DOCUMENTS on quality of pharmaceutical products

Batch Record
• What is Batch ?
• “A specific quantity of a drug or other material that is intended to have
uniform character and quality, within specified limits, and is produced
according to a single manufacturing order during the same cycle of
manufacture”
• It is a written document of the batch, prepared during pharmaceutical
manufacturing process. It contains actual data and step by step process
for manufacturing each batch.
• It is a proof that batches were properly made and checked by quality
control personnel
• should be prepared for each intermediate and API/formulation and
should include complete information relating to the production and
control of each batch.
• Should have unique batch or identification number and dated and signed
when issued
• Batch number should be immediately recorded in a logbook or by
electronic data processing system. The record should include date of
allocation, product identity, and size of batch.

Batch Record
• Two type: Batch Processing Records & Batch Packaging Records
• Batch Processing Records:
• Its maintained for each batch
• It should be based on approved Manufacturing formula & Processing
instructions
• Design of batch processing records should be such that it should
avoid any transcription errors
• Record must carry batch number of processed lot
• Before any processing begins, there should be recorded checks that
the equipment and work station are clear of previous products,
documents or materials not required for the planned process, and that
equipment is clean and suitable for use.

BATCH PROCESSING RECORD INCLUDES
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 in agreement by the
person responsible for the processing operations:
a) Name of the product
b) Dates and times of commencement, of significant intermediate stages and of completion
of production
c) Name of the person responsible for each stage of production
d) Initials of the operator of different significant steps of production and, where
appropriate, of the person who checked each of these operations (e.g. weighing);
e) The batch number and/or analytical control number as well as the quantities of each
starting material actually weighed (including the batch number and amount of any
recovered or reprocessed material added);
f) Any relevant processing operation or event and major equipment used;
g) A record of the in-process controls and the initials of the person(s) carrying them out,
and the results obtained;
h) The amount of product yield obtained at different and pertinent stages of manufacture;
i) Notes on special problems including details, with signed authorization for any deviation
from the Manufacturing Formula and Processing Instructions.

BATCH PACKAGING RECORDS
Be kept for each batch or part batch processed.
It should be based on the relevant parts of the Packaging
Instructions and the method of preparation of such records should
be designed to avoid transcription errors.
The record should carry 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.
Before any packaging operation begins, there should be recorded
checks that the equipment and work station are clear of previous
products, documents or materials not required for the planned
packaging operations, and that equipment is clean and suitable for
use.

The following information should be entered at the time each action is
taken and, after completion, the record should be dated and signed in
agreement by the person(s) responsible for the packaging operations:
a) The name of the product;
b) The date(s) and times of the packaging operations;
c) The name of the responsible person carrying out the packaging
operation;
d) The initials of the operators of the different significant steps;
e) Records of checks for identity and conformity with the Packaging
Instructions including the results of in-process controls;
• f) Details of the packaging operations carried out, including references
to equipment and the packaging lines used;

g) Whenever possible, samples of printed packaging materials used,
including specimens of the batch coding, expiry dating and any
additional overprinting;
• h) Notes on any special problems or unusual events including details
with signed authorization for any deviation from the Manufacturing
Formula and Processing Instructions;
• i) 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 obtained product, in order to
provide for an adequate reconciliation. (M.H.R.A., PIC/S GMP Guide)

BATCH MANUFACTURING RECORD
• is a product and batch specific document designed to give a
complete and reliable picture of the manufacturing history of
each batch of every product.
• shall be essentially based on the master formula record and shall
be compiled, checked, approved and authorized by competent
technical person responsible for production and quality control.
• Name of the product
• Batch number
• Date of commencement & completion of significant
intermediate stage
• Name of the person responsible for each stage of production
• Initials of operators who carried out significant processes and
initial of persons who checked, wherever applicable

BATCH MANUFACTURING RECORD
• Quantity, batch number, quality control report number of each
ingredient actually weighed and amount of any recovered material
added
• In-process controls carried out their results and signature of person
who performed
• Theoretical yield & actual yield at appropriate stage of production
together with explanation, if variation beyond expectation
observed
• Authorization of any deviation, if made.
Examples of Batch manufacturing records: BMR For Tablets:
Mixing, Drying, etc.

