This article is transcoded by SimpRead 简悦, original at www.zhihu.com
Ouyang Lingfeng
After reading through all the answers, I was shocked, specifically shocked by two things: 1. The country lacks popular science knowledge regarding drugs, and the public’s understanding of original drugs versus generics is surprisingly inadequate. 2. People in the pharmaceutical industry really dislike answering questions. For this question, anyone in the pharmaceutical industry knows the facts clearly, but among so many answers, I feel none are actually written by true pharmaceutical insiders.
To conclude first, currently in China, as long as you find the mark “Generic Drug Consistency Evaluation” on the packaging — like the image below:
The effect is equivalent to the original drug. If the generic drug does not have this mark, you should be suspicious. Without this mark, there is a high probability that the effect is worse than the original. Why is this the case?
The story begins with the former head of the drug regulatory bureau Zheng Xiaoyu, who was executed in 2007. This guy was the first ministerial-level cadre in new China to be executed. Why the death penalty? Because during his tenure managing the drug regulatory bureau, production approvals for drugs could be bought with money. This guy’s conscience was severely corrupted; he abused power for personal gain, accepted bribes, and sold drug production approvals — something closely related to public health. This caused a large number of ineffective drugs to receive national approval and enter the market. This is the root cause of why many generics are inferior to the original drugs now.
To rebuild a healthy pharmaceutical market, the state has continuously sought reforms but progress had been lukewarm. Between 2007 and 2015, the pharmaceutical industry was still highly irregular with rampant data falsification. Even the reports published by the National Medical Products Administration’s evaluation center stated that over 80% of clinical data prior to 2016 were fabricated, and most of the genuine data were from foreign enterprises. Hence, original drugs had good quality, since most original drugs entered the Chinese market only after being launched in developed European and American countries; manufacturers had no incentive to falsify data and ruin their reputation.
When is the turning point? The consensus point is the 2015 “722 incident,” known as a seismic event in the pharmaceutical industry. This brings up another drug regulatory bureau director, Bi Jingquan. The “722” incident happened under his watch; he took office as director in 2015. Previously, he was the Deputy Secretary-General of the State Council, showing the state’s determination to regulate the pharmaceutical market. I won’t elaborate on the details of the 722 incident, but after it, the pharmaceutical industry realized the state’s determination and dared no longer falsify data. They even withdrew submitted drug applications.
Pharmaceutical companies and hospitals no longer dared to falsify data, and new drug applications were strictly reviewed. However, the market still had many ineffective drugs; what to do? Starting in 2016, a re-evaluation of already marketed drugs began, called “consistency evaluation,” referring to the consistency between generic drugs and original drugs. Drugs that pass the consistency evaluation print the aforementioned mark on their packaging. Therefore, any drug with this mark is equally effective as the original.
As of now, the consistency evaluation is ongoing. After reaching certain stages, the state also introduced a centralized procurement policy, significantly reducing drug costs.
Today, consistency evaluation and centralized procurement have become standard work, and those in the pharmaceutical industry have become accustomed to them.
For ordinary people, just remember — any drug with the consistency evaluation mark, no matter how low the price, is safe because the low price is the result of the country’s significant efforts.
This article is mainly for popular science; many details are not expanded, such as the process of the 722 seismic event and the specifics of centralized procurement, which are very interesting. If readers are interested (more likes), I will consider adding more content.
Revision note: Many comments complained that the phrase “exactly the same” was eye-catching, so I replaced it.
Solari of the Sun City
How to determine whether factory wastewater meets discharge standards?
The best method is for enforcement agencies to send people to collect water samples from discharge outlets irregularly without notifying the factory.
The second-best approach is for enforcement agencies to regularly collect water samples monthly from factory discharge outlets.
However, currently with “centralized procurement drugs,” the enforcement agency calls the factory asking them to deliver two barrels of wastewater the next day for testing.
To Your World
Let’s talk about tips for choosing drugs. What constitutes a drug rated above 85 points and what is a failing drug?
The most important thing is to distinguish original drugs from generics. Original drugs usually score above 85, while only some generics exceed 60.
Original drugs are those produced by the enterprise that first developed the new drug. For example, metformin hydrochloride is the chemical name; the original drug’s brand name is “Glucophage,” and it was developed by Merck Pharmaceuticals.
Every new drug has a 20-year patent protection period. From launch to patent expiration, a drug can be sold for about 15 years or more. During this time, only that company sells the drug. After the patent expires, other pharmaceutical companies can produce and sell it. Those drugs produced by other companies after patent expiry are called generics.
Since most drug molecules are small molecules, on the very first day the original drug is launched, the pharmaceutical company publishes its chemical formula and structure in the drug manual. Thus, other companies have over a decade to study and copy it. Even secondary companies can synthesize similar molecules and produce the final capsules or tablets. These are generics.
