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Quality Assurance (QA) Management Procedures

In this episode you will find Standard Operating Procedures for establishing quality

assurance practices, such as preparation, maintenance, definition, classification and change

Control of Quality and Master file documentation necessary for your products; recording andreporting procedure for deviations management; quality concern investigation Process;

customer complaint handling procedure; quality audit procedures; vendor assessment,

evaluation and certification procedure; rework procedures for the defective manufactured

products; procedures on training for your staffs and many other procedures according toyour need.

All procedures have reference of prepared Forms and Templates for effective record keeping

and reporting purposes. Forms are attached at the end of each procedure. Templates are

listed separately.

SOP list

Writing Standard Operating Procedure

This SOP describes standard SOP format that you can create and use immediately for your

quality procedures. This SOP has instructions on how to write a formal Operating Procedures

for your systems which your people can follow everyday.

GMP Documents

In this SOP you will find all type of quality and Technical/Master file documents to build up a

good quality management system for your manufacturing sites, definition of documents,

their classification, approval requirements and retention requirements. This procedure has

schematic diagrams for your understanding of how different types of documents areprepared and stored in a typical documentation database.

Quality Documentation Change Control

This SOP describes how to generate new quality documents or change control of existing

documents, review of quality documents, satellite file management, role of document

author, approver, document control officer and satellite file administrator. In this SOP you

will also find numbering systems of different quality documents like audit files, SOPs, forms,


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manuals, training files, QA agreements, project files etc and their effective archivingsystem.

Documentation Rule

This SOP describes the principles to be followed in GMP documents, entry of data and

information, signature requirements and correction technique of incorrectly entered data orinformation.

Document Control

In this SOP you will find mainly the role of document control officer during the initiation,

creation, circulation and approval of new quality related documents. It also describes the

procedure of modification and review of existing document using a documentation database.

Management of existing and superseded documents is also a part of this procedure. You willsee all the forms referred during the instruction are attached at the end of the procedure.

Master GMP Documents

This SOP particularly focused on the management of master file documents like

specifications, control methods, raw materials, finished goods and packaging specification

and test reports, formulation, stability files etc required to generate during the product

registration in the market. This SOP gives instruction on their creation, change control,

numbering system, approval requirements and maintenance in a simple master file

database. You will see all the forms referred during the instruction are attached at the endof the procedure.

Deviation Reporting

It is a regulatory requirement to capture all sorts of deviations evolves in your systems in

order to maintain the continuous improvement of your processes and systems. This SOP

describes how to categorize the deviations between production, audit, quality

improvements, technical deviations, customer complaints and environmental, health and

safety deviations. It describes the management responsibilities of initiating deviation,

capture data, analysis, investigation, determination of assignable causes, generation ofmanagement report and initiatives to be taken on corrective and preventative actions.

Product Shelf Life


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This simple SOP describes the meaning of shelf life and provides direction on how to

interpret shelf lives and storage conditions for your raw materials from the Certificate of

Analysis, determining expiry date for your finished products by use of raw material date of

manufacturing and their shelf lives.

Vendor Management

This SOP describes the procedure to be followed during the vendor assessment and vendor

evaluation for purchasing of raw materials, critical and non critical packaging components,

laboratory supplies, engineering supplies and imported finished goods from the vendor.These instructions are essential for approving prospective vendor.

Vendor Certification

This procedure aims to describe the process by which a vendor may be certified to supplymaterials or services. This procedure applies to vendors that supply a material or service to

be used at any stage of manufacture by operations. Here you will get the roles of each

department in the process to certify an approved vendor.

Product Complaint

This procedure covers the receipt, logging, evaluation, investigation and reporting system of

all complaints received from customers for the marketed products. This SOP contains step

by step instruction to be followed in the customer complaint management like numbering of

complaint, registration, evaluation of complaints, determination of assignable cause for thecomplaint deviation, implementation of corrective and preventative actions, trending ofcomplaints and handling of counterfeit products.

Product Review

This procedure provides a guideline to annual product review which is required to be

performed for each product produced for the commercial market to evaluate data, trends

and to identify any preventative or corrective action that would lead to product qualityimprovements and report them to management.

Rework

This SOP contains the step by step instruction to be followed when the rework of an in-

process or completed finished good is required. This SOP covers the reworks of in-process

manufactured goods where new batch number is introduced for the reworked part and


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rework of manufactured finished good keeping the same batch number. This sop alsodescribes how to create rework protocols for each individual case.

Product Identification and Traceability

The purpose of this SOP is to define the method used for the identification of all contributing

materials that could affect product quality and to ensure their full traceability. Here you will

find instruction on all the records and documents used for the identification and traceability

of incoming raw materials and out going finished goods.

GMP Audits

This SOP describes the process of planning, performing, reporting and follow-up of different

audits for your systems like Internal Quality audit, Vendor audit, Environmental Health and

Safety (EHS) audit, EHS workplace inspection, Housekeeping audit. This SOP also describesthe process to be followed by manufacturing personnel during an audit from a Regulatoryauthority.

Batch Documentation

This SOP describes the identification of all documentation relevant to a production process

in the form of Batch Documentation Checklists and to ensure their collection by

completion of the checklists by Authorized Persons. This procedure is based on an example

of tablet packaging process described in the Manufacturing category.

Batch Document Evaluation for Release

This procedure describes the process of collection, evaluation and record of batch related

document generated during the production of a batch before an authorized person can

release the batch for sale. This procedure is based on an example of tablet packagingprocess described in the Manufacturing category.

GMP Training

This SOP describes how to design and deliver GMP related trainings for your manufacturing

staffs, training assessment design, recording of assessment and preparation of trainingreports.

GMP Training Materials


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This simple SOP contains instructions on how to write training materials, identification of

training requirements, available resources, preparation of training aid checklists for yourmanufacturing staffs.

House Keeping Audit

This SOP describes the requirements, checklists and reporting procedure on housekeeping

audits. Individual checklist forms are attached at end of the procedure for different areas

like process, laboratory, engineering stores, warehouses. This procedure also describes thehandling of non-compliance found during the housekeeping audits.

Contract Work

The procedure describes the management and control of contract work provided by the

contractors for packaging and finished products for your company as well as control ofcontract works done by your company on behalf of others.

Raw Material and Packaging Components Sourcing

The purpose of this SOP is to describe the process for approval of an external

vendor/manufacturer supplying products to your company. It covers raw materials

(including bulk products for subsidiaries and contract manufacturers), critical packaging

components in contact with product and imported finished goods. The SOP also references

affiliated documentation detailing the scope of active materials used and the approved

manufacturers of these materials.

Quality Investigation Process

This procedure contains instruction to be followed when conducting Investigations and to

raise and assess Deviation Report when an Investigation or Incident Investigation occurs.

This procedure is to be used in conjunction with Deviation management, which covers the

approval and follow-up activities associated with a Deviation Report. Here you will find

collection of information for an incident or a deviation, steps to be followed for a crossfunctional investigation, reporting and implementing of the outcomes of investigation.

Change Management System

This procedure provides a standardised procedure and framework for initiating, authorising,planning and implementing any change to a GMP system.


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Product Change Management requires that all planned permanent changes that have the

potential to impact on regulatory filings or the quality of an active pharmaceutical ingredient

or drug product must be evaluated, reviewed and approved. It also requires that the site

procedure must include provision for effectively tracking all quality and regulatory changesand provide a mechanism for review and approval by the Site Quality Team for all changes

Cross functional investigation

This procedure describes the guidelines for initiating, communicating, conducting and

documenting Cross-Functional Investigations (CFI) related to process, system, product,

material, facility and laboratory deviations. A CrossFunctional Investigation is an extended

investigation conducted in order to identify a Root Cause. Quality Control Laboratory

Procedures

In this episode you will find practical procedures on Retest Dating of Raw Materials;Calibration Policies for Laboratory Instruments; Archiving Laboratory Documentation;

Management of Reference Substances; GLP requirements of Laboratory Workbook; Creation

of Certificate of Analysis; Managing Analytical Reagents; Laboratory Waste Management;

Managing of Retention Samples in Laboratory; Laboratory Supplier Approval; Laboratory

Results-Out Of Specification Investigation; Raw Materials-Laboratory Testing and

Documentation; Finished Goods-Laboratory Testing and Documentation; Preparation and

Maintenance of Stability Protocols (pharmaceuticals); Stability and Trial Testing Procedure(pharmaceuticals).

