10 Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2019 P h a r mTe c h . c o m
Guidance Update
are expected to contain a sensitivity solution at
a concentration corresponding to the reporting
threshold, and a signal-to-noise requirement as a
part of system suitability requirements. This ap-
proach is used for both drug substance and drug
product monographs."
According to USP, FDA is concerned that in-
cluding reporting thresholds might present the
risk of toxic impurities not being identified or
reported. FDA commented to USP that report-
ing thresholds for drug products should be ad-
dressed as part of an application assessment.
FDA uses ICH reporting thresholds as guide-
lines and deviates from them as needed based
on appl icat ion-speci f ic considerat ions. T he
agency believes that similar concerns apply to
drug substance monographs. FDA commented
that since a drug substance may be used in dif-
ferent products with different maximum daily
doses, ICH Q3A limits (including repor ting
threshold) will vary due to product specific fac-
tors and should also be addressed as an applica-
tion assessment issue.
USP is therefore proposing a policy change to
the inclusion of reporting thresholds in drug
substance and drug product monographs. The
proposal includes the following changes:
• Expert Committees will be able to delete
the proposed reporting threshold.
• Depending on finalization of the policy,
reporting threshold will not be included in
Pharmacopeial Forum proposals for drug
substance and drug product monographs.
• A sensitivity solution and signal-to-noise
requirement in monographs will continue.
• Monographs that are already official will
not be revised to remove the reporting
threshold until they are up for revision as
part of the ongoing revision process.
The proposed revised policy is up for a 90-day
public comments period that ends Nov. 12, 2019.
Reporting thresholds will continue to be included
until the changed policy is finalized.
References
1. FDA, "FDA Patient-Focused Drug Development Guidance Se-
ries for Enhancing the Incorporation of the Patient's Voice in
Medical Product Development and Regulatory Decision Mak-
i ng," FDA.gov, w w w.fda .gov/d r ugs/development-approva l-
process-drugs/fda-patient-focused-drug-development-guid-
ance-series-enhancing-incorporation-patients-voice-medical
2. FDA, Draft Guidance for Industry: Rare Pediatric Disease Prior-
ity Review Vouchers (Rockville, MD, July 2019). www.fda.gov/
media/90014/download
3. FDA, Draf t Guidance for Industry: Providing Regulatory Sub-
missions in Electronic Format—Certain Human Pharmaceuti-
cal Product Applications and Related Submissions Using the
eCTD Specifications, (Rockville, MD, July 2019) www.fda.gov/
reg u lator y-i n for mat ion /sea rch-fd a-g u id a nce-doc u ment s/
providing-regulatory-submissions-electronic-format-certain-
human-pharmaceutical-product-applications-0
4. F DA , D ra f t G u i d a n c e f o r In d u s t r y : Po p u l a t i o n Ph a r m a -
c o k in e t i c s (Ro c k v i l le , M D, Ju ly 2 019), w w w. fd a . gov/re g-
u l a t o r y- i n f o r m a t i o n /s e a r c h - f d a - g u i d a n c e - d o c u m e n t s /
population-pharmacokinetics
5. FDA, Guidance for Industry: Risk Evaluation and Mitigation
Strategies: Modifications and Revisions, (Rockville, MD, July
2019), w w w.fda.gov/regulatory-information/search-fda-guid-
ance-documents/risk-eva luation-and-mitigation-strategies-
modifications-and-revisions-guidance-industr y-0
6. FDA, Draft Guidance for Industry: Instructions for Use—Patient
Labeling for Human Prescription Drug and Biological Products
and Drug-Device and Biologic-Device Combination Products—
Content and Format (Rockville, MD, July 2019), www.fda.gov/
reg u lator y-i n for mat ion /sea rch-fd a-g u id a nce-doc u ment s/
instructions-use-patient-labeling-human-prescription-drug-
and-biological-products-and-drug-device
7. FDA, M10 Bioanalytical Method Validation, June 2019, www.fda.
gov/regulatory-information/search-fda-guidance-documents/
m10-bioanaly tical-method-validation
8. FDA, Draft Guidance for Industry: Development of Therapeutic
Protein Biosimilars: Comparative Analytical Assessment and
Other Quality-Related Considerations (Rock v ille, MD, May
2019), w w w.fda.gov/media/125484/download
9. FDA, Draf t Guidance for Industry: Harmonizing Compendial
Standard s With Dr ug Application Approval Using the USP
Pending Monograph Process (Rockville, MD, July 2019), w w w.
fda.gov/media/128689/download
10. USP, "Reporting Threshold in USP-NF Monographs: Proposed
Policy Change for Public Comment," Press Release, Aug. 13,
2019, www.uspnf.com/notices/reporting-threshold-proposed-
change-for-comment
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