Pharmaceutical Quality and Accessibility of Emergency Contraceptive Levonorgestrel Tablets via Personal Importation in Japan

Abstract

Introduction: Levonorgestrel (LNG) tablets are used for emergency contraception and must be taken within 72 h after unprotected intercourse. In Japan, access had historically been restricted, although it has improved with the introduction of over-the-counter LNG tablets. However, barriers such as cost and convenience might still lead some individuals to obtain LNG through personal importation websites. We assessed the accessibility, regulatory compliance, and pharmaceutical quality—specifically, content assay and content uniformity—of LNG products obtained through these unregulated online pathways. Methods: We identified nine personal importation websites through a Google search and purchased one LNG product from each site, assessing characteristics such as price, delivery time, packaging method, and insert availability. We evaluated pharmaceutical quality through quantitative analysis and content uniformity testing. Results: Imported LNG tablets were cheaper than those available through official channels (mean: ¥1835/dose in 2022). However, the mean delivery time through personal importation was 19 d, making these products unsuitable for urgent use. Moreover, we observed missing instructions and foreign-language labeling. Quality testing revealed that five of the nine products were out of specification for the United States Pharmacopeia assay, and eight of the nine failed to meet the Japanese Pharmacopoeia XVIII content uniformity criteria. Discussion: Although recent regulatory changes have allowed LNG tablet purchases from pharmacies without a prescription, structural and regulatory barriers to timely access remain—specifically, prohibitive costs compared to other nations and limited pharmacy access. These barriers potentially lead individuals to rely on personal importation, posing public health concerns. Ensuring equitable and prompt access to emergency contraception through appropriate regulatory frameworks and information is essential.

INTRODUCTION

Levonorgestrel (LNG) is a critical emergency contraceptive, with a reported efficacy of approximately 85% when administered within 72 h of unprotected intercourse.¹⁾ The WHO classifies emergency contraception as an essential medicine, stating that all individuals at risk of unintended pregnancy have the right to access it.²⁾ In Japan, LNG tablets are currently the only approved emergency contraceptive. This study was initiated in 2022, a period when LNG was strictly prescription-only in Japan, making timely access a significant challenge. Although Japan subsequently transitioned LNG to OTC status in February 2026, structural barriers persist: administration must occur in the presence of a pharmacist, retail prices remain significantly higher than those in other countries, and access is restricted to pharmacies with specifically trained pharmacists.^3,4)

These constraints suggest that some individuals may still rely on personal importation as an alternative pathway, even after OTC conversion. Although small-quantity importation for personal use is permitted under specific conditions in Japan,⁵⁾ it presents substantial public health risks. These products are excluded from Japan’s Pharmaceutical Side Effect Victim Relief System, lack official domestic quality and safety approvals, and carry the risk of counterfeit circulation.^6,7)

Despite these concerns, empirical data on the pharmaceutical quality and distribution characteristics of LNG obtained through personal importation in Japan are scarce.^6–8) This study aimed to evaluate the availability of essential information upon purchase and the pharmaceutical quality (content and uniformity) of LNG tablets obtained via personal importation websites. By documenting the reality of these products, we provide essential evidence to inform public health policy and ensure safe, quality-assured access to emergency contraception in Japan.

MATERIALS AND METHODS

Website Selection and Product Procurement

In April 2022, nine personal importation websites were identified via Google using the keywords “emergency contraceptive pills AND personal import” in Japanese. Inclusion criteria primarily required online ordering, transparent pricing, and Japanese language support. To ensure a broad assessment of the market and avoid site-specific bias, only one LNG product was purchased from each website. If a website offered multiple LNG products, we selected the product that was listed on the fewest number of other websites to maximize the product diversity of available products. The website search was conducted from April 11 to 22, 2022, and orders for LNG products were placed from April 25 to 29, 2022. Site characteristics, inclusion criteria, and selection protocols are detailed in Supplementary Material 1.

Observational Assessment

At the time of product purchase, we examined whether each website provided the information required under the Act on Specified Commercial Transactions, including business identification details, pricing and shipping information, payment and delivery conditions, and return policies.⁹⁾ Furthermore, we identified and recorded whether detailed information was provided, such as recommendations to consult a physician or pharmacist, explanations of personal importation, and descriptions of the pharmaceutical products.

For each of the purchased products, the following items were observed and recorded: the condition of the packaging method upon arrival, the country of manufacture, the dosage and number of tablets per box, the time to delivery (from online order to receipt), the expiration date after arrival, the single-dose price (single and bulk purchases), and the presence of the package insert and its language. We calculated the purchase price, excluding shipping and importation fees. Data are presented as the mean ± standard deviation (S.D.).

