Introduction and aim of this article
In the third week of March 2016 almost all major newspapers in India and some abroad carried news in their first page that central government has banned of 344 Fixed Dose Combination drugs (FDCs).
While some newspapers carried matter of fact headlines, some others guessed about pharma companies 'immediate loss of 1k crore". Some also gave names of some popular over the counter medicines as banned. Some sub titles and opinion reports from pharma company side gave a wrong impression that the govt took a harsh decision overnight causing loss to the pharma companies. It also led people to believe that they are suddenly deprived of many popular medicines. The next day news items highlighted High Court stayed the ban of FDC drugs. That compounded the doubt and led ordinary people to take that government had done something illegal or unethical. The facts are different.
The aim of this article is to dispel the doubts of laymen and give some awareness in the matter.
What exactly did the Indian government do
The Ministry of Health & Family Welfare, Government of India- by a Gazette notification dated 10th March 2016- using section 26A of Drugs and Cosmetic Act 1940, prohibited manufacture and sale of 344 Fixed Dose Combinations of drugs for human use .
The notifications numbered 705 to 1048 are similarly worded except for the name of the banned drug combination. I quote below some relevant portion of notification for sample and understanding (as copied from the web site cdsco.in) but without showing the drug name:
" Whereas, the Central Government is satisfied that the use of the drug fixed dose combination of ................(name of FDc drugs) is likely to involve risk to human beings whereas safer alternatives to the said drug are available;
And Whereas, the matter has been examined by an Expert Committee appointed by the Central
Government and the said Expert Committee recommended to the Central Government that the said drug is found to have no therapeutic justification;...............................
Now, therefore, on the basis of the recommendations of the said Expert Committee and in exercise of powers conferred by section 26A of the Drugs and Cosmetics Act, 1940 (23 of 1940), the Central Government hereby prohibits the manufacture for sale, sale and distribution for human use of drug fixed dose combination..................(name of the FDC)"
Each of the 344 notification gives name of separate combination, thus totalling to 344 FDCs..
What is the reason for the ban on FDC s
The reason is self explanatory as can be found in the first and second para of notification as quoted above: "likely to involve risk to human beings whereas safer alternatives to the said drug are available;" and "drug is found to have no therapeutic justification"
Section 26A empowers government to prohibit the drugs for these reasons.
Though these FDC s were available commonly and people used them as self prescription various independent studies and also the government appointed experts panel also found that the combinations' have no therapeutic justification' and 'likely to cause 'risk to human beings'
The situation gets compounded because FDC drugs have been found in almost every common therapeutic use areas. They include the commonly used items like cough syrups having combinations of codeine ,Non-steroidal anti inflammatory drugs, analgesics and even antibiotics. They also include the item banned in many countries-Nimesulide -and its various combinations. It is only when the actual brand names are known that we will come to know that each of us are also consuming one or more of them most commonly. The newspapers gave prominence to names like Corex, Vicks Action500 etc as they are here for many years and gave their companies good revenue..( Reports later said that the respective manufactures have approached court and obtained stay).
What are Fixed Dose Combination(FDC) drugs
Now that we know that govt has banned these drugs as they are likely involve risks to human beings or they do not have the therapeutic value claimed, le us see what FDCs are.
Definition of FDC given in the Policy Guidelines For Approval Of Fixed Dose Combinations (FDCs) In India by Ministry of health and family welfare is: "A combination of two or more actives in a fixed ratio of doses. This term is used generically to mean a particular combination of actives irrespective of the formulation or brand. It may be administered as single entity products given concurrently or as a finished pharmaceutical product."
Food and Dugs Administration, USA defines FDC as 'a product composed of any combination of a drug and a device or a biological product and a device or a drug and a biological product or a drug, device, and a biological product'.
For a layman, to say in simple way, an FDC drug is a combination of two or more separate drugs combined in a fixed ratio and given as a single dose.
