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Voluntary Practice Alone of Pharma Marketing Code, Has Never Worked…Anywhere

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Since the last three and a half decades, ‘Code of Pharmaceutical Marketing Practices’, prepared by various global pharma trade associations and most of the large global pharma companies individually, have come into existence for strictest voluntary adherence. These are being relentlessly propagated as panacea for all marketing malpractices in the drug industry.

Squeaky clean ‘pharma marketing codes for voluntary practices’ can be seen well placed in the websites of almost all large global pharma players and their trade associations.

Though its concept and intent are both commendable, following the regular flow of media reports on this topic, a relevant question surfaces: Do the votaries, sponsors and creators of these codes “walk the talk”?

If yes, why then mind boggling sums in billions of dollars are being paid as settlement fees by large number of global pharma companies for alleged colossal marketing malpractices in different countries of the world.

This scenario prompts a large number of stakeholders believe, though over-hyped by the global pharma industry, ‘Voluntary Practices’ alone of Pharma Marketing Code’, has never worked anywhere in the world.

In this article, I shall discuss this very point in the Indian context, following the recent decisions and developments related to ‘Uniform Code of Pharmaceutical Marketing Practices (UCPMP)’.

No more proof required:

Although no further proof is required to vindicate the point, just to put this particular deliberation into perspective, I would cite below no more than a couple of recent examples of comments and arguments on this subject, out of so many, as are being frequently reported by the international media:

A February 24, 2014 article highlights that in the last few years alone pharmaceutical companies have agreed to pay over US$13 billion to resolve only U.S. Department of Justice allegations of fraudulent marketing practices.

On November 6, 2014, BBC News deliberated and commented, “Imagine an industry that generates higher profit margins than any other and is no stranger to multi-billion dollar fines for malpractice.”

It is worth noting, all those pharma players paying hefty fines due to alleged humongous marketing misadventures, also prominently display their well-crafted codes of pharma marketing practices for strict voluntary adherence in their respective websites.

Why are such wrongdoers not brought to book in India?

Instances of serious marketing malpractices by several pharma companies in India are also being widely reported from time to time by both the international and national media, including television channels. Even a Standing Committee of Indian Parliament had expressed its grave concern on the subject and urged the Government to place stringent deterrent measures in this area, soon.

Concernedly, instances of levying massive fines or for that matter any other punitive measures taken by any competent authority for similar delinquency in the local drug industry have not been reported from India, just yet. This is only because, India doesn’t have in place any specific regulatory and legal framework as deterrent that would detect, investigate and decide on punitive measures against the erring pharma companies for such misconducts, wherever justifiable.

Government decided to implement a globally failed model:

Personally I have high regards on a large number of astute bureaucrats in India, whom I had occasions to interact with both one-on-one and in groups. Most of their minds are razor sharp and the analytical ability is of the highest order. I am reasonably confident that they know quite well what would work and what would not, to get the expected results in India. The chronicle of the ‘Uniform Code of Pharmaceutical Marketing Practices (UCPMP)’ in that sense is intriguing.

Be that as it may, the bottom-line is, totally ignoring the reality in this regard, the Department of Pharmaceutical (DoP) wanted to make a beginning with the failed model of ‘Voluntary Practices’ of the UCPMP in India.

Accordingly, on December 12, 2014, by a circular to Pharma Industry Associations, namely, IPA, OPPI, IDMA, CIPI, FOPE and SPIC, the DoP announced ‘The Uniform Code of Pharmaceuticals Marketing Practices (UCPMP)’. The communique said that the code would be voluntarily adopted and complied with by the Pharma Industry in India for a period of six months effective January 1, 2015.

The DoP also stated that the compliance to this code would be reviewed thereafter on the basis of the inputs received.

I discussed the key issues related to this DoP circular on voluntary implementation of UCPMP in my blog post of December 29, 2014 titled, “India’s Pharma Marketing Code (UCPMP): Is It Crafted Well Enough To Deliver The Deliverables?”

The time for review:

Thereafter, the clock started ticking to catch the 6-month deadline. As June 2015 took its place in the pages of history, it was about time to ascertain the quality, depth, breadth and seriousness level of implementation of the UCPMP during the past six-month period.

Meanwhile a media report of August 4, 2015 speculated that the Government is planning to make the UCPMP mandatory on the drug and medical devices industry, making it tighter and providing teeth to it.

Has voluntary implementation of UCPMP made any difference?

