Good Manufacturing Practice (GMP)

Good Manufacturing Practice (GMP)

• GMP includes principles and procedures
• Therapeutic goods manufacturers follow them
• It helps to ensure products have the required quality
• GMP aims to reduce risks in pharmaceutical production
• Types of risks include cross-contamination in particular of unexpected contaminants
• Another risk is mix up confusion such as false labels being put on containers
• GMP becomes the standard benchmark required by governments

Basic Requirements of GMP

• Manufacturing processes must be defined, systematically reviewed by experts
• High-level assurance that medicines are manufactured to ensure safety, efficacy, and quality
• Qualification and validation must be performed
• Operators need to be trained to perform procedures correctly
• All necessary resources are provided
• Records need to be kept during manufacture with required procedures and instructions
• Proper product storage & distribution minimizes quality risks
• Marketed product complaints must be examined
• Quality medicines must comply with their marketing authorization

Components of GMP

Quality Management

• Quality management is overall intention and direction of an organization regarding quality
• Top management must formally express and authorize the organization's quality direction
• Basic elements of quality management include appropriate infrastructure or quality system encompassing organization structure, procedures, processes, and resources
• Also systematic actions ensure adequate confidence that a product satisfies requirements for quality

Quality Assurance (QA)

• Quality assurance includes all planned or systematic actions
• It provides adequate confidence that a product satisfies the necessary requirements for quality
• QA is company-based
• The system of Quality Assurance appropriate for the manufacture of medicinal Products ensures medicinal products are designed in a way that accounts for GMP requirements
• Also ensures managerial responsibilities are clearly specified, all necessary controls on intermediate products and any other in-process controls and validations are carried out
• Finished products are to be correctly processed and checked, according to defined procedures
• Medicinal products are not sold until quality control has been performed
• Self-inspection and/or quality audit procedures regularly appraise the QA system's effectiveness and applicability

Quality Control (QC)

• Quality control involves operational laboratory techniques
• It involves activities within an organization that help fulfill quality requirements
• QC is lab-based

Basic Requirements of Quality Control

• Adequate facilities, trained personnel, and approved procedures are available
• Personnel must take samples of starting materials, packaging materials, and finished products
• QC must approve of approved sample methods
• Test methods must be validated
• All deviations must be fully recorded and investigated
• Finished products must contain active ingredients complying with the marketing authorization
• An authorized person must certify a batch of product is done prior to release for sale
• Sufficient reference samples of starting materials and products must be retained
• They allow for future product examination

Sanitation and Hygiene

• Sanitation and hygiene must include cleaning and disinfection of personnel, premises, equipment, apparatus, production materials, containers, and products
• Written procedures should assign sanitation and cleaning responsibilities

Qualification and Validation

• Qualification relates to instruments and equipment
• Validation relates to processes
• Qualification and validation should provide documentary evidence
• Evidence says premises, supporting utilities, equipment, and processes have been designed, installed, and operated as required by GMP

Complaints and Product Recalls

• QA and GMP prevent errors
• QA systems should have a plan to deal with complaints if errors occur
• Knowledgeable staff must evaluate each complaint
• Complaint records provide the basis to assess validity and seriousness of deviations that caused complaints
• Complaint files determines whether any other similar complaints have been received on lots in question or other product lots

7- Contract Production and Analysis

• Contract production and analysis must be defined and controlled
• it avoids misunderstandings that could cause products, work, or analysis of unsatisfactory quality
• It can be achieved through a written contract
• The contract can sets out the duties of all parties and standards to be met
• The authorized person must give final approval for release in contract analysis

Self-Inspection, Quality Audits and Supplier Audits/Approval

• The purpose of self-inspection is to evaluate the manufacturer’s compliance with GMP in all aspects of production and quality control
• A self-inspection program should detect the implementation shortcomings of GMP and recommend corrective actions
• Self-inspections should be performed routinely and on special occasions
• An example occasion would be product recalls, repeated rejections, or inspections by health authorities
• The self-inspection team consists of personnel who can objectively evaluate GMP implementation
• Recommendations for corrective actions must be implemented
• Self-inspection procedures must be documented
• There should be an effective follow-up program

Quality Audit

• Supplement self-inspections with a quality audit
• A quality audit is an examination and assessment of all or part of a quality system
• Its specific purpose is to improve it
• External or independent specialists or a team designated by the management usually conduct the quality audits
• Audits may also be extended to suppliers and contractors

