Quality Assurance

UNIT 1

Quality Assurance and Quality Management Concepts

1.1 Introduction

Quality is an important factor when it comes to any product or service. With the high market competition, quality has become the market differentiator for almost all products and services. Therefore, all manufacturers and service providers out there constantly look for enhancing their product or the service quality.

In order to maintain or enhance the quality of the offerings, manufacturers use two techniques, quality control and quality assurance. These two practices make sure that the end product or the service meets the quality requirements and standards defined for the product or the service.

There are many methods followed by organizations to achieve and maintain required level of quality. Some organizations believe in the concepts of Total Quality Management (TQM) and some others believe in internal and external standards.

The standards usually define the processes and procedures for organizational activities and assist to maintain the quality in every aspect of organizational functioning. When it comes to standards for quality, there are many. ISO (International Standards Organization) is one of the prominent bodies for defining quality standards for different industries. Therefore, many organizations try to adhere to the quality requirements of ISO. In addition to that, there are many other standards that are specific to various industries. As an example, SEI-CMMi is one such standard followed in the field of software development.

Since standards have become a symbol for products and service quality, the customers are now keen on buying their product or the service from a certified manufacturer or a service provider. Therefore, complying with standards such as ISO has become a necessity when it comes to attracting the customers.

1.1.1 Quality Control

Many people get confused between quality control (QC) and quality assurance (QA). Let's take a look at quality control function in high-level. As we have already discussed, organizations can define their own internal quality standards, processes and procedures; the organization will develop these over time and then relevant stakeholders will be required to adhere by them.

The process of making sure that the stakeholders are adhered to the defined standards and procedures is called quality control. In quality control, a verification process takes place. Certain activities and products are verified against a defined set of rules or standards.

Every organization that practices QC needs to have a Quality Manual. The quality manual outlines the quality focus and the objectives in the organization. The quality manual gives the quality guidance to different departments and functions. Therefore, everyone in the organization needs to be aware of his or her responsibilities mentioned in the quality manual.

1.1.2 Quality Assurance

Quality Assurance is a broad practice used for assuring the quality of products or services. There are many differences between quality control and quality assurance. In quality assurance, a constant effort is made to enhance the quality practices in the organization. Therefore, continuous improvements are expected in quality functions in the company. For this, there is a dedicated quality assurance team commissioned.

Sometimes, in larger organizations, a 'Process' team is also allocated for enhancing the processes and procedures in addition to the quality assurance team. Quality assurance team of the organization has many responsibilities. First and foremost, responsibility is to define a process for achieving and improving quality.

Some organizations come up with their own process and others adopt a standard process such as ISO or CMMi. Processes such as CMMi allow the organizations to define their own internal processes and adhere by them.

Quality assurance function of an organization uses a number of tools for enhancing the quality practices. These tools vary from simple techniques to sophisticated software systems. The quality assurance professionals also should go through formal industrial trainings and get them certified. This is especially applicable for quality assurance functions in software development houses.

Since quality is a relative term, there is plenty of opportunity to enhance the quality of products and services. The quality assurance teams of organizations constantly work to enhance the existing quality of products and services by optimizing the existing production processes and introducing new processes.

1.1.3 GMP (Good Manufacturing Practices) and Requirements of Premises, Plant and Equipment

In order to ensure production of quality drug formulation, it is necessary on the part of the manufacturer to follow well established and ethical approach involving different operations of manufacture. It was on several occasions discussed in professional meetings and conferences that there is a need for well set mandatary guidelines required to be followed by manufactures of different dosage formulations. It was with this background; Good Manufacturing Practices under Schedule M were made mandatory conditions for manufacturing operations of pharmaceutical formulations.

The quality of drug formulations is the sole responsibility of the manufacturer. He has to ensure the production of desired quality formulations and their stability until, the formulation reaches the consumer across the retailing counter. The Schedule M is covered under Rules 71, 74, 76 and 78 and is in two parts.

Part I deals with GMP relating to factory premises and materials.

Part II deals with requirement of plant and equipment.

