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Mantras for success: FDCs and NDDS


Dr Gopakumar G Nair, CEO, Gopakumar Nair Associates, urges the Indian pharma industry to pursue the FDC plus NDDS route to ensure regulatory compliant pills with built-in patient convenience and evidence-based consumer benefits

Dr Gopakumar G Nair

“Every cloud has a silver lining”, it is said, “There is always light at the end of the tunnel”. Be it adages, maxims, proverbs and axioms or soothsayers’ predictions, crystal ball readings, priceless priestess Pythia’s Oracle at Apollo- statements, in current scenario of devastating confusions, FDC conundrums and Supreme Court hearings and pronouncements, they all become relevant for Indian pharmaceutical industry. The Indian pharma industry has been growing by leaps and bounds to the dismay of developed country peers. In calm regulatory waters, Indian pharma industry have been growing steadily, till recently when a plethora of problems cropped up, like the proverbial water hyacinth spreading in a pool with calm waters. The FDC controversy has evolved as the front-runner and the rest, like Lord Tennyson’s ‘Charge of the Light Brigade’, problems to left of them, problems to right of them, volleyed and thundered. I have always admired the Indian Pharma entrepreneur’s amazing ‘never say die’ attitude. The Big B, AB have parallels in this Industry and my prediction or prescription is to convert all adversities into advantages and challenges to opportunities. The Indian pharma entrepreneur is adept at it. This is the bottom line of this story.

Thanks to ‘Kokate Committee Report’ or the NGO sponsored tirades against combination therapies in pharma dosage forms, it is introspection and self-appraisal time for combinations, be it 344 or 294. For the Indian pharma entrepreneur, these adverse times should serve as an ideal time to fuel the skill and will to serve the quality pill to the global patient communities by igniting innovative instincts and coming with decades long experience in creating rational combination therapies for patient convenience and prescriber’s preferences. The more rational and evidence-based therapies with embedded quality and delivery systems, the better. More than ever, the road map is getting drawn, the regulatory pathways are being cleared and the rules of the ‘FDC’ game are being spelt out. This is the most ideal god-given or NGO thrusted gift that the Indian pharma industry must grab. While stability and BA/BE studies are becoming almost mandatory and clinical trial guidelines are clearly getting in place, Indian pharma entrepreneurs must take this as an opportunity and not only to put the house in order, but also to build better ‘quality’ houses to adorn with bright ‘FDC’ bulbs and ‘NDDS’ lamps.

Over the years, last many new drug policy proposals promises have been made, time and again to reward innovations and ‘patented’ processes and products, but the promises in the policies were never kept or implemented or delivered to the innovators. In this era of ‘start-ups’ and ‘jugaads’, pharma industry has been repeatedly let down by the National Pharmaceutical Pricing Authority (NPPA), refusing to follow the drug policy expectations to ‘innovative patented’ New Drug Delivery Systems such as MR, XR, ER and other delayed or prolonged release dosage forms, which not only reduce the toxicity and adverse side effects by keeping the blood level concentrations to the minimum desired or optimum levels, but also provide patients the convenience of a once-a-day or once-a-week pill with uniform blood level concentrations. While patented imported medicines are fully exempted from scrutiny and price control, medicines patented by Indian companies do not enjoy such exemptions. Time and again proposals, promises and provisions were incorporated in drug policies and DPCOs, but grossly ignored under NGO pressures, leading to arbitrary extension of price control by NPPA on Indian patented drugs. Having painfully traversed the onslaught of the NGOs through the judicial scrutinies and consequent pressures on DCG(I) and Central Drugs Standard Control Organisation (CDSCO), a clear guideline is emerging for pursuing these innovatively evidence-based new drug delivery systems and rational combination therapies.

Combination Therapy Systems and FDC dosage forms have originated predominantly from the creative stable of Indian pharma. While this ‘necessity is the mother of invention’ scenario, emanated or was created by excessive and indiscriminate extension of price- controlled basket or schedules violating the DPCO norms, the Indian pharma, for survival, opted for innovative exceptions, by inventing newer and novel combination therapies, often with built-in ‘immediate release/ delayed release,’ multilayer tablets or pellets or cores and coats. While many of these innovative combinations were welcomed by the medical profession and considered as a boon by the patients, as it happens in all such well-conceived innovative initiatives, a few irrational ones also crept in or were pushed in, spoiling the fair reputation and advantage of FDCs, in general. The irrational ones brought a bad name to all FDCs across the board. These FDC innovations from Indian pharma were not taken kindly by developed countries and their pharma giants and overseas regulators, too. The role played by Indian as well as overseas-sponsored NGOs harmed the progress and thrust made by Indian pharma in FDCs causing severe set-backs, albeit temporarily. The Indian pharma and regulators must be proud that the US FDA set up a ‘combination therapy’ window eventually and commenced granting permissions to FDCs for chronic and critical diseases. The lead that Cipla took in anti-retroviral combo therapies has made the world to wake up and take note. As if going by the adage ‘every action has an equal and opposite reaction,’ the success of the Indian FDCs fuelled the anti-propaganda and opportunistically motivated judicial challenges which led to the current adverse scenario. Instead of calling it a day or accepting defeat, Indian pharma industry should pursue the FDC plus NDDS route deploying already existing skills and renewed will to offer regulatory compliant pills with built in patient convenience and evidence-based consumer benefits.

The Indian pharma industries’ skills will be put to test in coming years, not only in their will to make a quality pill, but also in their will to pursue innovative and inventive processes and products which are patentable and also non-infringing. Currently, innovation in novel dosage forms and new delivery systems are receiving attention of researchers globally. Indian researchers will need to do their due diligence in pursuit of newer drug delivery systems and combination therapy to steer clear of infringing mine fields of already patented or published patent technologies.

With a view to attract attention of Indian pharma researchers to the alarming array of innovations in delivery systems and devices, a few examples of recent patents/ patent applications in the field are re-produced herein.

The technological advancement in novel delivery systems, targeted delivery dosage forms and device-based dosage delivery systems is extremely exciting as well as challenging. Exciting because newer vehicles, systems and concepts are emerging. Challenging because what is already patented cannot be worked, will be infringed and need to develop work-around strategies. For brevity and due to space constraints, only a few samples and examples can be quoted here, which is just a selection of nearly 5000 related patent applications on the database. Let us see one or two abstracts of pending patent applications in India for example.

Drug Delivery (IN201618041241)
(University of Leeds, UK)

A method and apparatus is disclosed for ejecting drug bearing material. The ejected material is ejected as liquid and liquid vapour via an explosive process which provide a very fast ejection as well as an ejection which has a large throw. The apparatus can provide a nebulizer, inhaler or needleless injector.

Nanoparticle Drug Conjugates (IN201617043358)
(Memorial Sloan Kettering Cancer Center & Cornell University)

Nanoparticle drug conjugates (NDCs) which in certain embodiments comprise a non-toxic multi modality clinically proven silica-based nanoparticle platform with covalently attached drug molecules/ moieties. The nanoparticle drug conjugates (NDCs) demonstrate imaging capability and targeting ligands which efficiently clear through the kidneys. Furthermore, the conjugates incorporate therapeutic agents for cancer detection prevention and/ or treatment.
A representative list of pending patent applications in the field as reproduced below provides insight to interested researchers on the vast array of advanced technologies on the anvil.

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