Personnel, Training, and Personal Hygiene

• Sufficient qualified personnel must carry out all tasks for which the manufacturer is responsible for GMP application
• Individual responsibilities should be defined, understood, and recorded for written job descriptions
• Personnel should be aware of GMP principles that affect them
• They should receive initial and continuing training, including hygiene instructions that are relevant to their needs

Premises

• Premises must be located, designed, constructed, adapted, and maintained to suit the operations carried out
• Premises layout and design should minimize error risks and permit effective cleaning/maintenance
• It avoids cross-contamination, dust build-up, and any adverse effect on product quality
• Electrical supply, lighting, temperature, humidity and ventilation must be appropriate
• Premises must be designed and equipped to afford maximum protection against insects or other animals
• Steps must prevent unauthorized people from entering
• Premises must be designed to ensure a logical flow of materials and personnel
• Premises used for finished product manufacturing must be designed and constructed to facilitate sanitation

Equipment

• Equipment must be capable of producing products, materials, and intermediates by the specified quality characteristics
• Equipment must be designed so that it is possible to clean it thoroughly
• Surfaces that touch come into contact with products should have smooth and polished finishes
• Smooth and polished finishes must not harbor contamination

Materials

• Materials include starting materials, packaging materials, gases, solvents, process aids, reagents, and labeling materials
• Materials used for operations such as cleaning, pest control, and lubrication of equipment should not come into direct product contact
• Such materials should be of a suitable grade to minimize health risks
• The main objective of a pharmaceutical plant is to produce finished products for patients by using a combination of starting and packaging materials

Waste Materials

• Provision should be made for waste and its safe storage awaiting disposal
• Toxic and flammable materials should be stored in suitably designed, separate, enclosed cupboards as required by national legislation
• Waste material must not accumulate
• It should be collected in suitable receptacles for removal to collection points
• It needs to be disposed of safely and sanitarily on a regular and frequent basis

Documentation

• Good documentation is essential to the QA system
• Documentation should exist for all aspects of GMP
• Documentation should also define the specifications and procedures for all materials, methods of manufacture, and control
• All manufacture personnel need to know what to do and when to do it
• Authorized persons must have all the information necessary to decide whether or not to release a medicine batch for sale
• Documented evidence, traceability, records, and an audit trail that will permit investigation are necessary

Maintaining Data

• Ensures data availability needed for validation, review, and statistical analysis
• Documentation may exist in paper-based, electronic, or photographic media

Holding and Distribution

• During the goods hold stage it is necessary to ensure that the goods remain in good condition
• Goods also should not become harmed or damaged through incorrect or unsuitable storage conditions or bad handling
• Quality goods have to be ensured to not be reduced to rubbish
• All goods must be stored in a clean, neat, orderly way
• Conditions must not affect quality or cause goods to deteriorate in any way

Inspection

• The role of the inspector has to ensure performance follows all license provisions
• Follows performance to GMP, GLP, GSP, and GCP
• Inspection objectives, include inspecting facilities/services according to GMP
• Products examination according to GMP guidelines
• Presentation of a detailed report on manufacturing standards
• Offering advice to improve in-process test procedure and serve the drug company
• Correction of any deficiencies
• Assisting and motivating manufacturers to comply with GMP and standards
• Inspector qualifications include having an excellent background about GMP, GLP, GSP, GCP regulations, ISO system, and evaluation of pharmaceutical products
• Inspectors Must have gained previous and post training, as well as practical experience in manufacture and quality control

Types of Inspection

• Routine: When manufacturers are newly established, renew a license to operate, produce a new product, modify a manufacturing process, or change equipment
• It can identify Non-compliance with GMP in every 3-5 years
• Concise Inspections: selected requirements of GMP are used as indicators of overall GMP performance
• Follow-up inspections: Monitors the result of corrective actions (6 weeks-6 months) after initial inspection involving specific GMP requirements need to be observed or defected
• Special inspections: Check following complaints, suspected quality defects in products
• All inspections types focus on one product, group of products, or operation (mixing, sterilization)
• They establish how a specific product is manufactured, gather specific information, and investigate the operations

Self-Inspection

• Evaluates a manufacturer’s compliance with GMP.

