Reacting strongly against the ban on 344 FDC drugs, industry veterans call it a hasty decision and question the government’s approval process which had earlier given the nod to these drugs. Edited excerpts of their insights By Usha Sharma
‘FDC ban will be bad for immediate financial health of any company’
There is substantial loss to companies as order prohibiting Fixed Dose Combination (FDC) was sudden. The industry has not been given any time and prohibition is with immediate effect. Companies have to stop production forthwith and it is expected that the packing material lying with them needs to be destroyed. The raw materials may be used in other formulations, the packing materials cannot.
Government’s move in banning FDCs
The issue to prohibit FDCs may be going on for the past 10 years. The new drug department was occupied more for assessing ‘new chemical entities’ and probably did not have enough resources to see that all FDCs need a closer look from patient safety angle. Few of the state licensing authorities were referring cases to them for clearance. It has appointed new drug approval committee (NDAC) and later expert committee. It did not have the machinery to see that all FDCs are first approved by the DCG(I) and then granted permission to manufacture.
Secondly, the government did not have any power to exercise control over the state licensing authority.
Alternative to FDCs
Physicians have to look for safer substitutes. Their source of information has to be very good. It may be easy in bigger cities, however, will be difficult in smaller cities and towns. A particular company’s price-to-sales ratio (PSR) who was promoting his FDC may not be in a position to inform about the safer alternative. Therefore for sometime when the patients will shift from FDC to single drug, they may suffer. Physicians need to be constantly consulted even for long-use products e.g. such products where physician prescribes for six months or even more. Patients who visit nursing homes or hospitals may face more difficulties. This may be beneficial when FDCs with some synergistic effects will only be available and rest are weeded out.
Impact on ‘Make in India’ initiative
The ‘Make in India’ initiative is to reduce dependency on anything that we are importing. FDC ban will definitely be bad for immediate financial health of any company. It may withdraw the zeal of a company to contribute to PM’s ‘Make in India’ initiative.
Alternative ways for growth
Companies, having strong R&D base, may go for technology improvement and increase acceptance of their brand. Simple products through nano-technology are appearing in the market now. I again emphasise different strategies for long-use and short-use products. Antibiotics are short-use products and I feel the FDCs may be marketed only when good synergistic action is demonstrated. Personally, I feel antibiotics need not be presented in FDCs except those where dose compliance has been demonstrated to be far superior to single antibiotics.
The discouragement of FDCs without scientific rationale is going to be there for some time with the Central Drugs Standard Control Organisation (CDSCO). Industry associations must emphasise to regulators that patient’s safety is equally their concern as well as that of regulatory bodies. Combination products need to be formulated with sound justification of each ingredient. Combinations are very useful for geriatric, illiterates and other patients for better medication compliance. Industry must address this aspect and approach the regulatory bodies. I am sure regulators will understand this. Industry has to be there for fulfilling patient’s need and unwarranted curbs. Sudden notification gives the impression that genuine manufacturers have little concern for patient and are only profiteering.
– Kapil Bhargava, Former Dy Drugs Controller
‘The DCG(I) has no business to ban FDCs which are in the market for more than 30 years’
The recent ban on FDCs by the office of DCG(I) is a knee-jerk reaction to the recent observations by international agencies on the relatively poor regulatory standards of the CDSCO and DCG(I).
With the increasing global trends of TBT/ NTB being built up and targeted towards India’s pharma exports, the Government of India (PMO, DIPP etc) has of late been pressuring the Ministry of Health and Family Welfare (MoHFW) and the CDSCO to join ICH and PICs at least as an observer. Fully realising the internal weaknesses of the system and the CDSCO, the MoHFW and DCG(I) has apparently deflected the external pressures on to the pharma industry, through this ‘irrational blanket and abrupt ban.’
It is admitted that India is weak on pharmacovigilance. Why so? Both IMA, DCG(I)-CDSCO, DoP and others are to blame. In the 70’s, all formulations used to be packed into cartons with product inserts indicating mode of use, indications, contra indications, warnings etc. With the increasing NGO influence, making ‘hue and cry’ about “Indian drug prices being highest in the world”, the NPPA started cutting drug prices to below practical levels, forcing the industry to abandon all ‘frills’ in packaging thereby throwing to the wind, all product information through leaflets, which would have helped in pharmacovigilance.
Phenacetin, Analgin, Diiodohydroxyquin, Iodochlorohydroxyquin, Cox-inhibitors such as valdecoxib and Rofecoxib, Propoxyphene and Dextro propoxyphene, Methaquolone were all single ingredient drugs which were in market for three to four decades before getting banned based on pharmacovigilance data i.e. evidence-based. Some of the 344 drugs which are now banned unilaterally and abruptly are not only having no reports of side effects or adverse drug reactions, but also these very same combination drugs have become synonyms for lifesaving and well-being.
