had no products in the U.S. market. It also committed to resolve all the issues

and make the revamp of its quality systems and processes its “top most priority.”

INSECTS LEAD TO RECALL

Baxter International Inc., of Deerfield, Ill., voluntarily recalled two lots of intravenous solutions after customers complained about insects in the plastic containers.

The customers spotted the insects before using the products, and no adverse events associated with the contamination have been reported to date, according to the company.

The recall involves 0.9 percent sodium chloride injection, used as a source of water and electrolytes and also as a priming solution in hemodialysis procedures, and 70 percent dextrose injection, indicated as a source of calories and water for hydration.

BioWorld Today | January 6, 2016

When Cadila informed the Bombay Stock Exchange of the warning letter Dec. 31, it clarified that the API facility had no products in the U.S. market.


INDUSTRY TO INDIAN GOVERNMENT: BULK UP ON API CAPABILITIES India’s dependence on China for pharmaceutical raw materials is threatening the country’s health care industry and pushing the government to take action.

India’s imports of active pharmaceutical ingredients (API) or bulk drugs from China reached $2.22 billion in 2015, or 5 percent up from the previous year, according to the latest statistics from the Indian Parliament. India produces a third of the world’s medicines, mostly in the form of generic drugs, with 300 large companies and more than 10,000 medium and small-scale companies in the sector. However, only less than one-fourth of them are producing APIs, while the majority—about 77 percent—make formulations.

“Many of India’s APIs and intermediates manufacturing plants have shut down,” said Ramesh Adige, a pharma expert who was formerly an executive director at Ranbaxy Laboratories Ltd., an Indian multinational pharmaceutical company. “China has emerged as the dominant player in the global API industry due to its large-scale manufacturing capabilities of APIs and intermediates. Chinese imports are cheaper and highly subsidized by the Chinese government.”

A study by the Boston Consulting Group and the Confederation of Indian Industry (CII) said the total imports of APIs and advanced intermediates grew at a compound annual growth rate (CAGR) of 18 percent from $800 million in 2004 to $3.4 billion in 2013. And among all the imports, made-in-China pharmaceutical products accounted for more than 80 percent.

The high dependence is a result of price competitiveness attributed to Chinese bulk drugs. China’s raw materials are relatively cheap; the small profit margin prevents India local manufacturers from competing.

Although the operation cost of local drugmakers goes down by using cheaper imported raw materials from China, importing from a single country means that India put all the bets on China’s bulk drugs. In other words, if anything endangers the APIs production in China, it will most likely bring the drug manufacturing in India to a halt, putting the health of 1.3 billion people at risk.

“A glimpse of just what could go wrong was evident during [the] Beijing Olympics 2008, when China closed down many of its API plants to cut environmental pollution,” said Adige. “This led to an immediate price rise of around 20 percent in some bulk drugs, which were being sourced, solely from China. We had no alternative since China has a near monopoly in several APIs.”

The disadvantageous position of Indian pharma companies causes outcries among the industry, calling for the government to take immediate action. “India should match the incentives which China gives to its API manufacturing units with fiscal support, monetary interventions such as low interest regime, subsidy for effluent treatment plants, setting up of large API manufacturing parks and special economic zones,” said Adige. “Public health is paramount, and budgetary support for this initiative should be provided. Profit motive should not be the only driving force.”

Although the operation cost of local drugmakers goes down by using cheaper imported raw materials from China, importing from a single country means that India put all the bets on China’s bulk drugs.

Pearl Liu BioWorld Staff Writer

“If anything endangers the APIs production in China, it will most likely bring the drug manufacturing in India

to a halt, putting the health of 1.3 billion people at risk.”


Speaking at an annual conference of pharmaceuticals and medical devices in New Delhi last December, India Minister for Chemicals and Fertilizers Ananth Kumar said the government would set up parks for bulk drugs, pharmaceuticals and medical devices, offering affordable and unencumbered land and common facilities to reduce manufacturing costs by almost a third.

The government also constituted a committee headed by former Health Secretary, VM Katoch, to outline a framework for bulk drug manufacturing. “The committee has since submitted its recommendations. After examining the recommendations, the government is now looking into the financial viability of supporting the proposal for providing assistance for common minimum facilities for three greenfield bulk drugs and API parks to the extent of INR2 billion [US$30 million] each,” said an official from the Ministry of Chemicals and Fertilizers.

The policy is warmly welcomed by the industry, but the real challenge is the timely implementation. “The government of India has realized that the situation will have national security implications. Health security is crucial to any nation,” said Adige. “This subject has been discussed by the government at the highest level over the last four years. We now need to roll out a policy quickly.

“India’s public sector units in the area of API manufacturing should also be encouraged and funded for making advanced intermediates such as erythromycin thiocyanate, 7-ACA (7-aminocephalosporanic acid), penicillin used in manufacturing antibiotics, OTBN (2-Cyano-4’-methylbiphenyl) used in manufacturing anti hypertensives.”

The country’s pharmaceutical sector was worth $6 billion in 2005 and $18 billion in 2012, and is expected to touch $45 billion by 2020, according to a study by Mckinsey.

BioWorld Today | May 11, 2016

“The government would set up parks for bulk drugs, pharmaceuticals and medical devices, offering affordable and unencumbered land and common facilities to reduce manufacturing costs by almost a third.”— Ananth Kumar

Minister for Chemicals and Fertilizers, India


U.K.’S NHS WIDENS BIOSIMILARS USE PLANS The U.K. is expanding the scope of its biosimilars adoption program as experience of using them grows, more products come onto the market and use begins to expand beyond hospital settings and into primary care.

Increased competition in the biologics market presents a significant opportunity for the National Health Service (NHS), according to Keith Ridge, chief pharmaceutical officer, who is spearheading the national implementation program.

“The financial headroom generated from competition between originator biological medicines and biosimilar medicines can support treatment and care of an increasing number of patients,” Ridge said. “It is important that the NHS makes the most of this.”

