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- 2026-04-13 17:39:03
- Policy
- The per capita GDP reference standard was deleted from ICER
- by Lee, Hye-Kyung Sep 27, 2021 05:51am
- The per capita GDP phrase was deleted from the ICER threshold used in the economic evaluation process of the first stage of new drug benefits. Although it has been changed to refer to the results of the existing deliberation, the phrase GDP per capita has been deleted, and the application of ICER values, one of the pharmaceutical industry's long-cherished projects, remains to be seen. On the 23rd, The HIRA unveiled the "Detailed Evaluation Criteria for Drugs Subject to Negotiation, such as New Drugs (Completed Amendment)." The revision of this standard includes the evaluation criteria deliberated and resolved at the 8th Pharmaceutical Benefit Appeal Committee held on September 3. The HIRA changed the standard, saying, "We will flexibly evaluate the disease by referring to the results of the existing deliberation considering its severity, social disease burden, impact on quality of life, and innovation." An additional content was added, "Refer to the results of the existing deliberation." The existing evaluation criteria will be applied first without linking GDP per capita in cost effectiveness. Kim Ae-ryeon, head of the drug management office, said, "We have decided to delete the application of per capita GDP standards to ICER values through meetings in the pharmaceutical industry, expert advice, and civic group opinions." She explained, "In the early days, expert advice was dominant that it was to apply health care priorities." She said,"Instead of deleting GDP standards to ICER, we need other standards." She added, "As we have accumulated experience while running the committee, the revision was carried out as opinions were gathered that it was reasonable to refer to the results of the existing deliberation." The pharmaceutical industry has been demanding expansion, pointing out that the domestic ICER threshold remains at the level of 25 million won, a reference to GDP in 2013.
- Company
- When does Sputnik ship in Korea?
- by Kim, Jin-Gu Sep 27, 2021 05:51am
- SputnikShipment of the domestic finished product of the COVID-19 vaccine Sputnik developed in Russia will begin as early as next month. The consortium centered on Korus has already secured 10 million finished products, and the Huons Global Consortium plans to start producing finished products by the end of this year. ◆Prospects of shipment of finished products next month, Russian media also report "imminent" According to Korus on the 17th, the Korus consortium, which consists of seven companies and institutions, plans to ship the finished product of Sputnik as early as next month. Korus has already started producing finished products and has completed the production of undiluted solutions for 10 million people. An official from the company explained that if a request is received from RDIF, it can be shipped immediately after filling. Korus has completed the submission of relevant data and is waiting for certification from the Russian government. It explains that initial shipments are possible as soon as authentication is completed. There have also been reports in Russia that shipments are imminent. Russian news agency TASS reported on the 16th (local time) that GL Rafa will ship Sputnik Light in the near future, and RDIF is planning a commemorative event related to this. Huons Global product production has begun, "The forecast of production of finished products by the end of this year Korus signed a contract with RDIF for consignment production of Sputnik V in September last year. Since then, Korus has formed a consortium with six companies and one institution, including Binex, Boryungbio, Isu Abxis, CKD Bio, Quratis, and Andong Animal Cell Demonstration Support Center. The consortium plans to build production facilities of more than 100 million doses per month. However, as product production and local approval were delayed due to local circumstances in Russia, questions were raised over the specific timing of shipment of finished products. An official from Korus said, "We signed the first Sputnik V consignment production contract, but with the release of Sputnik Light, which was improved with one inoculation, the originally planned schedule has been slightly delayed," adding, "We expect to be able to ship as early as next month." ◆Huons Global product production has begun, The forecast of production of finished products by the end of this year Huons Global Consortium also predicts that it will be possible to produce finished products within this year. Prestige Biopharma, Humedix, and BoranPharma are participating in the Huons Global Consortium. Huons Global announced on the 17th that it has started production of Sputnik V's products since this week. Prestige Biopharma is in charge of this production. Prestige Biopharma is in charge of manufacturing undiluted solutions at the Huons Global Consortium. After a Russian official checks the product, a Huons Global official predicted that production of the finished product will be from November to December. A meeting with Russian officials last August with Huons Global Consortium An official from Huons Global said, "It is expected that the validation confirmation process will be completed within this month. We will be able to start producing finished products within this year, he said. The produced products will be supplied to more than 70 countries that have approved Sputnik at the request of Russia, he said. Huons Global signed a contract with RDIF for consignment production of SputnikV in April.