Batch Formula record INCLUDES
• Dates , times
• Identity of major equipment used (e.g., reactors, driers, mills, etc.)
• Specific identification of each batch :weights, measures, batch numbers of raw materials,
intermediates, or any reprocessed materials used during manufacturing
• Actual results recorded for critical process parameters
• Any sampling performed
• Signatures of the persons performing & supervising / checking critical steps of operation
• In-process and laboratory test results
• Actual yield at specific stages
• Description of packaging and label
• Representative label (commercial supply)
• Any deviation noted, its evaluation, & investigation conducted
• Results of release testing
• All analytical records relating to the batch, or a reference that will permit their retrieval
• A decision for the release or rejection of the batch, with the date and signature of the
person responsible for the decision
• The production record review

MASTER FORMULA RECORD
• Master formula record is a product specific document compiled,
checked, authorized and approved by competent technical personnel
from different but interlinked functions such as development,
production, packaging and QC as necessary and appropriate.
• Master formula record shall be open for review, Changes, if any to be
approved by designated persons of production and QC
• Master formula record shall
a. Give patent/proprietary name of the product, and its strength.
b. Give pharmacopoeial/generic name of the product, and its strength.
c. Give dosage form (e.g. tablet, ampoule) and physical characteristics
of the product.
d. Give sufficient, detailed information of product pack and primary
packaging materials.
e. Give identity, quality and quantity of every ingredient, including
overages/assay value based quantities, if any, irrespective of whether,
or not, the material. Next →

i) is an active drug substance in the formulation/product,
ii) is used as a pharmaceutical aid (excipient).
iii) appears, or is detected/tested in the final product.
f. Briefly describe all the raw materials
g. Give broad outlines of the process of manufacture (as a flow-
chart, for example).
h. Give brief description of equipment/ machinery used for
manufacturing the product.
i. Give step-wise manufacturing process.
j. Give theoretical and practical (expected) yields at different stages
of manufacture.
k. Bring out in sufficient details precautions to be taken during
manufacturing to ensure birth product quality and personnel safety.
l. Give all analytical controls, including limits thereof, applicable to
the finished product.

m. Give stability test results covering the assigned shelf life..
n. Have a ‘product history’ data giving references in
manufacturing/packaging introduced over the year.
o. (Preferably) contain samples of printed packaging components.

STANDARD OPERATING PROCEDURES SOP
• SOP is written document or instruction detailing all steps and
activities of a process or procedure. These should be carried out
without any deviation or modification to guarantee the expected
outcome.
• Any modification or deviation from a given SOP should be
thoroughly investigated and outcomes of the investigation
documented according the internal deviation procedure.
• Quality impacting processes and procedures should be as per
Standard Operating Procedures (SOPs).
 LOOK FOR VARIOUS SOP FORMATS AVAILABLE AT GOOGLE

BENEFITS OF SOP
1. To provide people with all the safety, health, environmental and operational
information necessary to perform a job properly. Placing value only on
production while ignoring safety, health and environment is costly in the long
run. It is better to train employees in all aspects of doing a job than to face
accidents, fines and litigation later.
• 2. To ensure that production operations are performed consistently to maintain
quality control of processes and products. Consumers, from individuals to
companies, want products of consistent quality and specifications. SOPs specify
job steps that help standardize products and therefore quality.
• 3. To ensure that processes continue uninterrupted and are completed on a
prescribed schedule. By following SOPs, you help ensure against process shut-
downs caused by equipment failure or other facility damage.
• 4. To ensure that no failures occur in manufacturing and other processes that
would harm anyone in the surrounding community. Following health and
environmental steps in SOPs ensures against spills and emissions that threaten
plant neighbors and create community outrage.

