PHARMACEUTICAL QUALITY

MANAGEMENT-I (614-T)

STANDARDIZATION OF
PHARMACEUTICALS
CHAPTER# 6, LECTURE-3
COURSE INCHARGE: Ms. Syeda Zainab
 OVERVIEW OF PREVIOUS LECTURE
 Current Good Manufacturing Practices
 General GMP guidelines for pharmaceutical products
 We have covered
Personnel
Premises
Equipment
Material
Sanitation and hygiene
Good practices in production
Good practices in QC
 OBJECTIVE OF TODAY’s LECTURE
 To complete standardization of
Pharmaceuticals
General GMP guidelines for pharmaceutical
products (Remaining aspects)
Validation
Self-inspection and quality audit
Documentation
QUALIFICATION AND VALIDATION
 The key elements of a qualification and validation programme of a company
should be clearly defined and documented in a validation master plan
 Qualification and validation should establish and provide documentary
evidence that:
(a) the premises, supporting utilities, equipment and processes have been
designed in accordance with the requirements for GMP (design
qualification, or DQ);
(b) the premises, supporting utilities and equipment have been built and
installed in compliance with their design specifications (installation
qualification, or IQ);
(c) the premises, supporting utilities and equipment operate in accordance
with their design specifications (operational qualification, or OQ);
(d) a specific process will consistently produce a product meeting its
predetermined specifications and quality attributes (process validation, or
PV, also called performance qualification, or PQ)umented in a validation
master plan.
QUALIFICATION AND VALIDATION
 Any aspect of operation, including significant changes to the premises,
facilities, equipment or processes, which may affect the quality of the
product, directly or indirectly, should be qualified and validated.
 Validation studies are an essential part of GMP and should be
conducted in accordance with predefined and approved protocols.
 A written report summarizing the results recorded and the
conclusions reached should be prepared and stored.
 Processes and procedures should be established on the basis of the
results of the validation performed.
 It is of critical importance that particular attention is paid to the
validation of analytical test methods, automated systems and cleaning
procedures
SELF INSPECTION AND QUALITY AUDIT
Regular independent inspection is necessary to evaluate
the manufacturer’s compliance with GMP in all aspects of
manufacturing.
Procedure for self inspection shall be documented
indicating:
o Evaluation
o Conclusion
o Recommendations for Corrective action
DOCUMENTATION
A document is any written ,printed or computer
generated information that is going to provide some
evidence.
Documentation is any communicable material that is
used to describe explain or instruct regarding some
attributes of an object, system or procedure such as its
parts assembly, maintenance installation and uses.
Good documentation is an essential part of the quality
assurance system and, as such, should exist for all aspects
of GMP.
WHY DOCUMENTATION IS MANDATORY?
 Its aims are:
 to define the specifications and procedures for all materials and
methods of manufacture and control;
 to ensure that all personnel concerned with manufacture know
what to do and when to do it;
 to ensure that authorized persons have all the information
necessary to decide whether or not to release a batch of a drug
for sale,
 to ensure the existence of documented evidence, traceability.
 to ensure the availability of the data needed for validation,
review and statistical analysis
 and to provide records and an audit trail that will permit
investigation.
CHARACTERISTICS OF DOCUMENT

Have a clear title

Have an identification number
Be approved by authorized person
Have a date of issue
Have a due date of version
List to whom it has been issued
Page numbers
DOCUMENTS REQUIRED
LABELS
 Labels applied to containers, equipment or premises should be clear,
unambiguous and in the company’s agreed format. It is often helpful in
addition to the wording on the labels to use colours to indicate status (e.g.
quarantined, accepted, rejected, clean).
 All finished drug products should be identified by labelling, as required by the
national legislation, bearing at least the following information:
o the name of the drug product;
o a list of the active ingredients, showing the amount of each present and a
statement of the net contents (e.g. number of dosage units, weight, volume);
o the batch number assigned by the manufacturer;
o the expiry date;
o any special storage conditions or handling precautions that may be necessary;
o directions for use, and warnings and precautions that may be necessary;
o the name and address of the manufacturer or the company
SPECIFICATIONS FOR STARTING AND
PACKAGING MATERIALS
 Specifications for starting, primary and printed packaging materials
should provide, if applicable, a description of the materials, including:
(a) the designated name and internal code reference;
(b) the reference, if any, to a pharmacopoeial monograph;
(c) qualitative and quantitative requirements with acceptance limits.
 Depending on the company’s practice other data may be added to the
specification, such as:
(a) the supplier and the original producer of the materials;
(b) a specimen of printed materials;
(c) directions for sampling and testing, or a reference to procedures;
(d) storage conditions and precautions;
(e) the maximum period of storage before re-examination.
SPECIFICATIONS FOR FINISHED PRODUCTS
Specifications for finished products should include
(a) the designated name of the product and the code reference,
where applicable;
(b) the designated name(s) of the active ingredient(s)
(c) a description of the dosage form and package details;
(d) directions for sampling and testing or a reference to
procedures;
(e) the qualitative and quantitative requirements, with
acceptance limits;
(f) the storage conditions and precautions, where applicable;
(g) the shelf-life
MASTER FORMULA OR MASTER PRODUCTION
RECORD
 A formally authorized master formula should exist for each
product and batch size to be manufactured.
 The master formula and master production record should
include:
 the name of the product, with a product reference code

relating to its specification;

 a description of the dosage form, strength of the product and

batch size;
 a list of all starting materials to be used with the amount of

each, described
 a statement of the expected final yield with the acceptable

limits, and of relevant intermediate yields, where applicable;

