外資系企業における承認品目の傾向 PhRMA/EFPIA合同調査 ......2020/08/26 · •...
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㻼㼔㻾㻹㻭㻛㻱㻲㻼㻵㻭で実施した㻞㻜㻝㻥年度の合同調査結果は以下の通りであった。 審 査 期 間 と 承 認 品 目 ● 㻞㻜㻝㻥年度（㻞㻜㻝㻥年㻠月～㻞㻜㻞㻜年㻟月）における㻼㼔㻾㻹㻭及び㻱㻲㻼㻵㻭加盟会社の承認品目数は、新医薬品㻢㻠品目、再生医療等製品㻝品目 であった。 ● 新医薬品の審査期間は通常審査品目で㻝㻝㻚㻤ヵ月、優先審査品目（公知申請を含む）で㻤㻚㻢ヵ月（㻤㻜パーセンタイル値）であった。 ● 日米欧の審査期間はほぼ同じであり、審査期間のラグは解消されていることが示された。よって、日本における承認時期の欧米との 差は、開発及び申請時期の差によるものとみられた。 ● 日米欧での審査を迅速化する制度として、先駆け審査指定制度、㻮㼞㼑㼍㼗㼠㼔㼞㼛㼡㼓㼔指定制度、㻼㻾㻵㻹㻱指定制度等の利用状況を調査した。 その結果、日米欧での制度利用状況に差が認められ、特に米国では幅広い制度の活用が行われていた。 㻼 㻹 㻿 ● 㻼㻹㻿は承認品目㻢㻡品目中㻠㻤品目（㻣㻠％、㻡㻠件）で実施され、うち全例調査は㻝㻠件（㻞㻢％）であった。製造販売後データベース調査は㻝㻤 件で㻼㻹㻿全体の㻟㻟％を占めており、昨年度の㻝㻤％と比較し増加していた。 ● 製造販売後データベース調査において利用予定のデータベースは、㻹㻰㼂や㻹㻵㻰㻙㻺㻱㼀であったが、必要なデータを集められるか確認中 であるまたは信頼性の確保について調査中であること等を理由にデータベースを決めていない調査が㻡調査あった。 外 資 系 企 業 に お け る 承 認 品 目 の 傾 向 ～ PhRMA/EFPIA合 同 調 査 結 果 よ り ～ ○ 青 木 勇 （ ブ リ ス ト ル ・ マ イ ヤ ー ズ ス ク イ ブ ） 㻝 、 秋 本 美 紀 （ ブ リ ス ト ル ・ マ イ ヤ ー ズ ス ク イ ブ ） 㻝 、 池 田 晶 子 （ ヤ ン セ ン フ ァ ー マ ） 㻝 、 榎 本 朱 美 （ 日 本 イ ー ラ イ リ リ ー ） 㻝 、 春 日 井 正 文 （ ア ム ジ ェ ン ） 㻝 、 砂 村 一 美 （ フ ァ イ ザ ー 㻾 ＆ 㻰 ） 㻝 、 武 澤 恵 美 子 （ セ ル ジ ー ン ） 㻝 、 武 部 恭 子 （ ヤ ン セ ン フ ァ ー マ ） 㻝 、 靍 田 嘉 代 子 （ 日 本 イ ー ラ イ リ リ ー ） 㻝 、 中 谷 優 子 （ バ イ オ ジ ェ ン ・ ジ ャ パ ン ） 㻝 、 穂 積 香 織 （ ア ッ ヴ ィ ） 㻝 、 前 田 玲 （ 日 本 イ ー ラ イ リ リ ー ） 㻝 、 今 井 景 子 （ ヤ ン セ ン フ ァ ー マ ） 㻞 、 斉 藤 江 理 子 （ メ ル ク バ イ オ フ ァ ー マ ） 㻞 、 佐 々 木 一 尋 （ ヤ ン セ ン フ ァ ー マ ） 㻞 、 茶 木 啓 孝 （ バ イ エ ル 薬 品 ） 㻞 、 塚 本 修 （ 㻯 㻿 㻸 ベ ー リ ン グ ） 㻞 、 花 久 恭 子 （ ル ン ド ベ ッ ク ・ ジ ャ パ ン ） 㻞 、 本 庄 香 織 （ ノ バ ル テ ィ ス フ ァ ー マ ） 㻞 、 本 多 基 子 （ ヤ ン セ ン フ ァ ー マ ） 㻞 、 山 本 晶 子 （ ヤ ン セ ン フ ァ ー マ ） 㻞 １ 米 国 研 究 製 薬 工 業 協 会 （ 㻼 㼔 㻾 㻹 㻭 ） 、 ２ 欧 州 製 薬 団 体 連 合 会 （ 㻱 㻲 㻼 㻵 㻭 ） 㻯 㻻 㻵 開 示 ： 演 題 発 表 内 容 に 関 連 し 、 発 表 者 ら に 開 示 す べ き 利 益 相 反 は あ り ま せ ん 。 PhRMA-EFPIA Joint Survey 2020 • Review Period – Review time for new drug approvals in FY2019 – Utilization of expedited program – Submission/approval lag • Clinical Studies and Development Plan – Projects ongoing in FY2019 – Global and local studies ongoing in FY2019 – Interaction with the agency for global studies • PMS – PMS in approved new drugs Participating companies: PhRMA (11 companies) • Abbvie, Alexion, Amgen, Biogen Japan, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Pfizer, and Gilead Sciences EFPIA (15 companies) • AstraZeneca, Bayer, CHUGAI, CSL Behring, Ferring, GlaxoSmithKline, Janssen, LEO, Lundbeck, Merck Biopharma, Boehringer Ingelheim, Novartis, Novo Nordisk, Sanofi, and UCB The Number of New Drug Approvals in Japan 112 130 134 138 117 116 112 104 118 126 37 57 81 41 61 56 55 54 59 64 FY2010 FY2011 FY2012 FY2013 FY2014 FY2015 FY2016 FY2017 FY2018 FY2019 ALL PhRMA+EFPIA • Just over half (51%) of approved drugs were EFPIA + PhRMA’s in FY2019 Note: one regenerative medicine was excluded from FY2019 PhRMA+EFPIA Review Time for Priority Review Including Paper JNDAs 9.2 6.5 6.1 7.2 8.8 8.7 8.8 8.9 8.6 8.7 9.2 8.3 8.8 8.7 8.6 3 6 9 12 FY2010 (Median) FY2011 (Median) FY2012 (Median) FY2013 (Median) FY2014 (60%tile) FY2015 (60%tile) FY2016 (70%tile) FY2017 (70%tile) FY2018 (80%tile) FY2019 (80%tile) ALL PhRMA+EFPIA Months • Review time for “Priority Review” in FY2019 were less than 9 months in 80%tile Review Time for Standard Review 14.7 11.5 10.3 11.3 11.9 11.3 11.6 11.8 11.9 11.8 11.1 11.4 11.3 11.7 11.8 6 9 12 15 FY2010 (Median) FY2011 (Median) FY2012 (Median) FY2013 (Median) FY2014 (60%tile) FY2015 (70%tile) FY2016 (70%tile) FY2017 (80%tile) FY2018 (80%tile) FY2019 (80%tile) ALL PhRMA+FEPIA Months • Review time for “Standard Review” in FY2019 were less than 12 months in 80%tile Background of Approved Products PhRMA + EFPIA (N=65) 64 drugs and 1 regenerative medicine • “New indication” (44%) and “new active ingredient” (23%) were the majority of the JNDA • Small molecules accounted for 49%, and the remaining 51% was Biological products. • Oncology (23/65=35%) was the largest therapeutic area in FY2019 (It was 36% in FY2018) New active ingredient, N=15, 23% New combo, N=3, 4% New route, N=3, 5% New indication, N=29, 44% New form, N=3, 5% New dosage, N=9, 14% Biosimilar, N=3, 5% Category of New Drug Application 3 6 2 3 3 2 4 11 2 23 1 3 2 0 5 10 15 20 25 New Drug 1 (1) New Drug 1 (6-2) New Drug 2 (2) New Drug 2 (5) New Drug 3 (3-1) New Drug 3 (3-2) New Drug 4 (4) New Drug 4 (6-1) New Drug 4 (HIV) New Drug 5 (oncology) Regenerative (Gene therapy) Regenerative (Bio-CMC ) Vaccines (blood products) PMDA Review Division (Category) Biological products*, N=33, 51% Small Molecules, N=32, 49% Drug modalities (35%) *: antibodies, therapeutic proteins, nucleic acid-based therapeutics Yes, N=18, 28% No, N=47, 72% Orphan 28% Yes, N=3, 5% No, N=62, 95% Sakigake 5% • 29% of products approved through priority review and 28% were orphan drugs • Sakigake was only 5% (3 cases) and no conditional early approval in FY2019 Yes, N=19, 