Galelio

You CANNOT teach anything to a human being, You CAN only help him find what is already there in him.

GMP General Requirements

Premises Personnel Equipment: Maintenance, calibration, and validation Chemicals and Reagents

GMP
Good house keeping and safety Reference materials Microbiological Cultures Quality system Internal quality system audits Management review

GMP
Standard Operating Procedures Protocols and specifications archive Raw data Storage and archival

Quality Management

defining the overall policy of the organization towards quality, is over everything else. A working infrastructure = quality system

QA system

must ensure that products are formulated and developed in accordance with quality assurance principles must identify all management responsibilities, with written job descriptions and organization diagrams.

QA System

must provide SOPs for all manufacturing and testing methods must ensure that there are up-to-date written procedures for the supply and use of all starting and packaging materials must ensure that there are up-to-date, written procedures to control all starting materials, intermediate and bulk products

QA System
must also ensure that there are written, up-to-date SOPs describing how the product is to be processed and checked.

must ensure that no product is released for distribution without all the documents pertaining to it have been checked by an authorized person.

QA System

must ensure that appropriate conditions are provided for all storage and distribution. During product development, stability testing have been done must ensure that there is a self-inspection process available and implemented, leading to a programme of critical selfevaluation and continuous improvement backed up by quality audit, an independent internal organization, charged with looking at all departments

Quality

Fitness to use Fitness of purpose Consumer satisfaction Conformance to requirements Needs change with time Stated as in contract Implied as defined or identified

Quality Assurance

Action necessary to provide adequate confidence that product or service will satisfy the needs Understand the given needs Continuation evaluation of design/specifications Audits of facilities/operation providing evidence

Principals of GMP/GLP

To provide assurance that products are consistently manufactured & controlled to the quality standards appropriate to their intended use

Elements of GMP

Facilities Personnel Systems & Controls

Facilities

Premises Equipment Services

Personnel

Qualification Responsibilities Training Hygiene

Systems & Controls

Ware Housing Sampling/Testing/Release Production/Process Control Packing & Labeling Storage & Distribution Laboratory Control Expiration Dating Status Labeling Sanitation Documentation Change Control Qualification/Validation Contamination Control

Experience

Good Judgment comes from Experience Experience comes from Bad Judgment

Good Living Practices

Wash & Clean your hands after toilet. Regularly brush your teeth. Bathe every day. Wear clean clothes Wash hands before meals. Rinse your mouth & wash hands after meals. Spit only in washbasin. Secure valuables & cash.

GMP

Clearly defined and systematically reviewed manufacturing processes Critical steps of production processes are validated Appropriate resources: personnel, buildings, equipment and materials are available to produce a quality product

GMP

Manufacturing is based on clearly written procedures Operators are trained Complete records document the manufacturing process. Failure investigations are carried out if quality problems come up

GMP

Proper storage and distribution of the products A recall system providing a final safety net, in case quality problems are detected after release of the product Complaint handling procedures are established to react to feedback from the market

Ten Trouble-some sections

1.

2.
3. 4. 5. 6. 7. 8.

9.
10.

Water System Microbiology Non-sterile products Calibration Quality Assurance Quality Control Specification Document & SOP Validation Air Quality

Ten Commandments

Write procedures! Follow the written procedures! Document (record) the work! Validate the work! Design & build proper facilities! Maintain the facilities and equipment! Be competent! Be clean! Commit to quality! Audit for compliance!

Water System Why validate?

To prove the performance of the water system under all conditions expected to be encountered during future operations. Water is commonly used. Needs processing prior to use. Quality attributes vary. Compendia specifies different grades. Treatment systems highly dynamic. Test results available only after usage. Statutory requirement.

Define specifications for different grades. Determine possible variations. Develop methods of analysis. Locate sampling points. Define sources of Supply. Set up sampling Time-table. Compile SOPs. Train personnel. Establish ALERT & ACTION limits. Test & Review trends.

Water System How to validate?

Water System Possible Deficiencies

Incomplete distribution diagram. Storage Tanks wrongly located. Storage Tanks incorrect MOC. Storage Tanks not cleaned & not secured. SOPs not detailed. Contamination not controlled. Alert limits overlooked. Etc Etc Etc.

MICROBIOLOGY SCOPE

To monitor environment. To test R.M. P.M. & F.G. To evaluate different grades of water.

Define specifications. Develop methods of testing. Prescribe ALERT & ACTION limits. Identify Sampling Points . Evolve Sampling scheme. Compile SOPs.

RESPONSIBILITES

Design Parameters

Allocate suitable & adequate space. Locate suitably. Provide for independent access. Provide for Media preparation, LAF etc. Permit supervision without entering area. Provide for independent HEPA filtered air. Control temperature & humidity.

Calibration
Definition: Calibration is defined as a comparison of a measurement standard or instrument of known accuracy with another standard or instrument to Detect, Correlate, Report and / or Eliminate by adjustment any variation in the Accuracy of the item being compared. Why? Make a good business sense. To ensure accuracy. To meet statutory requirements. What? Analytical and Trade Balances, Weights, Spectrophotometer, Colorimeter, Polarimeter, pH meter, Micrometer, Thermometers, Temperature recorders, Gauges, Timers. Etc Etc

CALIBRATION SOP

Draft a policy for Calibration Assign responsibility & train the individual responsible. Prepare an inventory of instruments/devices. Select, audit and appoint a calibration agency Compile different SOPs. Define the calibration calendar Integrate with preventive maintenance. Review trend of performance & generate data to justify chosen frequency. Compile Sops to deal with out of calibration Maintain comprehensive records.