Why many common FDC are termed 'irrational'
The basic rationality of a fixed combination drug is that it should work better at such dose than when they are administered separately as independent active ingredients. The drugs should not have more harm or side effects.
On the contrary, many independent studies found that most of the FDCs in India are irrational because they don't have the therapeutic value as claimed, expose patients to unnecessary adverse effects . One example is Nimesulide+Paracetamol(included in the notification).It is known that Nimesulide by itself is more efficient in anti-pyretic properties (against fever ) than Paracetamol; better anti-inflammatory effect than aspirin and equalling any NSAID in analgesic properties. Thus, addition of Paracetamol is not likely to give any additional efficiency. Hence the combination is irrational. Moreover Nimesulide itself is banned or regulated in many countries.
Now, combination of anti-biotics. Antibiotics work only against specific infection. When given as combination, one or other antibiotic in them may be just useless and ineffective. The injudicious use can lead to emergence of drug resistant bacteria..
Many FDC s available in India are banned in US, UK, Israel, Germany etc. either as FDC s or individually.
What is the background for the present ban on FDC s
Earlier attempts of government to control FDC s did not yield results.. Prior to the present notification, in 2007 government placed a ban on 294 products approved through state licensing authorities. Some drug manufacturers challenged the ban in courts and Madras High Court stayed the ban notification. The cases are pending. Some other similar efforts were also opposed by manufacturers.
A study as of 2011 revealed that World Health Organisation in its 16 th Model list of essential medicines had 351 essential medicines including 26 FDCs, while Essential List of Medicines in India had 354 including 14 combination drugs. Still,(it was found) that there were about 1000 different brand medicines of 70 dangerous FDCs.
It was in this situation in May 2012, Parliamentary Standing Committee on Health and Family Welfare, in its 59th report presented some serious observations about the weakness and deficiencies in the area of CDSCO and DGCI on approval and regulation of pharmaceutical drugs in this country. They reported that manufacturing licenses for large numbers of fixed dose combination (FDC) drugs had been issued by state authorities without prior approval of the Central Drugs Standard Control Organization (CDSCO) in violation of rules
Subsequently in February 2013, as a follow up action to the Parliamentary committee report, the government constituted two expert committees:
(1) Expert committee, to formulate guidelines on SOPs, for approval of new drugs, clinical trials and banning of drugs; under Chairmanship of Dr Ranjit Roy Chaudhari, National Professor of Pharmacology.
(2) An expert committee to formulate policy guidelines and procedures for approval of fixed dose combinations, was formed under the Chairmanship of Prof. K.C.Kokate, Vice Chancellor, KLE University, Belgaum Ranjit Roya Committe submitted report in July 2013.
A study by Jayeshbhai Dineshchandra Balat and others in Ahemedabad published in 2014 conclude that FDC s are widely prescribed with seasonal influence in their use. FDCs containing banned or controversial ingredients were also prescribed widely.
A study report by PLOS Medicine shows that of the 175 formulations studied, only one third had the approval. These 175 formulations were available and sold in the market as 4000 products. So a simple calculation of two thirds of 4000, i.e about 2680 unapproved products freely available in the market and people were consuming them also.
An Economic Times report ( March 14, 2016) cited Prof Kokate saying that drug companies were given notice, three months after a sub-clause notice, asking them why their drugs be not banned. He reportedly said that the response from the industry was poor. Kokate committee studied over 6000 drug samples and recommended ban of the 300 plus combinations found to be irrational.
All the above justify the ban. After all government has to put public health as priority.
PART I conclusion
This part I article has given the background and logic of the government ban on FDCs. However there may be some more related doubts which need be clarified. They are dealt in PART II of this article.
Now that GST is to be implemented from July 1, 2017, in India the feeling is that medicines will become cheaper. If that materialises and the manufacturers pass on the benefit to the users, then that can happen and it will be great relief to the people. Affordable healthcare is the priority of a welfare state.