That calls for investment in education, disseminating experience in the use of biosimilars to date, establishing appropriate procurement and creating decision-making frameworks.

A report published last month discusses the state of play and sets out work that is required to further develop and drive forward with implementation.

Drawing on inputs from the industry, patient representatives and those responsible for commissioning biologics at a local level, the report looks at how to address the increasing complexity, in terms of the greater number of products and the increasing number of NHS staff who will be involved in their procurement, commissioning and administration.

Issues considered in the report include the potential for multiple switching from one

biosimilar to another; what structures are needed for products coming down the pipeline that are for use in primary care or self-administration; mechanisms for sharing the benefits of cost savings generated by increased competition; the resources required to administer programs of switching from innovator biologics to biosimilars; patient and clinician education; and pharmacovigilance.

“In this rapidly developing area, it is essential we continue to review the emerging evidence and carefully consider the implications of future developments, such as the increasing complexity of the [biologics] market, as the number of available products grows,” said Ridge.

After consulting the grass roots, the National Biosimilars Group, a body that includes the National Institute for Health and care Excellence (NICE), the Medicines and Healthcare products Regulatory Agency, NHS commissioning bodies, pharmacists, patient organizations and the industry, will oversee delivery of a program of work intended to ensure the appropriate use of biosimilars.

That will put in place a standard framework and tools to support local decision-makers, with the aim of avoiding duplication of effort and promoting uptake of biosimilars across the country.

Currently, the U.K. lags behind other countries in Europe in adoption, according to the British Biosimilars Association, an industry body set up in April to increase the use of biosimilars. (See BioWorld Today, April 19, 2016.)

Nuala Moran BioWorld Staff Writer

To date, seven biosimilars—somatropin, follitropin alfa, filgrastim, infliximab, epoetin alfa, insulin glargine and etanercept—have made it to market in the U.K. following the first approval of a biosimilar product 10 years ago.

“NHS guidelines published in August 2015 specified that biosimilars be

prescribed by brand name and banned substitution at a pharmacy level.”


To date, seven biosimilars—somatropin, follitropin alfa, filgrastim, infliximab, epoetin alfa, insulin glargine and etanercept—have made it to market in the U.K. following the first approval of a biosimilar product 10 years ago.

Biosimilar versions of Herceptin (trastuzumab), Mabthera (rituximab), Humira (adalimumab), Avastin (bevacizumab) and Neulasta (pegfilgrastim) are expected to be available over the next few years. A further 50 biosimilars are in development.

Adoption of biosimilars in the U.K. is framed by another initiative—in medicines optimization—which was established to address the fact that up to 50 percent of drugs are not taken as the prescriber intended. The goal is to support patients to take medication correctly, improving outcomes, cutting wastage and reducing adverse reactions.

Ridge said a patient-centered, outcomes-based and value-driven approach will help ensure safe, effective and consistent use of biosimilars and a sustainable market for biologics.

However, it is recognized that such an approach could limit or delay access if every patient has to be engaged in the development of a biosimilar switch program. Given this, the national implementation plan will set out guidelines on how to involve patient representatives in local decision-making; what considerations prescribers should bear in mind in assessing whether to switch patients; and how to gather feedback on patient experience to inform future switch programs.

“This kind of approach would support a holistic view of patient support across the country and help identify best practice,” the report noted.

In addition, more needs to be done to ensure the cost savings generated by increased competition lead to better patient access. The national plan should include model “gain-sharing” agreements for how benefits are distributed.

Some of the value should be transferred back to departments implementing switch programs. Savings also should be reinvested in biosimilars to ensure the market is sustainable.

Collecting data to show use of biosimilars improves patient access to biologic drugs would be a motivating factor, encouraging clinicians to support switch programs.

The lower cost of biosimilars will have an impact on NICE’s formula for assessing the cost-effectiveness of drugs, with the result that a biosimilar may be deemed cost-effective when an innovator was not.

For example, the lower cost of biosimilars for treating rheumatoid arthritis could shift the opportunity cost profile, allowing patients with less severe disease to be treated with an antibody rather than steroids.

The report said, “NICE should update its recommendations on the basis of changing prices.”

Increased adoption of biosimilars also creates a requirement to update and enforce adverse event reporting. In the U.K. the convention is to use international non-proprietary names in prescribing, raising the possibility of inaccurate attribution of an adverse event and unintended substitution at dispensing.

NHS guidelines published in August 2015 specified that biosimilars be prescribed by brand name and banned substitution at a pharmacy level. Doctors can only switch patients from one biologic to another if a monitoring program is in place. (See BioWorld Today, Aug. 14, 2015.)

However, retraining and a cultural shift are required to ensure these things happen in practice. The report recommends moves to improve clinicians’ awareness of the importance of recording the brand name and the batch number for monitoring adverse reactions.

BioWorld Today | August 9, 2016


BRAZILIAN PHARMA REGISTERS FIRST API BASED ON BIODIVERSITY A Brazilian pharma company based in Itapira, Sao Paulo, has obtained the very first biodiversity-based registration from Anvisa of a biological active pharmaceutical ingredient (API). Cristália’s API is an enzyme called collagenase Cristalia, used in ointments to treat wounds, burns and necrotic tissue. To date, Brazil has had to rely on imports of collagenase.

“Cristália’s collagenase represented the first biological API and finished product registration granted by Anvisa, 100 percent manufactured in Brazil and obtained from a Clostridial strain isolated from Brazilian biodiversity,” Marcos Alegria, director of biotechnology at Cristália, told BioWorld Today. “The manufacturing process applies an innovative medium, animal component free, and yields a superior collagenase with high quality and purity.”

It has been a long road for the Brazilian company to introduce its API to the market. The strain was discovered years ago on a farm in the state of Sao Paulo. In 2012 the company filed for patents in Brazil, Europe and the U.S.

“Further submissions, in order to include a wider range of countries and technologies are under analysis,” said Alegria.