I strongly feel that some of the drug combinations bed abruptly will hurt patients badly. I am surprised why the DCG(I) has not thought of this priority concern
The sad part of the story is that the regulator has totally ignored the misery to the patient all of a sudden, denying access to a drug they were relying on for years.
The DCG(I) has no business or powers to ban FDCs which are in use in the market place for more than 30 years or thereabout. The ban is ultra vires, devoid of natural justice and merits to be struck down. While fully agreeing that there are true black sheeps and genuinely ‘irrational’ combinations, DCG(I) needs to ask each of the pharma companies who own and market the 344 banned drugs to explain why they should not be banned. Having killed the ‘clinical trial’ and pharma BA/BE study facilities, through poor and passive response to Supreme Court (under pressure from NGOs), DCG(I) cannot and should not ask each of these brand owners to conduct fresh clinical trials and submit data for approval in new format. The historical data of use, benefit and lack of risk is good enough data to approve or formalise the approval.
If a high court judge in a patent injunction case, considers patient’s interest for access to treatment, the DCG(I), being custodian of patient health, on behalf of MoHFW, ought to have thought of the patients who were availing these combination drugs for years. If one looks at past history of ‘bans,’ they have all been through phasing out and not abrupt bans.
Actions against unapproved drugs
It is unfair to say that there are “many unapproved drugs in the Indian market.” Being in the pharma industry for nearly 50 years, I can safely vouch that if there are any “unapproved drugs” in the Indian market, it has to be spurious or illegal. Any person or company marketing or selling ‘unapproved’ drugs merit to be summarily put behind bars. All drugs legally sold in the Indian market are approved by one or other ‘licensing authority’. The dispute is due to the concurrent nature of Drugs & Cosmetics Act, which grants the power to approve both to the State FDAs as well as to Central CDSCO/DCG(I) in case (only) for ‘new drugs.’ ‘New drugs’ are defined in the Drugs Act, as those which are introduced for first time in Indian market. A ‘New Drugs’ ceases to be new drug after four years. If an ‘approved drug’ (whether by State FDA or CDSCO) is in the Indian market for more than four years (leave alone 40 years), it cannot be banned abruptly. The DCG(I) should give individual companies the opportunity to be heard, justify the combination, make changes if needed as per suggestion/advise of DCG(I)/ State FDA and seek ‘minimum’ additional evidence, if required. The actual market place data is many times more valuable, reliable and evidence-based than any data generated through volunteers.
Need of intense focus
The Indian pharma industry is being attacked on multiple fronts both openly as well as surreptitiously. Various treaties, agreements, non-tariff barriers, technical barriers etc. are being put up to stem the growth of Indian pharma. While the PMO, DIPP and Commerce Ministry is aware of this, the officers at the grass root level are becoming victims of NGOs and vested interests, both from within the country as well as overseas to dilute the gains made by Indian pharma industry post-1970 and mostly post-1995 (WTO-TRIPs).
The FDC ban will badly impact PM’s ‘Make in India’ initiative. It will also malign Indian pharma’s name in the global markets. This will also stem the otherwise strong potential of Indian pharma to be world leader in combination drugs and therapies.
The roadmap from here onwards for the Indian pharma industry is to unite in national interests, insist for industry representation in all technical, legal and statutory committees. Indian industry must take note (too late) of “JNU- Kanhaiya” type NGO activity, which is well-entrenched in the corridors of Delhi, the presence of which need to be alerted at the highest levels. These negative activities which are well planned to damage the fair name and contributions of Indian pharma industry, need to be countered unitedly by Indian pharma industry, at the same time identifying and weeding out the wrong doers within, if any.
– Dr Gopakumar G Nair, Chief Executive Officer, Gopakumar Nair Associates
‘FDC ban and the US FDA alerts are a wake up call for the industry’
The Indian pharma industry which has earned the distinction of being the ‘Pharmacy of the World’ is currently facing strong headwinds impacting its growth and profitability. Rigid price controls, weak IPR enforcement, US FDA alerts, intense competition from cheap API imports from China, reducing tax incentives for R&D etc. have taken its toll. As if this is not enough, CDSCO has now banned 344 FDCs with immediate effect many of which have been in the market for over two decades and some even approved by the DCG(I). Apparently some more are likely to be added to this ban, resulting in about ` 3500-crore loss in sales. This is also likely to slow down M&A activity many companies were pursuing for inorganic growth. While the Delhi High Court has given an interim stay on the ban, resolving issues through litigation has always been painful and time consuming process. While financial loss is only secondary to patient safety, in a science based industry like pharma, key decisions like this have to be taken based on scientific principles and laid down processes rather than knee jerk reaction as shown by the CDSCO. As regards the timing of the ban which came in to force one day prior to the PIL filed by the former Ranbaxy whistle blower Dr Dinesh Thakur in the Supreme Court against DCG(I) for failing to ensure product safety, gives rise to speculation.
