The Philippine Question of Bioequivalence

Is it possible to get good quality medicines at a lower cost?

If the Generics Act of 1988 (Republic Act 6675), which provides for the manufacture of off-patent medicines in the Philippines, is to be followed, then the answer should be yes.

However, the implementation of the law, has, over the years, raised questions about its effectiveness in providing efficacious medication at lower price points, especially since issues of bioequivalence among medicines continue to hound it.

The concept of bioequivalence, as defined by the United States Food and Drug Authority, states that the active molecules of the medicines in question should deliver the same pharmacological effects if delivered under the same conditions as the innovator molecule. These molecules are the building blocks of the medications used to treat symptoms in psychiatric and other medical conditions. Philippine law is silent on the concept of bioequivalence and provides no categorical definition to guide its implementation in the country.

Simply put, an alternative active molecule should have the same effect and side effect profile as the innovator molecule.

However, the practical situations that face clinicians and their patients in the country are different from theory.

In an interview at his clinic at the Asian Hospital and Medical Center in Alabang, Muntinlupa, neuro-psychiatrist Dr. Salvador Benjamin D. Vista observed that theoretically, all the generic drugs available in the Philippine market should be similar to the innovator drug they are mimicking.

Dr. Vista is also the current President of the Group for Addiction Psychiatry of the Philippines (GAPP) and has a clinical practice in Manila, as well.

“From the point of view of the clinician, although the drugs that are supposed to reach us are bioequivalent, we noticed that clinically, there are medicines that perform similarly to the originator molecule, what we call the innovator, (but) there are those that don’t perform similarly.  Although they are supposed to be bioequivalent, the outcome during treatment shows they are not bioequivalent,” Dr. Vista noted.

While loopholes in the policing and implementation system of the government, particularly through its designated agency the Food and Drug Administration (FDA) Philippines, may be cited for the occurrence of these discrepancies, the situation is more complex than it seems.

Our Family has made several attempts to get a response to its interview questions through e-mail from FDA Philippines, but the office has yet to send a reply as of press time.

“Are we pointing a finger at the generic company and say they doctored the results (of their bioequivalence studies) or submitted false documents to the FDA Philippines? I don’t know. I cannot speculate,” he stressed.

Dr. Vista explained that for instance, there are companies that do provide above board bioequivalence studies to secure approval for their formulation. However, these studies are conducted outside the Philippines, which has implications on the efficacy and side effect profile of the medicine on Filipino patients.

He said that it is standard practice for some companies to submit studies conducted in India, China, and Thailand to comply with FDA Philippines requirements. The practice poses a Catch 22 situation for doctors, patients, the government, and drug companies alike.

“If you ask me what we should do is do our own bioequivalence (studies) here for the simple reason that the patients on whom they tried the bioequivalence studies abroad are not Filipinos. You want to know what the effect is on the patient and there may be genetic differences. If I were to say what would be ideal, we should not market a product, or sell a product, or even prescribe a product that has not been tested for Filipinos,” Dr. Vista stressed.

For instance, he noted that in the United States, the standard effective dose of the anti-depressant Escitalopram is 20 milligrams per day. In the Philippines, psychiatrists rarely prescribe higher than 10 milligrams per day. Dr. Vista explained that such variations may be due to the way the liver processes the medicine or how the brain receptors react to it.

Still, he also noted: “But on the other side of the coin, the drug companies will tell you, bioequivalence studies cost a lot of money, around six to seven figures. If we do it in the Philippines, the cost of these trials will be passed on to the end user so that may mean higher medicine prices.”

In addition, because the pharmaceutical companies need to be efficient where they can, they maximize these studies to reduce time to market of their products, as well as keep costs down, especially if the study proves to be favorable to their formula.

Sun Pharmaceuticals Industries Ltd. (Sun Pharma) Senior Business Manager for International Marketing Mr. Kamlesh Sati said in a separate telephone interview that as a global concern, there are situations where the company has adequate bioequivalence studies and a proven track record across diverse markets, that they find offshore studies sufficient for their purposes.

Sun Pharma originates from India, which is among the countries that enjoy a successful generics industry. The company is present in 150 countries across five continents across the globe.

