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Good Manufacturing PracticesGMP Part IIGeneral 2 (GMP ) (GMP) (GMP ) ... . good manufacturing practice (GMP) . (GMP) . . (GMP ) .. (WHO ) . .... active ingredients .

adulterated (GMP ) ... .. .. . (GMP) .

.... .... (GMP ).. .. ( ! ) .. What is Good Manufacturing Practice ? (GMP).

GMP is a production and testing practice that helps to ensure a quality product. .

That combination of manufacturing and quality control procedures aimed at ensuring that products are consistently manufactured to their specifications... .

Good Manufacturing Practice is a set of regulations, codes, and guidelines for the manufacture of drug substances and drug products, medical devices, in vivo and in vitro diagnostic products, and foods. (GMP) ( ) .

Why GMP is important?.A poor quality medicine may contain toxic substances that have been unintentionally added. .

Why GMP is important?.A medicine that contains little or none of the claimed ingredient will not have the intended therapeutic effect. .

. . active ingredient . . . . GMP . GMP . 1Although there are a number of them, all guidelines follow a few basic principles: ( GMP ) :2 Manufacturing processes are clearly defined and controlled. .All critical processes are validated to ensure consistency and compliance with specifications. .

3Manufacturing processes are controlled, and any changes to the process are evaluated. .Changes that have an impact on the quality of the drug are validated as necessary. ( ) .

4 Instructions and procedures are written in clear and unambiguous language. . Operators are trained to carry out and document procedures. .

5 Records are made, manually or by instruments, during manufacture that demonstrate that all the steps required by the defined procedures and instructions were in fact taken and that the quantity and quality of the drug was as expected. .Deviations are investigated and documented. .

6 Records of manufacture (including distribution) that enable the complete history of a batch to be traced are retained in a comprehensible and accessible form. ( ) . The distribution of the drugs minimizes any risk to their quality. .

7A system is available for recalling any batch of drug from sale or supply. .Complaints about marketed drugs are examined, the causes of quality defects are investigated, and appropriate measures are taken with respect to the defective drugs and to prevent recurrence. :

8 GMP guidelines are not prescriptive instructions on how to manufacture products. (GMP ) They are a series of general principles that must be observed during manufacturing. .

9 When a company is setting up its quality program and manufacturing process, there may be many ways it can fulfill GMP requirements. (GMP).It is the company's responsibility to determine the most effective and efficient quality process. .

State of Control quality strength purity registration

premisesequipment methods personnel .. . compliance .. ELEMENTS OF COMPLIANCE DEFINITIONSCompliance The state of conformity of a regulated party (including a corporation, institution, individual or other legal entity) or a product with a legislative or regulatory requirement.. ( ) .Compliance Monitoring Actions planned to maintain regular surveillance in order to evaluate compliance with applicable requirements. This includes a wide variety of fact gathering and assessment activities such as inspections, market surveys and a product sampling program.

. . Compliance Verification Actions taken to verify compliance in response to information regarding known or suspected non-compliance with the applicable requirements of the regulations. This includes actions such as information gathering either off-site or via on-site visits ( ) ( ) . .

DEFINITIONSEnforcement Actions that may be taken to induce, encourage or compel compliance with the regulatory bodies. .

Inspection On-site monitoring and assessment against the applicable requirements of the regulations. Inspections are routinely conducted on a predetermined cycle or as required to assess compliance. . .

Inspector Any person designated as an inspector for the purpose of the enforcement of the regulations. .

Investigation Actions taken to gather evidence to support a case referral for potential judicial determination regarding specific violations of the regulations. .

(GMP ) .... (GMP ) .... . . (GMP ) .

GMP - Current Good Manufacturing Practices - ( cGMP) . . 2010 ( cGMP ) dietary supplements . ( GMP ) ( FDA ).

GMP ( WHO ) ( GMP) . Arab GMP (GMP ) GMP (GMP ) 1968 Medicines Act (GMP) .

Enforcement (GMP ) National Regulatory Agencies Medicines and Healthcare Products Regulatory Agency MHRA Therapeutical Goods Administration (TGA) Korea Food & Drug Administration - KFDA Medicines Control Council (MCC) Agencia Nacional de Vigilancia Sanitaria ANVISA FDA Central Drugs Standard Control Organization JFDA

( GMP) . ..pre-approval inspections (PAI)..