With the registration of its enzyme, the company aims to expand its presence not only in Brazil but also in global markets.

“Cristália has a leadership position in the Brazilian market of collagenase, over 60 percent, formulated as an ointment and currently the company is expanding the boundaries of this special product to other territories as the U.S., Europe, Latin America and Asia,” said Alegria.

“Since the brand new manufacturing process of this API was established, Cristália is discussing potential partnerships to introduce its collagenase in several countries,” he said. “The goal is to design targeted regulatory and marketing strategies in each territory in order to take an import share of these markets.”

According to Cristália, the size of the world market for these products has grown at a pace of 7 percent per year during the past three years.

“The potential market for API collagenase as a debridement agent on necrotic tissue is focused on ointments to treat many types of wounds, including chronic dermal ulcers, such as pressure, diabetic and venous ulcers, and burned areas,” said Alegria.

“Besides that, collagenase is used in injectable products to treat niche diseases such as Dupuytren’s contractures and Peyronie´s disease. In addition, collagenase is widely applied in tissue dissociation, which has proven to be a sharply growing market given the cell therapy development.”

The company expects significant growth due to the broad application of collagenase in different therapeutic areas.

“Currently, new formulations, associations, and dosage forms are also under development, aiming to increase our reach in several therapies,” said Alegria.

The company spent about eight months getting the necessary approvals to access Brazil’s biodiversity; a bureaucratic barrier that is limiting life sciences sector from accessing the almost

Sergio Held BioWorld Staff Writer

“The size of the world market for these products has grown at a pace of 7 percent per year during the past three years.”— Marcos Allegria

Director of Biotechnology, Cristália


unlimited quantity of material available in the region’s forests and jungles. Nearby Colombia have similar restrictions. (See BioWorld Today, Oct. 20, 2015.)

In 2015, Brazil introduced a policy to speed up the process to access and manipulate biodiversity.

“Currently, the new law replaces the authorization of access to genetic resources by an electronic registration, which simplifies the process and stimulates local R&D,” said Alegria.

The company has built a collagenase manufacturing facility that can supply local and foreign markets. It invested about R$120 million (US$34.4 million) in research and development.

“The innovative production process of collagenase, besides being animal component-free, generates an API with high collagenolytic activity, high purity grade and a remarkable manufacturing yield, which opens new perspectives, such as tissue dissociation, a sharply growing market (linked to) cell therapy development,” said Alegria.

In 2014, Anvisa issued a good manufacturing practices certificate that allows the Brazilian lab to produce biosimilars at its Itapira facility, so the company has been expanding its portfolio of products.

“Cristália’s biotechnology has also aimed at biosimilar development, such as human growth hormone, trastuzumab and etanercept,” said Alegria.

Those products are in the clinical trial phase in Brazil and overseas. At its R&D facility, the company also isolated more than 2,000 microorganisms, including rare and new species, from which a “broad spectrum of extracts were produced, submitted to in vitro assays and characterization, showing a variety of novel molecules, exhibiting antimicrobial, antifungal, antitumor and antiviral properties,” said Alegria.

To produce the Collagenase Cristalia enzyme, Cristália had to comply with several steps to access and manipulate Brazilian biodiversity.

BioWorld Today | June 23, 2016

The company has built a collagenase manufacturing facility that can supply local and foreign markets. It invested about R$120 million (US$34.4 million) in research and development.


TACKLING COUNTERFEIT DRUGS, INDIA BOLSTERS TRACK-AND-TRACE EFFORTS India is strengthening its ‘track and trace’ system for drugs by making it mandatory to put online information about barcodes on the packing of drugs being exported.

The new rules took effect at the end of April for large companies and starting April 2017 for small and medium companies (SMEs).

Indian companies already use barcodes in secondary packaging, the packaging outside the primary material containing the drug such as the cartons in which ampules are distributed. Barcodes are also used in tertiary packaging, the packaging for handling bulk merchandising in storehouses.

India’s Central Drugs Standard Control Organisation (CDSCO) has now made it mandatory for companies to feed the information on secondary and tertiary packaging into an online portal called the Drug Authentication and Verification Application, a senior official of the Indian Drug manufacturers’ Association (IDMA) explained.

In a notification in March, the CDSCO also clarified that no separate Indian barcode would be required for exporters who prefer to avail of the option to print their barcodes in the format specified by the governments of the importing countries and that have obtained a waiver from the Drug Controller General of India (DCGI).

The notification also noted that since the DCGI does not have the necessary mechanism to verify whether the exporting firm has actually printed its barcodes according to the specifications of the importing country, it would be more appropriate if the exemptions are issued by the Directorate General of Foreign Trade.

In a parallel track, India’s Ministry of Health and Family Welfare is finalizing an initial draft notification issued in 2015 for barcoding requirements for drugs sold in the domestic market.

“Most of the large companies have either implemented or are in the final stages of implementation. SMEs are still in the stage of planning out strategies for its implementation,” Kaushik Desai, honorary general secretary of the Indian Pharmaceutical Association (IPA), told BioWorld Today. “The discussion with all stakeholders on implementation has been ongoing

since more than three years. Government has also carried out training programs through Pharmexcil [Pharmaceuticals Export Promotion Council of India] for smooth implementation.”

Pharma industry associations such as the IDMA and IPA welcomed the move, saying it could help tackle the problem of counterfeit drugs, especially those made outside India but with fake Indian labels.

Desai, who is also an associate executive committee member of the Industrial Pharmacy Section, Federation of International Pharmaceutical Associations, said “counterfeiting of drugs is a global issue and many . . . times Asian countries are targeted for such supplies. The implementation of track-and-trace technology would bring India on par with global requirements and would support in enhancing the image of India in delivery of quality medicines.

“The initiative by the Indian government is most welcome in monitoring the export of medicines since Indian companies are following the requirements of importing countries and Indian regulatory norms normally monitor the quality of domestic supply,” he added. “There are minimum rules governing exports. This move by government will help in controlling the movement of counterfeit drugs in the global market.”

