SPECIAL REPORT: PUBLIC SAFETY AND SUBSTANDARD DRUGS
Poor-Quality,
Defective Drugs Are Undermining Generics Law
The Generics Law of 1988 was hailed as a landmark law that could benefit the public. But it has failed miserably, thanks to weak support from doctors, strong lobbying by multinational drug companies, and the health department’s incompetence. The recent cases of substandard generic drugs that kill or harm patients only served to further undermine this otherwise excellent piece of pro-poor legislation.
(Second of Three Parts)
By
MIKE AC-AC and RACHEL ANNE CALABIA
Hailed as a landmark legislation during the administration of former President Corazon Aquino, the Generics Law of 1988 laid the groundwork for establishing a local drug industry in the Philippines. But 13 years later, the industry remains foreign dominated. Multinational pharmaceutical companies have a monopoly of at least 75% of the local drug market. Among locals, United Laboratories corners 20% of the market with its mid-priced products while the remaining 5% is split among other Filipino manufacturers and importers of generic drugs.
The failure of the Generics Law had been attributed to weak support from doctors, coupled by strong lobbying against the policy by multinational drug companies. The Philippine Medical Association (PMA) itself has been blamed by some sectors for encouraging branded drug prescriptions.
Recent news of substandard drugs threatens to completely discredit the struggling generic-drug industry. While there are many reputable generic-drug companies, others have consistently violated government regulations on product standards and get away with it.
Concerned doctors have directly accused the Department of Health (DOH) of coddling violators by refusing to go hard on them. The pronouncements of Bureau of Food and Drug (BFAD) director William Torres himself reflect the bureau’s bias for the drug industry — including its most consistent violators — to the detriment of public safety.
The DOH under then Secretary Alberto Romualdez began receiving reports of substandard or the so-called “violative” drugs in 1998. That year, the department was involved in a scandal involving inferior ferrous-sulfate tablets. The incident led to the creation of a committee tasked to evaluate the government’s accreditation system for drug companies. By 1999, the BFAD had streamlined its list of accredited drug suppliers from 320 down to 70. Removed from the list were fly-by-night drug companies that existed mainly for government contracts.
Still, reports of violative drugs persisted. Random samples were collected nationwide and sent for testing at the laboratory of the BFAD in Manila. Data gathered by Ibon Features show that from March to June 1999, the bureau tested at least 49 different samples for quality and safety.
According to BFAD deputy director Kenneth Hartigan-Go, a drug can be classified as substandard merely from visual inspection. If a tablet or vial of injectable medicine shows any signs of physical contamination like precipitates, foreign particles and discoloration, the drug immediately fails the test and won’t have to go through further chemical testing on the active ingredients.
A drug that passes visual inspection is then subjected to a battery of tests using internationally accepted standards. The BFAD also checks for registration and labeling, so that even drugs that test positive for active ingredients can fail if the labeling has unregistered foreign markings or sticker-label expiry dates.
From the 1999 report of 49 sampled drugs from specific batches, 29 or around 60% failed. Of these, four drugs were found to have foreign matter, 20 failed their chemical testing, and five went against their registered label claims, among many other violations.
Alarmed by the results, Hartigan-Go opted for a more intensive and systematic study of the problem. This meant intensified sampling with the help of regional offices and government hospital personnel.
From January to August last year, the bureau found as violative drugs more than 460 drug samples, dispensed by the DOH nationwide and sold in the market. The list ranged from familiar analgesic paracetamol and antibiotics amoxycillin and cotrimoxazole, to so-called “life-and-death” injectables such as diazepam and promethazine HCl (an anti-allergic drug that is also used for sedating patients).
“You will see upon eyeballing that the solution in the vial is not clear, there are precipates. If you inject water, the solution turns into a urine-like color or white like milk. These are signs of impurities,” Hartigan-Go said.
“Based on that evidence from January to August, I recommended the removal of accreditation of some companies,” Hartigan-Go added. “But for all the pieces of evidence we were able to gather from January to August, the bureau was not able to shut down a single company.”
The evidence itself is not enough, clarified BFAD director Torres. He explained that the standard laboratory procedure for random testing is done for three samples of the same batch of drug to “exhaustively” double check safety, quality and efficacy.
This means a batch of drug can actually be tested three times by the BFAD and still pass the quality test. For instance, if a first sample passes and the second doesn’t, a third sample may be tested. If the third sample passes, then all previous negative findings are reversed.
