Thai Regulations on Drugs
The Drug Control Division has set a vision as an institute with reliability and good reputation in consumer protection. The public is thus assured of accessibility to safe and efficacious marketed pharmaceutical products of standard quality, to reliable and adequate information, and to advance technology. The Division promotes the production capacity of local pharmaceutical industries to the extent that they are able to export medicines of standard quality.
The Division carries out its mission in consultation or cooperation with experts in science, medicine, pharmacy and public health, consumers, manufacturers, importers, distributors and retailers of drugs. It works closely with several other organizations (e.g. universities, industries, hospitals, health-care professional groups, consumer groups, other relevant agencies and foreign governments) in the drug development and review processes.
The regulation of pharmaceutical products in Thailand began in 1909 when the adulteration of drug products and narcotic substances was prohibited. There had been practically no control of drugs before 1909. The first legislation promulgated in 1922 was the Harmful and Habit-forming Drugs Act. However, the duties for manufacturing and dispensing medicines were not assigned to pharmacists until 1929.
The manufacture and sale of alcoholic preparations containing indigenous medicinal herbs became more and more extensive until the widespread use caught the attention of the Medical Association of Thailand. The problems eventually led to the promulgation of the Sales of Drugs Act in B.E. 2479 (1936). The first legislative measure implemented in the field of pharmaceutical regulation dealt only with sale practices regardless of formulas or ingredients. At that time, neither manufacturers nor importers/retailers paid much attention or assumed their responsibilities to quality and safety of their drug products.
The improvement in pharmaceutical regulation in Thailand was observed after the Sales of Drugs Act of B.E. 2493 (1950) came into force in 1951. The Act encompassed many aspects of drug control other than the control of sale practices. For instance, the control of production and registration of pharmaceutical products as well as the standard requirements of drug quality were included in the Act.
The Act eliminated substandard, deteriorated and adulterated drug products on the local market. Consequently, manufacturing standards of local pharmaceutical firms and dispensaries were upgraded to some extent. The Act was applicable not only to production, importation and sale practices, but also to product registration, labeling requirements and pharmaceutical advertisement control. A few amendments to the Sales of Drugs Act were undertaken from time to time in order to make the law up to date and to cope with changing circumstances in the pharmaceutical business.
After several years of endeavor, the Drug Act of B.E. 2510 (1967) was promulgated to supersede the 1950 Sales of Drugs Act. The 1967 Drug Act covering substantial aspects in drug regulation was enforced for almost two decades. There were four amendments to the Act to cope with the growing numbers of pharmaceutical manufacturers and changing situations until the enactment of the Drug Act of B.E. 2530 (1987), which has major features as follows:
1. Medicines are classified into two major groups: modern and traditional drugs .
Modern Drugs are further divided into four categories, namely 1) household remedies whose sales require no licence; 2) ready-packed drugs that can be sold in drugstores by nurses or other medical professionals; 3) dangerous drugs; and 4) specially controlled drugs. Dangerous drugs can be bought without a prescription but must be dispensed by pharmacists. Drugs which may possess a potentially harmful effect on health, if misused, will be listed in the last category whose sales require a prescription.
Traditional drugs are those intended to be used in indigenous or traditional medical care as monographed in the official pharmacopoeia of traditional medicines or those declared by the Minister of Public Health as traditional medicines or those permitted to be registered as traditional medicines. The control and registration of drugs in this group are less stringent than those for modern drugs.
2. The Ministry of Public Health is authorized to publish in the Government Gazette a list of specially-controlled products, a list of dangerous drugs as well as the lists of particular drugs requiring additional labeling (e.g. expiration date, warning, etc.)
3. Licensing for manufacture, importation and sale of pharmaceutical products is required by law. Applications for licences are to be conducted in accordance with the rules, measures and conditions prescribed in the Ministerial Regulations.
4. Duties of licensees and pharmacists at the place of production, importation or sale are also described. For instance, a licensee who manufactures modern drugs must have finished products of each batch analyzed for quantities of their active constituents before the products are released to the market.
5. Licensees must register their products before manufacture or importation. Details of the products and their formulas, as being registered, cannot be altered without prior approval or permission from the authorities.
6. The Minister of Public Health is empowered to either suspend or revoke the licence from violating or non-compliance licensees.
Laws and Regulations
The Drug Act of B.E. 2510 (1967) is currently stilled in effect, whereas the new Drug Act of B.E.2546 (2003) is in the final stage of promulgation. Attempts to revise the Drug Act of B.E. 2530 (1987) are painstaking and time-consuming. When it becomes effective, many features will be changed accordingly, for example:
- Types of medicines will be reclassified into 3 new categories: prescription-only, pharmacy-dispensing and household remedies.