Pharmaceutical Quality Assessment

Pharmaceutical quality was evaluated through quantitative assay and content uniformity testing, using a domestic LNG tablet (Fuji Pharma Co., Ltd., Tokyo, Japan) as the reference. For sample preparation, tablets were extracted with methanol–water (1 : 1, v/v) under agitation and then filtered. LNG content was determined by HPLC-UV (200 nm, isocratic C₁₈ column, acetonitrile–water 1 : 1, v/v, 1.0 mL/min). Per United States Pharmacopeia (USP) 37, products within 90.0–110.0% of the labeled claim were considered acceptable.¹⁰⁾ Content uniformity was assessed following the 18th Edition of the Japanese Pharmacopoeia (JP XVIII), with an Acceptance Value (AV) ≤ 15 as the passing criterion.¹¹⁾

The analytical method was validated for linearity (0.5–5.0 μg/mL), accuracy, and intra-/inter-day precision (evaluated over nine days). Identification was confirmed by comparing retention times and UV spectra with those of a reference standard. Detailed analytical conditions are provided in Supplementary Material 2.

RESULTS

Website and Product Characteristics

Nine LNG products were procured from nine websites (Table 1). Compliance with the Act on Specified Commercial Transactions was inconsistent; several sites lacked representative names or telephone numbers (Table 2a). Although the assessed medications are classified as prescription-only or pharmacist-dispensed drugs in their countries of manufacture, only five of the nine websites (55.6%) included a recommendation to consult a physician or pharmacist (Table 2b). Additionally, none of the websites required a prescription at the time of order, and some actively advertised that no prescription or medical certificate was necessary for purchase.

Table 1. Overview of LNG Products Purchased for Trial Use

Product ID	Country of manufacture	Language of package insert	Amount of LNG per tablet (mg)	Dosage	Number of tablets per box	Availability period (d)	Expiration date after delivery (years)	Single-dose price (single purchase) (Yen)	Single-dose price (bulk purchase) (Yen)
A	Unknown	No attached document	1.5	1 tablet once	4	15	2.6	745	720
B	India	Hindi, English	1.5	1 tablet once	1	15	1.3	1140	798
C	Thailand	Thai	0.75	1 tablet + 1 after 12 h	2	8	4.2	1150	1150
D	India	Thai	0.75	1 tablet + 1 after 12 h	2	24	0.5	1300	1050
E	India	No attached document	1.5	1 tablet once	1	25	1.5	1400	532
F	Spain	Thai, English	1.5	1 tablet once	1	25	1.7	1849	504
G	India	English, Hindi, Marathi, Kannada, Malayalam, Bengali	1.5	1 tablet once	1	15	1.6	2280	665
H	France	Dutch, German, French	1.5	1 tablet once	1	25	3.5	3280	2494
I	Hungary	English, French (outer box)	0.75	2 tablets once	2	15	2.8	3370	1133

Summary of product types, purchase conditions, and basic characteristics of LNG tablets obtained through personal importation agent websites. With the exception of Sample A, each box represented a single-use unit. LNG: Levonorgestrel.

Table 2. Survey Results of Personal Importation Websites

a) Display status of items required under the Specified Commercial Transactions Act
Necessary information	Number of sites (n = 9)/Display rate (%)
1) Name of representative or person in charge	8 (88.9)
2) Name of business operator	9 (100)
3) Address	9 (100)
4) Telephone number	6 (66.7)
5) Sales price	9 (100)
6) Shipping costs	9 (100)
7) Payment date	9 (100)
8) Product delivery date	9 (100)
9) Payment method	9 (100)
10) Special provisions regarding returns	9 (100)
b) Description of items related to the Pharmaceutical Affairs Law and Public Health Guidance
Items to be listed	Number of sites (n = 9)/Display rate (%)
1) Recommendation to consult a doctor or pharmacist	5 (55.6)
2) Information on personal importation	8 (88.9)
3) Product information
Product name of the medicine	9 (100)
Photograph that clearly identifies the product	9 (100)
Dosage and administration	9 (100)
Efficacy and effects	9 (100)

Logistics, Costs, and Packaging

The mean delivery time was 18.6 ± 5.9 d, significantly exceeding the 72-h window required for effective emergency contraception (Table 1). The mean price per dose when purchased individually was ¥1834.9 ± ¥898.0 (range, ¥745 – ¥3370). When purchased in bulk (≥ 10 doses), the mean unit price per dose was ¥1005.1 ± ¥574.4 (range, ¥504.0–¥2494) (Table 1). Bulk purchase discounts (≥ 10 doses) were universally promoted, with some sites recommending quantities of up to 30 tablets without restriction. Regarding the packaging method, five samples lacked cushioning, and two arrived in plastic bags.

Labeling and Dosage Instructions

Two samples omitted package inserts entirely (Table 1). Available inserts were written in foreign languages (e.g., Hindi, Marathi, and Bengali), with no Japanese instructions provided. Notably, Sample A directed users to a nonexistent insert for administration details. Dosing regimens varied; Samples C and D required a two-dose schedule, differing from the single-dose 1.5 mg LNG regimen approved in Japan.

Pharmaceutical Quality

Quality assessment revealed that five of the nine products (55.6%) fell outside the USP quantitative assay range (90.0–110.0% of the labeled claim). Furthermore, eight of the nine products (88.9%) did not meet the content uniformity criteria, with AVs exceeding the limit of 15 (Table 3). In contrast, the Japanese-approved reference product met all regulatory standards for both assay and content uniformity.

