2015 dashboard of pharmaceutical & biologics regulatory sciences

Dash Board of 2015 Pharmaceutical & Biologic Regulatory

Science’s Review

Obaid Ali & Roohi B. Obaid, Pharmaceutical & Biological Regulatory Sciences Forum 26 Dec 2015, Karachi

Dash Board of 2015 Pharmaceutical Regulatory Science’s Review

Learn, De-learn & Re-learn

Not the view of DRAP

Current judgment of speaker

No obligation on DRAP

Regulatory experience

It has nothing to do with any specific

commercial product

It is just a knowledge sharing

exercise nothing more than that

DISCLAIMER

Background Review of Regulatory Sciences

Changes & Emerging shape of Regulatory Sciences

Discussion, Case Studies & Explanation

Relative Scale of Concerns

N

G

B

S E Q

S E Q

QES

Pre-Market Compliance Post-Market

G

B

N

SafetyEfficacyQuality

Background Review of Regulatory Sciences

Changes & Emerging shape of Regulatory Sciences

Discussion, Case Studies & Explanation

New

Too

ls

Approaches

Stan

dard

sE

Q

P

S

REGULATORY

SCIENCE

Globalization

Harmonization

ICH

International Generic Drugs Regulator Pilot

Collaboration Convergence Regulatory Mandate

Increased work load Globalization Scientific

complexity

Mutual Reliance

Work sharing

Efficient use of

Resource

Faster review

Greater availability Generics

EU

Australia Canada

Chinese Taipei

Switz

erla

nd

First Phase

Brazil

China

Japan

Korea

Mexico New Zealand

Russia Singapore

South Africa

Second Phase

Background Review of Regulatory Sciences

Changes & Emerging shape of Regulatory Sciences

Discussion, Case Studies & Explanation

Qua

lity

Integrity

Shor

tage

Supply chain

Integrity

Regulatory violations

Contamination Particles

Good Manufacturing Practices & Products

Culture of Quality Drug Shortage

Program

Quality Pharmaco

Chemo Econo

Metrics

UBER?

Connecting the Dots

Connecting the Dots

People

Regulation Science

Quality Metrics (Russell Wesdyk, Acting Director for the Office of Surveillance, OPQ, CDER, FDA

How is industry performing?

Who & what is out there?

Do we understand our industry?

What should Regulatory Authority do when they show up at the site?

Can we sum up what we have with data & transfer that data into knowledge?

Quality Metrics (Russell Wesdyk, Acting Director for the Office of Surveillance, OPQ, CDER, FDA

More information is better than less information

Business Model Shifting(Monika Cahilli, Green Mountain Quality Assurance)

Increased Outsourcing

Paper Tiger does not always work

Management needs to be fully engaged in Quality Agreements

Feedback mechanism for Control Strategy

Continuous review of electronic data

How many data points are involved to support the release of one product?

Learn to embrace in perfection in order to accept residual risk

Business Model Shifting(Monika Cahilli, Green Mountain Quality Assurance)

Data Integrity(Douglas Starn, Director Enforcement & Import Operations, FDA)

Integrity & Fraud are mostly close

Lack of integrity at one area raise question about others

Ability to assure safety & efficacy is doubtful

Data accountability is the only tool

Data integrity issues are not always easy to see and thus difficult to remediate

It is better to be safe than sorry…proper control can prevent and limit data integrity

issues

Data Integrity(Douglas Starn, Director Enforcement & Import Operations, FDA)

Quality & Innovations are linked(Lisa Zboril, Vice President Regulatory Affairs, Pfizer)

Product lifecycle … what occurs in manufacturing & how reflected in submission

Quality submission is planning, control & continuous improvement

Early planning to target product profile and label requirement

Regular communication of uncertainties

Continuous improvements include regulatory intelligence, deficiency tracking,

lessons learned & scientific rigor of data

In generic world, the key to success is being efficient, timely and accurate

Quality & Innovations are linked(Lisa Zboril, Vice President Regulatory Affairs, Pfizer)

Make the reviewer excited that they are getting an application from you

Quality & Innovations are linked(Ted Sherwood, Acting Director, Office of Regulatory Operations, FDA)

Background Review of Regulatory Sciences

Changes & Emerging shape of Regulatory Sciences

Discussion, Case Studies & Explanation

Proposed Product Manufacturing Classification System

Right particle

Best process

Difficult API

Good API

Ref: Lilly, GSK ……….

Highly Soluble & Highly Permeable

Highly Soluble & Less Permeable

Low Soluble & Highly Permeable

Less Soluble & Less Permeable

BCS

Direct Compression Dry Granulation

Wet Granulation Other Technologies

MCS

Direct Compression

Grind drug Intra-granular excipients Compression

Direct Compression

Grind drugIntra-

granular excipients

Roller compaction

Extra-granular excipient

Compression

Direct Compression

Grind drugIntra-

granular excipients

Granulation Wet Screen

DryingDry ScreenExtra-

granular excipient

Compression

Evolving shape of Biopharmaceuticals

Regulatory

PoliticalLegislative

Science of

Risk

Regulatory Oversight

Production Quality Reducing shortage

Facilitating development

Price, Value, Innovation

BreakthroughLife saving therapy is being coming

Hepatitis C

Cholesterol lowering agents

Cancer

drugs

Rare disease therapies

2014

41 new drugs

10 biologics

2015

1st Bio-similar approval in US

Zarxio from SandozOver 50 applications are in pipeline

Quick response on EbolaA beautiful collaborative demonstration of different organizations & countries to combat deadly virus