SOP lists

Retest Dating

The purpose of this procedure is to describe how to run the expired stock report; to describe

how to define the requirements for the retesting and assignment of storage periods for

active ingredients, excipients and raw materials; to instruct retesting procedure and todetermine the status of a finished goods batch with a shorter shelf life.

Calibration of Laboratory Instruments

This SOP describes the calibration policies of laboratory instruments/ equipments. It

describes labeling and security requirements of laboratory instruments/ equipments. This

SOP also describes the investigational steps to be required in the case of failed calibration.


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Archiving of Laboratory Documentation

This procedure describes retention and disposal procedures of laboratory documentation,

general laboratory documentation system that includes handling of rejected raw material

and finished product reports, finished goods certificate of analysis, finished goods register,

raw material certificate of analysis, raw material register, trend cards, procedure for long

term document retention.

Reference Substances

This SOP describes the ordering, referencing, storing, coding, use and general register

maintenance of primary and impurity reference substances, primary reagent reference

solutions, secondary raw material reference substance, assay testing procedure of

secondary raw material reference substance, use of secondary raw material reference

substance in the laboratory routine analysis, determination of expiry date and re-test date

of reference substances.

Laboratory Workbook

This SOP describes types of laboratory workbooks, general and GMP requirements of using

workbooks, analytical data entry in the workbook, formatting of laboratory workbooks for

routine testing, experiments and trials, workbook retention policy, instruction on data entryfor incomplete experiments and additional data.

Certificate of Analysis

The purpose of this procedure is to define the content and format of a Certificate of Analysis

(C/A) and Certificate of Manufacture (C/C) and to provide guidance for issuing a Certificate

of Analysis or Certificate of Manufacture and to locate the appropriate data required for this

task.

Analytical Reagents

This procedure identifies the need for all analytical reagents and solutions prepared from the

reagents, to have an assigned expiry date and storage conditions recorded on the label.Here you will find the procedure for purchase and management of analytical reagents andlaboratory prepared reagents.

Laboraotry Waste Management


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This simple procedure describes how to dispose off laboratory generated wastes of toxic,explosive, flammable, corrosive, oxidizing and biologically damaging natures.

Laboratory Retention Samples

The purpose of this SOP is to describe the finished good and raw material sample retention

procedures, products manufactured and/or received onsite and/or chemically tested by theLaboratory.

Laboratory Supplier Approval

In this simple SOP you will find the procedures for approving laboratory suppliers and

criteria for the purchase of equipment, instrumentation, consumables, durables and

glassware for the laboratory.

Laboratory Results Out Of Specification Investigation

This procedure describes the actions to be taken by an analyst in the event the result of a

test does not conform to raw material/components or finished products specifications for

physical and chemical tests. An out of specification (OOS) result does not necessarily mean

the batch under investigation fails and shall be rejected. The OOS results shall be

investigated and the findings of the investigation, including re-test results shall beinterpreted to evaluate the batch and reach a decision regarding release or rejection.

Laboratory Testing for Raw Materials

This SOP describes the procedure for sampling, location, pre-testing, testing and

documentation of all raw materials and components subject to test, out of specification

results, microbiological tests and release procedure for passed raw materials andcomponents.

Laboratory Testing For Finished Products

This SOP describes the procedure for sampling, location, pre-testing, testing and

documentation of all finished products subject to test, reagents and standards to be used

for analysis, management of out of specification results, microbiological tests and releaseprocedure for passed finished goods.

Stability Protocols


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This procedure describes the preparation and management of Stability Protocols for

marketed products. This procedure is applicable to all protocols for stability studies on

commercial products. The responsibility of the commercial Site Stability Manager for

creating and maintaining protocols that are required for studies that came as a result ofvalidation or process deviation.

Trial Testing

To describe the steps necessary to ensure the effective control of stability and trial testing

programs of new and existing products. This procedure is focused on setting up of stability

programs, testing, reporting, general sampling procedure for stability programs, data

generation and analysis, annual maintenance of stability, new product stability procedure,

procedure for in-house trials, reporting and interpretation of trials and conclusion of the trailprogram.

Preparation of Disinfactant Solution in the Lab

This procedure describes the preparation and use of disinfectant solutions (70% IPA) in theSterile Area and also outlines the procedure for Integrity testing of the 70% IPA Filter.

Laboratory Analytical Determinations

The purpose of this document is to describe the operational procedures to be followed when

carrying out analytical analyses in the Quality Control Laboratory at a GMP site. This SOP

outlines the system suitability (SST) and acceptance criteria for analysis by HPLC and UV-VIS Spectrophotometer; e.g. Composite Assay (Assay), Degradation Products / Related

Substances / Impurities (Degradation), Content Uniformity (CU), and Dissolution tests for

all Raw Materials, In-process, Finished Products and Stability Samples in the QC Laboratory.

This SOP also covers the number of standard and samples to be weighed for HPLC and UV-VIS Spectrophotometers analyses.

HPLC Reproducibility, Column Performance and Testing Guidelines

The purpose of this document is to describe the Reproducibility checks of the High

Performance Liquid Chromatograph, Column Performance and guidelines for assay testingon the HPLC.

HPLC Method Development & Validation Procedure


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The validation of an analytical method is the process by which it is established that the

performance characteristics of the method, such as Precision, Accuracy, Specificity,

Linearity, Limit of Detection (LOD), Limit of Quantitation (LOQ) and Robustness meet the

requirements for the intended applications. This SOP refers specifically to HPLC. However,

the same principles may be applied to validations of other types of analytical procedures.

Well-characterised reference materials with documented purity should be used to performthe validation.

The optimum wavelength for a method can be found by acquiring the chromatographic data

on a PDA detector over a large wavelength range, (e.g. 200-400nm). The optimum

wavelength is the wavelength, which maximises the response for all the components of

interest, but is outside the absorbance for the mobile phase. Before validating an HPLC

method, its Specificity must be determined. If the method does not comply with the

Specificity requirements, the method must be modified until the acceptance criteria are

met. Hence it is essential that the Specificity be adequate, before Precision, Linearity and

Accuracy, etc. are performed.

Laboratory In Process and Finished Product Quality Control

This purpose of this document is to outline the procedure to be followed for the receiving,

scheduling, testing, reporting, reviewing, approval and release of In-process and FinishedProducts in the QC Laboratory at a GMP site. Microbiology (Sterility) Laboratory Procedures

In this area you will find Standard Operating Procedures on Entry Procedure to Sterile FillingAreas, Validation of Aseptic Gowning Procedures, Microbiological Data Recording Procedure,

Destruction of Biological Waste in the Microbiology Laboratory, Depyrogenation of Glassware

In Micro. Lab. Oven, Media Preparation in Microbiology Laboratory, Aseptic Media Filling and

Micro. Integrity Leak (Soup) Testing Procedure, Aseptic Media Filling and Soup Test

Guideline, Environmental and Plant Hygene Monitoring Procedure, Microbial Limit Testing

Procedure by Using Laminar Flow Cabinets etc and many other procedures according to yourneed.


and reporting purposes. Forms are attached at the end of each procedure. Templates arelisted separately.

SOP List


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Sterile Entry

This SOP outlines the gowning procedure that must be followed by each and every person

who enters a Sterile Area. The procedure is designed to reduce the risk of contaminatingproduct with bacteria and/or particles

Aseptic Gowning Validation

Aseptic gowning is the ability to complete the gowning procedure without compromising the

sterility of the garment. This SOP outlines the sterile gowning validation procedure as

required for the final sign off for the initial sterile training and the revalidation of currently

trained Operators, Fitters, Electricians and Cleaners and all organization staff who areauthorized to enter Sterile areas.