Quality System Inspection

• It checks if a satisfactory quality assurance system is in operation
• This includes a quality policy outlining the organization’s purpose/objectives
• This details the resources, documentation, and audit processes
• Frequency & duration of inspections depends on size of company, purpose, number of inspectors, whether it will require all types of inspections, all companies, new companies, new facilities, or large companies Routine on regular schedule annually
• New companies that have yet to be licensed
• New facilities before start production
• 5 years for large companies that contain validity of manufacturing license
• GMP certificates can be a good choice for these inspections rather than lengthy inspections

Preparing for Inspection

• Begins at the desk of inspector
• Review available documents relating to the visited company which includes manufacturing license and marketing authorization
• Report on adverse drug reactions, complaints & recall records, results of regulatory testing, and the previous inspection reports

Reports

Forms of Reports

• Full report of complete firm inform
• Lists GMP compliance and contains inspector information, summary/conclusion, and the site master file with a list of all products
• Update report based on the previous report and reflects changes
• Abbreviated report detailing specific standards applied to a product
• Specific queries about the quality control of products
• Short & rapid information from case of defect or recall

Report Content

Inspector Information includes:

• Date and name, inspection activities, sample & results, assessment of the site master file, and GMP related recalls from market in last 2 years

Summary and Conclusion Includes:

• Inspection progress step by step, and any compliance or non-compliance issues with time to correct

The Site Master Includes:

• Document prepared by the firm and their general and specific information

General Information Includes:

• The firm name and address as well as contact information
• Site description
• Quality management description
• Number of employees
• Licensed pharmaceutical manufacturing activities
• Other activities
• The type of products they actual create
• Use of any outside analytical or technical support

Specific information includes:

• A- personnel qualifications, experience, responsibility
• B-Premises describing the plan, rooms, and area of handling
• C-Maintenance of building & equipment
• D-Storage of raw materials to finished products
• E- The equipment being used
• F- The means of the products is in process and being controlled
• G- The quality control measures
• H- Their documentation processes
• I-Sanitation and hygiene
• J- Validation & revalidation program
• K-Distribution, complaints & recall

Personnel Management

• Personnel management the planning, organizing, compensation, integration, and maintenance of people
• Its purpose assists contributing to organizational, individual, and societal goals

Role of Personnel Manager

• Personnel managers provide assistance to top management The top management are the people who decide and frame the primary policies of the concern All kinds of policies related to personnel or workforce can be framed effectively by the personnel manager
• He advises the line manager as a staff specialist Personnel managers act as a staff advisor and assists line managers when dealing with personnel matters
• They attend problems and grievances of employees and guides them
• personnel manager acts as a mediator
• He acts as a spokespersons in direct contact with the employees and represents the organization in committees. He represents company in training programmes

Objectives of Personnel Management

• Enterprise Objectives: Personnel management help achieve organizational goals There will be a need for co-operation from everyone in the organization for achieving business goals Such persons should be employed who are capable of taking up the jobs also assigned to them

• Personnel Objectives: Personnel management aims at the material and mental satisfaction to each employee Will be possible when employees are provided with proper work environment and job satisfaction Workplace should be neat and clean and properly ventilated Includes good remuneration, job security, avenues for promotion, financial, and any improving performance

Social Objectives:

• Personnel management aims at preserving and advancing the general welfare of the community
• It can serve society by creating more employment opportunities, producing quality goods at cheap rates It can also help society by using productive resources in a best possible way and minimizing their waste

Principles of Personnel Management

• Its about Maximum Personnel Development and should: Award personnel for development, use scientific selection, provide high morale, labor with dignity, team support, effective communication among employees, and joint management, establish fair reward, and ensure effective utilization of human resources.
• Its about the process of awarding proper training to the personnel for their development

Technology Transfer in Pharmaceutical industry

• "a logical procedure controls the transfer of any process together with its documentation and professional expertise It connects developments or between manufacture sites

• Technology transfer is helpful to develop dosage forms in process, maintains quality of product, standardize process, and facilitate cost effective production

• Technology transfer refers to successful progress from drug discovery to product development, clinical trials and full scale commercialization

• Important for such researcher to materialize and scale in commercialization especially in case of developing product

• A patentable aspect of production is not included in TT but also includes business processes

Technology transfer may be done because of :

• lack of manufacturing capacity requiring collaboration
• lack of marketing/ distribution capabilities thus requiring partnerships; or for
• exploitation in different field that does not have necessary access nor knowledge

Success of Technology Transfer

• Consists of Communication, Certainty, Challenges, Capacity and Commitment
• Communication: The technology transfer chain is often long in process
• Efficient two way communication and cooperation between key stakeholders will remove barriers
• Certainty: removing barriers to technology transfer translate to increase certainty for the key stakeholders
• Challenges: impediment occur at very node, technology restrictions will lead to a a lot of challenges in tt chain
• Capacity : enhancing the transfer of to create a more favorable circumstance for TT ensures all stakeholders have ability to fulfil their roles and meet their responsibilities
• Commitment: for a successful there may be a lot of obstacles in the transfer between users in terms of choice and safety of transfer