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I thought of a BASF podcast I heard a few months ago; pharmaceutical technology still has a high threshold.
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https://www.zhihu.com/question/618350435
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Let’s talk about the skills for choosing drugs. What is a drug scoring above 85 points and what is considered failing?
The most important thing is to distinguish between original brand drugs and generic drugs. Original drugs all score above 85 points, while only some generic drugs can exceed 60 points.
Original drugs refer to drugs produced by the company that initially developed the new drug. For example, metformin hydrochloride is the chemical component name, the original drug’s brand name is “Glucophage,” and the pharmaceutical company that developed it is Merck.
Each new drug has a 20-year patent protection period. From the time it is sold to the patent expiration, a drug can be sold for about 15 years or more. During this period, only this one company can sell the drug. After the patent expires, other companies can produce and sell it. These other companies’ drugs produced after the patent expiry are called generic drugs.
Because drug molecules are mostly small molecules, on the first day the original drug is marketed and sold, the pharmaceutical company publishes the chemical formula and chemical structure diagram of the drug in the drug instructions. So any other company willing to study it has more than ten years to imitate it. Even secondary companies can synthesize the same type of molecules and then make the final capsules or tablets. This is what generic drugs are.
After the patent period expires, because multiple companies are producing generics, the price of generic drugs is much lower, sometimes only 1/15 of the original brand drug’s price. Of course, once the patent period ends, the original brand drug also significantly lowers its price due to competition from generics, just not as cheap as generics.
You may ask, since the active ingredients are the same, why does one score above 85 points and the other usually fail?
This is the reality. It’s roughly like copying homework, how much you understand in the end is uncertain. There is a book you can read called The Truth About Generic Drugs. It was exposed by a former executive of the world’s largest generic drug manufacturer—India’s Ranbaxy. Later, a Fortune magazine reporter spent ten years investigating and wrote this book, which ultimately overthrew this pharmaceutical company.
This company’s generic drugs alone have $3 billion in orders annually just in the United States, and it is a supplier for the World Health Organization’s AIDS prevention program in Africa. They are also regularly inspected by FDA inspectors. In fact, entering the US market means passing the strictest audits. Among the world’s pharmaceutical companies, besides the original brand drug companies in Europe and the United States, next in line are Indian generic drug companies, and this company ranks first in India.
But in reality, how did they treat generic drugs?
About half of the reports they submitted to the FDA claiming their generic drugs matched the efficacy of the original brand drug were accurate, but the other half of the drug reports were fabricated data. And this is just the drugs supplied to the US. For drugs supplied to South America, Africa, China, including their own Indian generics, there is no longer any proportion that matches the original brand drug—it’s 100% fabricated.
Some might wonder, since the drug’s active ingredients are the same, why does fabricating data matter?
It really matters.
One is the purity and quantity of the drug’s active ingredient. Purification is a very meticulous process closely related to the pharmaceutical company’s R&D and manufacturing level. If the purification is insufficient, impurities often affect efficacy and may even cause many side effects that the original drug does not have.
Another more important metric is called the “dissolution curve,” which is the curve of the concentration of the active ingredient in the blood over time. If the active ingredient cannot be maintained at the required amount and duration in the blood, the drug will have no therapeutic effect. Therefore, generic drugs must try to fit the dissolution curve of the original brand drug as closely as possible — generally, a match of over 80% is considered qualified.
This is a big challenge for pharmaceutical companies. Although the active ingredient has been published since the first day the drug was marketed, the excipients (the raw materials and processes that ensure the dissolution curve is that particular line) are not disclosed by the original drug company. Whoever has the ability must develop it themselves. How to ensure a drug maintains a high concentration in metabolism for more than 6 hours? How to ensure it maintains sufficient absorption despite high-intensity gastric acid and food interference? These are core strengths of drug R&D.
Thus, many pharmaceutical companies without capabilities but wanting to sell drugs fabricate experimental reports at this stage, slightly modifying the original drug’s dissolution curve and submitting it for review. Even under the FDA’s strict approval, loopholes can still be exploited. And among the generic drug manufacturers, that Indian pharmaceutical company is already at a global first-tier level. So the quality of products from other generic manufacturers can be imagined.
This is also why we should choose drugs scoring above 85 points. For example, with metformin, I personally suggest sticking to Glucophage.
Naturally, the next question is, how do I know whether it is an original drug or a generic?
There is a method with an accuracy of 99% for your reference: if it is not produced by American or European pharmaceutical companies, it is a generic drug. Generally, those from the world’s top 10 or top 20 pharmaceutical companies are basically original brand drugs. These large pharmaceutical companies have long focused on new drug development and disdain producing generics. Only companies with much lower capabilities compete in the generic drug market.
For example, in China, Glucophage is produced by Shanghai Schering-Plough, and Claritin is produced by Shanghai Bayer. These joint ventures with European and American pharmaceutical companies also produce original brand drugs. The reason for joint ventures is similar to foreign car companies selling cars in China—they have to set thresholds and produce through joint venture pharmaceutical companies.
Of course, in some cases, the selection criteria can be relaxed, and choosing generics will not cause major problems.
For example, you can refer to the original brand drug’s drug instructions corresponding to the generic drug. If the instructions say, “The active ingredient concentration reaches its peak within 2 hours,” then the generic drug’s effect will not lose much.
Also, if the instructions do not specify whether to take the drug before or after meals—meaning the timing is flexible—or if the drug appears in a chemical form with relatively high solubility, such as “hydrochloride tablets,” there is not much problem choosing generics. Because such details in the instructions actually indicate that the drug’s efficacy does not strongly depend on the excipients’ design. As long as the active ingredient’s purity and quantity are sufficient, the original and generic drug effects are largely similar.
Conversely, for drugs requiring slow and uniform release of the active ingredient, for example, some drugs with names containing “sustained-release capsules,” it is better to prioritize original brand drugs.
Of course, these checks take some time. Sometimes when we take medicine but it doesn’t work, we can consider whether problems arise in this regard.
Also, recently many friends have caught colds, and they can take common cold medicines to relieve headaches and mild fevers.
But if you have read the above, you might develop a preference—not wanting to choose medicines named “Shangfeng Capsules” (Cold Relief Capsules), feeling it’s better to switch to another cold medicine such as Tylenol or Contac.
Because the drug name contains symptoms, and these are symptoms expressed in traditional medicine terms. To be strict, under stricter review standards, this is a sign of failure. Although these drugs might have some effect, they mostly masquerade under the guise of traditional medicine and secretly add acetaminophen-like components, making them a kind of hybrid drug. Therefore, it is still safer to take drugs scoring above 85 points.