Agnes Shanley is senior editor of Pharmaceutical Technology.

Agnes Shanley

	China and India are also increasing inspections and becoming more exigent about data integrity and cGMPs. The China Food and Drug Agency (CFDA) has increased its plant inspections from 35 in 2011 to 110 in 2015 says Lewis Ho, a Dechert LLP partner who leads the life scieces practice in Asia.  

	In India, FDA and the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) have been ramping up inspections for data integrity issues, says Hyman, Phelps, and McNamara, PC Principal, Doug Farquhar.In addition, regulators are sharing more information on violating plants, so that if one plant has failed numerous MHRA inspections, FDA will rely on that knowledge. However, notes Mark Schwartz, counsel with Hyman, Phelps, McNamara, FDA inspectors won’t be relying too much, or suspending inspections, based on positive reports from other ragencies.

	The CFDA has been learning a lot from FDA, says Ho. “When FDA inspectors come to look at a plant and its operations, a CFDA staffer usually accompanies them to learn and gain more insights into the way FDA handles inspection.  There is a lot of exchange of experience going on. And far more inspections are taking place,” he adds. China’s inspectors have taken the message of data integrity very much to heart, Ho says, and are focusing on that and data management, while unannounced inspections have become more frequent, and CFDA recently took away a company’s manufacturing license when it attempted to prevent an inspection.

	It is important to get to know any potential business partners based in China, and to understand their compliance practices clearly before working with them. “Inspections can become cultural issues. Many Chinese companies are following the US inspection style, but may still be using Chinese style where enforcement is concerned.  In general, they are not used to confrontational approaches, so companies need to send representatives with thorough knowledge of the language and customs, as ‘bridges’ if they are to understand the situation and handle it adequately,” says Ho. CFDA inspectors are also being sent to other countries to handle inspections, particularly in the European Union. Some CFDA inspectors have already issued critical reports.


	When referring to this article, please cite it as A. Shanley, "More inspections, and reulator collaboration, offshore," sidebar to “Ensuring Supply Chain Safety," 

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China and India are also increasing inspections and becoming more exigent about data integrity and cGMPs.

More inspections, and regulator collaboration, offshore

As FDA has stepped up inspection of API and finished drug manufacturing facilities outside the United States, its inspectors are uncovering more reasons for drug company sponsors to do what they should be doing anyway:  assessing and monitoring their suppliers’ and business partners operations, quality systems, employee training, and overall business practices. Caution is required with all business partners, but can be much more complicated when these partners are thousands of miles away and do business in another language and culture.

	Failure to be proactive can have far-reaching impacts. Drug shortages can result when FDA inspectors find problems at a sole offshore supplier’s API manufacturing plant and place that supplier on Import Alert. In other cases, contract manufacturer or supplier noncompliance can stop the development of a promising new drug, when a pre-approval inspection reveals a poor understanding of cGMPs, and FDA stops new or abbreviated new drug (NDA or ANDA) application review with a Complete Response Letter (CRL).  As Lachman Consultants’ Vice-President Arlene Ocampo recently warned (1), “Be ready, be smart, and be prepared.” That means making sure that your business partners are too, wherever they are based.

	These were some of the issues explored in a June 22, 2016 webcast jointly sponsored by the law firms Dechert, LLP and Hyman, Phelps and McNamara, P.C. Ominously entitled “The International Pharma Supply Chain: Imperiled Like Never Before,” the program (2) touched on problems that are converging to keep pharmaceutical executives up at night: data integrity problems, an immature compliance culture at many facilities in developing regions, and the emergence of corruption and bribery, already seen on the physician marketing side, as a potential supply chain safety issue.

	We’ve been hearing about serious manufacturing and quality issues at offshore facilities for some time. In an interview with attorneys at both firms preceding the webcast, Hyman Phelps Principal Douglas Farquhar said that the term “more imperiled” is anything but hype.

