good manufacturing practices for pharmaceuticals

GOOD MANUFACTURING PRACTICES FOR

PHARMACEUTICALS

2014/02/18 1Faculty of Pharmacy, Omar Al-Mukhtar University, Tobruk, Libya.

Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D

Department of PharmaceuticsFaculty of Pharmacy

Omer Al-Mukhtar UniversityTobruk, Libya.

E-mail: [email protected]

CONTENTS• Current GMP in manufacturing processes• Packaging and holding of drugs• Finished pharmaceuticals• General provisions• Organization and personnel• Building and facilities• Equipment• Control of components• Containers and closures• Production and process control• Packaging and labeling control• Holding and distribution• Records and reports• Returned savaged drug products• The inspection for compliance with GMP regulations• Controlled substances safeguards• References 2014/02/18 2Faculty of Pharmacy, Omar Al-Mukhtar University,

Tobruk, Libya.

Introduction


What is GMP ?(Good Manufacturing Practices)

• GMP is that part of Quality assurance which ensures that the products are consistently manufactured and controlled to the Quality standards appropriate to their intended use

• A set of principles and procedures which, when followed by manufacturers for therapeutic goods, helps ensure that the products manufacture will have the required quality.


Good Manufacturing Practices

• A basic tenet of GMP is that quality cannot be tested into a batch of product but must be built into each batch of product during all stages of the manufacturing process.

• It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product.


Some of the main risks are– Unexpected contamination of products, causing

damage to health or even death.

– Incorrect labels on containers, which could mean that patients receive the wrong medicine.

– Insufficient or too much active ingredient, resulting in ineffective treatment or adverse effects.

2014/02/18 Faculty of Pharmacy, Omar Al-Mukhtar University, Tobruk, Libya. 6

Why GMP is important

• A poor quality medicine may contain toxic substances that have been unintentionally added.

• A medicine that contains little or none of the claimed ingredient will not have the intended therapeutic effect.


QC

GMP

QA

GMP


QA: Quality AssuranceGMP: Good Manufacturing PracticesQC: Quality Control

QA, GMP & QC inter-relationship

It is the sum total of the organized arrangements with the objective of ensuring that

products will be of the quality required for their intended use

QA


GMP

Is that part of Quality Assurance

aimed at ensuring that products

are consistently manufactured to

a quality appropriate to their

intended use

GMP


QA, GMP & QC inter-relationship

Is that part of GMP concerned with sampling, specification & testing,

documentation & release procedures which ensure that the necessary & relevant tests are performed & the

product is released for use only after ascertaining it’s quality

QC


QC and QA

• QC is that part of GMP which is concerned with sampling, specifications, testing and with in the organization, documentation and release procedures which ensure that the necessary and relevant tests are carried out

• QA is the sum total of organized arrangements made with the object of ensuring that product will be of the Quality required by their intended use.


QC and QA

• Operational laboratory techniques and activities used to fulfill the requirement of Quality

• All those planned or systematic actions necessary to provide adequate confidence that a product will satisfy the requirements for quality


QC and QA

• QC is lab based • QA is company based


GMP

• The Quality of a formulation or a bulk drug depends on the Quality of those producing it

• GMP is the magic key that opens the door of the Quality

• In matter of GMP, swim with the current and in matter of Quality stand like a rock!


GMP helps boost pharmaceutical export opportunities

• Most countries will only accept import and sale of medicines that have been manufactured to internationally recognized GMP.

• Governments seeking to promote their countries export of pharmaceuticals can do so by making GMP mandatory for all pharmaceutical production and by training their inspectors in GMP requirements.


GMP Covers…• All aspects of production; from the starting materials,

premises and equipment to the training and personal hygiene of staff.

• Detailed, written procedures are essential for each process that could affect the quality of the finished product.

• There must be systems to provide documented proof that correct procedures are consistently followed at each step in the manufacturing process - every time a product is made.


