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Good Manufacturing PracticeGuidelines
ICH Q7A
Presented byMalangsha S
cGMP Vs GMP
Good Manufacturing PracticeGuidelines
ICH Q7A
Presented byMalangsha S
cGMP Vs GMP
cGMP Vs GMP
It is my understanding that , Ultimately GMP& cGMP both the aim is same, means toprevention of the product from bad qualityentering the market to endover peoples's life.GMP applies to pharmaceutical andhealthcare products and help to maintain highstandards in these products.cGMP is to remind accepting countries that allguidelines must be followed with latest andcurrent production processes i.e employtechnologies and systems which are
It is my understanding that , Ultimately GMP& cGMP both the aim is same, means toprevention of the product from bad qualityentering the market to endover peoples's life.GMP applies to pharmaceutical andhealthcare products and help to maintain highstandards in these products.cGMP is to remind accepting countries that allguidelines must be followed with latest andcurrent production processes i.e employtechnologies and systems which are
cGMP Vs GMP
up-to-date in order to comply with theregulation.FDA (Food and Drug Administration) includedthe word “current” to ensure that regulatedfirms use the most current GoodManufacturing Practices (I believe that somefirms would actually use outdated versions ofthe GMP’s to manufacture regulatedproducts.(the FDA have made their standards
up-to-date in order to comply with theregulation.FDA (Food and Drug Administration) includedthe word “current” to ensure that regulatedfirms use the most current GoodManufacturing Practices (I believe that somefirms would actually use outdated versions ofthe GMP’s to manufacture regulatedproducts.(the FDA have made their standards
cGMP Vs GMP
immediately identifiable i.e cGMP; Otherinternational bodies such as the ICH, WHOuse the term GMP, as do Canada, Japan andthe EMEA (European authority). In FDA viewcGMP means following 21 CFR 210 and 211and no other.)
immediately identifiable i.e cGMP; Otherinternational bodies such as the ICH, WHOuse the term GMP, as do Canada, Japan andthe EMEA (European authority). In FDA viewcGMP means following 21 CFR 210 and 211and no other.)
Objective of
• To produce products conforming topredetermined specification
• To produce Product of consistentquality
• To minimize contamination
• To produce products conforming topredetermined specification
• To produce Product of consistentquality
• To minimize contamination
What do mean by
Any substances or mixture of substances intended to beused in the manufacture of drug (medicinal) product andthat, when used in the production of a drug, becomes anactive ingredient of the drug product. Such substances areintended to furnish pharmacological activity or otherdirect effect in the diagnosis, cure, mitigation, treatment,or prevention of disease or to affect the structure andfunction of the body.
Any substances or mixture of substances intended to beused in the manufacture of drug (medicinal) product andthat, when used in the production of a drug, becomes anactive ingredient of the drug product. Such substances areintended to furnish pharmacological activity or otherdirect effect in the diagnosis, cure, mitigation, treatment,or prevention of disease or to affect the structure andfunction of the body.
Regulatory Agencies |
The United StatesFood and Drug Administration
International Conference onHarmonization. This consist of EU, US and Japan.
The United StatesFood and Drug Administration
European Directorate of QualityMedicines
ICH Modules
Q1 - Stability testingQ2 – Validation of Analytical ProceduresQ3 – ImpuritiesQ4 – Evaluation – Pharmacopoeia TextsQ4 – Evaluation – Pharmacopoeia TextsQ5 – Biotechnology ProductsQ6 – SpecificationsQ7 – Good Manufacturing PracticesQ8 – Pharmaceutical DevelopmentQ9 – Quality Risk ManagementQ10 – Pharmaceutical Quality System
PrinciplesQuality should be the responsibility of all persons involved inmanufacturing.
Responsibilities of the Quality Unit(s)involved in all quality-related matters.
review and approve
QUALITY MANAGEMENT
Establishing a system to release packaging and labelingmaterials
Internal Audits (Self Inspection)Regular internal audits should be performed in accordancewith an approved schedule.
Performing product quality reviews
Document audit findings and corrective actionsAgreed corrective actions should be completed in a timelyand effective manner.
Responsibility for Production Activities
QUALITY MANAGEMENT
production facilities are clean and when appropriate disinfected
The responsibility for production activities should bedescribed in writing
All deviations are reported and critical deviations areinvestigated and the conclusions recorded
the necessary calibrations are performed and records kept
new and, when appropriate, modified facilities and equipmentare qualified.
the necessary calibrations are performed and records kept
validation protocols and reports are reviewed and approved
Product Quality ReviewRegular quality reviews of APIs should be conducted with theobjective of verifying the consistency of the process.