	In the 12 months ending June 1, 2016, he notes, FDA issued 25 warning letters to pharmaceutical manufacturers, and, excluding compounding and marketing-related actions, 23 were issued to foreign facilities. “We’ve reached the point where 90% of warning letters are being issued to foreign facilities, many of which are in India and China,” Farquhar says. Considering that approximately 80% of the pharmaceuticals sold in the US are either made overseas or use APIs that are made offshore, he adds, “that’s a huge percentage of distribution.”

	His colleague, Hyman, Phelps and McNamara lawyer and FDA alumnus Mark Schwartz, notes that data integrity is most often cited in warning letters to offshore suppliers, accounting for 43% of FDA’s Center for Drug Evaluation and Research’s (CDER’s) warning letters in 2011, but 78% of warning letters in 2015. Chinese and Indian manufacturers were cited in 31% of warning letters in 2011, he says, but four years later, that number had risen to 70%.

	“Data integrity has become a huge problem, and CDER is now in a Catch-22 situation--either allow products into the country that could potentially violate requirements of the Federal Food,Drug,and Cosmetic Act and threaten to create a public health crisis, or put the manufacturers involved on import alert and potentially usher in drug shortages,” Schwartz says. Most common signs of poor data integrity include:

		Hiding time and date settings on test results

		Re-integrating analyses to achieve passing test results

	It’s likely that data integrity has surfaced as a problem because regulators are inspecting more--and more offshore--facilities. In 2015, FDA conducted approximately 180 inspections of facilities in India and China. As Farquhar noted on the webcast, the agency has 13 staffers in China and wants to triple that number, and to double the 9–10 it has in India.

	In addition, regulators in China, India and elsewhere are increasing their inspections, and including inspections of more foreign facilities, focusing currently on European suppliers (

	In the June webcast, Schwartz pointed out better inspection practices, singling out Peter Baker, FDA India’s assistant country director, for particular respect. Several years ago, Baker (3) began applying sophisticated methods to examine facility computers to find hidden data (such as additional “unofficial” test results) in computer hard drive directories.

	But fundamental issues are also at play, notes consultant John Avellanet, principal of Cerulean Associates, LLC.  “Nobody really teaches you not to backdate a lab notebook in college,” he says. “It’s a question of ethics, and then training by your company.”

	Poor data integrity practices are everywhere, but Avellanet says that it is about 10% easier for inspectors to find problems at facilities outside of Western Europe and North America than within them. European and North American companies are used to being inspected regularly, not only by regulatory agencies but also by third parties such as International Organization for Standardization (ISO) auditors.  “There’s a level of expectation that [outsiders] will come and look at our work, when we signed and dated documents, our training records, and so on,” says Avellanet. “People at facilities in the US and Europe are more prepared for the obvious red flags,” he adds.

	Even in developed regions, seasoned professionals may have difficulty translating good documentation into good electronic data practices. As a result, the people who evaluate offshore partners’ facilities are often from quality or purchasing departments. They may not really understand what good data integrity practices look like in day-to-day work, or know what to look for to find problems, he says. At the same time, Avellanet says, “Many pharma IT departments focus more on the ‘T’ than the ‘I,’ in IT, which makes it hard to translate IT-speak into quality or management language.”

	Senior managers, meanwhile, may be so focused on the bigger picture that these issues get short shrift. “There is no line item in budgets for data integrity,” says Avellanet. “Those most affected by it must distill data integrity down to three talking points, and try to get funding.  It’s a tough row to hoe, since management tends to think of quality as overhead to begin with,” he says--until the company receives a warning letter or has a new drug development program put on hold.

	Import alerts, which block APIs and finished pharmaceuticals from being sold in the US, may have given some companies a false sense of security, notes Farquhar.  More should take warning from current cases, and be sure to diversify their API suppliers. “For pharma companies that depend on, say, a single API supplier, it can take more than a year to recover once the supplier is listed,” he says.

	Supplier noncompliance can also play a major part in curtailing development of a new branded or generic drug via a new drug application or abbreviated new drug application (NDA or ANDA). If the API used to make the drug was made by a company on the Import Alert list, FDA will not approve the drug, says Farquhar.

	Since April 2016, FDA has issued two CRLs to two companies with new drug candidates (2). What was significant in these cases, Ocampo says, is that the CRLs were not based on the usual reasons (e.g., safety or efficacy problems with the drug), but because pre-approval inspections at offshore supplier facilities indicated cGMP compliance problems. “Within the past 12 months, we’ve had at least five clients come to us because their NDAs or ANDAs were not approved for this reason, says Farquhar.


	While the US government has brought numerous cases under the Foreign Corrupt Practices Act (FCPA) since it was enacted in 1979, US enforcement authorities have been particularly aggressive over the past decade, says Dechert partner and co-chair of its International Trade and Government Regulation practice, Jeremy Zucker. He notes that many past enforcement actions have targeted pharmaceutical companies that provided cash, trips, entertainment and other things of value to physicians at state-owned health systems to induce them to prescribe the companies’ products--and that Kara Brockmeyer, the chief of the FCPA unit at the US Securities and Exchange Commission (SEC), recently announced that the SEC again would focus on corrupt practices in the pharmaceutical industry. Zucker notes that supply chain is becoming an area of interest, and regulators are exploring whether local manufacturers and other partners are bribing foreign officials to secure commercial advantages. Local enforcement agencies in India, China, and other countries are increasing their own efforts to prosecute bribery, paying close attention to third parties, such as travel agencies and clubs, that could be involved in such deals.

	“There is great potential for bribery and corruption to affect the supply chain, because money can, in theory, so easily be funneled through third - party agencies,” says Kareena Teh, a Hong Kong-based litigation partner with Dechert who leads the investigation practice in Asia. In addition, she says, “we see a lot of issues around customs and getting things in and out of China, and the potential for ‘inducement’ payments to be attempted.”

	Inspection reports in some FDA warning letters, particularly those calling out basic plumbing issues with sinks and toilets at API manufacturers, beg the question of whether some local government official or inspector “greased the wheels” for manufacturers. “How else could these facilities pass local annual health and safety inspections when such problems existed?” Teh asked on the webcast (1).  She also recalled the case of Chen Wen-Hsiung, an inspector with the Taiwan FDA, who was reportedly paid more than $150,000 over two years, to warn local pharmaceutical companies of “surprise” cGMP inspections and help them pass (3).

	Questionable business practices can take other forms, too. This was seen with the 2008 heparin recall, in which some of the heads of the Chinese suppliers implicated in the recall were related to each other.

	Questions about heparin safety persist today. In March 2016, US representatives noted many inconsistencies that had not been explained or resolved, which reflect basic safety loopholes in the pharma supply chain (4). It’s important to be aware of contract wording, especially where additional payments are linked to milestones that involve other partners. Avellanet recalls a situation with a client who had outsourced a clinical project to an overseas contract research organization (CRO), with milestone payments built into the schedule. The CRO, in turn, provided milestone payments to local investigators, which resulted in fictional patient recruitment and the logic often found in these situations. “I get double the money if I enroll 10 patients instead of six. So who will know if I make up four more people? The sponsor doesn’t speak this language and by the time they get patient data, the trial will be over,” says Avellanet.

	So what is a sponsor to do?  Thorough due-diligence and vetting of suppliers are crucial. “Mock audits are critical….and companies need to look hard at data integrity issues and at electronic recordkeeping, 21 

 Part 11-type issues, including being sure to back up all data and store it remotely from the plant location,” says Farquhar, who believes in scheduling, and repeating, unannounced quality audits.

Reminder: International Pharma Supply Chain Imperiled Like Never Before

,” FDA Law Blog, June 16, 2016. 
	2. A. Ocampo, “

Complete Response Letters Due to Failed PAIs: More to Come?

” Lachman Consultants’ blog, June 2, 2016.
	2. E.K. Sharma, “

,” BusinessToday.com, March 16, 2014.
	3. T. Sandle, “

,”August 16, 2015, DigitalJournal.com.
	4. A. Shanley, “

US Representatives Question the Safety of the Heparin Supply


	When referring to this article, please cite it as A. Shanley, “Ensuring Supply Chain Safety," 

Data integrity and cGMP issues demand closer scrutiny of suppliers. Bribery and corruption may become the next supply chain flashpoint.

Ensuring Supply Chain Safety

Pharmaceutical track-and-trace regulations have been taking shape for several years now, with countries setting compliance deadlines. By 2017, US regulations demand that manufacturers be able to serialize product  (i.e., identify every package, using 2-D barcodes and a unique identifier that includes product ID, serial number, expiration date, and lot number). By 2023, regulations require that they be able to track each bottle or package back to the original manufacturer.

	That vision of end-to-end data exchange remains a long way off, says Joe Whyte, director of serialization and connected enterprise solutions at Rockwell Automation. “Companies are exchanging files but not tracking anything,” Whyte says. “Information exchange today relies mainly on electronic data interchange (EDI) Advance Ship Notice/Manifest (ASN), an electronic shipment notification document.There is no data to mine, analyze or use, and it doesn’t solve any counterfeit, diversion, manufacturing or supply chain problems. Without aggregation and GS-1’s EPCIS standards, you cannot capture any supply chain product event information, so there is no benefit to consumers and no ROI for manufacturers, wholesalers or distributors.”

	At this point, even achieving serialization, the first part of this journey to transparency, still challenges many manufacturers. With one year to go to meet US regulations and three years to meet European requirements, progress among small- to mid-sized pharma companies has been spotty, according to consultants and experts in serialization and traceability.

	Big Pharma companies, for the most part, began working on serialization strategy five or six years ago. “Large manufacturers are moving forward, while mid- to small-size manufacturers still struggle,” says Evren Ozkaya, founder and CEO of Supply Chain Wizard, a consulting firm that specializes in track-and-trace implementations.

	Differences in approach really have little to do with size or company type, however, and more with mindset, says John McKeon, technical director with Portalis, Ltd., based in Kerry, Ireland. At proactive companies, he explains, senior managers are aware of the challenges and benefits of serialization.  “They have approved a strategy for full product serialization with aggregation.  The solution is agreed upon among all stakeholders within the company, and ownership of the rollout is shared.  These companies are often technology leaders and committed to robust planning and risk mitigation,” he says.

	In reactive companies, there is no clear ownership of the strategy, which, he says, can prevent projects from being completed. Often, if a serialization solution design results, it is overly simplified and does not meet product or market requirements.  

	“Within our current customer base, the average level of completion for serialization is 25%,” says Jean-Pierre Allard, director of technology at Optel Vision.

	Currently, more than half of pharmaceutical contract manufacturing organizations (CMOs) lack the resources and capital required for compliance, says Ozkaya, while some smaller outsourced service companies may not yet be fully aware of what is needed. Generic-drug  companies are behind branded firms in serialization efforts, but larger generic drug manufacturers have been proactively reaching out to their CMOs. Many manufacturers are focusing on strategic CMOs only, and assessing risk.

	There are technical hurdles to clear in developing serialization and track-and- trace programs, but, experts say, it’s the human ones that are proving most difficult to surmount. Some deadlines and requirements that were set in the past wound up being postponed, and many manufacturers reacted by postponing serialization efforts and taking a “wait-and-see” approach, which, Whyte says, gave some companies a false sense of security.

	“Looking at legislation, the volume of work required and the time available, the industry is in for a bit of a wakeup,” says McKeon. It can be easy to underestimate the time required for serialization, he says.  There’s the 140 days or more between the time product leaves the warehouse until it reaches the pharmacy shelf.

	But before that, there is the eight to 12 weeks spent writing the user requirement specifications (URS) document, one to six months for bidding and selecting vendors, three months or more for technical discussions and drawing up a contract, four weeks for document preparation, two weeks for document approval, one week per line for installing equipment,  six to 12 weeks for line validation, 12 to 20 weeks lead time for machines, and time required for other steps. It adds up to a considerable amount.


	The fact that pharma is outsourcing more manufacturing and related functions has made serialization efforts more complex. In some cases, CMOs have been waiting for guidance from pharma clients, but haven’t received it, says McKeon. Most CMOs expect new contract terms to assist them with serialization solution design, capital expenses for the project, and a longer contract period within which to recoup investment, but issues of increased costs often hold up contracts.

	In addition, many large pharma companies are also CMOs to each other, under arrangements in which they package and distribute each other’s products in specific regions, based on company-to-company agreements, says McKeon. These agreements are less likely to result in the impasse that can occur between a large pharma company and its smaller CMOs, he says, especially when project scope changes and costs go up.

	“At least 25% of pharma CMOs have not started a project internally,” notes Allard.  However, he sees the situation changing rapidly, as customers push them, or even give them ultimatums (e.g., “eighteen months or else”) to get started with implementations. Brian Deleiden, vice-president of industry marketing for TraceLink, also sees the situation improving, with more operating companies taking a very “hands-on” approach to engaging CMO partners.

	Leadership can go in the other direction, too. In February 2016, the contract development and manufacturing organization (CDMO) Recipharm, disclosed plans to invest $44.4 million to set up serialization and track-and-trace capabilities to offer its pharma clients. The company figured that 85% of its client base needed help with serialization.  “When we understood how many programs and customers needed serialization, we decided to make this investment to support our customers,” says Asa Wilander, head of customer relations within Recipharm’s serialization task force. In 2015, the company established how teams at each of its sites would work on serialization. Recipharm has focused on working with one hardware and two software partners, and is using EPCIS standards.

	The biggest challenge in getting customers up and running is communication, she says. “We are proactively starting discussions with our customers around customer requirements and additional features that need to be adopted, but there is still a need for companies to place the serialization challenge higher up on their agendas,” she says, even after Europe’s Falsified Medicines Directive (FMD) set a compliance deadline.

	Pharma companies tend to be siloed, with different departments often reluctant to share information. Within this type of environment, McKeon says, it can be difficult to implement any change that affects every department directly.  

	This lack of communication is often first evident with the URS document, which establishes the foundation for any company’s track-and-trace efforts. “It’s important to take a holistic view from the beginning, even if you only implement serialization in phases … All stakeholders must participate up front, even if the work does not affect them for three years … the work must be holistic and cross-functional if you want to minimize imlementation costs and challenges and realize an ROI,” says Whyte.

Another challenge is finding the best basic approach for dealing with changing timeframes and expectations in other countries, says David Sheedy, serialization IT deployment manager at Zenith Technologies, which provides implementation support, and recently announced a partnership with technology provider SEA Vision.

	Brazil’s regulations were problematic last year, and, Allard says, the “get go” deadline remains unclear. Most companies that work or ship to Brazil are waiting until the directive is issued (expected in May 2016), before starting their efforts.

	EU requirements are also challenging. “Companies need to treat the EU FMD, not as a single harmonized track-and-trace law to meet, but, instead, as a standardized serialization, reporting and verification regulation that must be applied to product lines, depending on target EU markets,” says Daleiden.

	“European regulations are clear on requirements for print and at the packaging level,” says Allard, “and call for a tamper-evident device to protect the packaging. However, the device requires more space on the packaging lines, so manufacturers will need to buy new equipment in order to comply.”

	In some cases, European regulations also call for aggregation (or allocating a serial number on the shipper case and record of the association of the case serial number with the item serial numbers inside), he says, adding that the directive requires companies to notify the database when serialized products are shipped outside Europe. Without aggregation, recording and communicating the serial number on all the shipped products will quickly become cumbersome for distributors, Allard says. “If there is no serial number on the case, a company shipping products out of the European zone will need to open every shipped case and scan each individual item serial number,” Allard says.  “The “implicit aggregation requirement” consideration will only become real after the implementation deadline, he adds, so manufacturers are wondering whether they should integrate aggregation solutions now or wait for demands from their distributors.”