The root cause of this mess lies in having a dual regulatory control of state as well as centre. To remedy this anomaly, the central government appointed a committee under the chairmanship of reputed scientist Dr RA Mashelkar way back in year 2007. The committee’s recommendation of forming a Central Drug Authority (CDA) on the lines of US FDA was approved by the then Union Cabinet and the bill was introduced in the Rajya Sabha. Later, it was forwarded to the Parliamentary Committee which is lying on back burner since then.
Formation of CDA is of utmost importance as in many small states FDA is virtually non existent. The irony is, product approvals given by such state FDAs are valid throughout the country. Also, appointing IAS and police officers as State FDA commissioners should be stopped as many a times they lack the necessary domain knowledge required to run the FDA effectively. Sometimes pharma companies launch FDCs to differentiate their product from over 70,000 branded generics which have cluttered the market. At times FDC strategy was also used to circumvent DPCO, although this loop hole has now been closed.
While there are some FDCs which are irrational and unsafe, some are quite rational and offer the patient advantage of dosage convenience and reduced cost. For instance the recent 14th WHO model list of essential medicines lists 312 essential medicines of which only 18 are approved as FDCs. Since pharmacovigilance system is quite weak in our country, an FDC is safe just because it is available in the market for decades is a weak argument. Needless to mention the irrational FDCs should be weeded out in a phased manner based on the safety and efficacy data submitted by the manufacturer. The FDC ban and the US FDA alerts are a wake up call for the industry who should also introspect and take remedial action.
‘Make in India’ will remain just a slogan if pharma industry does not focus on quality, efficacy and patient safety as a priority.
– Dr Ajit Dangi, President and Chief Executive Officer, Danssen Consulting
‘The government’s averment to ban FDC drugs has been undertaken due to issues concerning patient safety’
Patient safety is of paramount importance and no matter how much is the economic loss, it cannot justify any sort of compromise with patient safety. While the notifications banning the FDC drugs state that the banned FDCs are ‘likely to involve risk in human beings whereas safer alternatives to the said drug are available’, there is still uncertainty on whether that is actually the case or not. The government in recent hearings has made averments that the move to ban FDC drugs has been undertaken in view of issues concerning patient safety. On the other hand, manufacture have stood by and asserted that these drugs are safe and beneficial for patients. The issue of economic loss has been taken into account by Delhi High Court while granting an interim stay against the applicability of notifications, however, such a stance would be irrelevant in case the government can establish that FDC drugs are unsafe.
Impact of ban
Uncertainty as to whether these popular FDC drugs would continue to be in the market, would certainly pose some questions on the prospects of growing horizontally. These FDCs in certain cases, represented more or less a fixed revenue stream for their respective manufacturers, which they cannot bank on, at least till the issue is resolved by Delhi High Court. While this might in some cases make the valuation attractive for merger and acquisition purposes, an uncertain legal/ regulatory environment can never be conducive for business in general.
Most of the drugs banned in the notifications were already manufactured in India so if it is upheld by the court, the same would surely have an adverse impact on the manufacturing activities in India.
– Abhijeet Das, Senior Associate, Singhania and Partners
Already hit by global recession, FDC ban will further dampen the spirit of Indian pharma industry
Both, Indian regulators and Indian pharma industry have been globally applauded for their work. But the scenario is very different at the national level. Far from the applause, the regulators and the industry have been questioned on various grounds, including high pricing, GMP implementation and now, very recently, on irrationality of combination drugs being sold.
The Central Government issued notification Nos 705(E) through 1048 (E) to ban the manufacture, sale and distribution of 344 FDCs. FDCs are combinations of two or more APIs, usually combined for a synergistic effect and patient compliance. The notifications banned 344 of such FDCs terming all of them as irrational combinations. It is noteworthy that the ban is not based on incidence of adverse effects observed on patients, but due to the rationality of the combining specific ingredients. Industry feels that generalisation of irrationality to all 344 combinations isn’t appropriate, and a second review, with all stakeholders on board, may be a good idea.
The domestic pharma industry is estimated to be over Rs 98000 crores, of which the 344 FDCs constitute around Rs 3800 crores. The sudden ban has come as a jolt to the trade and industry. It is estimated to have impacted around 17 per cent of the respiratory segment, around eight per cent of the diabetic segment and around four per cent of the anti-infective segment.
It is also estimated that a huge stock of these products will have to be recalled and destroyed. The distribution chain members — retailers, wholesalers and distributors will have a huge task in identifying, isolating and returning these products. The marketers and manufacturers have to undertake a herculean task in collecting these products and destroying them. This calls for immense cost, time and efforts. Some feel that the government ought to have given a window for clearance of goods from the market, limiting financial losses to the trade and industry.