Stakeholders are now curious to know, what difference has the voluntary UCPMP made during January – June 2015, period?

The mechanism as enunciated by the DoP in its above circular prescribes a virtually unimplementable review process, making the whole exercise subjective and creating a ‘your perception versus my perception’ sort of situation.

This gets vindicated when a leading news daily of India quoting an industry person reported, “There are (only) 15-20% black sheep who are bringing bad name to the entire industry”. Come on…this is a totally subjective, baseless and no more than just an off the cuff comment.

Voluntary implementation requirements of UCPMP grossly impractical:

The ‘Mode of Operation’ of voluntary UCPMP was listed by the DoP under point 8 of its above circular, as follows:

  • All the Indian Pharmaceutical Manufacturer associations will have UCMP uploaded on their website.
  • All the associations will upload on their website the detail procedure (as stated in Para 10) of lodging complaints.
  • All the associations will also have a provision on their website for uploading the details of complaints received i.e. the nature of complaint, the company against whom the complaint has been made, the action taken by the committees under the association including the present status in the complaint and such details of a complaint should remain uploaded in the website for three years. The details of proceedings in a complaint and decisions thereafter will be sent by the concerned Association on Quarterly basis, to National Pharmaceutical Pricing Authority, on following address: Member Secretary, NPPA, 3rd Floor, YMCA Cultural Centre Building, 1 Jai Singh Road, New Delhi.

The above UCPMP circular finally says:

“The Managing Director/CEO of the company is ultimately responsible for ensuring the adherence to the code and a self declaration, in the format given in annexure shall be submitted by the executive head of the company within two months of date of issue of UCPMP and thereafter within two months of end of every financial year to the Association for uploading the same on the website of the Association. The same must be uploaded on the website of the company also.”

Unrealistic review process:

I have two fundamental questions in this regard, as follows:

1. Do all pharma Trade Associations have websites?

It appeared from my Internet search that just one pharma trade association in India has a website. However, I could not gather the required details even from that particular association’s website.

The readers may also try to locate the very existence of other Indian pharma trade associations’ websites, if I have made any mistakes during my trip to the cyberspace, and attempt to get the relevant details on UCPMP as stated in the DoP circular.

2. Are all ‘voluntary compliance letters’ from the Managing Directors in place?

Are voluntary compliance letters on UCPMP from all Managing Directors of  all the pharma companies are with the Department of Pharmaceuticals by now? If not, based on which information the above news item reported that only 15-20 percent of the pharma companies did not comply with the voluntary UCPMP?

Relying only on ‘Voluntary Practice of Code’ is a globally failed model:

A healthy ecosystem for ethical marketing practices should be created and propagated within the pharma organizations of all size and scale of operation. In that sense, voluntary code of pharmaceutical marketing practices prepared by individual pharma organizations or their trade associations such as IFPMA play a commendable role. However, only those are not just enough anywhere in the world, as enumerated above.

Encouragement for voluntary practice of pharma marketing codes by the stakeholders is desirable in India too, predominantly to catalyze a change in the decades old and overall fragile ‘Jugaad’ mindset in this important area of pharma business.

In that sense, just as a starter, DoP’s initial push with voluntary practice of UCPMP is conceptually understandable, though the Department appeared to have messed up totally in its critical operationalization area for the purpose of a diligent review after 6-months.

Many countries initially relied on ‘voluntary practice’ of Pharma Marketing Codes crafted by the pharma players and their global trade associations, mostly in line with the Gold Standard of IFPMA Code of Pharmaceutical Marketing Practices. However, later on, all these countries had to put in place other regulatory and legal checks and balances for the interest of patients.

Why ‘voluntary practice’ concept alone, is not enough?

Strong internal and external performance pressures, while navigating through turbulent business environment facing strong head winds, could temporarily unnerve even the seasoned persons with nerves made of steel, as it were. It has been happening all the time, now more frequently, for different reasons.

Thus, all-weather ‘voluntary practice of marketing code model’ in isolation, has globally failed in the pharma industry, almost everywhere.

Appropriate regulations and robust laws promising justice to all, would always demonstrate a commendable role as a tough deterrent in those trying situations, unless any person or a legal entity is a hardcore manipulator focusing just on profiteering.

Related laws and regulation in other countries:

Most developed nations, such as Europe, United States, Canada, Australia, Japan, to name a few, have robust laws and regulations in this area, which act as serious deterrents to pharma marketing malpractices.

These deterrents fall primarily into the following three areas:

Specific anti-corruption regulatory and legal agencies:

Many Governments, such as, the United States and the member countries of the European Union (EU), are strictly enforcing appropriate legal and regulatory measures through dedicated enforcement agencies constituted specially for this purpose. These agencies can investigate any wrongdoings in the pharma marketing area and initiate judicial proceedings.

Specific anti-bribery Acts covering even overseas activities:

Current anti-bribery and anti-corruption laws in many countries, such as, the United States Foreign Corrupt Practices Act or the Bribery Act of the United Kingdom have impacted several global pharma players pretty hard, as these laws affect them even beyond the shores of their respective countries for indulging in marketing malpractices.

Public disclosures:

One such example is ‘The Physician Payment Sunshine Act’ of the United States. This was a part of its healthcare reform bill that was adopted in March 2010 and was finally released in March 2013.

Under the Sunshine Act, data on payments and gifts made to physicians and teaching hospitals by medical device and pharmaceutical companies must be publicly available on a searchable federal database, starting in September 2014.

What may happen, if UCPMP is made mandatory:

If UCPMP is made mandatory, I would suggest at least the following three actions:

  • Appropriate transparent rules, regulations and laws with adequate teeth to address this specific purpose either to be framed afresh or the existing anti-corruption and anti-bribery laws to be amended as required, besides others.
  •  A competent fully empowered authority within the Department of Pharmaceuticals (DoP) should be accountable for administration and implementation of the UCPMP effectively. The DoP may wish to revive its own idea of appointing an Ombudsman with quasi-judicial power for this purpose.
  • State FDAs should play an important role as detecting, investigating and prosecuting agency also for pharma marketing malpractices.
  • DoP website should provide comprehensive details of all punitive action taken against each erring company for this purpose.
  • A compliance certificate from the Managing Directors of the respective companies to the Central Board of Direct Taxes (CBDT) stating that the all sales and marketing expenditures computed for Corporate tax payments are in total conformity with the the UCPMP. Any false declaration should attract serious and exemplary penal consequences.

What would the pharma companies gain?

I would expect at least the following to happen:

  • From the sales and marketing perspective, this new ball game would help establish a level playing field for all the pharma players, to a great extent.
  • Expenditure on sales and marketing would obviously come down sharply, improving product margins significantly, even if a part of this saving is passed on to patients in form of price reductions.
  • Without the allurement of freebies, competitive and innovative brand marketing acumen of the pharma companies would get honed, which would ultimately emerge as the key differentiating factor for the balance of performance to tilt either towards success or failure.
  • Consequently, quality, depth and dimension of marketing inputs for a decisive competitive edge would me more cerebral and distinct in nature, unlike the marketing cacophony in today’s era of freebies.
  • With greater available resources, it would help the pharma players focusing more on talent, skill and technology development to attain sustainable business excellence.
  • The key focus would necessarily shift from ‘buying prescriptions’ to ‘creating prescriptions’ with value based innovative communication of bundled products and services.

Conclusion:

Relying solely on voluntary compliance of ‘Uniform Code of Pharmaceutical Marketing Practices (UCPMP)’, in my view, would not work in India, just as it has not worked even in the developed countries of the world.

This is primarily because, India does not currently have any serious deterrents in this area, including specific legal and regulatory systems, to limit pharma marketing malpractices, unlike many other developed nations of the world.

If the media speculation of DoP’s making the UCPMP mandatory is right, I would reckon, despite its intriguing circular of December 12, 2014, it is a courageous step in the right direction.

Although coming in form of a bitter pill, it would help the Indian pharma players embracing a long awaited and mandatory course correction for not just doing things right, but more importantly doing right things.

I would expect its longer term effect to be ‘win-win’ for all – pharmaceutical industry in India, the Government and above all the patients…well…of course, barring the regular recipients of freebies of all types, forms, kinds, nature and value.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

 

“Make in India…Sell Anywhere in The World”: An Indian Pharma Perspective

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In his Independent Day speech from the ramparts of the Red Fort on August 15, 2014, Indian Prime Minister Modi gave a clarion call to all investors of the world, “Come, make in India”, “Come, manufacture in India”, “Sell in any country of the world, but manufacture here”.

The Prime Minister did not stop there. In his inimitable style, following it through on September 25, 2014 he gave an official status to ‘Make in India’ slogan and launched a global campaign.

“My definition of FDI for the people of India is First Develop India. This is also a responsibility for the people of India,” he further clarified.

An Indian perspective:

If I juxtapose this vision of the Prime Minister in the Indian pharmaceutical industry perspective, one finds that many small, medium and large size local domestic manufacturers are currently manufacturing drugs not just for the domestic market, but are also exporting in large quantities to various countries of the world, including, North America, South America and Europe.

The United States (US) is one of the most critical markets for majority of the Indian drug exporters. This transaction was taking place without any major regulatory hitches since quite some time. Unfortunately, over the last few years, mostly the Federal Drug Administration of the US (USFDA) and the United Kingdom (UK)’s Medicines and Healthcare Products Regulatory Agency (MHRA) have started raising serious doubts on the quality of medicines manufactured in India, making a significant impact on the drug exports of the country.

Most of these quality issues are related to ‘Data Integrity’ in the dug manufacturing and its documentation processes.

The impact:

According to industry data, in 2013-14, Indian drug exports registered the slowest growth in nearly the last 15 years. In this fiscal year, pharma exports of the country with a turnover of US$ 14.84 billion grew at a meager 1.2 percent. Pharmexcil attributed its reason to USFDA related regulatory issues and increasing global competition.

US accounts for about 25 percent of India’s pharma exports and its Federal Drug Administration (USFDA) has been expressing, since quite a while, serious concerns on ‘Data Integrity’ at the agency’s  previously approved production facilities of a large number of Indian pharma players.

The issue is causing not just a serious concern to USFDA and some other overseas drug regulatory agencies, but also posing a huge threat to future growth potential of Indian drug exports.

It is worth noting that Indian government had set an objective, in its strategy document, to register a turnover of US$ 25 billion for pharma exports in 2014-15. In all probability, it would fall far short of this target at the end of this fiscal, predominantly for related reasons.

Why is so much of ‘fuss’ on ‘Data Integrity’?

Broadly speaking, ‘Data Integrity’ in pharmaceutical manufacturing ensures that finished products meet pre-established specifications, such as, for purity, potency, stability and sterility. If data integrity is breached in any manner or in absence of credible data, the product becomes of dubious quality in the eyes of drug regulators.

Manufacturing related ‘Data Integrity’ is usually breached, when data from a database is deliberately or otherwise modified or destroyed or even cooked.

Over the last several years, ‘Data Integrity’ related issues in India are attracting enormous attention of both the USFDA and the MHRA, UK. As a result, concerned pharma manufacturing facilities are receiving Import Alerts/Warning Letters from the respective overseas drug regulators, refusing entry of those medicines mostly in the United States and some in the UK.

Recent warning letters:

Just over a year – from May 2013 to July 2014, around a dozen ‘Warning Letters’ have been sent to the Indian drug manufacturers by the USFDA on ‘Data Integrity’ related issue, as follows:

Recent ‘Warning Letter’ issued to: Date of issue
1. Marck Biosciences Ltd. 08. 07. 2014
2. Apotex Pharmachem India Pvt Ltd. 17. 06. 2014
3. Sun Pharmaceutical Industries 07. 05. 2014
4. Canton Laboratories Private Limited 27. 02. 2014
5. USV Limited 06. 02. 2014
6. Wockhardt Limited 25. 11. 2013
7. Agila Specialties Private Limited 09. 09. 2013
8. Posh Chemicals Private Limited 02. 08. 2013
9. Aarti Drugs Limited 30. 07. 2013
10. Wockhardt Limited 18. 07. 2013
11. Fresenius Kabi Oncology Ltd 01. 07. 2013
12. RPG Life Sciences Limited 28. 05. 2013

(Source: RAPS, 19 August 2014)

Another report states that USFDA has, so far, banned at least 36 manufacturing plants in India from selling products in the US.

Importance of US for Indian generic players:

Generic drugs currently contribute over 80 percent of prescriptions written in the US. Around 40 percent of prescriptions and Over The Counter (OTC) drugs that are sold there, come from India. Almost all of these are cheaper generic versions of patent expired drugs. Hence, India’s commercial stake in this area is indeed mind-boggling.

The ‘Data Integrity’ issue is not restricted to just US or UK:

A report quoting researchers led by Roger Bate, an American Enterprise Institute scholar and funded by the The Legatum Institute and the Humanities Research Council of Canada, concluded that many Indian pharma companies follow double manufacturing standards, as they are sending poor quality drugs to Africa compared to the same pills sold in other countries. This study was based on tests of 1,470 samples produced by 17 Indian drug manufacturers.

Besides India, the researchers took drug samples from pharmacies in Africa and middle-income countries, including China, Russia and Brazil.

According to this paper, the researchers found that 17.5 percent of samples of the tuberculosis therapy rifampicin sold in Africa tested substandard, which means the drug has less than 80 percent of the active ingredient than what it should otherwise. Against this number, in India, 7.8 percent of the medicine sampled was found substandard.

Moreover, Almost 9 percent of samples of the widely used antibiotic ciprofloxacin sold in Africa tested substandard, as compared to 3.3 percent in India.

Thorny issues around golden opportunities:

Much reported breach in manufacturing ‘Data Integrity’ detected at the manufacturing sites in India, are throwing fresh doubts on the efficacy and safety profile of generic/branded generic medicines, in general, produced in the country and more importantly, whether they are putting the patients’ health at risk.

A new analysis by the U.S. National Bureau of Economic Research pointed out some thorny issues related to ‘Data Integrity’ of drugs produced by the Indian pharmaceutical companies, which supply around 40 percent of the generic drugs sold in the United States, as stated above.

The researchers examined nearly 1,500 India-made drug samples, collected from 22 cities and found that “up to 10 percent of some medications contained insufficient levels of the key active ingredients or concentrations so low, in fact, that they would not be effective against the diseases they’re designed to treat.”

The report also highlighted that international regulators detected more than 1,600 errors in 15 drug applications submitted by Ranbaxy. The Bureau Officials commented that these pills were “potentially unsafe and illegal to sell.”

Frequent drug recalls by Indian pharma majors:

The above findings came in tandem with a series of drug recalls made recently by the Indian pharma companies in the US.

Some of the reported recent drug recalls in America, arising out of manufacturing related issues at the facilities of two well-known Indian pharma majors, which are going to merge soon, are as follows:

  • Sun Pharmaceuticals recalled nearly 400,000 bottles of the decongestant cetirizine (Zyrtec) and 251,882 of the antidepressant venlafaxine (Effexor) this May, because the pills failed to dissolve properly. The drugs were distributed by the drug maker’s US subsidiary Caraco Pharmaceutical Laboratories, but were manufactured in India.
  • In the same month – May, Ranbaxy recalled 30,000 packs of the allergy drugs loratadine and pseudo-ephedrine sulphate extended release tablets because of manufacturing defects in packaging.
  • In March, Sun Pharma recalled a batch of a generic diabetes drug bound for the US after an epilepsy drug was found in it. A patient discovered the error after noticing the wrong medication in the drug bottle.
  • Again in March, Ranbaxy recalled nearly 65,000 bottles of the statin drug atorvastatin calcium (Lipitor) after 20-milligram tablets were found in sealed bottles marked 10-milligrams. A pharmacist in the U.S. discovered the mix up.

Indian media reinforces the point:

Indian media (TNN) also reported that there is no quality control even for life-saving generic drugs and the government is apathetic on ensuring that the quality protocol of these drugs is properly observed.

This happens, as the report states, despite government’s efforts to push generic drugs, as they are more affordable. The report gave an example of a life-saving drug, Liposomal Amphotericin B, which is used to treat fungal infections in critically ill patients.

Are all these drugs safe enough for Indian Patients?

Though sounds awkward, it is a fact that India is a country where ‘export quality’ attracts a premium. Unintentionally though, with this attitude, we indirectly accept that Indian product quality for domestic consumption is not as good.

Unfortunately, in the recent years, increasing number of even ‘export quality’ drug manufacturing units in India are being seriously questioned, warned and banned by the overseas drug regulators, such as USFDA and MHRA, UK, just to ensure dug safety for the patients in their respective countries.

Taking all these into consideration, and noting increasing instances of blatant violations of cGMP standards and ‘Data Integrity’ requirements for ‘export quality’ drugs, one perhaps would shudder to think, what could possibly be the level of conformance to cGMP for the drugs manufactured solely for the consumption of local patients in India.

A cause of concern, as generic drugs are more cost effective to patients:

It has been widely recognized globally that the use of generic drugs significantly reduces out-of-pocket expenditure of the patients and also payers’ spending.

The findings of a study conducted by the Researchers from Brigham and Women’s Hospital (BWH), Harvard Medical School and CVS Health has just been published in the Annals of Internal Medicine on September 15, 2014. In this study the researchers investigated whether the use of generic versus brand name statins can play a role in medication adherence and whether or not this leads to improved health outcomes. The study concluded that patients taking generic statins were more likely to adhere to their medication and also had a significantly lower rate of cardiovascular events and death.

In this study, the mean co-payment for the generic statin was US$10, as against US$48 for brand-name statins. It is generally expected that the generic drugs would be of high quality, besides being affordable.

I deliberated on a related subject in one of my earlier blog posts of November 11, 2013 titled, “USFDA” Import Bans’: The Malady Calls For Strong Bitter Pills”.

Conclusion:

According to USFDA data, from 2013 onwards, about 20 drug manufacturing facilities across India attracted ‘Import Alerts’ as against seven from China, two each from Australian, Canadian and Japanese units and one each from South African and German facilities.

Unfortunately, despite intense local and global furore on this subject, Indian drug regulators at the Central Drugs Standard Control Organization (CDSCO), very strangely, do not seem to be much concerned on the ‘Data Integrity’ issue, at least, not just yet.

In my view, ‘Data Integrity’ issues are mostly not related to any technical or other knowledge deficiency. From the “Warning Letters” of the USFDA to respective Indian companies, it appears that these breaches are predominantly caused by falsification or doctoring of critical data. Thus, it basically boils down to a mindset issue, which possibly pans across the Indian pharma industry, irrespective of size of operations of a company.

Indian Prime Minister’s passionate appeal aimed at all investors, including from India, to “Make in India” and “Sell Anywhere in The World”, extends to pharma industry too, both local and global. The drug makers also seem to be aware of it, but the ghost keeps haunting unabated, signaling that the core mindset has remained unchanged despite periodic lip service and public utterances for corrective measures by a number of head honchos.

Any attempt to trivialize this situation, I reckon, could meet with grave consequences, jeopardizing the thriving pharma exports business of India, and in that process would betray the Prime Ministers grand vision for the country that he epitomized with, “Make in India” and “Sell Anywhere in The World”.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Is Fraud or Negligence in Drug Quality Standards Not a Fraud on Patients?

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As we know, a substance is called a drug when it has scientifically proven and well documented efficacy and safety profile to reduce both mortality and morbidity of patients. Any fraud or negligence in the drug quality standards, for whatever may be the reasons or wherever these take place, is a fraud on patients and should warrant zero tolerance.

A perception survey on drug quality:

According to a poll released in 2010 by the ‘Pew Charitable Trusts’s Prescription Project’ of the United States:

  • More than three out of four voters are confident that prescription drugs made in the USA are free from contamination
  • While less than one in 10 feel confident about medications made in India or China.
  • 54 percent of Americans distrusted Indian drugs and 70 percent distrusted Chinese drugs.
  • “When you buy a shirt, it will say right on the label where it was made, but when you get a pharmaceutical, you don’t know.”

Despite all these, the survey points out that in 2007, 68 percent of the ingredients of all drugs sold worldwide came from India or China, as compared to 49 percent in 2004.

Experts comment that USFDA does not have either people or resources required to monitor manufacturing in the geographically widespread locations, as these are today.

Recent spate of charges against Indian pharmaceutical companies – a vindication?

Recent spate of charges against some top ranked Indian companies, will further dent the image of India not just in the United States or Europe, but also as a pharmacy of high quality yet low cost generic drugs for the developing countries of the world.

In May 2013, well known India-based pharma major Ranbaxy reported to have pleaded guilty to criminal charges of manufacturing and distributing some adulterated medicines, produced at its Paonta Sahib and Dewas, facilities and agreed to US$ 500-millon settlement. Can this be considered as a vindication of the above perception on the quality of ‘made in India’ drugs?

The view of WHO:

Interestingly the World Health Organisation (WHO) even after the above USFDA indictment has commented that at present it has no evidence that Ranbaxy manufactured medicines that are currently prequalified by WHO are of unacceptable quality.

Indian drug regulator initiates action:

It is good to know that the Drugs Controller General of India (DCGI) and the Ministry of Health will reportedly decide the way forward in this matter on completion of a fact-finding study initiated by the Central Drugs Standards Control Organization (CDSCO) on the subject.

Other incidents in India:

Following are examples of other reported serious regulatory violations involving the domestic pharmaceutical companies:

No.