Personnel QualificationsThere should be an adequate number of personnelqualified by appropriate education, training and/orexperience to perform and supervise the manufactureof intermediates and APIs.
Personnel Hygieneshould practice good sanitation and health habits.
should avoid direct contact with intermediates or APIs.
PERSONNEL
Consultants should have sufficient education, training, andexperience, or any combination thereof, to advise on thesubject
Consultants
should avoid direct contact with intermediates or APIs.
Personnel suffering from an infectious disease or havingopen lesions on the exposed surface of the body should notengage in activities that could result in compromising thequality of APIs.
BUILDINGS & FACILITIES
Buildings and facilities should be:Located, Designed, and Constructed to facilitatecleaning, maintenance, and operations as appropriate tothe type and stage of manufactureminimize potential contamination.
designed to limit exposure to objectionablemicrobiological contaminants
Utilities should be:Qualified and appropriately monitored
action should be taken when limits are exceeded..Drawings for these utility systems should be available
Water should be:Water used in the manufacture of APIs should bedemonstrated to be suitable for its intended use.
BUILDINGS & FACILITIES
ContainmentDedicated production areas, air handling equipmentand/or process equipment, should be employed in theproduction of highly sensitizing materials, such aspenicillins or cephalosporins.
Lighting should be:Adequate lighting should be provided in all areas tofacilitate cleaning, maintenance, and proper operations.Adequate lighting should be provided in all areas tofacilitate cleaning, maintenance, and proper operations.
disposed of in a safe, timely, and sanitary manner.Containers and/or pipes for waste material should beclearly identified.
Sewage should be:
Buildings should be properly maintained and repaired andkept in a clean condition and establish written procedures
Sanitation and Maintenance:
Design and ConstructionEquipment should be of appropriate design and adequatesize, and suitably located for its intended use
Equipment Maintenance and Cleaning
preventative maintenance of equipment.
PROCESS EQUIPMENT
Written procedures should be established
Cleaning procedures should contain sufficient details toclean each type of equipment in a reproducible andeffective mannerEquipment should be identified as to its contents and itscleanliness status
Acceptance criteria should be defined and justified.
CalibrationControl, weighing, measuring, monitoring and test equipmentthat is critical for assuring the quality of intermediates or APIsshould be calibrated according to written procedures and anestablished schedule.
Computerized Systems
installation qualification and operational qualification shoulddemonstrate the suitability to perform assigned tasks
PROCESS EQUIPMENT
GMP related computerized systems should be validated
installation qualification and operational qualification shoulddemonstrate the suitability to perform assigned tasks
Computerized systems should have sufficient controls to preventunauthorized access or changes to data.
Changes to the computerized system should be madeaccording to a change procedure
If system breakdowns or failures would result in thepermanent loss of records, a back-up system should beprovided.
Documentation System and SpecificationsAll documents related to the manufacture of intermediates orAPIs should be prepared, reviewed, approved and distributedaccording to written procedures. Such documents can be inpaper or electronic form.
Equipment Cleaning and Use RecordRecords of major equipment use, cleaning, sanitizationand/or sterilization and maintenance should show the date,time (if appropriate), product, and batch number of eachbatch processed in the equipment, and the person whoperformed the cleaning and maintenance.
DOCUMENTATION &RECORDS
Records of major equipment use, cleaning, sanitizationand/or sterilization and maintenance should show the date,time (if appropriate), product, and batch number of eachbatch processed in the equipment, and the person whoperformed the cleaning and maintenance.
Records should be maintained including: name, identity,quantity; name of the supplier; supplier's control number(s),the number allocated on receipt & date of receipt;
Raw Material Records
Master (approved) labels should be maintained forcomparison to issued labels.
Master Production and Control Records)To ensure uniformity from batch to batch, master productioninstructions for each intermediate and API should be prepared,dated, and signed by one person and independently checked,dated, and signed by a person in the quality unit(s).
Batch Production and Control Records)Batch production records should include completeinformation relating to the production and control of eachbatch.
DOCUMENTATION &RECORDS
Batch production records should include completeinformation relating to the production and control of eachbatch.
Documentation of completion of each significant step in thebatch production
Laboratory Control RecordsLaboratory control records should include complete dataderived from all tests conducted to ensure compliance withestablished specifications and standards, includingexaminations and assays,
These records should be numbered with a unique batch oridentification number, dated and signed when issued.
General ControlsThere should be written procedures describing the receipt,identification, quarantine, storage, handling, sampling, testing,and approval or rejection of materials.should have a system for evaluating the suppliers of criticalmaterials.Changing the source of supply of critical raw materialsshould be treated according to Change Control.
MATERIAL MANAGEMENT
Receipt and Quarantineeach container or grouping of containers of materials shouldbe examined visually
Changing the source of supply of critical raw materialsshould be treated according to Change Control.