Microbiological Data Recording

To describe procedures for the recording of Microbiological data using the in-house hard

copy and computerized recording system. All documents containing test results are legal

documents and therefore it is imperative that all the information required is recorded

accurately. Any changes/corrections to be made must be signed with that persons initials

and dated.

Biological Waste Destruction

To describe procedures for destroying all Laboratory Biological Waste to comply withQuarantine Regulations

Depyrogenation of Glassware

To outline the procedure for the depyrogenation of glassware using the Microbiology

Laboratory Qualtex Oven.

Media Preparation

To describe the procedures for the preparation of microbiological media for use in theMicrobiology Laboratory.

Micro. Integrity Leak (Soup) Testing


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One of the requirements of cGMP is a periodic evaluation of all aseptic processes by filling

media into the appropriate containers under normal production conditions. The media fill

should reflect the sterility of the entire process from the Sterilizing filter to the filled primary

container and should include all subsequent manufacturing steps. This SOP outlines the

procedures for both Media Fills and Microbiological Leak Tests. For Validation purposes, a

Microbiological Leak Test (Soup test) or a separate Protocol to verify the entire process fromthe Bioburden Reduction Filter to the primary container may be required.

Aseptic Media Filling and Soup Test

Media Fills are designed to verify the entire process, equipment and staff. This process

simulation should be performed as initial validation with three (3) consecutive satisfactory

simulation tests per shift and repeated at defined 6 monthly intervals (twice per year per

process per shift) and after any significant modification to the HVAC-system, equipment,

process and number of shifts for aseptically filled process. Soup test has to be conducted at

least once per year per shift for terminally sterilised lines and non-sterile process. Validationand re-validation media fills are to assure the sterility of the entire process. This process

simulation test should imitate as closely as possible the routine aseptic manufacturing

process and include all the critical subsequent manufacturing steps. The Media Fill should

challenge the worst case situation and should include all the possible interventions of a

normal production run. The duration of the media run should be at least 4 hours or half a

production shift to allow for all routine interventions.

Environmental and Plant Hygiene Monitoring

Description for Microbiological testing of areas of the environment which may influence oraffect product performance and/or quality-including, air, surfaces, personnel, clothing and

disinfectants. Daily monitoring of sterile grade areas during production is to be conducted

by trained production staff. The Microlab is to ensure that the necessary plates are delivered

on a daily basis so monitoring can take place. Once a test has been completed, the

responsible operator is to initial the plate and make sure that the batch number of the batch

running at the time of the test is written on the plate. Plates will be labeled with prompts to

ensure this isnt forgotten. If no batch is running at the time of the test N/A should be put

on the plate instead of a batch number. If an area of concern is noted during routine daily

testing, inform Micro immediately so that further steps can be taken.

Microbial Limit Testing Using Laminar Flow Cabinets.

To describe the procedures to be followed in conducting Microbial Limit Tests in the Laminarflow Cabinets in the Microbiology Lab.


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Microbiological Monitoring of Plant Water Systems

In this SOP you will find Sampling Procedure for Bioburden and Endotoxin Samples,

Bioburden Test Method and Results, Endotoxin Testing of WFI (Distilled Water), Bioburden

and Bacterial Endotoxin Alert and Action Levels, Diagrammatic Representations of a typical

purified Water Systems, Bioburden Waste Tank Water Sampling, Clean Steam Sampling &

Testing, OOL/OOS Result Actions etc

Sterility Testing Procedure

This sop is to describe the procedure for sterility testing of aqueous, injectable and

terminally sterilized non injectable products. To explain the correct interpretation of sterilityresults and to outline Stasis requirements for used sterility canisters.

Determination of Heat Resistance of Spore Forming Organisms

This SOP describes the method for calculating the Heat Resistance Factor, (D-value),of

spore-forming organisms. D-Value is defined as the time required for a population of a pure

culture of microorganisms to be decreased by 90% when exposed to a fixed temperature,e.g. 121C (+1C).

Identification of Microorganisms to Genus and Species Level

To describe the procedures for the preliminary identification of bacteria isolated from Plant

Water, Environmental, Personnel, Product and Raw Material sources. Bacteria that willrequire identification (ID) to at least genus level include organisms isolated from the

manufacturing environment, personnel, in-process and finished products, plant water and

other miscellaneous sources. SOPs detailing the microbiological testing procedures for each

of these samples will indicate the required level of ID of recovered organisms. The following

sections detail the procedures for the preliminary ID of micro-organisms. Further ID tospecies level is to be conducted for conformation.

Micro Evaluation on Bioburden, Non sterile and Raw Materials

This SOP describes the procedures for Microbiological Evaluation of Bioburdens, non-sterileProducts & raw materials. Bioburdens includes: Batches prior to membrane filtration, i.e.

solutions; Batches prior to sterilization i.e. filled containers; Face masks; IPA. This

procedure includes Equipment preperation for Non-sterile testing, Bulk Solution Bioburden

(BSB) Sampling; Filled Container Bioburdens (FCB); Raw Material Bioburdens (RMB);

Surgical Face Masks; Isopropyl Alcohol (70% IPA); Speciation Procedures for Organisms

found in Non Sterile Products and Raw Materials; Out-of-Specification Procedures for Non


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Sterile Products and Raw Materials; Retest and Repeat Procedures for Non-Sterile Productsand Raw Materials.

Bacterial Endo Toxin Testing (LAL) - Gel Clot Method

To describe the procedure for conducting a Bacterial Endotoxin Test by the LAL Gel-Clot

method. The gel-clot method for bacterial endotoxin testing described in this SOP is based

on the fact that Limulus Amoebocyte Lysate (LAL) will form a firm gel in the presence of

bacterial endotoxin.

Bacterial Endo Toxin Testing kCA Method

The purpose of this SOP is to outline the theory of Bacterial Endotoxin testing using Kinetic

Chromogenic Analysis (KCA). And to outline the procedure for routine product testing,

operator / reagent verification and product validation by KCA using the BioWhittaker KQCL(brand) reader. This Procedure also describes the routine maintenance procedures for theBioWhittaker KQCL (brand) reader.

Stock Suspension of Micro Organism

The objective of this SOP is: To describe the method for preparing and maintaining stock

suspensions of vegetative microorganisms and spores used within the Microbiology

Laborator;. To explain the procedure for growth promotion and media verification

requirements for all media used within the Laboratory; To outline requirements for Stasis

testing on sterility canisters after sterility testing has been completed.

Sterile Sampling Procedure for Microbiology Laboratory

To detail the procedure for taking Microbiological samples for Sterility testing, Bacterial

Endotoxin testing, Bioassay testing, Microbial Limit test and Micro status testing throughout

Production. This procedure includes sterilization charts, Settle plates (Fallout plates) andPersonnel monitoring.

Gel Clot Validation Method

The gel clot validation method for Bacterial Endotoxin testing described in this SOP, is to

determine the level of Inhibition/Enhancement of products on the LAL test for endotoxins

within the allowable Maximum Valid Dilution (MVD) for each type of product. The Gel-Clot

techniques detect or quantify endotoxins based on clotting of the LAL reagent in the

presence of endotoxin. To be determined for each type of product, using the highest and


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lowest concentration of active. If either concentration shows inhibition or enhancement,

then each remaining concentration must be tested. At least three (3) Production batches ofeach finished product should be tested for inhibition and enhancement.

Laboratory Investigation for Atypical and OOS Results

The purpose of this procedure is to provide guidance when investigating microbiology

laboratory out of specification (OOS) results associated with raw material samples, in-

process samples and finished product samples. This procedure describes the actions taken

by Microbiology Laboratory staff in the event the result of a test does not conform to

company specifications for microbiological release. This procedure will also provide guidance

for re-testing raw material samples, in-process samples and finished product samples when

it has been decided through a laboratory investigation that retesting is justified. Retesting

should be viewed as an investigational tool to aid in determination of the root cause of thediscrepant laboratory result.