1.1.4 PART I: Factory Premises and Materials (Salient Features)

•General Requirements

Good location; free from contamination due to sewage, drain, fumes, dust, smoke, etc.; hygienic conditions; prevention of entry of insect and/or rodents; interior surface of premises should be smooth; adequate lighting; proper ventilation; humidity control; underground drainage; concealed electrical and sanitary fittings in the premises; supply of pure water; regular cleaning and disinfection of premises; proper treatment of waste water; pollution control and disposal of pollutants.

•Warehousing Area

Adequate area for orderly warehousing of various categories of materials; adapted to ensure good storage condition; protection from adverse weather conditions; separate earmarked areas in same warehouse for quarantine status; separate sampling area; segregation for storage of rejected, recalled or returned materials; safe and secure areas for NDPS and hazardous substances; safe storage of printed packaging material; separate dispensing areas for Beta lactum, sex hormones, cytotoxic substances and other special categories; regular checks and rodent control.

•Sterile Products

Separate enclosed area with air locks; air supply through HEPA filters; routine microbial counts; laminar flow cabinets availability and access restricted only to authorized persons.

•Working Space

Adequate space for orderly placement of equipment and material; and separate storage area for raw material under test, approved and rejected. The pipe-work, electrical fittings and ventilation openings should be properly designed.

•Health, Clothing and Sanitation of Workers

The workers should be free from contagious diseases. It covers regular medical check-up facilities; proper toilet facility at a distance; personal cupboards and change room for workers.

•Medical Services

First-aid facility; medical examination of workers and all other staff at the time of recruitment; periodic medical check-up of all staff members once in a year; services of physicians available at short notice, proper facilities for vaccinations, etc.

•Sanitation in Manufacturing Premises

No accumulated waste; no dust particles as far as possible; proper disinfection and cleaning of premises and no stagnant water. The manufacturing premises should be used for specific purpose for which it is designed.

•Equipment

Properly installed to achieve operational efficiency; good quality equipment to be used. The equipment used should be such to facilitate through cleaning; prevent physical and chemical change through contact and minimize contamination. The written instructions for utilization of equipment be provided and accuracy, precision should be maintained.

•Raw Materials

Properly identified; analyzed; containers of raw materials inspected for any damage; stored at optimum temperature; labeled properly; systematically sampled by quality control personnel; tested for compliance of required standards; released from quarantine by quality control personnel through written instructions; and rejected materials destroyed or returned back to the supplier.

•Personnel Manufacture

Under direct supervision of competent technical staff; separate Head for Q.C. laboratory; qualified and experienced personnel for Quality Assurance and Quality Control Operations; labeling; quarantine and storage; batch numbering; testing, records of analysis; equipment assembly and calibration; maintenance; cleaning and sanitation; personnel; pest control; complaints, and recalls made and returns received.

•Manufacturing Operations and Controls

Competent technical staff supervision for weighing, measuring and other operations; nonsterile products free from E. coli and Salmonella microbes; conspicuously labelled with name, batch number, and other details; cross contamination avoided; and all process controls checked under master formula.

•Reprocessing and Recovery

The reason for reprocessing should be specified, corrective measures for recovery should be spelt out only if permitted in Master Formula.

•Product Containers

Compliance with pharmacopeial requirements; cleaning procedures and sterilization procedure should be properly followed. There should be written schedule for programs for cleaning of container. When bottles are not dried after washing, deionized water is used for rinsing.

•Labels and Other Printed Materials

Stored properly and separately; used as and when required and should not be inter-mixed.

•Distribution Records

Records properly maintained; records of complaints, adverse reactions and other reactions from consumers are also maintained.

•Quality Control System

Detailed instructions for quality control of raw materials and finished product; quality control for packaging and labeling; adequacy of storage, quality control procedure revised as and when possible and qualitative examination of returned products.

1.1.5 PART II: Plant and Equipment (Salient Features)

The Part II of Schedule M gives the details of the plant and equipment required for manufacture, quality control and quality assurance of different dosage forms. The specifications of equipments are also indicated. The details of requirements are categorized into 11 groups.

