Review on the Selection of Drugs in Thai Healthcare
Pharmaceutical drugs (also referred to as pharmaceutical medicine) play a critical role to cure or prevent disease and improve health, but they can be very harmful when uses inappropriately. Moreover, the production, distribution and dispensing of them also require special knowledge and expertise. Therefore, all aspects of them need an effective system for pharmaceutical management which entails a full cycle of operations beginning with drug selection, procurement, logistics and distribution and finally delivery to end-users.
Among these processes, the selection of pharmaceutical drugs is the most powerful tool because it has two facets which could contribute to both barriers and facilitates for patient access to medicines. In Thailand, the framework of pharmaceutical drugs’ selection can be divided into three levels. At country level, public hospital level and pharmaceutical industry level. At the country level, there are two main process:
(1) the Drug registration process which the Thai Food and Drug Administration (Thai FDA) under the authority of the Ministry of Public Health is responsible for implementing medicines regulation in order to ensure the efficacy, safety and quality of drugs freely sold in Thailand, and
(2) the National List of Essential Medicines (NLEM) which is the pharmaceutical reimbursement list for the three public health schemes namely the Civil Servant Medical Benefit Scheme (CSMBS), the Social Security Scheme (SSS), and the Universal Health Coverage Scheme (UCS).
At hospital level, this review focusses only public hospitals. There are the Pharmacy and Therapeutic Committees (PTC) which assess and select the drugs into the hospital formulary. At pharmaceutical industry level, manufacturers and importers play a key role to control the pharmacological products in markets in relation to different benefits and interests
1. Drug selection at Country level
1.1 Drug Registration
Thailand has a long history of implementing drug regulation for protecting consumer health with the Drug Acts B.E. 2510 and its various revisions and amendments since 1967 including the Drug Act B.E. 2518; B.E. 2522; B.E. 2527; B.E. 2530; and the latest Drug Act B.E.2562.
The Bureau of Drug control under the Thai FDA is responsible for implementing medicines regulation which governs the registration of drugs, licensing of drug manufacture, sales, and importation. Medicines are classified into two major groups: modern and traditional drugs which included medicines for both human and animals. However, this article focuses on the modern drugs registration including new drugs, generic drugs and new generic drugs during the period of 1936 to 2019. A brief historical evolution related drug regulatory is chronologically listed in Table illustrating the evolution of the selection process at the country level has been evolving to align with international standard and to adapt to changes in the trends of medical technology advancement with the aim to increase drug quality. Currently, there are 2,282 medicines (excluding repetition) with approximately 20,000 licenses in the market.
1.2 Selection of essential drugs into the National List of Essential Medicines (NLEM)
After regulatory approval, some of them can be proposed to the NLEM process. The Subcommittee on the NLEM under the National Committee of Drug System Development is responsible agency to develop and update the list regularly.
The first version of the NLEM developed in 1981, adopted the concept of the World Health Organization’s Model List of Essential Medicine in order to promote the rational use of medicines. There were 370 medicines (excluding duplicates) listings which was served initially as a basis for the medicine supply in the public sector. After Thailand faced the economic crisis in 1998; however, the list was a largely revised and then used as a reimbursement list for the Civil Servants Medical Benefit Scheme (CSMBS) in order to cut down unreasonable expenditure. As a result, the subcommittee appointed the 23 National Expert Panels representing different drug groups to select medicines based on criteria. At that time, the list was classified into five different categories regarding the level of health providers’ and prescribers’ specialty, as follows:
- Category A: Basic medicines for all health facilities, to use as first-line treatment
- Category B: Alternative, second line medicines of those in Category A
- Category C: Medicines prescribed only by specialists approved by the hospital director
- Category D: Medicines used only particular indication and disease, and these drugs will be subjected to Drug Utilization Evaluation (DUE) to ensure proper use
- Category E: Medicines used for special government projects (e.g., HIV/AIDS, TB drugs).
