UNIT- I

QUALITY MANAGEMENT IN THE DRUG INDUSTRY (WHO):

In the drug industry at large, quality management is usually defined as the aspect of management
function that determines and implements the “quality policy”, i.e. the overall intention and
direction of an organization regarding quality, as formally expressed and authorized by top
management. The basic elements of quality management are:  an appropriate
infrastructure or “quality system”, encompassing the organizational structure, procedures,
processes and resources;  systematic actions necessary to ensure adequate confidence that a
product (or service) will satisfy given requirements for quality.

QUALITY CONTROL:

 A system of maintaining standards in manufactured products by testing a sample of the output

against the specification. ISO 9000 defines quality control as "A part of quality management
focused on fulfilling quality requirements". It is that part of GMP concerned with sampling,
specification and testing, documentation and release procedures which ensure that the necessary
and relevant tests are performed and the product is released for use only after ascertaining its
quality.

RESPONSIBILITIES OF QC:

1. QC is responsible for day to day control of quality within the company.

2. QC is responsible for analytical testing of incoming raw materials and inspection of
packaging components, including labeling, they conduct in-process testing when
required, perform environmental monitoring, and inspect operations for compliance.
3. They also conduct the required tests on finished dosage form.
4. QC plays a major role in the selection of qualified vendors from whom raw materials are
purchased.
5. The environmental areas for manufacturing of various dosage forms are tested and
inspected by QC department.
QUALITY ASSURANCE:

DEFINITIONS: Quality assurance is a wide-ranging concept covering all matters that

individually or collectively influence the quality of a product. With regard to pharmaceuticals,
quality assurance can be divided into major areas: development, quality control, production,
distribution, and inspections. (WHO)

The totality of these actions is termed “quality assurance”.

Within an organization, quality assurance serves as a management tool. In contractual situations,

quality assurance also serves to generate confidence in the supplier. The concepts of quality
assurance, GMP and quality control are interrelated aspects of quality management. They are
described here in order to emphasize their relationship and their fundamental importance to the
production and control of pharmaceutical products.

ISO 9000 define QA as a Part of quality management focused on providing confidence that
quality requirements will be fulfilled. It is the totality of the arrangements made with the object
of ensuring that pharmaceutical products are of the quality required for their intended use.
Quality assurance therefore incorporates GMP and other factors, including those outside the
scope of this guide such as product design and development.

RESPONSIBILITIES OF QA

(a) Pharmaceutical products are designed and developed in a way that takes account of the
requirements of GMP and other associated codes such as those of good laboratory practice
(GLP) and good clinical practice (GCP).

(b) Production and control operations are clearly specified in a written form and GMP
requirements are adopted.

(c) Managerial responsibilities are clearly specified in job descriptions.

(d) Arrangements are made for the manufacture, supply and use of the correct starting and
packaging materials.
(e) All necessary controls on starting materials, intermediate products, and bulk products and
other in-process controls, calibrations, and validations are carried out.

(f) The finished product is correctly processed and checked, according to the defined procedures.
(g) Pharmaceutical products are not sold or supplied before the authorized persons) have certified
that each production batch has been produced and controlled in accordance with the
requirements of the marketing authorization and any other regulations relevant to the production,
control and release of pharmaceutical products.

(h) Satisfactory arrangements exist to ensure, as far as possible, that the pharmaceutical products
are stored by the manufacturer, distributed, and subsequently handled so that quality is
maintained throughout their shelf-life.

(i) There is a procedure for self-inspection and/or quality audit that regularly appraises the
effectiveness and applicability of the quality assurance system.

(j) Deviations are reported, investigated and recorded.

(k) There is a system for approving changes that may have an impact on product quality.

(l) Regular evaluations of the quality of pharmaceutical products should be conducted with the
objective of verifying the consistency of the process and ensuring its continuous improvement.

DIFFERENCE BETWEEN QA AND QC 

1. QA is process oriented and QC is product oriented.

2. QA is a set of activities for ensuring quality in the processes by which products are
developed QC is a set of activities for ensuring quality in the products.
3. The activities focus on identifying defects in the actual products produced.
4. QA is a managerial tool while QC is a corrective tool.
5. QA aims to prevent defects with a focus on the process used to make the product while
QC aims to identify and correct defects in the finished products.
 6. QA goal of QA is to improve development and test processes so that defects do not arise
when the product is being developed while Goal of QC is to identify defects after a
product is developed and before it’s released.
7. QA aim is to prevent the defect. While QC aim is to identify and improve the defects.
8. QA is the technique of managing the quality. While QC is method to verify the quality.
9. QA does not involve executing the program. While QC always involves executing the
program.
10. All team members are responsible for QA. While Testing team is responsible for QC. 
QA e.g. Verification. While QC e.g. Validation.
11. QA means Planning for doing a process. QC Means Action for executing the planned
process.
12. Statistical Technique used on QA is known as Statistical Process Control (SPC.)

