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GOOD MANUFACTURING PRACTICE

GUIDED BY:Mr. Darshil ShahAsst. PROFESSORQA DEPARTMENTL.J.INSTITUTE OF PHARMACY

PREPARED BY:Vishal H. Parikh

ROLL NO : 06M.PHARM QARA

SEMESTER - II

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CONTENT INTERODUCTION

DEFINITION

HISTORY

PRINCIPLE

PROCESS OF GMP

VALIDATION

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WHAT IS GMP?

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GMP regulations are promulgated and enforced by the FDA and primarily housed within the Federal Food, Drug, and Cosmetic Act

GMPs are based on industry best practices that continually evolve as science, technology, and manufacturing techniques change

Comprehensive system for ensuring products are consistently produced and controlled according to quality standards

Designed to minimize risks involved in any pharmaceutical production that cannot be eliminated through testing of final product alone

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MAJOR RISKS IN PHARMACEUTICAL PRODUCTION

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Contamination of products (microbial, particulate or other)

Incorrect labels on containers

Insufficient active ingredient

Excess active ingredient

Poor quality raw materials

Poor formulation practices

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ANALYSIS OF SUBSTANDARD MEDICINES

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Incorrect Ingredient16%

Incorrect Amount17%

No Active Ingredient60%

Correct Ingredient7%

Source: (WHO)

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THE BREADTH OF GMP

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Raw or starting materials

Finished products

Premises and environment

Equipment

Personnel

Training

Hygiene

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GMP PRINCIPLES

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Must be built into manufacturing process

Prevents errors that cannot be eliminated through quality control of finished product

Ensures all units of a medicine are of the same (within specified parameters) quality

Poor medicines leads to loss of credibility for everyone: manufacturers, health care workers and governments

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GMP: 1972

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Davenport disaster Intravenous fluids were contaminated & killed 6 people. Prompted GMP regulations

Sulphathiazole tablets contaminated with phenobarbital (1941 - 300 people died/injured)

Thalidomide tragedy

1976 Medical Device Amendments 1972 and 1973 -Pacemaker failures reported 1975 - hearing-Dalkon Shield intrauterine device

caused thousands of injuries

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CGMPS DEFINED

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Methods, facilities, or controls used in the production of drugs, devices, foods, and biological. These manufacturing practices are designed to ensure the safety, identity, strength, quality, and purity of such products.

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GMPs Regulations Address

Documentation/Records

Process and production controls

Physical plant, laboratory, and facility design

Personnel / Quality control oversight

Proper validation of processes

Maintain and calibrate equipment

Clinical trial requirements

GMPs Regulations also Address

Materials Management

Packaging & Labeling

Storage & Distribution

Laboratory Controls

Rejection and Reuse Materials

Complaints & Recalls

Agents, Brokers, Distributors, Repackers, and Relabellers

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TEN PRINCIPLES OF GMPS

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Principle 1• Writing detailed step-by-step procedures that provide a roadmap

for controlled and consistent performance.

Principle 2• Carefully following written procedures to prevent contamination,

mixups and errors.

Principle 3• Promptly and accurately documenting work for compliance and

traceability.

Principle 4• Proving that systems do what they are designed to do by

validation work.

Principle 5• Integrating productivity, product quality, and employee safety

into the design and construction of facilities and equipment.

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TEN PRINCIPLES OF GMPS CONT…

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Principle 6• Properly maintain facilities and equipment.

Principle 7• Clearly defining, developing and demonstrating job

competence.

Principle 8• Protecting products against contamination by making

cleanliness a daily habit.

Principle 9• Building quality into products by systematically controlling

our components and product related processes such as manufacturing, packaging and labelling, testing, distribution and marketing.

Principle 10• Conducting planned and periodic audits for compliance and

performance.

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GMP – DOCUMENTATION & RECORDS

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Maintain laboratory and production records - notebooks, electronic files, etc.

Track records through research and production Batch Package Records (BPR) Equipment usage, calibrating, cleaning, maintenance Laboratory control records Distribution records Records maintained Electronic signatures on documents are acceptable,

provided they are authenticated and secure

GMP – PROCESS AND PRODUCTION CONTROL Standards for weighing, measuring, storing,

controlled

Time limits (if applicable and necessary)

In-process assurance, sampling and controls

Blending, mixing, diluting substances

Contamination controls

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GMP – PHYSICAL PLANT, LABORATORY FACILITIES DESIGN

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Design and Construction Single use versus multiuse facility, proper separation

Utilities Air quality - Filtered, recirculation, one-pass

Natural Gas

Dust, humidity, temperature

Water Municipal versus well versus sterilized

Lighting (placed to facilitate cleaning in all areas) Sewage and Refuse Sanitation and Maintenance

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GMP – PERSONNEL / QUALITY CONTROL OVERSIGHT

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Quality should be the responsibility of all persons involved in manufacturing

Each manufacturer should establish, document, and implement an effective system for managing quality that involves the active participation of management and appropriate manufacturing personnel

All quality related activities should be recorded at the time they are performed

There should be a quality unit(s) which is independent of production, and which fulfills both quality assurance (QA) and quality control (QC) responsibilities

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GMP – PERSONNEL / QUALITY CONTROL OVERSIGHT CONT..

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In order to verify compliance with the principles of GMP, regular internal audits should be performed in accordance with an approved schedule Audit findings and corrective actions should be

documented Here should be an adequate number of personnel

qualified by appropriate education, training and/or experience to perform and supervise the processesResponsibilities of all personnel engaged in the

manufacture should be documented in writingTraining should be regularly conducted by qualified

individuals

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GMP - VALIDATION

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Policies, intentions, approaches, systems, cleaning procedures, and all other protocols should be validated/documented

Critical parameters, limitations, ranges and standards should be established

A written validation protocol should be established that specifies how validation of a particular process will be conducted

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GMP – VALIDATION CONT…

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Appropriate qualification of equipment and ancillary systems should be completed Design qualification, Installation qualification, Operational

qualification, Performance qualification

Validate processes to ensure protocols are being followed Number of process validations depends on complexity of the

tasks

Cleaning and maintenance validation should be obtained

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GMP – EQUIPMENT MAINTENANCE & CALIBRATION

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Equipment used should be of appropriate design and adequate size, and suitably located for its intended use, cleaning, sanitization (where appropriate), and maintenanceProduction equipment should only be used

within its qualified operating range Closed or contained equipment should be used

whenever appropriate Any substances necessary for the operation of

equipment, such as lubricants, heating fluids or coolants, should not contact tested items so as to alter their quality

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GMP – EQUIPMENT MAINTENANCE & CALIBRATION CONT…

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Schedules and procedures (including assignment of responsibility) should be established for the preventative maintenance of equipment

Written procedures should be established for cleaning of equipment and its subsequent release for use in the manufacture

Control, weighing, measuring, monitoring and test equipment that is critical for assuring quality should be calibrated according to written procedures and an established schedule

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