- Policy
- Reimbursed generics pour in with Xarelto's patent expiry
- by Kim, Jung-Ju Sep 24, 2021 05:57am
- More than 100 reimbursed generics of Xarelto will be pouring into the market next month with the substance patent expiry of the novel oral anticoagulant (NOAC) Xarelto (rivaroxaban). Among the drugs, products that are subject to premium pricing for being drugs from innovative pharmaceutical companies, etc. are Chong Kun Dang’s Riroxia Tab. 15mg, and 20mg that was released earlier in May. The two drugs will receive premium pricing for 7 months based on the release date of the 20mg strength. According to industry sources on the 23rd, the Ministry of Health and Welfare is working to amend the ‘Drug reimbursement list and reimbursement ceiling price table’ to include such changes. The changes will be effective from October 1st. First, the price of Korea Prime Pharm’s Xaito Tab. 10mg has been set at 85% of the highest price of same ingredient drugs that are already listed as it met only one of the two standards set for pricing of generic drugs, and only one other same ingredient drug is currently listed and priced at 53.55% of the ceiling price of same ingredient drugs. Twelve products will be listed at the same price as the highest price set for same ingredient drugs, 6 of which are rivaroxaban products. Sixty-eight products will be listed at 85% of the highest price of already listed same ingredient drugs. Among these, 60 products, including Han Poong’s Rivarell tab. 15mg, Boryung Biopharma’s Xarox tab. 15mg, Daewoong Bio’s Varelto tab. 15mg and 20mg, are rivaroxaban products. Also, the price of 32 products was set lower than the ceiling price of its higher strength product that was filed for listing at the same time. Such drugs include Daewoong Bio’s Varelto tab. 10mg, GC Pharm’s Neoroxaban tab. 10mg, Yuhan Phram’s Yuhan Rivaroxaban tab. 10mg, Yuyu Pharm’s Yuvaro tab. 10mg, Dong Wha Pharm’s Rivacor tab. 10mg, Aju Pharm’s Zatol tab. 10mg, Kolmar Pharma’s Newroxban tab. 10mg, and Whanin Pharm’s Jaroban tab. 10mg. Also, a new 10mg strength product of Chong Kun Dang’s Riroxia tab. that was already released in May will be newly listed. The drug’s price had been set at a price lower than the ceiling price of its already listed higher strength product. The government sets the ceiling price of lower strength products at a lower price than the ceiling price set for its higher strength counterpart when a higher strength drug with the same company, route of administration, ingredient, and formulation is already listed. Therefore, Chong Kun Dang’s Riroxia tab. 10mg’s price was set at ₩1,312 per tablet. Thirty-four products were set at the expected sales price. The government allows a drug’s price to be set at the expected sales price submitted by the manufactuer·congisnged manufacturer·importer applicant when the price is lower than the price set according to standards. Drugs that will be listed at the expected price are Boryung Biopharma’s Xarox tab. 10mg, Yooyoung Pharm’s Yooroxaban tab.10mg, Yungjin Pharm’s Xarex tab. 10mg, Samjin Pharm’s Rivoxaban Tab. 10mg, Hanmi Pharm’s Riroxban tab. 10mg, GC Pharm’s Neoroxaban tab. 15mg, Yuhan Pharm’s Yuhan Rivaroxaban Tab. 15mg, and JW Pharmaceutical’s Livalozet tab., etc. Meanwhile, 11 rivaroxaban products from 4 companies will be listed with a premium. The premium will expire in 7 months, on April 30th, 2022. The government allows premium pricing for one year from the first generic was listed for some drugs. For innovative pharmaceutical companies, the premium is set at 68% of the original drug price in the first year, then subsequently lowered to 53.55% after the term is terminated. Products that benefit from this premium pricing are Chong Kun Dang’s Riroxia Tab 15mg and 20mg that was released first among generics in May. As the premium pricing period is set based on the 20mg strength drug, the premium will be in effect for only 7 more months.