	Daleiden also points to new requirements taking shape in South Korea and India, and a draft regulation in Russia. One other challenge, says Allard, has been lack of guidance from FDA for the US market. Manufacturers are currently implementing solutions, assuming that FDA will regulate with GS-1 compatible solutions and endorse the guidance published by the Healthcare Distribution Management Association (HDMA).

	The second challenge for the US market is that the data transmission model (i.e., whether to use a centralized database hosted by FDA or to have decentralized passing of data from one stakeholder to the other) has not been defined, Allard says. So it is not really possible for distributors and wholesalers to prepare.

There have not been any formal studies of the return on investment (ROI) of track and trace, but consultant Robert Celeste of RP Partners notes potential benefits in operations and beyond. “It offers a unique opportunity to connect with patients,” he told listeners to a June 15, 2015 webcast sponsored by Rockwell Automation (1).

	A McKinsey report (2) estimates that, for a pharmaceutical manufacturer with 25 packaging lines and $4 billion in annual revenues, economic benefits could include the following:  

		$11 million/year from reducing inventory financing and holding

		$3-12 million/year in reducing cost of recalls

		$25-35 million/year from reducing financial impacts of counterfeiting.

	Darryl Brown, vice-president of global strategic marketing at Systech International, notes that more clients in Europe are starting to realize the potential power and value of the solutions.  “They’re asking how they can deliver intelligence back through the value chain,” he says. The next step, he believes, will be using the data to better understand patient engagement, to optimize supply chain management. “Customers may not be ready for this now, but at least they are thinking about it,” he says.

	In the US, he says, one customer is working toward item-level serialization, even though that approach is not mandated. “We are starting to see a more mature thought process,” says Brown.

	Companies must take an “outside in” approach to serialization programs, says Daleiden, not only to simplify traceability implementation but also ensure that packaging lines and serialization-enabled sites can meet the diverse regulation and business requirements that are coming into force.  A number of consultants suggest doing the work in phases, and tackling serialization and aggregation together, from the earliest stages.

Serialization Regulatory Compliance, an on-demand webcast

Strength in Unity: The Promise of Global Standards in Healthcare


	When referring to this article, please cite it as A. Shanley, "Waking up to Track-and-Trace Benefits," 

There are technical hurdles to clear in developing serialization and track-and- trace programs, but it’s the human ones that are proving most difficult to surmount.

Slow Serialization Efforts May Delay Business Benefits

	Recently, there have been more reports of compliance issues at API and drug manufacturing facilities in India. Kiran Mazumdar-Shaw, chairperson and managing director of Biocon, told Pharmaceutical Technology in an interview that investment in talent and infrastructure, more quality-by-design skills, and increased communication with global regulators will be needed.

: What do you think might have contributed to the FDA compliance issues that some Indian drug manufacturers have had over the past few years?  

: India has nearly 380 FDA-registered facilities, which is the largest number outside the United States. Seen in that context, the non-compliance warnings received by Indian companies are not disproportionate to those received by companies in China and other countries. India’s growing market share in the US draws greater FDA scrutiny.

	Despite all the media noise around compliance issues, the fact remains that Indian drug makers have the second-largest share of abbreviated new drug application (ANDA) approvals from FDA after US producers.

	A report recently released by FDA’s Office of Generic Drugs (OGD) (1) shows that, out of 90 first-time generic drug approvals in 2015, up to 14 were won by Indian drug companies, most of them for specialized treatments (2).  

	Over the past few years, regulators across the globe have opted for stricter norms to ensure the quality of medicines, which is evident from the fact that the total number of product recalls and warning letters to pharma companies globally tripled between 2008 and 2014.
	Indian pharma companies are working overtime to align their operations and improve their quality control procedures to meet Western regulatory expectations, and I expect the number of warnings to come down in due course.

Investments in facilities and training needed

: What will be needed to change the situation?