Another factor in the variances in patient reaction to generic medicines is “idiosyncratic reactions” to the drug.

“Theoretically, the components should be the same, but when you say bioequivalence, you measure effects and side effects. But it does not measure whether the other chemicals you mix into the tablet are exactly the same as the innovator. In a medicine you have the active molecule and the vehicle it attaches to. You never know what the equivalent ingredients are. Are they the same as the originator? Maybe not. Because that’s where the idiosyncratic reactions come in,” Dr. Vista noted.

The source of demand

Furthermore: “You also need to realize the Philippines is not a rich country, and many of the patients do not have health insurance and the high cost of medicine is a problem, especially for patients who take it for a chronic illness.”

“Maintenance medicines that are expensive will not be also clinically correct because if you get the patient well for six months, and after that time, they have no more money to buy the medicine, then they deteriorate, so you have to do it all over again. So in that way, you have to sit down with the patient and assess generic treatment for a longer time,” Dr. Vista added.

Thus, he believes that more than the practice of sound medicine, the psychiatrist has an ethical obligation to help the patient find the right medication with the optimal response to their condition, at the right price point, which will help them sustain it for the duration of the time they need to take it. Providing such assistance is essential since many psychiatric conditions require patients to take medication for protracted periods of time, even their lifetime.

“You’re duty bound to discuss that,” Dr. Vista emphasized.

But while most patients ask for the generics menu due to cost considerations, there are those who do not make the leap.

“(There are patients who will say), I’m spending more for the tablet that I take, but if I choose a cheaper one, and it turns out not to be bioequivalent, I may have symptoms again, and I may go into hospital again, and the sum of the cost of hospitalization might be many times more than maintaining the more expensive tablet,” Dr. Vista cited.

Still and all, the fact remains that the impoverished condition of many psychiatric patients in the country redounds to a great demand for generic alternatives.

When shifting patients to generic medication, Dr. Vista adheres to what he calls “personal clinical practice guidelines”.

“(You are) ethically bound to tell them that what they are choosing is not the innovator molecule and 

therefore you are not sure if the medicine they are choosing will perform in a similar way (to the former),” he added.

Moreover: “Theoretically, when you start shifting to generics, you (should) already know what the effect of the drugs are, that’s why I initially start with the innovator so you know the effect of these drugs and medications, then if cost becomes a consideration, that’s when you consider shifting. For me, I don’t think it’s proper to start with a generic brand mainly because you want to see the optimal effect of the original. Because if the original does not work, then why shift to generic, right?”

Not a price game

In a written correspondence with Our Family, Johnson and Johnson (Philippines), Inc. Country Medical Director Dr. Roberto Salvino said: “Because of the complex pharmacokinetic profile of anti-psychotic agents, the safety and efficacy of follow-on versions must be carefully assessed to ensure their bioequivalence and suitability.”

Johnson and Johnson is the innovator of Risperidone (brand name Risperdal), which was first approved in the Philippines in 1996 to treat schizophrenia, and recently, bipolar disorder. It has recently become off-patent medication.

The generics argument should also not be oversimplified to the singular matter of low price points.

Mr. Sati, whose company manufactures the Sizodon brand of Risperidone, says that their product is not the cheapest generic alternative in the market. However, he said, at 30% lower than the cost of the innovator medication, it offers comparable efficacy.

“There are brands that are admittedly cheaper than ours, but for instance if you need to take twice as much medication compared to ours, then you end up spending more,” he observed.

The same goes for the manufacture of its molecules. Being a global company, it needs to constantly assure consistency of quality and competitive pricing across its markets. This is the reason why its manufacturing processes, from start to finish, are in-house.

“Some Philippine companies source their molecules from various suppliers, here and abroad, which opens 

them to quality risks. There may be laboratories for testing here, but in-house manufacturing is also important. It gives you greater control over the quality of your product,” Mr. Sati stressed.

He further observed that often, these companies negotiate based on the lowest price so ”quality is hampered”.

Sun Pharma enjoys a respected reputation as a generics manufacturer globally, ranking 71^st among Forbes Magazine’s 100 Most Innovative Companies as of May 2015. Current financial statements show it has a $39 billion market capitalization and $2.79 billion in global sales.