QUALITY MANUAL

QUALITY MANUAL 

QUALITY MANUAL describes one comprehensive model for an effective pharmaceutical quality system that is based on the quality concepts, includes applicable Good Manufacturing Practice (GMP) regulations and complements serves as the Validation Road map, setting the course, justifying the strategy, outlining the preliminary test and acceptance criteria, and documenting the necessary programs that ensure a continuing state of validation.

Table of Contents.

• APPROVAL
• SIGNATURES
• COMPANY PROFILE
• QUALITY SYSTEM
• Introduction
• Objective
• Scope
• QUALITY SYSTEN ELEMENT
• MANAGEMENT RESPONSIBILTY
• Management Commitment
• Responsibility & Authority
• QUALITY SYSTEM MANAGEMENT
• Quality Management Documents
• Quality Risk Management
• Quality Planning
• Resource Management
• Internal Communication
• Management of Outsourced Activities and Purchased Materials
• SYSTEM CONTROL
• Change Control Management
• Deviation Control
• Market Complaints
• Product Recall
• Corrective and Preventive Action System (CAPA)
• Self-Inspection
• Out of Specification
• Annual Product Quality Review (APQR)
• Stability Testing
• QUALIFICATION
• Vendor Approval
• Equipment Qualification
• Personal Qualification
• Personal Qualification
• Medical Check-Up
• Personnel Hygiene
• Sanitation and Cleaning
• VALIDATION
• Process Validation
• Analytical Method Validation
• Water System
• Compressed Air System
• TRAINING
• GLOSSARY
• REFERENCES

COMPANY PROFILE: _______________________ is a quality driven pharmaceutical company. The company was established in the year ______________, with a mission of helping the medical fraternity in healing the ailing & protecting the healthy people of our society.

The existing facility is situated in a pollution free area at _______________ and is surrounded by natural green environment. The plant started commercial production in________ for the manufacturing of, DRY SYRUP, LVP & SVP (FFS, Glass Vials).

At ___________________ quality is of prime importance which is achieved through well-established quality norms and systems. The facility complies the cGMP standards and the company along with its employees is dedicated to performing with passion towards welfare of the society by timely provision of quality products in the market.

QUALITY SYSTEM – Introduction: A Quality Manual is a document that summaries the organization overall philosophy, intentions, and approach to be used for establishing performance adequacy.

This document describes one comprehensive model for an effective pharmaceutical quality system that is based on the quality concepts, includes applicable Good Manufacturing Practice (GMP) regulations and complements serves as the Validation Road map, setting the course, justifying the strategy, outlining the preliminary test and acceptance criteria, and documenting the necessary programs that ensure a continuing state of validation.

The validation program is designed to demonstrate the quality features built into the facility and processes to ensure that these quality features are fully functional and conforms to the relevant regulatory requirements. The aim is that, once validated, the facility described herein can be used for the manufacturing of drug.

Objective: The purpose of the Quality Manual is to describe the quality system adopted by the company. It has been prepared to outline, how the company conducts its own affairs with respect to the achievement and assurance of quality. It is also intended to serve as documents for the company’s own Management and staff for understanding the company’s policy and procedure.

This document applies to the systems supporting the development and manufacture of pharmaceutical drug products. The elements of Quality Manual should be applied in a manner that is appropriate and proportionate to each of the product lifecycle stages, recognizing the differences among, and the different goals of each stage.

Scope: Processes needed for the quality system are identified in this quality manual and in associated operational procedures and work instructions. The documentation defines this quality system processes and their sequence, interaction and instructs on how to implement and apply them throughout the organization.

Quality system documentation also defines criteria and methods needed to ensure that the operation and control of quality system processes are effective. This usually includes assignment of responsibilities and allocation of resources for the process, instructions on how to carry out (or operate) the process, and definition of methods for monitoring and/or measuring the effectiveness of the process.