CHALLENGES IN IMPLEMENTATION

Globally, the U.S. FDA has also beefed up its surveillance on counterfeit, contaminated and banned drugs, via a guidance on Drug Supply Security Act of 2013. Its track-and-trace norms will be enforced in phases starting from 2017, Desai pointed out.

The EMA and European Union (EU) also recently published new track-and-trace safety requirements. Their rules, which take effect in February 2019, mandate that manufacturers include a barcode that is a unique identification encryption and an anti-tampering device in the packaging of most medicines.

“India would be one of the fast emerging countries in implementation of track-and-trace technology in line with global regulatory requirements,” Desai added.

T.V. Padma BioWorld Staff Writer

“India is strengthening its ‘track and trace’ system for drugs by making it mandatory to put online information

about barcodes on the packing of drugs being exported.”


However, Indian drug companies still face challenges. Under the procedure for implementation of the track-and-trace system for export of drug formulations, companies have to print the barcode as per GS1 global standard at different packaging levels to facilitate tracking and tracing of their products. For the primary level, the companies will need to incorporate a 2D barcode with a unique and universal global product identification code in the format of 14 digits Global Trade Item Number (GTIN) along with batch number, expiry date and a unique serial number of the primary pack. The bar code labeling at primary level is exempted until further notification.

For the secondary level packaging, the government insists on 1D or 2D barcode encoding unique and universal global product identification code in the format of 14 digits GTIN along with batch number, expiry date and a unique serial number of the secondary pack.

“The main challenge for industry is capital investment in required machinery and the timely change in packing material to accommodate such system of barcoding,” said Desai. “Large companies have large volume of export business and, hence, it is not very difficult to invest, while SMEs have a big problem. There are not many players in the market for supplying such technology and [the] majority are with imported systems, hence, there is a sort of monopoly which makes it expensive.”

An additional problem is that the technology requires training and development of human resources for successful implementation, besides changes in packing material design. The products that are already registered in various EU countries and the U.S. also have to undergo coding change simultaneously.

BioWorld Today | May 4, 2016

Globally, the U.S. FDA has beefed up its surveillance on counterfeit, contaminated and banned drugs, via a guidance on Drug Supply Security Act of 2013.


CFDA ZEROES IN ON QUALITY, BUT CONDUCTED FEWER GMP INSPECTIONS IN CHINA Aiming to address a perceived disparity in the quality of manufacturing of drugs for the China market, the CFDA is ramping up its focus on offshore drug manufacturers. The regulator last year stepped up the number of overseas good manufacturing practice (GMP) inspections it carried out, while domestically, it put more of the onus on companies to police themselves.

The 2015 report on drug inspections released this month shows that the number of GMP inspections at pharmaceutical companies in Mainland China has fallen significantly over the past year while the number of overseas inspections has increased by one-fifth.

The CFDA released the latest report via its Center for Food and Drug Inspection (CFDI). In total, 698 inspections were carried out, including pharmaceutical GMP certification inspections, pre-approval inspections, GMP follow-up visits, good agricultural practice certification inspections for traditional Chinese medicine, unannounced inspections and overseas inspection.

Most noticeably, the number of enterprises that received GMP inspections was halved in the last year, 221 in 2015 compared to 482 in 2014. Only nine, or 4.1 percent, of these companies failed last year but 7.7 percent had to address some deficiencies compared with 4.4 percent the year before. The ratio of companies receiving warning letters rose marginally from 30.3 percent to 30.8 percent.

“The increase of self-inspection is the reason behind the decrease of CFDA’s GMP inspections,” a health care equity analyst in Shanghai told BioWorld Today. “The regulators are asking more and more companies to do self-inspections first, and withdraw pending applications online if they find problems ahead of the CFDA inspection. The quality of self-inspections is up, so the overall inspection number is down.”

Nine companies failed the CFDA GMP inspections in Shanxi, Liaoning, Jilin, Henan, Hunan, Guangxi and Shaanxi provinces.

On the biologics side, manufacturers of nine vaccine products, three blood products and 30 other biological drugs applied for GMP certification in 2015.

Among all the inspections the CDFI conducted last year, deficiencies were mainly found in laboratory and quality control systems, production systems and material systems.

As the number of domestic inspections dropped, the number of inspections of manufacturing facilities overseas increased 20 percent in 2015 from 28 to 34. And the regulator said more such increases are likely.

China started doing overseas inspection in April 2011. The CFDI has appointed 68 teams of inspectors to work on 73 drugs so far. All products for clinical trial applications, production applications, re-registration and supplementary application were considered, including 46 chemical drugs, 18 biological drugs (vaccines and blood products) and nine herbal medicines.

According to the report, in the first three years of overseas inspections, inspectors found that foreign companies often “didn’t value China’s pharmaceutical laws and regulations, didn’t produce as per China’s requirements, and had different treatments on products exported to China and to other countries.” So Chinese regulators expanded the scope of their overseas inspections.

Analysts see this as a way of the government to protect domestic drugmakers, giving them more time and space for their growth.

“The CFDA is leaning toward import substitution. All of the documents released by the National Health and Family Planning Commission and the CFDA [on drug inspection] have this inclination,

Cornelia Zou and Bonnie Wang

BioWorld Staff Writers

“Among all the inspections the CDFI conducted last year, deficiencies

were mainly found in laboratory and quality control systems, production

systems and material systems.”


so there are more and more overseas inspections,” said the equity analyst who’s been looking at the pharma market in China for three years.

In January, the CFDI released the list of foreign manufacturers to be inspected in 2016. The regulators aim to go to 49 companies, including one added in April, mainly in Europe, the U.S., Japan and Vietnam to do on-site drug manufacturing inspections. Subsidiaries of pharma majors such as Novartis Europharm Ltd., Glaxosmithkline Australia Pty. Ltd. and Glaxosmithkline Biologicals SA are on the list which may grow longer again later this year. The CFDA said in a May notice that the number will grow substantially this year.

