Download Substances - Japan Bioanalysis Forum

An overview of the draft concept paper on
“quantitative measurements of endogenous
biomarkers for drug developments”;
regulatory importance and future directions
「医薬品開発においてヒト内因性物質をバイオマーカー
として利用する際の定量分析法に関する留意点」
Takayoshi Suzuki, JBF Biomarker TF
A process lead to the concept paper
• Focused on the quantitative measurements of endogenous
substances because of time limitation
• A need for a guidance to measure endogenous substances as
biomarkers.
•
Preceding LC-MS and LBA guidelines
• Endogenous substances including biomarkers are out of scope
in these guidelines.
• Difficult points for a measurements of endogenous
substances to follow the LC and LBA guidelines were discussed.
• Considerations for those points were summarized.
Considerations for “quantitative measurements of
endogenous biomarkers for drug developments”
(Draft paper by the JBF TF)
1. Introduction
2. Application
3. Matrix
4. Standards
5. Specificity
6. Calibration curve
7. Detection Limit
8. Accuracy & Precision
9. Robustness
10. Kit s
はじめに
適用
マトリックス
標準物質（標準品）
選択性
検量線
定量下限
真度・精度
安定性
キット
Please refer to the poster presentation for detail
2．Applications（適用）
• 開発後期の臨床試験 Later-stage clinical studies
• 安全性評価に用いるバイオマーカーについては開発初期から
適応するのが望ましい場合もある。Applicable for safety
biomarkers from initial stage if they are important
• 患者の層別化を目的としたバイオマーカーは対象外
Biomarkers for patient selection (CDx) are excluded
• 対象となる分析法はLC,GC-(MS)とLBA
LC, GC (-MS) and LBA as methodology
• 分析対象物質は定量分析可能な内因性物質とし、臨床検査
項目等のバリデーション済みの内因性物質は除く
Targets are quantitatively measurable endogenous substances,
excluding already validated clinical laboratory tests
Reviewing the draft concept paper
• There are some difficulties to reach the consensus on
the draft paper with PMDA
• Mainly because of the usage of the term
“biomarker” in the introduction part.
• More discussion will be necessary.
But I have learned some discrepancy
between regulators and developers
Needs for a guidance
• Guideline or guidance can sometimes promote
a development.
• Guideline or guidance can reduce the unnecessary data for submission.
• Guideline or guidance can promote agreement
between regulators and developers
Ultimate purpose of building guideline is to facilitate approval process in drug application
Trends in Japanese Regulator
• Comfortable without a guideline
– Feel no needs for guidelines for items that never
became a problem
Trends in Japanese Developer
• Uncomfortable without a guideline
– Try to follow available similar guidelines
“Self-discipline”
自己規制
Guideline is not a “law”
• No need to follow the guideline when there are
enough scientific reasons to ignore it.
• There are always exceptions that do not necessary
follow the guideline.
• It is important to think about the scientific
justification rather than just follow the guideline.
• In such sense, it is better to have no guideline to
promote the innovative development
Biomarkers vs Endogenous substances
Biomarkers
Endogenous substances
Target for the concept paper
Biomarkers vs Companion Diagnostics
Biomarkers
Companion Dx
Classification of biomarkers
• Substances
– Protein/Peptide, DNA, RNA, miRNA, Cell
• Methods for detection
– LBA, LC-MS, RT-PCR, NGS, microarray, FCM
• Quantitative or Qualitative
• Purpose
– Companion Dx, efficacy, toxicity, ADME
• Timing to be used
– Early development, preclinical/clinical phase,
Later stage for application data
Fit for the “Purpose”
• What is the purpose for measuring biomarkers?
• Different level of requirements should be set
depending on the purpose.
• Companion Dx has highest level of requirements
for biomarker
• Validation of the biomarker for the purpose is
important before measuring it.
Importance of the Companion Dx
• Necessary for the development of new drugs
with a selection of proper patients
• Co-development of new drugs and the
companion Dx is required
• New paradigm for drug development is
required?
Who plays an important role for the
developments of the companion Dx
• Traditionally diagnostic company is responsible
• Needs collaboration with the diagnostic company
• Who covers the risk for the failure of drug development
• Establishments of new biomarkers and tests for their
measurements are very significant at the initial stage of
development.
Pharmaceutical companies should play an
important role for companion diagnostics !
Towards an establishment of a guidance for
biomarker measurements in drug developments
• General considerations for biomarkers
• Promote a usage of biomarkers for drug
developments
• What is agreeable or useful guidance for
regulators and developers?
• Considerations for the companion Dx
“Japanese regulators should have
strong visions and policies on regulation
to promote medical innovations."
Chia-Feng Lu, Lawyer at Baker & McKenzie
Acknowledgement
• JBF Biomarker Taskforce members
• 西川班バイオアナリシス分科会
バイオマーカーワーキンググループ