Year

Company

Issue

Status
2009 Lupin USFDA warning for Mandideep plant Resolved in 2010
2010 Claris Life Sciences USFDA ban products for manufacturing norms violations Ban revoked in 2012
2011 Zydus Cadila USFDA warns Co. over Moraiya, Gujarat Facility Ban revoked in 2012
2011 Dr Reddy’s USFDA bans sale of drugs from Mexico facility Ban revoked in 2012
2013 Jubilant Life Sciences Gets USFDA warning for Canada facility Company taking corrective steps
2013 Wockhardt Banned from exporting products from its Aurangabad factory to the US due to quality concerns In discussion

Source: The Economic Times (May 22, 2013), Financial Express (May 25, 2013)

Though some other countries also have faced bans from exporting products, it cannot be taken, I reckon, as any consolation by anyone.

A Mumbai Hospital demonstrated the mood of zero tolerance:

The above expression of good intent should not just remain as a ‘lip service’. Indian drug regulator is expected to take a leaf out of all these allegations and initiate appropriate audit as required. Otherwise, exhibiting zero tolerance, like Jaslok Hospital of Mumbai, many other institutions will ask their doctors not to prescribe products of these companies to protect patients’ interest. More hospitals reportedly are mulling similar action against Ranbaxy.

IMA expresses apprehension:

Even ‘The Indian Medical Association (IMA)’ has reportedly asked the DCGI to investigate quality of medicines manufactured by Ranbaxy.

It happens in the ‘heartland’ too just as in the ‘hinterland’:

Contrary to the above poll released in 2010 by the ‘Pew Charitable Trusts’s Prescription Project’, pointing accusing fingers, in this respect, exclusively to India and China, may not be just fair. Incidents of such regulatory violations are not just restricted to Indian pharmaceutical companies either. Unfortunately, these happen with the global majors too.

None of these should be condoned in any way by anyone and attract as much global publicity, public wrath and zero tolerance, as all these would possibly deserve.

Following are some examples:

No

Company

Issues with USFDA

Consent decree signed (year)

Issue status

Penalty amount
Schering-Plough GMP violations affecting four manufacturing sites and 125 products

Yes (2002)

Closed (2007)

 $500 Mn.
GlaxoSmithKline Manufacturing deficiencies found at Puerto Rico facility

Yes (2005)

Pending

 $650 Mn. Bond
Wyeth GMP violations at plant in Pennsylvania and New York which were producing FluShield

Yes (2000)

Pending

 $297 Mn. Plus 18.5% of sales of FluShield
Abbott Labs Non-conformance with quality system regulations for in vitro diagnostic products at an Illinois facility

Yes (1999)

Pending

 $212 Mn.
Boehringer Ingelheim To bring its Ohio facility into compliance with regulatory requirements

Yes (2013)

Pending

 Not specified

Source: Financial Express (May 25, 2013)

Further, in December 1998 the US FDA reportedly had stopped shipments of Abbott Laboratories’ clot-busting drug Abbokinase till the company had resolved undisclosed manufacturing problems at its plant. Abbott subsequently resolved this to the satisfaction of the drug regulator.

Even end May 2011, the USFDA reportedly raised concerns about contamination of drugs of the American pharmaceutical major – Hospira, at its Indian manufacturing facility.This issue was highlighted as the latest in a string of manufacturing and quality problems dogging the company since 2010.

American lawmakers demand thorough review of USFDA oversight procedures:

Pressure has reportedly started mounting in the United States for a thorough review into the effectiveness of oversight procedures for all bulk drugs and formulations manufactured in foreign facilities.

Simultaneously, there is also a specific demand for an in-depth review of all actions of the US regulator for so many years, which allowed Ranbaxy’s ‘massive fraud to remain unchecked’.

Beyond regulatory oversight, need robust internal system driven model as a fire-wall:

To address such issues only drug regulators interventions may not be just enough, maintaining total integrity of ‘Supply Chain’ of an organization proactively in a well structured, fool-proof and a system-driven way, will continue to play the most critical role. This will help creating ‘fire-wall’, which will be difficult to breach.

The scope of Supply Chain:

The scope of ‘Supply Chain’, which is comprised of the entire network of entities from vendors who supply raw and packaging materials, manufacturers who convert these materials into medicines, together with warehouses, distributors, retailers and healthcare centers who will reach these medicines ultimately to patients exactly the way these will deserve.

Thus, just not in the manufacturing process, any breach of security at any place of the supply chain can cause serious problems to patients. 

Accordingly, pharmaceutical companies need to adequately invest along with appropriate staff training programs to ensure that the Supply Chain Integrity is maintained, always.