29% No, N=46 , 71% Priority Review 29% Yes, N=0, 0% No, N=65, 100% Conditional Early Approval 0% Utilization of Expedited Program PhRMA + EFPIA (N=65) Type of Phase 3 study • Type of Phase 3 study consists of “Global studies” (54%), “Japan domestic studies” (23%) and “Extrapolation of overseas study” (14%) 9 Global Study, N=35, 54% Japan Domestic Study, N=15, 23% Extrapolation of overseas study, N=9, 14% Skip Ph3 study (global Ph2), N=5, 8% Unknown, N=1, 1% Type of Phase 3 Study Pediatric Development PhRMA + EFPIA (N=65) Pediatric only, N=4, 6% Adolescents, etc. evaluated with adults, N=11, 17% Adults only, N=50, 77% Applicability of Pediatric Development 23% • Pediatric development was shown in 23% of products, including pediatric only (6%), and adolescents evaluated with adults (17%) • Clinical data package for pediatrics come from mainly global studies • Only Global Study including Japanese subjects 6 (40%) • Global study including Japanese subjects • Domestic Japanese PK studies 2 (13%) • Domestic Japanese studies other than PK studies only 2 (13%) • Domestic Japanese PK studies • Domestic Japanese studies 1 (7%) Others Overseas study only (2) Domestic PK study only (1) Overseas study and Global study including Japanese (1) 4 (27%) Clinical Data Package for Pediatric Development (N=15) 10 Impact on JNDA timing by PMDA consultation PhRMA + EFPIA (N=65) 1.Yes, N=10, 15% 2.No, N=55, 85% 15% • Submission timing was delayed due to PMDA consultation for 15% of the products. • Additional study was requested in 9 cases. • More than half of the subjects had PMDA consultation in the late stage of development (EoP2 or pre-NDA). • 7 /10 (70%) were delayed by 1 year or more. Reason of “Yes” (Multiple answers allowed) • Additional study was requested (9) Japanese dose-finding study (3), Japanese long-term study (1), Phase 3 study (1), Japanese study (2), BE/BA study (1), and Additional clinical study (1) • JNDA with proposed data-package was denied(1) • Use of interim analysis results was not permitted(1) • Amendment of study design of local long-term study(1) • Agree with PMDA at the pre-JNDA consultation(1) • Gain consensus for patient groups and academic societies (1) Before Pre-Ph2, N=2, 20% End-of- Ph2, N=4, 40% Pre- JNDA, N=3, 30% Unknown, N=1, 10% Timing of PMDA consultation (N=10) 3 0 7 0 1 2 3 4 5 6 7 8 Delay of less than 3 months Delay of 3 months or more ~ less than 1 year Delay of 1 year or more Degree of the delay (N=10) 11 • About half of products (49%) aimed simultaneous JNDA filing at the planning phase , and 72% of those achieved simultaneous filing actually 12 Yes, N=32, 49% No, N=31, 48% Unknown, N=2, 3% Aiming simultaneous JNDA filing (within 3 months) at the planning phase Yes, N=23, 72% No, N=8, 25% Unknown, N=1, 3% Result of simultaneous JNDA filing (n=32) Reason of “No” • Preparation of application materials for Japan (3) • Changed the Data package for JNDA(2) • Others (3) Reason of “No” • Already approved overseas(9) • Japan stand alone development(4) • Preparation of application materials for Japan (ex. CMC) would be at least 3 months behind(4) • Additional data determined to be necessary in Japan(2) • In-licensed product(2) • Unknown(3) • Others (7) Simultaneous JNDA filing PhRMA + EFPIA (N=65) Drug lag for NME (New Molecular Entity) (N=15) 0.0 0.0 0.0 5.2 5.6 5.8 5.9 7.0 9.8 16.5 24.1 37.8 42.8 69.0 0.0 12.0 24.0 36.0 48.0 60.0 72.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Drug lag for Japan (Months) • 9 products had US as an international birth date, 3 products in Japan, 2 products in EU • Cause of drug-lag in Japan : Development start lag 41%, submission lag 25%, Review lag 17% Unknown 15 US, N=9, 60% Japan, N=3, 20% EU, N=2, 13% Unknown, N=1, 7% Country of the IBD (International Birth Date) (N=15) Development start lag • Japan could not join the MRCT as it was already started (1) • Licensed-in (2) • Not considered delay（2） 5 (41%) Submission lag • Preparation of Japanese Module 2.3 or approval application (specifications and test methods, manufacturing method) (1) • Wait for stability test results (1) • Preparation of Table of CTD (1) 3 (25%) Review lag • Expedited review was used in overseas (1) • Delay of review was occurred in Japan (1) 2 (17%) Unknown 2 (17%) Where is the cause that Japan approval was delayed? (N=12) 0.0 0.0 0.0 0.0 1.0 0.0 2.9 2.6 0.0 0.0 0.4 0.3 0.0 13.0 1.5 0.0 0.0 2.3 0.0 0.0 2.4 0.0 0.3 3.3 0.0 0.0 7.9 0.0 1.0 22.9 0.0 1.0 37.2 0.0 23.7 38.4 0.1 0.0 43.0 0.0 5.1 46.1 0.0 2.0 72.5 0 0 4.4 7.9 0.0 6.0 0.0 0.0 9.5 5.1 12.7 10.6 8.0 0.0 16.6 8.0 12.0 11.0 8.0 12.0 10.9 6.1 12.8 8.7 11.7 15.8 10.8 10.0 12.0 4.1 6.0 13.0 10.0 10.0 18.1 9.4 11.7 14.6 11.6 31.8 28.6 9.8 10.0 13.0 11.8 