Quality remains a Challenge

Predictable & timely approval

Reduced inspection burden

Quality Metrics on way

Smart & Progressive

vision

Able to detect quality

problems before they

occur

Changes Evolved

• CMC from pre-clinical/clinical through review to postapproval changes & generic drug developmentChanges in Review

• Continue to oversee innovators and biosimilarsBiotechnological Products

• Quality aspect during development & approvalNew drug product

• Post-marketing changes & generic drug developmentLifecycle

• Manufacturing operation, microbiology review & preapproval inspection Collaborative Oversight

Adoption of a Risk based Model

Target oversight where quality

failures are most likely to harm

patients

Product

Facilities

Process

Footprints of knowledge is in your backyard to navigate you …

Example Elemental impurities

Ref: Pharmaceutical Technology, March 2015, Andrew Teasdale et al.

Drug Product

DS

Excipients

Equipment Utilities

Container Closure

Footprints of knowledge is in your backyard to navigate you …

Drug Substance

Inorganic reagents

Organic material

Processing aids

Equipment Metal catalysts

Water & Solvents

Container Closure

Footprints of knowledge is in your backyard to navigate you …

Excipients

1. Mind (Talc)

2. Metal catalysts (Mannitol)

3. Plant origin (cellulose)

4. Animal origin (lactulose)

5. Without metal catalysts (colloidal

SiO2)

Footprints of knowledge is in your backyard to navigate you …

Limited solubility in DP & limited interaction but

High metal content in packaging

Highest risk (high conc. of metal in packaging; high degree of interaction b/w

packaging & DP)

Lowest risk (low conc. of metal in packaging;

limited interaction b/w packaging & DP)

Good solubility in DP, intimate contact, but low

metal content in packaging

From Packaging

Met

al C

onte

nt in

Pac

kagi

ng

Metal solubility in product

RISK

IN

PACKAGING

Footprints of knowledge is in your backyard to navigate you …

Security of internal supply chain

Control of vendor elemental impurity specifications & elemental impurity reporting on ingredient COA

Security of external supply chain + a quality history for each vendor

Audit history Level of complaints Recall etc.

PRIOR KNOWLEDGE IS THE WAY TO MOVE FORWARD

Footprints of knowledge is in your backyard to navigate you …

PDE Calculation

Residual active substance

Toxicology

Pharmacology

Industry & Regulatory Agencies on Global Watch

Lifecycle data management & Quality System

Innovative strategies to meet

timeframes

Global framework & collaborations to secure supply chain

Drug development & Drug Pricing

battle

Controversy on strategies &

Science Scale

Modernization in Manufacturing & Quality Initiatives

Efficient generic drug review regulatory framework

Policies to enhance drug safety &

security

ReferenceJill Wechsler, 2015

Lifecycle data management & Quality System

Alteration in System,

Formulation & Test Method

Variation submission

Costly & time consuming

Regulatory & Post approval

changes

Developing International

Quality StandardsIntegrations

Review, Inspection & Surveillance

Innovative strategies to meet timeframes

Expedite development &

approval of innovative drug

Quick results of reviews

Innovative risk mitigation strategies

Less stability data at submission

Accepting amendment during the review process

Increased post-marketing

commitmentEarly decision for

dosage form

Early decision for method validation strategies before

time

Global Framework & Collaborations to secure supply

Storm of counterfeit & adulterated drugs

Over 2000 incidences of pharmaceutical

crime reported in 2014

Theft, counterfeiting, diversions, illegal drug

websitesAggressive &

collaborative actions

June 2015 operation Pangea VIII by

InterpolePoor quality medicines

SSFFC (Substandard, Spurious, Falsely

Labeled, Falsified & Counterfeit)

Drug Development & Drug Pricing battle

Costing Therapeutic value

Free economy Innovation

Fee Liability Profit

Controversy on Strategies & Science Scale

Quality Metrics Overworking Increased burden

Reduced inspection

Reduced regulatory burden on post approval

Slow move

Modernization in Manufacturing & Quality Initiatives

More powers of inspection Recall power New Inspection

approach

Unannounced inspection

Tougher inspections

Disregarding the delaying, denying, limiting or refusing

of inspections

Efficient Generic Drug Review Regulatory Framework

API focus Inspections Quality & Complaints

Policies to enhance Drug Safety & Security

Meningitis outbreak

IV Compounding Contamination

Microbial Penicillin Standardization

Prospective data can

sometime bring irreversible

tragedy

Aseptic processing proven safe but not sterile

Incr

ease

d se

para

tion

of P

erso

nnel

Increased confidence in Sterility Assurance

Manual aseptic fill

Conventional aseptic fill

Barrier System

Open RABS

Closed RABS

Open Gloved Isolator

Closed Glove Isolator

Glove-less Isolator

Warm up

Inhalation of a non-sterile product (Ribavirin powder for solution) with microbial contamination ….

What is harm?

Inhalation of a non-sterile product (Ribavirin powder for solution) with microbial contamination ….

What is harm?

Increase risk of respiratory infection Patients are usually immuno-compromised and more

susceptible to infection

Inhalation of a non-sterile product (Ribavirin powder for solution) with microbial contamination ….

What is harm?

Increase risk of respiratory infection Patients are usually immuno-compromised and more

susceptible to infection

RECALL (Virazole Expiry date: Oct 2018)Valeant Pharmaceuticals, USA

If you want to go fast, go aloneIf you want to go far, go together

Thanks