Most of local companies are very serious about the inspections as the GMP certificate and pre-approval inspections are crucial to both their

production capability and profitability. But the eagerness to pass sometimes backfires.

“The number one rule of going through inspection is honesty,” said Tian Shaolei, deputy section chief from the CFDI during the recent DIA annual meeting in Beijing. “Sometimes companies go out of their way to pass their inspections. I inspected a company once and took notes in my notebook along the way, in the afternoon they handed me all the materials on the issues I wrote down in my notebook, which I left closed on the table while I was out for lunch.”

“It can be understood that companies want to do well in front of the CFDA inspectors, but there’s no need to over-do it, just study the standards and be honest,” Shaolei noted.

BioWorld Today | June 14, 2016

“The number one rule of going through inspection is honesty.”— Tian Shaolei,

Deputy Section Chief, CFDI


ACTIVITY, OPPORTUNITY PICKING UP FOR JAPAN’S BIOSIMILAR MARKET A flurry of activity over the past month suggests that the adoption of biosimilars in Japan is about to accelerate. Partnerships with Indian and U.S. companies are bringing new biosimilars to the market, while an association for the drugs was launched to help promote awareness of their benefits.

Fujifilm Pharma Co. Ltd. earlier this year released a biosimilar insulin glargine onto the Japanese market after licensing it from the Indian company Biocon Ltd. as part of a broader push in Japan to bring cheaper versions of biopharmaceutical treatments to patients. “Sales of the drug are going well and [it has been] well accepted,” said Kana Matsumoto, of Fujifilm’s corporate communications division.

The treatment, which is similar to Sanofi SA’s Lantus, received approval in March and was released into the market last month. It is still too early to tell whether the release in Japan of the insulin biosimilar will be successful, but Kiran Mazumdar-Shaw, Biocon’s chairman and managing director, said she was confident the agreement would bear fruit.

“We believe with Fujifilm Pharma’s commercial network, we will enable access to this world-class, prefilled disposable pen for better diabetes management for patients in Japan,” she said.

Glargine is registered by Biocon in 20 countries, and a biosimilar is expected to begin selling in Malaysia early next year, after recently receiving approval from authorities in Kuala Lumpur to put the drug on the market. The Japanese market for glargine is worth around $144 million and treats around 7.2 million people afflicted with the disease, according to the International Diabetes Federation.

For Fujifilm, the deal with Biocon may prove to be a one-off, as it has a joint venture with Kyowa Hakko Kirin Co. Ltd. to develop and launch biosimilars in Japan. “There is no decision on whether FujiFilm Pharma will license-in other insulin [products] from Biocon,” Matsumoto told BioWorld Today.

Still, its release in Japan shows that companies in the Northeast Asian nation, and the government, are looking for ways to cut costs beyond cutting the prices of drugs on the National Health Insurance scheme and introducing simple generics to the market. Biosimilars are one option.

In April, the Japan Biosimilar Association (JBSA) launched with a mission to get more products to the market through information exchange, research and lobbying. The organization will include six committees tackling drug safety, research and development, public relations, general affairs, health care systems and matters relating to medicine. Its first chairman is Tatsuo Kurokawa, a former bureaucrat at the Ministry of Health, Labour and Welfare.

The JBSA’s first four members are Nichi-iko Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Meiji Seika Kaisha Ltd. and Mochida Pharmaceutical Co. Ltd. “Both the benefits and definition of biosimilars are yet to become common knowledge in Japan,” Kurokawa said upon taking the chairmanship of the new association.

Outside of the new association, Daiichi Sankyo Co. Ltd. and Thousand Oaks, Calif.-based Amgen Inc. last month signed an agreement to commercialize nine biosimilars to Japan, including those for adalimumab (Humira, Abbvie Inc.), bevacizumab (Avastin, Roche Holdings AG) and trastuzumab

Richard Smart BioWorld Staff Writer

“A flurry of activity over the past month suggests that the

adoption of biosimilars in Japan is about to accelerate.”


(Herceptin, Roche Holding AG). Financial terms for the agreement were not disclosed, but Daiichi Sankyo will handle marketing approval, commercialization and distribution in Japan, while Amgen maintains control of manufacturing and development responsibilities. (See BioWorld Today, July 18, 2016.)

Fujifilm’s Matsumoto views the biosimilar market as having potential.

“The biosimilars market is set to expand rapidly throughout the world against the backdrop of escalating medical costs and patent expiration of a series of innovative biopharmaceuticals through to 2020,” she said.

Targeting the market, Fujifilm Kyowa Kirin Biologics Co. Ltd., was launched in 2012, equally co-funded with Kyowa Hakko Kirin. The joint venture currently has two biosimilars in development, one for adalimumab and another for bevacizumab. The company aims to become a leader in biosimilars by combining Kyowa Hakko Kirin’s pharmaceuticals technologies with production and quality control methods used by

Fujifilm during the years when it was primarily a manufacturer of photographic film. It was launched with ¥100 million (US$998,223) in capital.

The biosimilar for adalimumab, which treats rheumatoid arthritis, is currently in phase II trials in countries including the U.S. The biosimilar for bevacizumab, which can be used to treat colorectal and non-small-cell lung cancers, is in phase I trials in Europe. Last year, Fujifilm Kyowa Kirin Biologics set up a joint venture with Astrazeneca plc, of London, to get the drug to market. In exchange for allowing the new venture to market the drug, the Japanese company received a payment of $45 million. (See BioWorld Today, Aug. 4, 2015.)

While the market for biosimilars is likely to grow, Matsumoto said the drugs and technology will not likely face the same sort of commoditization that has damaged the market for standard pharmaceuticals. “Biosimilars will require an advanced level of reliability and quality equivalent to that of their original counterparts as well as low costs in order to achieve broad proliferation and expansion,” she said.