As a result of strong emphasis of the NLEM after this reform, the number of medicines has significantly increased by almost two folds between 1996 and 1999 (Figure 2). Since 2004, the NLEM Subcommittee has applied a more evidence-based approach for the revision of NLEM. The application of cost and criteria for comparative evaluation of products in term of “ISafE score” and “Essential Medical Cost Index (EMCI)” have been established. ISafE stands for Information, Safety, ease of use namely patient adherence, frequency of drug administration, and Efficacy of each medicine. The medicines with ISafE score (ranging from 0 to 1) above the 50thpercentile in the same group are further assessed for their treatment cost by the NLEM adjusted cost index (Essential Medicine Cost Index; EMCI). EMCI is the treatment cost for a medicine (defined daily dose) divided by the ISafE score. The medicines with low EMCI are likely to be adopted in the NLEM because these medicines are economical and cost-effective. In addition, the selection of drugs into the list became more transparent and participatory by including key stakeholders such as representatives from the three public health insurance schemes, health service providers, and patient groups. In 2008, the government was under increasing pressure to include new high-cost drugs into the list, NLEM category E was divided into two subgroups: E is the previous the category E, and E is majorly high-cost medicines for special situation customized for a particular patient. There were 10 medicines on the category E. After that, the mechanism for selecting high-cost drugs was introduced by adopting health technology Assessment (HTA), mainly health economic evaluation and budget impact analysis as evidence to support the decision-making process. Within this HTA step, the high-cost medicine was analyzed to determine whether it was cost-effective and affordable. But ultimately, the policy makers’ decision also depends on other decision tool such as financial burden of households, social and ethical issues, and program feasibility. These processes have been used since their inceptions to the present day. Currently, there are totally 780 medicines on the NLEM.
The challenges of the next step are the development tool for assessment of cost-effectiveness and appropriate funding mechanisms under the constraints of limited resources to be able to access the high-cost innovative medicine, especially the targeted drug or biological product which are the future trends.
2. Drug selection at public hospital level
According to “Thai Drug Management Manual, 1978”, all levels of public hospitals under the jurisdiction of Ministry Of Public Health (MoPH) must establish the Pharmacy and Therapeutic Committees (PTCs).PTCs were designed to: optimize rational use of medicines through establishing restricted drug use policies and practical guidelines for medical management; evaluate and select medicines for the formulary lists; manage procurement; and ensure adherence to the administrative guidelines. The PTCs consists of a multi-disciplinary panel of experts such as physicians, pharmacists, dentists, nurse and other health care professionals which the number of PTC members varies depending on each healthcare institution. The most important functions of the PTCs are drug evaluation and selection based on efficacy, safety, quality and price (or cost-effectiveness). Almost three decades, procurement of medicines into the hospital has been conformed to the Regulations of the Office of the Prime Minister on Procurement B.E. 2535 (1992) and the Regulation of the Office of the Prime Minister on Electronic Procurement B.E. 2549 (2006). The drugs’ price seem to be the main selection criterion to make decisions. However, the Government Procurement and Supplies Management Act B.E. 2560 (2017) was later enacted with the principles of anti-corruption and transparency on governmental procurement in order to standardize procurement and supplies management, apart from the previous regulations. In accordance with the new Act, the price-performance criteria was required for pharmaceutical procurement via bidder. Each hospital and its PTC set the criteria for compulsory and voluntary factors of decision making. There are two main aspects including the general quality criteria, and the specific quality criteria.
