Guidelines for nano drugsApril 9, 2019
The Department of Biotechnology (DBT) and Indian Society of Nano Medicine has come out with guidelines for evaluation of nanopharmaceuticals in India.
The guidelines are being framed in the backdrop of growing research and development and usage of nanomedicine in the country. According to reports, the nanomedicine market in the country is estimated to grow to around $1.6 billion in 10-15 years. Considering the growth of healthcare market in the country, which is expected to be in the top three among world healthcare markets by 2020, the need of the hour is to set standards for nano pharmaceuticals.
The guidelines aim to ensure quality, safety and efficacy as well as to encourage the commercialisation of nanotechnology-based innovation with high benefit to risk ratio, says the document.
DBT has given special emphasis to promoting nanobiotechnology that have applications in various sectors of life sciences. It has been funding R&D in this area since 2007, and various scientists and stakeholders have felt the need to have specific guidelines for the evaluation of products in various sectors of biological sciences developed through interventions of nanotechnology.
Nano pharmaceuticals is an emerging field that combines nanotechnology with pharmaceutical and biomedical science to improve efficacy and safety profile via targeted drug delivery. Alteration into nanoscale for drug delivery may significantly alter the pharmacokinetic, biodistribution and toxicokinetic parameters of conventional/traditional drugs, raising various concerns related to quality, safety and efficacy of nano pharmaceutical products, says the guideline. Considering the complexity of nanomaterial behaviour in the biological environment, certain degree of uncertainty may be inherent to such system.
Charting the course
There are no uniform, internationally acceptable guidelines for nanopharmaceuticals. The usual consensus for evaluation of quality, safety and efficacy of nanotechnology-based products is to have a ‘case by case approach’, taking into consideration of the physical, chemical and biological characteristics of the nanoparticle used and the route of administration, the indication for which the product is intended to be used and other related aspects.
These guidelines apply to nanopharmaceuticals in the form of a finished formulation as well as an API of a new molecule or an already approved molecule with altered dimensions, properties or phenomenon associated with the application of nanotechnology intended to be used for diagnosis, treatment, mitigation or prevention of diseases in human beings. In the guidelines, nanopharmaceuticals have been classified according to their degradability, organicity, function and status of approval. Accordingly, the safety and efficacy data requirements have been described.
Specific scientific evidence required for approval of any nano pharmaceutical and the strategies for pharmacovigilance of such products has also been incorporated in these guidelines. Each application should be considered on its own merit of the data submitted using scientific judgment and logical argument. For the new generation of nanomaterials, the development of methods for safety testing and risk assessment, and a better availability of quality data on nanomaterials for regulatory purposes are essential.
The guidelines define nano pharmaceutical as a pharmaceutical preparation containing nanomaterials intended for internal or external application on the body for the purpose of therapeutics, diagnostics and any other health benefit. These are the products that contain materials in the size scale range of 1 to 100nm in at least one dimension. However, if the particle size is >100nm and <1000 nm, it will also fall within the definition, provided it has altered or different pharmaceutical characteristics associated with the application of nanotechnology compared with the API. The size distribution of nano pharmaceuticals should be not less than 1% beyond the nanoparticle range 1 to 1000 nm. Further, the particles should be in the claimed nano-size range. At any time point during the claimed stability period, the particle size range should not decline/alter >10%.
The guidelines also stipulate various steps for the development of a nanomedicine, including research and development, clinical trials and the regulatory processes to be mandatorily undergone during the process. For instance, in some cases, the conventional/traditional form of the drug is approved in well-regulated countries and/or India, but the nanocarrier system is new and not approved in any country. For this category of nanoformulation product, the entire requirements of safety and efficacy data as specified in Schedule Y for Investigational New Drug (IND) may not be required. However, evidence of the safety and efficacy of the product should be documented
]To evaluate nano pharmaceutical or nanomedicine efficacy, pre-clinical research should generate data sets that evaluate the properties of product behaviour. Such properties include the accumulation of the drug at the disease site — for example, in case of an anti-cancer product, its accumulation in the tumour, intra-tumoural distribution, and the tumoural retention of the system. For brain-targeted nano pharmaceuticals, special studies should be done to measure drug concentration in different parts of the brain along with the API, the draft document says.
The guidelines have been released to garner the response of the industry and the public.