0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Submission lag Review period Submission/Approval Lag of NME (New Molecular Entities) (N=15) Review on-going • The submission timing seems to contribute the approval timing • 3 NMEs got first approval in Japan (#1,2,3) • The PMDA’s review time for NMEs are almost same or faster than FDA or EMA 0.0 0.4 3.3 0.0 0.0 3.3 0.0 0.0 3.9 0.0 3.0 4.3 12.0 0.0 16.4 0.0 0.7 6.3 0.0 2.1 8.0 0.0 0.7 9.0 0.0 0.0 13.0 33.0 0.0 46.6 12.0 0.0 29.2 10.0 0.0 27.5 15.8 0.0 33.8 0.0 0.0 18.5 4.0 0.0 30.5 27.4 0.0 62.2 0.0 3.0 40.4 9.9 8.1 11.9 5.9 11.6 9.0 11.9 20.2 10.0 6.0 7.0 11.0 13.0 9.0 11.9 7.9 0.0 8.8 4.3 11.8 8.9 12.9 16.9 11.9 6.0 9.0 8.3 6.0 10.0 10.5 10.0 12.0 3.9 13.0 8.0 11.7 6.0 13.2 11.7 10.0 11.0 10.7 11.0 10.0 11.9 14.2 15.6 10.4 11.0 10.0 11.0 0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 Submission Lag Review Period 3.8 0.0 0.7 0.0 1.5 0.0 0.0 0.0 0.5 0.0 0.4 0.8 4.9 0.0 5.8 0.0 0.4 1.1 0.0 1.9 1.6 0.0 0.1 1.7 0.0 1.0 1.8 0.0 0.0 1.9 1.0 0.0 3.2 0.0 8.4 2.2 0.0 0.3 2.3 4.0 0.0 6.5 0.0 0.8 2.5 0.0 2.0 2.7 0.0 10.0 3.1 0.0 12.5 11.9 9.0 10.9 11.8 10.0 13.0 10.6 3.5 7.9 8.5 11.9 12.4 10.7 6.0 11.4 9.7 5.1 8.7 10.7 3.3 9.2 7.6 4.0 7.0 10.4 6.0 11.0 10.2 6.0 9.0 10.0 9.9 0.0 9.7 6.0 7.6 8.5 7.0 10.0 8.7 5.0 10.9 11.3 6.0 10.0 8.5 10.0 0.0 10.2 0.0 5.0 10.0 15.0 20.0 FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA FDA EMA PMDA 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Submission/Approval Lag of LCM (Life Cycle Managements) (N=34) Review on-going • The submission timing seems to contribute the approval timing • The PMDA’s review time for LCMs are almost same as FDA or EMA Utilization of Expedited Program PhRMA+EFPIA’s PMDA approvals in FY2019 • Japan's expedited review system tends to rely on priority review (and orphan) and cannot utilize other pathway • Expedited program is widely granted in the US 㻼 㻹 㻰 㻭 㻔 㻺 㻩 㻡 㻞 㻕 㻲 㻰 㻭 㻔 㻺 㻩 㻡 㻜 㻕 㻱 㻹 㻭 㻔 㻺 㻩 㻡 㻞 㻕 㻿 㼍 㼗 㼕 㼓 㼍 㼗 㼑 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AA PR 44 45 BTD PR 46 47 48 49 50 51 PR Orphan Orphan 52 BTD 㻟 㻜 㻝 㻢 㻝 㻡 㻣 㻣 㻟 㻝 㻢 㻝 㻞 㻞 㻝 㻜 㻟 㻥 0 3 2 3 7 2 1 Before f to f meeting or 1st batch of query After f to f meeting Until 2wks before the document submissiondate for expert meeting After 2wks before the document submissiondate for expert meeting After the expert meeting After the drug committee Unknown 0 10 20 30 Timing of JPI finalization (N=18) 4 14 2 2 25 0 Before f to f meeting or 1st batch of query After f to f meeting Until 2wks before the document submissiondate for expert meeting After 2wks before the document submissiondate for expert meeting After the expert meeting After the drug committee 0 10 20 30 Timing of Query (N=47) PMDA Query to revise the safety related section of JPI Received the Query, N=47, 72% Not received, N=18, 28% 8 13 6 No preliminary discussion Suggested by query inadvance Suggested orally in advance 0 5 10 15 20 Prior discussion before the Query (N=27) 17 PMDA Query to revise the RMP, PMS etc. Received the query, N=32, 49% Not received, N=31, 48% Unknown, N=2, 3% 4 12 7 3 6 0 2 Before f to f meeting or 1st batch of query After f to f meeting Until 2wks before the document submissiondate for expert meeting After 2wks before the document submissiondate for expert meeting After the expert meeting After the drug committee Unknown 0 4 8 12 16 Timing of the query (N=32) 4 3 2 No preliminary discussion Suggested by query in advance Suggested orally in advance 0 2 4 6 Prior discussion before the Query 7 2 0 0 Useful Slightly Useful Slightly Useless Useless 0 2 4 6 8 Usefulness of the meting (N=9) Meeting with PMDA prior to the Expert Meeting Had a meeting, N=9, 14% No meeting, N=56, 86% 1 1 2 7 0 2 4 6 8 Indications Dosage & administration Precautions RMP/PMS etc. Agenda of the meeting (Multiple answers allowed) PMS Survey （N:26 companies [PhRMA: 11, EFPIA:15]) • PMS is conducted for all of NCE products approved • Products without PMS are predominately those approved for new indication and new dosage. • For most approved products, one PMS is conducted. • For most products without PMS, it was accepted that routine pharmacovigilance activities suffice. 