Ok Maybe i was not detailed in my observation.
The limitations of invitro & computer simulations are

1. the metabolic responses cannot be boxed. That is why even at second and third phases of clinical trials (where human subjects are used) there are still surprises and unexpected reactions and results. Some are good such that the clinical uses of the drug may be expanded but some are horrid that the drug is withdrawn. Case in point, the popular blue pill used for erectile dysfunction was originally being developed as a vasodilator for hypertension but alas the test subjects reported smiling benefits.
2. There are drugs that in them selves are inert and need to be metabolized into their active form. They are called prodrugs and these constitute a significant portion of the drugs out there and they exclude drugs that are active in themselves and also have active metabolites. All of which can not be found out invitro but invivo.
3. How do you determine doses and safety margins if invivo exposure and analysis do not take place? While there drugs that are safe at 20mg per Kg of body weight there are others that would most certainly result in death at 0.1mg per Kg of body weight. So how would know what dose is safe and what the limits are? How do you determine what doses would elicit the desire effects without invivo evaluation
4. How do you determine frequency of dosing? Different drugs are metabolised and excreted via different pathways and within different time frames. Its via tests on living tissues and subjects (animals & subsequently humans) that how a drug should administered is determine ie subcutaneous or intramuscular injection as against oral or intravenous administration. How long would it take the body to eliminate the drug ie should be administered once daily, every six or twelve hours as the case maybe.
5. You mentioned micro doses on human subjects how do you determine what doses can be considered as micro and what is mega taking my 3 point into consideration. Besides you could get very different results from different doses of the same drug where some organs were none responsive at lower doses, they could literally burnout at other doses.
6. How do you determine safety in pregnancy & breast feeding invitro? I am sure testing safety in pregnancy to determine teratogenic effects is not an ideal route anyone would want to go.
7. I think you should know that several life saving drugs like vaccines and insulin are extracts from animals and syntectic alternatives (especially for some types of vaccines) have not been developed.

In as much as i do not support animal cruelty, I also know that there is currently,as it were there are limitations in drug development and production without both animal testing and subsequently human testing.