- Policy
- Lynparza RSA renewed, adds reimbursement for ovarian cancer
- by Lee, Hye-Kyung Sep 24, 2021 05:56am
- In addition to the ongoing negotiations for RSA renewal, an insurance benefit standard will be newly established for ‘Lynparza (olaparib)’ as maintenance monotherapy. The Health Insurance Review and Assessment Service (HIRA) has announced that it has posted a public notice on the ‘Details of the standards and methods for applying insurance benefit to pharmaceuticals prescribed or administered to cancer patients,’ and will be reviewing opinions until the 27th. The amended details will be effective from October 1st. After reviewing the reimbursement standards for Lynparza in ovarian cancer, HIRA decided to allow its reimbursement as ‘first-line maintenance treatment for patients newly diagnosed with BRCA-mutated advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have responded to first-line platinum-based chemotherapy (partial or complete response)’; and ‘as second-line maintenance treatment for patients with BRCA-mutated advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have responded to second-line or higher platinum-based chemotherapy (PR or CR).” As for the administration period, reimbursement for maintenance treatment after first-line platinum-based chemotherapy will be allowed up to 2 years from initial treatment. For ovarian cancer, etc. that responds to second-line or higher platinum-based chemotherapy, reimbursement will be restricted to patients with a BRCA mutation. Details on the platinum-based chemotherapy that is administered immediately before the maintenance therapy will be specified in footnotes in consideration of the inclusion/exclusion criteria in its clinical trials, and eligible patients should have received platinum-based chemotherapy (excluding therapies that use bevacizumab) for at least 4 cycles with no history of PARP inhibitor use. Also, the increased scope of eligibility for ‘Zejula cap. (niraparib)’ in ovarian cancer and ‘Sprycel (dasatinib)’ in acute lymphoblastic leukemia led to an expansion in their reimbursement standards. For Zejula, a new reimbursement standard was added for BRCA mutated patients as ‘maintenance monotherapy for ovarian cancer (including fallopian tube cancer or primary peritoneal cancer) in adult patients who have shown response to first-line platinum-based chemotherapy (partial or complete response).’ For Sprycel, reimbursement standard was set for ‘use in combination with chemotherapy in pediatric patients aged 1 or older with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML)’
- Company
- Celltrion signed a contract with the U.S. for DiaTrust
- by Lee, Seok-Jun Sep 24, 2021 05:56am
- Celltrion will supply DiaTrustTM COVID-19 Rapid Test, co-developed with Humasis, an in vitro diagnostic company, to the United States through Celltrion USA. According to the company on the 23rd, Celltrion USA was finally selected as a supplier in a purchasing project conducted by DLA under the U.S. Department of Defense. As early as the 1st of next month, it will begin supplying DiaTrust to 25,000 designated procurement sites in the United States, including military facilities, nursing homes, regional inspection centers, and major facilities. The contract period is until September 16 next year. The contract amount can increase by up to 738.2 billion won depending on the situation, the largest among the selected suppliers. An official from Celltrion emphasized, "The fact that we participated as a supplier in the U.S. defense procurement project, which has strict standards, has been recognized for Celltrion's technology and supply capabilities." Unlike other rapid diagnostic kits, DiaTrust is a product that improves sensitivity and specificity by applying two antibodies that bind to the N protein and S protein of the COVID-19 virus, respectively, and can check for infection within 15 minutes. It is possible to check for infection immediately after examination without additional equipment, and it shows accuracy of 93.3% sensitivity and 99.0% specificity. DiaTrust is divided into POCT and OTC that can be used with the help of medical experts under permission to use. This contract is supplied as POCT.