48 (74%) 17 (26%) PMS in Approved Products （ N=65） Yes No 17 44 2 2 0 10 20 30 40 50 No PMS 1 2 3 Number of PMS per Product (N=65) 2 1 5 5 1 1 2 1 1 2 1 2 3 5 7 1 2 1 3 2 0 2 4 6 8 10 12 14 16 Office 1 Office 2 Office 3 Office 4 Office 5 RegMed Vaccine Product with PMS by PMDA Review Office & NDA category Biosimilar New dosage New formulation New Indication New route New Combo NCE 1 1 3 5 1 5 1 0 2 4 6 8 10 12 Office 1 Office 2 Office 3 Office 4 Office 5 RegMed Product without PMS by PMDA Review Office & NDA category Biosimilar New dosage New indication 2 15 0 2 4 6 8 10 12 14 16 Reason for No PMS (N=17) Routine pharmacovigilance activity only was accepted Other • Half of PMS surveys were proposed from applicants and accepted as planned. • More than 1/3 of PMS are DB survey and the number and proportion of DB survey increased from last year’s survey. • More than 1/3 of DB surveys were proposed by applicants and accepted. Background of PMS <2019 (N=54) > <2018 (N=49)> 55.6% (10) 68.2% (15) 11.2% (1) 16.7% (3) 27.3% (6) 22.3% (2) 55.6% (5) 27.8% (5) 4.6% (1) 11.2% (1) 0% 20% 40% 60% 80% 100% (n=18) (n=22) (n=9) Agreed with PMDA as proposed Initiallly no PMS proposed, however, consequently concluded to conduct PMS after discussion with PMDA Initially, DB survey was proposed but consequently concluded to conduct traditional PMS after discussion with PMDA Initially, Drug Use Survey was considered, however, after discussion with PMDA, changed to DB Survey Other 77% (10) 56.6 % (13) 38.9 % (7) 23.1% (3) 39.2% (9) 38.9% (7) 22.3% (4) 4.4% (1) 0% 20% 40% 60% 80% 100% Drug Use Survey (n=13) Specific Drug Use Survey (n=23) Post-Marketing DB survey (n=18) 2 4 6 1 3 2 4 9 3 1 1 6 4 6 2 0 2 4 6 8 10 12 14 16 18 Office 1 Office 2 Office 3 Office 4 Office 5 RegMed Vaccine Type of PMS by PMDA Review Office （ N=54） Post-Marketing DB Survey Specific Drug Use Survey Drug Use Survey 14, 26% 40, 74% Products with All-Case Survey (N=54) Yes No 8 4 3 11 10 2 2 1 1 6 5 1 0 5 10 15 20 Office 1 Office 2 Office 3 Office 4 Office 5 RegMed Vaccine All-Case Survery by PMDA Review Office (N=54) Yes No Details of PMS (Drug Use Survey and Specific Drug Use Survey) 7 12 7 3 5 7 19 5 3 6 0 5 10 15 20 ～24W(6M) 6M～52W 1Y～2Y 2Y～3Y >3Y Observation Period per Patient Not outsourced <100M Yen 100~300M Yen Individual PMS cost not abailable 23 2 5 3 31 5 3 1 Cost of Outsourced PMS Monitoring 2019：N=37 2018：N=40 ～1Y 1Y～2Y 2Y～3Y 3Y～5Y >5Y 1 14 9 5 6 1 14 14 5 4 Enrollment Period <100M Yen 100~300M Yen 300~500M Yen >500M yen 11 16 5 3 5 22 11 2 Cost of PMS excluding monitoring cost) • Less than 300 patients in size, 6 month to 1 year observation period and 1-2Y year enrollment period are most frequently seen among all PMS. • PMS with cost of 100 – 300 M Yen marked highest number and majority costs more than 100 M Yen. 0 10 20 30 ~300 300~500 500~1000 1000~2000 >3000 0 5 10 15 20 25 30 ~300 300~500 500~1000 1000~2000 Number of patients per PMS All-case surveys Non-all case 0 5 10 15 20 Paper EDC Hybrid Survey tools All-case surveys Non-all case 0 10 20 Paper EDC Hybrid 2018 2019 Reason for Database Survey Planned (N=18) Post-Marketing Database Survey 5 9 4 0 2 4 6 8 10 Not yet decided MDV MID-NET Database used for DB Survey (N=18) Suitable DB available for the disease and risk 7 DB enables comparison 7 Other (PMDA’s request) 2 No Answer 2 Reason for “Not yet decided” (Multiple answers allowed) • Confirming if the required data can be collected: 5 • Investigating DB quality: 3 • Difficulty of outcome setting: 1 Reason for DB Survey Not Considered 2019 (N=36) 2018 (N=40) Data can not be collected through DB DB is not suitable to evaluate specific risk Others Lack of understanding of usefulness about DB in company 24(67%) 8(22%) 4(11%) 26(65%) 12(30%) 1(2%) 1(3%) • The main reasons DB survey was planned were “DB could be suitable to evaluate the diseases and risks” or “DB enables comparison”. • The main reasons why DB was not considered were “Data can’t be collected through DB” or “DB is not suitable to evaluate specific risk”. The combined proportion of these two reasons increased from 67%(2018) to 89%(2019). It is presumed that applicants have come to be able to assess the appropriateness of DBsurvey. • MDV and MID-NET are planed for use and 28%(5/18) of DB surveys have not yet decided which database to use. PMS Operation (Company N = 23) Key finding： • PMS contract, enrollment and CRF collection are mainly conducted by company MR. • Approx. half of companies have PMS conducted by personnel other than company MR and the main reason is compliance risk. 16(69%) 2(9%) 2(9%) 3(12%) Company MR incl. contract Company PMS dedicated monitor Subcontractor monitor Others Who mainly conducts PMS Contract/Enrollment/CRF Collection 12 4 0 2 4 6 8 10 12 14 No Yes 10 6 0 2 4 6 8 10 12 No Yes Any PMS contracted by personnel other than company MR? Any PMS personnel other than company MR conducts enrollment/CRF collection? Reason why personnel other than company MR conducts contract Reason why personnel other than company MR conducts enrollment/CRF collection Compliance Risk 6 Others 3 Compliance Risk 6 Others 4 Others: - Company MR incl. contract & Subcontractor monitor: 2 - MR of the company which sells the product: 1
Transcript of 外資系企業における承認品目の傾向 PhRMA/EFPIA合同調査 ......2020/08/26 · •...