BENEFITS OF SOP
5. To ensure that approved procedures are followed in compliance with
company and government regulations. Well-written SOPs help ensure
that government regulations are satisfied. They also demonstrate a
company's good-faith intention to operate properly. Failure to write and
use good SOPs only signals government regulators that your company is
not serious about compliance.
• 6. To serve as a training document for teaching users about the process
for which the SOP was written.Thorough SOPs can be used as the basis
for providing standardized training for employees who are new to a
particular job and for those who need re-training.
• 7. To serve as a checklist for co-workers who observe job performance to
reinforce proper performance. The process of actively caring about
fellow workers involves one worker coaching another in all aspects of
proper job performance. When the proper procedures are outlined in a
good SOP, any co-worker can coach another to help improve work skills.

BENEFITS OF SOP
• 8. To serve as a checklist for auditors. Auditing job performance is a
process similar to observation mentioned in the previous item only it
usually involves record keeping. SOPs should serve as a strong basis when
detailed audit checklists are developed.
• 9. To serve as an historical record of the how, why and when of steps in
an existing process so there is a factual basis for revising those steps
when a process or equipment are changed. As people move from job to
job within and between companies, unwritten knowledge and skills
disappear from the workplace. Properly maintained written SOPs can
chronicle the best knowledge that can serve new workers when older ones
move on.
• 10. To serve as an explanation of steps in a process so they can be
reviewed in accident investigations. Although accidents are unfortunate,
view them as opportunities to learn how to improve conditions. A good
SOP gives you a basis from which to being investigating accidents.

Guidelines to prepare SOP
• Some guidelines are given below to prepare SOPS.
(i) Give a clear & descriptive title to each SOP.
(ii) Provide sufficient details. The SOP should meet the need of an
individual, all the same, it should be general enough for more than one user.
(iii) Flexibility should be written in the SOP wherever appropriate but it
should not be made too general for, it may be useless in meeting its
intended purpose
(iv) Organize SOPs according to order of sequence of events involved in
performing the operation. Write the text in straight forward and easy to
follow manner.
(v) After drafting SOP, use it in performing the operation to ensure that it
has sufficient details to perform the operation in intended manner.
(vi) Take into account the instructions from the manufacturer of the
equipment which is employed in performing the operation while drafting
SOP.
(vii) Indicate total number of pages so that user is certain that he is
performing the complete operation.
(viii) Indicate the effective date of the SOP.

Quality audit
• Auditing : Defined as inspection of a process or a system to make
sure that it complies with the requirements of its intended use.
• Quality Audit is key element of ISO quality system i.e. ISO 9001
• pharmaceutical industry: Audits are systematic, independent
examination of a Manufacturer’s quality system performed at
definite intervals & sufficient frequency.
Aims of Audit:
• To check that quality system activities and results comply with
Quality system procedures.
• Effective implementation of procedures
• Whether procedures are suitable to obtain quality system objective
If there are any deviations corrective measures can be taken to
bring the activities to normal

Quality audit
Aims of Audit:
• Assess company’s performance based on facts
• Obtain unbiased information on company’s activities
• To know facts, whether company is at risk?
• Evaluate Manufacturer complaince with GMP
• Identify deficiencies & faults, improve quality
• Investigate root cause of quality related problems
• Help Mgt. reducing cost
• Educate & train people within organization
• Control external activities like supplies by vendors, & outsorced
activities
• To make aware the suppliers about any quality related problems

TYPES Quality audit:
• Internal Audit (Self Inspection): Conducted within the premises
to monitor the implementation and respect of GMP. This is also
done to have prior information about the flaws in the system and
taking necessary corrective and preventive measures.
• Observations of internal team must be well documented
• Written instructions by company for internal audit, questionnaire
1. Personnel 2. Premises including personnel facilities
3. Maintenance of buildings & equipments
4. Storage of starting materials & finished products
5. Equipment 6. Production & in process controls
7. Q.C. 8. Documentation 9. Sanitation & HYGIENE
10. Validation & revalidation programmes 11. Recall procedure