1.1.5.1 External Preparations: It covers ointments, emulsions, lotions, solutions, pastes, creams, dusting powders and other identical preparations.

(a) Minimum area: 30 square meters for basic installation and 10 square meters for ancillary area.

(b) Requirements: Mixing and storage tanks, jacketed kettles of different types, electric mixer, planetary mixer, colloid mill, triple roller mill, liquid and tube filling equipments, etc.

1.1.5.2 Oral Liquid Preparations: It covers syrups, elixirs, emulsions and suspensions.

(a) Minimum area: 30 square meters for basic installation -and 10 square meters for ancillary area;

(b) Requirements: SS mixing and storage tanks, jacketed kettles of different types, electric stirrer, electric colloidal mill, emulsifier, filtration equipment, bottle filling machine, cap sealing machine, deionizer or water distillation unit, clarity testing unit, etc.

1.1.5.3 Tablets: For effective production, tablet production department is divided into four sections

Mixing, granulation and drying section

Tablet compression section

Packaging section (strip/blister)

Coating section

(a) Minimum area: A minimum of 60 square meters for basic installation and 20 square meters for ancillary area for un-coated tablets. For coated tablet, additional area of 30 square meters for coating section and 10 square meters for ancillary area.

(b) Requirements: Disintegrator, sifter, powder mixer, mass mixer, planetary mixer, rapid mixer granulator, granulator, hot air oven, weighing machines, compression machine (single, multi-punch, rotary), punches and dies storage cabinets, table de-duster, table inspection unit/belt, dissolution test apparatus, single pan balance, hardness tester, friability and disintegration test apparatus, strip/blister packaging machine, leak test apparatus, tablet counter, jacketed kettles of different types, SS coating pan, polishing pan, weighing balance, exhaust system and vacuum dust collector, airconditioning system (wherever applicable), etc.

1.1.5.4 Powders

(a) Area: Minimum 30 square meters; additional room for actual blending

(b) Requirements: Disintegrator, electric mixer, sifter, SS vessels and scoops of suitable sizes, filling equipment, weighing balance, etc.

1.1.5.5 Capsules

(a) Area: A separate enclosed area, suitably air-conditioned and dehumidified. A minimum area of 25 square meters for basic installation and 10 square meters for ancillary area each for penicillin and non-penicillin section.

(b) Requirements (for hard gelatin capsules): Electrical mixing and blending equipment, capsule filling units (semiautomatic and automatic), capsules counters, weighing balance, disintegration test apparatus, capsule polishing equipment, etc.

1.1.5.6 Surgical Dressings

(a) Area: Minimum 30 square meters for basic installation; for medicated dressing additional room required.

(b) Requirements: Rolling, staining, cutting, folding and pressing machines; mixing tanks, hot air oven, steam sterilizer, work tables, etc.

1.1.5.7 Ophthalmic Preparations

It includes eye-ointment, eye lotions and other preparations for external use. Separate enclosed areas with air-lock arrangements required.

(a) Area: Minimum 25 square meters for basic installation and 10 square meters for ancillary area.

(b) Requirements: Hot air ovens, jacketed kettles of different types, colloid mill, ointment mill, SS-mixing and storage tanks; tube washing, drying, cleaning and filling machines; automatic vial washing machine, vial drying machines, sintered glass funnels, autoclave, liquid filling equipment, laminar flow units, air conditioning and dehumidification arrangement. rubber bung washing machine, etc.

1.1.5.8 Pessaries and Suppositories

(a) Area: Minimum 25 square meters for basic installation

(b) Requirements: Mixing, pouring and molding equipments; weighing devices. For pessaries manufactured by granulation and compression, requirements shall be as given under tablet.

1.1.5.9 Inhalers and Vitrallae

(a) Area: Minimum 25 square meters for basic installation.

(b) Requirements : Mixing, graduated delivery and sealing equipments.

1.1.5.10 Repacking of Drugs and Pharmaceuticals

(a) Area: