The shruti (note placement) invariances do influence the design of musical instruments when they need to be used in Indian classical music. You need tunability, since even a minute deviation can create aberrations.
So keyed instrument that do not have tunability have limitations. For example, for best results, a harmonium must be tuned beforehand with respect to the reference note that the performer has chosen. This tuning not only covers the basic Sa-Pa ratio, but it also covers the placements of other notes used in the Raga.
A harmonium tuning for one raga for one choice of Sa (the chosen reference note or the drone) may not be usable for another Raga if you are too sensitive to minute changes. For most people, that difference may not be easily noticeable. However, this has lead to the development of tunable harmoniums.
For Indian classical music, an instrument also needs to have the ability to produce an unbroken, that is to say a continuous, frequency change from one note to another. This is achieved by techniques such as string pulling and sliding in the case of string instruments, and by controlling hole openings, flows, and pressures in the case of air-column based instruments such as flutes and shehnai, which use fixed hole placements.
With flutes, since the holes are not tunable once they are drilled in, they indeed need to get the perfect Sa-Pa invariance. The maths of the physics of sound is what goes into perfect drill placements in a flute.
If that goes wrong, you will see that such flutes do not produce the needed ratios correctly. On the other hand, string instruments can readily produce the needed ratios due to tunability.
One aspect they need to make sure of is the reachability of Pa and Sa from both directions on a continuously varying frequency scale. In most tunings, a string change may occur on these notes. So in such cases, the same notes are also produceable on another string at a different place not only directly, but more importantly, also through the continuous frequency change techniques listed above.