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Good Manufacturing Practices in 21st Century

By :Ady Sadek M.Sc. , P.Chem. proGamma Science Corporation 2011

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), MerckFrosstCanada ,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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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 . Adys 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 inprocess 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
1. 2. 3. 4. 5. Basic Requirements for GMP Clearly defined and systematically reviewed processes Critical steps of manufacturing processes and significant changes to the process are validated. Appropriate resources: personnel, buildings, equipment, materials Clearly written procedures 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. 2. 3. 4. 5. 6. Sampling approved by QC department Validated test methods Records Review and evaluation of production documentation Failure investigations for all deviations 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. 2. 3. 4. 5. 6. Establish QC procedures Reference standards Correct labelling Stability testing Complaint investigations 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


Training
Validation

CHANGE CONTROL

Document
Management
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?
The future Pharmaceutical Quality System

The Regulatory Quality System Quality Risk Management

Quality Risk Management (Q9)

For companies with : 1. Good design and control strategies 2. Good Risk Management strategies 3. Good Quality Systems

Quality Systems

Quality by Design (Pharmaceutical Development)

Quality by Design Reduced regulatory burden: (Q8) Reduction of

Existing GMP s

Quality Systems (Q10)

submissions on changes/variations Inspection of quality systems


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Tremendous Opportunity
Pharmaceutical Development: +
Quality by Design Q8

Quality Risk Management


Q9

+ Pharmaceutical Q10

Modern Effective

Quality Systems

Lower Risk Operations Innovation and Continual Improvement Optimized Change Management Process Flexible Regulatory Approaches
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Perhaps our vision should be updated?


Our vision: Quality By Design
The Regulatory Quality System

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Quality Risk Management (Q9)

Quality Risk Management

Quality
Systems

Product & Process Dev

(Q8)+

Quality by Design For companies implementin g Quality by Design


Reduced regulatory burden: Reduction of submissions on
changes/variations

Existing s GMP

Quality Systems (Q10)

Inspection of quality systems

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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

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. ii. iii. iv. v. vi. vii. viii. ix.

Customer Satisfaction Capacity and Utilization Do it right the first time Improve Operational Efficiency Compliance and Regulatory Affairs Business Processes and Systems Measurement Philosophy of Continuous Improvement PAT

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Pharmaceutical Plant Management in the 21st Century


2. Compliance and Quality Control
i. ii. iii. iv. v. vi. vii. viii. ix.

Product Release Quality Systems CAPA Program Self Inspection Program Incoming, in-process, Finished Goods Testing Stability Programs Documentation Technical transfers, Method Validations Paperless

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Pharmaceutical Plant Management in the 21st Century


3. Human Resources
i. ii. iii. iv. v. vi. vii. viii. ix.

Succession Planning Personnel Development Action Plans Hi Potentials/Mentorship Programs Union Negotiations Employee Relations Employee Benefits Retention Programs Management Training 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. ii. iii.

iv.
v. vi. vii.

viii.
ix. x. xi. xii. xiii.

Validation Master Plan IQ/OQ/PQ Cleaning Validation Computer Validation ERP Validation Change Control Program Documentation Control New Product Introduction Process Label Control Process Development Scale Up Clinical Considerations Formulation

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Pharmaceutical Plant Management in the 21st Century


6. Engineering
I. II.

III.
IV. V.

VI.
VII. VIII.

IX.
X.

Preventative Maintenance Predictive Maintenance Calibration Program Demand work orders Capital Programs Specialization Troubleshooting Utilities Daily Production Support 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
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
i.

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Thank you for inviting me Ady Sadek