Sources/variables of Quality Variation.

General Sources Causing Quality Variation.

 Variety of products are manufactured through complex procedures, so, a). Materials.
making the Industry a complex Industry.
1). Variation among suppliers of same product.
 There fore, the Industry must be aware of the responsibilities relating to
2).Variation among batches.
 Ethical
3). Variation within the batch.
 Legal
b). Machines.
 Economic aspects.
1). New.
 It must take into the account of Quality variables like:
2). Old.
 Raw materials and Packaging Materials.
3). Variation of equipment, technology --- etc.
 In Process.
c). Methods.
 Labeling.
1). Old.
 Finished Products.
2). New.
3). In exact procedures.
4). Negligence ------ etc.

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d). Men (Personnel).

Active raw Materials
1). Inadequate Training.
 No raw Material is absolutely pure and so must be tested for its:
2). Improper Working Conditions.
 Identity
3). Dishonesty.
 Purity
4). Qualifications/Experience.
 Quality
Control of these Variations
 It must be tested Quantitatively before utilization.
For example, for Raw materials which may be:  Synthetic products always contain undesirable substances in the form of
 Active ( Active Pharmaceutical Ingredients/Drugs). by-product and product of degradation.
 Inactive ( Excipients). Hence, their Limits should be tested for specifications.
 Printing and packaging materials.  Drug substances are also tested for their:
 Physical,
 Chemical and
 Biological activities -- so that Reproducible
products can be manufactured.

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GMPs: QM 7th Semester 1

 To start Printing and packaging materials.
Inactive Raw Materials (Excipients).  Officially labeling includes all written, printed and graphic materials and
 Inactive raw Materials are diluents, lubricants, glidants, disintegrants, consists of TWO components. i.e.
binders, buffers, antioxidants, coating materials etc.  Primary components e.g.. Closure and containers.
Quality of the product is influenced by:  Secondary components such as labels, inserts and cartons.
 Interaction with drug substances.  Printing and packaging materials must comply with official standard.
 Affecting the physical properties of the dosage forms.  All typographical mistakes should be corrected.
 Influencing the production process.  Label mix must be checked and measures should be adopted to avoid it.
 Excipients are checked as per official specifications at the time of receipt to NOTE:
avoid any Adverse reaction.  Manufacturer must send qualified expert, experienced and Capable
 Checking is conducted for : personnel to the suppliers to have a quality raw materials.
 Labels.  Instructions must be given for standard etc.
 Containers.
 Packing.
 After thorough checking at the top, bottom etc., The representative sample
is taken for analysis.

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 GMPs give the guidelines for minimum standard of quality.

Control of Manufacturing Practice. GMP Principles:
For a Quality product the Industry must follow:  Good manufacturing practice guidelines provides guidance for
 Good Manufacturing Practice (GMPs) & Quality Control (QC) manufacturing, testing, and quality assurance in order to ensure that drug
procedures. product is safe for human consumption.
 Current Good Manufacturing Practices (cGMPs).  Many countries have legislated that pharmaceutical and medical device
manufacturer must follow GMP procedures, and have created their own
 Good Manufacturing practices (GMP’s)
GMP guidelines that correspond with their legislation.
 Good manufacturing practices are the sets of the principles, regulations,
All guidelines follow a few basic principles:
codes (law or official standard), guidelines and procedures and part of
quality assurance system which must be followed by the manufacturers to  Hygiene: Pharmaceutical manufacturing facility must maintain a clean
ensure that the products that are consistently produce are of quality and hygienic manufacturing area.
standard and appropriate for their intended use and cover the manufacturing  Controlled environmental conditions in order to prevent cross
and testing of pharmaceutical dosage form and active pharmaceutical contamination of drug product from other drug or extraneous particulate
ingredients, diagnostics, foods, various other pharmaceutical products and matter which may render the drug product unsafe for human
medical devices. consumption.
 Current Good Manufacturing practices (cGMP’s)  Manufacturing processes are clearly defined and controlled. All critical
 cGMP’s are used for the technology that is up to date. processes are validated to ensure consistency and compliance with
specifications.

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GMPs: QM 7th Semester 2

  A system is available for recalling any batch of drug from sale
or supply.
 Manufacturing processes are controlled, and any changes to the  Complaints about marketed drugs are examined, the causes
process are evaluated. Changes that have an impact on the quality of quality defects are investigated, and appropriate measures
of the drug are validated as necessary. are taken with respect to the defective drugs and to prevent
 Instructions and procedures are written in clear and unambiguous recurrence.
language. Components of GMPs
 Operators are trained to carry out and document procedures. GMP has the followings main components.
 Records are made, manually or by instruments, during manufacture  Personnel.
that demonstrate that all the steps required by the defined  Building and Equipment.
procedures and instructions were in fact taken and that the quantity
and quality of the drug was as expected. Deviations are investigated
 Control of Records.
and documented.  Record of Master Formula.
 Records of manufacture that enable the complete history of a  Record of Batch Production.
batch to be traced are retained in a comprehensible and accessible  Control of Production Procedures.
form.  Manufacturing control.
 The distribution of the drugs minimizes any risk to their quality.  Packaging Control.