- Policy
- Rekirona are expanded to 50 years of age or older
- by Lee, Tak-Sun Sep 24, 2021 05:56am
- The MFDS approved the official approval based on the results report of phase 3 clinical trials of Celltrion's COVID-19 antibody treatment Rekirona, which completed phase 3 global submitted by the company. It has expanded the subject of administration. However, mild patients were not included. The MFDS announced on the 17th that it had carefully reviewed the results of a global phase 3 clinical trial of Rekirona (Regdanvimab), a domestic COVID-19 antibody treatment submitted by Celltrion on the 10th of last month, and approved the change to delete the permit conditions and expand the range of patients who can be administered. As the efficacy and effect of Rekirona was allowed to be changed to "treatment of mild and all secondary adult patients at high risk of COVID-19", the number of patients who can be treated increased. The previous high-risk patients were over 60 years old or with underlying diseases (one or more of cardiovascular disease, chronic respiratory disease, diabetes, and high blood pressure), which lowered the target's age to over 50 years old and added obese people (BMI index 30 or more), chronic kidney disease (including dialysis), chronic liver disease, bone marrow transplantation. The administration method also shortened the administration time from intravenous administration for 90 minutes to 60 minutes. The MFDS explained that the overall safety of Rekirona was good. In phase 3 clinical trials, the incidence of abnormal cases of Rekirona was similar to that of the placebo group, and most of the symptoms were mild or moderate. The most frequently reported abnormal cases included elevated liver enzyme levels and hyperglycermia, and significant abnormal cases were "injection-related reactions" (one patient), recovering within a few days. It has been confirmed that the effectiveness of Rekirona significantly reduces the duration of severe exacerbation and clinical recovery due to COVID-19. Among mild and secondary patients administered Rekirona, the rate of severe transmission from 446 high-risk patients decreased by 72% compared to placebo (434 patients), and the clinical recovery period was also shortened by 4.12 days compared to placebo (12.3 days). The MFDS explained that it consulted experts on the 3rd and the Central Pharmaceutical Affairs Council on the 10th on whether the results of Rekirona's phase 3 clinical trial could therapeutically confirm the effectiveness of the drug in the patient group that Celltrion applied for change. As a result, experts agreed that it is reasonable to delete the permit conditions and switch to formal permission, and that it is desirable to expand the scope of high-risk groups and apply them to high-risk mild and all secondary adult patients. However, in the case of mild symptoms other than high risk, the frequency of severe morbidity was low, and there was insufficient confirmation of effectiveness, so it was not included in the scope of use. In addition, it was suggested that it is reasonable not to include children over the age of 12 in the scope of use because they are not included in the clinical trial. The MFDS reviewed the results of the review and advisory opinions and decided on the scope of the drug's use as "all secondary adult patients in mild to high-risk groups" identified in the clinical trial.
- Company
- Trelegy Ellipta can be prescribed at general hospitals
- by Eo, Yun-Ho Sep 23, 2021 05:44am
- The COPD treatment Trelegy Ellipta can be prescribed at general hospitals. According to related industries, GSK Korea's COPA treatment Trelegy Ellipta (Fluticasone Furoate, Umecridinium Br, Villanterol Trifenate) passed DC at 38 medical institutions including Big 5 General Hospitals such as Seoul National University Hospital and Asan Medical Center. Since the insurance benefits in June, prescriptions have become possible quickly. Trelegy Ellipta is the first COPD complex approved in Korea in May 2018. It is prescribed as a maintenance therapy for moderate and severe COPD that is not properly controlled by persistent β2 agonist and inhalation corticosteroid combination therapy or LABA and LAMA combination therapy in adults. As for the benefit criteria, despite ▲ persistent beta 2 agonist and LAMA combination therapy, if FEV1 value is less than 60% of the normal prediction or acute exacerbation occurs more than twice a year, ▲If symptoms such as dyspnea are not properly controlled despite persistent beta 2 agonist and inhalation corticosteroid combination therapy, ▲If a patient who is simultaneously administering Vilanterol trifenate/Fluticasone furoate and Umecridinium Br satisfies each individual examination, this is the case when pt wants to switch to Trelegy. The validity of Trelegy Ellipta has been reaffirmed through a recent INTREPID phase 4 study. The study was conducted at 147 centers in five European countries, including the UK and Germany, with a total of 3,092 COPD patients participating. Patients were assigned to the Trelegy Ellipta treatment group and the multiple inhalation type three-drug combination treatment group on a one-to-one basis. The primary efficacy evaluation variable was the COPD Assessment Test (CAT) score, which is the COPD evaluation test, to evaluate patients' health status. As a result of measuring the ratio of patients whose CAT score decreased by more than 2 units to baseline at the 24th week of treatment, the median CAT score in the patient group treated with Trelegy Ellipta was 18.0 (8.0), and the median CAT score in the multiple inhalation groups was 19.1 (7.9), significantly improving overall health. The secondary efficacy evaluation variable based on the sub-analysis was the change in FEV1 identified at week 24 of treatment and the proportion of patients who committed more than one serious error when using each inhaler. As a result of the analysis, FEV1 in the Trelegy Ellipta treatment group was 77 mL, which showed statistically superior lung function improvement compared to the multiple inhalation treatment group (28 mL).