GMP guidelines• GMP as per Schedule “M”• GMP as per WHO• GMP as per MCA now known as MHRA• GMP as per TGA• GMP as per US FDA• GMP as per ICH guidelines

WHO: World Health OrganizationMHRA: Ministry of Health and Regulatory AffairsTGA: Therapeutic Goods AffairsFDA: Food And Drug AdministrationICH: International Conference on Harmonization


GMP guidelines• GMP as per Schedule “M” www.cdsco.nic.in• GMP as per WHO www.who.int• GMP as per MCA now known as MHRA www.mca.gov.uk• GMP as per TGA www.tga.gov.au• GMP as per US FDA www.fda.gov• GMP as per ICH guidelines www.ich.org2014/02/18 Faculty of Pharmacy, Omar Al-Mukhtar University,

Tobruk, Libya. 19

GMP

• GMP in solid dosage forms• GMP in semisolid dosage forms• GMP in Liquid orals• GMP in Parenterals Production• GMP in Ayurvedic medicines• GMP in Bio technological products• GMP in Nutraceuticals and cosmeceuticals


Ten Principles of GMP1. Design and construct the facilities and equipments

properly2. Follow written procedures and Instructions3. Document work4. Validate work5. Monitor facilities and equipment6. Write step by step operating procedures and work on

instructions7. Design ,develop and demonstrate job competence8. Protect against contamination9. Control components and product related processes 10. Conduct planned and periodic audits


List of important documents in GMP

• Policies• SOP (Standard Operating Procedure)• Specifications• MFR (Master Formula Record)• BMR (Batch Manufacturing Record)• Manuals• Master plans/ files• Validation protocols• Forms and Formats• Records


10 attributes of a good document

1. Accurate2. Clear3. Complete4. Consistent5. Indelible6. Legible7. Timely8. Direct 9. Authentic10. Authorized


API Manufacturing Process


Secondary Manufacturing Dosage Forms


Secondary Manufacturing Process - Tablets


Secondary Manufacturing Process – Sterile parenteral for

injection


Biotechnology Manufacturing Process


Current GMP in manufacturing processes (cGMP)


What are cGMPs?• cGMP refers to the Current Good Manufacturing

Practice regulations enforced by the US Food and Drug Administration (FDA).

• cGMP provide for systems that assure proper design, monitoring and control of manufacturing processes and facilities.

• Adherence to the cGMP regulations assures the identity, strength, quality and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations


Why are cGMP so important

• A consumer usually cannot detect (through smell, touch, or sight) that a drug product is safe or if it will work.

• While cGMPs require testing, testing alone is not adequate to ensure quality.

• In most instances testing is done on a small sample of a batch (for example, a drug manufacturer may test 1000 tablets from a batch that contains 2 million tablets), so that most of the batch can be used for patients rather than destroyed by testing.


Packaging


Packaging and holding of drugs

• Care shall be taken when using automatic tablet and capsule counting, strip and blister packaging equipment to ensure that all ‘rogue’ tablets, capsules or foils from packaging operation are removed before a new packaging operation is commenced.

• There shall be an independent recorded check of the equipment before a new batch of tablets or capsules is handled.


Finished pharmaceuticals

Appropriate specifications for finished products shall include: -

• The designated name of the product and the code reference.

• The formula or a reference to the formula and the pharmacopoeial reference.

• Directions for sampling and testing or a reference to procedures.


General provisions

• The processing of dry materials and products creates problems of dust control and cross-contamination. Special attention is therefore, needed in the design, maintenance and use of premises and equipment in order to overcome these problems. Wherever required, enclosed dust control manufacturing systems shall be employed.


Organization and personnel

1. Responsibilities of quality control unit.

2. Personnel qualifications.

3. Personnel responsibilities.

4. Consultants.


Building and facilities1. Design and construction features. 2. Lighting.3. Ventilation, air filtration, air heating and

cooling. 4. Plumbing. 5. Sewage and refuse. 6. Washing and toilet facilities. 7. Sanitation. 8. Maintenance.