Table 3. Results of the Quantitative Assay and Content Uniformity Test

Product ID	Reference product※	A	B	C	D	E	F	G	H	I
	Content (%)
	103.3	113.5	107.5	113.2	117.6	98.5	112.3	120.5	105.0	109.3
	95.0	119.8	107.8	116.7	121.3	95.8	113.7	126.6	107.2	115.2
	103.5	117.9	109.6	119.1	91.1	103.0	119.2	129.1	107.1	121.9
	104.0	114.5	109.8	115.9	104.8	93.0	100.7	111.7	102.5	102.6
	101.5	117.1	103.5	114.2	99.5	93.4	107.7	111.6	98.9	103.1
	103.2	123.8	110.5	114.7	109.7	94.4	107.8	113.4	102.1	106.0
	102.6	116.6	103.2	130.6	120.5	121.1	119.1	125.3	105.6	104.8
	104.1	119.1	101.9	139.3	123.5	121.0	124.0	125.8	106.0	106.9
	98.2	126.7	108.9	140.0	127.2	127.7	121.4	130.4	117.5	113.6
	100.0	131.7	103.7	148.6	131.9	119.0	137.7	130.3	120.3	103.9
Quantitative analysis
Mean content (%)	101.5	120.1	106.6	125.2	114.7	106.7	116.4	122.5	107.2	108.7
S.D.	2.97	5.69	3.21	13.18	13.01	13.82	10.39	7.63	6.69	6.31
Content uniformity test
Acceptance value	7.2	32.2	12.9	55.4	44.4	38.4	39.8	39.3	21.8	22.4
Judgment		Fail	Pass	Fail	Fail	Fail	Fail	Fail	Fail	Fail

^※The reference product refers to a Levonorgestrel tablet approved and marketed for use in Japan. S.D.: standard deviation.

Method Validation

The analytical method for LNG demonstrated an accuracy of 0.1%. The relative S.D. for intra-day precision was 1.7%, while that for inter-day precision was 0.5%. The calibration curve for LNG showed good linearity over the tested concentration range, passing through the origin, with a coefficient of determination of ≥ 0.995.

DISCUSSION

This study demonstrates that LNG tablets are easily accessible through personal importation websites in Japan at a significantly lower cost (mean ¥1835) than through domestic medical consultations or the current OTC system (approx. ¥7000–¥20000). While these websites offer a low-cost alternative, they operate outside the formal regulatory framework, raising significant concerns regarding pharmaceutical quality and user safety.

Pharmaceutical Quality

In the present study, 55.6% of the imported LNG products failed to meet the assay specifications defined by the USP (90.0–110.0%). Moreover, in the content uniformity test, 88.9% of the products displayed AV scores exceeding the maximum allowable limit of 15 and thus failed to satisfy the JP XVIII acceptance criteria. These results indicate substantial tablet-to-tablet variability in the active ingredient content. Although no defects posing an immediate, acute health risk—such as lethal overdose or the absence of active ingredients—were identified in this specific sample set, the lack of consistent quality is highly concerning. Previous studies have documented that personal importation channels often involve products with sub-therapeutic doses or even counterfeits produced under unhygienic conditions.^12–17) Although we did not directly assess product authenticity, the “out-of-specification” results found here underscore the risk that these products may not consistently meet the quality standards expected by consumers.

Barriers to Safe Use

Beyond pharmaceutical quality, significant barriers to safe use were identified. The mean delivery time of 18.6 d makes these products inherently unsuitable for immediate emergency use, suggesting that they are primarily purchased for “stockpiling.” However, the inability to confirm expiration dates in advance and the lack of Japanese or English package inserts pose serious risks for misuse. In some cases, the packaging units did not align with the recommended single-dose regimen, which could lead to suboptimal dosing. Although these findings are derived from our 2022 survey, they highlight the inherent risks that persist as long as individuals utilize unregulated channels. While the transition of LNG to OTC status in February 2026 was a step forward, structural barriers—including high costs and the limited number of authorized pharmacies staffed by specially trained pharmacists—may potentially remain as factors that incline individuals toward uncertain importation pathways.

Limitations

Due to practical constraints, we did not examine all LNG-containing products available through personal importation websites. Because our selection criteria prioritized product diversity, our sampling strategy may not reflect the representativeness of the actual market. Furthermore, these results should be interpreted with caution, as product authenticity was not assessed, and it remains unknown whether the products are counterfeit or whether the accompanying product information is official. Nevertheless, this study provides case-based evidence suggesting that LNG tablets available from easily accessible personal importation websites might not be consistently supported by comprehensive quality assurance and complete safety-related information.

In conclusion, although this study confirms that personal importation provides an affordable route, it lacks the quality assurance and institutional protections of the formal healthcare system. Emergency contraception is an essential medicine that must be timely, affordable, and safe.²⁾ From a public health perspective, further discussions are warranted regarding policy efforts to improve the affordability and accessibility of quality-assured products within the domestic formal system to address potential reliance on unregulated pathways.

Acknowledgments

We would like to express our sincere gratitude to the members of the Laboratory of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, for their kind support and cooperation.

DECLARATIONS

Conflict of Interest

The authors declare no conflict of interest.

Supplementary Materials

This article contains supplementary materials.

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