IPA Contamination Testing Procedure

To describe the test sometimes used to check the purity of the IPA used in the factory as adisinfectant.

Control of Microbiology Test Methods

This document details the writing, control, and distribution of Microbiological Test Methods

(MTM) for use in the GMP Microbiology Lab. This procedure applies to Microbiological TestMethods that are controlled from beginning to end by the Microbiology Lab Manager.

Handling of Test Sample in Microbiology Laboratory

This document details the handling of test samples (raw materials, bulk product and

stability samples) processed for Microbial Limits Testing (MLT) in the Microbiology

Laboratory. This procedure applies to samples tested for Microbial Limits within the Quality

Control Microbiology Laboratory.

Documentation Requirement For Micro Test Method Validation

The procedure describes the process for accessing and using protocol templates for

documentation of test method validation activities in the Microbiology laboratories. This

procedure applies to Microbiology personnel responsible for the validation or verification of

microbiological test methods. The procedure outlines the requirements for approval of


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method development protocols, validation/verification protocols and final validationsummary reportsProcess, Cleaning and Methodology Validation Procedures

In this area you will find procedures on validation-concept and procedure, revalidation

procedure, method validation procedure, procedure for cleaning validation, validation oflaboratory instruments, equipment specification and qualification and in-house trialprocedure.


and reporting purposes. Forms are attached at the end of each procedure. Templates arelisted separately.

SOP list

Concept and Procedure of Validation

This procedure describes general validation concepts and practices, the way processes and

systems must be qualified/validated and the confirmatory documentation required. Here you

will find the philosophy of validation, responsibilities, validation approaches of design

qualification, installation qualification, operational qualification, performance qualification,

cleaning validation, method validation, computer validation, general and specific criteria of

validation, validation documentation and change control, validation reporting, guidelines of

validation acceptance criteria.

Revalidation

This procedure contains step by step instruction on initiation of revalidation categories,

changes that warrant revalidation programs, basic steps of revalidation procedure,

revalidation activities and specific responsibilities, revalidation protocols, revalidation timing,

equipment checklist, revalidation discrepancy procedure, release of revalidated equipment,

preparation of the revalidation reporting file.

Method Validation

This procedure provides a guideline for a validation Technician on the characteristics that

must be considered during the validation of an analytical testing procedure. The procedures

set out in this SOP apply to qualitative and quantitative analytical methods which are used

to test finished goods, in-process material, excipients and raw materials in support of


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registration documentation and cleaning validations and management responsibilitiestowards completing those method validation tasks.

Cleaning Validation

This SOP describes the types of cleaning process and cleaning agents of process equipments

and their validation, complete instruction on cleaning validation procedure, calculation of

acceptance limits for rinse and swab samples, calculation of acceptance limits for swabs,

analytical method validation for cleaning, cleaning validation test protocols and changecontrol for revalidation.

Validation of Laboratory Instruments

This procedure describes the validation practices for laboratory instrument/equipment to be

validated or calibrated and the confirmatory documentation required showing that theinstrument/equipment is capable and operating effectively for its intended purpose. This

procedure has practical instruction on Installation Qualification (IQ), Operational

Qualification (OQ) and Performance Qualification (PQ) to be performed by the qualified

equipment service technician in the presence of the laboratory staff with reference to theinstrument/equipment manual.

Equipment Specification and Qualification

This procedure describes in detail the procedures for the procurement of equipment,

incorporating standardized demand specifications and Installation Qualificationdocumentation, to ensure that equipment procured complies with in-house requirements

and standards and conform to Good Engineering Practice, to detail the general procedure to

be followed regarding the reporting of Factory and Site Acceptance Tests, to detail themanner by which the equipment Installation Qualification is documented.

In-House Trial

The purpose of this SOP is to define common procedures to follow when organizing

Trials/Evaluation Studies for the purpose of process improvement, equipment capability and

validation studies. It defines the responsibilities within the trial process and documents that

need to be considered when preparing the Trial documentation to ensure that the trial

meets GMP and where applicable validation requirements. This SOP defines the procedures

for conducting in house stand-alone trials on systems, processes and equipment. There can

be an overlap between a trial and validation in that Trial documentation may form part of a

latter process validation, (i.e. concurrent and prospective validation) and qualifications (OQ,PQ).


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Computerized Systems Validation

To overview the procedure to be followed for the Qualification/Validation of computerized

systems. This procedure applies to all computer systems (including embedded systems)

directly associated with, or supporting, regulatory compliance requirements for thedevelopment, testing, manufacture and distribution of medicinal products.

Impact Assessment for Computerized Systems

The purpose of this SOP is to provide a method of assessing and determining the validation

requirements for computerized systems and controllers. The SOP identifies the typical

qualification activities required for those systems having a Direct or Indirect impact on

product/process quality and data integrity, should the system fail or malfunction. These

activities are in addition to Good Engineering Practice (GEP), which is appropriate for all

systems, and is also outlined

Functional Testing Guide for Computerized System

This SOP provides guidance on functional testing during the development or change of

computerized systems which have GxP impact at a GMP manufacturing site. What

constitutes a change to a computerized system is described in manufacturing change controlprocedure.

Design Qualification Guidelines

The purpose of this document is to provide guidelines on conducting Design Qualification

(DQ) during the conceptual and detail design phase for the implementation of a GMP facility,

process and equipment (including computerized systems) to ensure conformance to

operational and regulatory expectations. The guideline will provide the basis for conducting

and documenting Design Qualification to all projects involving the introduction of, or

significant change to, any facility, system or equipment that potentially impacts on productquality and is suitable for its intended purpose.

Protecting the Reliability of Electronic GMP Records

This SOP applies to records created, processed, used or stored by (or for) the GMP

Manufacturing site, that are the output of a computerized system. It is of particular

relevance to records that have a GMP role, i.e. supporting product quality, patient safety or

regulatory compliance. The guideline may also be used for other computerized systems

that are classified as business critical. GMP | Manufacturing Procedures


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In this area you will find exciting procedures on Clothing Requirements Inside the Factory

Area, Cleaning Responsibilities and Methods for Employees, Factory Cleaning Procedure,

Manufacturing Pest Control, Tours of Factory, Requirements of Production Logbook,

Packaging Configuration for Production Line, Checking of Components Prior to Use, Tag Out

Procedure, Procedures for Line Clearance, Line Opening and Line Cleaning, Reconciliation of

Component and Product, Operation of Barcode Reader as an example, Intermediate Bulk

Container (IBC) Operation and Cleaning, Tablet Packing Machine and Cartoner-construction,

operation and cleaning as an example, Manufacturing Instruction for Tablet Packing as an

example, Mop Cleaning Procedure, Scheduling Production Lines, Vacuum Leak Testing

Procedure, Weighing Equipment - Checking and Calibration, Operation of Checkweigher as

an example, Tablet Packing-Start up and In-process Testing as an example, Packed TabletSampling by Production Personnel for Testing as an example

All procedures have reference of prepared Forms and Visual Displays for effective recordkeeping and reporting purposes. Forms are attached at the end of each procedure.

SOP list

Clothing Requirements

This SOP covers the clothing requirements needed in all Factory areas for your

manufacturing site. The different levels of cleanliness must be maintained to minimize

microbial and particle contamination. This procedure contains general rules and restriction

to be followed by your manufacturing employees, defining different environmentally gradedareas and entry requirements for those areas.

Cleaning Responsibilities and Methods

This SOP describes the cleaning procedures to be followed by all employees working in the

manufacturing area in order to prevent contamination of product by foreign materials from

another batch, or by dirty parts, which may contain bacteria. This SOP contains instruction

on responsibility of cleaning, degree of cleaning to be done, popular cleaning aids andsolutions permitted to use for cleaning, rubbish removal and outline of cleaning methods fordifferent environmentally graded areas.