Equipment

1. Equipment design, size, and location. 2. Equipment construction. 3. Equipment cleaning and maintenance. 4. Automatic, mechanical, and electronic

equipment. 5. Filters.


Control of components1. General requirements. 2. Receipt & storage of untested components, drug product

containers and closures. 3. Testing and approval or rejection of components, drug

product containers and closures. 4. Use of approved components, drug product containers, and

closures. 5. Retesting of approved components, drug product

containers, and closures. 6. Rejected components, drug product containers, and

closures.7. Drug product containers and closures.


Containers and closures

• All containers and closures intended for use shall comply with the pharmacopoeial requirements. Suitable validated test methods, sample sizes, specifications, cleaning procedure and sterilization procedure, wherever indicated, shall be strictly followed to ensure that these are not reactive, additive, absorptive, or leach to an extent that significantly affects the quality or purity of the drug. No second hand or used containers and closures shall be used.


Production and process control

1. Written procedures; deviations. 2. Charge-in of components.3. Calculation of yield. 4. Equipment identification. 5. Sampling and testing of in-process materials

and drug products. 6. Time limitations on production. 7. Control of microbiological contamination.8. Reprocessing.


Packaging and labeling control

1. Materials examination and usage criteria. 2. Labeling issuance. 3. Packaging and labeling operations. 4. Tamper-evident packaging requirements for

over-the-counter (OTC) human drug products.

5. Drug product inspection. 6. Expiration dating.


Packaging and labeling control


Holding and distribution

1. Warehousing procedures.

2. Distribution procedures.


Holding and distribution• Prior to distribution or dispatch of given batch of a drug, it

shall be ensure that the batch has been duly tested, approved and released by the quality control personnel. Pre-dispatch inspection shall be performed on each consignment on a random basis to ensure that only the correct goods are dispatched. Detailed instructions for warehousing and stocking of Large Volume Parenterals, if stocked, shall be in existence and shall be complied with after the batch is released for distribution. Periodic audits of warehousing practices followed at distribution centers shall be carried out and records thereof shall be maintained. Standard Operating Procedures shall be developed for warehousing of products.


Holding and distribution


Records and reports1. General requirements. 2. Equipment cleaning and use log. 3. Component, drug product container, closure, and

labeling records. 4. Master production and control records. 5. Batch production and control records. 6. Production record review. 7. Laboratory records. 8. Distribution records. 9. Complaint files.


Returned savaged drug products

1. Returned drug products. 2. Drug product salvaging.


Returned savaged drug products

• Adequate areas shall be designed to allow sufficient and orderly warehousing of returned or recalled products.

• Segregation shall be provided for the storage of rejected, recalled or returned materials or products.


The inspection for compliance with GMP regulations

• Short description of the self inspection system indicating whether an outside, independent and experienced external export was involved in evaluating the manufacturer’s compliance with Good manufacturing Practices in all aspects of production.

• Periodic inspection of the garments shall be done by responsible staff.


Controlled substances safeguards

• Hazardous, toxic substances and flammable materials shall be stored in suitably designed and segregated, enclosed areas in conformity with Central and State Legislations.

• Highly hazardous, poisonous and explosive materials such as narcotics, psychotropic drugs and substances presenting potential risks of abuse, fire or explosion shall be stored in safe and secure areas. Adequate fire protection measures shall be provided in conformity with the rules of the concerned civic authority.


References

• EU Good Manufacturing Practice (GMP) Guidelines, Volume 4 of “The rules governing medicinal products in the European Union”

• US FDA current Good Manufacturing Practice (cGMP) for finished pharmaceuticals, 21 CFR, 210 and 211

• WHO Good Manufacturing Practices for pharmaceutical products, Annex 4 to WHO Technical Report Series, No. 908, 2003



E-mail: [email protected]

good manufacturing practices for pharmaceuticals

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