- Policy
- Pfizer voluntarily recalls Champix 10 days after MFDS annc.
- by Lee, Tak-Sun Sep 23, 2021 05:44am
- Some lots of Pfizer’s leading smoking cessation treatment, Champix, will be voluntarily recalled. Although the drugs were not subject to recall under the MFDS announcement on the 7th, Pfizer opted to voluntarily recall its products as the drugs exceeded the MFDS's temporary release standards. The standards that the company applied for recall were stricter than the initial recall standards set by the Ministry of Food and Drug Safety that had raised controversy over how the initial standards were set. On the 17, the MFDS announced that 9 lots of Pfizer Korea's ‘Champix 1mg (varenicline tartrate)’ will be voluntarily recalled by its seller. The lot numbers of the recalled products are 00026756, 00025815, 00025121, 00024632, 00024054, 00022720, 00021762, 00021761, and 00022721. The above products were manufactured from May 2019 to December of last year. As for the reason for the recall, the company wrote that the move was a ‘voluntary recall for products exceeding the temporary lot release standards of NNV (N-nitroso-varenicline).’ The said products were not subject to recall under the NNV safety investigation results that were announced by MFDS on the 7th. At the time, the MFDS explained that drugs with NNV exceeding 733 ng/day were to be voluntarily recalled. Based on the standards, Pfizer’s Champix, with NNV 151~632ng/day detected, was not subject to recall. However, Pfizer belatedly started to recall its product based on the temporary release standard at 185 ng/day rather than the recall standard. MFDS investigation data regarding safety of NNV containing varenicline that was announced on the 7th Controversy had arose as the NNV level of 733ng/day that was set for voluntary recall by the MFDS was based on Pfizer’s standards. The minutes of the Central Pharmaceutical Affairs Council that was disclosed on the webpage on the 17th stated that Pfizer's standards were inevitably applied for the recall. The minutes showed that CPAC had decided to maintain the voluntary recall standard at NNV of 733ng/day as set by Pfizer. However, as the standards set by Pfizer exclude Pfizer’s Champix from recalls, controversy arose as to whether the measures were unfairly supporting a specific company. Pfizer's decision to recall its products based on the temporary release standards (185ng/day), settled the controversy over the fairness of CPAC’s standards. However still, the fact that the authorities had decided to manage NNV impurities with different standards set for lot release and recall is still expected to raise some eyebrows.
- Policy
- Varenicline recalls were based on Pfizer's standards
- by Lee, Tak-Sun Sep 23, 2021 05:43am
- On why the recall and lot release standards were set differently for the smoking cessation treatment ‘varenicline,’ which was found to have nitrosamine impurities, is gaining attention. This difference in standards had allowed Pfizer’s Champix from being recalled. While announcing the N-nitroso-varenicline (NNV) impurity test results on varenicline products on the 7th, the Ministry of Food and Drug Safety announced that products with less than 185ng/day of NNV may temporarily be approved for lot release. On the other hand, products with NNV of 733ng/day or more were to be voluntarily recalled by their manufacturers. Regarding the set standards, the MFDS had explained that it had referenced cases from other major countries including the U.S. The minutes from the ‘Deliberation on feasibly of the human impact assessment results on pharmaceuticals containing impurities’ at the Central Pharmaceutical Affairs Council that was disclosed on the webpage on the 17th, also showed that the decision reflects cases from the U.S. and other countries. The meeting had been held on the 31st of last month before the measures were announced on the 7th. However, controversy is expected as the minutes of the CPAC meeting indicate that the U.S case also adopted the voluntary recall standards of a specific company – Pfizer. The recall standards that were set above the lot release standards allowed Pfizer’s ‘Champix’ from being subject to recalls. In the minutes, the MFDS stated that the ‘FDA has acknowledged the voluntary recall standards set by Company A (presumed to be Pfizer, 733ng/day), which allowed the company to recall lot numbers that exceeded the set standards. The FDA announcement on its webpage also contains the phrase that 'products that exceed the company’s voluntary recall standards were recalled.' Company A reported to MFDS that there was no case in which the company recalled products that contain less NNV than its set standards (733 ng/day) worldwide." On this, committee members who attended the CPAC generally agreed that it was inevitable and reasonable to maintain the voluntary recall standards set by Company A. One member said, “The