Factory Cleaning


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This SOP defines the methods, frequency and the intensity of Factory Cleaning. The purpose

of cleaning is to remove debris from within the plant in a sanitary and effective manner and

to avoid contamination from dust or foreign materials. This procedure describes which

popular cleaning aids and solutions are to be used to clean the floors, walls, sinks and

windows in the Production areas, office areas, change rooms, workshops, laboratories,

stores, canteens, plus the toilet facilities. This procedure also describes the scope andresponsibility of contract cleaners.

Manufacturing Pest Control

This SOP describes the responsibilities of all employees and pest control services,

classification of pests, frequency of the pest control service and effective treatments against

all types of pest.

Production Logbook

This procedure outlines the generation, maintenance and filing of Production logbooks.

Production logbooks form part of the documentation system required by the Code of GMP to

provide complete and up-to-date histories of all batches of product. The logbook provides akey link in the process of traceability.

Packaging Configuration for Production Line

This SOP provides an alphabetically indexed diagram of shipper packing and pallet packing

configurations for any packaging process. This procedure contains schematic diagrams ofdifferent packaging configurations and calculations of total unit to be packed per containerwhich can be useable into your packing lines.

Checking of Components before Use

This SOP sets out a procedure to ensure that only components of correct code and batch

number are issued for a batch and only issued components will be used in a finished product

batch. This SOP also describes the procedure to be followed during returning of componentsto warehouse from the production lines.

Tag Out Procedure

This SOP describes how to prevent the risk of personal injury or damage to equipment likely

to be caused by operating or attempting to operate machinery or equipment diagnosed as

being unsafe, in need of repair or maintenance or formally removed from service. The SOP


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covers all isolation, condemning, repair or maintenance work that necessitates a device or

machine to be taken out of service. This SOP applies to any situation where energy (either

supplied to equipment, or stored within it) needs to be isolated to ensure the safety of any

person working on or near equipment, processes or services - for any reason whatsoever.

Line Clearance, Line Opening and Line Cleaning

This SOP describes the procedure and order to be followed when performing a Line

clearance, Line opening and Line cleaning for a batch production. The procedure has been

established to prevent mix-ups of products, containers, components, labels and mistakes in

documentations. Mix-ups and mistakes can occur when correct procedure and GMP are not

followed. Particular care should be taken when starting a new operation, at the change of

shift and when additional components are needed. In this procedure you will find example ofline clearance, opening and cleaning checklist based on an example of tablet packing line.

Reconciliation of Component and Product

This simple SOP describes the concept of reconciliation, how to reconcile finished goods anddetermine the allowable discrepancies of components and products when reconciled.

Construction, Operation and Cleaning of Tablet Packing Machine

This procedure describes the machine construction and operation, machine start up and

cleaning of a typical tablet Blistering machine and the Cartoner for tablet packing. You will

be able to create a new procedure for your packing line based on the format of this SOP.

Manufacturing Instruction for Packing

This procedure describes how to create a complete manufacturing instruction for your

process line to be followed by your manufacturing employees. To make the instruction more

practical and easy to understand, a sample instruction is added in the form of a protocol for

a typical tablet packing process. All the related blank forms are attached at the end of the

procedure for a better understanding.

Mop Cleaning

This simple procedure outlines the operation of the factory laundry in a safe and hazard-free

manner. This procedure can be used in any manufacturing site for the purpose of mopcleaning.


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Scheduling of Production Lines

This procedure describes how to produce a monthly manufacturing schedule following an

agreed 12 months plan, to provide a sequence of work that will enable the scheduling of

support groups (i.e. Quality, Technical and Warehousing), incorporate any planned

engineering down time (i.e. project work, calibration and preventative maintenance), create

and release batches according to the agreed weekly schedule, provide key dates for productsupply to support Customer Service.

Vacuum Leak Testing Procedure

This SOP describes the set up and operation of a standard vacuum Leak Tester for the verypopular vacuum leak testing used in a typical packing line.

Tablet Packing-Start up and In-process Testing

This procedure contains instructions that enable the production operators working in a

typical packing line to carry out Start-Up and In-Process Tests required in order to produce

quality products and to ensure in-process controls. A typical tablet packing process is usedhere as an example.

Finished Product Sampling for Testing

This procedure describes the process of sampling manufactured finished good required to be

taken by production personnel for the laboratory testing. A typical tablet packing process isused here as an example.

Returning Components from Packaging Floor

This procedure describes the steps to be followed when there are packaging components to

be returned to the warehouse after the packaging operation has been completed.


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Warehouse Management Procedures

In this area you will find procedures on Receipt of Incoming Goods, Raw Material and

Components-Incoming-Handling by Sampler, procedure for Warehouse to Processing Issues,

Returns and Rejects, Dispatch of Goods from Warehouse, Warehouse InventoryManagement, Warehouse Locations and Storage Area, Finished Goods Transfer to

Quarantine and Distribution Warehouse, Sampling of Raw Materials, Sampling of

Components and Printed Materials, Work in Progress Area, Safety Procedure of Warehouse

Racking, Forklift Operation in Warehouse, Tablet Dispensary Procedure as an example, Raw

Material Tablet Sampling by Dispensary as an example, Material Purchasing Information

Record and Source List, Generation of Purchase Order For Inventory and Consumables

SOP List

Incoming Goods

This SOP contains step by step instruction on condition of accepting incoming goods in the

warehouse, booking In procedure of component and non component goods, how to

complete movements of incoming goods into different storage locations within the

warehouse maintaining full traceability. Here you will find generation and filing ofdocuments related to receipt of incoming goods.

In-coming Raw Material and Components Handling

This procedure describes quarantining, sampling, testing and releasing of incoming raw

materials to Production. Here you will find the labeling requirement for component to be

sampled, checking requirements of components, sampling and re-sampling of incoming

goods for laboratory testing, generation of documentation during the movement ofcomponents in order to maintain complete traceability.

Processing Issues Return and Rejects

This SOP contains step by step instruction on issue of tested and QC released componentsfor batch production, documentation needed for capturing identification and traceability

information during the picking, assembling and transferring of those components from

warehouse to production. This procedure also has instruction to follow during the return andreject processing of raw materials and components from production to warehouse.


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Dispatch of Goods from Warehouse

This SOP contains instruction and documentation on movement of finished goods to

quarantine until release for sale, dispatching procedure and documentation needed for

transferring of finished goods from quarantine to warehouse store and subsequently to out

side the manufacturing site maintaining a complete traceability of finished goods.

Inventory Management

In this procedure you will find a complete inventory management system by stock counting

instruction, stock classification and reconciliation programs. Here you will find instruction on

cycle counting by material code, counting by bin sheet information and reconciling/cross

checking of those counts by physical counting of the stock, determination of material gain orloss and filing instruction.

Warehouse Locations and Storage Area

This SOP is designed to understand and draw an schematic diagram of ideal warehouse and

production areas, identifying in-coming goods storage unit types and storage bin types,

quarantines, reject cage, cool room, flammable storage, dispensary booths, production

area, finished goods quarantine area and finished goods storage areas. This procedure

defines how storage unit types and storage bins are numbered. This SOP is to be used as a

guide to define the types of storage units and bins, movement direction within thewarehouse and production areas.

Finished Goods Transfers to areas

This simple SOP contains instruction and documentation on movement of finished goods

from production to warehouse finished goods quarantine location until the samples are

tested and released by the authorized persons.

Sampling of Raw Materials

This procedure primarily concerned with risk associated with sampling, precaution to be

followed when sampling, general sampling procedures for raw materials, critical and noncritical components, chemicals and secondary reference standards for laboratory.

Sampling of Components and Printed Materials


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This procedure is an elaboration of SOP WAR-045 and mainly concerned with sampling plans

and instructions of components and printed materials for quality testing before release forproduction use.

Work in Progress

This simple procedure describes the construction and locations of different work in progress

areas between production and warehouse for temporary storage of raw materials,

component and finished goods.

Warehouse Racking

This SOP outlines the measures to be taken to ensure the safety of all goods and personnel

when using the storage racking system in order to avoid injury to staff or damage to

property. This procedure concerned with the handling and storage of materials or productsand to report any damage which may be occurred. This SOP particularly relates to theactivities of the staff of the receiving and distribution warehouse.