3. Drug Selection at the Pharmaceutical Industry Level
The Thai pharmaceutical industry can be divided into state and private manufacturers. The Government Pharmaceutical Organization (GPO) is the key state pharmaceutical manufacturer while private manufacturers can be further divided into those producing drugs locally or importers. The processes for selecting drugs to bring to the market will vary between these different types of manufacturers. For local producers, the key considerations are whether the drug is in the NLEM, drugs with high market values, and high priority drugs, as the unmet pharmaceutical needs and drugs with the potential return on investment at an acceptable level. Importers are mainly multi-national companies (MNCs) and generally import drugs which fulfil unmeet health needs including those to treat diseases for which no effective treatment exists in the market or those which increase convenience and adherence for the patients. However, there are government policies related to drug registration, price control and reimbursement policies, which can be a positive or negative influence. Manufacturers take into account all these considerations about which drugs are suitable for market entry.
In addition, local companies import branded drugs from abroad for which the selection criteria are somewhat similar to MNCs’ practices but may also consider the patent expiration/ duration and the ability for a domestic producer to manufacture the drug locally. This information on pharmaceutical industries was taken from excerpts from interviews in July 2019. For GPO, its main mission is to supply drugs, acquired through production and procurement, in adequate quantities to meet the needs of government hospitals and hence the drugs that would be mainly selected are essential drugs in the NLEM, drugs which are not yet produced locally, and those which support urgent health policies such as vaccines. In addition, there is mission to research and develop new pharmaceutical products and medical supplies to respond to the need and necessity of the Thai society. Due to the non-perfectly competitive pharmaceutical markets, Thai government has a strong attempt to create incentives for encouraging the new development of safe and effective drugs or bringing new pharmaceuticals into the market. There are two cases of government regulation:
- The Orphan Drug List’s policy
- Targeted list of priority Medicines’ policy
in order to organize the highest level of accessible and equitable drug possible and protect public safety.
3.1 The orphan drug list
In Thailand the orphan drug has been developed siince 1992, initially serving as a basis for temporarily and permanently stock out of drugs needed in the public sector, and approval drug needed but approval and available in other countries. The National Drug Committee appointed the Subcommittee on Orphan Drug which coordinated by the Bureau of Drug Control of the Thai FDA. This Subcommittee’s roles and responsibilities are to address the problems and advise proper solutions. The definition of an orphan drug is specified as a drug needed with the problem on drug shortage. After accomplishment, the first Orphan Drug List (1994) was publicly announced with 43 medicines. Later in 2005, more features were added to this definition which included 3 main criteria:
(1) drugs were in need for diagnosis, alleviation, treatment, and cure
(2) drugs were in need with any of these causes: a rare disease, a severe disease, a disease can cause prolonged disability, a drug with low consumption and no drug alternatives
(3) drugs with shortage
These criteria based on both the status of rare diseases and drug shortage issues were different to the definition/criteria for orphan drug in other countries such as the US, Canada, Australia and EU. In 2006, Thai FDA has developed a guideline regarding the registration of orphan drugs which was subsequently revised and published in 2013. According to the guideline, some requirements for the assessment of orphan drugs are exempted, particularly if the orphan drugs have been used more than 10 years and its efficacy and safety have been well established. In such cases, the Thai FDA would allow submitting without preclinical or clinical modules. Also, Thai FDA granted the privilege for these drugs in order to create more incentives for manufacturers and importers such as ‘fast track’ regulatory registration and exemption of drug registration fees including approval and other amendments’ fee.
At present, the updated list in 2019 is announced with 76 medicines (excluding repetitions). Most of them, both public and private pharmaceutical companies would like to assist with production or importation. However, 29 drugs in this category remained unavailable in the market. Therefore, Thai government has put efforts to increase patients’ access to the medicines through tariff policy for orphan drugs’ imports. Eventually, there is the Cabinet Resolution in November 2019 stipulated orphan drugs’ importation to be entirely exempted from the customs tariff.