Yet according to Dr. Reynaldo Lesaca, a former member of the National Drug Committee under the Philippine National Drug Policy Program of the DOH, only one negative result is enough to recall and destroy an entire batch. “If one sample fails, then the rest must be withdrawn from the market,” he said. “Safety first for the patient and the consumer – that is the foremost concern.”
Hartigan-Go calls this “batch variability.” One defective sample assumes that others in the batch of manufactured drugs may also be defective.
An interesting case study would be batches SP91 and SP92 of hydrocortisone sodium succinate 100m vials, with expiry date October 2001, as produced by Samarth Pharmaceuticals India and distributed locally by Phil Pharmawealth. When effective, the steroid suppresses immune response and is usually used to treat asthma.
Five different samples of batch SP91 and SP92 were sent to the BFAD over a period of six months last year and all failed.
The first sample was sent from Iloilo City and tested in June. This sample failed its assay test. But upon receiving the test results, the BFAD failed to disseminate the information immediately to other hospitals to stop future procurement of this particular batch of medicine.
In August, second and third samples of the defective hydrocortisone were sent in from Pampanga and La Union, respectively. The sample from Pampanga was a milky white powder, which formed milky white precipitates when reconstituted with water. The sample from La Union was a yellow powder that did not completely dissolve and had brown-black foreign matter sticking to the walls of the vial.
In November, two more complaints regarding the same batch of hydrocortisone sodium succinate came in, one from a regional hospital in Mindanao and another in Manila. The samples were examined separately, one week apart from each other -- and again both failed.
It is difficult to dismiss the findings of the defective hydrocortisone sodium succinate. Five different samples were collected from different areas of the country and tested separately over a long period of time. It should also be noted that these are exactly the same batches of Phil Pharmawealth drugs that the hospitals in Silay City and Cauayan, Negros Occidental, refused to use.
The drug should have been withdrawn from the market as soon as the first report came in. Yet the BFAD had failed to address this due to many factors, which may include incompetence and negligence.
According to an insider in a government hospital who spoke on condition of anonymity, 10 vials of hydrocortisone from his area were used before it was sent for analysis.
“It was analyzed in September and the results were sent down to the Bureau Information Unit. They’re the ones who are supposed to send out the results back to the provinces. But it got stuck there. The results were given only in December or January.”
In the meantime, other hospitals have either purchased or are still unwittingly using the same defective batch. The source seriously questions the BFAD’s lack of regional coordination and information dissemination regarding this case.
Hartigan-Go has suggested that the reluctance to computerize the reports on the violative drugs enable consistent offenders -- like the defective hydrocortisone sodium succinate -- to be tested again and again without proper reference to its track record.
Without any systematic cross-referencing database of pharmaceutical companies, distribution, and batch numbers, it is simply impossible to keep track of thousands of drugs on the market and whether they are effective or harmful.
In the “violative” reports released by the DOH last year, the names of several local drug manufacturers and importers consistently appear.
According to DOH-BFAD documents, these companies include AD Drugstel Pharmaceutical Laboratories, Am-Europharma Corporation, Ashford Pharmaceutical Laboratories, Compact Pharmaceuticals, Danlex Research Laboratories Inc., Diamond Laboratories Inc., Drugmakers Biotech Research Laboratories, Duopharma Trace Phil., Hizon Laboratories, J.B. Orchids, Myrex Ethica Laboratories, Phil Pharmawealth Inc., Philmed Laboratories Inc., PNF Pharmaceuticals Inc., San Marino Laboratories, and Virgo Pharmaceuticals.
Despite being multimillion peso ventures in their own right, many of these firms do not have the capacity to manufacture. For instance, Phil Pharmawealth imports generics from various Indian pharmaceutical suppliers like Mercury Lab., Harson, OBOI Laboratories, Samarth, and Strides Inc. Out of its reported line of 75 drugs, 52 samples have been classified as violative. (As of press time, the office of Phil Pharmawealth said that their legal representative was out of the country and would not be available for comment.)
Other companies like AD Drugstel and AM Europharma have more than 20 violations, while others only have one.
A former BFAD consultant who spoke to Ibon Features noted that the number of violations doesn’t make any difference when public safety is concerned. “Whether one violation or 20, it still means that the company is not following the guidelines for good manufacturing practices.”
Good manufacturing practices (GMP) is the internationally accepted standard that has yet to be implemented fully by the BFAD for local manufacturers and importers.
