Module 3 Chapter 1086 Update

7/27/2019 Module 3 Chapter 1086 Update

http://slidepdf.com/reader/full/module-3-chapter-1086-update 1/23



General Chapter Update:

<1086> Im urities in Dru Productsand Drug Substances



USP <1086>

USP <1086> Impurities in Drug Substances and Drug Products

“Impurities” is one of the major areas of focus for drugs due to

otential im act on safet & efficac

– No clinical benefit

– Potentially toxic –

formation / process fate is not well understood

– High potential for variability/change in qualitative/quantitative profiles

.

One of the critical quality attributes (CQA) of DS and DP

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USP <1086>

Topic of Impurities is significantly changing due to advances in

science and technology

– Scientific understanding, especially toxicology – Technology changes, especially analytical techniques/methodology

measurements, assessments and controls of impurity

have been updated to meet the current standards

– ICH Q3A (Drug Substance)

– – ICH Q3C (Residual Solvents)

Similar standards set for generic drugs (ANDAs)

– FDA Guidance for Industry, November 2010: “ANDAs: Impurities in Drug

Products”4



USP <1086> - Why Revise?

Impurities in new drugs and new generic drugs are covered

by ICH or equivalent standards

However, OTC products and many Rx (older generic)products rely on USP standards

< > as some e emen s o mpur y

information (e.g. definitions), BUT –

(tests/methods/acceptance criteria)

– It is an Informational chapter and non enforceable

Notices (GN) 5.60: Impurities and Foreign Substances

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<466> Ordinary Impurities – Impurities that do not have significant undesired biological activity (toxicity)

– Reporting and Specifications: 2.0% unless otherwise specified in the

individual monograph

– Methodology: unless otherwise specified in the monograph, estimate by

re a ve me o s an no y us ng re erence s an ar s

– Typical evaluation by TLC

GN 5.60. Impurities and Foreign Substances – GN 5.60.10 Other Impurities in USP and NF Articles

Other Impurity: Impurities other than Ordinary impurities – new impurity?

Presence of any unlabeled other impurity is a variance from the standard

s > . - s s a accep ance cr er on Total (ordinary + other) NMT 2.0%

Bottom line: USP Impurity related sections need revision

– Outdated, unclear

– Not in line with current scientific standards6




In addition to gaps in Impurity chapters, there are major gaps

in OTC and Rx drug substance/product monographs

– OTC monographs (majority) are outdated compared to current standards• Missing impurity specifications for 80 DS and 319 for DPs

• Lack of specific analytical procedures for 57 DSs and 13 for DPs

– Older Rx product monographs are also outdated

• Missing Impurity specifications for 243 DSs and 1168 for DPs

• Lack of specific analytical procedures for 156 DSs and 15 for DPs

– OTC drug product monographs are incomplete

u c an regu a ory expec a on s a pro uc s orolder generic products will have comparable quality to Rx

roducts when it comes to safet and efficac

Bottom line: Monographs also need major updates

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USP’s Mission: To improve the health of people around the world

through public standards and related programs that help ensure the

quality, safety, and benefit of medicines and foods.

Keeping the quality standards commensurate with scientific and

technolo ical advancement is the ri ht thin to do & ex ected

Already efforts are in progress in many areas

– Monograph modernization efforts – ress new nee s , e e e or ev se

• <467>Residual Solvents

• <231> Heavy Metals

• <233> Elemental Impurities – Procedures

Conclusion: USP <1086> and related Sections <466> and GN

5.60 on Im urities have to be brou ht u to standard

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USP <1086> Expert Panel

Expert Panel formed in August 2011

– Good representation of members from key stakeholders

–

• Gregory Amidon, Chair • Antonio Hernandez-Cardoso, Sr. Scientific Liaison

• Prabu Nambiar, Ph.D. – Chair

• Shaukat Ali Ph.D.

• Mary Seibel, B.S.

• Robert Buice Ph.D.

• Kevin A. Swiss, Ph.D

• Abdullah M. Al-Mohizea

• David Rogers, Ph.D.

• Gregory Davies, B.Sc.

• Xiaorong He, Ph.D., M.B.A.

• Steven Baertschi, Ph.D.

•

• Michael Koberda, Ph.D.

• Judy P. Boehlert, Ph.D

•, . .

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Charter of the Expert Panel:

The purpose of this Expert Panel will be to revise the USP

< > -

regulatory thinking with regard to OTC and generic producttesting, and to evaluate the advantages and disadvantages of

any ee ngs ave een e

– Telecon 1 - September 2011

– First face-to-face meeting - December 2011

– Telecon 2 - Jan 2012

– Telecon 3 - March 2012

– - - –

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Status Update

– ,

overall objectives and understood the deliverables• Provide a recommendation to the Expert Committee about how

o up a e < > an re a e sec ons

• Discussions resulted in 4 possible options

1Update, clarify terminology,

include note re: TDINone

Eliminate <466>

Revise <1086> & bring below

1000


include note re: TDIRevise

Eliminate <466>Develop new GC

Update, clarify terminology,

nc u e no e re: , nc u e

language to ensure compliance

ev se m na e < >

4Eliminate statement regarding

im uritiesRevise

Eliminate <466>

Develo new GC11



Contact Information

Antonio Hernandez-Cardoso

[email protected]

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Status Update

– ,

voted to move forward with Option 2

O tion General Notices GN <1086> General Cha ter <466>


include note re: TDIRevise

Eliminate <466>

Develop new GC

– During the March 2012 Telecon, a sub-group of the Panel

volunteered to write a communication article to

ssem na e e upcom ng c anges o e mpur essections to potential stakeholders

– Stimuli article or hot to ic? Timin is of essence. So Hot

topic seems to fit the timing needs.

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Status Update

– - -

• Finalize the Hot topic article

• Devise O tion 2 Im lementation lans

• Panel will divide into 3 sub-groups and start

brainstorming about the process to prepare therev s ons o enera o ces, man a ory enera

Chapter and <1086>

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Anticipated Challenges

–

chapter will require major revisions to existing monographs – OTC products are complex products due to multiple

actives and intended uses

• Might require sophisticated analytical techniques

•

– Do ICH Q3A and Q3B apply for OTC products?

– How to address issues such as “genotoxic impurities for

age o pro uc s – Can OTC products use safety data from prolonged use of

the roduct to ustif different a roach

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Anticipated Challenges

– How to Implement the change seamlessly

• Internal

• External stakeholders

– How to implement the change in concert with monograph

modernization?

– How to ensure compliance….and many more

ome ra eg es

– USP’s experience of implementing changes for USP<467> and

<231> is ex ected to be extremel valuable

– Will continue to discuss lessons learned.

– Will tap into appropriate resources

–

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Backup Slides

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USP <1086>

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General Notice

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General Notice

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USP <466>

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USP <466>

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Module 3 Chapter 1086 Update

Documents

Transcript of Module 3 Chapter 1086 Update