Materials should be held under quarantine until they havebeen sampled, examined or tested as appropriate, andreleased for use.
Each container or grouping of containers (batches) ofmaterials should be assigned and identified with adistinctive code, batch, or receipt number.
Sampling and TestingSampling should be conducted at defined locations
MATERIAL MANAGEMENT
Containers from which samples are withdrawn should be markedto indicate that a sample has been taken.
At least one test to verify the identity of each batch of materialshould be conducted,A supplier's Certificate of Analysis can be used in place ofperforming other tests
Re-evaluation
Materials should be handled and stored in a manner toprevent degradation, contamination, and cross-contamination.
Materials should be re-evaluated as appropriate todetermine their suitability for use
Rejected materials should be identified and controlled undera quarantine system
Storage
A supplier's Certificate of Analysis can be used in place ofperforming other tests
Production OperationsRaw materials for intermediate and API manufacturing should beweighed or measured under appropriate conditions that do notaffect their suitability for use.The processing status of major units of equipment should beindicated either on the individual units of equipment
Materials to be reprocessed or reworked should be appropriatelycontrolled to prevent unauthorized use.
PRODUCTION AND IN-PROCESS CONTROLS
In-process Sampling and Controls
time limits should be met to ensure the quality ofintermediates and APIs
Written procedures should be established to monitor theprogress and control the performance of processing
Intermediates held for further processing should be storedunder appropriate conditions to ensure their suitability foruse.
Time Limits
Materials to be reprocessed or reworked should be appropriatelycontrolled to prevent unauthorized use.
Production OperationsRaw materials for intermediate and API manufacturing should beweighed or measured under appropriate conditions that do notaffect their suitability for use.The processing status of major units of equipment should beindicated either on the individual units of equipment
Materials to be reprocessed or reworked should be appropriatelycontrolled to prevent unauthorized use.
PRODUCTION AND IN-PROCESS CONTROLS
In-process Sampling and Controls
time limits should be met to ensure the quality ofintermediates and APIs
Written procedures should be established to monitor theprogress and control the performance of processing
Intermediates held for further processing should be storedunder appropriate conditions to ensure their suitability foruse.
Time Limits
Materials to be reprocessed or reworked should be appropriatelycontrolled to prevent unauthorized use.
Blending BatchesBlending is defined as the process of combining materials withinthe same specification to produce a homogeneous intermediateor API.Blending processes should be adequately controlled, tested forconformance and documented
The batch record of the blending process should allowtraceability back to the individual batches that make up theblend.
PRODUCTION AND IN-PROCESS CONTROLS
Contamination Control
Precautions to avoid and prevent contamination
Residual materials can be carried over into successivebatches of the same intermediate or API if there is adequatecontrol.
The batch record of the blending process should allowtraceability back to the individual batches that make up theblend.
GeneralPackaging and labelling materials should conform to establishedspecifications.
Packaging MaterialsContainers should be clean, provide adequate protectionagainst deterioration or contamination
Records should be maintained for each shipment of labels andpackaging materials
PACKAGING & LABELING
If containers are re-used, they should be cleaned inaccordance with documented procedures
Containers should be clean, provide adequate protectionagainst deterioration or contamination
Label Issuance and ControlAccess to the label storage areas should be limited toauthorised personnel.Obsolete and out-dated labels should be destroyed.
Packaging and Labelling Operations
Labels used on containers of intermediates or APIs shouldindicate the name or identifying code, the batch number of theproduct, and storage conditions, when such information iscritical to assure the quality of intermediate or API.
PACKAGING & LABELING
Labels used on containers of intermediates or APIs shouldindicate the name or identifying code, the batch number of theproduct, and storage conditions, when such information iscritical to assure the quality of intermediate or API.
For intermediates or APIs with a retest date, the retest dateshould be indicated on the label and/or Certificate ofAnalysis.
Warehousing ProceduresFacilities should be available for the storage of all materialsunder appropriate conditions
Distribution ProceduresAPIs and intermediates should only be released fordistribution to third parties after they have been released bythe quality unit(s).
separate storage areas should be assigned for their temporarystorage until the decision as to their future use has been taken.
STORAGE & DISTRIBUTION
transported in a manner that does not adversely affect theirquality.
APIs and intermediates should only be released fordistribution to third parties after they have been released bythe quality unit(s).
Special transport or storage conditions for an API orintermediate should be stated on the label.
A system should be in place by which the distribution can bereadily determined to permit its recall.
General Controlsadequate laboratory facilities.