で実施した 年度の合同調査結果は以下の通りであった。
審査期間と承認品目
● 年度（ 年 月～ 年 月）における 及び 加盟会社の承認品目数は、新医薬品 品目、再生医療等製品 品目
であった。
● 新医薬品の審査期間は通常審査品目で ヵ月、優先審査品目（公知申請を含む）で ヵ月（ パーセンタイル値）であった。
● 日米欧の審査期間はほぼ同じであり、審査期間のラグは解消されていることが示された。よって、日本における承認時期の欧米との
差は、開発及び申請時期の差によるものとみられた。
● 日米欧での審査を迅速化する制度として、先駆け審査指定制度、 指定制度、 指定制度等の利用状況を調査した。
その結果、日米欧での制度利用状況に差が認められ、特に米国では幅広い制度の活用が行われていた。
● は承認品目 品目中 品目（ ％、 件）で実施され、うち全例調査は 件（ ％）であった。製造販売後データベース調査は
件で 全体の ％を占めており、昨年度の ％と比較し増加していた。
● 製造販売後データベース調査において利用予定のデータベースは、 や であったが、必要なデータを集められるか確認中
であるまたは信頼性の確保について調査中であること等を理由にデータベースを決めていない調査が 調査あった。
外資系企業における承認品目の傾向
～PhRMA/EFPIA合同調査結果より～
○青木勇（ブリストル・マイヤーズ スクイブ） 、秋本美紀（ブリストル・マイヤーズ スクイブ） 、池田晶子（ヤンセンファーマ） 、榎本朱美（日本イーライリリー） 、春日井正文（アムジェン） 、
砂村一美（ファイザー ＆ ） 、武澤恵美子（セルジーン） 、武部恭子（ヤンセンファーマ） 、靍田嘉代子（日本イーライリリー） 、中谷優子（バイオジェン・ジャパン） 、穂積香織（アッヴィ） 、
前田玲（日本イーライリリー） 、 今井景子（ヤンセンファーマ） 、斉藤江理子（メルクバイオファーマ） 、佐々木一尋（ヤンセンファーマ） 、茶木啓孝（バイエル薬品） 、塚本修（ ベーリング） 、
花久恭子（ルンドベック・ジャパン） 、本庄香織（ノバルティス ファーマ） 、本多基子（ヤンセンファーマ） 、山本晶子（ヤンセンファーマ）
１ 米国研究製薬工業協会（ ）、 ２ 欧州製薬団体連合会（ ）
開示：演題発表内容に関連し、発表者らに開示すべき利益相反はありません。
PhRMA-EFPIA Joint Survey 2020• Review Period
– Review time for new drug approvals in FY2019– Utilization of expedited program– Submission/approval lag
• Clinical Studies and Development Plan– Projects ongoing in FY2019– Global and local studies ongoing in FY2019– Interaction with the agency for global studies
• PMS– PMS in approved new drugs
Participating companies:PhRMA (11 companies)• Abbvie, Alexion, Amgen, Biogen Japan, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD,
Pfizer, and Gilead Sciences
EFPIA (15 companies)• AstraZeneca, Bayer, CHUGAI, CSL Behring, Ferring, GlaxoSmithKline, Janssen, LEO, Lundbeck,
Merck Biopharma, Boehringer Ingelheim, Novartis, Novo Nordisk, Sanofi, and UCB
The Number of New Drug Approvals in Japan
112
130 134 138
117 116 112104
118126
37
57
81
41
61 56 55 54 59 64
FY2010 FY2011 FY2012 FY2013 FY2014 FY2015 FY2016 FY2017 FY2018 FY2019
ALL PhRMA+EFPIA
• Just over half (51%) of approved drugs were EFPIA + PhRMA’s in FY2019
Note: one regenerative medicine was excluded from FY2019 PhRMA+EFPIA
Review Time for Priority ReviewIncluding Paper JNDAs
9.2
6.56.1
7.2
8.8
8.7
8.8 8.9 8.6 8.79.2
8.38.8 8.7 8.6
3
6
9
12
FY2010FY2010(Median)
FY2011FY2011(Median)
FY2012FY2012(Median)
FY2013FY2013(Median)
FY2014FY2014(60%tile)
FY2015FY2015(60%tile)
FY2016FY2016(70%tile)
FY2017FY2017(70%tile)
FY2018FY2018(80%tile)
FY2019FY2019(80%tile)
ALL PhRMA+EFPIA
9
Mon
ths
• Review time for “Priority Review” in FY2019 were less than 9 months in 80%tile
Review Time for Standard Review
14.7
11.5
10.3
11.311.9
11.311.6 11.8 11.9 11.8
11.111.4 11.3
11.7 11.8
6
9
12
15
FY2010(Median)
FY2011(Median)
FY2012(Median)
FY2013(Median)
FY2014(60%tile)
FY2015(70%tile)
FY2016(70%tile)
FY2017(80%tile)
FY2018(80%tile)
FY2019(80%tile)
ALL PhRMA+FEPIA
Mon
ths
• Review time for “Standard Review” in FY2019 were less than 12 months in 80%tile
Background of Approved Products PhRMA + EFPIA (N=65)64 drugs and 1 regenerative medicine
• “New indication” (44%) and “new active ingredient” (23%) were the majority of the JNDA• Small molecules accounted for 49%, and the remaining 51% was Biological products.• Oncology (23/65=35%) was the largest therapeutic area in FY2019 (It was 36% in FY2018)
New active ingredient, N=15, 23%
New combo, N=3, 4%
New route, N=3, 5%
New indication, N=29, 44%
New form, N=3, 5%
New dosage, N=9, 14%
Biosimilar, N=3, 5%
Category of New Drug Application
3
6
2
3
3
2
4
11
2
23
1
3
2
0 5 10 15 20 25
New Drug 1 (1)
New Drug 1 (6-2)
New Drug 2 (2)
New Drug 2 (5)
New Drug 3 (3-1)
New Drug 3 (3-2)
New Drug 4 (4)
New Drug 4 (6-1)
New Drug 4 (HIV)
New Drug 5 (oncology)
Regenerative (Gene therapy)
Regenerative (Bio-CMC )
Vaccines (blood products)
PMDA Review Division (Category)
Biological products*,
N=33,51%
Small Molecules,
N=32, 49%
Drug modalities
(35%)
*: antibodies, therapeutic proteins, nucleic acid-based therapeutics
Yes, N=18, 28%
No, N=47, 72%
Orphan
28%
Yes, N=3, 5%
No, N=62, 95%
Sakigake
5%
• 29% of products approved through priority review and 28% were orphan drugs• Sakigake was only 5% (3 cases) and no conditional early approval in FY2019
Yes, N=19, 29%
No, N=46, 71%
Priority Review
29%
Yes, N=0, 0%
No, N=65, 100%
Conditional Early Approval
0%
Utilization of Expedited Program PhRMA + EFPIA (N=65) Type of Phase 3 study
• Type of Phase 3 study consists of “Global studies” (54%), “Japan domestic studies” (23%) and “Extrapolation of overseas study” (14%)
9
