連続生産研究会で何を期待し、何をするか。
愛知学院大学特任教授、岐阜薬科大学名誉教授 川嶋 嘉明(副会長）
連続生産が、医薬品製造で話題になっています。その背景には、医療費高騰歯止めの国家戦略として医薬品の生産効率の向上による原価の低減があります。一般の化学工業に比べると、従来、医薬品産業では、回分操作が主流で連続操作の取り込みは、大変遅れています。その訳は、医薬品は、原料の大半が粉体であり多品種少量生産であること。そのため、連続生産における滞留時間（反応時間）に分布が生じます。粉体物性との関係を明らかにする大きな課題があります。また、製品が人に投与されるため、品質の保証・管理には、最大級の注意が必要となります。製品の切り換え時の交叉汚染の防止や、回分法から、連続法にした時の、品質の恒常性、安定性の確保も大きな課題です。QbDに基づいた規制の整備も必要となります。これらの課題克服には、産・官・学共通の場で、情報を共用し、明確な科学的根拠に立脚した議論をすることから始まるとの考えから本研究会を立ち上げることにしました。FDAでQbDによる品質保証のイニシアティブをとったHussaine博士が‟適切な規制はイノベーションを産む”と訴えた講演を思い出します。PATの発展がQbDの実現に大きな役割を果たしたように、連続生産においても多くのイノベーションが期待されます。これによって、規制の概念は、大きくリニュウアルされるでしょう。産・官・学の3つの歯車がうまくかみ合ってはじめて、最も効率の良い医薬品の連続生産が実現するものと確信します。
What Can We Expect from and Do with Continuous Manufacturing Study Group?
Yoshiaki Kawashima, Honorary Professor of Gifu Pharmaceutical University and
Associate Professor of Aichi Gakuin University
Continuous manufacturing is a hot topic in the pharmaceutical industry. This is driven by the national strategy to put the brakes on the soaring medical expenses by improving pharmaceutical production efficiency and reducing costs. Historically, batch operation is the mainstream and the introduction of continuous manufacturing process is very slow in the pharmaceutical industry in comparison with other general chemical industries. This is because the majority of raw materials used in the pharmaceutical industry are powders, and a wide variety of products are produced in small quantities, which causes a wide distribution of residence time (reaction time) in continuous manufacturing. There is a great challenge to clarify the relationship between residence time and physical properties of powders. The greatest care is required to ensure quality assurance and quality management because products in the pharmaceutical industry are administered to human beings. Another great challenge is how to prevent cross-contamination that may take place during product change-over and assure the constancy and stability of product quality when batch manufacturing is replaced by continuous manufacturing. Regulatory improvement based on QbD will be also required. We decided to establish this Study Group as we concluded that solving these issues starts with sharing information and holding clear scientific evidence-based discussions among the sectors of industry, government and academia. I remember the presentation given by Dr. Hussaine who had taken the initiative for the QbD-based quality assurance in the FDA, asserting that “appropriate regulations promote innovations.” As the progress of PAT played a great role in putting QbD on the right track, many innovations are expected in continuous manufacturing. This will markedly renew the concept of regulations. It is no doubt that the most effective continuous manufacturing for drug products is not in place until a good orchestration among industry, government and academia is achieved.
東邦大学名誉教授、高崎健康福祉大学 薬学部 教授 寺田勝英(副会長）
医薬品の品質保証における新たな潮流といったテーマで十数年前からICH Qトリオ、PAT、QbDなどをいろんな場で議論してきたことを思い出します。今思えば、その頃から、近い将来には医薬品製造は連続生産になっていくのだということが暗示されていたのだと思います。
さて、連続生産は2014年5月米国FDAのJanet Woodcook氏の呼びかけで開催された第1回International Symposium on Continuous Manufacturing of Pharmaceuticalsに端を発したものと理解しています。その後、様々な場で検討が進められ、連続生産に関する技術的側面ではPAT技術、ソフトセンサー、ケモメトリックスなどの解析ツールを用いた工程モニタリングなどに著しい進歩がみられます。
一方、連続生産に関するロットの定義、管理戦略の要素、プロセスバリデーション、工程管理を含む連続生産の重要項目の特定や定義、品質リスクマネジメント、原料のトレーサビリティー、工程モニタリングやその管理などについては、行政側と更なる共通の認識や理解が必要になると思います。
今後は産学官が一緒になって、連続生産による製造から承認申請までの様々なハードルを実験も含めた検討や議論を通じて推進していきたいと思います。研究会を立ち上げますので、是非、ご参加ください。
Katsuhide Terada (Vice Chairman), Professor of Faculty of Pharmacy,
Takasaki University of Health and Welfare and Honorary Professor of Toho University
I remember our discussions on ICH Q8/Q9/Q10, PAT, QbD, etc. held in various occasions under the theme of new trends of quality assurance in the pharmaceutical field since a little over a decade ago. Thinking back about it now, the shift to continuous manufacturing in the pharmaceutical sector in the foreseeable future was already shown in those days.
I personally understand that continuous manufacturing is originally out of the first International Symposium on Continuous Production of Pharmaceuticals held on the initiative of Janet Woodcook from FDA in May 2014. Since then, it has been reviewed and deliberated in various occasions, and remarkable technical progress has been made in the continuous manufacturing engineering aspect including process monitoring using PAT techniques, soft-sensor and chemometrics and other analytical tools.
On the other hand, we will need to share further recognitions and understandings with the government with respect to the definition of the term of “lot” in continuous manufacturing, elements of control strategies, process validation, the identification and definition of critical items for continuous manufacturing including process control, quality risk management, traceability of raw materials, and process monitoring and management.
We will work to overcome diverse hurdles related to continuous manufacturing processes from production to application for approval through discussions and studies including experiments in collaboration among industry, government and academia. We appreciate for your participation in the Study Group to be launched soon.
株式会社じほう 広報部長 橋都なほみ
今年６月に開催された医薬品規制調和国際会議（ICH）の神戸会議で，ガイドライン化を目指す新トピックとして連続生産がQ13として採択され，わが国においても医薬品製造に大きなインパクトを与える技術として注目を集めています。月刊誌「ファームテクジャパン」でも連続生産に関する臨時増刊号や通常号でトピックスとしてたびたび取り上げさせていただいています。今後も本研究会の活動内容も含めて広くお伝えしていきたいと考えています。
Nahomi Hashizume, PR Director, Jiho Inc.
Continuous production was adopted as a new topic and introduced into Q13 Guideline at the Kobe Convention of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) held in June this year, and is drawing attention also in Japan as a technology having huge impact on the pharmaceutical production. We also have often feature articles of continuous manufacturing in special and regular editions of our monthly magazine, “PHARM TECH JAPAN.” We plan to continue reporting wide ranging aspects of continuous manufacturing including the activities of this Study Group.