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Good Manufacturing Practices in 21st Century By :Ady Sadek M.Sc. , P.Chem. proGamma Science Corporation 2011

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Good Manufacturing Practices

in 21st Century

By :Ady Sadek M.Sc. , P.Chem.

proGamma Science Corporation

2011

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proGamma Science Corporation

About Us

proGamma Science Corp: www.progamma.ca

Based in Montreal 1985. We provide implementation consulting and professional training in the

following major divisions of the Pharmaceutical, biopharmaceutical , Natural Health Products

and medical devices industries :

1.Quality assurance and Regulatory Affairs

2. Technical Operations : Product development, Manufacturing, Packaging, Validation services,

Automation , Process Validation , Equipment qualification

3. Quality System Management , Risk Assessment

4. Computerization including: Software Engineering, PAT, Computer system validation services

5. Professional cutting edge training

Partial Client List :

Abbott Labs Ltd , AeternaLabs , Astra-Zenica, Apotex, Agilent Technologies , Bioniche ,

Confab Labs., Church & Dwight Canada, Delmar Chemicals , Dermtek Pharmaceuticals Ltd.,

DraxisPharma Inc. PharmaLab, Pharmetics, Galderma Production, Health Canada (TPD), Merck-

FrosstCanada ,Novopharm , Novartis Pharmaceuticals ,Omega ValtecLtd. , PharmaScience,

Pfizer Canada ,ProDoc,RivaLabs , Sandoz , Sanofi-Aventis , Schering-Plough, Sandoz

,ratiopharm Inc, Tyco HealthCare, Valeant Pharma

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proGamma Science Corporation

Ady Sadek M.Sc, P.Chem

is president of proGamma Science Corporation, previously he spent 20 years

in the pharmaceutical industry with BioResearch, Schering-Plough and

Novartis Pharmaceuticals, holding positions such as Manager of Analytical &

Development Labs, Director of Quality and Director of QualityAudit. He

holds two master degrees in Organic and analytical chemistry and is an ISO

9000 lead auditor . Ady’s vast experience in GMP compliance ,process design

and validation started in 1981, when developing new formulations for FDA

submissions. He has been involved in many Plant GMP training , Audits

validations and his experience extends from formulation development to scale

up commercial batches and technology transfer. He has consulted and lectured

throughout Canada, USA and Europe to several multinationals.

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Agenda

The History

What is GMP?

Why we need GMP?

GMP sections

Modern GMP progress in 21st century

Pharmaceutical Plant management in the 21st Century

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What is GMP ?

Although quality assurance has its value in almost every industry, it has

special justification in the drug and medical device industries due to the

nature of the product and complex government regulations.

During the past 30 years many new regulations passed into law have

required drug and medical device industries to substantially modify their

business methods

One of the most well known sets of regulations that have had a major

impact on the drug and medical device industries are called Good

Manufacturing Practices (GMP)

a document published by Health Canada which sets out the minimum

activities required for drug manufacturers in Canada. Legally enforced

through the Canadian Food & Drugs Regulations, Division 2, Part C.

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These regulations describe the minimum requirements that

governments consider necessary for the production of human drugs,

veterinary drugs, or medical device products

GMP refers to the Good Manufacturing Practice Regulations

promulgated by Health Canada under the authority of the Food and

Drug Act.

The branch responsible for GMP of health Canada is : Health

Products and Food Branch Inspectorate (HPFBI)

These regulations, which have the force of law, require that

manufacturers, packager/Labeller, Importor and distributor of drug

product take proactive steps to ensure that their products are :

Safe

pure

and effective

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GMP regulations require a quality approach to

manufacturing, enabling companies to minimize or

eliminate instances of contamination, mix ups, and errors.

This in turn, protects the consumer from purchasing a

product which is not effective or even dangerous.

Failure of firms to comply with GMP regulations can

result in very serious consequences including recall,

seizure and fines.

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WHAT IS GMP?….

These regulations apply to:

Buildings

Equipment

Personnel

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WHAT IS GMP?….

Ensures that:

Procedures

Controls (QA)

Are available in place and followed

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GMP regulations address issues including recordkeeping,

personnel qualifications, sanitation, cleanliness, equipment

verification, process validation, and complaint handling.

Most GMP requirements are very general and open-ended,

allowing each manufacturer to decide individually how to best

implement the necessary controls.

This provides much flexibility, but also requires that the

manufacturer interpret the requirements in a manner which

makes sense for each individual business.

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Why we need GMP?