Operational Procedure, Document Control, explains in more detail how quality system processes are defined and documented.

QUALITY SYSTEM ELEMENT – QUALITY POLICY –The same is brief as:

Quality standards in the Technologies: With the ever-increasing introduction of newer drug combinations, the company is also using the mix of science and technology to meet and complete the challenges.

Quality standards in the Products: Necessary skill and expertise in practical applications of techniques have been put to increase the Therapeutic Efficacy of the drug so as to give the patient maximum relief in minimum time.

Quality standards in the Services: To combat any unexpected delay, the management prepares time framed schedules, well in advance, so as to keep pace with the services.

Implementation of quality policy is done through Quality System based on current Good Manufacturing Practices in conformance with national and international regulatory standards.

Organization Chart: The Organization chart of the company is indicated in site master file; The Chart is shown to the extent it is relevant to the implementation and maintenance of the Quality System.

SENIOR MANAGEMENT RESPONSIBILTY & COMMITMENT:

1. Senior management is responsible for assigning a management representative to develop and maintain the QMS, acting as representative in all issues concerning quality.
2. Communication to all concerned employees related to quality objectives i.e. Customer’s requirements as well as the statutory and regulatory requirements (where applicable) is ensured.
3. The quality manual, quality policies, and quality objectives are in place in the organization.
4. Management reviews meeting are performed on a regular basis to ensure that resources required are made available & are reviewed from time to time.
5. System to ensure creation of an environment that ensures involvement & development of people.
6. All necessary resources are provided.
7. Communication flows are timely within the organization and the supply chain
8. An organizational structure capable of supporting the elements of the quality policy and quality objectives.
9. Continuous improvement through corrective action and preventative action (CAPA), audits, and management reviews, and QMS planning and commitment.
10. System to define descriptions for measurement of the organization’s performance in order to determine whether planned results have been met.
11. System to ensure that knowledge related to statutory and regulatory requirements that apply to organization’s products/processes and activities are gained.
12. System to ensure that customer’s requirements are clearly understood & delivered.
13. Senior management has the ultimate responsibility to ensure that an effective pharmaceutical quality system is in place, is adequately resourced, and that roles, responsibilities, and authorities are defined, communicated and implemented throughout the organization. Senior management’s leadership and active participation in the pharmaceutical quality system is essential. This shall ensure the support and commitment of staff at all level and sites within the organization to the pharmaceutical quality system.

Responsibility & Authority: The responsibility and authority in principle, everyone in the organization shall be responsible for the execution of his/her own task and quality of performance.

In addition, the complete organization structure is designed in “House Structure” where in each module has its own part to deliver.

Parts/Elements of the Structure:

Quality Assurance: QA Department is in place to put in place the systems for qualification, validation and control of the procedures. The department takes care of all the documentation control, issuance, distribution & archival.

Production: Production Department comprises of Warehouse and all Production Processes Areas. The department responsibility and authority encompass production planning, production execution, production system control, production area maintenance, production validations.

Quality Control: QC comprises of Chemical Section and Microbiology Section. The department controls and monitors the quality aspect of the production, environment and systems through controlled procedures.

Engineering: Engineering department is in place to provide the complete utility support for the smooth functioning of all the departments. The departments responsibility is to maintain the health of all the utility supplies and regular compliance of the supply quality.

Personnel & Administration: P&A department is in place to provide the support & services of personnel and staff along with the material procurement for complete system working.

Management: The overall house works under the environment and culture governed and provided by the Management. The role encompasses to provision of all resources and conducive environment for all departments to work independently as well as a team towards the final goal of quality output.

QUALITY SYSTEM MANAGEMENT: Product and process knowledge should be managed from development through the commercial life of the product up to and including product discontinuation. For example, development activities using scientific approaches provide knowledge for product and process understanding. Knowledge management is a systematic approach to acquiring, analyzing, storing and disseminating information related to products, manufacturing processes and components. Sources of knowledge include but are not limited to prior knowledge (public domain or internally documented); pharmaceutical development studies; technology transfer activities; process validation studies over the product lifecycle; manufacturing experience; innovation; continual improvement; and change management activities.