FDA also set a different level for temporary lot release and recall. The decision may have been made in consideration of the patient’s right of choice and the potential lack of supply.” The member also inquired about the potential supply status expected for Korea if the temporary lot release standard of ‘185ng/day’ is applied. The MFDS explained that “Based on the domestic market shares, 90% of the products currently on the market will be subject to recall, and a supply shortage is expected to occur.” Another member had said, “As cancer caused by smoking is also a serious concern, I believe the doctor should fully explain the situation to the patient and allow the patient to make the decision. Also, it would be more reasonable to maintain the recall standards at the level set by Company A (744ng/day) until more drugs that meet the temporary lot release standard (185ng/day) are supplied, as it is not desirable for patients to not have the right to choice due to supply shortage.” With more agreeing to the MFDS’s proposal, the chairperson said, “We submit the opinion that Company A’s voluntary recall standard (733ng/day) should be applied and products with NNV that exceeds 185ng/day but lower than 733ng/day should be temporary allowed for distribution in consideration of the supply shortage, patient treatment and other case references from overseas including the FDA,” to which most members agreed. As a result, the MFDS set the recall standards to NNV of ‘733ng/day,’ under which CTC Bio recalled 19 lot numbers of 3 products that exceeded the set standards. The recall standards indicated in the minutes are Pfizer’s standards, and the concern over supply shortage is expected to have been the biggest factor in the decision. The problem is that Pfizer’s standards have excluded Pfizer’s original product ‘Champix’ from recalls. Pfizer’s self-investigation showed that its varenicline product contained NNV between 151~632ng/day. If the recall standards were set at the same level as the lot release, as ‘185ng/day,’ Pfizer’s products would also have been subject to recall. In other words, using Pfizer’s recall standards had led to Pfizer’s products avoiding recalls. As the decision, despite being made with considerations for patient treatment and supply shortages, had led to benefit Pfizer, the criticism arose that the Ministry of Food and Drug Safety was more considerate of the company's position rather than concerns over safety of impurities.
- Company
- It surpassed ₩1 trillion in monthly drug imports
- by Kim, Jin-Gu Sep 23, 2021 05:43am
- In August, pharmaceutical imports surpassed ₩1 trillion for the first time. This is due to the fact that imports of Pfizer, Moderna vaccines were reflected in statistics following July. Drug exports rose 10% year-on-year to ₩700 billion last month. However, as imports increased sharply around the COVID-19 vaccine, the deficit in the drug trade balance hit the highest level since December 2019. ◆In August, vaccine imports amounted to ₩340 billion, the highest ever According to the Korea Customs Service on the 15th, imports of domestic medicines in August were $870.81 million. This is the first time that monthly drug imports have surpassed 1 trillion won. Compared to $50.32 million in August last year, it jumped 64%. It renewed its highest import amount ever for two consecutive months following July. In July, drug imports amounted to $819.58 million. As imports of COVID-19 vaccines began in earnest, the total amount of medicines imported increased significantly. Domestic vaccine imports were only $34.45 million by February this year, but as COVID-19 vaccine imports began in earnest, they surged to $49.82 million in March, $54.91 million in April, $58.88 million in May, $15.51 million in June, and $211.62 million in July. It recorded $291.53 million in August, once again breaking the record for the highest amount set in July. Considering that the domestic supply of Moderna vaccine has been disrupted in July and August, it is predicted that vaccine imports may increase further after September. Excluding vaccine imports, monthly drug imports remain around $600 million, similar to last year. ◆Pharmaceutical exports amounted to ₩690 billion, the largest trade deficit in 20 months Exports of medicines in August amounted up to 10% from$50.303 million a year earlier. As imports increased significantly compared to pharmaceutical exports, the domestic pharmaceutical trade deficit increased significantly. The drug trade balance recorded a deficit of $277.78 million in August. The deficit is the largest in 20 months after recording $317.24 million in December 2019. The domestic drug trade balance has steadily recorded a surplus from August last year to March this year, except for October last year, due to increased biosimilar exports. However, since the import of COVID-19 vaccines began in earnest, the deficit has gradually increased.