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Example

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GMP sections

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Quality Management

Determines and implements the “quality policy”

The basic elements are:

an appropriate infrastructure or “quality system” encompassing the Procedures, Processes, and Resources

the systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for “Quality”

The totality of these actions is termed “Quality Assurance”

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Adopted Health Canada QA Systems

1. Drugs are designed and developed in a way that takes into account the GMP requirements

2. Managerial responsibilities are clearly specified

3. Systems, facilities and procedures are adequate

4. Production and control operations are clearly specified and validated

5. Arrangements are made for the supply and use of the correct raw and packaging materials;

6. All necessary controls on intermediates, and any other in-process monitoring, and is carried out;

7. Outsourced activities are subject to appropriate oversight controls and meet GMP requirements;

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8. Fabrication, packaging/labelling, testing, distribution, importation, and wholesaling are performed in accordance with established procedures

9. Drugs are not sold or supplied before the quality control department has indicated certified that each lot has been produced and controlled in accordance with the marketing authorization and of any other regulations relevant to the production, control and release of drugs;

10. Satisfactory arrangements exist for ensuring that the drugs are stored, distributed, and subsequently handled in such a way that quality is maintained throughout their shelf life

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11.The effectiveness and applicability of the quality management system

is ensured through regular self-inspection and management review

12. Annual product quality review of all drugs should be conducted with

the objective of verifying the consistency of the existing process, the

appropriateness of current specifications for both raw materials and

finished product to highlight any trends and to identify product and

process improvements.

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Quality Management

GMP

Ensure that products are consistently produced

and controlled

Diminishes risks that cannot be controlled by

testing of product

Cross-contamination

Mix-ups

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Quality Management

Basic Requirements for GMP

1. Clearly defined and systematically reviewed processes

2. Critical steps of manufacturing processes and significant

changes to the process are validated.

3. Appropriate resources: personnel, buildings, equipment,

materials

4. Clearly written procedures

5. Trained operators

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Quality Management

6. Records :

manually or by instruments

demonstrate that all the steps are followed

Deviations are investigated and documented;

7. Records of fabrication, packaging, labelling, testing, distribution,

importation and wholesaling that enable the complete history of a lot

to be traced are retained in a comprehensible and accessible form

8. Control of storage, handling, and transportation distribution of the

drugs minimizes any risk to their quality

9. Recall system

10.Complaint handling

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Quality Management

Quality relationships

Quality Management

Quality Assurance

GMP

Quality Control

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Quality Management

Quality Control (QC)

QC is part of GMP that is concerned with

sampling, specifications, testing,

documentation and release procedures

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Quality Management

Quality Control (QC) Department

Each holder of a Establishment Licence should

have a QC Department

Independence from production and other

departments is considered to be fundamental

Under the authority of an appropriately qualified

and experienced person with one or several

control laboratories at his or her disposal.

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Quality Management

Basic Requirements for Quality Control

Resources Adequate facilities

Trained personnel

Approved procedures

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Quality Management

Basic Requirements for Quality Control

Tasks Sampling

Inspecting

Testing

Monitoring

Releasing/rejecting

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Quality Management

Basic Requirements for Quality Control

1. Sampling approved by QC department

2. Validated test methods

3. Records

4. Review and evaluation of production documentation

5. Failure investigations for all deviations

6. Ingredients comply with the marketing authorization

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Quality Management

Basic Requirements for Quality Control

7. Ingredients are of the required purity

8. Proper containers

9. Correct labelling

10. Release of batches by the authorized person

11. Retained samples of starting materials and

products

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Quality Management

Other Duties of the Quality Control Department

1. Establish QC procedures

2. Reference standards

3. Correct labelling

4. Stability testing

5. Complaint investigations

6. Environmental monitoring

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Quality Management

Assessment of Finished Products

Should embrace all relevant factors. For example:

production conditions

in-process test results

manufacturing documentation

compliance with finished product specification

examination of the finished pack

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Quality Management

Quality Control - summary

QC is part of GMP

sampling

specifications

testing

release procedures

recalls and complaints

decision-making in all

quality matters

authorization

definition of product

quality

laboratory operations

release decisions

investigation and

reporting

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Sanitation

Influence on quality:

Sanitation in a pharmaceutical plant influences the quality

of drug products as well as employee attitude.

The quality requirement for drug products demand that

such products be fabricated and packaged in areas that

are free from environmental contamination and free from

contamination by another drug.

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Examples

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Why is this Important?

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Why is this Important?

Hair nets are important for two reasons : They help keep hair out of products and help keep human hands away from hair

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Jewelry is not allowed

Jewelry should be limited to a plain wedding band. Jewelry can be a physical hazard and can be heavily contaminated with bacteria. Wearing jewelry can also be dangerous to the employee. For example, a necklace could get caught in a mixing machine and cause harm to the operator.

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Who is responsible

Integrates all your quality systems

Document Management

Valid

atio

n

CHANGE

CONTROL

Training

State of

Control

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Modern GMP progress in 21st century

FDA initiative 2002

Risk management approach

Process Analytical Technology PAT

Goal to ensure final product quality

Enhance process understanding and control

of manufacturing process

World acceptance of FDA initiative

ICH , FDA and EMEA new regulations

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Modern GMP progress in 21st century

ICH Q8 pharmaceutical development Quality by design

Design space

ICH Q9 quality Risk management Risk Management process

Risk Assessment and risk control

Risk Management tools : FMEA, FTA ....