BioWorld Today, August 17, 2016

“Biosimilars will require an advanced level of reliability and quality equivalent to that of their original counterparts as well as low costs in order to achieve broad proliferation and expansion.”— Kana Matsumoto,

Corporate Communications, Fujifilm


KOREA’S HANMI INVESTS $200M IN CHINA-BASED MANUFACTURING PLANT Taking another step to strengthen its presence in the promising Chinese market, South Korea-based Hanmi Science Co. Ltd. (KS:008930) will pour about $200 million into a new plant in the fast growing neighboring market.

Hanmi, the holding company of leading research-based drug developer Hanmi Pharmaceutical Co. Ltd. (KS:128940), had earlier bought 200,000 square meters of land in the Yantai Economic and Technological Development Zone in Shandong Province, China, for about $10 million.

The company plans to invest $200 million in the next 10 years to build new facilities for the production of biologic, chemical drugs and health supplements, as well as set up a research and development center for new drug development in Yantai.

This will be the group’s second facility in China. The first one, Beijing Hanmi Pharmaceutical Co. Ltd., was established in the country’s capital in 1996, and has been growing by around 20 percent per year since. It mainly focuses on new biologics for treatments of diabetes and obesity, bio production and product discovery using the company’s Lapscovery platform, which can be used to produce next-generation products and is a proprietary long-acting protein and peptide discovery platform.

Hanmi products are already marketed through more than 9,000 hospitals in China and have a leading position in the pediatric drug market.

In 2015, Beijing Hanmi had total revenue of KRW204.7 billion (US$178 million), up 18.5 percent year-on-year and net profits hit KRW27.1 billion. In comparison, total sales of Hanmi Pharmaceutical last year were KRW1,317.5 billion.

The solid performance encouraged the company to further expand its business in China but in a new location.

“Because of environmental issues, for example, the haze, the Chinese government has strictly limited building new manufacturing facilities in Beijing and its neighborhood,” a Hanmi spokeswoman told BioWorld Today. “Yantai is easy to access. It’s about an hour away by plane from Korea. Many Korean corporates, such as LG, Hyundai and Posco have set up their plants there.”

Further details of the projects, including a kick-off date and a breakdown of the total investment for different facilities, have yet to be announced, she said, but did not rule out the possibility of the drugmaker expanding further in China or that it might collaborate with local Chinese partners.

The company in 2014 inked a partnership with China’s Luye Pharma Group Ltd. (HK:2186) to develop and sell poziotinib, a pan-HER inhibitor,

Pearl Liu BioWorld Staff Writer

Hanmi products are already marketed through more than 9,000 hospitals in China and have a leading position in the pediatric drug market.


which according to Hamni, has a novel, oral mechanism that blocks EGFR receptors and may be effective against various forms of cancer. The Yantai-based biopharmaceutical company is one of the largest drugmakers in Mainland China. (See BioWorld Today, Aug. 27, 2014.)

Last November, Shanghai’s Zai Labs acquired the China rights for the late-stage non-small-cell lunch cancer therapy HM61713, for an undisclosed amount and, in the same month, the company signed deals with French pharma major Sanofi SA and Janssen Pharmaceuticals Inc., a unit of Johnson & Johnson. (See BioWorld Today, Nov. 25, 2015 and Nov. 10, 2015.)

More international drugmakers have been attracted to China’s biotech drug market, which is currently worth an estimated $50 billion, one-third of its pharmaceutical market, thanks to government support for the sector.

During the previous Five Year Plan (2011-2015), the central government injected $2 billion in subsidies to spur biotech innovation.

“China is lagging behind the game in terms of chemical drugs. Currently about 95 percent to 97 percent of chemical drugs produced in the country are generics, and only a small proportion are novel therapies. However, biopharmaceuticals is a new area, even in U.S. and E.U., which leaves an opportunity for China to catch up,” said Chris Hsia, senior manager at InterChina Consulting, an international strategy and M&A advisory firm.

In the U.S., the pharmaceutical market is approaching $350 billion, with approximately half devoted to biotech and drug discovery.

Hanmi Pharma released its annual results in March. The Korean drug maker recorded total revenue of KRW1,317.5 billion in 2015, up by 73 percent year-on-year. Net income hit KRW162.1 billion, which is almost four times that of 2014.

BioWorld Today, April 12, 2016

“China is lagging behind the game in terms of chemical drugs. Currently about 95 percent to 97 percent of chemical drugs produced in the country are generics, and only a small proportion are novel therapies.”— Chris Hsia,

Senior Manager, InterChina Consulting


ADVICE FOR BIOPHARMAS IN CHINA? MIND THE GAP SHANGHAI—In China, meeting the country’s unmet medical needs is a frequent topic of discussion. For biopharmas, that can mean filling the substantial gap between which drugs are available in developed markets and which are available for patients here.

Nobody underscored that topic more indelibly than Michael Yu, founder and CEO of Innovent Biologics Inc., of Suzhou, who presented during the two-day China Healthcare Investment Conference, or CHIC, event. Innovent is a company clearly on a roll. A biologics developer and manufacturer, it has raised more than $200 million in investment and signed a historic billion-dollar development deal with Eli Lilly and Co. (See BioWorld Today, Oct. 14, 2015.)

It has 12 products in the pipeline, eight investigational new drug (IND) filings, three clinical trial application approvals with two products in the clinic.

But when Yu said he looks at the top 20 drugs sold in China by market share, innovative biologics are nowhere to be seen. In 2014, the top-selling drug in China was sodium chloride, according to research done by Citi Research. The third is human serum albumin. Yu noted that is in stark contrast to the top 10 best-selling drugs globally, where biologics dominate seven of the top spots—Humira (adalimumab, Abbvie Inc.), Remicade (infliximab, Johnson & Johnson), Enbrel (etanercept, Amgen Inc. Lantus (insulin glargine, Sanofi SA), Rituxan (rituximab, Biogen Inc. and Roche AG), Avastin (bevacizumab, Roche AG) and Herceptin (trastuzumab, Roche AG).