Any out-of-specification result obtained should beinvestigated and documented according to a procedure
documented procedures describing sampling, testing, approvalor rejection of materials
primary reference standard & Secondary reference standards,reagents and standard solutions
LABORATORY CONTROLS
Testing of Intermediates and APIs
primary reference standard & Secondary reference standards,reagents and standard solutions
An impurity profile describing the identified and unidentifiedimpurities present should normally be established for each API.
Appropriate microbiological tests should be conducted on eachbatch
Validation of Analytical ProceduresCertificates of Analysis
Authentic Certificates of Analysis should be issued for each batch
The Certificate should list each test performed in accordancewith compendial or customer requirements, including theacceptance limits, and the numerical results obtained (if testresults are numerical).
LABORATORY CONTROLS
The Certificate should list each test performed in accordancewith compendial or customer requirements, including theacceptance limits, and the numerical results obtained (if testresults are numerical).
Stability Monitoring of APIs
Expiry and Retest Dating
Reserve/Retention Samples
A documented, on-going testing program should be designed tomonitor the stability characteristics of APIs,
API expiry or retest date should be based on an evaluation ofdata derived from stability studies.
Validation Policy
Validation Documentation
The critical parameters/attributes should normally be identifiedduring the development stage or from historical data,
The company's overall policy, intentions, and approach tovalidation,
A written validation protocol should specify critical process stepsand acceptance criteria as well as the type of validation to beconducted
VALIDATION
Qualification
A written validation protocol should specify critical process stepsand acceptance criteria as well as the type of validation to beconducted
A validation report cross-referencing the validation protocolsummarising the results obtained, commenting on any deviationsobserved, should be prepared
Before starting process validation activities, appropriate qualificationof critical equipment and ancillary systems should be completed.Design Qualification (DQ), Installation Qualification (IQ),Operational Qualification (OQ) & Performance Qualification (PQ)
Approaches to Process Validation
Process Validation Programretrospective validation
There are three approaches to validation.Process Validation (PV), Prospective validation & Concurrentvalidation
VALIDATION
The number of process runs
Periodic Review of Validated Systems
The number of process runs
Critical process parameters
Process validation should confirm that the impurity profile foreach API is within the limits specified.
Systems and processes should be periodically evaluated to verifythat they are still operating in a valid manner.
Cleaning ValidationIn general, cleaning validation should be directed to situations orprocess steps where contamination or carryover of materialsposes the greatest risk to API quality.
VALIDATION
Validation of cleaning procedures should reflect actualequipment usage patterns
cleaning validation protocol
Validation of Analytical Methods
Sampling should include swabbing, rinsing, or alternativemethods
Analytical methods should be validated unless the methodemployed is included in the relevant pharmacopoeia or otherrecognised standard reference.
Appropriate qualification of analytical equipment
CHANGE CONTROLchange control system
Any proposals for GMP relevant changes should be drafted,reviewed, and approved
Evaluate potential impact of the proposed change on the quality
CHANGECONTROL
Evaluate potential impact of the proposed change on the quality
When implementing approved changes, measures should betaken to ensure that all documents affected by the changes arerevised.
REJECTION
Intermediates and APIs failing to meet established specificationsshould be identified as such and quarantined. The finaldisposition of rejected materials should be recorded.
Introducing back into the process and reprocessing by repeatinga crystallization step or other appropriate chemical or physicalmanipulation steps is generally considered acceptable.
REPROCESSING
REJECTION AND REUSE OFMATERIALS
Introducing back into the process and reprocessing by repeatinga crystallization step or other appropriate chemical or physicalmanipulation steps is generally considered acceptable.
Before a decision is taken to rework batches that do not conformto established standards or specifications, an investigation intothe reason for non-conformance should be performed.
REWORKING
All quality related complaints, whether received orally or inwriting, should be recorded and investigated according to awritten procedure.
There should be a written procedure that defines thecircumstances under which a recall of an intermediate or APIshould be considered.
COMPLAINTS ANDRECALLS
The recall procedure should designate who should be involved inevaluating the information, how a recall should be initiated, whoshould be informed about the recall, and how the recalledmaterial should be treated.
There should be a written procedure that defines thecircumstances under which a recall of an intermediate or APIshould be considered.
Recovery of Materials and SolventsSolvents can be recovered and reused in the same processes orin different processes,
RECOVERY & RETURNS
Fresh and recovered solvents and reagents can be combined ifadequate testing has shownSolvents can be recovered and reused in the same processes orin different processes,
Returned intermediates or APIs should be identified as such andquarantined.
Records of returned intermediates or APIs should be maintained.
Returns
If the conditions under which returned intermediates or APIshave been stored casts doubt on their quality, the returnedintermediates or APIs should be reprocessed, reworked, ordestroyed, as appropriate.
Solvents can be recovered and reused in the same processes orin different processes,