INTERNAL Quality audit
12. Calibration of instruments 13. Complaints Mgt
14. Labeling control
15. Results of previous self inspections & corrective measures taken
STEPS OF INTERNAL QUALITY AUDIT
1. Constitution of Internal audit team: Team members from out
side or inside the company constituted by Mgt. , Expert should be
experienced, familiar of GLP concept
2. Frequency of Audit: At least once a year, stated in procedure
3. Audit Report: At completion of process, report of results,
evaluation, conclusions of inspection along with the corrective
measures
4. Follow up action: Company should evaluate internal audit &
recommend corrective measures to be followed timely for
effective results

EXTERNAL Quality audit
External Audit: Conducted for the suppliers or any outsourcing
operations carried out by the pharmaceutical industry. The contract giver
(Industry) is responsible to access the competence of the Contract
acceptor (supplier or any other outsource operations department) as per
the GMP guidelines.
Done to evaluate the ability of suppliers (raw material, packaging
materials etc.) to conform GLP std. Pharmaceutical company may
conduct audits of their suppliers – External audits
STEPS
1. Notification: To alert the company, Date & time of audit. List of
documents auditors wants to review can be provided
2. Planning: The auditor identify key areas of risk & areas of concern to
be evaluated during audit
3. Opening Meeting: Meeting b/w auditors & staff of company under
audit. Process of audit is described. Company under audit – explains
auditors about schedule of employees, areas of concern of audit

STEPS
4. Start of Audit procedure: After opening meeting, final audit plan
is prepared. Company employees are notified of audit sch. &
procedure starts
5. Communication: Audit team should be in touch with company’s
audit team for clarifications on procedures, for access to company
docs.
6. Draft audit report: After completion of audit, draft report is
prepared. It contains outcomes of audit, list of concerns. Then
submitted to company Mgt. for review & suggestions if any
7. Mgt response: Final audit report is prepared and submitted to
company Mgt. The Mgt is requested for there agree/ disagree with
report, any corrective measures, problems etc. & expected date of
addressal of problems or compliance.

STEPS
8. Final Meeting: Between auditors & company officials/ Mgt. to
close loose ends, discuss Mgt. response & sccope of audit
9. Report distribution: Distribution of final audit report to
concerned officials inside & outside audit area
10. Feedback: Audited company implements recommended
changes & auditors review, test quality, adherence effects of
implemented changes.

Quality audit
• It is mandatory that there should be a well written procedure for
conducting an audit whether it is an internal or external audit.
Important points in Quality Audit
• Frequency of Audit: The procedure how frequency of audit must
be defined and as per that frequency must be set and followed
accordingly.
• Responsibilities: The audit team must be defined that who will be
responsible for conducting and reviewing the audit reports. The
people in the audit team must be well equipped with the operations
and procedures that are being audited.
• Documentation: It is important to document each and every audit
conducted as it not only helps from regulatory perspective but also
act as reference document to have a insight of flaws previously
faced.

Quality audit
CONDUCTING AUDIT:
• The audit team must abide rules and regulations specific to the
operations carried out at the premises. Ex: if the audit is conducted
in aseptic section it is mandatory to put the safety clothing as per
cGMP that is must for everyone who so ever enter that portion.
• The audit must be done by communicating by the audit team with
the personnel working and all the findings must be documented.
But it is also important to explain the observations that make it
more realistic rather than just noting it down and explaining later
on.
• The audit team must be flexible. The procedure to meet the
requirements of cGMP could be different in different industries
hence the auditor must focus on the results and then decide about
the observations.
• The conclusions obtained must be prepared, documented and
finally completed as a audit report.

Quality review & Quality documentation
• Quality Review is the last stage in QC procedure, before the
dispatch of product
• It ensures that the finished product released for sale, all the
relevant records (production and control records) are cross
checked i.e. reviewed.
• Thorough investigation of any batch not conforming to standards
• Other batches of same product with specific failure needs to be
investigated
• Written record of investigation, conclusion of investigation, follow
up (remedial measures) must be kept
Objective of Product Quality Review:
To evaluate compliance status of manufacture & identify areas of
improvements
It should involve personnel from QC unit, production,
engineering, maintenance, Purchase etc.