It is not that China’s regulators have declined to approve biologics. According to CFDA Center for Drug Evaluation data compiled by Yu, as of 2014, China has approved 96 biologics, although “99 percent are copies, not even biosimilars,” he said. If broken down by category, China has approved 42 cytokines, 17 growth factors, 15 insulin products, seven enzymes, seven monoclonal products and two fusion proteins (with five more unspecified).

Out of the 96 marketed biologics, four were invented in China and classified by Yu as innovative: Gendicin (2003), Oncorine (2005), Iodine[131I] Metuximab (2005) and Conbercept (2013). Yu was in fact involved with the invention

of both Oncorine, the world’s first oncolytic virus product, indicated for head and neck cancer, and Conbercept, China’s first novel antibody product for ocular diseases.

For Yu, China’s biologics market is not an arduous uphill battle to educate doctors and patients on the value of quality biologics; rather it is an incredible market waiting to be supplied. “The China market for biologics is large and growing,” he said. “Biologics are growing two to three times faster than the pharma industry as a whole.”

Starting from a low point in 2009, the biologics market had a 27 percent compound annual growth rate (CAGR) in the six years ending 2014, for a market value of $9.53 billion. That growth will only continue, he said, thanks to an aging population with a rising prevalence of diseases such as cancer and autoimmune disorders, for which biologics have proved to be highly effective with fewer side effects.

In the next five years, the biologics market is expected to grow 21 percent CAGR, he predicted.

That is backed up by health care expert and McKinsey partner, Fangning Zhang, who shared data that China’s pipeline of local innovative class I oncology drugs (biologics and new chemical entities) is reaching scale: 37 IND candidates; 41 candidates in human study, with 20 seeking new drug application approval. A tipping point might be just around the corner.

CLEAR CONSTRAINTS

When trying to close the gap, it also helps to see how wide it is. In the U.S., biologics are 20 percent of the overall drug market. But in China, they comprise only 5 percent. If the U.S. can be viewed as a benchmark, then it indicates there is a long way to go.

When narrowing in on monoclonal antibodies (MAbs), they are the fastest growing segment in China. The MAb market grew by 40 percent between 2010 and 2013, according to Equity Research data, capping off at $670 million in 2013. Yet with only 6 percent market penetration in China, MAbs are a great growth opportunity, Yu said.

Shannon Ellis BioWorld Staff Writer


The only glitch in that otherwise rosy picture is finding a way to pay for high-priced biologics. Innovent’s strategy is to develop both biosimilars and novel candidates as a way to tackle both the high-volume business possible if included on the National Drug Reimbursement List, as well as the high-margin business of those who can afford self-pay.

“But the rewards for innovation face clear constraints,” said McKinsey’s Zhang. “Despite the economic growth of the past decade, China per capita spend for health care still significantly lags behind developed countries.”

China only spends 5.6 percent of GDP on health care expenditure, while the U.K. spends 9.1 percent and Japan spends 10.3 percent. Meanwhile, the U.S. spends 17.1 percent GDP on health care, according to World Bank and World Health Organization figures compiled by Zhang.

Put another way, China spends $370 per person each year, adding up to about $510 billion in total health care expenditure. In contrast, the U.S. spends $9,150 per person, for a total health care expenditure of $2.87 trillion.


China only spends 5.6 percent of GDP on health care expenditure, while the U.K. spends 9.1 percent and Japan spends 10.3 percent.


EMCURE’S WARNING LETTER HIGHLIGHTS ONGOING DATA INTEGRITY ISSUES IN INDIA The U.S. FDA has rapped yet another Indian pharma company with a warning letter that drew attention to “significant violations of current good manufacturing practice (cGMP) regulations for finished pharmaceuticals.”

In the recent letter to Pune-based Emcure Pharmaceuticals Ltd., the agency said it noticed the violation during an inspection conducted from Jan. 27 to Feb. 4, 2015. The FDA said that “the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, cGMP.”

It added that the company “failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes.”

The FDA investigators observed numerous problems of the facility, including poor aseptic processing techniques that could compromise the sterility of the injectable products, especially during aseptic filling operations; poor sterilization practices; flawed facility design that could represent an additional contamination risk to the products being manufactured; and unreliable personnel and environmental monitoring.

The U.S. regulator said the company’s environmental and personnel monitoring data were not reliable; nor was the company’s visual documentation program.

The FDA directed Emcure to submit in writing the steps the company has taken to correct and prevent the recurrence of violations within 15 working days of receipt of the warning letter. It also directed it to include third-party assessment of the extent of inaccuracies of the recorded and reported data; a risk assessment of the potential effects of observed failures on the quality of its drug products; and a management strategy for correction and prevention of future errors.

This is not the first time Emcure has had compliance issues. Nearly 23,000 bottles of methyldopa tablets the company manufactured for Israeli firm Teva Pharmaceutical Industries Ltd. were recalled due to violation of cGMP in 2014; two lots of injectable agent made for Sagent Pharmaceuticals Inc., of Schaumburg, Ill., were also recalled in February 2015. The FDA then imposed an import alert on almost everything Emcure makes.

Emcure did not respond to BioWorld Today’s queries for comment. There’s no update on Emcure’s response to the U.S. FDA, either.

‘WE DO HAVE A QUALITY PROBLEM’

The data integrity and quality assurance issues highlighted in the FDA warning letter to Emcure have long been the bane of several Indian pharma firms, and several representatives have been cautioning that the entire India brand gets affected by lapses and violations of protocols by a handful of firms.

T.V. Padma BioWorld Staff Writer

Several representatives have been cautioning that the entire India brand gets affected by lapses and violations of protocols by a handful of firms.

“ A shortage of human resources and excessive work pressures could

lead to inaccurate or incomplete documentation, and eventually

could impact the product quality.”


Last month, Aditya Berlia, a member of the management board of the Apeejay Svaran Institute for Biosciences & Clinical Research, during a conference organized by the Associated Chambers of Commerce and Industry of India, said of the evolving landscape of the Indian health care industry that “we [the Indian pharma industry] do have a quality problem.”

