Good Manufacturing Practices

Neeraj ShrivastavaQuality Assurance Team

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The Early Beginning1. 1900s house-

calls 2. Home

remedies, ointments and “miracle elixirs”

3. Entertainment and music

4. No regulations until 1902

Fig. 1. Animation of ancient medicine show

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Public Involvement• 1905 - The Jungle by

Upton Sinclair.• Exposure of unsanitary

conditions in meat packing plants.

• Public awareness and involvement.

• Pure Food and Drug Act.

• False labeling became illegal.

Fig. 2. The Jungle by Upton Sinclair

Fig. 3. 1906 Meat processing plant

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1941 Initiation of GMP Sulfathiaziole Tablets• Contaminated with phenobarbital.• About - 300 people died/injured.• FDA to enforce and revise manufacturing and quality control requirements. Fig. 4 1906 Certificate of Purity signed by

doctor

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1941 - GMP is born

• The beginning of modern standards for good manufacturing practices can be traced to an incident that began in December 1940, when the Winthrop Chemical Company of New York put on the market sulfathiazole tablets contaminated with Phenobarbital.

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1962 Kefauver-Harris Drug Amendments

Thalidomide Tragedy•Thousands of children born with birth defects due to adverse drug reactions of morning sickness pill taken by mothers.

Fig 5. Kennedy signing the Kefauver –Harris Drug Amendments

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Images of Thalidomide tragedy

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1976 Medical Device Amendments

•1972 and 1973 -Pacemaker failures reported

•1975 - hearing-Dalkon Shield intrauterine device caused thousands of injuries

Fig.6 President Gerald Ford signs the Medical Device Amendments

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1976 Medical Device Amendments

• Class I, II and III medical devices – based on degree of control necessary to be safe and effective.

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1980 Infant Formula Act•1978 - major manufacturer of infant formula reformulated two of its soy products•1979 - Infants diagnosed with hypochloremic metabolic alkalosis.

Fig.8 Parody on Infant Formula Act

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1980 Infant Formula Act

• Greater regulatory control over the formulation and production of infant formula• Modification of industry’s and FDA’s recall procedures

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HistoryFOOD AND DRUGS ACT1. FOOD AND DRUG REGULATIONS

DIVISION 2 : GOOD MANUFACTURING PRACTICES2. 1900’S- ADULTERATED FOOD

FIRST PURITY LAWS ENACTED3. 1930’S- SULFANILIMIDE

DRUGS HAD TO BE PROVEN SAFE4. 1960’S- THALIDOMIDE

DRUGS HAD TO BE PROVEN SAFE AND EFFECTIVE THROUGH CLINICAL TRIALS

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GMP Agencies Worldwide Enforcement• In US :- USFDA : United States Food and

Drug Administration.• In UK :- MHRA : Medicines and

HealthcareProducts Regulatory Agency.

• In Australia :- TGA : Therapeutic Good Administration.

• In India :-

FDA : The Ministry of Health, Food and drug Administration.follow Schedule-M Part of Drug & Cosmetic Act 1945.

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Introduction to cGMP

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cGMP Legal Principles

• Current = dynamic– Standards evolve over time current, to

emphasize that the expectations are dynamic.

• Good practices–Minimal standards–Not “best practices”• Unless “best” is, in fact, current minimal

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Objectives GMP Training Acquire basic knowledge of current Good Manufacturing Practices (cGMP).1. Good Manufacturing Practices.2. Contamination.3. General Employee Hygiene.4. Food Handling Practices.

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What are GMPs..?GMP is that part of Quality assurance which ensures that the products are consistently manufactured and controlled to the desired Quality standards appropriate for intended use

"GMP" - A set of principles and procedures which, followed by manufacturers for therapeutic goods, helps ensure that the products manufactured the required quality.

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Why are cGMPs important?• GOVERNMENT REQUIREMENT.• ENSURE QUALITY PRODUCT.• REDUCE REJECTS, RECALLS.• SATISFIED CUSTOMERS.• MAINTAIN MANUFACTURING CONSISTENCY.• COMPANY IMAGE AND REPUTATION.