Global Study,
N=35, 54%Japan Domestic
Study,N=15, 23%
Extrapolation of overseas study,
N=9, 14%
Skip Ph3 study
(global Ph2), N=5, 8%
Unknown, N=1, 1%
Type of Phase 3 Study
Pediatric Development PhRMA + EFPIA (N=65)
Pediatric only, N=4, 6%
Adolescents, etc. evaluated
with adults, N=11, 17%
Adults only, N=50, 77%
Applicability of Pediatric Development
23%
• Pediatric development was shown in 23% of products, including pediatric only (6%), and adolescents evaluated with adults (17%)
• Clinical data package for pediatrics come from mainly global studies
• Only Global Study including Japanese subjects
6 (40%)
• Global study including Japanese subjects • Domestic Japanese PK studies
2 (13%)
• Domestic Japanese studies other than PK studies only
2 (13%)
• Domestic Japanese PK studies • Domestic Japanese studies
1 (7%)
Others Overseas study only (2) Domestic PK study only (1) Overseas study and Global study including
Japanese (1)
4 (27%)
Clinical Data Package for Pediatric Development (N=15)
10
Impact on JNDA timing by PMDA consultation PhRMA + EFPIA (N=65)
1.Yes, N=10, 15%
2.No, N=55, 85%
15%
• Submission timing was delayed due to PMDA consultation for 15% of the products.• Additional study was requested in 9 cases.• More than half of the subjects had PMDA consultation in the late stage of development (EoP2 or pre-NDA).• 7 /10 (70%) were delayed by 1 year or more.
Reason of “Yes” (Multiple answers allowed)• Additional study was requested (9)
Japanese dose-finding study (3), Japanese long-term study (1), Phase 3 study (1), Japanese study (2), BE/BA study (1), and Additional clinical study (1)
• JNDA with proposed data-package was denied(1)• Use of interim analysis results was not permitted(1)• Amendment of study design of local long-term study(1)• Agree with PMDA at the pre-JNDA consultation(1)• Gain consensus for patient groups and academic societies (1)
Before Pre-Ph2,
N=2, 20%
End-of-Ph2, N=4, 40%
Pre-JNDA, N=3, 30%
Unknown, N=1, 10%
Timing of PMDA consultation (N=10)
3
0
7
0 1 2 3 4 5 6 7 8
Delay of less than 3 months
Delay of 3 months or more ~ less than 1 year
Delay of 1 year or more
Degree of the delay (N=10)
11 • About half of products (49%) aimed simultaneous JNDA filing at the planning phase , and 72% of those achieved simultaneous filing actually
12
Yes, N=32, 49%No,
N=31, 48%
Unknown, N=2, 3%
Aiming simultaneous JNDA filing(within 3 months) at the planning phase
Yes, N=23, 72%
No,N=8,25%
Unknown, N=1, 3%
Result of simultaneous JNDA filing (n=32)
Reason of “No”• Preparation of application materials for
Japan (3)• Changed the Data package for JNDA(2)• Others (3)
Reason of “No” • Already approved overseas(9)• Japan stand alone development(4)• Preparation of application materials for
Japan (ex. CMC) would be at least 3 months behind(4)
• Additional data determined to be necessary in Japan(2)
• In-licensed product(2)• Unknown(3)• Others (7)
Simultaneous JNDA filing PhRMA + EFPIA (N=65)
Drug lag for NME (New Molecular Entity) (N=15)
0.0
0.0
0.0
5.2
5.6
5.8
5.9
7.0
9.8
16.5
24.1
37.8
42.8
69.0
0.012.024.036.048.060.072.0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Drug lag for Japan (Months)
• 9 products had US as an international birth date, 3 products in Japan, 2 products in EU• Cause of drug-lag in Japan : Development start lag 41%, submission lag 25%, Review lag 17%
Unknown 15
US, N=9, 60%
Japan, N=3, 20%
EU, N=2, 13%
Unknown, N=1, 7%
Country of the IBD (International Birth Date) (N=15)
Development start lag• Japan could not join the MRCT as it
was already started (1)• Licensed-in (2)• Not considered delay（2）
5 (41%)
Submission lag• Preparation of Japanese Module
2.3 or approval application (specifications and test methods, manufacturing method) (1)
• Wait for stability test results (1)• Preparation of Table of CTD (1)
3 (25%)
Review lag• Expedited review was used in
overseas (1)• Delay of review was occurred in
Japan (1)
2 (17%)
Unknown 2 (17%)
Where is the cause that Japan approval was delayed? (N=12)
0.00.00.00.01.0
0.02.92.6
0.00.00.40.30.0
13.01.5
0.00.0
2.30.00.0
2.40.00.3
3.30.00.0
7.90.01.0
22.90.01.0
37.20.0
23.738.4
0.10.0
43.00.0
5.146.1
0.02.0
72.5
00
4.47.9
0.06.00.00.0
9.55.1
12.710.6
8.00.0
16.68.0
12.011.0
8.012.0
10.96.1
12.88.7
11.715.8
10.810.0
12.04.1
6.013.0
10.010.0
18.19.4
11.714.6
11.631.8
28.69.8
10.013.0
11.8
0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDA
12
34
56
78
910
1112
1314
15
Submission lagReview period