“There is a dichotomy. On the one hand, we have world-class pharma companies, and on the other, several others have been suffering blows in Europe and the U.S.”

Berlia also warned that if companies did not gear up to meet the stringent U.S. FDA standards, “50 to 70 percent of pharma firms in India will need to be shut down. That is in addition to Indian pharma companies losing ground to Bangladesh, China and Vietnam that are setting up U.S. FDA quality plants.”

Last year, Krishna Ella, managing director of Hyderabad-based Bharat Biotech International Ltd., repeatedly stressed the need to improve data integrity in the pharma sector.

Indian firms do not take the trouble of verifying whether new recruits had previous track records of poor data quality maintenance in their previous organizations, said Ella. That means that an employee who gets sacked from one firm for not maintaining records properly can get a job somewhere else and repeat the same mistakes.

A 2015 Ernst & Young (EY) survey also concluded that the Indian pharma industry was struggling with data integrity issues. The survey, conducted from January to March 2015, was based on responses from 170 people from the pharma industry. It highlighted serious issues of lax

documentation, absence of data reviews and severe work pressures to demonstrate key performance indicators of products. (See BioWorld Today, July 15, 2015.)

Almost 21 percent of the respondents said their organizations did not always have organized audit trails on laboratory equipment, which means there would sometimes be no records of captured data. That could pose a serious problem during inspections by global inspectors and invite action by them.

And “57 percent admitted seeing manufacturing personnel being under immense work pressure, impacting overall efficiency of processes,” despite their signing forms on understanding and compliance of good manufacturing practices.

One-third of the pharma firms have not conducted reviews to assess potential gaps in data integrity, noted EY’s survey report. A shortage of human resources and excessive work pressures could lead to inaccurate or incomplete documentation, and eventually could impact the product quality.

Other key issues that cropped up in the survey included the need for technology upgrade, with more than 25 percent of the respondents saying that they were unaware of the 21 Code Federal Regulation Part 11 standards prescribed by the U.S. FDA, which establishes the criteria to record data in electronic form.

As for solutions, the EY report pointed out that regular and proactive data integrity reviews that evaluate if data records are accurate, complete and maintained in their original context in electronic or paper form, can ensure accuracy and consistency of GMP data.



PERU’S PHARMA GUILD EVALUATES GUIDELINES FOR BIOSIMILARS Less than two months after Peru issued technical standards to register and re-register biosimilars, the new regulations are generating buzz in the country’s biopharma space.

The Peruvian Directorate General of Medicines, Supplies and Drugs (Digemid is its acronym in Spanish) released the standards after much ado earlier this year, although the Latin American country does not produce any biosimilars at the moment. (See BioWorld Today, Nov. 10, 2014.)

“The new regulation meets the minimum standards of the World Health Organization [WHO] in relation to biosimilarity, so we can say that it is designed so that any attempt [has to prove] the biosimilarity through clinical and preclinical comparability studies,” Augusto Rey, executive director of the Peruvian National Association of Pharmaceutical Labs (Alafarpe), told BioWorld Today. The guild represents both domestic and international pharma companies.

But it is concerned about dossiers that Digemid is studying.

“The disappointing thing is that the rule established that pending files will be [registered] without proof of safety and efficacy, and then they will undergo a gradual schedule to prove biosimilarity in five years,” said Rey. “We understand that this gradualness applies to products already on the market, but not those that are not. Why allow the entry of substandard products for five years after the adoption of the standard?

“The laxity with pending dossiers is regrettable,” he added.

The new rules do not provide a process to directly approve drugs that have been approved by other agencies such as the U.S. FDA. Rather, the regulation provides that the process will follow recommendations from the WHO, the Pan American Network for Drug Regulatory Harmonization, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, the EMA, Health Canada and the FDA.

“We believe that the standard has sought to preserve the consensus of the scientific community to keep as reference comparability standards of the WHO,” said Rey. “The enforcement of this new regulation, if administered properly, will be beneficial for the country, especially for patients, to whom it will ensure that the biosimilar product to be available in the future is really similar to the original reference.”

Several countries in the region have developed legal frameworks for biosimilars in the past few years, as biotech patents expire and biosimilars gain market share. Peru’s neighbor Colombia issued its biotech regulations back in 2014, but it also took about two years and five drafts for the government in Bogota to issue those guidelines. (See BioWorld Today, Sept. 23, 2014.)

A concern across the region is the quality of biosimilars entering the Latin American market.

“The most important [consideration] is the patient and the quality of medicines which are provided,” said Rey. “We should not have differences of quality between [the reference drugs and biosimilars], as it endangers the lives of patients.”

Sergio Held BioWorld Staff Writer

“The most important consideration is the patient and the quality of medicines which are provided.”— Augusto Rey,

Executive Director, Peruvian National Association of Pharmaceutical Labs (Alafarpe)


In 2011, the Latin American country issued its current policy to register pharmaceutical products and medical devices. The rules provided for 180 days for the authorities to issue the required guidelines to regulate the entrance of biosimilars to the Peruvian market, but it was not until almost five years later that those guidelines were issued. And critics said that Peru still has a long way to go in developing a stronger regulation for biosimilars entering the country.

“There are other steps to take in addition to the implementation of the regulation of biosimilars: the adoption of the rules of interchangeability, which will allow generics to be equivalent to the reference and not like now, that they have

not demonstrated safety and efficacy,” said Rey. “Furthermore, we must take serious steps toward implementing an effective pharmacovigilance. We must always put the patient ahead.”

Although there have been no problems yet, Rey’s concerns have to do with safety, and any potential issues that could arise out of rules that are not thoroughly thought out.

According to Alafarpe, in 2015 the Peruvian pharmaceutical market grew by 8 percent. The health sector represents 5.3 percent of the country´s GDP.

BioWorld Today, May 9, 2016

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