Statistical Technique used on QC is known as Statistical Quality Control (SPC.)

1. QA makes sure you are doing the right things. QC makes sure the results of what you’ve
done are what you expected.
2. QA Defines standards and methodologies to followed in order to meet the customer
requirements. QC ensures that the standards are followed while working on the product.
3. QA is the process to create the deliverables. QC is the process to verify that deliverables.
4. QA is responsible for full software development life cycle. QC is responsible for software
testing life cycle.

GOOD MANUFACTURING PRACTICE (GMP):

Good Manufacturing Practice is a part of quality assurance which ensure that the products are
consistently produced and controlled according to quality standards appropriate to their intended
use.  GMP – A set of principles and procedures which, when followed by manufacturers for the
therapeutic goods, helps ensure that the products manufactured will have the required quality  It
is designed to minimize the risks involved in any pharmaceutical production that cannot be
eliminated through testing the final product.
GMP COVERS:  All aspects of production; from the starting materials, premises and
equipment to the training and personal hygiene of staff.  Detailed, written procedures are
essential for each process that could affect the quality of the finished product.  There must be
systems to provide documents proof that correct procedures are consistently followed at each
step in the manufacturing process every time a product is made.

WHO GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL

PRODUCTS:

MAIN PRINCIPLES  GMP is that part of quality management which ensures that products are
consistently produced and controlled according to the quality standards appropriate to their
intended use and as required by the marketing authorization, clinical trial authorization or
product specification. GMP is concerned with both production and QC. GMP is aimed primarily
at managing and minimizing the risks inherent in pharmaceutical manufacture to ensure the
quality, safety and efficacy of products.

UNDER GMP:

a)All manufacturing processes are clearly defined, systematically reviewed for associated risks in
the light of scientific knowledge and experience, and shown to be capable of consistently
manufacturing pharmaceutical products of the required quality that comply with their
specifications.

b) Qualification and validation are performed.

c) All necessary resources are provided, including:  sufficient and appropriately qualified and
trained personnel,  adequate premises and space,  suitable equipment and services, 
appropriate materials, containers and labels,  approved procedures and instructions,  suitable
storage and transport,  adequate personnel, laboratories and equipment for in- process controls;

d) Instructions and procedures are written in clear and unambiguous language, specifically
applicable to the facilities provided.

e) Procedures are carried out correctly and personnel are trained to do so.
f) Records are made (manually and/or by recording instruments) during manufacture to show
that all the steps required by the defined procedures and instructions have in fact been taken and
that the quantity and quality of the product are as expected. Any significant deviations are fully
recorded and investigated with the objective of determining the root cause and appropriate
corrective and preventive action is implemented.

g) Records covering manufacture and distribution, which enable the complete history of a batch
to be traced, are retained in a comprehensible and accessible form.

h) The proper storage and distribution of the products minimizes any risk to their quality and
takes account of good distribution practices (GDP).

i) A system is available to recall any batch of product from sale or supply.

j) Complaints about marketed products are examined, the causes of quality defects investigated
and appropriate measures taken in respect of the defective products to prevent recurrence.

LISTS OF IMPORTANT DOCUMENTS IN GMP

Policies, Standard operating procedures SOP, Specifications, Master formula records MFR,
Batch manufacturing record BMR, Manuals, Master plans/Files, Validation protocols, Forms
and formats, Records.
•An applicant laboratory is expected to submit to NABL 5 copies of the application
and 5 copies of Quality Manual.
•The Quality Manual will be forwarded by NABL to a Lead Assessor to judge the
adequacy of the Quality Manual as to whether it is in compliance with ISO 15189
standards.
•Thereafter the Lead Assessor will conduct a PreAssessment of the laboratory for
one day. Based on the Pre-Assessment report the laboratory may have to take certain
corrective actions, so as to be fully prepared for the final assessment.
•It is essential for the applicant as well as accredited laboratories to satisfactorily
participate in Proficiency testing/ Interlaboratory comparisons/External quality
assessment programme suchas Asia Pacific Laboratory Accreditation Cooperation
(APLAC) Mutual Recognition Arrangement calls for mandatory participation in
such programmes.
•Finally when the laboratory is ready, the Lead Assessor and a team of technical
assessors will conduct the final assessment.The number of technical assessors
will depend on the number of disciplines applied for.
• The accreditation process involves a thorough assessment of all the elements of
the laboratory that contribute to the production of accurate and reliable test data.
These elements include staffing, training, supervision, quality control,
equipment, recording and reporting of test results and the environment in
which the laboratory operates.
•The laboratory may have to take certain corrective actions, after the final
assessment. After satisfactory corrective actions are taken by the laboratory
(within a period of 3 months), the Accreditation Committee will examine the
report and if satisfied recommend accreditation.
•The time required for the process of accreditation will depend upon the
preparedness of the laboratory and its response to the non - conformances
raised during the pre-assessment and final assessment. The total duration
ranges between 6 and 8 months.