: Despite the recent spate of quality-related issues, the reality is that Indian pharmaceutical manufacturers continue to command a good reputation in pharmaceutical manufacturing. Besides the FDA-approved facilities, there are 1400 manufacturing plants with World Health Organization (WHO) GMP approval and over 250 plants that have been cleared by the European Directorate of Quality Medicines (EDQM).

	The Indian pharma industry will need to focus and invest more in high-quality manufacturing to maintain its edge as a destination of choice for the production of safe, effective, and affordable medicines. Besides investing in physical infrastructure, companies must invest in talent to ensure an optimal mix of quality control staff and shop floor personnel for delivering the highest quality. There is also a need for greater dialogue with Western regulators to keep pace with the evolving quality and regulatory regime and align people and processes accordingly.

: There has been some retrenching and ‘onshoring,’ as some US companies have begun to source APIs and other materials from the US and Europe. What will be needed to reverse this trend and regain any lost credibility, on the part of some API suppliers?

: To achieve the goal of ‘make in India for the world,’ Indian pharmaceutical companies will have to adhere to current good manufacturing practice (cGMP) guidelines, backed by quality by design (QbD). They will need to bring in more checks on manufacturing processes and rigorously focus on monitoring, causality, and documentation.  

	It is also imperative that Indian companies ramp up skills on QbD. There is a need to build a strong quality brand to sustain leadership on the mantra of ‘highest quality at the lowest cost’.

: What unique strengths do you see Indian pharma contributing to the global market over the long term?  What will be needed to get there?  

: The Indian pharmaceutical industry has played a disruptive role by developing critical drugs at relatively affordable levels. By bringing down the prices of drugs used to treat life-threatening diseases such as HIV, tuberculosis, and cancer by as much as 90%, Indian generic-drug makers have enabled access and saved millions of lives across the developing world.

	India’s strengths in drug development and cost-effective drug manufacturing can be key to realizing the vision of addressing unmet medical needs through affordable biopharmaceuticals globally. India can make as much of an impact on global healthcare with biosimilars in the coming years as it has done with small-molecule generics in the past.

	Access to capital, quality infrastructure, high-end talent, and an optimal ecosystem that encourages innovation in the country will spur India’s evolution as a biopharma hub and the preferred destination for innovation.

: What are your plans in the biosimilars business?  What role do you see Indian suppliers playing in this niche?

: Biocon, with its rich pipeline of biosimilars under development, is preparing to meet the widespread global demand for affordable biosimilars from patient advocacy groups, non-profits that support healthcare initiatives, and governments with overstretched healthcare budgets. The global market opportunity for biosimilars is estimated to reach around US$24 billion in 2019 (3).

	Today, Biocon has one of the largest portfolios of generic insulins and biosimilar protein therapeutics in advanced stages of development and is on track to file for regulatory approvals in US and Europe for four of them in fiscal year 2017. Biocon is confident that, together with our partners around the world, we can build a strong global presence in biosimilars to address the huge need for affordable access to these life-saving and life-enhancing biologics.

	India has been among the early adopters, and established the regulatory framework for biosimilars as early as 2012. The industry is well poised to provide cost-effective alternatives to expensive reference biologics for patients and an opportunity for governments across the world to rein in burgeoning healthcare costs.

, Office of Generic Drugs.
	2. A. Malik, “

USFDA Grants 14 First-Time Generic Drug Approvals to Indian Firms in 2015

,” Indian Business Times, April 15, 2016.
	3. C. Challener, “


	When referring to this article, please cite as A. Shanley sidebar to, “Steps Closer to the Adoption of Continuous Processing," 

Investment in talent and infrastructure, more quality-by-design skills, and increased communication with global regulators will be needed to combat compliance issues at API and drug manufacturing facilities in India.

Indian Pharma Is Committed to the Future, Says Biocon Managing Director

Electrophilic and other reactive compounds, and their precursors, must be measured and removed to ensure patient safety.

Measuring and Removing Genotoxic Impurities

Intact enables aseptic filling in non-classified environments, maintains sterility throughout the process, and reduces costs, timelines, and contamination risks.