After the patent expires, because multiple companies manufacture generics, the price drops significantly, sometimes to only 1/15th of the original drug’s price. Of course, after patent expiry, the original drug also lowers prices substantially due to generic competition, but not as cheaply as generics.
You ask, since the active ingredients are the same, why is one rated above 85 and the other generally failing?
That is the reality. It’s roughly like copying homework — how much you understand varies. There is a book you can read called “The Truth About Generic Drugs.” It was revealed by a senior executive of the world’s largest generic drug manufacturer — India’s Ranbaxy — and written after a decade-long investigation by Fortune magazine journalists, which ultimately exposed the company.
This company produces generics with $3 billion in annual orders just in the US alone. They supply drugs for WHO’s AIDS prevention program in Africa and are regularly inspected by FDA officials. In fact, being able to enter the US market means passing the strictest regulatory review. Among global drug manufacturers, apart from European and American original drug manufacturers, the next tier is a group of Indian generic manufacturers, with this company being top-tier in India.
But how do they actually manage their generics?
About half of their reports submitted to the FDA claiming that their generics matched the original drugs’ efficacy were true; the other half fabricated the data. This is just for supply in the US. For South America, Africa, China, and their domestic Indian generics, it’s no longer a matter of what percentage, but 100% of data are fabricated.
Some might wonder: if the active ingredients are the same, what does fabricating data matter?
It really matters.
First, the purity and quantity of the active ingredient matter. Purification is a meticulous process closely related to the R&D and manufacturing capabilities of the pharmaceutical company. If purification is inadequate, impurities often affect efficacy and can cause many side effects that the original drug does not have.
Another important metric is the “dissolution curve,” which depicts how the concentration of the active ingredient in the blood changes over time. If the active ingredient cannot maintain concentration and duration in the blood as required, the drug loses efficacy. Therefore, generics must closely match the dissolution curve of the original drugs, generally over 80% match being considered qualified.
This is a big challenge for pharmaceutical companies. Although the active ingredient was public from day one the drug was marketed, the excipients — the raw materials and processes that ensure that dissolution curve — are not disclosed by original drug companies; whoever is capable must develop it themselves. How to guarantee that a drug maintains high blood concentration for over 6 hours during metabolism? How to ensure high absorption despite strong gastric acid and interference from food? These are core strengths of drug R&D.
Thus, many companies lacking capabilities but wanting to sell drugs fabricate experimental reports here, slightly modifying the original drug’s dissolution curve before submission. Even under FDA’s strict review, loopholes exist. Among generic drug producers, that India drug company is already world-class. Hence, the quality of products from other generic manufacturers is easy to imagine.
This is why we need to choose drugs rated above 85. For example, for metformin, I personally recommend sticking to Glucophage.
The next question is naturally: how do I know if it’s original or generic?
There’s a method with 99% accuracy: if the drug is not produced by an American or European pharmaceutical company, it’s generic. Generally, drugs from the top 10 or top 20 global pharmaceutical companies are originals. These big pharma focus on new drug development and disdain producing generics. Only companies with much lower capability compete in the generic market.
For example, in China, Glucophage is produced by Shanghai Bristol-Myers Squibb, and Claritin by Shanghai Bayer — these joint ventures with European and American large pharma are originals. Joint ventures exist similarly to foreign car companies selling in China, which must set up joint ventures.
Of course, in some cases, the choice criteria can be relaxed. Choosing generics won’t cause major problems.
For example, you can refer to the original drug’s label corresponding to the generic. If it states, “the time to peak concentration of active ingredient is within 2 hours,” the generic’s effect will lose little.
Also, if the label does not specify whether to take before or after meals — i.e., timing is flexible — or if the drug is in a highly soluble chemical form like “hydrochloride tablets,” selecting generics is acceptable. Because these details indicate the drug’s efficacy does not strongly depend on excipient design. As long as the active ingredient purity and amount are sufficient, originals and generics have similar effects.
In contrast, drugs requiring slow and uniform release of active ingredient — for example, those named with “sustained-release capsules” — are better to choose originals.
Of course, these inquiries require time. Sometimes if a drug you took doesn’t work, it might be related to this issue.
Also, some recently come down with colds can take regular cold medicines to alleviate headache and mild fever.
But once you’ve read the above, you may develop a preference — avoiding drugs named “Cold Relief Capsules,” and preferring other cold medicines like Tylenol or Contac.
Because the drug name includes symptoms and uses ancient medical terminology for symptoms. To be precise, under stricter review standards, this is a failing mark. Although these medicines may have some effect, most are counterfeit in the guise of ancient medicine, secretly adding acetaminophen-like compounds. So it’s safer to choose drugs rated above 85 points.