Recent developments in modern biotechnology such as the use of RNA interference (RNAi) have broadened the scope of crop genetic modification. RNAi strategies have led to significant achievements in crop protection against biotic and abiotic stresses, modification of plant traits, and yield improvement. As RNAi-derived varieties of crops become more useful in the field, it is important to examine the capacity of current regulatory systems to deal with such varieties, and to determine if changes are needed to improve the existing frameworks. We review the biosafety frameworks from the perspective of developing countries that are increasingly involved in modern biotechnology research, including RNAi applications, and make some recommendations. Malaysia and India have approved laws regulating living modified organisms and products thereof, highlighting that the use of any genetically modified step requires regulatory scrutiny. In view of production methods for exogenously applied double-stranded RNAs and potential risks from the resulting double-stranded RNA-based products, we argue that a process-based system may be inappropriate for the non-transformative RNAi technology. We here propose that the current legislation needs rewording to take account of the non-transgenic RNAi technology, and discuss the best alternative for regulatory systems in India and Malaysia in comparison with the existing frameworks in other countries.