Quality Management Documents:  This Quality Manual outlines the structure of the documentation used in the quality management system. This Quality Manual makes reference to supporting procedures including technical procedures and is maintained up to date.

This quality management system is structured in three tiers of documentation. The tiers are as follows:

1. Validation master plan
2. Standard Operating Procedures, Specification and Test Methods
3. Records

For most customers, this Quality Manual and the associated documents form a general Quality Plan. If necessary, specific Quality Plans will be prepared on a ‘per-customer’ basis. These Quality Plans will modify the general requirements stated in the Manual and associated documents. All of the above documents are controlled documents.

The following records and directive documents are referenced in the Quality Manual, but maintained separately:

1. Organization chart
2. Copies of the Quality Policy Statement posted in the company
3. Identification of resources and management review
4. Job descriptions of employees
5. Test reports
6. Identification of employees approved signatures
7. Laboratory’s scope of tests
8. Equipment inventory and records
9. Calibration status indicators
10. Reference standards inventory
11. Verification records
12. Change control
13. Quality control plan / criteria for workmanship
14. Corrective and preventive maintenance action records
15. Customer complaint records
16. Audit schedule and records
17. Procurement and subcontracting records
18. Training records
19. Master list of document
20. Confidentiality agreements
21. Agreements
22. Validation of test methods
23. Facility floor plan (Layout)

Quality Risk Management: Quality risk management is integral to an effective pharmaceutical quality system. It can provide a proactive approach to identifying, scientifically evaluating and controlling potential risks to quality. It facilitates continual improvement of process performance and product quality throughout the product lifecycle. The Quality System Management provides principles and examples of tools for quality risk management that can be applied to different aspects of pharmaceutical quality.

Quality Planning: 

(a) Senior management should ensure the quality objectives needed to implement the quality policy are defined and communicated.

(b) Quality objectives should be supported by all relevant levels of the company.

(c) Quality objectives should align with the company’s strategies and be consistent with the quality policy.

(d) Management should provide the appropriate resources and training to achieve the quality objectives.

(e) Performance indicators that measure progress against quality objectives should be established, monitored, communicated regularly and acted upon as appropriate as described of this document.

Resource Management: Management should determine and provide adequate and appropriate resources (human, financial, materials, facilities, equipment and instruments) to implement and maintain the pharmaceutical quality system and continually improve its effectiveness.

Management should ensure that resources are appropriately applied to a specific product, process or site.

Internal Communication: Management should ensure appropriate communication processes are established and implemented within the organization.

Communications processes should ensure the flow of appropriate information between all levels of the company.

Communication processes should ensure the appropriate and timely escalation of certain product quality and pharmaceutical quality system issues.

Management of Outsourced Activities and Purchased Materials:

The pharmaceutical quality system, including the management responsibilities described in this section, extends to the control and review of any outsourced activities and quality of purchased materials. The pharmaceutical company is ultimately responsible to ensure processes are in place to assure the control of outsourced activities and quality of purchased materials.

SYSTEM CONTROL: The Quality Management System in the plant through system control through following elements:

Change Control Management: In order to evaluate, approve and implement these changes properly, a company should have an effective change management system. There is generally a difference in formality of change management processes prior to the initial regulatory submission and after submission, where changes to the regulatory filling might be required under regional requirements.

The change management system ensures continual improvement is undertaken in a timely and effective manner. It should provide a high degree of assurance there are no unintended consequences of the change.

Change in raw material, packing components, production processes, quality control documents, test methods and specifications shall be documented, reviewed by a cross functional team and approved by Quality Assurance and wherever applicable. The approved change implemented shall be evaluated to confirm if the desired objective of making the change is achieved and there is no impact of the product quality.

Deviation Control: Deviations are defined as any time being deviate from a specific procedure, system, utilities, material, practice or protocol at any stages of manufacturing, testing, storage or distribution of semi-finished & finished drug products.

PLANNED DEVIATIONS: Deviation, which is planned, i.e. when there is a temporary change with respect to minor breach of cGMP requirements.

In case of planned deviations, the related investigation activities shall be studied before their implementation to assess its probable effect on product quality, safety, and efficacy and over all compliance status. Planned deviation should be carried out unless approved and authorized by quality assurance.

UNPLANNED DEVIATIONS: Deviation which are type of a failure to the chemical components, packing components, API’s, processes, system, equipment, utilities, and facilities, used to produce and control the drug products. The events typically, with some exceptions, fall into one of the following categories:

• Failure of system at site.
• Manufacturing zone environmental results outside the action limits.
• Product mix-up or cross contamination.
• Process or equipment failure.
• Reconciliation of yield.
• Product or material integrity issues.
• Procedure or system failure, damage and or contamination in storage or handling.

In case of unplanned deviations, head of QA with cross functional team immediately shall assess the investigation details and mentioned in the form and decide from the approval or rejection of the deviation along with the concerned/user department. He also arranges for the checking of the implementation and effectiveness of the CAPA.

Market Complaints: Complaints show customer dissatisfaction about the quality of a pharmaceutical product. Eurocrit Lab international pvt Ltd have an effective complaint handling system to improve the quality of their products, being a good tool for the maintenance of Good Manufacturing Practices and a way to establish a committed relationship with their customers. A systematic procedure is in place and implemented in order to register and investigate each complaint received and not only the Quality Assurance area must be involved.

Market Complaints shall be investigated by qualified, trained individuals and concluded with a written summary report. Complaint files shall be investigation of a complaint to ensure that finished products may have contributed to the product is quarantined, wherever applicable.

Product Recall: This guideline shall be applicable to, hold and/ or recall of drug products from distribution or market due to certain non-confirmatory aspects or instruction from regulatory agency. Hold and/ or recall of drug products sold in domestic and/ or export market.

A product recall may be defined as the retrieval from the marketplace of a batch (es) of a medicinal product as a result of a quality defect or other issue being identified with the batch (es) which resulted in the batch (es) not to be in compliance with the terms of the product marketing authorization. In addition, a product recall may be warranted due to the emergence of new safety information relating to a product or class of products.

A system shall be designed to promptly remove known or suspected defective product from the market place. Recalled products shall be identified and stored separately.

Procedures shall be in place which outlines Managements decision making process to recall, the mechanism for Regulatory Agency/Health Authority notification, the identification of distribution agents/wholesalers, hospitals, physicians and other to be contacted and the details for collecting, accounting, accounting for, and disposing of the recalled product.

Corrective and Preventive Action System (CAPA): Written procedures for implementation of Corrective and Preventive Actions resulting from the investigation of complaints, product rejection, non-conformances, recalls, deviations, audits, regulatory audit findings and trends from process performance and product quality monitoring shall be established and followed.

The Effectiveness of CAPA shall be evaluated and recorded. Procedures shall be established which define a planned approach to the investigation process with the objective of determining the root cause.

Remedial action: Immediate action to reduce or eliminate the non- conformity.

Corrective action: Action taken to eliminate the cause of an existing non-conformity, defect, or other undesirable situation in order to prevent re-occurrence.

Preventive Action: Action taken to eliminate the cause of a potential non-conformity, defect, or other undesirable situation in order to prevent re- occurrence.

Self-Inspection : The self-inspection planning with the intent to direct the inspection effort to the areas within the quality system that represent higher risk to the quality of the product and the achievement of the quality objectives.

Internal (Self) inspection shall be conducted in order to monitor the implementation of Quality principles and of applicable GMP and to propose necessary corrective measures.