- Physicians will no longer be allowed to compound medicines for their patients.
- Manufacturers who are unable to comply with the good manufacturing practices (GMP) principles can no longer proceed with the drug business.
- The new law provides more flexibility for revising the GMP requirements. Under the new law, the GMP requirements may be revised and approved by the Drug Committee and declared by the Minister of Public Health; no need to get approval from the Parliament as required in the 1987 law.
- Government-owned enterprises or agencies will no longer be exempted from the requirements of licensing and product registration.
- Pharmaceutical products may be registered in either of the two channels: one for general medicines and the other for Thai traditional medicines.
- Product licences must be renewed every five years.
- The Drug Committee will be authorized to withdraw any drug products if later evidence proves that the products are not scientifically efficacious.
- The Food and Drug Administration will be able to declare certain charges for its services related to licensing, registration, dossier evaluation and approval processes, including expenses for testing the products.
- Product liability will be implemented for the first time. Consumers may directly sue and get compensation from drug manufacturers if there is any serious harm occurring to them after consumption, provided that product indications are strictly followed.
- The deviation of statements in advertisement from those permitted will have to be made known to the public through further apology advertisement along with the correct statements.
- The amounts of fines will be increased up to tenfold, compared to the previous ones.
- A pharmacist will be allowed to work in as many drugstores as he/she can.
According to the Drug Act, the Drug Committee is appointed by the Minister of Public Health every two years to advise him/her on both regulatory and technical aspects concerning the administration of pharmaceutical control. The committee is also authorized to approve or withdraw pharmaceutical registration, standard specifications, criteria and guidelines, including suspending or withdrawal of licences to manufacture, import, distribute or sell. There are 14 regular members on the Drug Committee: five of them being ex officio members who are appointed based on their positions in pharmaceutical-related organizations and the others being appointed from among pharmaceutical and medical experts. The Committee can then appoint subcommittees to assist them with certain tasks. Presently, nineteen subcommittees have been appointed:
- Subcommittee on review and approval for registration of traditional and herbal medicines
- Subcommittee on review and approval for registration of modern medicines (new drugs) for human use
- Subcommittee on review and approval for registration of modern medicines (generic drugs) for human use
- Subcommittee on review and approval for registration of modern medicines (biological products) for human use
- Subcommittee on review and approval for registration of modern medicines for veterinary use
- Subcommittee on re-evaluation of registered medicines for human use
- Subcommittee on surveillance of safety of drug utilization
- Subcommittee on review and approval of drug advertisements
- Subcommittee on establishment of good manufacturing practices (GMP) requirements
- Subcommittee on approval of manufacturing or importing medicines for clinical studies
- Subcommittee on establishment of requirements for bioequivalence studies
- Subcommittee on GCP inspection of clinical studies
- Subcommittee on establishment of guidelines on problem-solving of pharmaceutical raw materials and products for veterinary use
- Subcommittee on evaluation and approval of pharmaceutical quality and testing for compliance with quality standards
- Subcommittee on licensing approval of manufacturers, importers, distributors and drugstores
- Subcommittees on specific assignments:
a. Subcommittee on policy development and promotion of biological products
b. Subcommittee on establishment of requirements for biological products
c. Subcommittee on the exemption of certificates of free sale in the registration of certain products (such as Remune)
d. Subcommittee on approval for registration of growth hormone products.
The Drug Act requires that any person who wishes to sell, manufacture or import drugs into the Kingdom must obtain a licence from the licensing authorities. The Drug Control Division is the licensing and registration authority for manufacturing, import and sale of drugs within Bangkok metropolis and its territories. Provincial Public Health Offices are the licensing authorities for manufacture and import of traditional drugs and sale of drugs in other p rovinces.
Applications for licences must be submitted to the licensing authority. Their buildings and facilities will then be inspected. A licence will be issued after the inspection has confirmed that the applicant has adequate capabilities of doing such business, and he/she can secure appropriate facilities and personnel for that purpose.
Licences are issued, according to the business of the applicant, in nine different categories:
- Licence to manufacture modern medicines
- Licence to import modern medicines
- Licence to sell modern medicines
- Licence as a wholesaler of modern medicines
- Licence to sell modern medicines in sealed packages which are classified as neither dangerous nor specially-controlled medicines
- Licence to sell modern veterinary medicines in sealed packages
- Licence to manufacture traditional medicines
- Licence to sell traditional medicines
- Licence to import traditional medicines
The registration process is necessary to ensure quality, safety and efficacy of the drugs being marketed in the country. Only authorized licensees are qualified to apply for product registration. Manufacturing plants, in which drug products are manufactured, are subject to inspection for GMP compliance.
According to the new Drug Act (expected to be enacted within 2003), a certificate of product registration is valid for five years as from the date of issuance. The process of drug registration will be carried out in 2 channels, which differ in degrees of control and dossier submission:
1. Registration of general medicines
2. Registration of Thai traditional medicines
Due to some differences in the requirements for dossiers to be submitted for product approvals, the general medicines will have to be further defined as:
– Generics whose registrations require only dossiers on product manufacturing and quality control along with product information;
– New medicines whose registrations require a complete set of product dossiers;
– New generics whose registrations require dossiers of bioequi-valence studies in addition to the required dossiers for generics submission.
Generics mean pharmaceutical products with the same active ingredients and the same dosage forms as those of the original products, but manufactured by different manufacturers.
New medicines include products of new chemicals, new indications, new combinations or new delivery systems and new dosage forms.
New generics are medicines with the same active ingredients, doses and dosage forms as those of the new compounds registered after 1992.
The amended registration procedure for new drug products, adopted in August 1989, involves a two-year period of safety monitoring program. This means that new drug products will be firstly approved for use only in hospitals or clinics for at least two years. Then safety reports must be submitted for consideration as to whether general marketing should be allowed. Meanwhile, new generic products have to pass bioequivalence studies to assure comparatively therapeutic outcomes. The bioequivalence data must be submitted to the authorities as proofs of the product bioavailability along with product information and quality dossiers.
Quality assurance of drug safety and efficacy before marketing can undoubtedly be achieved through good manufacturing practices. Inspection of drug manufacturers and sampling of drug samples from manufacturers, importers or retail pharmacies for analyses by the regulatory authorities cannot effectively solve the problems encountered. Drug manufacturers, importers and distributors must establish their quality assurance systems according to the GMP guidelines to ensure that the drug products have and continue to have the quality as claimed.
The Thai FDA has begun campaigning on GMP compliance since 1984. Projects on development of local pharmaceutical industry up to internationally acceptable standards were part of the Sixth National Economic and Social Development Plan (1987–1991) and also of the Seventh Plan (1992–1996). The projects aimed to promote and support local drug manufacturers in implementing good manufacturing practices. The first guidelines of Thai Good Manufacturing Practices were published in 1987. Since then numerous workshops, seminars and conferences as well as consultative visits have been held or carried out to promote the guidelines adoption.
Control of Drug Advertisement
Drug information available to health-care professionals and consumers is as important as drug quality for the safe use of drugs. Drug advertisements and other promotional materials need to ensure truthfulness and non-exaggeration. Advertisements through any means must be approved by the authorities before actually being disseminated. Advertisements of prescription or pharmacy-dispensed medicines are permitted only to professionals but prohibited to the general public. Drugs in the household remedy category may be advertised directly to consumers or the general public.
The control of drug advertisements is presently focused on the increasing advertisements on the Internet. A majority (>85%) of such advertisements are being run without FDA permission. Due to the fast growing numbers of and difficulties in catching up with these advertisements, the monitoring of violation as well as guidelines and measures for the violation control must therefore be comprehensive and updated periodically.
To further ensure quality, safety and efficacy of the approved drug products, the marketed products are regularly sampled for testing at the drug analysis laboratory of the Medical Sciences Department, Ministry of Public Health. In addition, contracts have been signed with some qualified laboratories of local universities to assist in solving the problems of drug quality. The surveillance tasks involve the following ;
Inspection of GMP compliance at manufacturing sites;
– Monitoring of manufacturing process changes to ensure no adverse effects on the safety or efficacy of the medicines;
– Monitoring of the use of marketed drugs for unexpected health risks, taking action if risks are detected by informing the public, investigating the cause and removing the drugs from the market;
– Receiving and handling of complaints;
– Safety monitoring program for new drugs;
– Re-evaluation of pharmaceutical products.
Re-evaluation of Pharmaceutical Products
Even though drugs have been strictly examined for their quality, efficacy and safety before being approved for marketing, chronological consumption data in a large population, new findings and pharmaceutical progress may later reveal very serious side effects that were not previously seen. A balance between efficacy/benefit and potential risks or serious adverse reactions is frequently questioned, especially those in combination. The Drug Committee in 1991 appointed a subcommittee to evaluate the registered products. Some criteria have been set and the evaluation process has been ongoing.