Forklift Operation in Warehouse

This SOP gives instructions on operation requirements and maintenance of forklifts used inthe warehouse, safety precaution to be taken during the operation of forklift under load.

Dispensary Procedure

This procedure is mainly concerned with dispensing plans and instructions of released raw

materials for production use. An example of tablet dispensary procedure is prepared for

better explanation and understandings of dispensing. You will be able to follow the

instruction for dispensing of any raw materials in your facility.

Material Purchasing Information Record

This simple procedure describes how to keep purchasing information for approved materials,

vendors, manufacturers, standard and current pricing and third party agreements.

Generation of Purchase Order


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This procedure describes the steps to be followed by planning and procurement department

to create purchase order for inventory items to be purchased from overseas and localsuppliers.


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Quality Guidance

Validation of Analytical Test Methods

This guideline provides guidance for the validation of analytical test methods. These

analytical test methods include those tests which evaluate API, Raw Materials, In Process

samples (e.g. reaction monitoring) and early intermediate materials (prior to theintroduction of the first critical intermediate). This also include Risk Assessment andPrioritization, System Suitability, Precision and Accuracy, Quantitation and Detection Limit

Linearity, Range and Specificity, Robustness,

Calculations of Residue Limits for Drug Product for Equipment Cleaning

This guideline provides equations and examples for calculating the Maximum Allowable

Residue and Residue Acceptability Limits for Drug Products and Non-Therapeutics. Examples

are provided for determining the acceptable equipment cleaning residue limits fortherapeutic drug products and for non-therapeutic ingredients.

Swab Sampling for API Equipment

This guidance provides recommendations related to the selection and application of swabsampling and visual inspection for various types of API equipment.

Product and Equipment Grouping and Worst - Case Product Selection

This procedure defines the criteria that should be considered when grouping Active

Pharmaceutical Ingredient (API) and Drug Product (DP) equipment or product for thepurposes of cleaning validation.

Validation of Test Method for Rinsate and Swab Sample

The guidance describes recommended approaches to develop and validate sampling andtest methods for cleaning verification using rinse and swab samples.

Visual Inspection and Quantitation in Equipment Cleaning

Visual inspection is the minimum requirement for all clean and test regimes required for

Cleaning and Cleaning Validation. Five aspects of visual inspection discussed in this

guidance. Which are visual inspection following or during manual cleaning; visual inspection


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of dedicated equipment; routine visual inspection of multi-purpose equipment; visualinspection during validation and Visual Quantitation

Documentation and Instruction in Cleaning Validation

This guidance addresses recommendations for developing and documenting the rationale to

support the product contact equipment cleaning program and to justify the validationstrategy. This documentation may be described as a Cleaning Evaluation Report.

Critical Process Parameters for Drug Product

This guidance provides recommendations and examples for evaluating a process to identifyand define the critical process parameters.

Identification of the Critical Steps for Drug Manufacturing Process

This guidance provides recommendations for selecting critical process parameters andcritical process steps based on the understanding of a drug product process.

Equipment Cleaning Validation for API

This procedure provides guidance in the validation of cleaning processes for equipment usedin the manufacture of Active Pharmaceutical Ingredients (API).

Equivalence Criteria of Impurities in API Process Validation

This guidance provides recommendations for demonstrating equivalence of impurities tohistoric batches during validation of API processes for small molecules.

Equivalency Comparison of Drug Product

This guidance addresses the equivalency comparison of manufacturing process data fromdrug product (DP) validation batches to previous batches (called reference batches), whenapplicable.

Calculation of Clean Equipment Hold Times


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This guidance describes considerations and risks for determining if the establishment of

clean equipment hold times for equipment producing drug product and ActivePharmaceutical Ingredients (API) are required

Evaluation of Non-cleaned Equipment Hold Time

This guidance outlines considerations and risks associated with hold times between

equipment use and cleaning. The recommendations to evaluate if the time between

equipment use and cleaning needs to be established and controlled are described for Active

Pharmaceutical Ingredients (APIs) and Drug Products. When they are determined to be

critical, recommendations on how to establish and extend existing hold times are alsodescribed.

Potential Impact of Changes in Process Validation

This guidance provides recommendations and examples for evaluating the process

validation impact of changes to manufacturing processes used for manufacture of API, Drug

Products and packaging processes.

Process Validation Sampling

This guidance addresses recommendations for good sampling practices. Validation samplingplans must be specified or referenced in the protocol.

Determination of Swab & Visual Inspection Sampling Locations

This guidance provides recommendations related to the selection and application of swabsampling and visual inspection for various types of Drug Product equipment.

Bulk Drug Product Holding Times

This Guidance sets out guidelines for the determination and validation of in-process andbulk product holding times.

Demonstration of Active Pharmaceutical Ingredient (API) Batch Homogeneity

This guidance provides information on demonstrating batch homogeneity of final APIs (small

and large molecules) and critical intermediates.This procedure provides guidance for

performing a homogeneity evaluation in support of API process validation. The following


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components of the evaluation are described: Materials to be tested, Selection of test

methods for examining homogeneity, Sampling plan when to collect samples, from what

locations, and the number of samples, Selecting acceptance criteria for evaluating

homogeneity test results.

Continuous Quality Verification

This guidance provides an example of documentation to support the use of Continuous

Quality Verification for demonstrating that a manufacturing process is in a validated state.

Supporting Documentation for Continuous Quality Verification

This guidance describes the documentation needed to support the use of Continuous Quality

Verification to demonstrate that a drug product or active pharmaceutical ingredient process

is in a validated state. It also describes some similarities and differences betweenContinuous Quality Verification and traditional process validation using three discrete lots.

Dose & Toxicity Data for Cleaning Limit Calculation

This guidance provides points to consider when selecting Dosage and Toxicity data for usein the Cleaning Limits calculations.

Inspection Attributes in Non Sterile Packaging Validation

This procedure provides examples and guidance on classification of defects for packagednon-sterile drug products.

Laboratory Instrument Qualification

This procedure provides guidance in the qualification of simple, moderate, and complex

laboratory equipment that is used in an analytical laboratory in a Good ManufacturingPractices (GMP) environment associated with products in or intended for the market place.

Matrices and Bracketing in Process Validation

Bracketing and matrixing allow a most appropriate challenge condition to be defined for a

process or drug product family (the same drug product with different dosage strengths).

This risk-based approach can allow the validation to be focused on the most challenging


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circumstances, or worst cases. Use of this approach can provide a significant benefit toreduce the overall validation effort.

Considerations for Selecting Packaging Lot Sizes During Packaging

Examples of primary and secondary packaging validation, both manual and automated

operations are provided in this guidance. This also provides guidance on aspects to consider

for packaging validation. Explanations of factors to consider for acceptable packaging

validation and lot size are provided with various practical examples.

Non-Sterile Active Pharmaceutical Ingredient (API) Manufacturing Area

This guidance is to address environmental control for existing, new, and modified non-

sterile API processing areas used for the manufacture of commercial materials. This includes

non-sterile API manufacturing areas where the API will subsequently be used to producesterile Drug Product.

Potential Critical Process Parameters and Validation Practices

This Guidance provides a tabulation of potential critical process parameters and quality

attributes of typical steps of primary solid drug product (i.e. dry products) packaging

processes. It also includes packaging validation items such as evaluation of equipment,

protocol and report contents, amount of data (e.g. number of runs) and if warranted,

microbiological studies.

Process Validation Sampling for Non-Sterile Liquid Semi Solid Drug Products

This guidance provides Process Validation Sampling guidelines for non-sterile liquid

(solutions and suspensions) and semi-solid (ointments, creams, pastes, gels and lotions)drug product dosage forms.

Process Validation Sampling for Non-Sterile Solid Dose Drug Products

This guidance provides Process Validation Sampling guidelines for non-sterile solid dose

drug product dosage forms. The purpose of this guidance is to provide the general principlesand approaches that should be considered for sampling non-sterile solid dosage forms.