Internal (Self) inspection shall be documented including observations, proposals for corrective measures and corrective actions taken.

The frequency and level (time, number of inspectors) of self-inspections, and allocation of inspectors to particular self-inspections (considering their experience and skills) based on the estimated levels of risk. This forms the basis for a risk-based inspection planning and enables refer as per SOP.

Out of Specification: The purpose of the investigation is to determine the cause of the OOS result. The source of the OOS result should be identified either as an aberration of the measurement process (laboratory error) or an aberration of the manufacturing process.

The laboratory testing of all starting raw materials (Active / In-actives), Packaging materials bulk, in-process & finished products.

Chemistry based laboratory testing and microbiological testing of all above materials for release, stability, product complaints & any other analysis where the material has regulatory or compendia limit associated with it.

Any laboratories test result of any of the above material, which is “out of specification”.

Analytical results of are not considered to be OOS, when the test was performed as a part of the training exercise or analytical method Development.

Annual Product Quality Review (APQR): The objective of documenting this annual review of Product report is to Review & Conclude product’s behavior with respect to all the parameters out lined in the protocol.

The overall review of the Product & the Process is of value addition, if required to improve or maintain the desired quality of the product to be delivered into the market with appropriate conclusions & with appropriate recommendations to the respective areas.

The Annual Product Review is intended to prove that the Manufacturing Process used for any Product is consistent based on the review of historical data of Manufacturing Process and quality parameters for the period of one year.

Documents for compilation of data required for APR are Batch Manufacturing Record, Batch Packing Record, Analytical data and Stability Data and Validation Protocol and other Related Documents.

Represent the Data related to each processing and testing parameters for the batches in Tabular or Graphical Form.

Compile process control charts.

List down the critical processing parameters and quality parameters of the product.

Check the data for compliance to specifications and variability.

Stability Testing: A testing program shall be performed on an adequate number of product batches to assess its stability characteristics including the determination of appropriate storage conditions and expiration dates. Adequate records shall be maintained to provide the data for stability reports.

The purpose of stability testing is to provide evidence on how the quality of a drug product varies with the time under influence of a variety of environmental factors such as temperature, humidity and light, air & to establish a shelf life for the drug product & recommended storage conditions.

QUALIFICATION:

Vendor Approval: Manufacturer of starting materials are assessed before procurement. Assessment is done through either by pre-purchase samples analysis, questionnaires or auditing the facility. SOP for approval of venders is in place.

A competent team is assessing the vendors to certify and approve. Periodic assessment of vendors is carried out to ensure cGMP compliance level for Vendor evaluation, & qualification procedure for raw & packing materials (e.g., audits, material evaluations, qualification)

Equipment Qualification:

Design Qualification (DQ): Design qualification is pre-qualification (Vendor Specification, Design & Operation check out) stage of the Validation Programmed.

DQ is carried out to evaluate and select the equipment / system according to pre-determined design requirements.

The critical quality and cGMP attributes of manufacturing equipment or systems shall be identified and included in the Design Qualification.

DQ shall be performed as a key stage of the validation life cycle on all-manufacturing systems, facilities and equipment.

The results of the DQ process shall be documented to provide evidence that the design is satisfactory.

Installation Qualification (IQ):

Pre – Installation Qualification – Selection criteria shall be mentioned for equipment to be purchased. The selection criteria shall be based on specific functions to be carried out by the equipment & the efficiency of the equipment.

Installation Qualification: IQ is to ensure that the equipment or system is installed according to written and pre-approved specifications.

• IQ shall involve in identification of all system elements, service, gauges and a documented records that the installed equipment satisfies the planned requirements.
• Identification and documenting of maintenance requirements for each installed item and the collection and collation of supplier operating and working instructions
• During Installation qualification a formal and systematic check of all installed equipment against specifications shall be carried out.
• The equipment shall be given a unique code for future identification and traceability.
• The process flow diagrams shall be documented at the time of Installation Qualification.