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 Building and Equipment.

 Personnel  Building.
 For manufacturing quality product, following steps must be taken: o Proper construction with;
o Creation of quality conscious in personnel.  Adequate space.
o Proper training, selection and motivation.  Ventilation (air handling unit AHU , HVAC).

o Personnel motivation works through that every one feels pride of  Sanitation facilities.
producing quality product. o Proper design to avoid Cross-contamination of Raw materials.
o Employing qualified, experienced, expert and skilled personnel capable
of executing any assignment. o For Parenteral and other specific Dosage Forms (Eye preps.,
Infusion, Vaccines & sera etc.), special measures must be taken as;
o Atmosphere to work honestly and with responsibility.
• Sterilization of work area.
o Supervisor in every section.
• Bacterial contamination should be avoided.
o Counter sign by supervisor
• Construction and maintenance of clean rooms

o Prevention of dissemination of micro-organisms.

NOTE.
Motivation etc. --- leads to ZERO DEFECT concept which works
through Prevention rather than Detection of Errors and Mistakes.

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GMPs: QM 7th Semester 3

  Control of Records.
 Equipment.  Record of Master Formula.
 These should be of suitable size, design and location to accomplish  Record of Batch Production.
GMP.  Record of Master Formula
o Equipment may be of many types.  “Master formula means a document or set of documents specifying
o Should be of; the starting materials with their quantities and the packaging
• Suitable accuracy AND materials, together with a description of the procedure and the
precautions required to produce a specified quantity of a finished
• Reproducibility.
product as well as the processing instructions, including the in-
o They should be : process controls”.
• Inert. • Master formula for each product is prepared by competent and
• Non-reactive responsible person and must be checked by another responsible
• Non-additive person.
• Written neatly and clearly to avoid any mistake and misleading.

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 Control of Production Procedures

 Master formula differs from product to product. However, it should  Manufacturing control.
contain the followings information:  Packaging Control.
i. The name of the product with dosage form and its strength.  To have proper Identity, Purity, Strength and Quality of product, the In
ii. List of all ingredients with their characteristics. Process Quality Control (IPQC) procedures are observed rigidly and
iii. Quantity of all ingredients (wt. & vol.) regularly for each Batch
iv. The standard and specifications of all ingredients.  IPQC are observed from the receipt of raw material and its consumption
v. Manufacturing and control instructions. in different dosage forms
vi. Detailed instructions along with precautions about:  IPQC helps in minimizing the error and mistake.
• Closure  Though planning and manufacturing operational control sheet differs
from one organization to another, however, common things are as
• Label below:
• Container  Production planning department issues the formula and planning
• Packaging sheet containing;
• Storage i. Names and quantities of all ingredients.
 Record of Batch Production. ii. Identification number.
Record of each Batch is kept for its iii. Specified procedures.
iv. Precautions AND
 Production including all information.
v. Quality standard.
 Procedure and Batch number etc.
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GMPs: QM 7th Semester 4

 Statistical Quality Control (SQC).
 It provides Theoretical Yield at all stages.
 Characteristics of product from both Qualitative and Quantitative point of
 Coupon/Material Tickets are sent to store by production views are related to meet the established standards.
department.
 Quality of process and product is observed.
Statistical Quality Control (SQC)  SQC gives a logic approach to the Quality variations.
The monitoring of quality by application of statistical methods in all  SQC based on Theory of Probability.
stages of production.”  Parameters are assessed using Significant level from the official table.
Or  Meaningful decisions can be made regarding Quality variations.
“The application of statistical methods to quality control.”  SQC depends upon:
 It refers to characteristics of product from both quantitative and i. Types of measurements.
qualitative point of view to meet established standards. ii. Methods of sampling.
 By using charts and collecting few frequent samples, we can detect iii. Design of experiment.
the change in process that may affect the quality.
iv. Type of distribution (simple, binomial or any other distribution).

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 Analysis of Data is done using an appropriate method of analysis ---

e.g.
 “t-value” is calculated and from table its “p value” is noted. If “p ˂
0.05 (less than), then it is Non-significant. If “p ˃ 0.05, (greater
than), then it is Significant difference. CONCLUSIONS.
 More than TWO populations are compared using some other methods  To control the sources of Quality Variables namely Materials, Methods,
e.g. ANOVA (one way or two way) etc. Machines and Men (personnel).
NOTE.  To ensure GMP and cGMP.
 SQC predicts whether variations are by chance or can be  To observe standards or established specifications.
attributed to “assignable causes” like machines or process or
 Stability study and stability data along with other activities of the product
material etc.
should be maintained through a well organized “Total Quality Assurance
 By “SQC” magnitude of chance variation or assignable Organization/department”.
variation can be detected and minimized.

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GMPs: QM 7th Semester 5