MASTER FORMULA OR MASTER PRODUCTION
RECORD
 a statement of the processing location and the principal
equipment to be used;
 detailed step-wise processing instructions (e.g. checks on

materials, pre-treatments, sequence for adding materials,

mixing times, temperatures);
 the instructions for any in-process controls with their limits;
 where necessary, the requirements for storage of the

products, including the container, the labelling, and any special

storage conditions;
 any special precautions to be observed
BATCH PROCESSING/MANUFACTURING
RECORDS
 It is a product and batch specific document designed to give a
complete and reliable picture of the of each batch of every product.
 During processing, the following information should be recorded at the
time each action is taken, and after completion the record should be
dated and signed by the person responsible for the processing
operations:
 the name of the product;
 the number of the batch being manufactured;

 dates and times of commencement, of significant intermediate

stages, and of completion of production;

 the name of the person responsible for each stage of production;
 the initials of the operator(s) of different significant steps of

production and, where appropriate, of the person(s) who checked

each of these operations (e.g. weighing)
BATCH PROCESSING/MANUFACTURING
RECORDS
 the batch number and/or analytical control number and the
quantity of each starting material actually weighed (including
the batch number and amount of any recovered or
reprocessed material added);
 any relevant processing operation or event and the major

equipment used;
 the in-process controls performed, the initials of the person(s)

carrying them out, and the results obtained;

 the amount of product obtained at different and pertinent

stages of manufacture (yield), together with comments or

explanations for significant deviations from the expected yield;
 notes on special problems including details, with signed

authorization for any deviation from the master formula.

BATCH PACKAGING RECORDS
 A batch packaging record should be kept for each batch or part batch
 processed.
 The following information should be recorded at the time each action
is taken, and the date and the person responsible should be clearly
identified by signature or electronic password:
 the name of the product, the batch number and the quantity of bulk

product to be packed, as well as the batch number and the planned

quantity of finished product that will be obtained, the quantity
actually the reconciliation;
 the date(s) and time(s) of the packaging operations;
 the name of the responsible person carrying out the packaging

operation;
 the initials of the operators of the different significant steps;
 the checks made for identity and conformity with the packaging

instructions, including the results of in-process controls

BATCH PACKAGING RECORDS
 whenever possible, samples of the printed packaging materials
used, including specimens bearing the approval for the
printing of and regular check (where appropriate) of the batch
number, expiry date, and any additional over printing;
 notes on any special problems, including details of any

deviation from the packaging instructions, with written

authorization by an appropriate person;
 the quantities and reference number or identification of all

printed packaging materials and bulk product issued, used,

destroyed or returned to stock and the quantities of product
obtained to permit an adequate reconciliation
LABORATORY RECORDS
 It should include the complete data derived from the tests
necessary to assure the established specification and standard,
including examination and assay.
 A description of the sample received for the testing with

identification of source.
 Quantity, lot number, or other distinctive code, date and date

of sample was received for testing

 We have to mention the container number.

 A statement of each method used in the testing of the sample.

 If the method employed in the pharmacopoeia or in any other

recognized standard , the reference will suffice.

LABORATORY RECORDS
 A statement of the result and how they compare with established
standards of identity, strength, quality and purity for the
component, drug product tested.
 Records must indicates who performed each test( printed and
typed names should also be shown)
 Complete records shall be maintained of any modification of an

established method employed in testing.

 Complete records should be maintained of any standardization

of laboratory working standards, reagent and their solution.

 Record for periodic calibration for laboratory instruments,

apparatus, gauges, and recording devices and all stability testing

performed as per the requirement.
DISTRIBUTION RECORDS
It contain name and strength of the product and
description of the dosage form, name and address of the
consignee, date quantity shipped, and lot or control
number of the drug product.
Distribution records include a wide range of
documentation such as invoices, bill of lading, customer
receipts, and internal warehouse storage and inventory
records.
STANDARD OPERATING PROCEDURES
(SOP) AND RECORDS
 Standard operating procedures and associated records of actions
taken should be available for:
 equipment assembly and validation;
 analytical apparatus and calibration;
 maintenance, cleaning and sanitization;
 personnel matters including qualification, training, clothing

and hygiene;
 environmental monitoring;
 pest control;
 complaints;
 recalls;
 returns.
 SUMMARY
 We have completed
 Standardization of Pharmaceuticals
 REFERENCES
EU Good Manufacturing Practice (GMP) Guidelines, Volume 4
of “The rules governing medicinal products in the European
Union”
US FDA current Good Manufacturing Practice (cGMP) for
finished pharmaceuticals, 21 CFR, 210 and 211
WHO_QualityAssurancePharmVol2
FDA “Guidance for Industry: Q7A Good Manufacturing Practice
Guidance for Active Pharmaceutical Ingredients,” Section 19.
ICH Q7 Good Manufacturing Practice Guide For Active
Pharmaceutical Ingredients. Current step 4 version; November
2000