Operational Qualification (OQ): OQ is to verify that the system operates according to written and pre-approved specifications throughout all specified ranges. Operational Qualification is oriented to the Engineering function.

The plans for the O.Q shall identify the critical variables studies to be undertaken, the sequence of those studies, the measuring equipment to be used and the acceptable criteria to be met.

The critical variable studies shall incorporate specific details and tests that have been developed from specialty knowledge of the process and how the equipment will work.

Critical variable studies shall include a condition or set of conditions encompassing processing or operation limits.

The completion of Operational Qualification shall allow the finalization of Standard Operating Procedures for the equipment operation and cleaning, subsequently training shall be imparted to the operators.

Performance Qualification (PQ): The Performance Qualification of equipment / system is measured with respect to the quality attributes of the product & the results obtained are documented to ensure effective operation. This is called Performance Document of the equipment. The Performance Qualification shows the equipment / system is performing as intended using a representative of the process in which it is used.

Instrument Calibration: The calibration of all equipment / instrument at suitable interval based on manufacturer’s recommendation, historical experience and criticality of use, used in the process of manufacturing, packing, Q.C., maintenance and warehouse. This procedure is to be applied for both in-house calibration and outside party calibration. The instrument / equipment is planned for calibration as per Calibration Policy.

Personal Qualification: Each person engaged in the manufacturing, processing, packing or storage of a medicine shall have the adequate Education, Training and Experience or combination thereof, to enable that person to perform the assigned functions. They shall have authority to discharge their responsibilities impartially (e.g. Quality Control, Quality Assurance etc.). An adequate number of staff and Quality Assurance persons shall be provided to manufacture and test the products. In the Quality Control Laboratory all the analysts performing work shall be validated.

Medical Check-Up: All new employees are examined for medical fitness by Registered Medical Practitioner.

Annual health check-up record of each employee examined by a qualified medical Practitioner will be maintained.

All the personnel working in core manufacturing area are monitored by the immediate supervisor for absence of any infectious disease open lesions or open wounds. These persons are not allowed to work in areas where the products or immediate packing materials are handled in open condition.

Medical checkup shall be submitting his/her fitness certificate for resuming duty.

Periodic Visual examination is to be done for the employees who are engaged in Optical checking e.g. Personnel from Production, Quality Control, Quality Assurance and Warehouse.

Personnel Hygiene: All personnel are keeping body, hair, face, hands and fingernails Clean and not wears deodorant, after shave lotion, nail polish and make-up, wear cleaned linen appropriate before entry into the respective production and quality control areas.

For entry into the plant production area there are separate change rooms: staffs, workman (gents), workman (ladies) and visitors with adequate facilities for personnel cleanliness.

There is adequate facility for linen washing and storage. Uniforms, gloves, face mask, and footwear are provided and are used by employees. There are clear instructions on the usage and change of uniforms for primary and secondary gowning. Primary uniforms are cleaned on weekly basis by external services and secondary gown are cleaned everyday by in house laundry facility.

Eating, drinking, chewing and smoking are prohibited in the manufacturing area.

Sanitation and Cleaning: Written specification and procedures are there for cleaning manufacturing areas and equipments and records kept. The objective of sanitation and cleaning is to prove that the system is consistently cleaned from product, detergent and microbial residues to an acceptable level and to prevent contamination and cross-contamination. There is well established SOP which describes for procedure for cleaning, cleaning agents and their concentration used for and frequency of cleaning. Disinfectant have been tested for their efficacy against the microorganism and validated for further use. Cleaning procedures are validated and routinely monitored by chemical and microbial methods.

VALIDATION:

Process Validation: Process Validation is the means of ensuring and providing documentary evidence that processes (within their specified design parameters) are capable of repeatedly and reliably producing a finished product of the required quality.