Quality review & Quality documentation
• Review of following should be done periodically & documented:
• Starting materials/ packaging material used, sources, supply chain
• Critical in process controls & finished product test
• Failed batches with results of investigation
• Significant deviations, investigations, preventive measures taken
• Changes done in process & analytical methods
• Sales authorization submitted, granted, rejected for third party
(Exports) dossiers
• Stability monitoring results, adverse trends
• All quality related returns, complaints, recalls, investigation made
• Previous product, process or equipment corrective measures
• Post marketing commitments, new marketing authorizations etc
• Qualifying status of equipments, utilities used: HVAC

QUALITY DOCUMENT (GDP Good document practices)
• Document is any written statement or proof of any activity in
pharmaceuticals. Documentations are to define the manufacturers
system of information & control, to minimize the risk of
misinterpretation & errors inherent in oral or casually written
communication, to provide unambiguous procedures to be followed to
provide confirmation of performance, to allow calculations to be
checked & to allow tracing of batch history
• Good documentation is a systematic procedure of preparation,
checking, verifying, issuing, storing and reviewing of any documents.
• prevent errors of various activities in pharma
• Purpose of Documentations
• Defines specifications and procedures for all materials and methods
of manufacture and control
• Ensures all personnel know what to do and when to do it
• Ensure that authorized persons have all information necessary for
release of product
• Ensures documented evidence, traceability, provide records and
audit trail for investigation
• Ensures availability of data for validation, review and statistical
analysis.

• Classification of Documentation
• organization & Personnel.
• For Buildings & facilities
• For Equipments.
• For Handling of R.M.& P.M.
• For Production & process control.
• For Packaging & Labeling control.
• For Holding & Distribution
• For Laboratory Control.
• For Records & Reports.
• For Return & Salvaged finished products.

• Preparation, issues and uses of Documents
Documents should be carefully and logically specify to prevent
wrong uses. All necessary information’s are written
unambiguously. Each document includes:
1. Company name
2. Purpose and title of documents
3. Identification No and revision No.
4. Date of authorization
5. Date of review
6. Signature of prepared by, checked and authorized by.
7. Distribution list
8. Page no.
9. Reason for revision should be documented.
10. Abbreviation and reference

Quality
Manual
POLICY
PROCEDURE
Working
instruction
Records
Outlines company’s Goal, mission, vision
Define the quality objectives
Describes what should be done, by
whom,, how, when, where
Description of activities
Quality documentation system
HEIRARCHY OF QUALITY DOCUMENTATION SYSTEM

QUALITY MANUAL
• It is guiding document, approved by upper management, outlines
companies goals, vision and mission,
• Describes the scope of QMS: what to be included in Quality system
• Explains each & every requirement of ISO 9001
It should include:
• Title & table of contents
• Scope of QMS
• Exclusions from ISO 9001
• Version information & approval
• Quality policy & objectives
• QMS description
• Business process model of organization
• Definition of responsibilities for all personnel for all personnels
• References to relevant documents
• Relevant appendices

QUALITY MANUAL
• Purpose of QUALITY MANUAL:
• Communicate mgt’s expectations for quality to the organization
• Organizations conformity with ISO 9001 requirements
• Measure for compliance to Mgt’s expectations for Internal audits:
ISO Registrar audits, customer audits
QUALITY POLICY:
• It is declaration by the organization
• It defines the quality objectives to which the organization strives.
• Should provide outline for creating, stating, measuring the
performance of quality objectives
• Ex: To provide products & services meeting the expectations of
customers. Actively pursue ever improving quality by various
programs so to enable the employees to do the wok correctly for
the first time and ever

QUALITY MANUAL
• QUALITY PROCEDURES:
• Can be described by text, tables, flowcharts to make them effective
• Elements of quality procedures:
1. Title: Identifies procedure
2. Purpose: Explain why this procedure
3. Scope: what expects will be covered in procedure & what will not
4. Responsibilities of all persons, functions to be the part
5. Records as a result of activities done as per procedure
6. Document control: Identification of changes, date of review, approval
& version of document should be included in procedure
7. Description of activities: This relates all other elements of procedures,
describes what to be done, by whom, how, when & where. Its most
imp. Inputs & outputs of activities must be explained
8. Appendices to be included if required

QUALITY MANUAL
Work Instructions: covers following
1. Manner in which work will be done
2. Equipment & tools that will be used
3. Environment or location associated with the work
4. Material handling requirements
5. Safety alerts for all employees
6. Cross reference to any other required process or instructions
7. Critical process & Product parameters to be monitored including
instructions of monitoring
8. Equipment maintenance procedures
9. Methods for verifying that product meets specs
10. Other non product related criteria for the final product

QUALITY MANUAL
RECORDS:
• It is final tier of Quality Documentation system. All data,
information's, records, forms etc are achieved. Quality records
management shows that quality system has been executed.
• It describes how the quality of end product was verified to meet
the specs, meeting the customers satisfaction and needs.
• SOURCES QUALITY RECORDS
• Non conformance investigations
• CAPA’s (Corrective & preventive action)
• AUDIT RESULTS
• SUPPLIER DOCUMENTATION
• CALIBRATION RESULTS
• MAINTENANCE RECORDS

Model of document
• D- Design, development, dossiers, drug master file for regulated
markets, distribution records
• O- Operational procedures, techniques, methods, out of specs. (OOS),
Out of trend (OOT)
• C- Cleaning, calibration, controls, complaints, containers, closures,
contamination, change control
• U- User requirement specs, utilities likewater systems, HVAC, AHU (air
handling unit) etc
• M- Man, materials, machines, methods, maintenance, mfg, mfg
operations & control, monitoring, Master formula, manuals (quality,
safety, environment), medical records
• E- Engg. Control & practices, Envion. Control, equipment qualification,
documents,
• N- Non routine activities, New products & substances
• T- Technology transfer, training, testing, trend analysis, technical
dossiers
• S- SOP, safety practices, sanitation, storage, self inspection,
standardization, supplier qualification, specification & standard test
procedures & site master file

Reports & documents
• They are used through out manufacturing process, and in
supporting process (QA/QC). It must meet Good Documentation
Process. Various records/ reports are (some)
• Batch Record Form * Bill of materials
• Specifications * Policies
• Protocols * SOP’s
• Work instructions * Checklist
• Forms/ Log sheets * Certificate of analysis
• Technical transfer reports * Technical agreements
• Technical reports * Test methods
• Training assessments * Worksheets, logbooks, etc
• Validation docs * Quality manual
• Audit plans * Manufact./ pack. Instructions
• Quality system docs * Deviation reports etc

DISTRIBUTION RECORDS
• Good distribution practices (GDP) : Proper storage & distribution of
drug products minimizes risk of its quality
• These are written data of distribution of drug products from Mfg. to
distributors
• Records of distribution retained, accessible to trace history if req.
• Helps in recall of product when in need
• Distribution Records contain information on wholesalers, direct
costumers
• SOP’s of warehousing & distribution of products to be adopted
• Periodic audit of warehouse & distribution centers
• Before dispatch of a batch, ensure about the testing, approval, & release
by QC,
• Random inspection on consignments to ensure correctness of goods
must be done
• Maintain Distribution registers having details about distribution: Name,
strength, dosage form description, consignees name & address, date &
quantity shipped, lot number of drug product. Maintain inventory card
also to find the position of stock.

FORMAT OF INVENTORY CARD
M/S Name & address of company
Name of Poduct
Receipt No Date of issue
Transfer No.
Quantity Received
Quantity Issued Invoice No.
Batch No.
Address of distributor
Balance Sign of issuing person
Inventory card

• Checklist of distribution records
1. Whether pre dispatch inspections are carried out before release
Y/N
2. Whether periodic audit of distribution centre are carried out to
access warehousing practices Y/N
3. Whether distribution records are part of batch record. If not
how batch wise distribution record up to retail levels are
maintained Yes/N
4. Whether instruction for warehousing & stocking of products
like Low volume parentrals (LVP’s), heat sensitive etc. are
available in store Yes/N
5. Whether Good distribution practices followed Y/N
Inventory card

DOCUMENTS on quality of pharmaceutical products

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