CALIBRATION Choosing a Contractor

Reputed, Reliable & Accredited. Adequate trained staff. Traceable testing equipment. SOPs Comprehensive documents & records. Communications for quick access. WHEN YOU DO IT RIGHT, NO ONE REMEMBERS. WHEN YOU DO IT WRONG, NO ONE FORGETS.

QUALITY CONTROL
Responsible to QA Mgr. Implements controls Determines sampling scale Defines sampling method Samples materials Tests samples. Reviews COA Assigns & labels status Calibrates instruments. Validates test methods Ensures GLP Retains control samples & Records Ensures safety in lab.

QUALITY ASSURANCE
Responsible to CEO Motivates & trains personnel Develops product design Lays down specifications. Evaluates vendors. Reviews records & authorizes disposition Reviews stability studies Validates processes Audit facilities Investigates complaints Appraises performance

QUALITY CONTROL SYSTEM

Establish QC Laboratories. Compile SOPs. Assign responsibilities. Define Specifications. Permit access of QC personnel to all areas. Collect, evaluate and retain reference samples for 3 months after date of expiry. No batch of products to be released for sale unless certified by authorized personnel. Regularly calibrate & validate instruments & procedures. Review & revise specifications as necessary. Provide Pharmacopea, technical books, reference standard & spectra

SPECIFICATIONS
What are Specifications? Why are these required? How are these evolved? Who receives copies of RM specifications? What is the consequence of not having Specifications for printed labels? What is included in FG specifications? What do you understand by release specifications? Which specification will you use if any RM is included in IP, BP & USP? Compile a SOP for defining specifications. How will you deal with superceded specifications?

STANDARD OPERATING PROCEDURES TEN COMMANDMENTS

COMPILE VERIFY CONFIRM AUTHORISE DISTRIBUTE IMPLEMENT CONTROL STORE AUDIT REVIEW

DOCUMENTATION & RECORDS

Design, prepare, review and control documents Authorize personnel to approve & sign documents. Include title, nature & purpose of documents. Ensure legibility of reproduced copies. Regularly review and update documents. Sign & date any alteration. Record entries concurrently. Retain records and SOPs at least 1 year after expiry. Retain hard copies of Master Formula & operating procedures. Permit access to only authorized personnel. Restrict access by password. Independently check critical data Record changes and deletions. Provide backup for EDP Batch records. Ensure ready availability during retention period.

PROCESS VALIDATION
Process

validation is established documented evidence which provides a High Degree of Assurance that a specific process will consistently produce a product meeting its predetermined Specifications & Quality Attributes

WHY VALIDATE

GMP Risks Product Quality Risk. Regulatory requirement. Consistent Operation Good Business Practice Increased Confidence To meet Export requirement

WHAT TO VALIDATE

All machines, processes, systems that impact GMP & Product quality. Facilities & Utilities (Water, HVAC, Compressed Air) QC Methods Equipment cleaning methods Computers. Personnel Performance. Housekeeping.

VALIDATION PROCESS

Constitute a Validation Team & designate a Team Leader Evolve a Master Validation plan. Identify Equipment, Processes & Personnel. Establish Acceptance criteria. Compile SOPs & Protocols. Develop Testing methods.

VALIDATION MASTER PLAN

Developed at Project commencement. Managed & enforced throughout life cycle. Defines Validation approach. Specifies responsibilities. Draws up Validation calendar. SOP for Failure & Deviation Resolution.

HVAC & Air Quality

To avoid contamination & cross contamination. To provide suitable environment for production & testing of materials & finished products. To maintain required levels of cleanliness. To permit storage at prescribed conditions. To provide comfort & suitable working conditions. To ensure that product does not contain materials other than that what is stated in

The System components

Refrigeration system, Compressor & Condenser, Heat exchanger, Cooling tower, Expansion & mixing valves, Air handling unit, Filters, Blowers, Evaporative coil, Dehumidifiers, Supply and return air ducting, grills, Fresh air & Exhaust.

HVAC VALIDATION QUALIFICATIONS IQ, OQ, PQ

Personnel responsible for HVAC validation should be involved in the Design Process from early conceptual meetings. The goal is to verify & document the integrity of HVAC systems. In validating HVAC systems, knowledge of the Qualification Criteria is fundamental for implementing proper validation protocol. A PROTOCOL is a document in which a specific check or validation procedure is outlined-a document which assures the systems perform within specified parameters A protocol should clearly define the scope, equipment, methodology, acceptance & rejection levels as well as recording required in each case. My repairman refused to come & fix my air-conditioner. Claims it was too hot in my apartment.

Failure may lead to

Ordered component missing. Supplied component not per specifications. Installation not per manufacturers instruction. Nullification of guarantee. Encountering operational problems. Equipment damage. Cost over- run. Endangering product quality. Risk to personnel & property. Statutory non-compliance.

I have five years full guarantee on my new airconditioner- if I dont use it.

GMP

Self Inspection and Quality Audit. Quality Control System. Specifications. Master Formula Records. Packaging Records. Batch Packaging Records. Batch Processing Records.

GMP

Manufacturing Operations and Controls. Sanitation in the Manufacturing premises. Raw Materials. Equipment. Documentation and records. Labels and other printed materials. Quality Assurance.

GMP

Standard Operating Procedures (SOPs) & Records. Reference Samples. Reprocessing and Recoveries. Distribution Records. Validation & Process Validation. Product Recalls. Complaints and Adverse Reaction. Site Master File.