Over and above, the loss due to stock destruction, the money spent in developing and marketing these brands will also go to drain. This is a big financial dent to the pharma trade and industry. This step has dampened the spirits of the pharma industry that is already facing the heat of global recession.
Few of the FDCs from this list have been prescribed widely by medical fraternity and used for over decades, without any serious adverse effects being reported. Industry people feel that many combinations could have been continued to be allowed considering their therapeutic value, leaving it at the discretion of the prescribers to weigh the pros and cons before prescribing them. Some of these FDCs have been approved after studies or may have clinical evidences to back them. Some FDCs may have been approved even before FDCs came under the ambit of the New Drug definition. Affected industry players have such arguments for the debate.
Another argument that runs in the industry circles is that none of these molecules are individually banned. It is just the combinations that are. There is no mechanism to stop the co-prescription of these drugs by the prescribers. Assuming that it is irrational to combine these drugs, the real benefits to the patients cannot be achieved unless co-prescription is also banned.
The matters have already reached courts, and it is for the honourable courts to evaluate the legal aspects of the entire episode. However, on medical grounds, the industry and the government need to sit together to rethink what went wrong from each side, and ensure adequate corrective and preventive actions. The pharma industry and regulators in India have traditionally worked together constructively on several issues in the past, and one more time they need to hold hands and come out with a solution to this challenge.
– Viranchi Shah, Vice Chairman- Indian Drugs Manufacturers Association, Gujarat State Board
‘Government failed to act with imagination, information, speed’
The authorities should have approached the subject in a time-bound manner rather than banning them overnight. They had the best opportunity and time to approach companies to self regulate in a given time frame keeping the safety aspect of FDCs for a patient. This should have been the prime factor for any FDC.
It is unfortunate. The government could have educated our doctors too on this but the drug department and the government who control had a total disconnect with the medical profession on this subject.
The recipient doctor or doctors could have been sensitised too on this which would have automatically created a climate of safety for patients.
Indian Medical Association and other federating associations of different faculties in medicine could have played a major role in sensitisation of doctors. Even Pharmacy Council of India could have thrown their weight around by educating manufacturing pharmacists.
Handling situation wisely
Certain short duration timelines need to be set by the Drug Controller General (India) in doing this because from time to time the global regulatory authorities of different countries do spell and convey the unapproved drugs and their reasons in different forums.
The government has failed to act with imagination, information and speed on this.
After all, this phenomenon was done for the patient’s safety globally. There is no segmentation in patients like an American or African or Indian. Patients are patients irrespective of their country. Doctors are capable of prescribing drugs and drug combinations individually and adopt a definite counselling session with the patient.
Will growth down?
Now pharma companies are temporarily in a fix but can recover through self regulation themselves. Mergers can be delayed instead of distress mergers. All that they have to do is to modify the FDC in such a way that the FDC fits into the regulatory profile as well as of the safety profile of the patient. This is only a question of time. The best attitude for the industry is to be proactive with the regulatory authorities of the country and thus create a climate of mutual trust and credibility in the industry.
Effect on ‘Make in India’ initiative
One cannot think so because the healthcare industry is going to be a progressive process. The doctors will resort to change in their habits. The companies will sell alternative formulations. In fact there will be an overall systematic change of perception in the manufacturing of both single ingredient products and FDCs henceforth.
A shock treatment of this nature was imminent and necessary and it will only promote a robust, accepted and trusted growth. Thus Make in India in no way will suffer but add more teeth to the manufacturing.
The road map for the pharma industry should be such that
- Their focus in the organisation should be with the scientific department more than marketing and sales
- There has to be a holistic approach while designing an FDC by putting a lot of clinical substantiation and promote the products in such a way that the doctor translates the information as credible rather than useful.
- The companies should promote the indications of the product surely but they also should convey the likely adverse reactions when used on a patient thus keeping the medical fraternity fully informed.
- In fact the doctors too should be encouraged to know the safety profiles of the products as many products are consumed for a long period due to the chronic nature of the disorders.
- A proactive attitude towards the regulatory authorities of the country and the state by establishing a full proof information system of manufacturing FDCs through reports.
– SR Vaidya, Director, Bliss GVS Pharma and Chairman, SME Committee, Indian Drug Manufacturers’ Association
FDCs ban is long overdue and must be lauded
MoHFW’s initiative to ban irrational Fixed Dose Combinations (FDCs), in the interest of patient safety, is long overdue and must be lauded. However, the overnight imposition of a blanket ban on 344 products remains a concern. Many of these FDCs have been previously approved by the Drugs Controller General India (DCG(I) as safe and efficacious. Some of these approved products currently have no alternatives; and banning them with immediate effect denies access for patients to medicines that are approved as safe and effective in India and abroad
– Ranjana Smetacek, Director General, Organisation of Pharmaceutical Producers of India (OPPI)