Process Validation is essential part of cGMP, and it is conducted as per predefined protocols, which includes processing, testing and cleaning procedures.

The results are evaluated, analyzed and compared with acceptance criteria.

Processes and procedures are established on the basis of validation study and undergo periodic revalidation to ensure that they remain capable of achieving the intended results. Critical processes are validated prospectively and retrospectively.

A written report summarizing recorded results and conclusions is prepared, documented and maintained. Process validation is used for establishing documented evidence that a facility and processes do what they purport to do, based on information generated during actual implementation of the process.

Analytical Method Validation: Analytical method validation is the process by which shall be established, by laboratory studies, that the performance characteristics of the method meet the requirements for the intended analytical applications.  Methods need to be validated or revalidated.

• Before their introduction into routine use
• Whenever the conditions change for which, the method has been validated, e.g. instrument with different characteristics.
• Whenever the method is changed and the change is outside the original scope of the method.

Strategy of Validation Methods: The validity of a specific method should be demonstrated in laboratory experiments using samples or standards that are similar to the unknown samples analyzed in the routine.

In case of compendial method, it shall check for method suitability. In case of any specific regulatory recommendation total validation exercise shall be performed.

For non-compendial method, validation shall be performed for selected parameters depending upon the type of product and analytical method (instrumental / non-instrumental / microbiological). In case of new product, the developed method shall be checked for desired validation parameters as per the protocol to ensure its robustness.

Procedures for quality control in the routine (e.g. system suitability tests) Representative plots, e.g. chromatograms, spectra and calibration curves.

• Method acceptance limits performance data.
• The expected uncertainty of measurement results.
• Criteria for revalidation.
• Person who developed and initially validated the method.
• Summary and conclusions.

The following parameters should be considered for the Validation:

• Specificity with standards
• Linearity
• Precision of amounts
• Accuracy
• Intermediate precision
• Limit of Detection
• Limit of Quantization
• Specificity with sample
• Ruggedness
• Robustness

Water System, WFI System& Pure Steam System:

The Water System, WFI System& Pure Steam System treatment, storage and distribution systems designed, installed, commissioned, validated and maintained to ensure the reliable production of an appropriate quality. These are operated beyond their designed capacity.

Water System, WFI System& Pure Steam produced, stored and distributed in a manner that prevents unacceptable microbial, chemical or physical contamination (e.g. with dust and dirt). The use of the systems following installation, commissioning, validation and any unplanned maintenance or modification work approved by the quality assurance (QA) department. If approval is obtained for planned preventive maintenance tasks, they need not be approved after implementation.

Sources and treated Water, WFI & Pure Steam is monitored regularly for quality and for chemical, microbiological and, as appropriate, endotoxin contamination. The performance of water purification, storage and distribution systems is also monitored.

Records of the monitoring results and any actions taken are maintained for an appropriate length of time, where chemical sanitization of the systems is part of the bio contamination control programmed. A validated procedure is followed to ensure that the sanitizing agent has been effectively removed.

Compressed Air System: The compressed air system is designed to generate and distribute the desired quality of air at desired pressure for pneumatic operations of various functions in automatic control of equipment’s. The compressor collects the air from the environment through inlet filter silencer. The inlet filter silencer prevents the dust particles from entering the compressor cylinder and to minimize the noise. Air drier is a fully enclosed cabinet with temperature switch and moisture separator to remove condensate moisture and reduce levels of gaseous hydrocarbons. Control system is provided to regulate the operation of the compressor. A filtration unit is provided to eliminate the gross particulate matter such as fibers and metal particles etc.

The compressed air is distributed to the production area through pipeline with filter are provided at the user points in production area. Suitable instrumentations are provided on the compressor to regulate the pressure and temperature.

TRAINING: Every employee of the organization is trained on his / her area of operation prior to start of the work. The training is imparted depending on the nature of job and responsibilities and the cGMP training is mandatory for employee.

