Context: Some of these estimates also take into account the opportunity cost of investing capital many years before revenues are realized (see Time-value of money). Because of the very long time needed for discovery, development, and approval of pharmaceuticals, these costs can accumulate to nearly half the total expense. A direct consequence within the pharmaceutical industry value chain is that major pharmaceutical multinationals tend to increasingly outsource risks related to fundamental research, which somewhat reshapes the industry ecosystem with biotechnology companies playing an increasingly important role, and overall strategies being redefined accordingly. Some approved drugs, such as those based on re-formulation of an existing active ingredient (also referred to as Line-extensions) are much less expensive to develop.

Question: What drugs are the least expensive to develop?
Answer: those based on re-formulation of an existing active ingredient

Question: What accounts for nearly half of the costs to develop drugs?
Answer: opportunity cost of investing capital

Question: What is the consequence in the value chain?
Answer: increasingly outsource risks related to fundamental research

Question: What happens when companies outsource?
Answer: somewhat reshapes the industry ecosystem with biotechnology companies

Question: What is re-formulations of active ingredients referred to?
Answer: Line-extensions

Question: Investing capital can increase drug development costs by how much?
Answer: nearly half the total expense

Question: What kind of companies have had a more important role in drug development?
Answer: biotechnology

Question: What firms tend to outsource drug development?
Answer: major pharmaceutical multinationals

Question: What drugs are the least fundamental to develop?
Answer: Unanswerable

Question: What accounts for nearly half of the costs to develop companies?
Answer: Unanswerable

Question: What is the consequence in the research chain?
Answer: Unanswerable

Question: What happens when companies approve drugs?
Answer: Unanswerable

Question: What is re-formulations of approved drugs referred to?
Answer: Unanswerable