3.2 Targeted list of priority Medicines (PRIMEs)
Due to the rise in drug spending, the government introduce an initiative in 2017 called “targeted list of priority medicines (PRIMEs)”. Initially, the PRIMEs list included 144 medicines which were the drug needed for public health, sold in either a monopoly or oligopoly and could potentially encounter problems of drug access and security. The government encourages the pharmaceutical industries including manufacturers and importers to bring the generic on the PRIMES list into the drug market as soon as possible. The following measures were also implemented to promote the entry of generic substitution to highcost original drugs: l The reduction of registration fees by 50% as per the Thai FDA announcement on 5th September 2016 and 8 February 2018 l Drug patent information search to provide local manufacturers/importers with the data to develop plans related to the introduction of generic drugs l Development of reference prices for public procurement.
From these measures that took place between 2017 and 2018, there were 102 registered drugs with 57 manufactured locally and 45 imported from other countries. After announcing the first and second of PRIMEs, the number of registered drugs have all increased and included in the NLEM due to lower costs and budget impact. For example, the number of approved brands for entecavir (treatment of hepatitis B) increased from 2 to 5 registrations, and donepezil (treatment of Alzheimer’s disease) increased from 7 to 16 registrations.
In this article we have mainly described of the development of drug selection policies at the country level, particularly the process of drug registration and NLEM listing. For the drug selection at the public hospital level, we included only the general guidelines, which provide the direction for hospitals to conduct drug selection. However, in actual practice, this may vary from one hospital to another. Furthermore, it should be noted that information relating to how manufacturers select drugs to bring to market may be highly sensitive and what is presented here gives just a general framework on what was considered during the process. Having said that, we were able to summarize the progress and evolution policy implemented at the Thai FDA level in terms of the impact on the availability of the orphan drug listed and the targeted list of priority medicines in the market. There was an increase in the registration of generic drugs and subsequent accessibility to Thai population. It has been illustrated that the selection process at the country level has been evolving to align with international standard and to adapt to changes in the trends of medical technology advancement which aimed to increase drug quality. One of the key reason is the introduction of Good Manufacturing Practice (GMP) in 2003 as one of the requirements for drug producers to comply, leading to the use of stability data in drug manufacturing regulation.
Also, bioequivalence study was required to show that generic drugs are as effective in treating diseases compared to its original counterpart, and therefore, the prescribers can use these generic drugs with confidence. However, there are key challenges in the drug registration process as following:
1) Drug definition which the regulatory pathway can be improved to international standard by reducing complexity in the criteria and guidelines. For example, the process for generic approval can be subdivided in to ‘new generic’ and ‘existing generic’. While the process for new generic drugs is up to international standard and bioequivalence data is required for registration, the existing generic which a formulation has been registered before 1991 is exempt. This can create confusion and potentially lead to exposure to unsafe medicine to the public.
2) The fees in the registration processes and other related activities (e.g. registration maintenance) are low, which could lead to manufacturer filing for registration-related activities unnecessarily. The NLEM selection process has been improved over the years by adopting the evidence-based ISafe and EMCI system to make it more systematic and transparent. In the case of high-cost drugs, economic evaluation and budget impact analysis have been used in both the decision making and price negotiations to increase access. However, with the advance in technology and new treatment paradigm in biologic drugs, the issue of balancing the timely access to these innovative drugs and limited availability of budget and resources will be increasing, and hence there is an on-going need to develop this process further. Additionally, the policy to promote traditional medicine may be hindered by the lack of reliable evidence in order to help with the decision making in whether to include a traditional medicine formulation in the NLEM. There has been no major change in how drug selection is conducted at hospital level.
On the other hand, the process to select drugs by the manufacturers has been significantly influenced by the targeted medicine list introduced in 2016 and the orphan drug listed which create an additional incentive to the existing criteria based unmet needs and profitability to promote these necessary drugs to market. However, despite these improvements in the chemical-based drugs, the impact is minimal in the area of biologic drugs. This may be due to the fact that there were only five local manufactures with the capacity to handle the complexity of manufacturing biologic products, the lack of technical staff and infrastructure, and the high barrier to obtain this capability due to high investment costs which there were no major incentives for the private sector to pursue.
Source Journal of Health Science, Ministry of Public Health