Submission/Approval Lag of NME (New Molecular Entities) (N=15)
Review on-going
• The submission timing seems to contribute the approval timing
• 3 NMEs got first approval in Japan (#1,2,3)• The PMDA’s review time for NMEs are almost same
or faster than FDA or EMA
0.00.4
3.30.00.0
3.30.00.0
3.90.0
3.04.3
12.00.0
16.40.00.7
6.30.0
2.18.0
0.00.7
9.00.00.0
13.033.0
0.046.6
12.00.0
29.210.0
0.027.5
15.80.0
33.80.00.0
18.54.0
0.030.5
27.40.0
62.20.0
3.040.4
9.98.1
11.95.9
11.69.0
11.920.2
10.06.0
7.011.0
13.09.0
11.97.9
0.08.8
4.311.8
8.912.9
16.911.9
6.09.0
8.36.0
10.010.5
10.012.0
3.913.0
8.011.7
6.013.2
11.710.011.0
10.711.0
10.011.9
14.215.6
10.411.0
10.011.0
0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0FDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
1819
2021
2223
2425
2627
2829
3031
3233
34
Submission Lag
Review Period
3.80.00.7
0.01.5
0.00.00.00.50.00.40.8
4.90.0
5.80.00.41.1
0.01.91.6
0.00.1
1.70.01.01.8
0.00.0
1.91.0
0.03.2
0.08.4
2.20.00.3
2.34.0
0.06.5
0.00.8
2.50.0
2.02.7
0.010.0
3.1
0.012.511.9
9.010.9
11.810.0
13.010.6
3.57.9
8.511.9
12.410.7
6.011.49.7
5.18.710.7
3.39.2
7.64.0
7.010.4
6.011.0
10.26.0
9.010.0
9.90.0
9.76.0
7.68.5
7.010.0
8.75.0
10.911.3
6.010.08.5
10.00.0
10.2
0.0 5.0 10.0 15.0 20.0FDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
FDAEMA
PMDAFDA
EMAPMDA
12
34
56
78
910
1112
1314
1516
17
Submission/Approval Lag of LCM (Life Cycle Managements) (N=34)
Review on-going
• The submission timing seems to contribute the approval timing
• The PMDA’s review time for LCMs are almost same as FDA or EMA
Utilization of Expedited Program PhRMA+EFPIA’s PMDA approvals in FY2019
• Japan's expedited review system tends to rely on priority review (and orphan) and cannot utilize other pathway• Expedited program is widely granted in the US
1 Sakigake PR Orphan BTD FT PR Orphan PRIME AA Orphan2 Sakigake PR Orphan BTD AA Orphan Orphan3 Sakigake PR Orphan BTD AA PR Orphan PRIME AA Orphan4 PR Orphan5 PR Orphan AA Orphan6 PR Orphan PR7 PR Orphan PR8 PR Orphan n/a n/a n/a n/a n/a Orphan9 PR Orphan10 PR Orphan AA Orphan Orphan11 PR Orphan n/a n/a n/a n/a n/a12 PR Orphan Orphan Orphan13 PR Orphan14 PR Orphan Orphan Orphan15 PR Orphan PR Orphan16 PR17 PR18192021222324 BTD AA PR2526 PR272829 FT PR30 Orphan3132 FT PR AA333435 PR3637383940 PR41 BTD AA Orphan CMA Orphan42 PR Orphan43 AA PR4445 BTD PR464748495051 PR Orphan Orphan52 BTD
0
3
2
3
7
2
1
Before f to f meeting or 1st batchof query
After f to f meeting
Until 2wks before the documentsubmissiondate for expert meeting
After 2wks before the documentsubmissiondate for expert meeting
After the expert meeting
After the drug committee
Unknown
0 10 20 30
Timing of JPI finalization (N=18)
4
14
2
2
25
0
Before f to f meeting or 1st batch of query
After f to f meeting
Until 2wks before the documentsubmissiondate for expert meeting
After 2wks before the documentsubmissiondate for expert meeting
After the expert meeting
After the drug committee
0 10 20 30
Timing of Query (N=47)
PMDA Query to revise the safety related section of JPI
Received the Query,
N=47, 72%
Not received, N=18, 28%
8
13
6
No preliminary discussion
Suggested by query inadvance
Suggested orally in advance
0 5 10 15 20
Prior discussion before the Query (N=27)
17
PMDA Query to revise the RMP, PMS etc.
Received the query,
N=32, 49%Not received,
N=31, 48%
Unknown,N=2, 3%
4
12
7
3
6
0
2
Before f to f meeting or 1st batchof query
After f to f meeting
Until 2wks before the documentsubmissiondate for expert
meetingAfter 2wks before the document
submissiondate for expertmeeting
After the expert meeting
After the drug committee
Unknown
0 4 8 12 16
Timing of the query (N=32)
4
3
2
No preliminary discussion
Suggested by query inadvance
Suggested orally in advance
0 2 4 6
Prior discussion before the Query
7
2
0
0
Useful
Slightly Useful
Slightly Useless
Useless
0 2 4 6 8
Usefulness of the meting (N=9)
Meeting with PMDA prior to the Expert Meeting
Had a meeting, N=9, 14%
No meeting,
N=56, 86%
1
1
2
7
0 2 4 6 8
Indications
Dosage & administration
Precautions
RMP/PMS etc.
Agenda of the meeting(Multiple answers allowed)
PMS Survey （N:26 companies [PhRMA: 11, EFPIA:15])
• PMS is conducted for all of NCE products approved• Products without PMS are predominately those approved
for new indication and new dosage.• For most approved products, one PMS is conducted.• For most products without PMS, it was accepted that
routine pharmacovigilance activities suffice.