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Good Manufacturing Practices

DEAL WITH CONTAMINATION:-•BY PEOPLE•BY FOOD MATERIALS•BY PACKAGING MATERIALS•BY HAZARDOUS MATERIALS•BY MISCELLANEOUS MATERIALS

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Hygiene

All employees working in direct contact

with food, food contact surfaces and

food packaging must conform to

hygienic practices. This protects against

food contamination by microorganisms

or unwanted material.

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Prevent contamination

Careless employee practices can cause product contamination.

The best way to avoid contamination is to prevent it.

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Any behavior that could result in food contamination such as eating, use of tobacco, chewing gum or other unhygienic practices, is not allowed in manufacturing & packing areas.

How do we prevent contamination?

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Hygiene & Communicable Diseases

• Clothing• Hair• Personal habits• Hand washing• Personal effects

and jewelry.

• Illness and disease • Injuries• Visitors• Training.

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Production employees- Bathe daily.- No perfume, aftershave, fragrant creams.- No jewellery.- No false nails or nail polish.- Fingernails should be trimmed short.- Use metal detectable bandages covered

with gloves.- No eating, drinking or chewing gum.

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Clothing - Everyone must wear pants and

covered sleeves.- Separate shoes (no open toes or

high heels) are to be worn in the factory.

- Personal belongings and street clothing must be stored in locker rooms.

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Illness• Doctor’s certificate on hiring• Inform your supervisor or HR if you

are ill with symptoms that could contaminate ingredients or products.• No medication allowed in factory.• Ensure that a clean bandage covers

any open wounds.

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Hand washingAll employees must wash their hands thoroughly:

• When they enter food handling areas• Before starting work.• After handling contaminated materials• After breaks.• After using toilet facilities.

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Personnel- Do not leave gloves, masks, etc. lyingaround while on break or at shift end. - Crates, boxes, containers or bucketsmust not be placed directly on thefloor.- Store brooms and dust pans at stations Provided.

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Product- Keep hand contact with ingredients to

a minimum.- Check ingredients for expiration dates

to ensure that fresh ingredients are used.

- Cooling product should always be kept covered.

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Equipment and containers

- Return tools and attachments to their proper place after use.

- Check product surfaces before starting equipment. Remove any foreign objects or dirt.

- Replace brushes that lose bristles.

GMP Categories•SALES•PREMISES•EQUIPMENT•PERSONNEL•SANITATION•RAW MATERIAL TESTING•MANUFACTURING CONTROL

•QUALITY CONTROL DEPARTMENT•PACKAGING MATERIAL TESTING•FINISHED PRODUCT TESTING•RECORDS•SAMPLES•STABILITY

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Sales

•NO DISTRIBUTOR … AND NO IMPORTER SHALL SELL A DRUG UNLESS IT HAS BEEN FABRICATED, PACKAGED/LABELED, TESTED, AND STORED IN ACCORDANCE WITH THE REQUIREMENTS OF THIS DIVISION.

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Premises & Equipments

• Permits effective cleaning.• Prevents contamination.• Orderly conditions.• Good state of repair.

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LOCATION AND SURROUNDINGS• Environmentally polluted areas and industrial

activities which produce disagreeable or obnoxious odour, fumes, excessive soot, dust, smoke, chemical or biological emissions and pollutants, and which pose a serious threat of contaminating food,

• Areas subject to flooding,• Areas prone to infestations of pests, and

areas where wastes, either solid or liquid, cannot be removed effectively.

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Personnel• Appropriate education, training and

experience.• Sufficient number of people• Receive cGMP training–Initial and continuing training as

relevant to job responsibilities.

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Sanitation• Sanitation Program to prevent contamination• Cleaning procedures for facilities & equipment• Pest control.• Environmental monitoring.• Documented evidence.• Keep contact surfaces clean and free of

contamination from tools, cords, cleaning utensils, machine parts, lubricants and paper.