.. unannounced. FDA 704(A) .... reasonable time open for business

Harmonization harmonise ( GMP ) .. internationally standardized version of the requirements .... active substances17 cosmetics.ICH ICHInternational Conference on Harmonization ( GMP ) 1999 ( GMP ) .ICH ( GMP) ....Active Pharmacuetical Ingredients ( API ) . GMP.. API An active pharmaceutical ingredient is defined in ICH Q7A as any substance or mixture of substances intended to be used in the manufacture of a drug product and that, when used in the production of a drug, becomes an active ingredient in the drug product. ICH : Other good practicesGood laboratory practice (GLP), Good clinical practice (GCP), Good regulatory practice (GRP), Good Distribution Practice (GDP) Good Transportation Practice (GTP) .

GxPCollectively, these and other good-practice requirements are referred to as "GxP" requirements, all of which follow similar philosophies. GxP . GMP CoversALL 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. process .

GMP CoversThere 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. .

Scope of GMP (GMP ) : quality assurance premises equipment personnel documentation Scope of GMPproduction raw materials quality control complaints & recalls validation & self inspection Ten principles of GMPDesign and construct the facilities and equipments properlyFollow written procedures and InstructionsDocument work

. Ten principles of GMPValidate workMonitor facilities and equipmentWrite step by step operating procedures and work on instructions

. . . Ten principles of GMPDesign ,develop and demonstrate job competenceProtect against contaminationControl components and product related processes Conduct planned and periodic audits.

. . . . GMP basic requirements Manufacturing processes are clearly defined and controlled to ensure consistency and compliance with approved specifications;

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GMP basic requirements 2. Critical steps of manufacturing processes and significant changes to the process are validated;

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. .GMP basic requirements 3. All necessary key elements for GMP are provided, including the following: : - qualified and trained personnel, - adequate premises and space, - suitable equipment and services, - correct materials, containers and labels, - approved procedures and instructions, - suitable storage and transport. GMP basic requirements 4. Instructions and procedures are written in clear and unambiguous language; .

GMP basic requirements 5. Operators are trained to carry out and document procedures; .

GMP basic requirements 6. Records are made during manufacture that demonstrate that all the steps required by the defined procedures and instructions were in fact taken and that the quantity and quality of the drug was as expected. Deviations are investigated and documented . . GMP basic requirements 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; .GMP basic requirements 8. Control of storage, handling, and transportation of the drugs minimizes any risk to their quality; .

GMP basic requirements 9. A system is available for recalling of drugs from sale; .GMP basic requirements 10. Complaints about drugs are examined, the causes of quality defects are investigated, and appropriate measures are taken with respect to the defective drugs and to prevent recurrence. .

Certifying agenciesICH. www.ich.org

WHO. www.who.int

US FDA. www.fda.gov

EU/EMEA. www.emea.europa.eu

: ( ) : . .. ISOHACCPTQM6 SIGMALEANKAIZENISO International Standardization Organization 1946 132 . 75% 9000 1987 .

76ISO :

. .

77ISO

: 9000 : 9001 9002 9003 .

78ISO 9001: 20 .- 79ISO 9002 18 . .

80ISO 9003: .

81ISO 9004 : 9001 9002 9003 9004 .

82 HACCP . . : . Hazard Analysis of Critical Control Points 83HACCP Approach1 ( ) CCP - : . .84HACCP Approach2 . .

85 HACCP : Hazard Analysis. .

86 HACCP : Critical Control Points .

87 HACCP : critical limits . ( ). 88 HACCP : . .

89 HACCP : corrective action . monitoring . 90 HACCP : . .

91 HACCP : . . .

92 .

93 . . . .. /.. . . . . .94 . . . . . .95 . . . . .96 . .. . . . zero defect.

97 . . . . .

: .

98 . . .... . 99 . process 3.4 . . .

100 standard deviation process control chart. . .

101 : . . - . 102LEAN .

: .

1 ... :: .. .. .. . .. .1052: - gemba .. .. .. .. .... .1063: muda : (1) (2) . . : .. ..

1074 : inconsistency mura . .. . standardization.. .... .. .. .. . 1085 : .... .. muri

.. .. .109 management validationpersonnel premises equipment and systems raw materials including water management .. .... . validation . . .personnel . .... .. .. premises . . . .equipment and systems . raw materials . .Beyond GMPReduce pollution - Zero discharge

Beyond GMPAdaptation of environment friendly methods .

Beyond GMPConsideration for better and healthier life tomorrow. .

Beyond GMPConsideration of ethics in life. . .. .Beyond GMPOne should begin with end in mind otherwise it will be the beginning of the end.

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GMP (GMP ) . .. . ( WHO ) ( ICH ) .

GMP . . .. .. ..DocumentationBottom Line Document, Document, Document!!!

In FDA-speak:

If it is not documented . . .it did not happen! or, its a rumor!

.. .. !!!

FDA

.. .. !