Performance Qualification Versus Process Validation


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This guidance compares and contrasts Performance Qualification (PQ) to Process Validation

(PV). This guidance describes the differences between PQ and PV. It clarifies how the PQ

term is applied to systems and to processes. As applied to processes, PQ batches are used

to demonstrate the robustness of a process and PV batches are intended to demonstrate the

reproducibility of the process. As applied to systems, PQ testing is intended to verify that

integrated systems function together as required

Periodic Review of Processes and Systems

This guidance addresses the application of a risk-based approach to: Prioritize the systems

and processes for periodic review (PR); Justify frequency and schedule of PR (if applicable);Routine revalidation of processes.

Release of Drug Product and API Pre-Validation and Validation Batches For Commercial Use

This guidance addresses considerations for commercial release of batches of product

manufactured prior to completion of process validation (PV) activities, and considerations

for release of batches associated with performance qualification (PQ) and PV activities.

Selection of Critical Process Parameters for Validation

This guidance discusses the term critical process parameter and considerations are

described for identifying the term CPP that need validation. It is applicable to the

manufacture of commercial intermediates, API, Drug Products and packaging.

Critical Process Parameters for Semi-Solid Dosage Forms

This guidance provides an explanation of the semi-solid Drug Product dosage form and

recommendations for analysis of the manufacturing process critical process parameters.

Semi-solids come in a variety of dosage forms, yet significant steps and equipment used for

the manufacturing processes share commonality. The critical process parameters will oftenbe the same from process to process.

Potential Critical Process Parameters Solid Oral Dosage Forms

This guidance provides an overview of potential critical process parameters for the

manufacturing of solid oral dosage forms. Solid oral drug products come in a variety of

dosage forms frequently with common steps and equipment. The potential critical process

parameters are often the same from process to process. This guidance provides an overview

of process steps and typical equipment involved in manufacturing of solid oral dosage


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products and notes what might be critical process parameters associated with these processsteps and equipment.

Solvent Recovery Validation Example

This guidance provides an example of the documentation for validation of a solvent recovery

process. Solvent recovery validation is needed in some situations such as where the

recovered solvent is intended for general site wide reuse into suitable manufacturing

processes, including other API manufacturing processes than those from which the usedsolvent originated

Test Deviations During Validation

Out-of-specification (OOS) results and any other deviations that may impact the

acceptability of the qualification/validation should be documented, investigated, root causedetermined, corrective action taken and reported. Several examples are included.

Validation Activities During Technology Transfers

This document provides guidance for qualification and validation activities that take place as

a result of the Technology Transfer for approved commercial Active Pharmaceutical

Ingredient (API) and Drug Produc processes. Other aspects of Tech transfers such as

regulatory changes, stability impact, etc must also be considered as described in relevant

guidance, but these other activities are outside the scope of this guidance.

Validation Considerations for Re-work and Re-process of Active Pharmaceutical Ingredients

This document provides guidance to determine if validation of re-work and/or re-processing

steps are required for Active Pharmaceutical Ingredient (API) processes. This guidance

provides recommendations for evaluating the potential impact on product quality todetermine if a given re-work or re-process step requires validation

Validation Documentation

This guidance provides recommendations for the content of the planning, testing andreporting types of validation documentation.

Shipping Validation for Biopharmaceutical Materials


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The risk of compromising biopharmaceutical materials in shipping is relatively high, as these

materials are particularly vulnerable to degradation when exposed to various environmental

and handling conditions. The risks can be managed effectively through qualification of

packaging, handling, and transport procedures.

System Level Impact Assessment for Information Systems

This document explains how the Commissioning and Qualification System Level Impact

Assessment template can be used for Information Systems. To classify Information Systems

as Direct, Indirect or No impact systems, only one question is applicable for Information

Systems. By means of three typical examples, this guidance explains how systemclassification could be performed, based on the use of the system and its data.

Clean Pure Steam System Commissioning , Qualification and Sampling Plans

This document recommends sampling locations, frequencies and testing activities associated

with the commissioning and qualification of new installations or major revisions of

Clean/Pure Steam Systems (e.g. the addition of new subloops or other system wide

retrofitting). This guidance defines the sampling location, frequency, and testing activities

utilizing a risk based approach for supporting the commissioning and qualification for aclean/pure steam system.

Product Quality Complaint Handling

This Complaint Handling guidance defines practices for establishing and maintaining aproduct quality complaint handling system, and for monitoring and reporting correctiveactions based on the findings

Application of Quality Risk Management to Periodic Review of SOPs

Application of Quality Risk Management to Periodic Review of SOPs is intended to provide a

tool for determining the optimal review frequency that will ensure those SOPs which relate

to GMP systems or processes and therefore bear the greatest potential for impact on

product quality are reviewed/revised in a timely and possibly more frequent manner thanthose which are determined to be less critical or reflect stable processes.

Statistical Rationale for Raw Material Sampling

The practice of using the N+1 as a rule for sample size is common in the pharmaceuticalindustry.


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Quality Risk Management Application for Critical Instrument Calibration

This document offers a risk assessment approach to document a critical instrumentcalibration interval change request.

Structured On-the-Job Training System

This document discusses considerations for a site Structured On-the-Job Training systemincluding GMP tasks and knowledge necessary to perform those tasks.

Training system for Aseptic and Preparation forAseptic Operators and Support Staff

This document discusses considerations for a robust training system for those working in orin support of a preparation for aseptic processing area.

Disposal of Rejected and Waste Materials

This document provides guidance for the handling, collecting and disposing of wastematerials.

Quality Assurance Audit

This document provides guidance in the conduct of Quality Assurance Audits to verify and

assure the effectiveness of on-going quality systems, practices and programs and to identify

potential procedural gaps or system weaknesses at Manufacturing Production and logisticSites.

Annual Product Records Review

This document provides guidance in the performance of annual product record reviews to

evaluate data and trending to: Verify consistency of the process; Identify the need to

modify specifications, and Identify any preventive or corrective actions that would lead toproduct quality improvements.

Receipt, Approval and Use of Labels and Labeling


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This document provides guidance on the printing, receipt, storage, use and reconciliation of

product labels and labeling for active pharmaceutical ingredients (API), medical devices, anddrug products.

Weighing and Measuring Practices In Manufacturing Operations

This document provides guidance in the weighing and measuring of materials used in the

manufacture of drug products, active pharmaceutical ingredients (API), medical devices,

and intermediates.

Material Supplier Approval

This document provides guidance in the process for identifying suppliers to be audited and

the process for conducting and documenting such audits and approving suppliers.

Storage & Distribution of Drug Products and Medical Devices

This document provides guidance the storage and distribution requirements for Drug

Products, Medical Devices and related Production Materials from a GMP Site or LogisticsCenters, and/or transported between manufacturing and Logistic Sites.

Control of Manufacturing and Packaging Defects Non Sterile

This document provides guidance on the inspection of non-sterile drug products and non-

sterile medical devices for manufacturing and packaging defects.

Pest Control

This document provides guidance in the implementation and maintenance of pest control

program for buildings and facilities at a GMP Site and Logistics Centers that are used forproduction, testing, or storage of pharmaceutical ingredients.

Receipt and Storage of Raw Materials and Packaging Materials

This document provides guidance for receipt and storage of raw materials (RM),

components, and packaging materials used in the manufacture and packaging of activepharmaceutical ingredients (API), drug products, and medical devices.


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Sampling of Production Materials and Finished Goods

This document provides guidance for a sampling program for Raw Materials (RM), Starting

Materials, Packaging Materials, Labeling, In-Process Materials, Intermediates, Active

Pharmaceutical Ingredients (API), Drug Products, Biologics, Medical Devices, Medical Device

Components and Materials with Direct or Potential Product Contact.

Water Purification, Storage and Distribution for Pharmaceutical Production

This document provides guidance for the purification, storage and distribution of water used

for Production including water used for cleaning of product contact equipment, containers,and closures.