BFAD director Torres doesn’t think that the number of violations are significant either, but for different reasons. “A company may have 200 products and one type of drug can be singled out. If you keep on blaming them for that one drug, then many companies will fail,” he said.
For DOH Secretary Manuel Dayrit, the problem lies with the quality of raw materials used by the drug manufacturer. “Sometimes your supplier runs out of raw materials and so you have to get from other sources,” he said.
Dayrit even used rice cakes as analogy. “It’s like baking rice cakes. Sometimes you get substandard margarine and flour. When you get good quality margarine and flour, you get better rice cakes.”
He also said that “the production process for drugs is complicated. Some manufacturers have erratic sources of raw materials. So it can happen that a batch of their product is substandard when they change suppliers.”
But Dr. Romeo Quijano of the University of the Philippines does not understand why the DOH is taking the cudgels for the drug manufacturer. “The quality of the product, including raw materials, is the responsibility of the drug company – whether it is a manufacturer, an importer or distributor… When a drug is found to be ‘substandard’, the batch from where it came should be removed immediately from circulation to prevent potential harm to patients.”
And “if this happens three or more times, or if other products from the same drug company are found to be ‘substandard’, that company should be closed down… The interest of the patients should not be sacrificed just so these companies could have their way.”
In the case of Phil Pharmawealth, BFAD’s Torres believes it wasn’t the fault of the importer because some of their foreign suppliers do not practice GMP. “I told them to get another supplier and they agreed. It seems their new products will pass since supplies from Thailand are of better quality. So it was not Phil Pharmawealth’s fault but their suppliers’,” he said.
Regarding the substandard drug list released last year, Torres said: “Some have been used up already; there’s nothing we can do about it. The remaining ones were withdrawn.”
In the interest of protecting the small local industries, Torres believes it is necessary to give a second chance to erring manufacturers in order for them to shape up and slowly conform to GMP. “We only gave them a warning. For all we know the substandard product may have just been one in a million. You can’t just withdraw a company’s license or a product registration because of one defective product.”
He hopes that by 2004, the local pharmaceutical industry would be able to comply with GMP in time for the implementation of the ASEAN Free Trade Area (AFTA), which will usher in stiff foreign competition.
Torres’ second-in-command, Hartigan-Go, strongly disagreed however. He said that the slow approach is detrimental to the drug industry and more so to the general public. “In the interest of public health, you need to shut down these companies. They will never comply with GMP as long they are given leeway not to comply with it. In the long run, they will also suffer because they can’t compete with foreign competition.”
Dr. Quijano, meanwhile, said that “Protecting the health of the public is more important than protecting the business of small pharmaceutical companies. If substandard drugs get into the market and are eventually used by consumers, this means that the government is failing miserably in its constitutional mandate to protect public health and welfare.”
According to a practicing doctor who spoke with Ibon Features, generic drugs produced and imported by local companies are already suffering from a backlash from doctors who refuse to prescribe them. “Many residents from my regional hospital do not want to administer questionable drugs to their patients. Even if there are good and bad generic-drug companies, how can you tell them apart? The multinationals are just benefiting from the situation,” the source concluded.
While this matter raises concern on the quality of generic drugs, this should not be taken as proof that a generic-drugs policy is bad, Dr. Quijano clarifies. “The substandard drug preparations were substandard not because they were generic preparations but because the companies were substandard -- they are not qualified to manufacture or distribute drug preparations.”
“The substandard companies could have labeled their products with brand names and they would have been still substandard in quality. Small companies mainly sell generic preparations because they cannot afford to do promotional and advertising campaign for branded preparations and they don’t have patented drugs. Big companies sell mainly branded drugs because they can create product loyalty (mainly through advertising and promotions), impose a higher price, and create monopoly control by using brand names.”
Dr. Quijano maintains that “even if the small generic companies are out of business, the generic-drugs policy could still be implemented by requiring the big companies to label their products according to the generic names of the drugs and by ensuring that there is no monopoly control of the pharmaceutical industry.”
In fact, he pointed out, big pharmaceutical companies are required by the Generics Law to manufacture and distribute the generically labeled equivalents of their branded formulations. Unfortunately, this particular provision of the Generics Law is not being implemented.”
(Part Three: Thanks to BFAD, Erring Drug Firms Are Getting Away With Murder)
Part One: Substandard Drugs Are Killing Poor Filipinos