Longe Sunday Anthony

Head- Quality Assurance

May & Baker Nigeria Plc.

Pharmacentre, Ota, Nigeria

eaglesconsult@gmail.com; Slonge@may-Baker.com .

Quality Risk Management

(ICH Q9): WHO Model for Sustainable Quality

Medicines

• The Pharmaceutical Industry is constantly being challenged to comply with rigorous regulatory requirements. Therefore the need to ensure that a company’s processes are being operated at a level of control using risk management approach

• Compliance is evolving from a “reactive approach” - Inspection, checks and comprehensive testing to a “Proactive approach” scientific and risk management approach.

• However, compliance is not a one-time event and organizations are redesigning their compliance programs to make them repeatable processes that could be sustained.

Preamble

Challenges

• Rising Standards of Quality

• Rising Regulatory requirements and reporting

mandates- ADR’s, ADE’s etc.

• Competitive sector within a harsh business

environment- Conversion Cost vs Quality

Compliance is not just a regulatory requirement, but a Quality Culture that guarantees good quality product.

Who Governs

cGMP Current Good

Manufacturing Practices

21 CFR Part 211 ( Pharma )

21 CFR Part 820 ( Med devices)

21 CFR Part 110 ( Food )

21 CFR 600 – 680 Biologics

GAMP Good Automated

Manufacturing Practices

GAMP 5(ISPE) Guide

GALP Good Automated Laboratory Practices

EPA Directive 2185 ( 1995 Ed. )

GCP Good Clinical Practices

21 CFR 312 Sub part

GLP Good Laboratory Practices

21 CFR Part 58

40 CFR Part 160 ( EPA )

ICH Guidelines Quality, Efficacy, Safety, CTD / e – CTD

Regulators Speak through

Regulations

Q1A(R2)

Q1B

Q1C Stability Testing

Q1D

Q1E

Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

Q8(R1) Pharmaceutical Development

Q9 Quality Risk Management

Q10 Pharmaceutical Quality System

M4(R3)* Organization of the Common Technical Document for the Registration of

Pharmaceuticals for Human Use

-The assessment of individual risks related to specific

products and starting materials and the recognition of hazards

at specific stages of production or distribution.

- Quality risk management (QRM) is a process that is relevant

to all countries and should provide a rationale to understand

risk and mitigate it through appropriate and robust controls.

- QRM is the overall and continuing process of appropriately

managing risks to product quality throughout the product's

life-cycle in order to optimize its benefit–risk balance.

Concept of Quality Risk Management

ICH Q9 Quality Risk

Management

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Road to Compliance

Importance of Vendor Development & Qualification

“Using a pharmaceutical ingredient without a

knowledge of the specific manufacturing site,

Regulatory status, and how it got to you is like

traveling without a definite destination.”

MATERIAL CONTROL

API Manufacturers & Vendors

Are responsible for assuring that ingredients they supply comply with GMP, are not misbranded or contaminated, are packaged/stored appropriately, and adhere to signed Quality Agreement.

FPP (MAH) & Regulators

Are ultimately responsible for the use of appropriate ingredients

and assuring ingredient quality at every stage of the supply chain

and Storage before final conversion.

Pharmaceutical Ingredient Supply

Chain – A Shared Responsibility!

Process Control

CCP

Dispensing

Equipment e.g.

RLAF, Balance, scoops

Cross contamination, inaccurate

quantities,Failure incidence;

Reprocessing/re-work, Overdosing or underdosing, Poor

product quality

Environment e.g. HVAC, Drains, lightings

MAN

Temp/RH/DP

out of control;

contamination

Material Mix-

ups; inaccurate

weighing etc.

•Equipment must be located, designed, constructed, adapted and maintained to suit the operations to be carried out.

•The layout and design of equipment must aim to minimize the risk of errors.

•Permit effective cleaning and maintenance in order to avoid cross-contamination, build-up of dust or dirt, and, in general, any adverse effect on the quality of products.

Equipment Controls

URS

(To specify the

end use requirement)

Design

(By manufacturer to

meet expectations)

Manufacturing of

Equipment

(Easy to handle,

Easy to clean.

Good surface

Finishing)

FAT

(To ensure for

functioning as per

expectation at

manufacturing site)

SAT

(Receive at site

In proper condition)

IQ/OQ

Qualify equipment

as per SOP

PQ

Placebo run

(Matrix approach to

qualify for

intended use)

PM

(Preventive Maintenance

to maintain equipment

as per functionality)

BM

Breakdown

Maintenance

(Trending)

Usage Evaluation

Retirement/ decommissioning

What ?

• A set of operations that establish, under specified conditions, the relationship between the

values of quantities indicated by a measuring instrument or measuring system, or values

represented by a material measure or a reference material, and the corresponding values

realized by its standards.

Why ?

• When process measuring instruments age and experience physical stress or temperature

variations, critical performance gradually declines. This is called drift.

• The slow variation with time of metro logical characteristics of the measuring instruments.

As a result of this, the measurement results become unreliable and ultimately the production

quality can suffer.

• Drift cannot be eliminated, but it can be discovered through calibration.

Calibration

•Risk-based approach. •Conduct appropriate levels of product impact and

critical risk assessment of systems and system functionality early in the planning stage and then throughout the validation life cycle as required.

•Qualification •URS, DQ, FAT, SAT, IQ,OQ, PQ

•Process Validation & Cleaning Validation Process & equipment Design Vs Equipment

performance are critical to process validation and cleaning validation success.

Qualification & Validation

• Calibrated equipment provides confidence that

products/services meet their specifications.

• Calibration:

-Increases production yields, Optimizes resources,

- Assures consistency and ensures measurements

are compatible with those made elsewhere.

• Ensures measurements are appropriate based

on National and International standards and

traceable.

• Avoid wastages due to uncertainties.

“

Calibration Benefits

Concept Stages Outcome

Process

Validation:

General

Principles

and

Practices

WEF: Jan'11

Stage 1- Process design: (The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities).

Stage 2 – Process Qualification: (During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing).

Stage 3 – Continued Process

Verification: (Ongoing assurance

is gained during routine production

that the process remains in a state

of control). PQR for each year

Robust

manufacturing

process.

Compliance to the

regulatory

requirement.

New FDA guidance on Process Validation

January 2011

Laboratory Controls

• Qualified personnel

• Effective sample management

• Approved specifications and methods

• Appropriate Qualified instruments

• Effective calibration program

• Effective preventive maintenance program

• Adequate SOP for OOS and OOT

• Trending of laboratory failures and CAPA

management.

Glassware

Controls

Quality by Statistical Process Control

Review of historical output of process to

identify the limits of a stable process and

source of error.

Quality by Inspection

Inspect Approve / Reject

Pharmaceutical Quality System

Training

Change Control

Planned Deviation

Incidence Investigation

Market Complaint

CAPA

Internal Quality Audit

Product Quality

Reviews/ Management

reviews

Pharmaceutical Quality System

Complaints Internal

Inspections

Supplier Audits

Regulatory Audits

Non-conforma

nces Deviations

Out of Specification

Out of Specification

Adverse Drug

Reactions

Adverse Events

Incoming Inspections

And others…

CAPA Sources

Road to Compliance

When it comes to ensuring drug product quality

and ultimately Consumer/Patient Safety . . . We

need to think and act globally!