Use of a Risk-Based Approach To Establish External Quality Assurance Audit Frequency

The purpose of this document is to provide guidance for GMP Quality Audits stakeholders

responsibility to utilize a risk-based approach for determining External

Quality Assurance Audit prioritization and frequencies.

Reduced Testing Program

This guidance document defines a science and risk-based approach for the evaluation and

implementation of a reduced testing program for the release of starting materials,

intermediates, APIs, excipients and packaging components at a GMP user site upon receiptfrom vendors (manufacturer/supplier). The guidance also provides an example of the

application of Quality Risk Management principles in the implementation of a reducedtesting program.

GMP Training System

This document discusses considerations for site GMP Training systems including training onregulations, GMP concepts, GMP tasks and knowledge necessary to perform those tasks.

Stability Testing

This document provides guidance for the stability testing for drug products, consumer non-

drug products (e.g., cosmetics), Active Pharmaceutical Ingredients (API), API Intermediates

for Sale and medical devices manufactured at GMP facilities.


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Quality Risk Management application to identify Deviations vs. Events

Often times, deviations that occur during the handling, manufacturing, testing or

distribution of materials/products have little or no impact on product quality or to its

registration filing. The purpose of this guidance is to provide a process for assessing if a

deviation does or does not impact the product quality or its filing through the use of a

Quality Risk management tool.

Implementation of Real Time Release

This document provides practical guidance on how to implement a Real Time Release (RTR)

testing approach as part of a manufacturing control strategy to ensure product quality whileenabling the rapid release of API, intermediate and/or finished products.

Preventive Maintenance

This document provides guidance in for Preventive Maintenance of direct impact systems

and associated critical components used in production, storage, and testing that may affect

the safety, identity, strength, quality, or purity of active pharmaceutical ingredients, drug

products, drug product raw materials, API starting materials, critical in-process materials,

critical intermediates, biologics, or medical devices.

Calibration

This document provides guidance for the calibration of equipment, instruments, andstandards used in production, storage and testing that may affect the identity, strength,

quality or purity of Pharmaceutical drug products, active pharmaceutical ingredients andmedical devices.

Determining Testing Patterns and Acceptance Criteria for Analytical Method Transfers

This document provides guidance for setting experimental testing patterns and acceptance

criteria for Analytical Method Transfer Exercises. This document provides guidance to GLP

sites in identifying lots and number of samples for testing, setting appropriate acceptance

criteria for conducting transfers.

Quality Risk Management Application to Establishment of Weighing Device Performance

Testing Intervals

Application of Quality Risk Management to performance checks for weighing devices such as

balances and scales is intended to provide a tool for determining the acceptability of


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decreasing the frequency of verifying the performance of a weighing device from the currentfrequency (e.g. daily) to an alternative schedule.

Analytical Laboratory Management

This document provides guidance for the management of analytical laboratories including

the following: Personnel training; Proper handling of samples; Hazardous materials; Control

and maintenance of reagents, reference standards, and buffers; Laboratory facilities and

equipment; and Documentation and control of test results.

Microbiology Laboratory Management

This document provides guidance for the management of microbiology laboratories including

the following: Proper handling of samples; Control and maintenance of reagents, reference

standards, buffers, microbial cultures, and microbiological culture media; Monitoring andcontrol of the microbiology laboratory environment; Calibration and maintenance oflaboratory equipment; and Documentation and control of microbiological test results.

Transfer of Analytical Methods

This document provides guidance for establishing a documented process for the transfer ofanalytical methods, microbiological and/or bioanalytical methods.

Quality Agreements

This document provides general guidance to site Quality Teams responsible for writing,revision and maintenance of Quality Agreements with suppliers of materials.

Clean Steam Systems

This document provides guidance for clean steam used in aseptic applications, and

applications where the steam or condensate directly contacts products or materials, ordirect product contact surfaces (i.e., equipment, containers, closures).

Cleaning and Sterilization of Aseptic Manufacturing Equipment

This document provides guidance in the cleaning and sterilization of aseptic manufacturingequipment to minimize the risk of particulate and microbiological contamination.


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Container Closure Integrity for Sterile Drug Products

This document provides guidance for ensuring that the integrity of the container closuresystem will protect the product over its shelf life.

Controlling the Microbiological Quality of Solid Oral Dosage Forms

To control the microbial quality of a non-sterile Solid Oral Dosage form, it is recommended

to perform a risk assessment of the manufacturing process to identify potential sources of

microbial contamination. The intention of this document is to provide guidance to determineand control these sources of microbial contamination.

Defining Worst Case Conditions for Aseptic Process Simulations

Aseptic process simulation tests (e.g. media fills) are used extensively and are recognized

as an effective way to validate aseptic filling processes for the purpose of complying with

regulatory GMP expectations. A media fill begins at the point where the final sterilization of

the product takes place (i.e. where aseptic operations are performed) through thecompletion of filling operations with the sealing of the filled containers.

Evaluation of Repeat Testing and Retesting During Microbiological OOS Investigation

During a laboratory investigation, confusion may arise as to the difference between theseterms and their overall purpose. This document provides a more detailed explanation of

these differences and the individual importance of these tools during a microbiological OOS

laboratory investigation. In addition, this guidance will also briefly clarify similarities and

differences of these definitions as compared to analytical OOS laboratory investigations.

Gamma Radiation Sterilization

This document provides guidance for validation of gamma radiation sterilization processes

used to sterilize active pharmaceutical ingredients, drug products, medical devices and non-

product items, such as, APA gowning articles, containers, and closures with direct orpotential contact with sterile raw materials, APIs, drug products or medical devices.

Microbial Attributes Testing of Non-Sterile Solid Oral Dosage Forms and Materials

The intention of this document is to provide guidance to determine the need for performing

microbial attributes testing of drug product raw materials, non-sterile excipients, active


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pharmaceutical ingredients and finished drug products. This guidance is recommended inorder to ensure the microbiological quality of any non-sterile solid oral dosage form.

Microbiological Testing in Cleaning Validation

This document describes the rationale and recommended microbiological methodology for

consideration during cleaning validation of product contact surfaces for ActivePharmaceutical Ingredients and drug products.

Overview of Trending of Environmental Monitoring Data

This guidance establishes the need for trending of environmental monitoring data and gives

recommendations on aspects of trending such as categorization of data, frequency of

trending, trend definition, and content of trend reports.

Packaging System Integrity for Sterile Medical Devices

This document provides guidance for determining the suitability of packaging materials and

the evaluation and testing of the integrity of packaging systems

for sterile Medical Devices manufactured and/or packaged by GMP sites.

Cross Contamination Prevention

This document provides guidance for the prevention of cross contamination in productionprocesses, warehousing, material transfer, and distribution.

Prevention and Control of Fungal Contamination in Tablets

What steps can be taken to prevent and control of fungal contamination in tablets? The

presence of water is the key element in the growth of fungal contamination. This document

discusses the prevention and control of fungal contamination in tablets production to

include: raw material and API testing, manufacturing processes, environmental monitoring,

and final product testing.

Sanitant Rotation in a Routine Sanitization Program


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What are the expectations for industry for the inclusion of different sanitization agents

within a routine sanitization program? Additionally, are there tangible benefits to routinelyrotating sanitization agents? Finally, how is sanitant performance defined?

Sterilization/Depyrogenation Validation for Equipments and Containers

This procedure provides guidance for validating sterilization and depyrogenation of

equipment and containers and closures with direct or potential contact with sterile medical

devices, sterile drug products or sterile active pharmaceutical ingredients.

Unplanned Cleanroom Power Outage Time Limit and Recovery

How can the time between a cleanroom power outage and loss of environmental control in

the critical area be determined? Once the power is restored, how can the time it takes to

recover the desired environmental conditions be determined? An interruption of powersupply to the HVAC systems may produce a loss of control which can be defined as a

breech in the integrity of the controlled areas in sterile manufacturing. Appropriate steps to

be taken during and after an

interruption of air supply to the aseptic processing area.

Use of Sterilized Goggles Within the Aseptic Processing Area

This document will discuss the