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Sanitation• Keep everything off the floor and area clean

and floors swept.• Work areas should be cleaned regularly

throughout the shift.• Keep your immediate working area swept or

dust mopped. Wipe or mop up spilled liquids promptly.

• Scrape the floor around the work area after completing a job.

• Leave your work area clean at the end of your shift.

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Sanitation• Hygiene

1. Health and eye examinations.2. Report adverse health conditions.3. Clothing requirements• No direct skin contact with product.• Wash hands.• No jewelry or excessive makeup.

4. No smoking, eating, drinking, chewing, or keeping of plants in operations areas.

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Raw Material Testing• Each lot or batch of raw material is tested to– confirm the identity of the raw materials.–provide assurance that quality of the drug

in dosage form will not be altered by raw material defects.–assure that raw materials have the

characteristics that will provide the desired quantity or yield in manufacturing process.

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RM, PM and Finished Product Testing• Samples of incoming materials are

collected and tested before use.• Approved test methods and

specifications are used.• Results must conform to specifications

for release for use or sale.• Transportation and storage records.

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Manufacturing Control• Written procedures are established

and followed.–Master formulae, manufacturing

order and packaging order.• Critical processes are validated.• 2nd person verification of activities.• Quarantine system.• Labelling requirements.

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Manufacturing Control

• Recall Programme• Self-Inspection Programme• Ensure compliance with

vendors /contractors.

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Manufacturing Control (cont’d)

• Validation: the documented act of demonstrating that any procedure, process, equipment, material, activity, or system will consistently lead to the expected results.–Design Qualification (DQ)– Installation Qualification (IQ)–Operational Qualification (OQ)–Performance Qualification (PQ)

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Quality Control Department

• Quality Control Responsibilities–Testing of bulk components prior to

use by production.–Testing of finished product prior to

release for sale.–Stability program (in association with

QA).

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Samples and Stability• Samples–Retain samples of each lot of raw

material and finished product for specified period of time.

• Stability– Establish the length of time in

which the product meets all specifications.–Monitor the drug for this period of

time.

Quality Assurance• Wide-ranging concept – covers all matters that individually or

collectively influence the quality of a product.

• Totality of the arrangements– to ensure that the drug is continuously of

the right quality for the intended use.• Quality Assurance incorporates GMP–and also includes product design and

development, with special focus on process design.

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Quality Assurance Department

• Quality Assurance Responsibilities–Ensure cGMP compliance.–Review batch records, labels.–Release product, based on QC test results.–Authorize all master documents and SOPs.–Training, auditing.–Handling customer complaints.–Recall.

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Key Quality Terms• CHANGE CONTROL–Written procedure that describes the

action to be taken if a change is proposed to facilities, etc. used in fabrication, packaging, and testing of drugs or any change that may affect quality or support system operation.

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Key Quality Terms

• DEVIATION–Planned or unplanned temporary

departure from an approved process, specification or procedure with the potential to impact product quality.

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Records• Document all cGMP activities.• Use Good Documentation

Practices (GDP).• Records must be readily

available.• Needed to prove activities

were done.

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Good Documentation Practices• Documentation must be:–Permanent (blue ink)–Legible, clear, concise.–Accurate.–Timely.–Consistent.–Complete.

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Our GoalsSafety: Product is free of unwanted side effects when used appropriately by patient.Identity: Product exactly matches the labeling and related documents.

Purity: Product is free from contamination.Strength: Product has correct concentration, potency or therapeutic activity of active ingredient.Quality: Product meets all standards, expectations; performs as claimed and product made consistently.

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Summary1. PHARMACEUTICAL INDUSTRY IS REGULATED

BY GMP AND IT MUST BE FOLLOWED.2. GMP’S ENSURE DRUG PRODUCTS ARE SAFE,

PURE AND EFFECTIVE. 3. QUALITY SHOULD BE BUILT INTO THE

PRODUCT.4. GMP'S ARE VERY SIMILAR AND ARE REALLY

GOOD COMMON SENSE.5. GOOD PRACTICES COVER ALL ASPECTS OF

MANUFACTURING ACTIVITIES PRIOR TO SUPPLY.

Thank you..