48(74%) 17 (26%)
PMS in Approved Products（N=65）
Yes
No
17
44
2
2
0 10 20 30 40 50
No PMS
1
2
3
Number of PMS per Product (N=65)
2 1
5 5
1 1
2
11
2
1
2 3
5 7
1
2
13
2
0
2
4
6
8
10
12
14
16
Office 1 Office 2 Office 3 Office 4 Office 5 RegMed Vaccine
Product with PMS by PMDA Review Office & NDA category
Biosimilar
New dosage
New formulation
New Indication
New route
New Combo
NCE 1 13
5
1
5
10
2
4
6
8
10
12
Office 1 Office 2 Office 3 Office 4 Office 5 RegMed
Product without PMS by PMDA Review Office & NDA category
Biosimilar
New dosage
New indication
215
0 2 4 6 8 10 12 14 16
Reason for No PMS (N=17)
Routine pharmacovigilance activity only was accepted Other
• Half of PMS surveys were proposed from applicants and accepted as planned.
• More than 1/3 of PMS are DB survey and the number and proportion of DB survey increased from last year’s survey.
• More than 1/3 of DB surveys were proposed by applicants and accepted.
Background of PMS<2019 (N=54) > <2018 (N=49)>
55.6% (10)
68.2% (15)
11.2% (1)
16.7% (3)
27.3% (6)
22.3% (2) 55.6% (5)
27.8% (5)
4.6% (1)
11.2% (1)
0% 20% 40% 60% 80% 100%
(n=18)
(n=22)
(n=9)
Agreed with PMDA as proposedInitiallly no PMS proposed, however, consequently concluded to conduct PMS after discussion with PMDAInitially, DB survey was proposed but consequently concluded to conduct traditional PMS after discussion with PMDAInitially, Drug Use Survey was considered, however, after discussion with PMDA, changed to DB SurveyOther
77% (10)
56.6 % (13)
38.9 % (7)
23.1% (3)
39.2% (9)
38.9% (7) 22.3% (4)
4.4% (1)
0% 20% 40% 60% 80% 100%
Drug Use Survey(n=13)
Specific Drug UseSurvey (n=23)
Post-Marketing DBsurvey (n=18)
24
6
13
24
93
11
6
4
6
202468
1012141618
Office 1 Office 2 Office 3 Office 4 Office 5 RegMed Vaccine
Type of PMS by PMDA Review Office（N=54）
Post-Marketing DB Survey
Specific Drug Use Survey
Drug Use Survey
14, 26%40, 74%
Products with All-Case Survey (N=54)
YesNo
84 3
11 10
2 2
1
1
65
10
5
10
15
20
Office 1 Office 2 Office 3 Office 4 Office 5 RegMed Vaccine
All-Case Survery by PMDA Review Office (N=54)
YesNo
Details of PMS (Drug Use Survey and Specific Drug Use Survey)
712
73
5
719
53
6
0 5 10 15 20
～24W(6M)6M～52W
1Y～2Y2Y～3Y
>3Y
Observation Period per Patient
Not outsourced
<100M Yen
100~300M Yen
Individual PMS cost not abailable
23
2
5
3
31
5
3
1
Cost of Outsourced PMS Monitoring
2019：N=372018：N=40
～1Y
1Y～2Y
2Y～3Y
3Y～5Y
>5Y
1
14
9
5
6
1
14
14
5
4
Enrollment Period
<100M Yen
100~300M Yen
300~500M Yen
>500M yen
11
16
5
3
5
22
11
2
Cost of PMSexcluding monitoring cost)
• Less than 300 patients in size, 6 month to 1 year observation period and 1-2Y year enrollment period are most frequently seen among all PMS.
• PMS with cost of 100 – 300 M Yen marked highest number and majority costs more than 100 M Yen.
0 10 20 30
~300300~500
500~10001000~2000
>3000
0 5 10 15 20 25 30
~300300~500
500~10001000~2000
Number of patients per PMS
All-case surveys Non-all case
0 5 10 15 20
PaperEDC
Hybrid
Survey tools
All-case surveys Non-all case
0 10 20
PaperEDC
Hybrid
2018 2019
Reason for Database Survey Planned (N=18)
Post-Marketing Database Survey
5
9
4
0 2 4 6 8 10
Not yet decided
MDV
MID-NET
Database used for DB Survey (N=18)Suitable DB available for the disease and risk 7
DB enables comparison 7
Other (PMDA’s request) 2
No Answer 2
Reason for “Not yet decided”(Multiple answers allowed)• Confirming if the required
data can be collected: 5• Investigating DB quality: 3• Difficulty of outcome setting: 1
Reason for DB Survey Not Considered
2019 (N=36)2018 (N=40)Data can not be collected through DBDB is not suitable to evaluate specific riskOthersLack of understanding of usefulness about DB in company
24(67%)
8(22%)4(11%)
26(65%)
12(30%)
1(2%)1(3%)
• The main reasons DB survey was planned were “DB could be suitable to evaluate the diseases and risks” or “DB enables comparison”.
• The main reasons why DB was not considered were “Data can’t be collected through DB” or “DB is not suitable to evaluate specific risk”. The combined proportion of these two reasons increased from 67%(2018) to 89%(2019). It is presumed that applicants have come to be able to assess the appropriateness of DBsurvey.
• MDV and MID-NET are planed for use and 28%(5/18) of DB surveys have not yet decided which database to use.
PMS Operation (Company N = 23)
Key finding：• PMS contract, enrollment and CRF collection are mainly
conducted by company MR.• Approx. half of companies have PMS conducted by
personnel other than company MR and the main reason is compliance risk.
16(69%)2(9%)
2(9%)3(12%)
Company MR incl. contract Company PMS dedicated monitor Subcontractor monitor Others
Who mainly conducts PMS Contract/Enrollment/CRF Collection
12
4
0 2 4 6 8 10 12 14
No
Yes
10
6
0 2 4 6 8 10 12
No
Yes
Any PMS contracted by personnel other than company MR?
Any PMS personnel other than company MR conducts enrollment/CRF collection?
Reason why personnel other than company MR conducts contract
Reason why personnel other than company MR conducts enrollment/CRF collection
Compliance Risk 6
Others 3
Compliance Risk 6
Others 4
Others: - Company MR incl. contract & Subcontractor monitor: 2- MR of the company which sells the product: 1