Training Plan: Monthly training schedule is prepared by Individual department with the start of new Year.

Selection of Trainer: QA head has expertise and authority to evaluate the Trainer of different department. Head – Quality Assurance in consultation with Plant head identifies internal trainer from different departments based on his / her qualification, communication / presentation skills, experience, knowledge and expertise or combination of thereof in the different areas of operation. Identified trainer shall conduct pre-certification training on the identified topic based on his / her area of expertise; on the basis of training the trainer shall be evaluated.

Types of Training:

Induction Training: It is imparted to all new technical employees.

The purpose of induction training is to help the new employee to settle down quickly into the job by becoming familiar with other employees, surroundings, job and the work environment. Induction Training shall be given to all new employees.

On Job related Training: It is imparted to all the technical employees their respective department, briefing them about their job descriptions, inter-departmental job responsibilities, at workplace etc. On Job training include operations, Standard Operating Procedure, maintenance, calibration of equipments and instruments, recent developments, and updates in functional area.

General Training: It shall include training on general SOPs guidelines, Good Manufacturing Practices, safety, Good Documentation Practice, Good Laboratory Practice, Housekeeping, Personnel Hygiene, Skill development, Attitude, Leadership etc.

External Training: External trainees whenever hired shall have to provide the evidence of their qualification, experience, expertise with their name, address and record in report of the same shall be maintained.

Employees shall be sent to the outside of the organization to attend the trainings, technical conferences, seminars arranged by external agencies to upgrade the skills as well as the developments in the field of GMP, Safety, behavior, communication or any other relevant areas.

GLOSSARY:

Change Management: A systematic approach to proposing, evaluating, approving, implementing and reviewing changes.

Continual Improvement: Recurring activity to increase the ability to fulfill requirements.

Control Strategy: A planned set of controls, derived from current product and process understanding, that assures process performance and product quality. The controls can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control.

Corrective Action: Action to eliminate the cause of a detected non-conformity or other undesirable situation. NOTE: Corrective action is taken to rectify the occurrence whereas preventive action is taken to prevent reoccurrence.

Design Space: The multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality.

Enabler: A tool or process which provides the means to achieve an objective.

Feedback / Feedforward:

Feedback: The modification or control of a process or system by its results or effects.

Feedforward: The modification or control of a process using its anticipated results or effects.

Feedback/ feedforward can be applied technically in process control strategies and conceptually in quality management.

Knowledge Management: Systematic approach to acquiring, analyzing, storing, and disseminating information related to products, manufacturing processes and components.

Outsourced Activities: Activities conducted by a contract acceptor under a written agreement with a contract giver.

Performance Indicators: Measurable values used to quantify quality objectives to reflect the performance of an organization, process or system, also known as “performance metrics,” in some regions.

Pharmaceutical Quality System (PQS): Management system to direct and control a pharmaceutical company with regard to quality.

Preventive Action: Action to eliminate the cause of a potential non-conformity or other undesirable potential situation. NOTE: Preventive action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence.

Product Realization: Achievement of a product with the quality attributes appropriate to meet the needs of patients, health care professionals, and regulatory authorities (including compliance with marketing authorization) and internal customers’ requirements.

Quality: The degree to which a set of inherent properties of a product, system or process fulfils requirements.

Quality Manual: Document specifying the quality management system of an organization.

Quality Objectives: A means to translate the quality policy and strategies into measurable activities.

Quality Planning: Part of quality management focused on setting quality objectives and specifying necessary operational processes and related resources to fulfill the quality objectives.

Quality Policy: Overall intentions and direction of an organization related to quality as formally expressed by senior management.

Quality Risk Management: A systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle.

Senior Management: Person(s) who direct and control a company or site at the highest levels with the authority and responsibility to mobilize resources within the company or site based in part on

State of Control: A condition in which the set of controls consistently provides assurance of continued process performance and product quality.

SITE MASTER FILE