Supply Chain Security (SCS) is critical:

SCS, therefore, deserves to be of prime importance for the pharmaceutical companies across the globe. Recent high profile SCS related cases, as mentioned above, have exposed the vulnerability in addressing this global menace effectively.

All pharmaceutical players should realize that not just ‘show-off’, an effective integrated approach is of paramount importance to eliminate this crime syndicate, which is taking lives of millions of patients the world over.

Mixing-up counterfeit drugs with this menace may not be prudent:

Shouting for counterfeit drugs involving mainly intellectual property related issues, may be  important, but will in no way help resolving self-created menaces arising out of breach of supply chain integrity endangering million of lives, in another way.

Though an expensive process, can’t be compromised:

It is worth repeating, securing pharmaceutical supply chain on a continuous basis is of critical importance for all the pharmaceutical players across the globe. However, the process will no doubt be expensive for any company.

Like other industries, in the pharmaceutical sector, as well, cost effective procurement is critical, which entices many pharmaceutical players, especially, in the generic industry not to go for such expensive process just to maintain the SCS.

A serious SCS related tragedy:

I would like to reinforce my argument on the importance of SCS with the following example of the ‘Heparin tragedy’ where the supply chain integrity was seriously violated with ‘ingeneuity’.

In the beginning of 2008, there were media reports on serious adverse drug events, some even fatal, with Heparin, a highly sulfated glycosaminoglycan of Baxter International. Heparin is widely used as an injectable anticoagulant. Baxter voluntarily recalled almost all their Heparin products in the U.S. Around 80 people died from contaminated Heparin products in the U.S. The US FDA reported that such contaminated Heparin was detected from at least 12 other countries.

A joint investigation conducted by Baxter and the US FDA ascertained that the Heparin used in batches associated with the serious adverse drug events was contaminated with Over Sulfated Chondroitin Sulfate (OSCS). It was reported that Heparin Scientific Protein Laboratories, Changzhou, China supplied Heparin to Baxter.

The cost of OSCS is just a fraction of the ingredient used in Heparin. Being driven by the criminal profiteering motive the manufacturers in Changzhou, China had reportedly used OSCS for highly sulfated glycosaminoglycan, as the former could not be detected by the pharmacopeia test in use, until 2008. This is because OSCS mimics Heparin in the pharmacopeia test. Post this criminal event, at present, all over the world more specific pharmacopeia test methods have been adopted for Heparin.

Stakeholders need to be extremely vigilant:

Considering all these, pharmaceutical players and the drug regulators from across the world should put proper ‘fool proof’ systems in place to eliminate the growing menace of criminal adulteration of APIs, drug intermediates, excipients entering in the supply chain together with preventing any breach in their logistics support systems.

Apprehension against generic drugs as a class:

Taking advantage of the situation, one can possibly say, as some vested interests have already started propagating that generic equivalents of the branded drugs are really not quite the same in quality.

However, the point that cannot be ignored is the comment of a senior USFDA, who was quoted in the same article saying, “I have heard it enough times from enough people to believe that there are a few products that aren’t meeting quality standards.“

Generic drug manufacturers should make serious note of such comments and act accordingly to allay prevailing lurking fear on the use of generic medicines, in general, though small in number.

Conclusion:

Following the recent series of incidents including that of Ranbaxy, the image of India as a low cost generic drugs manufacturer of high quality could get adversely impacted. Although there are enough instances that such things happen in the developed world, as well, including the United States.

Moreover, in the backdrop of high decibel quality concerns raised by USFDA, the level of apprehension regarding effectiveness of generic drugs made in India may increase significantly, unless some tangible, well thought out and highly publicized remedial measures are taken forthwith.

The decision of Jaslok Hospital, Mumbai advising their doctors for not using Ranbaxy products to patients on the same ground, will further strengthen the public apprehension.

Whatever may be the reason, as long as any company is in the business of manufacturing medicines, there should be demonstrable zero tolerance on any compromise, fraud or negligence in the drug quality standards. Any fraud and negligence in drug quality, I reckon, is virtually a fraud against humanity.

That said, changing mindset towards a strong corporate governance by walking the talk, all pharmaceutical companies must guarantee safe and high quality medicines to the society, come what may.

This, I believe, could be achieved by putting in place a robust SCS system and ensuring that this is not compromised in any way… anywhere…ever… for patients’ sake…both globally and locally.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.