ICH Q10 Pharmaceutical Quality System Product Realization

Knowledge Management and quality risk management

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Process Validation : the magic 3 is no longer magic

Process Design

Process qualification

Continued Process Verification

Quality by Design – CMC

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Why QBD?

Existing Existing GMP GMP ’ ’ s s

Quality by Design

(Pharmaceutical Development)

Quality Risk Management

The Regulatory Quality System

The future Pharmaceutical Quality System

Quality

Systems

Quality Systems (Q10)

For companies with : 1. Good design and

control strategies 2. Good Risk

Management strategies 3. Good Quality Systems

Quality Risk Management

(Q9)

Quality by Design

(Q8)

Reduced regulatory burden:

• Reduction of submissions on changes/variations

• Inspection of quality systems

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Tremendous Opportunity

Lower Risk Operations Innovation and Continual Improvement Optimized Change Management Process Flexible Regulatory Approaches

Pharmaceutical Development: Quality by Design Q8

Quality Risk Management Q9

Modern Effective Pharmaceutical Quality Systems Q10

+ +

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Perhaps our vision should be updated?

Our vision: Quality By Design

Reduced regulatory

burden:

• Reduction of

submissions on

changes/variations

• Inspection of quality

systems

Existing Existing GMP GMP ’ ’ s s

Quality Risk Management

The Regulatory Quality System

Quality

Systems

Quality Systems (Q10)

Quality Risk Management

(Q9)

(Q8)+ Product & Process Dev

Quality by Design

For companies implementing Quality by Design

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Process Validation and product life cycle

Progress in Quality system application in

pharmaceutical industry

ISO 9000

Six Sigma

Multivariate statistics to measure and better

improve process performance

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Modern Facility Management in the

21st Century

Overall Customer Satisfaction

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Pharmaceutical Plant Management in

the 21st Century

Course Outline

1. Operational Excellence

2. Compliance and Quality Control

3. Human Resources

4. Business Processes and Systems

5. Technical Services

6. Engineering

7. Environment and Safety

8. Regulatory Excellence

9. Business Development and Commercial

10. Supply Chain

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Pharmaceutical Plant Management in

the 21st Century

1. Operational Excellence i. Customer Satisfaction

ii. Capacity and Utilization

iii. Do it right the first time

iv. Improve Operational Efficiency

v. Compliance and Regulatory Affairs

vi. Business Processes and Systems

vii. Measurement

viii. Philosophy of Continuous Improvement

ix. PAT

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Pharmaceutical Plant Management in

the 21st Century

2. Compliance and Quality Control

i. Product Release

ii. Quality Systems

iii. CAPA Program

iv. Self Inspection Program

v. Incoming, in-process, Finished Goods Testing

vi. Stability Programs

vii. Documentation

viii. Technical transfers, Method Validations

ix. Paperless

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Pharmaceutical Plant Management in

the 21st Century

3. Human Resources

i. Succession Planning

ii. Personnel Development Action Plans

iii. Hi Potentials/Mentorship Programs

iv. Union Negotiations

v. Employee Relations

vi. Employee Benefits

vii. Retention Programs

viii. Management Training

ix. Recognition Programs

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Pharmaceutical Plant Management in

the 21st Century

4. Business Processes and Systems

i. ERP

ii. Planning/Forecasting

iii. Capacity Planning

iv. Purchasing

v. Inventory Control and Management

vi. Warehousing/Logistics

vii. Finance

viii. Shop Floor Control

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Facility Management for the 21st

Century

5. Technical Operations i. Validation Master Plan

ii. IQ/OQ/PQ

iii. Cleaning Validation

iv. Computer Validation

v. ERP Validation

vi. Change Control Program

vii. Documentation Control

viii. New Product Introduction Process

ix. Label Control

x. Process Development

xi. Scale Up

xii. Clinical Considerations

xiii. Formulation

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Pharmaceutical Plant Management in

the 21st Century

6. Engineering

I. Preventative Maintenance

II. Predictive Maintenance

III. Calibration Program

IV. Demand work orders

V. Capital Programs

VI. Specialization

VII. Troubleshooting

VIII. Utilities

IX. Daily Production Support

X. Project Management

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Pharmaceutical Plant Management in

the 21st Century

7. Environment and Safety

i. Recycle, reuse, reduce

ii. Regulations

iii. Hazardous Waste

iv. Inspections

v. Committees

vi. Employee Involvement

vii. Training

viii. Safety Programs

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Pharmaceutical Plant Management in

the 21st Century

8. Regulatory Excellence

i. Plant Master Files

ii. Licenses

iii. Government Inspections

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Pharmaceutical Plant Management in

the 21st Century

9. Business Development/Commercial

i. Pipeline/New Sales

ii. Current Account/Product Management

iii. New Product Management

iv. Negotiation

v. Pricing/Contracts

vi. Legal

vii. Market Research

viii. Marketing of product portfolio

10. Supply Chain

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Thank you for inviting me

Ady Sadek